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New and Noteworthy Information—January 2018
Sleep Improves After Retirement
Transition to statutory retirement is associated with a decrease in sleep difficulties, especially waking up too early in the morning and nonrestorative sleep, according to a study published online ahead of print November 16, 2017, in Sleep. The study included 5,807 public sector employees who retired between 2000 and 2011. Participants were administered the Jenkins Sleep Problem Scale Questionnaire before and after retirement in surveys conducted every four years. At the last study wave before retirement, 30% of the participants had sleep difficulties. The risk ratio for having sleep difficulties in the first study wave following retirement, compared with the last study wave preceding retirement, was 0.89. The decreases in sleep difficulties occurred primarily among people with psychologic distress, suboptimal self-rated health, short sleep duration, and job strain before retirement.
Myllyntausta S, Salo P, Kronholm E, et al. Changes in sleep difficulties during the transition to statutory retirement. Sleep. 2017 Nov 16 [Epub ahead of print].
Vigorous Exercise May Delay Parkinson’s Disease Progression
High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson’s disease, according to a study published online ahead of print December 11, 2017, in JAMA Neurology. The randomized clinical trial included 128 participants between ages 40 and 80. Participants were at an early stage of the disease and not taking Parkinson’s disease medication. Investigators randomized the population to high-intensity exercise, moderate-intensity exercise, or a control condition. At baseline and six months, clinicians assessed the participants using the Unified Parkinson’s Disease Rating Scale (UPDRS). Participants in the study had a UPDRS score of about 20 at baseline. At six months, the high-intensity group’s score stayed at 20, and the moderate exercise group worsened by 1.5 points. The control group’s score worsened by three points.
Schenkman M, Moore CG, Kohrt WM, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2017 Dec 11 [Epub ahead of print].
Can Exposure to Terror Raise the Risk of Headache?
Exposure to terror increases the risk of persistent weekly and daily migraine and tension-type headache in adolescent survivors above expected levels, according to a study published online ahead of print December 13, 2017, in Neurology. Investigators interviewed 213 survivors of a terror attack in Norway. Half were male, the mean age was 17.7, and 13 survivors were severely injured. Participants provided information about their headache frequency four to five months after the attack. For each survivor, eight matched controls were drawn from the Young-HUNT3 Study. After exposure to terror, the odds ratio for migraine was 4.27, and that for tension-type headache was 3.39, as estimated in multivariable logistic regression models adjusted for injury, sex, age, family structure and economy, prior exposure to physical or sexual violence, and psychologic distress.
Stensland SØ, Zwart JA, Wentzel-Larsen T, Dyb G. The headache of terror: a matched cohort study of adolescents from the Utøya and the HUNT Study. Neurology. 2017 Dec 13 [Epub ahead of print].
Diet Reduces Disability and Symptoms of MS
A healthy diet and a composite healthy lifestyle are associated with less disability and symptom burden in multiple sclerosis (MS), according to a study published online ahead of print December 6, 2017, in Neurology. The study involved 6,989 people with MS who completed questionnaires about their diet as part of the North American Research Committee registry. The questionnaire estimated intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats. Researchers constructed an overall diet quality score for each individual based on the food groups. Participants with diet quality scores in the highest quintile had lower levels of disability and lower depression scores. Individuals reporting a composite healthy lifestyle had lower odds of reporting severe fatigue, depression, pain, or cognitive impairment.
Fitzgerald KC, Tyry T, Salter A, et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2017 Dec 6 [Epub ahead of print].
What Are the Effects of Childhood Convulsive Status Epilepticus?
Childhood convulsive status epilepticus (CSE) is associated with substantial long-term neurologic morbidity, but primarily in people who have epilepsy, neurologic abnormalities, or both before the episode of CSE, according to a study published online ahead of print December 5, 2017, in Lancet Child & Adolescent Health. Researchers followed a population-based childhood CSE cohort. Of 203 survivors, 134 were assessed at a median follow-up of 8.9 years. Lasting neurologic conditions, including epilepsy, learning disabilities, and movement problems, were more common among participants than expected for children from the general population. Children who had existing neurologic or developmental issues at the time of CSE were more likely to have a neurologic problem at follow-up. Children without a neurologic or developmental issue tended to have better outcomes.
Pujar SS, Martinos MM, Cortina-Borja M, et al. Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study. Lancet Child Adolesc Health. 2017 Dec 5 [Epub ahead of print].
Protein Aggregation May Not Affect Cognition in Parkinson’s Disease
Patterns of cortical β-amyloid and tau do not differ between people with Parkinson’s disease who are cognitively normal (PD-CN), people with Parkinson’s disease with mild cognitive impairment (PD-MCI), and healthy older adults, according to a study published online ahead of print December 11, 2017, in JAMA Neurology. This cross-sectional study included 29 patients with Parkinson’s disease from a tertiary care medical center and research institutions. Imaging measures were compared with those of 49 healthy control participants. Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. Of the participants, 47 were female, and the mean age was 71.1. Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and between patients with Parkinson’s disease and β-amyloid-negative controls, did not reveal significant differences.
Winer JR, Maass A, Pressman P, et al. Associations between tau, β-amyloid, and cognition in Parkinson disease. JAMA Neurol. 2017 Dec 11 [Epub ahead of print].
Hormone Therapy Not Linked to Increased Stroke Risk
Postmenopausal hormone therapy is not associated with increased risk of stroke, provided that it is started early, according to a study published November 17 in PLoS Medicine. Researchers analyzed data on postmenopausal hormone therapy from five cohort studies including 88,914 women, combined with data from national registries on diagnoses and causes of death during a follow-up period. During a median follow-up of 14.3 years, 6,371 first-time stroke events (1,080 hemorrhagic) were recorded. Hormone therapy was not linked to increased risk of stroke if the therapy was initiated within five years of menopausal onset, regardless of means of administration, type of therapy, active substance, and treatment duration. In subanalyses, researchers observed an increase in risk for hemorrhagic stroke if the therapy contained the active substance conjugated equine estrogens.
Carrasquilla GD, Frumento P, Berglund A, et al. Postmenopausal hormone therapy and risk of stroke: a pooled analysis of data from population-based cohort studies. PLoS Med. 2017;14(11):e1002445.
Restless Sleep May Be Linked to Parkinson’s Disease
In patients with idiopathic REM sleep behavior disorder (IRBD), PET shows increased microglial activation in the substantia nigra, along with reduced dopaminergic function in the putamen, according to a study published in the October 2017 issue of Lancet Neurology. This prospective, case–control PET study included 20 patients with IRBD and no clinical evidence of parkinsonism and cognitive impairment recruited from tertiary sleep centers and 19 healthy controls. 11C-PK11195 binding was increased on the left side of the substantia nigra in patients with IRBD, compared with controls, but not on the right side. 11C-PK11195 binding was not significantly increased in the putamen and caudate of patients with IRBD. 18F-DOPA uptake was reduced in IRBD in the left putamen and right putamen, but not in the caudate.
Stokholm MG, Iranzo A, Østergaard K, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2017;16(10):789-796.
Can Playing Video Games Benefit the Brains of Older Adults?
Playing 3D video games may prevent mild cognitive impairment and, perhaps, Alzheimer’s disease, according to a study published December 6, 2017, in PLoS One. In two separate studies, adults in their 20s played 3D video games on platforms such as Super Mario 64. The gray matter in their hippocampus increased after training. Researchers examined whether the results could be replicated in healthy seniors. Thirty-three people, ages 55 to 75, were randomly assigned to one of three groups. The video game experimental group engaged in 3D-platform video game training over six months. An active control group took a series of self-directed, computerized piano lessons, and a no-contact control group did not engage in any intervention. Participants in the video-game cohort had increases in gray matter volume in the hippocampus and cerebellum. Their short-term memory also improved.
West GL, Zendel BR, Konishi K, et al. Playing Super Mario 64 increases hippocampal grey matter in older adults. PLoS One. 2017;12(12):e0187779.
FDA Approves Vercise Deep Brain Stimulation System
The FDA has approved the Vercise Deep Brain Stimulation System (DBS) to treat symptoms of Parkinson’s disease. The approval is based on the INTREPID study, a multicenter, prospective, double-blind, randomized, sham-controlled trial of DBS for Parkinson’s disease in the US. The study evaluated the system’s safety and efficacy in 292 patients at 23 sites. The Vercise DBS System successfully met its primary end point of mean change in waking hours with good symptom control. The filing also was supported by safety data from the VANTAGE study, in which 40 patients treated with the system demonstrated a 63% improvement in motor function at 52 weeks from baseline, as measured by the Unified Parkinson’s Disease Rating Scale III. Boston Scientific markets Vercise.
Can Social Relationships Aid Cognitive Function?
Although superagers (ie, people older than 80 with episodic memory as good as that of a middle-aged adult) and their cognitively average-for-age peers report similarly high levels of psychological well-being, superagers demonstrate greater levels of positive social relationships, according to a study published October 23, 2017, in PLoS One. Thirty-one superagers and 19 cognitively average-for-age peers completed the Ryff 42-item Psychological Well-Being questionnaire, which includes subscales of autonomy, positive relations with others, environmental mastery, personal growth, purpose in life, and self-acceptance. The groups did not differ on demographic factors, including estimated premorbid intelligence. Compared with cognitively average-for-age peers, superagers endorsed greater levels of positive relations with others. Superagers had a median overall score of 40 in positive relations with others, compared with 36 in the control group.
Cook Maher A, Kielb S, Loyer E, et al. Psychological well-being in elderly adults with extraordinary episodic memory. PLoS One. 2017;12(10):e0186413.
—Kimberly Williams
Sleep Improves After Retirement
Transition to statutory retirement is associated with a decrease in sleep difficulties, especially waking up too early in the morning and nonrestorative sleep, according to a study published online ahead of print November 16, 2017, in Sleep. The study included 5,807 public sector employees who retired between 2000 and 2011. Participants were administered the Jenkins Sleep Problem Scale Questionnaire before and after retirement in surveys conducted every four years. At the last study wave before retirement, 30% of the participants had sleep difficulties. The risk ratio for having sleep difficulties in the first study wave following retirement, compared with the last study wave preceding retirement, was 0.89. The decreases in sleep difficulties occurred primarily among people with psychologic distress, suboptimal self-rated health, short sleep duration, and job strain before retirement.
Myllyntausta S, Salo P, Kronholm E, et al. Changes in sleep difficulties during the transition to statutory retirement. Sleep. 2017 Nov 16 [Epub ahead of print].
Vigorous Exercise May Delay Parkinson’s Disease Progression
High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson’s disease, according to a study published online ahead of print December 11, 2017, in JAMA Neurology. The randomized clinical trial included 128 participants between ages 40 and 80. Participants were at an early stage of the disease and not taking Parkinson’s disease medication. Investigators randomized the population to high-intensity exercise, moderate-intensity exercise, or a control condition. At baseline and six months, clinicians assessed the participants using the Unified Parkinson’s Disease Rating Scale (UPDRS). Participants in the study had a UPDRS score of about 20 at baseline. At six months, the high-intensity group’s score stayed at 20, and the moderate exercise group worsened by 1.5 points. The control group’s score worsened by three points.
Schenkman M, Moore CG, Kohrt WM, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2017 Dec 11 [Epub ahead of print].
Can Exposure to Terror Raise the Risk of Headache?
Exposure to terror increases the risk of persistent weekly and daily migraine and tension-type headache in adolescent survivors above expected levels, according to a study published online ahead of print December 13, 2017, in Neurology. Investigators interviewed 213 survivors of a terror attack in Norway. Half were male, the mean age was 17.7, and 13 survivors were severely injured. Participants provided information about their headache frequency four to five months after the attack. For each survivor, eight matched controls were drawn from the Young-HUNT3 Study. After exposure to terror, the odds ratio for migraine was 4.27, and that for tension-type headache was 3.39, as estimated in multivariable logistic regression models adjusted for injury, sex, age, family structure and economy, prior exposure to physical or sexual violence, and psychologic distress.
Stensland SØ, Zwart JA, Wentzel-Larsen T, Dyb G. The headache of terror: a matched cohort study of adolescents from the Utøya and the HUNT Study. Neurology. 2017 Dec 13 [Epub ahead of print].
Diet Reduces Disability and Symptoms of MS
A healthy diet and a composite healthy lifestyle are associated with less disability and symptom burden in multiple sclerosis (MS), according to a study published online ahead of print December 6, 2017, in Neurology. The study involved 6,989 people with MS who completed questionnaires about their diet as part of the North American Research Committee registry. The questionnaire estimated intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats. Researchers constructed an overall diet quality score for each individual based on the food groups. Participants with diet quality scores in the highest quintile had lower levels of disability and lower depression scores. Individuals reporting a composite healthy lifestyle had lower odds of reporting severe fatigue, depression, pain, or cognitive impairment.
Fitzgerald KC, Tyry T, Salter A, et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2017 Dec 6 [Epub ahead of print].
What Are the Effects of Childhood Convulsive Status Epilepticus?
Childhood convulsive status epilepticus (CSE) is associated with substantial long-term neurologic morbidity, but primarily in people who have epilepsy, neurologic abnormalities, or both before the episode of CSE, according to a study published online ahead of print December 5, 2017, in Lancet Child & Adolescent Health. Researchers followed a population-based childhood CSE cohort. Of 203 survivors, 134 were assessed at a median follow-up of 8.9 years. Lasting neurologic conditions, including epilepsy, learning disabilities, and movement problems, were more common among participants than expected for children from the general population. Children who had existing neurologic or developmental issues at the time of CSE were more likely to have a neurologic problem at follow-up. Children without a neurologic or developmental issue tended to have better outcomes.
Pujar SS, Martinos MM, Cortina-Borja M, et al. Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study. Lancet Child Adolesc Health. 2017 Dec 5 [Epub ahead of print].
Protein Aggregation May Not Affect Cognition in Parkinson’s Disease
Patterns of cortical β-amyloid and tau do not differ between people with Parkinson’s disease who are cognitively normal (PD-CN), people with Parkinson’s disease with mild cognitive impairment (PD-MCI), and healthy older adults, according to a study published online ahead of print December 11, 2017, in JAMA Neurology. This cross-sectional study included 29 patients with Parkinson’s disease from a tertiary care medical center and research institutions. Imaging measures were compared with those of 49 healthy control participants. Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. Of the participants, 47 were female, and the mean age was 71.1. Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and between patients with Parkinson’s disease and β-amyloid-negative controls, did not reveal significant differences.
Winer JR, Maass A, Pressman P, et al. Associations between tau, β-amyloid, and cognition in Parkinson disease. JAMA Neurol. 2017 Dec 11 [Epub ahead of print].
Hormone Therapy Not Linked to Increased Stroke Risk
Postmenopausal hormone therapy is not associated with increased risk of stroke, provided that it is started early, according to a study published November 17 in PLoS Medicine. Researchers analyzed data on postmenopausal hormone therapy from five cohort studies including 88,914 women, combined with data from national registries on diagnoses and causes of death during a follow-up period. During a median follow-up of 14.3 years, 6,371 first-time stroke events (1,080 hemorrhagic) were recorded. Hormone therapy was not linked to increased risk of stroke if the therapy was initiated within five years of menopausal onset, regardless of means of administration, type of therapy, active substance, and treatment duration. In subanalyses, researchers observed an increase in risk for hemorrhagic stroke if the therapy contained the active substance conjugated equine estrogens.
Carrasquilla GD, Frumento P, Berglund A, et al. Postmenopausal hormone therapy and risk of stroke: a pooled analysis of data from population-based cohort studies. PLoS Med. 2017;14(11):e1002445.
Restless Sleep May Be Linked to Parkinson’s Disease
In patients with idiopathic REM sleep behavior disorder (IRBD), PET shows increased microglial activation in the substantia nigra, along with reduced dopaminergic function in the putamen, according to a study published in the October 2017 issue of Lancet Neurology. This prospective, case–control PET study included 20 patients with IRBD and no clinical evidence of parkinsonism and cognitive impairment recruited from tertiary sleep centers and 19 healthy controls. 11C-PK11195 binding was increased on the left side of the substantia nigra in patients with IRBD, compared with controls, but not on the right side. 11C-PK11195 binding was not significantly increased in the putamen and caudate of patients with IRBD. 18F-DOPA uptake was reduced in IRBD in the left putamen and right putamen, but not in the caudate.
Stokholm MG, Iranzo A, Østergaard K, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2017;16(10):789-796.
Can Playing Video Games Benefit the Brains of Older Adults?
Playing 3D video games may prevent mild cognitive impairment and, perhaps, Alzheimer’s disease, according to a study published December 6, 2017, in PLoS One. In two separate studies, adults in their 20s played 3D video games on platforms such as Super Mario 64. The gray matter in their hippocampus increased after training. Researchers examined whether the results could be replicated in healthy seniors. Thirty-three people, ages 55 to 75, were randomly assigned to one of three groups. The video game experimental group engaged in 3D-platform video game training over six months. An active control group took a series of self-directed, computerized piano lessons, and a no-contact control group did not engage in any intervention. Participants in the video-game cohort had increases in gray matter volume in the hippocampus and cerebellum. Their short-term memory also improved.
West GL, Zendel BR, Konishi K, et al. Playing Super Mario 64 increases hippocampal grey matter in older adults. PLoS One. 2017;12(12):e0187779.
FDA Approves Vercise Deep Brain Stimulation System
The FDA has approved the Vercise Deep Brain Stimulation System (DBS) to treat symptoms of Parkinson’s disease. The approval is based on the INTREPID study, a multicenter, prospective, double-blind, randomized, sham-controlled trial of DBS for Parkinson’s disease in the US. The study evaluated the system’s safety and efficacy in 292 patients at 23 sites. The Vercise DBS System successfully met its primary end point of mean change in waking hours with good symptom control. The filing also was supported by safety data from the VANTAGE study, in which 40 patients treated with the system demonstrated a 63% improvement in motor function at 52 weeks from baseline, as measured by the Unified Parkinson’s Disease Rating Scale III. Boston Scientific markets Vercise.
Can Social Relationships Aid Cognitive Function?
Although superagers (ie, people older than 80 with episodic memory as good as that of a middle-aged adult) and their cognitively average-for-age peers report similarly high levels of psychological well-being, superagers demonstrate greater levels of positive social relationships, according to a study published October 23, 2017, in PLoS One. Thirty-one superagers and 19 cognitively average-for-age peers completed the Ryff 42-item Psychological Well-Being questionnaire, which includes subscales of autonomy, positive relations with others, environmental mastery, personal growth, purpose in life, and self-acceptance. The groups did not differ on demographic factors, including estimated premorbid intelligence. Compared with cognitively average-for-age peers, superagers endorsed greater levels of positive relations with others. Superagers had a median overall score of 40 in positive relations with others, compared with 36 in the control group.
Cook Maher A, Kielb S, Loyer E, et al. Psychological well-being in elderly adults with extraordinary episodic memory. PLoS One. 2017;12(10):e0186413.
—Kimberly Williams
Sleep Improves After Retirement
Transition to statutory retirement is associated with a decrease in sleep difficulties, especially waking up too early in the morning and nonrestorative sleep, according to a study published online ahead of print November 16, 2017, in Sleep. The study included 5,807 public sector employees who retired between 2000 and 2011. Participants were administered the Jenkins Sleep Problem Scale Questionnaire before and after retirement in surveys conducted every four years. At the last study wave before retirement, 30% of the participants had sleep difficulties. The risk ratio for having sleep difficulties in the first study wave following retirement, compared with the last study wave preceding retirement, was 0.89. The decreases in sleep difficulties occurred primarily among people with psychologic distress, suboptimal self-rated health, short sleep duration, and job strain before retirement.
Myllyntausta S, Salo P, Kronholm E, et al. Changes in sleep difficulties during the transition to statutory retirement. Sleep. 2017 Nov 16 [Epub ahead of print].
Vigorous Exercise May Delay Parkinson’s Disease Progression
High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson’s disease, according to a study published online ahead of print December 11, 2017, in JAMA Neurology. The randomized clinical trial included 128 participants between ages 40 and 80. Participants were at an early stage of the disease and not taking Parkinson’s disease medication. Investigators randomized the population to high-intensity exercise, moderate-intensity exercise, or a control condition. At baseline and six months, clinicians assessed the participants using the Unified Parkinson’s Disease Rating Scale (UPDRS). Participants in the study had a UPDRS score of about 20 at baseline. At six months, the high-intensity group’s score stayed at 20, and the moderate exercise group worsened by 1.5 points. The control group’s score worsened by three points.
Schenkman M, Moore CG, Kohrt WM, et al. Effect of high-intensity treadmill exercise on motor symptoms in patients with de novo Parkinson disease: a phase 2 randomized clinical trial. JAMA Neurol. 2017 Dec 11 [Epub ahead of print].
Can Exposure to Terror Raise the Risk of Headache?
Exposure to terror increases the risk of persistent weekly and daily migraine and tension-type headache in adolescent survivors above expected levels, according to a study published online ahead of print December 13, 2017, in Neurology. Investigators interviewed 213 survivors of a terror attack in Norway. Half were male, the mean age was 17.7, and 13 survivors were severely injured. Participants provided information about their headache frequency four to five months after the attack. For each survivor, eight matched controls were drawn from the Young-HUNT3 Study. After exposure to terror, the odds ratio for migraine was 4.27, and that for tension-type headache was 3.39, as estimated in multivariable logistic regression models adjusted for injury, sex, age, family structure and economy, prior exposure to physical or sexual violence, and psychologic distress.
Stensland SØ, Zwart JA, Wentzel-Larsen T, Dyb G. The headache of terror: a matched cohort study of adolescents from the Utøya and the HUNT Study. Neurology. 2017 Dec 13 [Epub ahead of print].
Diet Reduces Disability and Symptoms of MS
A healthy diet and a composite healthy lifestyle are associated with less disability and symptom burden in multiple sclerosis (MS), according to a study published online ahead of print December 6, 2017, in Neurology. The study involved 6,989 people with MS who completed questionnaires about their diet as part of the North American Research Committee registry. The questionnaire estimated intake of fruits, vegetables and legumes, whole grains, added sugars, and red and processed meats. Researchers constructed an overall diet quality score for each individual based on the food groups. Participants with diet quality scores in the highest quintile had lower levels of disability and lower depression scores. Individuals reporting a composite healthy lifestyle had lower odds of reporting severe fatigue, depression, pain, or cognitive impairment.
Fitzgerald KC, Tyry T, Salter A, et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2017 Dec 6 [Epub ahead of print].
What Are the Effects of Childhood Convulsive Status Epilepticus?
Childhood convulsive status epilepticus (CSE) is associated with substantial long-term neurologic morbidity, but primarily in people who have epilepsy, neurologic abnormalities, or both before the episode of CSE, according to a study published online ahead of print December 5, 2017, in Lancet Child & Adolescent Health. Researchers followed a population-based childhood CSE cohort. Of 203 survivors, 134 were assessed at a median follow-up of 8.9 years. Lasting neurologic conditions, including epilepsy, learning disabilities, and movement problems, were more common among participants than expected for children from the general population. Children who had existing neurologic or developmental issues at the time of CSE were more likely to have a neurologic problem at follow-up. Children without a neurologic or developmental issue tended to have better outcomes.
Pujar SS, Martinos MM, Cortina-Borja M, et al. Long-term prognosis after childhood convulsive status epilepticus: a prospective cohort study. Lancet Child Adolesc Health. 2017 Dec 5 [Epub ahead of print].
Protein Aggregation May Not Affect Cognition in Parkinson’s Disease
Patterns of cortical β-amyloid and tau do not differ between people with Parkinson’s disease who are cognitively normal (PD-CN), people with Parkinson’s disease with mild cognitive impairment (PD-MCI), and healthy older adults, according to a study published online ahead of print December 11, 2017, in JAMA Neurology. This cross-sectional study included 29 patients with Parkinson’s disease from a tertiary care medical center and research institutions. Imaging measures were compared with those of 49 healthy control participants. Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. Of the participants, 47 were female, and the mean age was 71.1. Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and between patients with Parkinson’s disease and β-amyloid-negative controls, did not reveal significant differences.
Winer JR, Maass A, Pressman P, et al. Associations between tau, β-amyloid, and cognition in Parkinson disease. JAMA Neurol. 2017 Dec 11 [Epub ahead of print].
Hormone Therapy Not Linked to Increased Stroke Risk
Postmenopausal hormone therapy is not associated with increased risk of stroke, provided that it is started early, according to a study published November 17 in PLoS Medicine. Researchers analyzed data on postmenopausal hormone therapy from five cohort studies including 88,914 women, combined with data from national registries on diagnoses and causes of death during a follow-up period. During a median follow-up of 14.3 years, 6,371 first-time stroke events (1,080 hemorrhagic) were recorded. Hormone therapy was not linked to increased risk of stroke if the therapy was initiated within five years of menopausal onset, regardless of means of administration, type of therapy, active substance, and treatment duration. In subanalyses, researchers observed an increase in risk for hemorrhagic stroke if the therapy contained the active substance conjugated equine estrogens.
Carrasquilla GD, Frumento P, Berglund A, et al. Postmenopausal hormone therapy and risk of stroke: a pooled analysis of data from population-based cohort studies. PLoS Med. 2017;14(11):e1002445.
Restless Sleep May Be Linked to Parkinson’s Disease
In patients with idiopathic REM sleep behavior disorder (IRBD), PET shows increased microglial activation in the substantia nigra, along with reduced dopaminergic function in the putamen, according to a study published in the October 2017 issue of Lancet Neurology. This prospective, case–control PET study included 20 patients with IRBD and no clinical evidence of parkinsonism and cognitive impairment recruited from tertiary sleep centers and 19 healthy controls. 11C-PK11195 binding was increased on the left side of the substantia nigra in patients with IRBD, compared with controls, but not on the right side. 11C-PK11195 binding was not significantly increased in the putamen and caudate of patients with IRBD. 18F-DOPA uptake was reduced in IRBD in the left putamen and right putamen, but not in the caudate.
Stokholm MG, Iranzo A, Østergaard K, et al. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study. Lancet Neurol. 2017;16(10):789-796.
Can Playing Video Games Benefit the Brains of Older Adults?
Playing 3D video games may prevent mild cognitive impairment and, perhaps, Alzheimer’s disease, according to a study published December 6, 2017, in PLoS One. In two separate studies, adults in their 20s played 3D video games on platforms such as Super Mario 64. The gray matter in their hippocampus increased after training. Researchers examined whether the results could be replicated in healthy seniors. Thirty-three people, ages 55 to 75, were randomly assigned to one of three groups. The video game experimental group engaged in 3D-platform video game training over six months. An active control group took a series of self-directed, computerized piano lessons, and a no-contact control group did not engage in any intervention. Participants in the video-game cohort had increases in gray matter volume in the hippocampus and cerebellum. Their short-term memory also improved.
West GL, Zendel BR, Konishi K, et al. Playing Super Mario 64 increases hippocampal grey matter in older adults. PLoS One. 2017;12(12):e0187779.
FDA Approves Vercise Deep Brain Stimulation System
The FDA has approved the Vercise Deep Brain Stimulation System (DBS) to treat symptoms of Parkinson’s disease. The approval is based on the INTREPID study, a multicenter, prospective, double-blind, randomized, sham-controlled trial of DBS for Parkinson’s disease in the US. The study evaluated the system’s safety and efficacy in 292 patients at 23 sites. The Vercise DBS System successfully met its primary end point of mean change in waking hours with good symptom control. The filing also was supported by safety data from the VANTAGE study, in which 40 patients treated with the system demonstrated a 63% improvement in motor function at 52 weeks from baseline, as measured by the Unified Parkinson’s Disease Rating Scale III. Boston Scientific markets Vercise.
Can Social Relationships Aid Cognitive Function?
Although superagers (ie, people older than 80 with episodic memory as good as that of a middle-aged adult) and their cognitively average-for-age peers report similarly high levels of psychological well-being, superagers demonstrate greater levels of positive social relationships, according to a study published October 23, 2017, in PLoS One. Thirty-one superagers and 19 cognitively average-for-age peers completed the Ryff 42-item Psychological Well-Being questionnaire, which includes subscales of autonomy, positive relations with others, environmental mastery, personal growth, purpose in life, and self-acceptance. The groups did not differ on demographic factors, including estimated premorbid intelligence. Compared with cognitively average-for-age peers, superagers endorsed greater levels of positive relations with others. Superagers had a median overall score of 40 in positive relations with others, compared with 36 in the control group.
Cook Maher A, Kielb S, Loyer E, et al. Psychological well-being in elderly adults with extraordinary episodic memory. PLoS One. 2017;12(10):e0186413.
—Kimberly Williams
New and Noteworthy Information—December 2017
Brain Glucose Level Is Associated With Alzheimer’s Disease Severity
Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to Alzheimer’s disease pathogenesis, according to a study published online ahead of print October 19 in Alzheimer’s & Dementia. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, researchers measured brain glucose concentration and assessed the ratios of serine, glycine, and alanine to glucose. Investigators also quantified protein levels of the neuronal and astrocytic glucose transporters. In addition, study authors assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower neuronal glucose transporters were related to severity of Alzheimer’s disease pathology and the expression of Alzheimer’s disease symptoms. Longitudinal increases in fasting plasma glucose levels were associated with higher brain tissue glucose concentrations.
An Y, Varma VR, Varma S, et al. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. 2017 Oct 19 [Epub ahead of print].
Is it Better to Be Asleep or Awake for DBS Implantation?
Patients with Parkinson’s disease who undergo deep brain stimulation (DBS) device implantation while asleep have better communication, cognition, and speech outcomes, according to a study published November 7 in Neurology. Thirty DBS candidates with Parkinson’s disease underwent imaging-guided implantation while asleep. Their six-month outcomes were compared to those of 39 patients who previously had undergone implantation while awake.
Brodsky MA, Anderson S, Murchison C, et al. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease. Neurology. 2017;89(19):1944-1950.
Is Inflammation During Middle Age Linked to Brain Shrinkage Later On?
People with blood biomarkers of inflammation during midlife may have more brain shrinkage decades later than people without these biomarkers, according to a study published online ahead of print November 1 in Neurology. Plasma levels of fibrinogen, albumin, white blood cells, von Willebrand factor, and Factor VIII were assessed at baseline in 1,633 participants in the Atherosclerosis Risk in Communities Study. Each standard deviation increase in midlife inflammation composite score was associated with 1,788 mm3 greater ventricular volume, 110 mm3 smaller hippocampal volume, 519 mm3 smaller occipital volume, and 532 mm3 smaller Alzheimer disease signature region volumes and reduced episodic memory 24 years later. Compared with participants with no elevated midlife inflammatory markers, participants with elevations in three or more markers had 5% smaller hippocampal and Alzheimer’s disease signature region volumes.
Walker KA, Hoogeveen RC, Folsom AR, et al. Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study. Neurology. 2017 Nov 1 [Epub ahead of print].
Novel Wristbands Improve Seizure Detection
Wrist-worn convulsive seizure detectors provide more accurate seizure counts than previous automated detectors do, while maintaining tolerable false alarm rates (FAR) for ambulatory monitoring, according to a study published in the November issue of Epilepsia. Hand-annotated video-EEG seizure events were collected from 69 patients at six clinical sites. Two novel wristbands and one current wristband were used to record electrodermal activity and accelerometer signals, obtaining 5,928 hours of data, including 55 convulsive epileptic seizures in 22 patients. The novel wristbands consistently outperformed the current wristband. The best wristband had a sensitivity of 94.55% and an FAR of 0.2 events per day. When increasing the sensitivity to 100%, the FAR was as much as 13 times lower than with the current detector. Automatically estimated seizure durations were correlated with true durations.
Onorati F, Regalia G, Caborni C, et al. Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors. Epilepsia. 2017;58(11):1870-1879.
Focused Ultrasound Reduces Parkinson’s Disease Tremor
Focused ultrasound thalamotomy for patients with tremor-dominant Parkinson’s disease demonstrates improvement in medication-refractory tremor by Clinical Rating Scale for Tremor assessments, even in the setting of a placebo response, according to a study published online ahead of print October 30 in JAMA Neurology. Researchers randomized 20 patients to unilateral focused ultrasound thalamotomy and seven to a sham procedure. Twenty-six participants were male, and the median age was 67.8. The predefined primary outcomes were safety and difference in improvement between groups at three months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor. On-medication median tremor scores improved 62% from a baseline of 17 points following focused ultrasound thalamotomy, and 22% from a baseline of 23 points after sham procedures.
Bond AE, Shah BB, Huss DS, et al. Safety and efficacy of focused ultrasound thalamotomy for patients with medication-refractory, tremor-dominant Parkinson disease: a randomized clinical trial. JAMA Neurol. 2017 Oct 30 [Epub ahead of print].
Biomarker of Multiple Sclerosis Identified
MicroRNAs associated with circulating exosomes are informative biomarkers for the diagnosis of multiple sclerosis (MS) and for predicting disease subtype with a high degree of accuracy, according to a study published October 30 in Scientific Reports. Exosome-associated microRNAs in serum samples from 25 patients with MS and 11 matched healthy controls were profiled using small RNA next-generation sequencing. In addition to identifying biomarkers that distinguish healthy people from people with MS, researchers identified nine microRNA molecules that differentiate between relapsing-remitting MS and progressive MS. Study authors also validated eight out of nine microRNA molecules in an independent group of 11 patients with progressive MS. The blood test may enable earlier treatment of MS and help neurologists identify the most appropriate treatment for a patient, said the authors.
Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017;7(1):14293.
Does Oral Anticoagulation in Atrial Fibrillation Reduce Dementia Risk?
The risk of dementia in patients with atrial fibrillation is higher among those who do not take oral anticoagulants, compared with those who do, according to a study published online ahead of print October 24 in the European Heart Journal. This Swedish retrospective registry study included 444,106 patients with hospital diagnosis of atrial fibrillation and no previous diagnosis of dementia between 2006 and 2014. At baseline, 54% of patients were not taking oral anticoagulants. Investigators performed propensity score matching, used falsification end points, and performed intention-to-treat and on-treatment analyses. Patients on anticoagulant treatment at baseline had a 29% lower risk of dementia than patients without anticoagulant treatment, and a 48% lower risk analyzed on treatment. Direct comparison between new oral anticoagulants and warfarin showed no difference.
Friberg L, Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J. 2017 Oct 24 [Epub ahead of print].
Dendritic Spine Plasticity May Protect Against Dementia
Dendritic spine plasticity protects older people with Alzheimer’s disease pathology from developing dementia, according to a study published in the October issue of Annals of Neurology. Researchers compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 of the dorsolateral prefrontal cortex in 12 age-matched healthy controls, eight controls with Alzheimer’s disease pathology (CAD), and 21 people with Alzheimer’s disease. The investigators created digital reconstructions of dendritic structure for morphologic analyses. Spine density was similar among control and CAD cases, but was reduced significantly in Alzheimer’s disease. Thin and mushroom spines were reduced significantly in Alzheimer’s disease, compared with CAD brains, and stubby spine density was decreased significantly in CAD and Alzheimer’s disease, compared with controls.
Boros BD, Greathouse KM, Gentry EG, et al. Dendritic spines provide cognitive resilience against Alzheimer’s disease. Ann Neurol. 2017;82(4):602-614.
Opioid Versus Nonopioid Treatment for Acute Migraine
IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the emergency department and should not be used as first-line therapy, according to a study published online ahead of print October 18 in Neurology. This study was conducted in two emergency departments and included patients who met international criteria for migraine if they had not used an opioid within the previous month. Participants received hydromorphone (1 mg) or prochlorperazine (10 mg) and diphenhydramine (25 mg). The primary outcome was achieving a headache level of mild or none within two hours of treatment and maintaining that level for 48 hours without rescue medication. Approximately 60% of the prochlorperazine arm achieved the primary outcome, compared with 31% of the hydromorphone arm.
Friedman BW, Irizarry E, Solorzano C, et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. 2017 Oct 18 [Epub ahead of print].
Frontotemporal Degeneration Entails High Economic Burden
The economic burden of frontotemporal degeneration may be twice as high as that of Alzheimer’s disease, according to a study published online ahead of print October 4 in Neurology. An Internet survey was administered to 674 primary caregivers of patients with behavioral-variant frontotemporal degeneration, primary progressive aphasia, frontotemporal degeneration with motor neuron disease, corticobasal syndrome, or progressive supranuclear palsy. Direct costs for these disorders equaled $47,916, and indirect costs equaled $71,737. Patients age 65 or older, those with later stages of disease, and those with behavioral-variant frontotemporal degeneration had higher direct costs, while patients younger than 65 and men had higher indirect costs. Mean household income ranged from $75,000 to $99,000 at 12 months before frontotemporal degeneration diagnosis, but declined to $50,000 to $59,999 after diagnosis.
Galvin JE, Howard DH, Denny SS, et al. The social and economic burden of frontotemporal degeneration. Neurology. 2017 Oct 4 [Epub ahead of print].
FDA Approves Vimpat for Partial-Onset Seizures in Pediatric Epilepsy
The FDA has approved a label extension for Vimpat (lacosamide) CV as an oral option for the treatment of partial-onset seizures in pediatric patients age 4 and older. The safety and efficacy profile of Vimpat as monotherapy and adjunctive therapy for the treatment of partial-onset seizures in adults was previously established in four multicenter, randomized, controlled clinical trials. The expanded indication for Vimpat is based on extrapolation of efficacy data from adults to children and is supported by safety and pharmacokinetics data collected in children. Adverse reactions in pediatric patients are similar to those in adult patients. UCB, which markets Vimpat, is headquartered in Brussels.
—Kimberly Williams
Brain Glucose Level Is Associated With Alzheimer’s Disease Severity
Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to Alzheimer’s disease pathogenesis, according to a study published online ahead of print October 19 in Alzheimer’s & Dementia. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, researchers measured brain glucose concentration and assessed the ratios of serine, glycine, and alanine to glucose. Investigators also quantified protein levels of the neuronal and astrocytic glucose transporters. In addition, study authors assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower neuronal glucose transporters were related to severity of Alzheimer’s disease pathology and the expression of Alzheimer’s disease symptoms. Longitudinal increases in fasting plasma glucose levels were associated with higher brain tissue glucose concentrations.
An Y, Varma VR, Varma S, et al. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. 2017 Oct 19 [Epub ahead of print].
Is it Better to Be Asleep or Awake for DBS Implantation?
Patients with Parkinson’s disease who undergo deep brain stimulation (DBS) device implantation while asleep have better communication, cognition, and speech outcomes, according to a study published November 7 in Neurology. Thirty DBS candidates with Parkinson’s disease underwent imaging-guided implantation while asleep. Their six-month outcomes were compared to those of 39 patients who previously had undergone implantation while awake.
Brodsky MA, Anderson S, Murchison C, et al. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease. Neurology. 2017;89(19):1944-1950.
Is Inflammation During Middle Age Linked to Brain Shrinkage Later On?
People with blood biomarkers of inflammation during midlife may have more brain shrinkage decades later than people without these biomarkers, according to a study published online ahead of print November 1 in Neurology. Plasma levels of fibrinogen, albumin, white blood cells, von Willebrand factor, and Factor VIII were assessed at baseline in 1,633 participants in the Atherosclerosis Risk in Communities Study. Each standard deviation increase in midlife inflammation composite score was associated with 1,788 mm3 greater ventricular volume, 110 mm3 smaller hippocampal volume, 519 mm3 smaller occipital volume, and 532 mm3 smaller Alzheimer disease signature region volumes and reduced episodic memory 24 years later. Compared with participants with no elevated midlife inflammatory markers, participants with elevations in three or more markers had 5% smaller hippocampal and Alzheimer’s disease signature region volumes.
Walker KA, Hoogeveen RC, Folsom AR, et al. Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study. Neurology. 2017 Nov 1 [Epub ahead of print].
Novel Wristbands Improve Seizure Detection
Wrist-worn convulsive seizure detectors provide more accurate seizure counts than previous automated detectors do, while maintaining tolerable false alarm rates (FAR) for ambulatory monitoring, according to a study published in the November issue of Epilepsia. Hand-annotated video-EEG seizure events were collected from 69 patients at six clinical sites. Two novel wristbands and one current wristband were used to record electrodermal activity and accelerometer signals, obtaining 5,928 hours of data, including 55 convulsive epileptic seizures in 22 patients. The novel wristbands consistently outperformed the current wristband. The best wristband had a sensitivity of 94.55% and an FAR of 0.2 events per day. When increasing the sensitivity to 100%, the FAR was as much as 13 times lower than with the current detector. Automatically estimated seizure durations were correlated with true durations.
Onorati F, Regalia G, Caborni C, et al. Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors. Epilepsia. 2017;58(11):1870-1879.
Focused Ultrasound Reduces Parkinson’s Disease Tremor
Focused ultrasound thalamotomy for patients with tremor-dominant Parkinson’s disease demonstrates improvement in medication-refractory tremor by Clinical Rating Scale for Tremor assessments, even in the setting of a placebo response, according to a study published online ahead of print October 30 in JAMA Neurology. Researchers randomized 20 patients to unilateral focused ultrasound thalamotomy and seven to a sham procedure. Twenty-six participants were male, and the median age was 67.8. The predefined primary outcomes were safety and difference in improvement between groups at three months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor. On-medication median tremor scores improved 62% from a baseline of 17 points following focused ultrasound thalamotomy, and 22% from a baseline of 23 points after sham procedures.
Bond AE, Shah BB, Huss DS, et al. Safety and efficacy of focused ultrasound thalamotomy for patients with medication-refractory, tremor-dominant Parkinson disease: a randomized clinical trial. JAMA Neurol. 2017 Oct 30 [Epub ahead of print].
Biomarker of Multiple Sclerosis Identified
MicroRNAs associated with circulating exosomes are informative biomarkers for the diagnosis of multiple sclerosis (MS) and for predicting disease subtype with a high degree of accuracy, according to a study published October 30 in Scientific Reports. Exosome-associated microRNAs in serum samples from 25 patients with MS and 11 matched healthy controls were profiled using small RNA next-generation sequencing. In addition to identifying biomarkers that distinguish healthy people from people with MS, researchers identified nine microRNA molecules that differentiate between relapsing-remitting MS and progressive MS. Study authors also validated eight out of nine microRNA molecules in an independent group of 11 patients with progressive MS. The blood test may enable earlier treatment of MS and help neurologists identify the most appropriate treatment for a patient, said the authors.
Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017;7(1):14293.
Does Oral Anticoagulation in Atrial Fibrillation Reduce Dementia Risk?
The risk of dementia in patients with atrial fibrillation is higher among those who do not take oral anticoagulants, compared with those who do, according to a study published online ahead of print October 24 in the European Heart Journal. This Swedish retrospective registry study included 444,106 patients with hospital diagnosis of atrial fibrillation and no previous diagnosis of dementia between 2006 and 2014. At baseline, 54% of patients were not taking oral anticoagulants. Investigators performed propensity score matching, used falsification end points, and performed intention-to-treat and on-treatment analyses. Patients on anticoagulant treatment at baseline had a 29% lower risk of dementia than patients without anticoagulant treatment, and a 48% lower risk analyzed on treatment. Direct comparison between new oral anticoagulants and warfarin showed no difference.
Friberg L, Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J. 2017 Oct 24 [Epub ahead of print].
Dendritic Spine Plasticity May Protect Against Dementia
Dendritic spine plasticity protects older people with Alzheimer’s disease pathology from developing dementia, according to a study published in the October issue of Annals of Neurology. Researchers compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 of the dorsolateral prefrontal cortex in 12 age-matched healthy controls, eight controls with Alzheimer’s disease pathology (CAD), and 21 people with Alzheimer’s disease. The investigators created digital reconstructions of dendritic structure for morphologic analyses. Spine density was similar among control and CAD cases, but was reduced significantly in Alzheimer’s disease. Thin and mushroom spines were reduced significantly in Alzheimer’s disease, compared with CAD brains, and stubby spine density was decreased significantly in CAD and Alzheimer’s disease, compared with controls.
Boros BD, Greathouse KM, Gentry EG, et al. Dendritic spines provide cognitive resilience against Alzheimer’s disease. Ann Neurol. 2017;82(4):602-614.
Opioid Versus Nonopioid Treatment for Acute Migraine
IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the emergency department and should not be used as first-line therapy, according to a study published online ahead of print October 18 in Neurology. This study was conducted in two emergency departments and included patients who met international criteria for migraine if they had not used an opioid within the previous month. Participants received hydromorphone (1 mg) or prochlorperazine (10 mg) and diphenhydramine (25 mg). The primary outcome was achieving a headache level of mild or none within two hours of treatment and maintaining that level for 48 hours without rescue medication. Approximately 60% of the prochlorperazine arm achieved the primary outcome, compared with 31% of the hydromorphone arm.
Friedman BW, Irizarry E, Solorzano C, et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. 2017 Oct 18 [Epub ahead of print].
Frontotemporal Degeneration Entails High Economic Burden
The economic burden of frontotemporal degeneration may be twice as high as that of Alzheimer’s disease, according to a study published online ahead of print October 4 in Neurology. An Internet survey was administered to 674 primary caregivers of patients with behavioral-variant frontotemporal degeneration, primary progressive aphasia, frontotemporal degeneration with motor neuron disease, corticobasal syndrome, or progressive supranuclear palsy. Direct costs for these disorders equaled $47,916, and indirect costs equaled $71,737. Patients age 65 or older, those with later stages of disease, and those with behavioral-variant frontotemporal degeneration had higher direct costs, while patients younger than 65 and men had higher indirect costs. Mean household income ranged from $75,000 to $99,000 at 12 months before frontotemporal degeneration diagnosis, but declined to $50,000 to $59,999 after diagnosis.
Galvin JE, Howard DH, Denny SS, et al. The social and economic burden of frontotemporal degeneration. Neurology. 2017 Oct 4 [Epub ahead of print].
FDA Approves Vimpat for Partial-Onset Seizures in Pediatric Epilepsy
The FDA has approved a label extension for Vimpat (lacosamide) CV as an oral option for the treatment of partial-onset seizures in pediatric patients age 4 and older. The safety and efficacy profile of Vimpat as monotherapy and adjunctive therapy for the treatment of partial-onset seizures in adults was previously established in four multicenter, randomized, controlled clinical trials. The expanded indication for Vimpat is based on extrapolation of efficacy data from adults to children and is supported by safety and pharmacokinetics data collected in children. Adverse reactions in pediatric patients are similar to those in adult patients. UCB, which markets Vimpat, is headquartered in Brussels.
—Kimberly Williams
Brain Glucose Level Is Associated With Alzheimer’s Disease Severity
Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to Alzheimer’s disease pathogenesis, according to a study published online ahead of print October 19 in Alzheimer’s & Dementia. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, researchers measured brain glucose concentration and assessed the ratios of serine, glycine, and alanine to glucose. Investigators also quantified protein levels of the neuronal and astrocytic glucose transporters. In addition, study authors assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower neuronal glucose transporters were related to severity of Alzheimer’s disease pathology and the expression of Alzheimer’s disease symptoms. Longitudinal increases in fasting plasma glucose levels were associated with higher brain tissue glucose concentrations.
An Y, Varma VR, Varma S, et al. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. 2017 Oct 19 [Epub ahead of print].
Is it Better to Be Asleep or Awake for DBS Implantation?
Patients with Parkinson’s disease who undergo deep brain stimulation (DBS) device implantation while asleep have better communication, cognition, and speech outcomes, according to a study published November 7 in Neurology. Thirty DBS candidates with Parkinson’s disease underwent imaging-guided implantation while asleep. Their six-month outcomes were compared to those of 39 patients who previously had undergone implantation while awake.
Brodsky MA, Anderson S, Murchison C, et al. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease. Neurology. 2017;89(19):1944-1950.
Is Inflammation During Middle Age Linked to Brain Shrinkage Later On?
People with blood biomarkers of inflammation during midlife may have more brain shrinkage decades later than people without these biomarkers, according to a study published online ahead of print November 1 in Neurology. Plasma levels of fibrinogen, albumin, white blood cells, von Willebrand factor, and Factor VIII were assessed at baseline in 1,633 participants in the Atherosclerosis Risk in Communities Study. Each standard deviation increase in midlife inflammation composite score was associated with 1,788 mm3 greater ventricular volume, 110 mm3 smaller hippocampal volume, 519 mm3 smaller occipital volume, and 532 mm3 smaller Alzheimer disease signature region volumes and reduced episodic memory 24 years later. Compared with participants with no elevated midlife inflammatory markers, participants with elevations in three or more markers had 5% smaller hippocampal and Alzheimer’s disease signature region volumes.
Walker KA, Hoogeveen RC, Folsom AR, et al. Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study. Neurology. 2017 Nov 1 [Epub ahead of print].
Novel Wristbands Improve Seizure Detection
Wrist-worn convulsive seizure detectors provide more accurate seizure counts than previous automated detectors do, while maintaining tolerable false alarm rates (FAR) for ambulatory monitoring, according to a study published in the November issue of Epilepsia. Hand-annotated video-EEG seizure events were collected from 69 patients at six clinical sites. Two novel wristbands and one current wristband were used to record electrodermal activity and accelerometer signals, obtaining 5,928 hours of data, including 55 convulsive epileptic seizures in 22 patients. The novel wristbands consistently outperformed the current wristband. The best wristband had a sensitivity of 94.55% and an FAR of 0.2 events per day. When increasing the sensitivity to 100%, the FAR was as much as 13 times lower than with the current detector. Automatically estimated seizure durations were correlated with true durations.
Onorati F, Regalia G, Caborni C, et al. Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors. Epilepsia. 2017;58(11):1870-1879.
Focused Ultrasound Reduces Parkinson’s Disease Tremor
Focused ultrasound thalamotomy for patients with tremor-dominant Parkinson’s disease demonstrates improvement in medication-refractory tremor by Clinical Rating Scale for Tremor assessments, even in the setting of a placebo response, according to a study published online ahead of print October 30 in JAMA Neurology. Researchers randomized 20 patients to unilateral focused ultrasound thalamotomy and seven to a sham procedure. Twenty-six participants were male, and the median age was 67.8. The predefined primary outcomes were safety and difference in improvement between groups at three months in the on-medication treated hand tremor subscore from the Clinical Rating Scale for Tremor. On-medication median tremor scores improved 62% from a baseline of 17 points following focused ultrasound thalamotomy, and 22% from a baseline of 23 points after sham procedures.
Bond AE, Shah BB, Huss DS, et al. Safety and efficacy of focused ultrasound thalamotomy for patients with medication-refractory, tremor-dominant Parkinson disease: a randomized clinical trial. JAMA Neurol. 2017 Oct 30 [Epub ahead of print].
Biomarker of Multiple Sclerosis Identified
MicroRNAs associated with circulating exosomes are informative biomarkers for the diagnosis of multiple sclerosis (MS) and for predicting disease subtype with a high degree of accuracy, according to a study published October 30 in Scientific Reports. Exosome-associated microRNAs in serum samples from 25 patients with MS and 11 matched healthy controls were profiled using small RNA next-generation sequencing. In addition to identifying biomarkers that distinguish healthy people from people with MS, researchers identified nine microRNA molecules that differentiate between relapsing-remitting MS and progressive MS. Study authors also validated eight out of nine microRNA molecules in an independent group of 11 patients with progressive MS. The blood test may enable earlier treatment of MS and help neurologists identify the most appropriate treatment for a patient, said the authors.
Ebrahimkhani S, Vafaee F, Young PE, et al. Exosomal microRNA signatures in multiple sclerosis reflect disease status. Sci Rep. 2017;7(1):14293.
Does Oral Anticoagulation in Atrial Fibrillation Reduce Dementia Risk?
The risk of dementia in patients with atrial fibrillation is higher among those who do not take oral anticoagulants, compared with those who do, according to a study published online ahead of print October 24 in the European Heart Journal. This Swedish retrospective registry study included 444,106 patients with hospital diagnosis of atrial fibrillation and no previous diagnosis of dementia between 2006 and 2014. At baseline, 54% of patients were not taking oral anticoagulants. Investigators performed propensity score matching, used falsification end points, and performed intention-to-treat and on-treatment analyses. Patients on anticoagulant treatment at baseline had a 29% lower risk of dementia than patients without anticoagulant treatment, and a 48% lower risk analyzed on treatment. Direct comparison between new oral anticoagulants and warfarin showed no difference.
Friberg L, Rosenqvist M. Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J. 2017 Oct 24 [Epub ahead of print].
Dendritic Spine Plasticity May Protect Against Dementia
Dendritic spine plasticity protects older people with Alzheimer’s disease pathology from developing dementia, according to a study published in the October issue of Annals of Neurology. Researchers compared dendritic spines within layer II and III pyramidal neuron dendrites in Brodmann area 46 of the dorsolateral prefrontal cortex in 12 age-matched healthy controls, eight controls with Alzheimer’s disease pathology (CAD), and 21 people with Alzheimer’s disease. The investigators created digital reconstructions of dendritic structure for morphologic analyses. Spine density was similar among control and CAD cases, but was reduced significantly in Alzheimer’s disease. Thin and mushroom spines were reduced significantly in Alzheimer’s disease, compared with CAD brains, and stubby spine density was decreased significantly in CAD and Alzheimer’s disease, compared with controls.
Boros BD, Greathouse KM, Gentry EG, et al. Dendritic spines provide cognitive resilience against Alzheimer’s disease. Ann Neurol. 2017;82(4):602-614.
Opioid Versus Nonopioid Treatment for Acute Migraine
IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the emergency department and should not be used as first-line therapy, according to a study published online ahead of print October 18 in Neurology. This study was conducted in two emergency departments and included patients who met international criteria for migraine if they had not used an opioid within the previous month. Participants received hydromorphone (1 mg) or prochlorperazine (10 mg) and diphenhydramine (25 mg). The primary outcome was achieving a headache level of mild or none within two hours of treatment and maintaining that level for 48 hours without rescue medication. Approximately 60% of the prochlorperazine arm achieved the primary outcome, compared with 31% of the hydromorphone arm.
Friedman BW, Irizarry E, Solorzano C, et al. Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine. Neurology. 2017 Oct 18 [Epub ahead of print].
Frontotemporal Degeneration Entails High Economic Burden
The economic burden of frontotemporal degeneration may be twice as high as that of Alzheimer’s disease, according to a study published online ahead of print October 4 in Neurology. An Internet survey was administered to 674 primary caregivers of patients with behavioral-variant frontotemporal degeneration, primary progressive aphasia, frontotemporal degeneration with motor neuron disease, corticobasal syndrome, or progressive supranuclear palsy. Direct costs for these disorders equaled $47,916, and indirect costs equaled $71,737. Patients age 65 or older, those with later stages of disease, and those with behavioral-variant frontotemporal degeneration had higher direct costs, while patients younger than 65 and men had higher indirect costs. Mean household income ranged from $75,000 to $99,000 at 12 months before frontotemporal degeneration diagnosis, but declined to $50,000 to $59,999 after diagnosis.
Galvin JE, Howard DH, Denny SS, et al. The social and economic burden of frontotemporal degeneration. Neurology. 2017 Oct 4 [Epub ahead of print].
FDA Approves Vimpat for Partial-Onset Seizures in Pediatric Epilepsy
The FDA has approved a label extension for Vimpat (lacosamide) CV as an oral option for the treatment of partial-onset seizures in pediatric patients age 4 and older. The safety and efficacy profile of Vimpat as monotherapy and adjunctive therapy for the treatment of partial-onset seizures in adults was previously established in four multicenter, randomized, controlled clinical trials. The expanded indication for Vimpat is based on extrapolation of efficacy data from adults to children and is supported by safety and pharmacokinetics data collected in children. Adverse reactions in pediatric patients are similar to those in adult patients. UCB, which markets Vimpat, is headquartered in Brussels.
—Kimberly Williams
New and Noteworthy Information—November 2017
Can a Fatty Diet Increase Relapse Risk in Children With MS?
In children with multiple sclerosis (MS), high energy intake from fat, especially saturated fat, may increase the hazard of relapse, while vegetable intake may be independently protective, according to a study published online ahead of print October 9 in the Journal of Neurology, Neurosurgery & Psychiatry. A total of 219 patients with pediatric relapsing-remitting MS or clinically isolated syndrome with disease onset before age 18 and duration of less than four years were enrolled in a multicenter study that was completed at 11 pediatric MS centers. Investigators used the Block Kids Food Screener to examine dietary intake during the week before enrollment. Each 10% increase in energy intake from fat increased the hazard of relapse by 56%, and each 10% increase in saturated fat tripled this hazard.
Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Oct 9 [Epub ahead of print].
Cooling Reduces Risk of Epilepsy After Perinatal Asphyxia
Administering therapeutic hypothermia to babies with perinatal asphyxia can reduce their risk of epilepsy in childhood, according to a study published online ahead of print September 29 in Epilepsia. From 2006 to 2013, 151 infants with perinatal asphyxia underwent 72 hours of cooling. Clinical and amplitude-integrated EEG with single-channel EEG-verified neonatal seizures were treated with antiepileptic drugs (AEDs). MRI was assessed using a severity score that ranged from 0 to 11. One hundred thirty-four children were assessed at 18–24 months. Babies born after 2007 who received therapeutic hypothermia had a lower rate of epilepsy than those born before this method was introduced. At two years, 6% of the children had epilepsy, and 2% were receiving AEDs. Before therapeutic hypothermia was introduced, the rate of death or moderate or severe disability was about 66%.
Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017 Sep 29 [Epub ahead of print].
Risk Factors Are Increasing in People With Stroke
The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in acute ischemic stroke increased between 2004 and 2014, according to a study published online ahead of print October 11 in Neurology. Researchers used the National Inpatient Sample to identify 922,451 adult hospitalizations for ischemic stroke. In all, 92.5% of patients with stroke had one or more risk factors. Age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively. The prevalence of carotid stenosis, chronic renal failure, and coronary artery disease were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age, race, and sex. The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse increased annually by 1.4%, 2%, 7%, 5%, and 7%, respectively.
Otite FO, Liaw N, Khandelwal P, et al. Increasing prevalence of vascular risk factors in patients with stroke: a call to action. Neurology. 2017 Oct 11 [Epub ahead of print].
Transcranial Direct-Current Stimulation for MS-Related Fatigue
People with multiple sclerosis (MS) who undergo a noninvasive form of electrical brain stimulation have significantly reduced fatigue, according to a study published online ahead of print September 1 in the Multiple Sclerosis Journal. Twenty-seven people with MS were randomized to receive transcranial direct-current stimulation or a placebo while playing a cognitive training game that targets processing speed and working memory. After 20 sessions, participants reported their level of fatigue using the Patient-Reported Outcomes Measurement Information System. Higher numbers correlated with greater fatigue. The researchers reported a statistically significant reduction in the group that underwent transcranial direct-current stimulation, compared with the placebo group. Intervention participants had a 5.6-point drop in fatigue on average, while control participants had a 0.9-point increase in fatigue.
Charvet LE, Dobbs B, Shaw MT, et al. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: results from a randomized, sham-controlled trial. Mult Scler. 2017 Sep 1 [Epub ahead of print].
New Genetic Risk Variants for RLS Identified
Thirteen previously unknown genetic risk variants for restless legs syndrome (RLS) have been identified, according to a study published in the November issue of Lancet Neurology. Researchers combined three genome-wide association studies’ datasets with diagnosis data collected from 2003 to 2017. The latter data came from interviews and questionnaires and included 15,126 cases and 95,725 controls. Significant genome-wide signals were tested for replication in an independent genome-wide association study of 30,770 cases and 286,913 controls. Investigators identified and replicated 13 new risk loci for RLS and confirmed six previously identified risk loci. MEIS1 was confirmed as the strongest genetic risk factor for RLS. Gene prioritization, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance, synapse formation, and neuronal specification.
Schormair B, Zhao C, Bell S, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol. 2017;16(11):898-907.
High Blood Pressure Associated With Increased Dementia Risk in Women
Hypertension is more common in men, but is only associated with dementia risk in women, according to a study published online ahead of print October 4 in Neurology. Researchers evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7) and 1978 to 1985 (mean age, 44.3) and were members as of January 1, 1996 (mean age, 59.8). A total of 532 people were diagnosed with dementia. Mid-adulthood (circa age 44) hypertension was associated with 65% increased dementia risk among women, but not among men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women, compared with stable normotension. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.
Gilsanz P, Mayeda ER, Glymour MM, et al. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4 [Epub ahead of print].
A Risk Factor for Major Bleeding During Treatment With NOACs
Among patients taking non-vitamin K oral anticoagulants (NOACs) for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin, compared with the use of NOACs alone, is associated with increased risk of major bleeding, according to a study published October 3 in JAMA. Researchers retrospectively examined data for 91,330 patients with nonvalvular atrial fibrillation who received at least one NOAC prescription of dabigatran, rivaroxaban, or apixaban from 2012 through 2016. They analyzed the bleeding risk associated with the concurrent use of 12 commonly prescribed medications. A total of 4,770 major bleeding events occurred. The incidence rate of major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. Physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs, the researchers said.
Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250-1259.
Discontinuing Aspirin Therapy May Increase Cardiovascular Risk
In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding is associated with a greater-than-30% increased risk of cardiovascular events, according to a study published September 26 in Circulation. Researchers performed a cohort study of 601,527 participants taking low-dose aspirin for heart attack and stroke prevention between 2005 and 2009. Participants were older than 40, cancer-free, and had an adherence rate of 80% or greater during the first year of treatment. During a median of 3.0 years of follow-up, 62,690 cardiovascular events were reported. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37), corresponding to an additional cardiovascular event observed per year in one of every 74 patients who discontinued aspirin.
Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: a Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.
FDA Approves 80-mg Ingrezza Capsule for Tardive Dyskinesia
The FDA has approved an 80-mg capsule of Ingrezza (valbenazine) for the treatment of adults with tardive dyskinesia. In clinical studies, Ingrezza 80 mg provided significant, rapid, and meaningful improvement in tardive dyskinesia severity, compared with placebo, at six weeks. Results were seen as early as two weeks, and continued reductions were observed through 48 weeks of treatment. The drug was FDA-approved in April and has been available as 40-mg capsules. Neurocrine Biosciences markets Ingrezza.
FDA Approves Generic Version of Copaxone
The FDA has approved Mylan’s glatiramer acetate injection 40 mg/mL for thrice-weekly injection. The drug is a substitutable generic version of Teva’s Copaxone 40 mg/mL. The agency also approved Mylan’s glatiramer acetate injection 20 mg/mL for once-daily injection, a substitutable generic version of Teva’s Copaxone 20 mg/mL. Both products are indicated for the treatment of patients with relapsing forms of multiple sclerosis. As part of its applications, Mylan submitted side-by-side analyses demonstrating that its glatiramer acetate injections have the same active ingredient, dosage form, route of administration, and strength as their branded counterpart.
FDA Approves Gocovri for Dyskinesia in Parkinson’s Disease
The FDA has approved Gocovri (amantadine) extended-release capsules for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy with or without concomitant dopaminergic medications. Gocovri, previously granted orphan drug status by the FDA, is the first medicine approved by the FDA for this indication. Gocovri is a high-dose (274 mg) formulation of amantadine (equivalent to 340 mg of amantadine HCl) taken once-daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day. Adamas Pharmaceuticals markets the drug.
FDA Has Approved Lyrica CR for Two Indications
The FDA has approved Lyrica CR (pregabalin) extended-release tablets CV as once-daily therapy for the management of neuropathic pain associated with diabetic peripheral neuropathy and the management of postherpetic neuralgia. The efficacy and safety of Lyrica CR in postherpetic neuralgia was established in a randomized placebo-controlled clinical trial conducted in 801 patients with postherpetic neuralgia who entered single-blind treatment with Lyrica CR. In the study, 73.6% of patients in the Lyrica CR group achieved at least 50% improvement in pain intensity, compared with 54.6% in the placebo group. The postherpetic neuralgia data also supported the diabetic peripheral neuropathy indication. Pfizer markets Lyrica CR.
—Kimberly Williams
Can a Fatty Diet Increase Relapse Risk in Children With MS?
In children with multiple sclerosis (MS), high energy intake from fat, especially saturated fat, may increase the hazard of relapse, while vegetable intake may be independently protective, according to a study published online ahead of print October 9 in the Journal of Neurology, Neurosurgery & Psychiatry. A total of 219 patients with pediatric relapsing-remitting MS or clinically isolated syndrome with disease onset before age 18 and duration of less than four years were enrolled in a multicenter study that was completed at 11 pediatric MS centers. Investigators used the Block Kids Food Screener to examine dietary intake during the week before enrollment. Each 10% increase in energy intake from fat increased the hazard of relapse by 56%, and each 10% increase in saturated fat tripled this hazard.
Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Oct 9 [Epub ahead of print].
Cooling Reduces Risk of Epilepsy After Perinatal Asphyxia
Administering therapeutic hypothermia to babies with perinatal asphyxia can reduce their risk of epilepsy in childhood, according to a study published online ahead of print September 29 in Epilepsia. From 2006 to 2013, 151 infants with perinatal asphyxia underwent 72 hours of cooling. Clinical and amplitude-integrated EEG with single-channel EEG-verified neonatal seizures were treated with antiepileptic drugs (AEDs). MRI was assessed using a severity score that ranged from 0 to 11. One hundred thirty-four children were assessed at 18–24 months. Babies born after 2007 who received therapeutic hypothermia had a lower rate of epilepsy than those born before this method was introduced. At two years, 6% of the children had epilepsy, and 2% were receiving AEDs. Before therapeutic hypothermia was introduced, the rate of death or moderate or severe disability was about 66%.
Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017 Sep 29 [Epub ahead of print].
Risk Factors Are Increasing in People With Stroke
The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in acute ischemic stroke increased between 2004 and 2014, according to a study published online ahead of print October 11 in Neurology. Researchers used the National Inpatient Sample to identify 922,451 adult hospitalizations for ischemic stroke. In all, 92.5% of patients with stroke had one or more risk factors. Age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively. The prevalence of carotid stenosis, chronic renal failure, and coronary artery disease were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age, race, and sex. The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse increased annually by 1.4%, 2%, 7%, 5%, and 7%, respectively.
Otite FO, Liaw N, Khandelwal P, et al. Increasing prevalence of vascular risk factors in patients with stroke: a call to action. Neurology. 2017 Oct 11 [Epub ahead of print].
Transcranial Direct-Current Stimulation for MS-Related Fatigue
People with multiple sclerosis (MS) who undergo a noninvasive form of electrical brain stimulation have significantly reduced fatigue, according to a study published online ahead of print September 1 in the Multiple Sclerosis Journal. Twenty-seven people with MS were randomized to receive transcranial direct-current stimulation or a placebo while playing a cognitive training game that targets processing speed and working memory. After 20 sessions, participants reported their level of fatigue using the Patient-Reported Outcomes Measurement Information System. Higher numbers correlated with greater fatigue. The researchers reported a statistically significant reduction in the group that underwent transcranial direct-current stimulation, compared with the placebo group. Intervention participants had a 5.6-point drop in fatigue on average, while control participants had a 0.9-point increase in fatigue.
Charvet LE, Dobbs B, Shaw MT, et al. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: results from a randomized, sham-controlled trial. Mult Scler. 2017 Sep 1 [Epub ahead of print].
New Genetic Risk Variants for RLS Identified
Thirteen previously unknown genetic risk variants for restless legs syndrome (RLS) have been identified, according to a study published in the November issue of Lancet Neurology. Researchers combined three genome-wide association studies’ datasets with diagnosis data collected from 2003 to 2017. The latter data came from interviews and questionnaires and included 15,126 cases and 95,725 controls. Significant genome-wide signals were tested for replication in an independent genome-wide association study of 30,770 cases and 286,913 controls. Investigators identified and replicated 13 new risk loci for RLS and confirmed six previously identified risk loci. MEIS1 was confirmed as the strongest genetic risk factor for RLS. Gene prioritization, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance, synapse formation, and neuronal specification.
Schormair B, Zhao C, Bell S, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol. 2017;16(11):898-907.
High Blood Pressure Associated With Increased Dementia Risk in Women
Hypertension is more common in men, but is only associated with dementia risk in women, according to a study published online ahead of print October 4 in Neurology. Researchers evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7) and 1978 to 1985 (mean age, 44.3) and were members as of January 1, 1996 (mean age, 59.8). A total of 532 people were diagnosed with dementia. Mid-adulthood (circa age 44) hypertension was associated with 65% increased dementia risk among women, but not among men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women, compared with stable normotension. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.
Gilsanz P, Mayeda ER, Glymour MM, et al. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4 [Epub ahead of print].
A Risk Factor for Major Bleeding During Treatment With NOACs
Among patients taking non-vitamin K oral anticoagulants (NOACs) for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin, compared with the use of NOACs alone, is associated with increased risk of major bleeding, according to a study published October 3 in JAMA. Researchers retrospectively examined data for 91,330 patients with nonvalvular atrial fibrillation who received at least one NOAC prescription of dabigatran, rivaroxaban, or apixaban from 2012 through 2016. They analyzed the bleeding risk associated with the concurrent use of 12 commonly prescribed medications. A total of 4,770 major bleeding events occurred. The incidence rate of major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. Physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs, the researchers said.
Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250-1259.
Discontinuing Aspirin Therapy May Increase Cardiovascular Risk
In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding is associated with a greater-than-30% increased risk of cardiovascular events, according to a study published September 26 in Circulation. Researchers performed a cohort study of 601,527 participants taking low-dose aspirin for heart attack and stroke prevention between 2005 and 2009. Participants were older than 40, cancer-free, and had an adherence rate of 80% or greater during the first year of treatment. During a median of 3.0 years of follow-up, 62,690 cardiovascular events were reported. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37), corresponding to an additional cardiovascular event observed per year in one of every 74 patients who discontinued aspirin.
Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: a Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.
FDA Approves 80-mg Ingrezza Capsule for Tardive Dyskinesia
The FDA has approved an 80-mg capsule of Ingrezza (valbenazine) for the treatment of adults with tardive dyskinesia. In clinical studies, Ingrezza 80 mg provided significant, rapid, and meaningful improvement in tardive dyskinesia severity, compared with placebo, at six weeks. Results were seen as early as two weeks, and continued reductions were observed through 48 weeks of treatment. The drug was FDA-approved in April and has been available as 40-mg capsules. Neurocrine Biosciences markets Ingrezza.
FDA Approves Generic Version of Copaxone
The FDA has approved Mylan’s glatiramer acetate injection 40 mg/mL for thrice-weekly injection. The drug is a substitutable generic version of Teva’s Copaxone 40 mg/mL. The agency also approved Mylan’s glatiramer acetate injection 20 mg/mL for once-daily injection, a substitutable generic version of Teva’s Copaxone 20 mg/mL. Both products are indicated for the treatment of patients with relapsing forms of multiple sclerosis. As part of its applications, Mylan submitted side-by-side analyses demonstrating that its glatiramer acetate injections have the same active ingredient, dosage form, route of administration, and strength as their branded counterpart.
FDA Approves Gocovri for Dyskinesia in Parkinson’s Disease
The FDA has approved Gocovri (amantadine) extended-release capsules for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy with or without concomitant dopaminergic medications. Gocovri, previously granted orphan drug status by the FDA, is the first medicine approved by the FDA for this indication. Gocovri is a high-dose (274 mg) formulation of amantadine (equivalent to 340 mg of amantadine HCl) taken once-daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day. Adamas Pharmaceuticals markets the drug.
FDA Has Approved Lyrica CR for Two Indications
The FDA has approved Lyrica CR (pregabalin) extended-release tablets CV as once-daily therapy for the management of neuropathic pain associated with diabetic peripheral neuropathy and the management of postherpetic neuralgia. The efficacy and safety of Lyrica CR in postherpetic neuralgia was established in a randomized placebo-controlled clinical trial conducted in 801 patients with postherpetic neuralgia who entered single-blind treatment with Lyrica CR. In the study, 73.6% of patients in the Lyrica CR group achieved at least 50% improvement in pain intensity, compared with 54.6% in the placebo group. The postherpetic neuralgia data also supported the diabetic peripheral neuropathy indication. Pfizer markets Lyrica CR.
—Kimberly Williams
Can a Fatty Diet Increase Relapse Risk in Children With MS?
In children with multiple sclerosis (MS), high energy intake from fat, especially saturated fat, may increase the hazard of relapse, while vegetable intake may be independently protective, according to a study published online ahead of print October 9 in the Journal of Neurology, Neurosurgery & Psychiatry. A total of 219 patients with pediatric relapsing-remitting MS or clinically isolated syndrome with disease onset before age 18 and duration of less than four years were enrolled in a multicenter study that was completed at 11 pediatric MS centers. Investigators used the Block Kids Food Screener to examine dietary intake during the week before enrollment. Each 10% increase in energy intake from fat increased the hazard of relapse by 56%, and each 10% increase in saturated fat tripled this hazard.
Azary S, Schreiner T, Graves J, et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Oct 9 [Epub ahead of print].
Cooling Reduces Risk of Epilepsy After Perinatal Asphyxia
Administering therapeutic hypothermia to babies with perinatal asphyxia can reduce their risk of epilepsy in childhood, according to a study published online ahead of print September 29 in Epilepsia. From 2006 to 2013, 151 infants with perinatal asphyxia underwent 72 hours of cooling. Clinical and amplitude-integrated EEG with single-channel EEG-verified neonatal seizures were treated with antiepileptic drugs (AEDs). MRI was assessed using a severity score that ranged from 0 to 11. One hundred thirty-four children were assessed at 18–24 months. Babies born after 2007 who received therapeutic hypothermia had a lower rate of epilepsy than those born before this method was introduced. At two years, 6% of the children had epilepsy, and 2% were receiving AEDs. Before therapeutic hypothermia was introduced, the rate of death or moderate or severe disability was about 66%.
Liu X, Jary S, Cowan F, Thoresen M. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017 Sep 29 [Epub ahead of print].
Risk Factors Are Increasing in People With Stroke
The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse in acute ischemic stroke increased between 2004 and 2014, according to a study published online ahead of print October 11 in Neurology. Researchers used the National Inpatient Sample to identify 922,451 adult hospitalizations for ischemic stroke. In all, 92.5% of patients with stroke had one or more risk factors. Age- and sex-adjusted prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse were 79%, 34%, 47%, 15%, and 2%, respectively. The prevalence of carotid stenosis, chronic renal failure, and coronary artery disease were 13%, 12%, and 27%, respectively. Risk factor prevalence varied by age, race, and sex. The prevalence of hypertension, diabetes, dyslipidemia, smoking, and drug abuse increased annually by 1.4%, 2%, 7%, 5%, and 7%, respectively.
Otite FO, Liaw N, Khandelwal P, et al. Increasing prevalence of vascular risk factors in patients with stroke: a call to action. Neurology. 2017 Oct 11 [Epub ahead of print].
Transcranial Direct-Current Stimulation for MS-Related Fatigue
People with multiple sclerosis (MS) who undergo a noninvasive form of electrical brain stimulation have significantly reduced fatigue, according to a study published online ahead of print September 1 in the Multiple Sclerosis Journal. Twenty-seven people with MS were randomized to receive transcranial direct-current stimulation or a placebo while playing a cognitive training game that targets processing speed and working memory. After 20 sessions, participants reported their level of fatigue using the Patient-Reported Outcomes Measurement Information System. Higher numbers correlated with greater fatigue. The researchers reported a statistically significant reduction in the group that underwent transcranial direct-current stimulation, compared with the placebo group. Intervention participants had a 5.6-point drop in fatigue on average, while control participants had a 0.9-point increase in fatigue.
Charvet LE, Dobbs B, Shaw MT, et al. Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: results from a randomized, sham-controlled trial. Mult Scler. 2017 Sep 1 [Epub ahead of print].
New Genetic Risk Variants for RLS Identified
Thirteen previously unknown genetic risk variants for restless legs syndrome (RLS) have been identified, according to a study published in the November issue of Lancet Neurology. Researchers combined three genome-wide association studies’ datasets with diagnosis data collected from 2003 to 2017. The latter data came from interviews and questionnaires and included 15,126 cases and 95,725 controls. Significant genome-wide signals were tested for replication in an independent genome-wide association study of 30,770 cases and 286,913 controls. Investigators identified and replicated 13 new risk loci for RLS and confirmed six previously identified risk loci. MEIS1 was confirmed as the strongest genetic risk factor for RLS. Gene prioritization, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance, synapse formation, and neuronal specification.
Schormair B, Zhao C, Bell S, et al. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis. Lancet Neurol. 2017;16(11):898-907.
High Blood Pressure Associated With Increased Dementia Risk in Women
Hypertension is more common in men, but is only associated with dementia risk in women, according to a study published online ahead of print October 4 in Neurology. Researchers evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age, 32.7) and 1978 to 1985 (mean age, 44.3) and were members as of January 1, 1996 (mean age, 59.8). A total of 532 people were diagnosed with dementia. Mid-adulthood (circa age 44) hypertension was associated with 65% increased dementia risk among women, but not among men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women, compared with stable normotension. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.
Gilsanz P, Mayeda ER, Glymour MM, et al. Female sex, early-onset hypertension, and risk of dementia. Neurology. 2017 Oct 4 [Epub ahead of print].
A Risk Factor for Major Bleeding During Treatment With NOACs
Among patients taking non-vitamin K oral anticoagulants (NOACs) for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin, compared with the use of NOACs alone, is associated with increased risk of major bleeding, according to a study published October 3 in JAMA. Researchers retrospectively examined data for 91,330 patients with nonvalvular atrial fibrillation who received at least one NOAC prescription of dabigatran, rivaroxaban, or apixaban from 2012 through 2016. They analyzed the bleeding risk associated with the concurrent use of 12 commonly prescribed medications. A total of 4,770 major bleeding events occurred. The incidence rate of major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. Physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs, the researchers said.
Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA. 2017;318(13):1250-1259.
Discontinuing Aspirin Therapy May Increase Cardiovascular Risk
In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding is associated with a greater-than-30% increased risk of cardiovascular events, according to a study published September 26 in Circulation. Researchers performed a cohort study of 601,527 participants taking low-dose aspirin for heart attack and stroke prevention between 2005 and 2009. Participants were older than 40, cancer-free, and had an adherence rate of 80% or greater during the first year of treatment. During a median of 3.0 years of follow-up, 62,690 cardiovascular events were reported. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37), corresponding to an additional cardiovascular event observed per year in one of every 74 patients who discontinued aspirin.
Sundström J, Hedberg J, Thuresson M, et al. Low-dose aspirin discontinuation and risk of cardiovascular events: a Swedish nationwide, population-based cohort study. Circulation. 2017;136(13):1183-1192.
FDA Approves 80-mg Ingrezza Capsule for Tardive Dyskinesia
The FDA has approved an 80-mg capsule of Ingrezza (valbenazine) for the treatment of adults with tardive dyskinesia. In clinical studies, Ingrezza 80 mg provided significant, rapid, and meaningful improvement in tardive dyskinesia severity, compared with placebo, at six weeks. Results were seen as early as two weeks, and continued reductions were observed through 48 weeks of treatment. The drug was FDA-approved in April and has been available as 40-mg capsules. Neurocrine Biosciences markets Ingrezza.
FDA Approves Generic Version of Copaxone
The FDA has approved Mylan’s glatiramer acetate injection 40 mg/mL for thrice-weekly injection. The drug is a substitutable generic version of Teva’s Copaxone 40 mg/mL. The agency also approved Mylan’s glatiramer acetate injection 20 mg/mL for once-daily injection, a substitutable generic version of Teva’s Copaxone 20 mg/mL. Both products are indicated for the treatment of patients with relapsing forms of multiple sclerosis. As part of its applications, Mylan submitted side-by-side analyses demonstrating that its glatiramer acetate injections have the same active ingredient, dosage form, route of administration, and strength as their branded counterpart.
FDA Approves Gocovri for Dyskinesia in Parkinson’s Disease
The FDA has approved Gocovri (amantadine) extended-release capsules for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy with or without concomitant dopaminergic medications. Gocovri, previously granted orphan drug status by the FDA, is the first medicine approved by the FDA for this indication. Gocovri is a high-dose (274 mg) formulation of amantadine (equivalent to 340 mg of amantadine HCl) taken once-daily at bedtime that delivers consistently high levels of amantadine from the morning and throughout the day. Adamas Pharmaceuticals markets the drug.
FDA Has Approved Lyrica CR for Two Indications
The FDA has approved Lyrica CR (pregabalin) extended-release tablets CV as once-daily therapy for the management of neuropathic pain associated with diabetic peripheral neuropathy and the management of postherpetic neuralgia. The efficacy and safety of Lyrica CR in postherpetic neuralgia was established in a randomized placebo-controlled clinical trial conducted in 801 patients with postherpetic neuralgia who entered single-blind treatment with Lyrica CR. In the study, 73.6% of patients in the Lyrica CR group achieved at least 50% improvement in pain intensity, compared with 54.6% in the placebo group. The postherpetic neuralgia data also supported the diabetic peripheral neuropathy indication. Pfizer markets Lyrica CR.
—Kimberly Williams
New and Noteworthy Information—October 2017
Is Vitamin D Deficiency a Risk Factor for MS?
Vitamin D deficiency is a risk factor for multiple sclerosis (MS), according to a study published online ahead of print September 13 in Neurology. Researchers conducted a prospective nested case-control study among more than 800,000 women in the Finnish Maternity Cohort who had blood samples taken during pregnancy. Investigators identified 1,092 women with MS diagnosed an average of nine years after giving the blood samples. Researchers compared their vitamin D levels with those of 2,123 women who did not develop MS. Each 50 nmol/L increase in vitamin D levels in the blood was associated with a 39% reduced risk of developing MS. In addition, women who had deficient levels of vitamin D (ie, < 30 nmol/L) had a 43% higher risk of MS, compared with women who had adequate levels of vitamin D (ie, ≥ 50 nmol/L).
Munger KL, Hongell K, Åivo J, et al. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. 2017 Sep 13 [Epub ahead of print].
Can Eye Changes Signal Frontotemporal Degeneration?
Frontotemporal degeneration (FTD) is associated with outer retina thinning, and this thinning correlates with disease severity, according to a cross-sectional study published online ahead of print September 8 in Neurology. Researchers examined retinal structure using standard spectral-domain optical coherence tomography in 38 consecutively enrolled patients with FTD and 44 controls. The researchers excluded patients with presumed Alzheimer’s disease, eyes with poor image quality, or confounding diseases. Adjusting for age, sex, and race, patients with FTD had a thinner outer retina, compared with controls. Patients with FTD also had a thinner outer nuclear layer and ellipsoid zone, compared with controls. The groups had similar thicknesses for inner retinal layers.
Kim BJ, Irwin DJ, Song D, et al. Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration. Neurology. 2017 Sep 8 [Epub ahead of print].
A New Diagnostic Test for Alzheimer’s Disease
Blood sample analysis may help diagnose Alzheimer’s disease and distinguish between different types of neurodegenerative disorders, according to a study published online ahead of print September 5 in the Proceedings of the National Academy of Sciences. Investigators used attenuated total reflection FTIR spectroscopy combined with chemometric techniques to analyze blood plasma samples from 347 participants with neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of APOE ε4 information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. The test segregated Alzheimer’s disease from dementia with Lewy bodies (n = 34) with 90% sensitivity and specificity.
Paraskevaidi M, Morais CLM, Lima KMG, et al. Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood. Proc Natl Acad Sci U S A. 2017 Sep 5 [Epub ahead of print].
New Indication for Briviact CV
The FDA has approved a supplemental new drug application for Briviact (brivaracetam) CV as monotherapy for partial-onset seizures in patients age 16 and older with epilepsy. Briviact previously was approved as adjunctive treatment for partial-onset seizures in this age group. UCB, which markets Briviact, applied for the monotherapy indication after the FDA advised that it is acceptable to extrapolate the efficacy and safety of drugs approved as adjunctive therapy for the treatment of partial-onset seizures to their use as monotherapy for the treatment of partial-onset seizures. Gradual dose escalation is not required when initiating treatment with Briviact for monotherapy or adjunctive therapy, which allows clinicians to initiate treatment at a therapeutic dose. Briviact formulations include film-coated tablets, oral solution, and injection. UCB is headquartered in Brussels.
Less REM Sleep Is Associated With Greater Dementia Risk
REM sleep may be associated with risk of dementia, according to a study published online ahead of print August 23 in Neurology. Researchers examined associations between sleep architecture and the prospective risk of incident dementia in a subset of 321 Framingham Heart Study Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998, and were older than 60 at the time of sleep assessment (mean age, 67; 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for up to 19 years for incident dementia. Researchers observed 32 cases of incident dementia. Each percentage reduction in REM sleep was associated with an approximately 9% increase in the risk of incident dementia (hazard ratio, 0.91).
Pase MP, Himali JJ, Grima NA, et al. Sleep architecture and the risk of incident dementia in the community. Neurology. 2017 Aug 23 [Epub ahead of print].
Mononucleosis May Increase Risk of MS
Epstein-Barr nuclear antigen-1 seropositivty is independently associated with increased risk of multiple sclerosis (MS) or clinically isolated syndrome (CIS), according to a study published online ahead of print August 30 in Neurology. Researchers recruited 1,090 black, Hispanic, and white people with MS or CIS and matched controls over a three-year period. Participants were tested for the Epstein-Barr virus antibody and were asked whether they had ever had mononucleosis. Blacks who had had mononucleosis were more than four times more likely to develop MS, compared with those who had not had mononucleosis. Hispanics and whites who had had mononucleosis were nearly four times and two times, respectively, more likely to develop MS or CIS, compared with those who had not had mononucleosis.
Langer-Gould A, Wu J, Lucas R, et al. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: a multiethnic study. Neurology. 2017 Aug 30 [Epub ahead of print].
Asthma Medicine May Decrease Risk of Parkinson’s Disease
Salbutamol, a brain-penetrant asthma medication, is associated with reduced risk of Parkinson’s disease, according to a study published September 1 in Science. Researchers used an unbiased screen targeting endogenous gene expression to discover that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene. Research has indicated that excess production of α-synuclein may be a causative factor in Parkinson’s disease. Over 11 years of follow-up in four million Norwegians, the β2AR agonist salbutamol was associated with reduced risk of Parkinson’s disease (rate ratio, 0.66). A β2AR antagonist correlated with increased risk.
Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science. 2017;357(6354):891-898 [Epub ahead of print].
Odds of Developing Alzheimer’s Disease Same for Men and Women With APOE Genotype
Men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing Alzheimer’s disease from age 55 to 85, but women have an increased risk at younger ages, according to a study published online ahead of print August 28 in JAMA Neurology. Researchers analyzed data from 27 studies with nearly 58,000 participants. Homogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks. Age-adjusted odds ratios and 95% confidence intervals for developing mild cognitive impairment and Alzheimer’s disease were calculated for men and women across APOE genotypes. Men and women with the APOE ε3/ε4 genotype from ages 55 to 85 did not show a difference in Alzheimer’s disease risk. Women had an increased risk of Alzheimer’s disease compared with men between the ages of 65 and 75.
Neu SC, Pa J, Kukull W, et al. Apolipoprotein e genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol. 2017 Aug 28 [Epub ahead of print].
Does Dimethyl Fumarate Prevent MS Reactivation After Natalizumab Discontinuation?
Dimethyl fumarate appears generally safe and may be a promising drug for patients at high risk of progressive multifocal leukoencephalopathy (PML) who discontinue natalizumab, according to an article published online ahead of print August 26 in the Journal of Neurology, Neurosurgery and Psychiatry. Thirty-nine patients with relapsing-remitting multiple sclerosis (MS) at high risk of PML were switched from natalizumab to dimethyl fumarate and underwent neurologic and 3T MRI monitoring for two years. Clinical and MRI data regarding the two-year period preceding natalizumab treatment, the two years of natalizumab treatment, and the two years of dimethyl fumarate treatment were collected. During the dimethyl fumarate phase, one or more relapses occurred in five patients (12.8%), increased disability progression occurred in four patients (10.3%), and MRI activity occurred in eight patients (20.5%). Post-natalizumab rebound effect was observed in one patient. Almost 80% of the patients had no evidence of disease activity after two years of dimethyl fumarate treatment. No carryover PML among investigated cases was observed.
Calabrese M, Pitteri M, Farina G, et al. Dimethyl fumarate: a possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events. J Neurol Neurosurg Psychiatry. 2017 Aug 26 [Epub ahead of print].
Austedo Approved for Treatment of Tardive Dyskinesia in Adults
The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of tardive dyskinesia in adults. The approval was based on results from two phase III randomized, double-blind, placebo-controlled, parallel group studies assessing the efficacy and safety of Austedo in reducing the severity of abnormal involuntary movements associated with tardive dyskinesia. Austedo was previously approved in April for the treatment of chorea associated with Huntington’s disease. The most common adverse reactions (ie, 4% of Austedo-treated patients and greater than placebo) in controlled clinical studies of patients with tardive dyskinesia were nasopharyngitis and insomnia. Teva Pharmaceutical Industries, which markets Austedo, is headquartered in Jerusalem.
Orphan Drug Designation Granted for EPX-300
The FDA has granted Orphan Drug Designation for EPX-300 for the treatment of patients with Dravet syndrome. EPX-300 is a repurposed antidepressant that acts via modulation of serotonin signaling pathways. Researchers discovered its potential as a treatment for patients with Dravet syndrome using a phenotype-based zebrafish drug screening platform. Using the zebrafish model for Dravet syndrome, investigators identified drug candidates from a screen of more than 3,000 drugs that suppress seizures and other symptoms associated with neurologic diseases. Epygenix Therapeutics, which is developing EPX-300, is headquartered in Paramus, New Jersey.
FDA Approves Expanded Indication for Aptiom
The FDA has approved a supplemental new drug application to expand the indication for Aptiom (eslicarbazepine acetate) to include treatment of partial-onset seizures in children age 4 to 17. The safety and efficacy of Aptiom as monotherapy and adjunctive therapy for the treatment of partial-onset seizures in adults was established in five multicenter, randomized, controlled clinical trials. Data from three clinical trials supported the safety and tolerability of Aptiom for the treatment of partial-onset seizures in pediatric patients. Pharmacokinetic analyses of adult and pediatric data supported its use in the pediatric population. Aptiom is a once-daily, immediate release drug that can be taken whole or crushed, with or without food. Sunovion Pharmaceuticals, which markets Aptiom, is headquartered in Marlborough, Massachusetts.
—Kimberly Williams
Is Vitamin D Deficiency a Risk Factor for MS?
Vitamin D deficiency is a risk factor for multiple sclerosis (MS), according to a study published online ahead of print September 13 in Neurology. Researchers conducted a prospective nested case-control study among more than 800,000 women in the Finnish Maternity Cohort who had blood samples taken during pregnancy. Investigators identified 1,092 women with MS diagnosed an average of nine years after giving the blood samples. Researchers compared their vitamin D levels with those of 2,123 women who did not develop MS. Each 50 nmol/L increase in vitamin D levels in the blood was associated with a 39% reduced risk of developing MS. In addition, women who had deficient levels of vitamin D (ie, < 30 nmol/L) had a 43% higher risk of MS, compared with women who had adequate levels of vitamin D (ie, ≥ 50 nmol/L).
Munger KL, Hongell K, Åivo J, et al. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. 2017 Sep 13 [Epub ahead of print].
Can Eye Changes Signal Frontotemporal Degeneration?
Frontotemporal degeneration (FTD) is associated with outer retina thinning, and this thinning correlates with disease severity, according to a cross-sectional study published online ahead of print September 8 in Neurology. Researchers examined retinal structure using standard spectral-domain optical coherence tomography in 38 consecutively enrolled patients with FTD and 44 controls. The researchers excluded patients with presumed Alzheimer’s disease, eyes with poor image quality, or confounding diseases. Adjusting for age, sex, and race, patients with FTD had a thinner outer retina, compared with controls. Patients with FTD also had a thinner outer nuclear layer and ellipsoid zone, compared with controls. The groups had similar thicknesses for inner retinal layers.
Kim BJ, Irwin DJ, Song D, et al. Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration. Neurology. 2017 Sep 8 [Epub ahead of print].
A New Diagnostic Test for Alzheimer’s Disease
Blood sample analysis may help diagnose Alzheimer’s disease and distinguish between different types of neurodegenerative disorders, according to a study published online ahead of print September 5 in the Proceedings of the National Academy of Sciences. Investigators used attenuated total reflection FTIR spectroscopy combined with chemometric techniques to analyze blood plasma samples from 347 participants with neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of APOE ε4 information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. The test segregated Alzheimer’s disease from dementia with Lewy bodies (n = 34) with 90% sensitivity and specificity.
Paraskevaidi M, Morais CLM, Lima KMG, et al. Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood. Proc Natl Acad Sci U S A. 2017 Sep 5 [Epub ahead of print].
New Indication for Briviact CV
The FDA has approved a supplemental new drug application for Briviact (brivaracetam) CV as monotherapy for partial-onset seizures in patients age 16 and older with epilepsy. Briviact previously was approved as adjunctive treatment for partial-onset seizures in this age group. UCB, which markets Briviact, applied for the monotherapy indication after the FDA advised that it is acceptable to extrapolate the efficacy and safety of drugs approved as adjunctive therapy for the treatment of partial-onset seizures to their use as monotherapy for the treatment of partial-onset seizures. Gradual dose escalation is not required when initiating treatment with Briviact for monotherapy or adjunctive therapy, which allows clinicians to initiate treatment at a therapeutic dose. Briviact formulations include film-coated tablets, oral solution, and injection. UCB is headquartered in Brussels.
Less REM Sleep Is Associated With Greater Dementia Risk
REM sleep may be associated with risk of dementia, according to a study published online ahead of print August 23 in Neurology. Researchers examined associations between sleep architecture and the prospective risk of incident dementia in a subset of 321 Framingham Heart Study Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998, and were older than 60 at the time of sleep assessment (mean age, 67; 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for up to 19 years for incident dementia. Researchers observed 32 cases of incident dementia. Each percentage reduction in REM sleep was associated with an approximately 9% increase in the risk of incident dementia (hazard ratio, 0.91).
Pase MP, Himali JJ, Grima NA, et al. Sleep architecture and the risk of incident dementia in the community. Neurology. 2017 Aug 23 [Epub ahead of print].
Mononucleosis May Increase Risk of MS
Epstein-Barr nuclear antigen-1 seropositivty is independently associated with increased risk of multiple sclerosis (MS) or clinically isolated syndrome (CIS), according to a study published online ahead of print August 30 in Neurology. Researchers recruited 1,090 black, Hispanic, and white people with MS or CIS and matched controls over a three-year period. Participants were tested for the Epstein-Barr virus antibody and were asked whether they had ever had mononucleosis. Blacks who had had mononucleosis were more than four times more likely to develop MS, compared with those who had not had mononucleosis. Hispanics and whites who had had mononucleosis were nearly four times and two times, respectively, more likely to develop MS or CIS, compared with those who had not had mononucleosis.
Langer-Gould A, Wu J, Lucas R, et al. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: a multiethnic study. Neurology. 2017 Aug 30 [Epub ahead of print].
Asthma Medicine May Decrease Risk of Parkinson’s Disease
Salbutamol, a brain-penetrant asthma medication, is associated with reduced risk of Parkinson’s disease, according to a study published September 1 in Science. Researchers used an unbiased screen targeting endogenous gene expression to discover that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene. Research has indicated that excess production of α-synuclein may be a causative factor in Parkinson’s disease. Over 11 years of follow-up in four million Norwegians, the β2AR agonist salbutamol was associated with reduced risk of Parkinson’s disease (rate ratio, 0.66). A β2AR antagonist correlated with increased risk.
Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science. 2017;357(6354):891-898 [Epub ahead of print].
Odds of Developing Alzheimer’s Disease Same for Men and Women With APOE Genotype
Men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing Alzheimer’s disease from age 55 to 85, but women have an increased risk at younger ages, according to a study published online ahead of print August 28 in JAMA Neurology. Researchers analyzed data from 27 studies with nearly 58,000 participants. Homogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks. Age-adjusted odds ratios and 95% confidence intervals for developing mild cognitive impairment and Alzheimer’s disease were calculated for men and women across APOE genotypes. Men and women with the APOE ε3/ε4 genotype from ages 55 to 85 did not show a difference in Alzheimer’s disease risk. Women had an increased risk of Alzheimer’s disease compared with men between the ages of 65 and 75.
Neu SC, Pa J, Kukull W, et al. Apolipoprotein e genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol. 2017 Aug 28 [Epub ahead of print].
Does Dimethyl Fumarate Prevent MS Reactivation After Natalizumab Discontinuation?
Dimethyl fumarate appears generally safe and may be a promising drug for patients at high risk of progressive multifocal leukoencephalopathy (PML) who discontinue natalizumab, according to an article published online ahead of print August 26 in the Journal of Neurology, Neurosurgery and Psychiatry. Thirty-nine patients with relapsing-remitting multiple sclerosis (MS) at high risk of PML were switched from natalizumab to dimethyl fumarate and underwent neurologic and 3T MRI monitoring for two years. Clinical and MRI data regarding the two-year period preceding natalizumab treatment, the two years of natalizumab treatment, and the two years of dimethyl fumarate treatment were collected. During the dimethyl fumarate phase, one or more relapses occurred in five patients (12.8%), increased disability progression occurred in four patients (10.3%), and MRI activity occurred in eight patients (20.5%). Post-natalizumab rebound effect was observed in one patient. Almost 80% of the patients had no evidence of disease activity after two years of dimethyl fumarate treatment. No carryover PML among investigated cases was observed.
Calabrese M, Pitteri M, Farina G, et al. Dimethyl fumarate: a possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events. J Neurol Neurosurg Psychiatry. 2017 Aug 26 [Epub ahead of print].
Austedo Approved for Treatment of Tardive Dyskinesia in Adults
The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of tardive dyskinesia in adults. The approval was based on results from two phase III randomized, double-blind, placebo-controlled, parallel group studies assessing the efficacy and safety of Austedo in reducing the severity of abnormal involuntary movements associated with tardive dyskinesia. Austedo was previously approved in April for the treatment of chorea associated with Huntington’s disease. The most common adverse reactions (ie, 4% of Austedo-treated patients and greater than placebo) in controlled clinical studies of patients with tardive dyskinesia were nasopharyngitis and insomnia. Teva Pharmaceutical Industries, which markets Austedo, is headquartered in Jerusalem.
Orphan Drug Designation Granted for EPX-300
The FDA has granted Orphan Drug Designation for EPX-300 for the treatment of patients with Dravet syndrome. EPX-300 is a repurposed antidepressant that acts via modulation of serotonin signaling pathways. Researchers discovered its potential as a treatment for patients with Dravet syndrome using a phenotype-based zebrafish drug screening platform. Using the zebrafish model for Dravet syndrome, investigators identified drug candidates from a screen of more than 3,000 drugs that suppress seizures and other symptoms associated with neurologic diseases. Epygenix Therapeutics, which is developing EPX-300, is headquartered in Paramus, New Jersey.
FDA Approves Expanded Indication for Aptiom
The FDA has approved a supplemental new drug application to expand the indication for Aptiom (eslicarbazepine acetate) to include treatment of partial-onset seizures in children age 4 to 17. The safety and efficacy of Aptiom as monotherapy and adjunctive therapy for the treatment of partial-onset seizures in adults was established in five multicenter, randomized, controlled clinical trials. Data from three clinical trials supported the safety and tolerability of Aptiom for the treatment of partial-onset seizures in pediatric patients. Pharmacokinetic analyses of adult and pediatric data supported its use in the pediatric population. Aptiom is a once-daily, immediate release drug that can be taken whole or crushed, with or without food. Sunovion Pharmaceuticals, which markets Aptiom, is headquartered in Marlborough, Massachusetts.
—Kimberly Williams
Is Vitamin D Deficiency a Risk Factor for MS?
Vitamin D deficiency is a risk factor for multiple sclerosis (MS), according to a study published online ahead of print September 13 in Neurology. Researchers conducted a prospective nested case-control study among more than 800,000 women in the Finnish Maternity Cohort who had blood samples taken during pregnancy. Investigators identified 1,092 women with MS diagnosed an average of nine years after giving the blood samples. Researchers compared their vitamin D levels with those of 2,123 women who did not develop MS. Each 50 nmol/L increase in vitamin D levels in the blood was associated with a 39% reduced risk of developing MS. In addition, women who had deficient levels of vitamin D (ie, < 30 nmol/L) had a 43% higher risk of MS, compared with women who had adequate levels of vitamin D (ie, ≥ 50 nmol/L).
Munger KL, Hongell K, Åivo J, et al. 25-Hydroxyvitamin D deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology. 2017 Sep 13 [Epub ahead of print].
Can Eye Changes Signal Frontotemporal Degeneration?
Frontotemporal degeneration (FTD) is associated with outer retina thinning, and this thinning correlates with disease severity, according to a cross-sectional study published online ahead of print September 8 in Neurology. Researchers examined retinal structure using standard spectral-domain optical coherence tomography in 38 consecutively enrolled patients with FTD and 44 controls. The researchers excluded patients with presumed Alzheimer’s disease, eyes with poor image quality, or confounding diseases. Adjusting for age, sex, and race, patients with FTD had a thinner outer retina, compared with controls. Patients with FTD also had a thinner outer nuclear layer and ellipsoid zone, compared with controls. The groups had similar thicknesses for inner retinal layers.
Kim BJ, Irwin DJ, Song D, et al. Optical coherence tomography identifies outer retina thinning in frontotemporal degeneration. Neurology. 2017 Sep 8 [Epub ahead of print].
A New Diagnostic Test for Alzheimer’s Disease
Blood sample analysis may help diagnose Alzheimer’s disease and distinguish between different types of neurodegenerative disorders, according to a study published online ahead of print September 5 in the Proceedings of the National Academy of Sciences. Investigators used attenuated total reflection FTIR spectroscopy combined with chemometric techniques to analyze blood plasma samples from 347 participants with neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of APOE ε4 information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. The test segregated Alzheimer’s disease from dementia with Lewy bodies (n = 34) with 90% sensitivity and specificity.
Paraskevaidi M, Morais CLM, Lima KMG, et al. Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood. Proc Natl Acad Sci U S A. 2017 Sep 5 [Epub ahead of print].
New Indication for Briviact CV
The FDA has approved a supplemental new drug application for Briviact (brivaracetam) CV as monotherapy for partial-onset seizures in patients age 16 and older with epilepsy. Briviact previously was approved as adjunctive treatment for partial-onset seizures in this age group. UCB, which markets Briviact, applied for the monotherapy indication after the FDA advised that it is acceptable to extrapolate the efficacy and safety of drugs approved as adjunctive therapy for the treatment of partial-onset seizures to their use as monotherapy for the treatment of partial-onset seizures. Gradual dose escalation is not required when initiating treatment with Briviact for monotherapy or adjunctive therapy, which allows clinicians to initiate treatment at a therapeutic dose. Briviact formulations include film-coated tablets, oral solution, and injection. UCB is headquartered in Brussels.
Less REM Sleep Is Associated With Greater Dementia Risk
REM sleep may be associated with risk of dementia, according to a study published online ahead of print August 23 in Neurology. Researchers examined associations between sleep architecture and the prospective risk of incident dementia in a subset of 321 Framingham Heart Study Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998, and were older than 60 at the time of sleep assessment (mean age, 67; 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for up to 19 years for incident dementia. Researchers observed 32 cases of incident dementia. Each percentage reduction in REM sleep was associated with an approximately 9% increase in the risk of incident dementia (hazard ratio, 0.91).
Pase MP, Himali JJ, Grima NA, et al. Sleep architecture and the risk of incident dementia in the community. Neurology. 2017 Aug 23 [Epub ahead of print].
Mononucleosis May Increase Risk of MS
Epstein-Barr nuclear antigen-1 seropositivty is independently associated with increased risk of multiple sclerosis (MS) or clinically isolated syndrome (CIS), according to a study published online ahead of print August 30 in Neurology. Researchers recruited 1,090 black, Hispanic, and white people with MS or CIS and matched controls over a three-year period. Participants were tested for the Epstein-Barr virus antibody and were asked whether they had ever had mononucleosis. Blacks who had had mononucleosis were more than four times more likely to develop MS, compared with those who had not had mononucleosis. Hispanics and whites who had had mononucleosis were nearly four times and two times, respectively, more likely to develop MS or CIS, compared with those who had not had mononucleosis.
Langer-Gould A, Wu J, Lucas R, et al. Epstein-Barr virus, cytomegalovirus, and multiple sclerosis susceptibility: a multiethnic study. Neurology. 2017 Aug 30 [Epub ahead of print].
Asthma Medicine May Decrease Risk of Parkinson’s Disease
Salbutamol, a brain-penetrant asthma medication, is associated with reduced risk of Parkinson’s disease, according to a study published September 1 in Science. Researchers used an unbiased screen targeting endogenous gene expression to discover that the β2-adrenoreceptor (β2AR) is a regulator of the α-synuclein gene. Research has indicated that excess production of α-synuclein may be a causative factor in Parkinson’s disease. Over 11 years of follow-up in four million Norwegians, the β2AR agonist salbutamol was associated with reduced risk of Parkinson’s disease (rate ratio, 0.66). A β2AR antagonist correlated with increased risk.
Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science. 2017;357(6354):891-898 [Epub ahead of print].
Odds of Developing Alzheimer’s Disease Same for Men and Women With APOE Genotype
Men and women with the APOE ε3/ε4 genotype have nearly the same odds of developing Alzheimer’s disease from age 55 to 85, but women have an increased risk at younger ages, according to a study published online ahead of print August 28 in JAMA Neurology. Researchers analyzed data from 27 studies with nearly 58,000 participants. Homogeneous data sets were pooled in case-control analyses, and logistic regression models were used to compute risks. Age-adjusted odds ratios and 95% confidence intervals for developing mild cognitive impairment and Alzheimer’s disease were calculated for men and women across APOE genotypes. Men and women with the APOE ε3/ε4 genotype from ages 55 to 85 did not show a difference in Alzheimer’s disease risk. Women had an increased risk of Alzheimer’s disease compared with men between the ages of 65 and 75.
Neu SC, Pa J, Kukull W, et al. Apolipoprotein e genotype and sex risk factors for Alzheimer disease: a meta-analysis. JAMA Neurol. 2017 Aug 28 [Epub ahead of print].
Does Dimethyl Fumarate Prevent MS Reactivation After Natalizumab Discontinuation?
Dimethyl fumarate appears generally safe and may be a promising drug for patients at high risk of progressive multifocal leukoencephalopathy (PML) who discontinue natalizumab, according to an article published online ahead of print August 26 in the Journal of Neurology, Neurosurgery and Psychiatry. Thirty-nine patients with relapsing-remitting multiple sclerosis (MS) at high risk of PML were switched from natalizumab to dimethyl fumarate and underwent neurologic and 3T MRI monitoring for two years. Clinical and MRI data regarding the two-year period preceding natalizumab treatment, the two years of natalizumab treatment, and the two years of dimethyl fumarate treatment were collected. During the dimethyl fumarate phase, one or more relapses occurred in five patients (12.8%), increased disability progression occurred in four patients (10.3%), and MRI activity occurred in eight patients (20.5%). Post-natalizumab rebound effect was observed in one patient. Almost 80% of the patients had no evidence of disease activity after two years of dimethyl fumarate treatment. No carryover PML among investigated cases was observed.
Calabrese M, Pitteri M, Farina G, et al. Dimethyl fumarate: a possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events. J Neurol Neurosurg Psychiatry. 2017 Aug 26 [Epub ahead of print].
Austedo Approved for Treatment of Tardive Dyskinesia in Adults
The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of tardive dyskinesia in adults. The approval was based on results from two phase III randomized, double-blind, placebo-controlled, parallel group studies assessing the efficacy and safety of Austedo in reducing the severity of abnormal involuntary movements associated with tardive dyskinesia. Austedo was previously approved in April for the treatment of chorea associated with Huntington’s disease. The most common adverse reactions (ie, 4% of Austedo-treated patients and greater than placebo) in controlled clinical studies of patients with tardive dyskinesia were nasopharyngitis and insomnia. Teva Pharmaceutical Industries, which markets Austedo, is headquartered in Jerusalem.
Orphan Drug Designation Granted for EPX-300
The FDA has granted Orphan Drug Designation for EPX-300 for the treatment of patients with Dravet syndrome. EPX-300 is a repurposed antidepressant that acts via modulation of serotonin signaling pathways. Researchers discovered its potential as a treatment for patients with Dravet syndrome using a phenotype-based zebrafish drug screening platform. Using the zebrafish model for Dravet syndrome, investigators identified drug candidates from a screen of more than 3,000 drugs that suppress seizures and other symptoms associated with neurologic diseases. Epygenix Therapeutics, which is developing EPX-300, is headquartered in Paramus, New Jersey.
FDA Approves Expanded Indication for Aptiom
The FDA has approved a supplemental new drug application to expand the indication for Aptiom (eslicarbazepine acetate) to include treatment of partial-onset seizures in children age 4 to 17. The safety and efficacy of Aptiom as monotherapy and adjunctive therapy for the treatment of partial-onset seizures in adults was established in five multicenter, randomized, controlled clinical trials. Data from three clinical trials supported the safety and tolerability of Aptiom for the treatment of partial-onset seizures in pediatric patients. Pharmacokinetic analyses of adult and pediatric data supported its use in the pediatric population. Aptiom is a once-daily, immediate release drug that can be taken whole or crushed, with or without food. Sunovion Pharmaceuticals, which markets Aptiom, is headquartered in Marlborough, Massachusetts.
—Kimberly Williams
New and Noteworthy Information—September 2017
Statin Prescription Varies in Stroke Belt
Less than half of patients with stroke discharged from the hospital receive a prescription for statins, and the likelihood of a prescription varies by patients’ location, sex, age, and race, according to a study published August 2 in the Journal of the American Heart Association. Researchers analyzed discharge medications for 323 participants hospitalized for an ischemic stroke during follow-up of the Reasons for Geographic and Racial Differences in Stroke study. In the Stroke Belt, participants ages 65 and older were 47% less likely to be discharged on a statin, compared with people younger than 65. Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin, while men outside the Stroke Belt were more likely to be discharged on a statin.
Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the stroke belt: evidence from the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6(8).
Midlife Vascular Risk Factors Increase Risk of Dementia
Midlife vascular risk factors are associated with increased risk of dementia in blacks and whites, according to a study published online ahead of print August 7 in JAMA Neurology. In the Atherosclerosis Risk in Communities study, investigators measured demographic and vascular risk factors at baseline (ie, obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia), along with the presence of the APOE ε4 genotype. After the baseline visit, participants had four additional in-person visits. In all, 1,516 cases of dementia (57.0% female and 34.9% black, with a mean age at visit 1 of 57.4) were identified among 15,744 participants. Black race, older age, lower educational attainment, and APOE ε4 genotype were associated with increased risk of dementia, as were midlife smoking, diabetes, prehypertension, and hypertension.
Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017 August 7 [Epub ahead of print].
Resistance Training May Slow the Progression of MS
Progressive resistance training may have a neuroprotective or neuroregenerative effect in relapsing-remitting multiple sclerosis (MS), according to a study published online ahead of print July 1 in Multiple Sclerosis Journal. This study was a 24-week randomized controlled crossover trial. Participants were assigned to training or to a wait list. Assessments included disability measures and MRI. The MS Functional Composite score improved in the training group, but disability, lesion load, and global brain volumes did not differ between groups. The researchers noted higher absolute cortical thickness values in 19 of 74 investigated cortical regions after progressive resistance training. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups in the anterior cingulate gyrus, temporal pole, orbital sulcus, and inferior temporal sulcus.
Kjølhede T, Siemonsen S, Wenzel D, et al. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2017 Jul 1 [Epub ahead of print].
Noninvasive Device Measures Intracranial Pressure
A noninvasive device measures intracranial pressure (ICP) accurately, according to research published online ahead of print August 8 in the Journal of Neurosurgery. In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, researchers recorded ICP using the gold-standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured ICP noninvasively with a device that uses advanced signal-analysis algorithms for acoustic signals propagating through the cranium. Data were collected in 14 patients, yielding 2,543 data points of continuous parallel ICP values. For measurements at the ≥ 17-mm Hg cutoff, the sensitivity and specificity of the noninvasive device were 0.7541 and 0.8887, respectively. ICP values obtained using noninvasive and invasive monitoring methods correlated well.
Ganslandt O, Mourtzoukos S, Stadlbauer A, et al. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2017 Aug 8 [Epub ahead of print].
Strokes Decline Among Men, But Not Women
The rate of stroke in the US has declined among men, but not among women, according to a study published online ahead of print August 9 in Neurology. Researchers collected data on 1.3 million adults in Ohio and Kentucky between 1993 and 2010. They used medical records to identify first-ever strokes during four one-year periods. The researchers observed 7,710 incident strokes in the four periods, and 57% of them were among women. The incidence of all strokes decreased over time in men (263 to 192), but not in women (217 to 198). The researchers found a similar sex difference in the change in the rate of ischemic stroke (ie, a decline from 238 to 165 among men, and a change from 193 to 173 among women).
Madsen TE, Khoury J, Alwell K, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017 Aug 9 [Epub ahead of print].
Link Between Alcohol Intake and Cognitively Healthy Longevity
Older adults who consume alcohol moderately on a regular basis are more likely to live to age 85 without dementia or other cognitive impairments than nondrinkers, according to a study published in the August issue of the Journal of Alzheimer’s Disease. Researchers examined 1,344 older community-dwelling adults and assessed alcohol intake by questionnaire in 1984–1987. They evaluated cognitive function in approximately four-year intervals between 1988 and 2009. About 49% of participants reported moderate alcohol intake, and 48% reported drinking almost daily. Relative to nondrinkers, moderate and heavy drinkers had significantly higher adjusted odds of survival to age 85 without cognitive impairment. Near-daily drinkers had two- to threefold higher adjusted odds of cognitively healthy longevity versus living to at least age 85 with cognitive impairment or death before age 85.
Richard EL, Kritz-Silverstein D, Laughlin GA, et al. Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo Study. J Alzheimers Dis. 2017;59(3):803-814.
MRI Shows Brain Differences in Genetic Autism
In two genetically related cohorts at high risk for autism, reciprocal neuroanatomic abnormalities were associated with cognitive and behavioral impairments, according to a study published online ahead of print August 8 in Radiology. Researchers performed MRI on 79 carriers of a deletion at 16p11.2, 79 carriers of a duplication at 16p11.2, 64 unaffected family members, and 109 controls. The participants completed cognitive and behavioral tests, and neuroradiologists reviewed the images for development-related abnormalities. The researchers found differences in the brain structures of deletion and duplication carriers, compared with noncarriers. Deletion carriers had brain overgrowth, and duplication carriers had brain undergrowth. When investigators compared cognitive assessments to imaging findings, they found that any imaging feature associated with the deletion carriers indicated worse daily living, communication, and social skills.
Owen JP, Bukshpun P, Pojman N, et al. Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2. Radiology. 2017 Aug 8 [Epub ahead of print].
FDA Clears Stimpod NMS460 for Relief of Chronic Pain
The FDA has cleared Stimpod NMS460, a noninvasive neuromodulation device, for the symptomatic relief and management of chronic intractable pain. The unit also can be used for the adjunctive treatment of postsurgical pain, posttraumatic acute pain, and pain control due to rehabilitation. The device has a pulsed radio frequency waveform that creates electromagnetic effects similar to those of invasive pulsed radio frequency treatments. Treatment is applied transcutaneously. Case studies have shown quick and notable relief of chronic intractable pain. The treatment has no known side effects. The Stimpod NMS460 also incorporates nerve-locating technology that includes a nerve-mapping probe that enables practitioners to evaluate the treatment progress of damaged nerves. Xavant Technology, which markets Stimpod NMS460, is headquartered in Pretoria, South Africa.
Longer Sleep Is Associated With Lower BMI
Adults who have poor sleep patterns are more likely to be overweight or obese and have poorer metabolic health, according to a study published July 27 in PLoS One. Researchers analyzed associations between sleep duration and adiposity, selected metabolic health markers, and diet using National Diet and Nutrition Survey data. In all, 1,615 adults (57.1% female) between ages 19 and 65 completed questions about sleep duration and three to four days of food diaries. Investigators recorded blood pressure and waist circumference. Fasting blood lipids, glucose, glycated hemoglobin, thyroid hormones, and high-sensitivity C-reactive protein were measured in a subset of participants. After adjusting for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with BMI and waist circumference. Sleep duration was positively associated with high-density lipoprotein cholesterol.
Potter GDM, Cade JE, Hardie LJ. Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: findings from the National Diet and Nutrition Survey. PLoS One. 2017; 12(7):e0182195.
Can Bleeding Risk After Stroke Be Predicted?
The S2TOP-BLEED score can estimate three-year major bleeding risk in patients with transient ischemic attack (TIA) or ischemic stroke who use antiplatelet agents, according to a study published online ahead of print August 2 in Neurology. To develop this prediction model, researchers combined data from six trials investigating antiplatelet therapy after TIA or ischemic stroke. They performed Cox regression analyses stratified by trial to study the association between predictors and major bleeding. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed three-year risk of major bleeding was 4.6%. The investigators identified male sex, smoking, type of antiplatelet agents, outcome on modified Rankin Scale ≥ 3, prior stroke, high blood pressure, lower BMI, elderly status, Asian ethnicity, and diabetes as predictors of major bleeding.
Hilkens NA, Algra A, Diener HC, et al. Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology. 2017 Aug 2 [Epub ahead of print].
Questionnaires Predict Survival in MS
The way patients with multiple sclerosis (MS) answer questionnaires could help to predict their survival rate from the disease, according to a study published July 10 in PLoS Medicine. From July 15, 2004, onward, 2,126 people with MS completed MS Impact Scale-29 (MSIS-29) questionnaires. By 2014, 264 participants had died. Higher baseline MSIS-29 physical score and higher baseline MSIS-29 psychologic score were associated with reduced survival time. In participants with high baseline MSIS-29 scores, mortality risk was greater if the MSIS-29 score worsened over one year. MSIS-29 physical scores were associated with survival time, independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis.
Raffel J, Wallace A, Gveric D, et al. Patient-reported outcomes and survival in multiple sclerosis: a 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29. PLoS Med. 2017;14(7):e1002346.
—Kimberly Williams
Statin Prescription Varies in Stroke Belt
Less than half of patients with stroke discharged from the hospital receive a prescription for statins, and the likelihood of a prescription varies by patients’ location, sex, age, and race, according to a study published August 2 in the Journal of the American Heart Association. Researchers analyzed discharge medications for 323 participants hospitalized for an ischemic stroke during follow-up of the Reasons for Geographic and Racial Differences in Stroke study. In the Stroke Belt, participants ages 65 and older were 47% less likely to be discharged on a statin, compared with people younger than 65. Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin, while men outside the Stroke Belt were more likely to be discharged on a statin.
Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the stroke belt: evidence from the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6(8).
Midlife Vascular Risk Factors Increase Risk of Dementia
Midlife vascular risk factors are associated with increased risk of dementia in blacks and whites, according to a study published online ahead of print August 7 in JAMA Neurology. In the Atherosclerosis Risk in Communities study, investigators measured demographic and vascular risk factors at baseline (ie, obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia), along with the presence of the APOE ε4 genotype. After the baseline visit, participants had four additional in-person visits. In all, 1,516 cases of dementia (57.0% female and 34.9% black, with a mean age at visit 1 of 57.4) were identified among 15,744 participants. Black race, older age, lower educational attainment, and APOE ε4 genotype were associated with increased risk of dementia, as were midlife smoking, diabetes, prehypertension, and hypertension.
Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017 August 7 [Epub ahead of print].
Resistance Training May Slow the Progression of MS
Progressive resistance training may have a neuroprotective or neuroregenerative effect in relapsing-remitting multiple sclerosis (MS), according to a study published online ahead of print July 1 in Multiple Sclerosis Journal. This study was a 24-week randomized controlled crossover trial. Participants were assigned to training or to a wait list. Assessments included disability measures and MRI. The MS Functional Composite score improved in the training group, but disability, lesion load, and global brain volumes did not differ between groups. The researchers noted higher absolute cortical thickness values in 19 of 74 investigated cortical regions after progressive resistance training. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups in the anterior cingulate gyrus, temporal pole, orbital sulcus, and inferior temporal sulcus.
Kjølhede T, Siemonsen S, Wenzel D, et al. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2017 Jul 1 [Epub ahead of print].
Noninvasive Device Measures Intracranial Pressure
A noninvasive device measures intracranial pressure (ICP) accurately, according to research published online ahead of print August 8 in the Journal of Neurosurgery. In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, researchers recorded ICP using the gold-standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured ICP noninvasively with a device that uses advanced signal-analysis algorithms for acoustic signals propagating through the cranium. Data were collected in 14 patients, yielding 2,543 data points of continuous parallel ICP values. For measurements at the ≥ 17-mm Hg cutoff, the sensitivity and specificity of the noninvasive device were 0.7541 and 0.8887, respectively. ICP values obtained using noninvasive and invasive monitoring methods correlated well.
Ganslandt O, Mourtzoukos S, Stadlbauer A, et al. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2017 Aug 8 [Epub ahead of print].
Strokes Decline Among Men, But Not Women
The rate of stroke in the US has declined among men, but not among women, according to a study published online ahead of print August 9 in Neurology. Researchers collected data on 1.3 million adults in Ohio and Kentucky between 1993 and 2010. They used medical records to identify first-ever strokes during four one-year periods. The researchers observed 7,710 incident strokes in the four periods, and 57% of them were among women. The incidence of all strokes decreased over time in men (263 to 192), but not in women (217 to 198). The researchers found a similar sex difference in the change in the rate of ischemic stroke (ie, a decline from 238 to 165 among men, and a change from 193 to 173 among women).
Madsen TE, Khoury J, Alwell K, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017 Aug 9 [Epub ahead of print].
Link Between Alcohol Intake and Cognitively Healthy Longevity
Older adults who consume alcohol moderately on a regular basis are more likely to live to age 85 without dementia or other cognitive impairments than nondrinkers, according to a study published in the August issue of the Journal of Alzheimer’s Disease. Researchers examined 1,344 older community-dwelling adults and assessed alcohol intake by questionnaire in 1984–1987. They evaluated cognitive function in approximately four-year intervals between 1988 and 2009. About 49% of participants reported moderate alcohol intake, and 48% reported drinking almost daily. Relative to nondrinkers, moderate and heavy drinkers had significantly higher adjusted odds of survival to age 85 without cognitive impairment. Near-daily drinkers had two- to threefold higher adjusted odds of cognitively healthy longevity versus living to at least age 85 with cognitive impairment or death before age 85.
Richard EL, Kritz-Silverstein D, Laughlin GA, et al. Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo Study. J Alzheimers Dis. 2017;59(3):803-814.
MRI Shows Brain Differences in Genetic Autism
In two genetically related cohorts at high risk for autism, reciprocal neuroanatomic abnormalities were associated with cognitive and behavioral impairments, according to a study published online ahead of print August 8 in Radiology. Researchers performed MRI on 79 carriers of a deletion at 16p11.2, 79 carriers of a duplication at 16p11.2, 64 unaffected family members, and 109 controls. The participants completed cognitive and behavioral tests, and neuroradiologists reviewed the images for development-related abnormalities. The researchers found differences in the brain structures of deletion and duplication carriers, compared with noncarriers. Deletion carriers had brain overgrowth, and duplication carriers had brain undergrowth. When investigators compared cognitive assessments to imaging findings, they found that any imaging feature associated with the deletion carriers indicated worse daily living, communication, and social skills.
Owen JP, Bukshpun P, Pojman N, et al. Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2. Radiology. 2017 Aug 8 [Epub ahead of print].
FDA Clears Stimpod NMS460 for Relief of Chronic Pain
The FDA has cleared Stimpod NMS460, a noninvasive neuromodulation device, for the symptomatic relief and management of chronic intractable pain. The unit also can be used for the adjunctive treatment of postsurgical pain, posttraumatic acute pain, and pain control due to rehabilitation. The device has a pulsed radio frequency waveform that creates electromagnetic effects similar to those of invasive pulsed radio frequency treatments. Treatment is applied transcutaneously. Case studies have shown quick and notable relief of chronic intractable pain. The treatment has no known side effects. The Stimpod NMS460 also incorporates nerve-locating technology that includes a nerve-mapping probe that enables practitioners to evaluate the treatment progress of damaged nerves. Xavant Technology, which markets Stimpod NMS460, is headquartered in Pretoria, South Africa.
Longer Sleep Is Associated With Lower BMI
Adults who have poor sleep patterns are more likely to be overweight or obese and have poorer metabolic health, according to a study published July 27 in PLoS One. Researchers analyzed associations between sleep duration and adiposity, selected metabolic health markers, and diet using National Diet and Nutrition Survey data. In all, 1,615 adults (57.1% female) between ages 19 and 65 completed questions about sleep duration and three to four days of food diaries. Investigators recorded blood pressure and waist circumference. Fasting blood lipids, glucose, glycated hemoglobin, thyroid hormones, and high-sensitivity C-reactive protein were measured in a subset of participants. After adjusting for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with BMI and waist circumference. Sleep duration was positively associated with high-density lipoprotein cholesterol.
Potter GDM, Cade JE, Hardie LJ. Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: findings from the National Diet and Nutrition Survey. PLoS One. 2017; 12(7):e0182195.
Can Bleeding Risk After Stroke Be Predicted?
The S2TOP-BLEED score can estimate three-year major bleeding risk in patients with transient ischemic attack (TIA) or ischemic stroke who use antiplatelet agents, according to a study published online ahead of print August 2 in Neurology. To develop this prediction model, researchers combined data from six trials investigating antiplatelet therapy after TIA or ischemic stroke. They performed Cox regression analyses stratified by trial to study the association between predictors and major bleeding. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed three-year risk of major bleeding was 4.6%. The investigators identified male sex, smoking, type of antiplatelet agents, outcome on modified Rankin Scale ≥ 3, prior stroke, high blood pressure, lower BMI, elderly status, Asian ethnicity, and diabetes as predictors of major bleeding.
Hilkens NA, Algra A, Diener HC, et al. Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology. 2017 Aug 2 [Epub ahead of print].
Questionnaires Predict Survival in MS
The way patients with multiple sclerosis (MS) answer questionnaires could help to predict their survival rate from the disease, according to a study published July 10 in PLoS Medicine. From July 15, 2004, onward, 2,126 people with MS completed MS Impact Scale-29 (MSIS-29) questionnaires. By 2014, 264 participants had died. Higher baseline MSIS-29 physical score and higher baseline MSIS-29 psychologic score were associated with reduced survival time. In participants with high baseline MSIS-29 scores, mortality risk was greater if the MSIS-29 score worsened over one year. MSIS-29 physical scores were associated with survival time, independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis.
Raffel J, Wallace A, Gveric D, et al. Patient-reported outcomes and survival in multiple sclerosis: a 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29. PLoS Med. 2017;14(7):e1002346.
—Kimberly Williams
Statin Prescription Varies in Stroke Belt
Less than half of patients with stroke discharged from the hospital receive a prescription for statins, and the likelihood of a prescription varies by patients’ location, sex, age, and race, according to a study published August 2 in the Journal of the American Heart Association. Researchers analyzed discharge medications for 323 participants hospitalized for an ischemic stroke during follow-up of the Reasons for Geographic and Racial Differences in Stroke study. In the Stroke Belt, participants ages 65 and older were 47% less likely to be discharged on a statin, compared with people younger than 65. Compared with women, men in the Stroke Belt were 31% less likely to be discharged on a statin, while men outside the Stroke Belt were more likely to be discharged on a statin.
Albright KC, Howard VJ, Howard G, et al. Age and sex disparities in discharge statin prescribing in the stroke belt: evidence from the Reasons for Geographic and Racial Differences in Stroke Study. J Am Heart Assoc. 2017;6(8).
Midlife Vascular Risk Factors Increase Risk of Dementia
Midlife vascular risk factors are associated with increased risk of dementia in blacks and whites, according to a study published online ahead of print August 7 in JAMA Neurology. In the Atherosclerosis Risk in Communities study, investigators measured demographic and vascular risk factors at baseline (ie, obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia), along with the presence of the APOE ε4 genotype. After the baseline visit, participants had four additional in-person visits. In all, 1,516 cases of dementia (57.0% female and 34.9% black, with a mean age at visit 1 of 57.4) were identified among 15,744 participants. Black race, older age, lower educational attainment, and APOE ε4 genotype were associated with increased risk of dementia, as were midlife smoking, diabetes, prehypertension, and hypertension.
Gottesman RF, Albert MS, Alonso A, et al. Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol. 2017 August 7 [Epub ahead of print].
Resistance Training May Slow the Progression of MS
Progressive resistance training may have a neuroprotective or neuroregenerative effect in relapsing-remitting multiple sclerosis (MS), according to a study published online ahead of print July 1 in Multiple Sclerosis Journal. This study was a 24-week randomized controlled crossover trial. Participants were assigned to training or to a wait list. Assessments included disability measures and MRI. The MS Functional Composite score improved in the training group, but disability, lesion load, and global brain volumes did not differ between groups. The researchers noted higher absolute cortical thickness values in 19 of 74 investigated cortical regions after progressive resistance training. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups in the anterior cingulate gyrus, temporal pole, orbital sulcus, and inferior temporal sulcus.
Kjølhede T, Siemonsen S, Wenzel D, et al. Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis? Mult Scler. 2017 Jul 1 [Epub ahead of print].
Noninvasive Device Measures Intracranial Pressure
A noninvasive device measures intracranial pressure (ICP) accurately, according to research published online ahead of print August 8 in the Journal of Neurosurgery. In patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, researchers recorded ICP using the gold-standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured ICP noninvasively with a device that uses advanced signal-analysis algorithms for acoustic signals propagating through the cranium. Data were collected in 14 patients, yielding 2,543 data points of continuous parallel ICP values. For measurements at the ≥ 17-mm Hg cutoff, the sensitivity and specificity of the noninvasive device were 0.7541 and 0.8887, respectively. ICP values obtained using noninvasive and invasive monitoring methods correlated well.
Ganslandt O, Mourtzoukos S, Stadlbauer A, et al. Evaluation of a novel noninvasive ICP monitoring device in patients undergoing invasive ICP monitoring: preliminary results. J Neurosurg. 2017 Aug 8 [Epub ahead of print].
Strokes Decline Among Men, But Not Women
The rate of stroke in the US has declined among men, but not among women, according to a study published online ahead of print August 9 in Neurology. Researchers collected data on 1.3 million adults in Ohio and Kentucky between 1993 and 2010. They used medical records to identify first-ever strokes during four one-year periods. The researchers observed 7,710 incident strokes in the four periods, and 57% of them were among women. The incidence of all strokes decreased over time in men (263 to 192), but not in women (217 to 198). The researchers found a similar sex difference in the change in the rate of ischemic stroke (ie, a decline from 238 to 165 among men, and a change from 193 to 173 among women).
Madsen TE, Khoury J, Alwell K, et al. Sex-specific stroke incidence over time in the Greater Cincinnati/Northern Kentucky Stroke Study. Neurology. 2017 Aug 9 [Epub ahead of print].
Link Between Alcohol Intake and Cognitively Healthy Longevity
Older adults who consume alcohol moderately on a regular basis are more likely to live to age 85 without dementia or other cognitive impairments than nondrinkers, according to a study published in the August issue of the Journal of Alzheimer’s Disease. Researchers examined 1,344 older community-dwelling adults and assessed alcohol intake by questionnaire in 1984–1987. They evaluated cognitive function in approximately four-year intervals between 1988 and 2009. About 49% of participants reported moderate alcohol intake, and 48% reported drinking almost daily. Relative to nondrinkers, moderate and heavy drinkers had significantly higher adjusted odds of survival to age 85 without cognitive impairment. Near-daily drinkers had two- to threefold higher adjusted odds of cognitively healthy longevity versus living to at least age 85 with cognitive impairment or death before age 85.
Richard EL, Kritz-Silverstein D, Laughlin GA, et al. Alcohol intake and cognitively healthy longevity in community-dwelling adults: The Rancho Bernardo Study. J Alzheimers Dis. 2017;59(3):803-814.
MRI Shows Brain Differences in Genetic Autism
In two genetically related cohorts at high risk for autism, reciprocal neuroanatomic abnormalities were associated with cognitive and behavioral impairments, according to a study published online ahead of print August 8 in Radiology. Researchers performed MRI on 79 carriers of a deletion at 16p11.2, 79 carriers of a duplication at 16p11.2, 64 unaffected family members, and 109 controls. The participants completed cognitive and behavioral tests, and neuroradiologists reviewed the images for development-related abnormalities. The researchers found differences in the brain structures of deletion and duplication carriers, compared with noncarriers. Deletion carriers had brain overgrowth, and duplication carriers had brain undergrowth. When investigators compared cognitive assessments to imaging findings, they found that any imaging feature associated with the deletion carriers indicated worse daily living, communication, and social skills.
Owen JP, Bukshpun P, Pojman N, et al. Brain MR imaging findings and associated outcomes in carriers of the reciprocal copy number variation at 16p11.2. Radiology. 2017 Aug 8 [Epub ahead of print].
FDA Clears Stimpod NMS460 for Relief of Chronic Pain
The FDA has cleared Stimpod NMS460, a noninvasive neuromodulation device, for the symptomatic relief and management of chronic intractable pain. The unit also can be used for the adjunctive treatment of postsurgical pain, posttraumatic acute pain, and pain control due to rehabilitation. The device has a pulsed radio frequency waveform that creates electromagnetic effects similar to those of invasive pulsed radio frequency treatments. Treatment is applied transcutaneously. Case studies have shown quick and notable relief of chronic intractable pain. The treatment has no known side effects. The Stimpod NMS460 also incorporates nerve-locating technology that includes a nerve-mapping probe that enables practitioners to evaluate the treatment progress of damaged nerves. Xavant Technology, which markets Stimpod NMS460, is headquartered in Pretoria, South Africa.
Longer Sleep Is Associated With Lower BMI
Adults who have poor sleep patterns are more likely to be overweight or obese and have poorer metabolic health, according to a study published July 27 in PLoS One. Researchers analyzed associations between sleep duration and adiposity, selected metabolic health markers, and diet using National Diet and Nutrition Survey data. In all, 1,615 adults (57.1% female) between ages 19 and 65 completed questions about sleep duration and three to four days of food diaries. Investigators recorded blood pressure and waist circumference. Fasting blood lipids, glucose, glycated hemoglobin, thyroid hormones, and high-sensitivity C-reactive protein were measured in a subset of participants. After adjusting for age, ethnicity, sex, smoking, and socioeconomic status, sleep duration was negatively associated with BMI and waist circumference. Sleep duration was positively associated with high-density lipoprotein cholesterol.
Potter GDM, Cade JE, Hardie LJ. Longer sleep is associated with lower BMI and favorable metabolic profiles in UK adults: findings from the National Diet and Nutrition Survey. PLoS One. 2017; 12(7):e0182195.
Can Bleeding Risk After Stroke Be Predicted?
The S2TOP-BLEED score can estimate three-year major bleeding risk in patients with transient ischemic attack (TIA) or ischemic stroke who use antiplatelet agents, according to a study published online ahead of print August 2 in Neurology. To develop this prediction model, researchers combined data from six trials investigating antiplatelet therapy after TIA or ischemic stroke. They performed Cox regression analyses stratified by trial to study the association between predictors and major bleeding. Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed three-year risk of major bleeding was 4.6%. The investigators identified male sex, smoking, type of antiplatelet agents, outcome on modified Rankin Scale ≥ 3, prior stroke, high blood pressure, lower BMI, elderly status, Asian ethnicity, and diabetes as predictors of major bleeding.
Hilkens NA, Algra A, Diener HC, et al. Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets: S2TOP-BLEED. Neurology. 2017 Aug 2 [Epub ahead of print].
Questionnaires Predict Survival in MS
The way patients with multiple sclerosis (MS) answer questionnaires could help to predict their survival rate from the disease, according to a study published July 10 in PLoS Medicine. From July 15, 2004, onward, 2,126 people with MS completed MS Impact Scale-29 (MSIS-29) questionnaires. By 2014, 264 participants had died. Higher baseline MSIS-29 physical score and higher baseline MSIS-29 psychologic score were associated with reduced survival time. In participants with high baseline MSIS-29 scores, mortality risk was greater if the MSIS-29 score worsened over one year. MSIS-29 physical scores were associated with survival time, independent of age, sex, and patient-reported Expanded Disability Status Scale score in a Cox regression analysis.
Raffel J, Wallace A, Gveric D, et al. Patient-reported outcomes and survival in multiple sclerosis: a 10-year retrospective cohort study using the Multiple Sclerosis Impact Scale-29. PLoS Med. 2017;14(7):e1002346.
—Kimberly Williams
New and Noteworthy Information—August 2017
Brain Training Shows Little Benefit
Commercial brain training with Lumosity has no effect on decision making or cognitive function beyond practice effects on training tasks, according to a study published online ahead of print July 10 in the Journal of Neuroscience. Researchers tested whether training executive cognitive function could influence choice behavior and brain responses. In a randomized controlled trial, 128 young adults (71 male) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. The participants also completed a series of cognitive tests that were not part of the training. Although both groups showed improvement, commercial brain training did not lead to more improvement than online video games did.
Kable JW, Caulfield MK, Falcone M, et al. No effect of commercial cognitive training on neural activity during decision-making. J Neurosci. 2017 Jul 10 [Epub ahead of print].
Sense of Purpose Linked to Better Sleep
A higher level of meaning and purpose in life among older adults is associated with better sleep quality and appears to protect against symptoms of sleep apnea and restless legs syndrome (RLS), according to a study published online ahead of print July 10 in Sleep Science and Practice. Included in this study were 825 nondemented older African Americans (n = 428) and whites (n = 397), from the Minority Aging Research Study and the Rush Memory and Aging Project. Participants completed a 32-item questionnaire assessing sleep quality and symptoms of sleep apnea, RLS, and REM sleep behavior disorder. Longitudinal follow-up data indicated that higher levels of purpose in life were associated with lower risk of sleep apnea at baseline, one-year follow-up, and two-year follow-up, and with reduced RLS symptoms at one-year and two-year follow-up.
Turner AD, Smith CE, Ong JC. Is purpose in life associated with less sleep disturbance in older adults? Sleep Sci Pract. 2017 July 10 [Epub ahead of print].
Can Breastfeeding Reduce MS Risk in Mothers?
Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis (MS), according to a study published online ahead of print July 12 in Neurology. Researchers recruited women with newly diagnosed MS or clinically isolated syndrome (CIS) and matched controls into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. An in-person questionnaire was administered to collect behavioral and biologic factors to calculate ovulatory years. Among women who had live births, a cumulative duration of breastfeeding for 15 months or more was associated with a reduced risk of MS and CIS (adjusted odds ratio, 0.47). Being age 15 or older at menarche also was associated with a lower risk of MS and CIS (adjusted odds ratio, 0.56).
Langer-Gould A, Smith JB, Hellwig K, et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology. 2017 July 12 [Epub ahead of print].
Does Added Weight Increase Survival After Stroke?
People who are overweight or mildly obese survive strokes at a higher rate, compared with people of normal body weight, according to a study published June 24 in the Journal of the American Heart Association. Participants from the Framingham Heart Study were followed for as long as 10 years, with BMI measured prior to their strokes. Researchers compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. There were 782 stroke cases and 2,346 controls. The association of reduced mortality with BMI of 25 or higher, compared with BMI of 18.5 to less than 25, was pronounced among ischemic stroke cases, but diminished with inclusion of hemorrhagic strokes.
Aparicio HJ, Himali JJ, Beiser AS, et al. Overweight, obesity, and survival after stroke in the Framingham Heart Study. J Am Heart Assoc. 2017;6(6).
Poor Sleep Linked to CSF Biomarkers
Self-reported poor sleep is associated with greater Alzheimer’s disease-related pathology in cognitively healthy adults at risk for Alzheimer’s disease, according to a study published online ahead of print July 5 in Neurology. Researchers investigated the relationship between sleep quality and CSF Alzheimer’s disease biomarkers in a cohort enriched for parental history of sporadic Alzheimer’s disease. In all, 101 participants completed sleep assessments and CSF collection and were cognitively normal. CSF was assayed for biomarkers of amyloid metabolism and plaques, tau pathology, neuronal and axonal degeneration, neuroinflammation and astroglial activation, and synaptic dysfunction and degeneration. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater Alzheimer’s disease pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
Sprecher KE, Koscik RL, Carlsson CM, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Jul 5 [Epub ahead of print].
Is There a Link Between Parkinson’s Disease and Melanoma?
Melanoma and Parkinson’s disease may be associated, according to a study published in the July issue of Mayo Clinic Proceedings. For phase I of the Rochester Epidemiology Project, investigators used records to identify patients with Parkinson’s disease and match three controls per case. During phase II of this study, all Rochester Epidemiology Project cases of melanoma were identified, with one control per case. Investigators used a Cox proportional hazards model to assess the risk of developing Parkinson’s disease after the index date in cases versus controls, and performed Kaplan-Meier analysis to determine the 35-year cumulative risk of Parkinson’s disease. Patients with Parkinson’s disease had a 3.8-fold increased likelihood of having preexisting melanoma, compared with controls. Patients with melanoma had a 4.2-fold increased risk of developing Parkinson’s disease.
Dalvin LA, Damento GM, Yawn BP, et al. Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc. 2017;92(7):1070-1079.
Zolpidem Treats Various Neurologic Disorders
A systematic review shows that zolpidem can treat various neurologic disorders, most often related to movement disorders and disorders of consciousness, according to a literature review published online ahead of print June 26 in JAMA Neurology. The investigators searched for English-language articles, published by March 20, 2015, that examined the use of zolpidem for noninsomnia neurologic disorders. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. In all, 67 articles were eligible for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions. The effects of zolpidem were wide ranging and generally lasted for one to four hours before the participant returned to baseline. Sedation was the most common adverse effect.
Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017 Jun 26 [Epub ahead of print].
Colored Light Triggers Responses in Migraineurs
Lights trigger more changes in autonomic functions and negative emotions during migraine than in control subjects, and the association between light and positive emotions is stronger in control subjects than in migraineurs, according to a study published online ahead of print June 26 in the Proceedings of the National Academy of Sciences. Researchers showed different colored lights to 81 migraineurs and 17 people who had never had a migraine. The effects of light and color were tested three times. Investigators found that all colors of light triggered unpleasant physiologic sensations in patients with migraines, during and between attacks. Additionally, migraineurs reported intense emotional responses such as anger, nervousness, hopelessness, sadness, depression, anxiety, and fear when exposed to all light colors except green.
Noseda R, Lee AJ, Nir RR, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci. 2017 Jun 26 [Epub ahead of print].
TBI May Not Hasten Cognitive Decline
Having a history of traumatic brain injury (TBI) with loss of consciousness does not affect the rate of cognitive change over time for people with normal cognition or people with Alzheimer’s disease, according to a study published online ahead of print June 22 in the Journal of Alzheimer’s Disease. Researchers compared performance on cognitive tests over time for 432 participants with normal cognition and 274 participants with probable Alzheimer’s disease. They matched participants with a history of TBI with loss of consciousness to an equal number of demographically and clinically similar participants without a history of TBI. Mixed-effects regressions showed that a history of TBI with loss of consciousness did not affect rates of cognitive change in APOE ε4 carriers and noncarriers.
Tripodis Y, Alosco ML, Zirogiannis N, et al. The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimers Dis. 2017 Jun 22 [Epub ahead of print].
Visual Changes in Parkinson’s Disease
Visual system alterations can be detected in early stages of Parkinson’s disease, and the entire intracranial visual system can be involved, according to a study published online ahead of print July 11 in Radiology. Twenty patients with newly diagnosed Parkinson’s disease and 20 age-matched control subjects were studied. Researchers used diffusion-weighted imaging to assess white matter changes and voxel-based morphometry (VBM) to investigate concentration changes of gray and white matter. In patients with Parkinson’s disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density, a significant increase in optic radiation mean diffusivity, and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes.
Arrigo A, Calamuneri A, Milardi D, et al. Visual system involvement in patients with newly diagnosed Parkinson disease. Radiology. 2017 Jul 11 [Epub ahead of print].
—Kimberly Williams
Brain Training Shows Little Benefit
Commercial brain training with Lumosity has no effect on decision making or cognitive function beyond practice effects on training tasks, according to a study published online ahead of print July 10 in the Journal of Neuroscience. Researchers tested whether training executive cognitive function could influence choice behavior and brain responses. In a randomized controlled trial, 128 young adults (71 male) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. The participants also completed a series of cognitive tests that were not part of the training. Although both groups showed improvement, commercial brain training did not lead to more improvement than online video games did.
Kable JW, Caulfield MK, Falcone M, et al. No effect of commercial cognitive training on neural activity during decision-making. J Neurosci. 2017 Jul 10 [Epub ahead of print].
Sense of Purpose Linked to Better Sleep
A higher level of meaning and purpose in life among older adults is associated with better sleep quality and appears to protect against symptoms of sleep apnea and restless legs syndrome (RLS), according to a study published online ahead of print July 10 in Sleep Science and Practice. Included in this study were 825 nondemented older African Americans (n = 428) and whites (n = 397), from the Minority Aging Research Study and the Rush Memory and Aging Project. Participants completed a 32-item questionnaire assessing sleep quality and symptoms of sleep apnea, RLS, and REM sleep behavior disorder. Longitudinal follow-up data indicated that higher levels of purpose in life were associated with lower risk of sleep apnea at baseline, one-year follow-up, and two-year follow-up, and with reduced RLS symptoms at one-year and two-year follow-up.
Turner AD, Smith CE, Ong JC. Is purpose in life associated with less sleep disturbance in older adults? Sleep Sci Pract. 2017 July 10 [Epub ahead of print].
Can Breastfeeding Reduce MS Risk in Mothers?
Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis (MS), according to a study published online ahead of print July 12 in Neurology. Researchers recruited women with newly diagnosed MS or clinically isolated syndrome (CIS) and matched controls into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. An in-person questionnaire was administered to collect behavioral and biologic factors to calculate ovulatory years. Among women who had live births, a cumulative duration of breastfeeding for 15 months or more was associated with a reduced risk of MS and CIS (adjusted odds ratio, 0.47). Being age 15 or older at menarche also was associated with a lower risk of MS and CIS (adjusted odds ratio, 0.56).
Langer-Gould A, Smith JB, Hellwig K, et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology. 2017 July 12 [Epub ahead of print].
Does Added Weight Increase Survival After Stroke?
People who are overweight or mildly obese survive strokes at a higher rate, compared with people of normal body weight, according to a study published June 24 in the Journal of the American Heart Association. Participants from the Framingham Heart Study were followed for as long as 10 years, with BMI measured prior to their strokes. Researchers compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. There were 782 stroke cases and 2,346 controls. The association of reduced mortality with BMI of 25 or higher, compared with BMI of 18.5 to less than 25, was pronounced among ischemic stroke cases, but diminished with inclusion of hemorrhagic strokes.
Aparicio HJ, Himali JJ, Beiser AS, et al. Overweight, obesity, and survival after stroke in the Framingham Heart Study. J Am Heart Assoc. 2017;6(6).
Poor Sleep Linked to CSF Biomarkers
Self-reported poor sleep is associated with greater Alzheimer’s disease-related pathology in cognitively healthy adults at risk for Alzheimer’s disease, according to a study published online ahead of print July 5 in Neurology. Researchers investigated the relationship between sleep quality and CSF Alzheimer’s disease biomarkers in a cohort enriched for parental history of sporadic Alzheimer’s disease. In all, 101 participants completed sleep assessments and CSF collection and were cognitively normal. CSF was assayed for biomarkers of amyloid metabolism and plaques, tau pathology, neuronal and axonal degeneration, neuroinflammation and astroglial activation, and synaptic dysfunction and degeneration. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater Alzheimer’s disease pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
Sprecher KE, Koscik RL, Carlsson CM, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Jul 5 [Epub ahead of print].
Is There a Link Between Parkinson’s Disease and Melanoma?
Melanoma and Parkinson’s disease may be associated, according to a study published in the July issue of Mayo Clinic Proceedings. For phase I of the Rochester Epidemiology Project, investigators used records to identify patients with Parkinson’s disease and match three controls per case. During phase II of this study, all Rochester Epidemiology Project cases of melanoma were identified, with one control per case. Investigators used a Cox proportional hazards model to assess the risk of developing Parkinson’s disease after the index date in cases versus controls, and performed Kaplan-Meier analysis to determine the 35-year cumulative risk of Parkinson’s disease. Patients with Parkinson’s disease had a 3.8-fold increased likelihood of having preexisting melanoma, compared with controls. Patients with melanoma had a 4.2-fold increased risk of developing Parkinson’s disease.
Dalvin LA, Damento GM, Yawn BP, et al. Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc. 2017;92(7):1070-1079.
Zolpidem Treats Various Neurologic Disorders
A systematic review shows that zolpidem can treat various neurologic disorders, most often related to movement disorders and disorders of consciousness, according to a literature review published online ahead of print June 26 in JAMA Neurology. The investigators searched for English-language articles, published by March 20, 2015, that examined the use of zolpidem for noninsomnia neurologic disorders. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. In all, 67 articles were eligible for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions. The effects of zolpidem were wide ranging and generally lasted for one to four hours before the participant returned to baseline. Sedation was the most common adverse effect.
Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017 Jun 26 [Epub ahead of print].
Colored Light Triggers Responses in Migraineurs
Lights trigger more changes in autonomic functions and negative emotions during migraine than in control subjects, and the association between light and positive emotions is stronger in control subjects than in migraineurs, according to a study published online ahead of print June 26 in the Proceedings of the National Academy of Sciences. Researchers showed different colored lights to 81 migraineurs and 17 people who had never had a migraine. The effects of light and color were tested three times. Investigators found that all colors of light triggered unpleasant physiologic sensations in patients with migraines, during and between attacks. Additionally, migraineurs reported intense emotional responses such as anger, nervousness, hopelessness, sadness, depression, anxiety, and fear when exposed to all light colors except green.
Noseda R, Lee AJ, Nir RR, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci. 2017 Jun 26 [Epub ahead of print].
TBI May Not Hasten Cognitive Decline
Having a history of traumatic brain injury (TBI) with loss of consciousness does not affect the rate of cognitive change over time for people with normal cognition or people with Alzheimer’s disease, according to a study published online ahead of print June 22 in the Journal of Alzheimer’s Disease. Researchers compared performance on cognitive tests over time for 432 participants with normal cognition and 274 participants with probable Alzheimer’s disease. They matched participants with a history of TBI with loss of consciousness to an equal number of demographically and clinically similar participants without a history of TBI. Mixed-effects regressions showed that a history of TBI with loss of consciousness did not affect rates of cognitive change in APOE ε4 carriers and noncarriers.
Tripodis Y, Alosco ML, Zirogiannis N, et al. The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimers Dis. 2017 Jun 22 [Epub ahead of print].
Visual Changes in Parkinson’s Disease
Visual system alterations can be detected in early stages of Parkinson’s disease, and the entire intracranial visual system can be involved, according to a study published online ahead of print July 11 in Radiology. Twenty patients with newly diagnosed Parkinson’s disease and 20 age-matched control subjects were studied. Researchers used diffusion-weighted imaging to assess white matter changes and voxel-based morphometry (VBM) to investigate concentration changes of gray and white matter. In patients with Parkinson’s disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density, a significant increase in optic radiation mean diffusivity, and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes.
Arrigo A, Calamuneri A, Milardi D, et al. Visual system involvement in patients with newly diagnosed Parkinson disease. Radiology. 2017 Jul 11 [Epub ahead of print].
—Kimberly Williams
Brain Training Shows Little Benefit
Commercial brain training with Lumosity has no effect on decision making or cognitive function beyond practice effects on training tasks, according to a study published online ahead of print July 10 in the Journal of Neuroscience. Researchers tested whether training executive cognitive function could influence choice behavior and brain responses. In a randomized controlled trial, 128 young adults (71 male) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. The participants also completed a series of cognitive tests that were not part of the training. Although both groups showed improvement, commercial brain training did not lead to more improvement than online video games did.
Kable JW, Caulfield MK, Falcone M, et al. No effect of commercial cognitive training on neural activity during decision-making. J Neurosci. 2017 Jul 10 [Epub ahead of print].
Sense of Purpose Linked to Better Sleep
A higher level of meaning and purpose in life among older adults is associated with better sleep quality and appears to protect against symptoms of sleep apnea and restless legs syndrome (RLS), according to a study published online ahead of print July 10 in Sleep Science and Practice. Included in this study were 825 nondemented older African Americans (n = 428) and whites (n = 397), from the Minority Aging Research Study and the Rush Memory and Aging Project. Participants completed a 32-item questionnaire assessing sleep quality and symptoms of sleep apnea, RLS, and REM sleep behavior disorder. Longitudinal follow-up data indicated that higher levels of purpose in life were associated with lower risk of sleep apnea at baseline, one-year follow-up, and two-year follow-up, and with reduced RLS symptoms at one-year and two-year follow-up.
Turner AD, Smith CE, Ong JC. Is purpose in life associated with less sleep disturbance in older adults? Sleep Sci Pract. 2017 July 10 [Epub ahead of print].
Can Breastfeeding Reduce MS Risk in Mothers?
Mothers who breastfeed longer may be at lower subsequent risk of developing multiple sclerosis (MS), according to a study published online ahead of print July 12 in Neurology. Researchers recruited women with newly diagnosed MS or clinically isolated syndrome (CIS) and matched controls into the MS Sunshine Study from the membership of Kaiser Permanente Southern California. An in-person questionnaire was administered to collect behavioral and biologic factors to calculate ovulatory years. Among women who had live births, a cumulative duration of breastfeeding for 15 months or more was associated with a reduced risk of MS and CIS (adjusted odds ratio, 0.47). Being age 15 or older at menarche also was associated with a lower risk of MS and CIS (adjusted odds ratio, 0.56).
Langer-Gould A, Smith JB, Hellwig K, et al. Breastfeeding, ovulatory years, and risk of multiple sclerosis. Neurology. 2017 July 12 [Epub ahead of print].
Does Added Weight Increase Survival After Stroke?
People who are overweight or mildly obese survive strokes at a higher rate, compared with people of normal body weight, according to a study published June 24 in the Journal of the American Heart Association. Participants from the Framingham Heart Study were followed for as long as 10 years, with BMI measured prior to their strokes. Researchers compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. There were 782 stroke cases and 2,346 controls. The association of reduced mortality with BMI of 25 or higher, compared with BMI of 18.5 to less than 25, was pronounced among ischemic stroke cases, but diminished with inclusion of hemorrhagic strokes.
Aparicio HJ, Himali JJ, Beiser AS, et al. Overweight, obesity, and survival after stroke in the Framingham Heart Study. J Am Heart Assoc. 2017;6(6).
Poor Sleep Linked to CSF Biomarkers
Self-reported poor sleep is associated with greater Alzheimer’s disease-related pathology in cognitively healthy adults at risk for Alzheimer’s disease, according to a study published online ahead of print July 5 in Neurology. Researchers investigated the relationship between sleep quality and CSF Alzheimer’s disease biomarkers in a cohort enriched for parental history of sporadic Alzheimer’s disease. In all, 101 participants completed sleep assessments and CSF collection and were cognitively normal. CSF was assayed for biomarkers of amyloid metabolism and plaques, tau pathology, neuronal and axonal degeneration, neuroinflammation and astroglial activation, and synaptic dysfunction and degeneration. Worse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater Alzheimer’s disease pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42.
Sprecher KE, Koscik RL, Carlsson CM, et al. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology. 2017 Jul 5 [Epub ahead of print].
Is There a Link Between Parkinson’s Disease and Melanoma?
Melanoma and Parkinson’s disease may be associated, according to a study published in the July issue of Mayo Clinic Proceedings. For phase I of the Rochester Epidemiology Project, investigators used records to identify patients with Parkinson’s disease and match three controls per case. During phase II of this study, all Rochester Epidemiology Project cases of melanoma were identified, with one control per case. Investigators used a Cox proportional hazards model to assess the risk of developing Parkinson’s disease after the index date in cases versus controls, and performed Kaplan-Meier analysis to determine the 35-year cumulative risk of Parkinson’s disease. Patients with Parkinson’s disease had a 3.8-fold increased likelihood of having preexisting melanoma, compared with controls. Patients with melanoma had a 4.2-fold increased risk of developing Parkinson’s disease.
Dalvin LA, Damento GM, Yawn BP, et al. Parkinson disease and melanoma: confirming and reexamining an association. Mayo Clin Proc. 2017;92(7):1070-1079.
Zolpidem Treats Various Neurologic Disorders
A systematic review shows that zolpidem can treat various neurologic disorders, most often related to movement disorders and disorders of consciousness, according to a literature review published online ahead of print June 26 in JAMA Neurology. The investigators searched for English-language articles, published by March 20, 2015, that examined the use of zolpidem for noninsomnia neurologic disorders. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. In all, 67 articles were eligible for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions. The effects of zolpidem were wide ranging and generally lasted for one to four hours before the participant returned to baseline. Sedation was the most common adverse effect.
Bomalaski MN, Claflin ES, Townsend W, Peterson MD. Zolpidem for the treatment of neurologic disorders: a systematic review. JAMA Neurol. 2017 Jun 26 [Epub ahead of print].
Colored Light Triggers Responses in Migraineurs
Lights trigger more changes in autonomic functions and negative emotions during migraine than in control subjects, and the association between light and positive emotions is stronger in control subjects than in migraineurs, according to a study published online ahead of print June 26 in the Proceedings of the National Academy of Sciences. Researchers showed different colored lights to 81 migraineurs and 17 people who had never had a migraine. The effects of light and color were tested three times. Investigators found that all colors of light triggered unpleasant physiologic sensations in patients with migraines, during and between attacks. Additionally, migraineurs reported intense emotional responses such as anger, nervousness, hopelessness, sadness, depression, anxiety, and fear when exposed to all light colors except green.
Noseda R, Lee AJ, Nir RR, et al. Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine. Proc Natl Acad Sci. 2017 Jun 26 [Epub ahead of print].
TBI May Not Hasten Cognitive Decline
Having a history of traumatic brain injury (TBI) with loss of consciousness does not affect the rate of cognitive change over time for people with normal cognition or people with Alzheimer’s disease, according to a study published online ahead of print June 22 in the Journal of Alzheimer’s Disease. Researchers compared performance on cognitive tests over time for 432 participants with normal cognition and 274 participants with probable Alzheimer’s disease. They matched participants with a history of TBI with loss of consciousness to an equal number of demographically and clinically similar participants without a history of TBI. Mixed-effects regressions showed that a history of TBI with loss of consciousness did not affect rates of cognitive change in APOE ε4 carriers and noncarriers.
Tripodis Y, Alosco ML, Zirogiannis N, et al. The effect of traumatic brain injury history with loss of consciousness on rate of cognitive decline among older adults with normal cognition and Alzheimer’s disease dementia. J Alzheimers Dis. 2017 Jun 22 [Epub ahead of print].
Visual Changes in Parkinson’s Disease
Visual system alterations can be detected in early stages of Parkinson’s disease, and the entire intracranial visual system can be involved, according to a study published online ahead of print July 11 in Radiology. Twenty patients with newly diagnosed Parkinson’s disease and 20 age-matched control subjects were studied. Researchers used diffusion-weighted imaging to assess white matter changes and voxel-based morphometry (VBM) to investigate concentration changes of gray and white matter. In patients with Parkinson’s disease, significant alterations were found in optic radiation connectivity distribution, with decreased lateral geniculate nucleus V2 density, a significant increase in optic radiation mean diffusivity, and a significant reduction in white matter concentration. VBM analysis also showed a significant reduction in visual cortical volumes.
Arrigo A, Calamuneri A, Milardi D, et al. Visual system involvement in patients with newly diagnosed Parkinson disease. Radiology. 2017 Jul 11 [Epub ahead of print].
—Kimberly Williams
New and Noteworthy Information—July 2017
Device Helps Patients Move Paralyzed Hands After Stroke
Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.
Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].
Pyrimethamine Lowers Levels of ALS Biomarker
Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.
Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].
Statin Use Linked to Higher Risk of Parkinson’s Disease
Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.
Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.
Is Moderate Drinking Associated With Cognitive Decline?
Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.
Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].
Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease
Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.
Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].
Elevated Brain Amyloid Increases Likelihood of Cognitive Decline
Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.
Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.
Seven Risk Genes for Insomnia Found
Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1,
Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].
Is Telemedicine for Headache as Effective as In-Person Visit?
In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.
Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].
Minocycline Reduces Risk of Conversion From CIS to MS
The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.
Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.
Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?
In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.
Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].
Support From Children Reduces Risk of Dementia
Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.
Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.
—Kimberly Williams
Device Helps Patients Move Paralyzed Hands After Stroke
Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.
Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].
Pyrimethamine Lowers Levels of ALS Biomarker
Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.
Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].
Statin Use Linked to Higher Risk of Parkinson’s Disease
Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.
Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.
Is Moderate Drinking Associated With Cognitive Decline?
Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.
Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].
Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease
Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.
Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].
Elevated Brain Amyloid Increases Likelihood of Cognitive Decline
Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.
Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.
Seven Risk Genes for Insomnia Found
Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1,
Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].
Is Telemedicine for Headache as Effective as In-Person Visit?
In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.
Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].
Minocycline Reduces Risk of Conversion From CIS to MS
The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.
Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.
Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?
In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.
Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].
Support From Children Reduces Risk of Dementia
Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.
Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.
—Kimberly Williams
Device Helps Patients Move Paralyzed Hands After Stroke
Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.
Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].
Pyrimethamine Lowers Levels of ALS Biomarker
Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.
Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].
Statin Use Linked to Higher Risk of Parkinson’s Disease
Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.
Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.
Is Moderate Drinking Associated With Cognitive Decline?
Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.
Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].
Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease
Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.
Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].
Elevated Brain Amyloid Increases Likelihood of Cognitive Decline
Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.
Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.
Seven Risk Genes for Insomnia Found
Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1,
Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].
Is Telemedicine for Headache as Effective as In-Person Visit?
In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.
Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].
Minocycline Reduces Risk of Conversion From CIS to MS
The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.
Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.
Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?
In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.
Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].
Support From Children Reduces Risk of Dementia
Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.
Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.
—Kimberly Williams
New and Noteworthy Information—June 2017
Can Biomarkers Predict Cognitive Deficits in Parkinson’s Disease?
Biomarkers may predict which patients with Parkinson’s disease will have significant cognitive deficits within the first three years after diagnosis, according to a study published May 17 in PLOS One. Researchers conducted an international, prospective study of 423 newly diagnosed and untreated patients with Parkinson’s disease with no signs of cognitive impairment at the time of enrollment in 2010. Investigators conducted brain scans, genetic tests, and analyses of CSF at baseline and during follow-up. At three years, between 15% and 38% of participants had developed cognitive impairment. Brain scans identified dopamine deficiency and decreased brain volume as predictors of cognitive decline. Low CSF beta-amyloid level and single-nucleotide polymorphisms (SNPs) in COMT and BDNF also predicted cognitive decline. These SNPs previously had been associated with cognitive impairment.
Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 2017 May 17;12(5):e0175674.
Service Members With Concussive Blast TBI Have Worsening Outcomes
Military service members with concussive blast traumatic brain injury (TBI) have considerable decline in clinical outcomes over five years, according to a study published online ahead of print May 1 in JAMA Neurology. This prospective longitudinal study enrolled active-duty US military after concussive blast injury in the acute to subacute stage and combat-deployed control individuals in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. Physicians in the United States performed one- and five-year clinical evaluations. Among the 94 participants, global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI, compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the five-year evaluation.
Mac Donald CL, Barber J, Jordan M, et al. Early clinical predictors of 5-year outcome after concussive blast traumatic brain injury. JAMA Neurol. 2017 May 1 [Epub ahead of print].
Biomarker Linked to Increased Risk of Ischemic Stroke in Women
High levels of β2-microglobulin are associated with an increased risk of ischemic stroke among women, according to a study published online ahead of print May 10 in Neurology. Researchers performed a nested case–control study among women enrolled in the Nurses’ Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. Investigators measured β2-microglobulin levels in 473 ischemic stroke cases and 473 controls matched on age, race, and other variables. Median levels of β2-microglobulin were 1.86 mg/L in cases and 1.80 mg/L in controls. Women in the highest β2-microglobulin quartile had a multivariable-adjusted increased risk of ischemic stroke, compared with women in the lowest quartile (odds ratio, 1.56). Results were similar when restricted to those without chronic kidney disease.
Rist PM, Jiménez MC, Rexrode KM. Prospective association between β2-microglobulin levels and ischemic stroke risk among women. Neurology. 2017 May 10 [Epub ahead of print].
Female Hormones May Cause Headache in Girls With Migraine
Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine, according to a study published online ahead of print May 8 in Cephalalgia. The study included 34 girls with migraine grouped into three age strata (ie, prepubertal, pubertal, and postpubertal). Participants collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide and pregnandiol glucuronide, and the daily change in each was calculated. The primary outcome measures were headache onset days and headache severity. Models of headache onset days demonstrated a significant interaction between age and pregnandiol glucuronide. Change in pregnandiol glucuronide was associated with headache severity.
Martin VT, Allen JR, Houle TT, et al. Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: an observational cohort study. Cephalalgia. 2017 Jan 1 [Epub ahead of print].
PTSD Is Associated With Risk for Dementia Diagnosis
Posttraumatic stress disorder (PTSD) diagnosis is associated with an increased risk for dementia diagnosis that varies with psychotropic medication, according to a study published in the May issue of the Journal of the American Geriatrics Society. Researchers examined information from 417,172 veterans age 56 and older without dementia or mild cognitive impairment. During the study’s nine-year follow-up period, participants had a clinical encounter every two years. PTSD diagnosis significantly increased the risk for dementia diagnosis. The hazard ratio for dementia diagnosis among veterans diagnosed with PTSD who did not use psychotropic medications was 1.55. Among veterans diagnosed with PTSD and prescribed psychotropic medication, the hazard ratio for dementia diagnosis ranged from 1.99 for SSRIs to 4.21 for atypical antipsychotics.
Mawanda F, Wallace RB, McCoy K, Abrams TE. PTSD, psychotropic medication use, and the risk of dementia among US veterans: a retrospective cohort study. J Am Geriatr Soc. 2017;65(5):1043-1050.
Screening for Atrial Fibrillation Recommended
Screening for asymptomatic atrial fibrillation in people age 65 and older and treating it with anticoagulant medications could greatly reduce the risk of stroke and premature death, according to the AF-SCREEN International Collaboration report published May 9 in Circulation. In 2016, 60 members of the collaboration, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare a draft document. They concluded that screen-detected atrial fibrillation found at a single timepoint or by intermittent ECG recordings over two weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. Handheld ECG devices are preferred as screening tools because they provide a verifiable ECG trace that guidelines require for diagnosis, said the authors.
Freedman B, Camm J, Calkins H, et al. Screening for atrial fibrillation: a report of the AF-SCREEN international collaboration. Circulation. 2017;135(19):1851-1867.
Can Music Reduce Depressive Symptoms in Dementia?
Providing people with dementia with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms, but has little or no effect on agitation or aggression, according to a study published online ahead of print May 2 in the Cochrane Database of Systematic Reviews. Researchers searched ALOIS on April 14, 2010, using the terms “music therapy,” “music,” “singing,” “sing,” and “auditory stimulation.” Sixteen studies with a total of 620 participants contributed data to meta-analyses. Participants in the studies had dementia of varying severity. The investigators found that music-based therapeutic interventions may have little or no effect on emotional well-being and quality of life, overall behavior problems, and cognition. Study authors also found moderate-quality evidence that these interventions reduce depressive symptoms, but do not decrease agitation or aggression.
van der Steen JT, van Soest-Poortvliet MC, van der Wouden JC, et al. Music-based therapeutic interventions for people with dementia. Cochrane Database Syst Rev. 2017 May 2 [Epub ahead of print].
FDA Approves Radicava for Treatment of ALS
The FDA has approved Radicava (edaravone) as an IV treatment for amyotrophic lateral sclerosis (ALS). A phase III study evaluated the efficacy and safety of Radicava, compared with placebo, in 137 people with ALS. After a 12-week preobservation period, eligible patients were randomized 1:1 to receive 60 mg of Radicava in an IV for 60 minutes or placebo during a six-month double-blind phase. People given Radicava showed significantly less decline in physical function, compared with controls, as measured by the ALS Functional Rating Scale-Revised. The most common adverse reactions that occurred in greater than 10% of patients and greater than placebo were bruising, walking difficulties, and headache. Radicava is administered in 28-day cycles. MT Pharma America, headquartered in Jersey City, New Jersey, markets Radicava.
Can Cooling the Body Reduce Brain Injury?
Cooling the body may reduce brain injury for people in a coma after being revived from cardiac arrest, according to a guideline published online ahead of print May 10 in Neurology. Researchers reviewed evidence from studies of methods to reduce brain injury in people who are comatose after resuscitation from cardiac arrest. The guideline found that for patients who are treated with electric shocks to the heart after out-of-hospital cardiac arrest and who are in a coma, cooling the body to 89.6 to 93.2 °F for 24 hours effectively improves the chance of recovering brain function. The authors also found that keeping the body cooled to 96.8 °F for 24 hours, followed by rewarming to 99.5 °F over eight hours, effectively reduces brain injury after cardiac arrest.
Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: reducing brain injury following cardiopulmonary resuscitation: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 May 10 [Epub ahead of print].
Granger Causality Analysis Can Localize Ictal Networks
Granger causality analysis has the potential to help localize ictal networks from interictal data, according to a study published online ahead of print May 2 in Neurosurgery. For this study, 20-minute interictal baselines were obtained from 25 patients with hard-to-treat epilepsy who previously had had long-term EEG monitoring. The Granger causality maps were quantitatively compared with conventionally constructed surgical plans by using rank order and Cartesian distance statistics. In 16 of 25 participants, the interictal Granger causality rankings of the electrodes in the ictally active electrode set were lower than predicted by chance. The Granger causality maps thus likely correlated with ictal networks. The distance from the highest Granger causality electrode to the ictally active electrode set and to the resection averaged 6 and 4 mm, respectively.
Park EH, Madsen JR. Granger causality analysis of interictal iEEG predicts seizure focus and ultimate resection. Neurosurgery. 2017 May 2 [Epub ahead of print].
Tourette Disorder Risk Genes Identified
Researchers have identified the first risk gene for Tourette disorder and three other probable risk genes, according to a study published May 3 in Neuron. Researchers analyzed genomic data from 311 trios of children with Tourette disorder and their parents. Data were collected by the Tourette International Collaborative Genetics group. The authors found strong evidence that variants of WWC1 can play a significant role in triggering the disorder. Investigators conducted a replication study in 173 trios and found the same results. Extrapolating from the number of de novo variants, investigators estimated that approximately 12% of Tourette disorder cases are likely to involve de novo variants. The genes CELSR3, NIPBL, and FN1 were identified as having at least 70% probability of contributing to Tourette disorder.
Willsey AJ, Fernandez TV, Yu D, et al. De novo coding variants are strongly associated with Tourette disorder. Neuron. 2017;94(3):486-499.
—Kimberly Williams
Can Biomarkers Predict Cognitive Deficits in Parkinson’s Disease?
Biomarkers may predict which patients with Parkinson’s disease will have significant cognitive deficits within the first three years after diagnosis, according to a study published May 17 in PLOS One. Researchers conducted an international, prospective study of 423 newly diagnosed and untreated patients with Parkinson’s disease with no signs of cognitive impairment at the time of enrollment in 2010. Investigators conducted brain scans, genetic tests, and analyses of CSF at baseline and during follow-up. At three years, between 15% and 38% of participants had developed cognitive impairment. Brain scans identified dopamine deficiency and decreased brain volume as predictors of cognitive decline. Low CSF beta-amyloid level and single-nucleotide polymorphisms (SNPs) in COMT and BDNF also predicted cognitive decline. These SNPs previously had been associated with cognitive impairment.
Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 2017 May 17;12(5):e0175674.
Service Members With Concussive Blast TBI Have Worsening Outcomes
Military service members with concussive blast traumatic brain injury (TBI) have considerable decline in clinical outcomes over five years, according to a study published online ahead of print May 1 in JAMA Neurology. This prospective longitudinal study enrolled active-duty US military after concussive blast injury in the acute to subacute stage and combat-deployed control individuals in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. Physicians in the United States performed one- and five-year clinical evaluations. Among the 94 participants, global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI, compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the five-year evaluation.
Mac Donald CL, Barber J, Jordan M, et al. Early clinical predictors of 5-year outcome after concussive blast traumatic brain injury. JAMA Neurol. 2017 May 1 [Epub ahead of print].
Biomarker Linked to Increased Risk of Ischemic Stroke in Women
High levels of β2-microglobulin are associated with an increased risk of ischemic stroke among women, according to a study published online ahead of print May 10 in Neurology. Researchers performed a nested case–control study among women enrolled in the Nurses’ Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. Investigators measured β2-microglobulin levels in 473 ischemic stroke cases and 473 controls matched on age, race, and other variables. Median levels of β2-microglobulin were 1.86 mg/L in cases and 1.80 mg/L in controls. Women in the highest β2-microglobulin quartile had a multivariable-adjusted increased risk of ischemic stroke, compared with women in the lowest quartile (odds ratio, 1.56). Results were similar when restricted to those without chronic kidney disease.
Rist PM, Jiménez MC, Rexrode KM. Prospective association between β2-microglobulin levels and ischemic stroke risk among women. Neurology. 2017 May 10 [Epub ahead of print].
Female Hormones May Cause Headache in Girls With Migraine
Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine, according to a study published online ahead of print May 8 in Cephalalgia. The study included 34 girls with migraine grouped into three age strata (ie, prepubertal, pubertal, and postpubertal). Participants collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide and pregnandiol glucuronide, and the daily change in each was calculated. The primary outcome measures were headache onset days and headache severity. Models of headache onset days demonstrated a significant interaction between age and pregnandiol glucuronide. Change in pregnandiol glucuronide was associated with headache severity.
Martin VT, Allen JR, Houle TT, et al. Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: an observational cohort study. Cephalalgia. 2017 Jan 1 [Epub ahead of print].
PTSD Is Associated With Risk for Dementia Diagnosis
Posttraumatic stress disorder (PTSD) diagnosis is associated with an increased risk for dementia diagnosis that varies with psychotropic medication, according to a study published in the May issue of the Journal of the American Geriatrics Society. Researchers examined information from 417,172 veterans age 56 and older without dementia or mild cognitive impairment. During the study’s nine-year follow-up period, participants had a clinical encounter every two years. PTSD diagnosis significantly increased the risk for dementia diagnosis. The hazard ratio for dementia diagnosis among veterans diagnosed with PTSD who did not use psychotropic medications was 1.55. Among veterans diagnosed with PTSD and prescribed psychotropic medication, the hazard ratio for dementia diagnosis ranged from 1.99 for SSRIs to 4.21 for atypical antipsychotics.
Mawanda F, Wallace RB, McCoy K, Abrams TE. PTSD, psychotropic medication use, and the risk of dementia among US veterans: a retrospective cohort study. J Am Geriatr Soc. 2017;65(5):1043-1050.
Screening for Atrial Fibrillation Recommended
Screening for asymptomatic atrial fibrillation in people age 65 and older and treating it with anticoagulant medications could greatly reduce the risk of stroke and premature death, according to the AF-SCREEN International Collaboration report published May 9 in Circulation. In 2016, 60 members of the collaboration, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare a draft document. They concluded that screen-detected atrial fibrillation found at a single timepoint or by intermittent ECG recordings over two weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. Handheld ECG devices are preferred as screening tools because they provide a verifiable ECG trace that guidelines require for diagnosis, said the authors.
Freedman B, Camm J, Calkins H, et al. Screening for atrial fibrillation: a report of the AF-SCREEN international collaboration. Circulation. 2017;135(19):1851-1867.
Can Music Reduce Depressive Symptoms in Dementia?
Providing people with dementia with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms, but has little or no effect on agitation or aggression, according to a study published online ahead of print May 2 in the Cochrane Database of Systematic Reviews. Researchers searched ALOIS on April 14, 2010, using the terms “music therapy,” “music,” “singing,” “sing,” and “auditory stimulation.” Sixteen studies with a total of 620 participants contributed data to meta-analyses. Participants in the studies had dementia of varying severity. The investigators found that music-based therapeutic interventions may have little or no effect on emotional well-being and quality of life, overall behavior problems, and cognition. Study authors also found moderate-quality evidence that these interventions reduce depressive symptoms, but do not decrease agitation or aggression.
van der Steen JT, van Soest-Poortvliet MC, van der Wouden JC, et al. Music-based therapeutic interventions for people with dementia. Cochrane Database Syst Rev. 2017 May 2 [Epub ahead of print].
FDA Approves Radicava for Treatment of ALS
The FDA has approved Radicava (edaravone) as an IV treatment for amyotrophic lateral sclerosis (ALS). A phase III study evaluated the efficacy and safety of Radicava, compared with placebo, in 137 people with ALS. After a 12-week preobservation period, eligible patients were randomized 1:1 to receive 60 mg of Radicava in an IV for 60 minutes or placebo during a six-month double-blind phase. People given Radicava showed significantly less decline in physical function, compared with controls, as measured by the ALS Functional Rating Scale-Revised. The most common adverse reactions that occurred in greater than 10% of patients and greater than placebo were bruising, walking difficulties, and headache. Radicava is administered in 28-day cycles. MT Pharma America, headquartered in Jersey City, New Jersey, markets Radicava.
Can Cooling the Body Reduce Brain Injury?
Cooling the body may reduce brain injury for people in a coma after being revived from cardiac arrest, according to a guideline published online ahead of print May 10 in Neurology. Researchers reviewed evidence from studies of methods to reduce brain injury in people who are comatose after resuscitation from cardiac arrest. The guideline found that for patients who are treated with electric shocks to the heart after out-of-hospital cardiac arrest and who are in a coma, cooling the body to 89.6 to 93.2 °F for 24 hours effectively improves the chance of recovering brain function. The authors also found that keeping the body cooled to 96.8 °F for 24 hours, followed by rewarming to 99.5 °F over eight hours, effectively reduces brain injury after cardiac arrest.
Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: reducing brain injury following cardiopulmonary resuscitation: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 May 10 [Epub ahead of print].
Granger Causality Analysis Can Localize Ictal Networks
Granger causality analysis has the potential to help localize ictal networks from interictal data, according to a study published online ahead of print May 2 in Neurosurgery. For this study, 20-minute interictal baselines were obtained from 25 patients with hard-to-treat epilepsy who previously had had long-term EEG monitoring. The Granger causality maps were quantitatively compared with conventionally constructed surgical plans by using rank order and Cartesian distance statistics. In 16 of 25 participants, the interictal Granger causality rankings of the electrodes in the ictally active electrode set were lower than predicted by chance. The Granger causality maps thus likely correlated with ictal networks. The distance from the highest Granger causality electrode to the ictally active electrode set and to the resection averaged 6 and 4 mm, respectively.
Park EH, Madsen JR. Granger causality analysis of interictal iEEG predicts seizure focus and ultimate resection. Neurosurgery. 2017 May 2 [Epub ahead of print].
Tourette Disorder Risk Genes Identified
Researchers have identified the first risk gene for Tourette disorder and three other probable risk genes, according to a study published May 3 in Neuron. Researchers analyzed genomic data from 311 trios of children with Tourette disorder and their parents. Data were collected by the Tourette International Collaborative Genetics group. The authors found strong evidence that variants of WWC1 can play a significant role in triggering the disorder. Investigators conducted a replication study in 173 trios and found the same results. Extrapolating from the number of de novo variants, investigators estimated that approximately 12% of Tourette disorder cases are likely to involve de novo variants. The genes CELSR3, NIPBL, and FN1 were identified as having at least 70% probability of contributing to Tourette disorder.
Willsey AJ, Fernandez TV, Yu D, et al. De novo coding variants are strongly associated with Tourette disorder. Neuron. 2017;94(3):486-499.
—Kimberly Williams
Can Biomarkers Predict Cognitive Deficits in Parkinson’s Disease?
Biomarkers may predict which patients with Parkinson’s disease will have significant cognitive deficits within the first three years after diagnosis, according to a study published May 17 in PLOS One. Researchers conducted an international, prospective study of 423 newly diagnosed and untreated patients with Parkinson’s disease with no signs of cognitive impairment at the time of enrollment in 2010. Investigators conducted brain scans, genetic tests, and analyses of CSF at baseline and during follow-up. At three years, between 15% and 38% of participants had developed cognitive impairment. Brain scans identified dopamine deficiency and decreased brain volume as predictors of cognitive decline. Low CSF beta-amyloid level and single-nucleotide polymorphisms (SNPs) in COMT and BDNF also predicted cognitive decline. These SNPs previously had been associated with cognitive impairment.
Caspell-Garcia C, Simuni T, Tosun-Turgut D, et al. Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One. 2017 May 17;12(5):e0175674.
Service Members With Concussive Blast TBI Have Worsening Outcomes
Military service members with concussive blast traumatic brain injury (TBI) have considerable decline in clinical outcomes over five years, according to a study published online ahead of print May 1 in JAMA Neurology. This prospective longitudinal study enrolled active-duty US military after concussive blast injury in the acute to subacute stage and combat-deployed control individuals in Afghanistan or after medical evacuation to Germany from November 1, 2008, through July 1, 2013. Physicians in the United States performed one- and five-year clinical evaluations. Among the 94 participants, global disability, satisfaction with life, neurobehavioral symptom severity, psychiatric symptom severity, and sleep impairment were significantly worse in patients with concussive blast TBI, compared with combat-deployed controls, whereas performance on cognitive measures was no different between groups at the five-year evaluation.
Mac Donald CL, Barber J, Jordan M, et al. Early clinical predictors of 5-year outcome after concussive blast traumatic brain injury. JAMA Neurol. 2017 May 1 [Epub ahead of print].
Biomarker Linked to Increased Risk of Ischemic Stroke in Women
High levels of β2-microglobulin are associated with an increased risk of ischemic stroke among women, according to a study published online ahead of print May 10 in Neurology. Researchers performed a nested case–control study among women enrolled in the Nurses’ Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. Investigators measured β2-microglobulin levels in 473 ischemic stroke cases and 473 controls matched on age, race, and other variables. Median levels of β2-microglobulin were 1.86 mg/L in cases and 1.80 mg/L in controls. Women in the highest β2-microglobulin quartile had a multivariable-adjusted increased risk of ischemic stroke, compared with women in the lowest quartile (odds ratio, 1.56). Results were similar when restricted to those without chronic kidney disease.
Rist PM, Jiménez MC, Rexrode KM. Prospective association between β2-microglobulin levels and ischemic stroke risk among women. Neurology. 2017 May 10 [Epub ahead of print].
Female Hormones May Cause Headache in Girls With Migraine
Age and pubertal development could moderate the effect of ovarian hormones on days of headache onset in girls with migraine, according to a study published online ahead of print May 8 in Cephalalgia. The study included 34 girls with migraine grouped into three age strata (ie, prepubertal, pubertal, and postpubertal). Participants collected daily urine samples and recorded the occurrence and severity of headache in a daily diary. Urine samples were assayed for estrone glucuronide and pregnandiol glucuronide, and the daily change in each was calculated. The primary outcome measures were headache onset days and headache severity. Models of headache onset days demonstrated a significant interaction between age and pregnandiol glucuronide. Change in pregnandiol glucuronide was associated with headache severity.
Martin VT, Allen JR, Houle TT, et al. Ovarian hormones, age and pubertal development and their association with days of headache onset in girls with migraine: an observational cohort study. Cephalalgia. 2017 Jan 1 [Epub ahead of print].
PTSD Is Associated With Risk for Dementia Diagnosis
Posttraumatic stress disorder (PTSD) diagnosis is associated with an increased risk for dementia diagnosis that varies with psychotropic medication, according to a study published in the May issue of the Journal of the American Geriatrics Society. Researchers examined information from 417,172 veterans age 56 and older without dementia or mild cognitive impairment. During the study’s nine-year follow-up period, participants had a clinical encounter every two years. PTSD diagnosis significantly increased the risk for dementia diagnosis. The hazard ratio for dementia diagnosis among veterans diagnosed with PTSD who did not use psychotropic medications was 1.55. Among veterans diagnosed with PTSD and prescribed psychotropic medication, the hazard ratio for dementia diagnosis ranged from 1.99 for SSRIs to 4.21 for atypical antipsychotics.
Mawanda F, Wallace RB, McCoy K, Abrams TE. PTSD, psychotropic medication use, and the risk of dementia among US veterans: a retrospective cohort study. J Am Geriatr Soc. 2017;65(5):1043-1050.
Screening for Atrial Fibrillation Recommended
Screening for asymptomatic atrial fibrillation in people age 65 and older and treating it with anticoagulant medications could greatly reduce the risk of stroke and premature death, according to the AF-SCREEN International Collaboration report published May 9 in Circulation. In 2016, 60 members of the collaboration, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare a draft document. They concluded that screen-detected atrial fibrillation found at a single timepoint or by intermittent ECG recordings over two weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. Handheld ECG devices are preferred as screening tools because they provide a verifiable ECG trace that guidelines require for diagnosis, said the authors.
Freedman B, Camm J, Calkins H, et al. Screening for atrial fibrillation: a report of the AF-SCREEN international collaboration. Circulation. 2017;135(19):1851-1867.
Can Music Reduce Depressive Symptoms in Dementia?
Providing people with dementia with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms, but has little or no effect on agitation or aggression, according to a study published online ahead of print May 2 in the Cochrane Database of Systematic Reviews. Researchers searched ALOIS on April 14, 2010, using the terms “music therapy,” “music,” “singing,” “sing,” and “auditory stimulation.” Sixteen studies with a total of 620 participants contributed data to meta-analyses. Participants in the studies had dementia of varying severity. The investigators found that music-based therapeutic interventions may have little or no effect on emotional well-being and quality of life, overall behavior problems, and cognition. Study authors also found moderate-quality evidence that these interventions reduce depressive symptoms, but do not decrease agitation or aggression.
van der Steen JT, van Soest-Poortvliet MC, van der Wouden JC, et al. Music-based therapeutic interventions for people with dementia. Cochrane Database Syst Rev. 2017 May 2 [Epub ahead of print].
FDA Approves Radicava for Treatment of ALS
The FDA has approved Radicava (edaravone) as an IV treatment for amyotrophic lateral sclerosis (ALS). A phase III study evaluated the efficacy and safety of Radicava, compared with placebo, in 137 people with ALS. After a 12-week preobservation period, eligible patients were randomized 1:1 to receive 60 mg of Radicava in an IV for 60 minutes or placebo during a six-month double-blind phase. People given Radicava showed significantly less decline in physical function, compared with controls, as measured by the ALS Functional Rating Scale-Revised. The most common adverse reactions that occurred in greater than 10% of patients and greater than placebo were bruising, walking difficulties, and headache. Radicava is administered in 28-day cycles. MT Pharma America, headquartered in Jersey City, New Jersey, markets Radicava.
Can Cooling the Body Reduce Brain Injury?
Cooling the body may reduce brain injury for people in a coma after being revived from cardiac arrest, according to a guideline published online ahead of print May 10 in Neurology. Researchers reviewed evidence from studies of methods to reduce brain injury in people who are comatose after resuscitation from cardiac arrest. The guideline found that for patients who are treated with electric shocks to the heart after out-of-hospital cardiac arrest and who are in a coma, cooling the body to 89.6 to 93.2 °F for 24 hours effectively improves the chance of recovering brain function. The authors also found that keeping the body cooled to 96.8 °F for 24 hours, followed by rewarming to 99.5 °F over eight hours, effectively reduces brain injury after cardiac arrest.
Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: reducing brain injury following cardiopulmonary resuscitation: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2017 May 10 [Epub ahead of print].
Granger Causality Analysis Can Localize Ictal Networks
Granger causality analysis has the potential to help localize ictal networks from interictal data, according to a study published online ahead of print May 2 in Neurosurgery. For this study, 20-minute interictal baselines were obtained from 25 patients with hard-to-treat epilepsy who previously had had long-term EEG monitoring. The Granger causality maps were quantitatively compared with conventionally constructed surgical plans by using rank order and Cartesian distance statistics. In 16 of 25 participants, the interictal Granger causality rankings of the electrodes in the ictally active electrode set were lower than predicted by chance. The Granger causality maps thus likely correlated with ictal networks. The distance from the highest Granger causality electrode to the ictally active electrode set and to the resection averaged 6 and 4 mm, respectively.
Park EH, Madsen JR. Granger causality analysis of interictal iEEG predicts seizure focus and ultimate resection. Neurosurgery. 2017 May 2 [Epub ahead of print].
Tourette Disorder Risk Genes Identified
Researchers have identified the first risk gene for Tourette disorder and three other probable risk genes, according to a study published May 3 in Neuron. Researchers analyzed genomic data from 311 trios of children with Tourette disorder and their parents. Data were collected by the Tourette International Collaborative Genetics group. The authors found strong evidence that variants of WWC1 can play a significant role in triggering the disorder. Investigators conducted a replication study in 173 trios and found the same results. Extrapolating from the number of de novo variants, investigators estimated that approximately 12% of Tourette disorder cases are likely to involve de novo variants. The genes CELSR3, NIPBL, and FN1 were identified as having at least 70% probability of contributing to Tourette disorder.
Willsey AJ, Fernandez TV, Yu D, et al. De novo coding variants are strongly associated with Tourette disorder. Neuron. 2017;94(3):486-499.
—Kimberly Williams
New and Noteworthy Information—May 2017
The Biomarkers for Infant Brain Injury Score can identify infants with acute intracranial hemorrhage, according to a study published online ahead of print April 10 in JAMA Pediatrics. Binary logistic regression was used to develop a multivariable model incorporating three serum biomarkers and one clinical variable (total hemoglobin). The Biomarkers for Infant Brain Injury Score was applied to 599 infants (mean age, 4.7 months) at increased risk for abusive head trauma. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive and 48.0% specific for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.
The FDA has approved Ocrevus (ocrelizumab), an IV infusion, to treat adults with relapsing forms of multiple sclerosis (MS) and primary progressive MS. This drug is the first to be approved by the FDA for primary progressive MS. The efficacy of Ocrevus for the treatment of relapsing-remitting MS was shown in two clinical trials including 1,656 participants treated for 96 weeks. In both studies, patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability, compared with patients receiving interferon beta-1a. In a study of 732 participants with primary progressive MS treated for at least 120 weeks, participants receiving Ocrevus had a longer time to the worsening of disability, compared with participants receiving placebo. Common side effects include infusion-related reactions and upper respiratory tract infection. Genentech markets Ocrevus.
Unemployed men and women and reemployed men have an increased risk of hemorrhagic and ischemic stroke and mortality, according to a study published online ahead of print April 6 in Stroke. This prospective study included 21,902 men and 19,826 women, ages 40 to 59, from nine public health centers across Japan. Participants were followed up from 1990–1993 to the end of 2009–2014. During the follow-up period, 973 incident strokes and 275 deaths from stroke occurred in men, as well as 460 strokes and 131 deaths from stroke in women. Compared with continuously employed subjects, the multivariable hazard ratio (HR) for total stroke incidence was 1.58 in unemployed men and 1.51 in unemployed women. HR for total stroke mortality was 2.22 in men and 2.48 in women.
In people with uncomplicated childhood-onset epilepsy and five-year terminal remission, young adult social outcomes are comparable to those of sibling controls, according to a study published online ahead of print April 4 in Epilepsia. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, which included 361 individuals with epilepsy and 173 controls. Social outcomes for cases with uncomplicated epilepsy with five or more years’ terminal remission were comparable to those of controls. Cases with uncomplicated epilepsy and less than five years of seizure freedom were more likely to be less productive and not to have a driver’s license. Complicated cases with epilepsy and less than five years of seizure freedom had worse outcomes across multiple domains, including not graduating high school.
Deep brain stimulation of the ventralis oralis internus and centromedian-parafascicular thalamus is an effective and relatively safe treatment for severe, refractory Tourette syndrome, according to a study published online ahead of print April 7 in the Journal of Neurosurgery. Researchers retrospectively reviewed outcomes in 13 patients with refractory Tourette syndrome who underwent medial thalamic deep brain stimulation for seven years. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale. Patients showed an average decrease of 37% in total tic severity at their first postoperative visit. During their most recent visit, patient scores decreased from preoperative scores by an average of 50%, which was statistically significant. Device-related complications occurred in two patients, necessitating additional surgeries.
The FDA has approved Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia. Ingrezza is a selective vesicular monoamine transporter 2 inhibitor. The approval of Ingrezza was based on data from the Kinect 3 study, a phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study comparing once-daily Ingrezza (80 mg and 40 mg) to placebo over six weeks in patients with schizophrenia, schizoaffective disorder, or mood disorder. The mean change from baseline to week six in the AIMS dyskinesia total score was –3.2 for patients receiving 80 mg/day of Ingrezza, compared with –0.1 for controls. Ingrezza also was generally well tolerated, with somnolence as the only adverse event occurring at a rate of 5% or greater and twice the rate associated with placebo. Neurocrine Biosciences markets Ingrezza.
Benzodiazepine use is associated with an increased risk of pneumonia among patients with Alzheimer’s disease, according to a study published April 10 in CMAJ. Researchers obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland between 2005 and 2011 from the Medication use and Alzheimer’s disease cohort. Incident users of benzodiazepines and nonbenzodiazepines were identified using a one-year washout period and matched with nonusers through propensity scores. Among 49,484 eligible participants with Alzheimer’s disease, 5,232 taking benzodiazepines and 3,269 taking nonbenzodiazepines were matched 1:1 with people not taking these drugs. Benzodiazepine and nonbenzodiazepine use was associated with a 22% increased risk of pneumonia. When analyzed separately, benzodiazepine use was significantly associated with a 28% increased risk of pneumonia, but nonbenzodiazepine use was not.
Hospitalization rates for acute ischemic stroke in young adults are increasing, along with the prevalence of traditional stroke risk factors, according to a study published online ahead of print April 10 in JAMA Neurology. Hospitalization data from the National Inpatient Sample from 1995 through 2012 were used to analyze acute stroke hospitalization rates among people ages 18 to 64. The 2003–2004 set included 362,339 hospitalizations, and the 2011–2012 set included 421,815 hospitalizations. Acute ischemic stroke hospitalization rates increased significantly for men and women, and for certain racial and ethnic groups, among younger adults ages 18 to 54. The prevalence of stroke risk factors among people hospitalized for acute ischemic stroke continued to increase from 2003–2004 through 2011–2012 for men and women ages 18 to 64.
A polygenic hazard score may help quantify individual differences in age-specific genetic risk for Alzheimer’s disease, according to a study published March 21 in PLOS Medicine. The investigators reviewed single-nucleotide polymorphisms associated with Alzheimer’s disease risk. Using a Cox proportional hazard model, they calculated polygenic hazard scores for participants in the Alzheimer’s Disease Genetics Consortium and tested them in two independent cohorts. People in the top polygenic hazard score quartile developed Alzheimer’s disease at a considerably lower age and had the highest yearly Alzheimer’s disease incidence rate. Among people who did not have the APOE ε3 allele, polygenic hazard score modified the age of expected onset by more than 10 years between the lowest and highest deciles. In independent cohorts, the polygenic hazard score strongly predicted age of Alzheimer’s disease onset.
Generalized anxiety disorder (GAD) is associated with migraine, according to a study published in the March issue of Headache. Researchers performed a secondary data analysis of the 2012 Canadian Community Health Survey-Mental Health. The first subsample included people with and without migraine. The second subsample was restricted to people with migraine. Six percent of people with migraine had had GAD in the previous year, compared with 2.1% of people without migraine. The adjusted odds of previous year GAD were 2.5 times higher among people with migraine than among people without. In the sample containing only migraineurs, the factors associated with higher odds of 12-month GAD included having a university degree, having low income, being without a confidant, and being male.
The rates of childhood epilepsy increase with maternal overweight or obesity in a dose-response manner, according to a study published online ahead of print April 3 in JAMA Neurology. Researchers conducted a population-based cohort study of 1,441,623 live single births at 22 or more gestational weeks in Sweden from January 1, 1997, to December 31, 2011. The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women to 12.4 per 10,000 child-years among women with grade III obesity. Risk of epilepsy increased by 11% in children of overweight mothers, compared with children of normal-weight mothers. Grade I obesity was associated with a 20% increased risk, grade II obesity was associated with a 30% increased risk, and grade III obesity was associated with an 82% increased risk.
The FDA has approved a label expansion for Trokendi XR (topiramate) to include migraine prophylaxis in adults and adolescents age 12 and older. Trokendi XR is a once-daily extended release formulation. The drug previously was approved as initial monotherapy and adjunctive therapy in patients age 6 and older with partial onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients age 6 and older with seizures associated with Lennox-Gastaut syndrome. Trokendi XR is available in 25-mg, 50-mg, 100-mg, and 200-mg capsules. The drug may cause sudden decrease in vision, secondary angle closure glaucoma, or decreased sweating. Approximately one in 500 people who take Trokendi XR may have suicidal thoughts. Supernus Pharmaceuticals markets Trokendi XR.
The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Austedo was previously referred to by the name SD-809 and was granted Orphan Drug Designation by the FDA. Austedo is the second product approved for Huntington’s disease. The approval was based on phase III results in a randomized, double-blind, placebo-controlled, multicenter trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period, compared with approximately 1.9 units in the placebo group. At the week 13 follow-up visit (one week after discontinuation of the study drug), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline levels. Teva Pharmaceutical Industries markets Austedo.
—Kimberly Williams
The Biomarkers for Infant Brain Injury Score can identify infants with acute intracranial hemorrhage, according to a study published online ahead of print April 10 in JAMA Pediatrics. Binary logistic regression was used to develop a multivariable model incorporating three serum biomarkers and one clinical variable (total hemoglobin). The Biomarkers for Infant Brain Injury Score was applied to 599 infants (mean age, 4.7 months) at increased risk for abusive head trauma. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive and 48.0% specific for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.
The FDA has approved Ocrevus (ocrelizumab), an IV infusion, to treat adults with relapsing forms of multiple sclerosis (MS) and primary progressive MS. This drug is the first to be approved by the FDA for primary progressive MS. The efficacy of Ocrevus for the treatment of relapsing-remitting MS was shown in two clinical trials including 1,656 participants treated for 96 weeks. In both studies, patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability, compared with patients receiving interferon beta-1a. In a study of 732 participants with primary progressive MS treated for at least 120 weeks, participants receiving Ocrevus had a longer time to the worsening of disability, compared with participants receiving placebo. Common side effects include infusion-related reactions and upper respiratory tract infection. Genentech markets Ocrevus.
Unemployed men and women and reemployed men have an increased risk of hemorrhagic and ischemic stroke and mortality, according to a study published online ahead of print April 6 in Stroke. This prospective study included 21,902 men and 19,826 women, ages 40 to 59, from nine public health centers across Japan. Participants were followed up from 1990–1993 to the end of 2009–2014. During the follow-up period, 973 incident strokes and 275 deaths from stroke occurred in men, as well as 460 strokes and 131 deaths from stroke in women. Compared with continuously employed subjects, the multivariable hazard ratio (HR) for total stroke incidence was 1.58 in unemployed men and 1.51 in unemployed women. HR for total stroke mortality was 2.22 in men and 2.48 in women.
In people with uncomplicated childhood-onset epilepsy and five-year terminal remission, young adult social outcomes are comparable to those of sibling controls, according to a study published online ahead of print April 4 in Epilepsia. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, which included 361 individuals with epilepsy and 173 controls. Social outcomes for cases with uncomplicated epilepsy with five or more years’ terminal remission were comparable to those of controls. Cases with uncomplicated epilepsy and less than five years of seizure freedom were more likely to be less productive and not to have a driver’s license. Complicated cases with epilepsy and less than five years of seizure freedom had worse outcomes across multiple domains, including not graduating high school.
Deep brain stimulation of the ventralis oralis internus and centromedian-parafascicular thalamus is an effective and relatively safe treatment for severe, refractory Tourette syndrome, according to a study published online ahead of print April 7 in the Journal of Neurosurgery. Researchers retrospectively reviewed outcomes in 13 patients with refractory Tourette syndrome who underwent medial thalamic deep brain stimulation for seven years. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale. Patients showed an average decrease of 37% in total tic severity at their first postoperative visit. During their most recent visit, patient scores decreased from preoperative scores by an average of 50%, which was statistically significant. Device-related complications occurred in two patients, necessitating additional surgeries.
The FDA has approved Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia. Ingrezza is a selective vesicular monoamine transporter 2 inhibitor. The approval of Ingrezza was based on data from the Kinect 3 study, a phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study comparing once-daily Ingrezza (80 mg and 40 mg) to placebo over six weeks in patients with schizophrenia, schizoaffective disorder, or mood disorder. The mean change from baseline to week six in the AIMS dyskinesia total score was –3.2 for patients receiving 80 mg/day of Ingrezza, compared with –0.1 for controls. Ingrezza also was generally well tolerated, with somnolence as the only adverse event occurring at a rate of 5% or greater and twice the rate associated with placebo. Neurocrine Biosciences markets Ingrezza.
Benzodiazepine use is associated with an increased risk of pneumonia among patients with Alzheimer’s disease, according to a study published April 10 in CMAJ. Researchers obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland between 2005 and 2011 from the Medication use and Alzheimer’s disease cohort. Incident users of benzodiazepines and nonbenzodiazepines were identified using a one-year washout period and matched with nonusers through propensity scores. Among 49,484 eligible participants with Alzheimer’s disease, 5,232 taking benzodiazepines and 3,269 taking nonbenzodiazepines were matched 1:1 with people not taking these drugs. Benzodiazepine and nonbenzodiazepine use was associated with a 22% increased risk of pneumonia. When analyzed separately, benzodiazepine use was significantly associated with a 28% increased risk of pneumonia, but nonbenzodiazepine use was not.
Hospitalization rates for acute ischemic stroke in young adults are increasing, along with the prevalence of traditional stroke risk factors, according to a study published online ahead of print April 10 in JAMA Neurology. Hospitalization data from the National Inpatient Sample from 1995 through 2012 were used to analyze acute stroke hospitalization rates among people ages 18 to 64. The 2003–2004 set included 362,339 hospitalizations, and the 2011–2012 set included 421,815 hospitalizations. Acute ischemic stroke hospitalization rates increased significantly for men and women, and for certain racial and ethnic groups, among younger adults ages 18 to 54. The prevalence of stroke risk factors among people hospitalized for acute ischemic stroke continued to increase from 2003–2004 through 2011–2012 for men and women ages 18 to 64.
A polygenic hazard score may help quantify individual differences in age-specific genetic risk for Alzheimer’s disease, according to a study published March 21 in PLOS Medicine. The investigators reviewed single-nucleotide polymorphisms associated with Alzheimer’s disease risk. Using a Cox proportional hazard model, they calculated polygenic hazard scores for participants in the Alzheimer’s Disease Genetics Consortium and tested them in two independent cohorts. People in the top polygenic hazard score quartile developed Alzheimer’s disease at a considerably lower age and had the highest yearly Alzheimer’s disease incidence rate. Among people who did not have the APOE ε3 allele, polygenic hazard score modified the age of expected onset by more than 10 years between the lowest and highest deciles. In independent cohorts, the polygenic hazard score strongly predicted age of Alzheimer’s disease onset.
Generalized anxiety disorder (GAD) is associated with migraine, according to a study published in the March issue of Headache. Researchers performed a secondary data analysis of the 2012 Canadian Community Health Survey-Mental Health. The first subsample included people with and without migraine. The second subsample was restricted to people with migraine. Six percent of people with migraine had had GAD in the previous year, compared with 2.1% of people without migraine. The adjusted odds of previous year GAD were 2.5 times higher among people with migraine than among people without. In the sample containing only migraineurs, the factors associated with higher odds of 12-month GAD included having a university degree, having low income, being without a confidant, and being male.
The rates of childhood epilepsy increase with maternal overweight or obesity in a dose-response manner, according to a study published online ahead of print April 3 in JAMA Neurology. Researchers conducted a population-based cohort study of 1,441,623 live single births at 22 or more gestational weeks in Sweden from January 1, 1997, to December 31, 2011. The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women to 12.4 per 10,000 child-years among women with grade III obesity. Risk of epilepsy increased by 11% in children of overweight mothers, compared with children of normal-weight mothers. Grade I obesity was associated with a 20% increased risk, grade II obesity was associated with a 30% increased risk, and grade III obesity was associated with an 82% increased risk.
The FDA has approved a label expansion for Trokendi XR (topiramate) to include migraine prophylaxis in adults and adolescents age 12 and older. Trokendi XR is a once-daily extended release formulation. The drug previously was approved as initial monotherapy and adjunctive therapy in patients age 6 and older with partial onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients age 6 and older with seizures associated with Lennox-Gastaut syndrome. Trokendi XR is available in 25-mg, 50-mg, 100-mg, and 200-mg capsules. The drug may cause sudden decrease in vision, secondary angle closure glaucoma, or decreased sweating. Approximately one in 500 people who take Trokendi XR may have suicidal thoughts. Supernus Pharmaceuticals markets Trokendi XR.
The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Austedo was previously referred to by the name SD-809 and was granted Orphan Drug Designation by the FDA. Austedo is the second product approved for Huntington’s disease. The approval was based on phase III results in a randomized, double-blind, placebo-controlled, multicenter trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period, compared with approximately 1.9 units in the placebo group. At the week 13 follow-up visit (one week after discontinuation of the study drug), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline levels. Teva Pharmaceutical Industries markets Austedo.
—Kimberly Williams
The Biomarkers for Infant Brain Injury Score can identify infants with acute intracranial hemorrhage, according to a study published online ahead of print April 10 in JAMA Pediatrics. Binary logistic regression was used to develop a multivariable model incorporating three serum biomarkers and one clinical variable (total hemoglobin). The Biomarkers for Infant Brain Injury Score was applied to 599 infants (mean age, 4.7 months) at increased risk for abusive head trauma. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive and 48.0% specific for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.
The FDA has approved Ocrevus (ocrelizumab), an IV infusion, to treat adults with relapsing forms of multiple sclerosis (MS) and primary progressive MS. This drug is the first to be approved by the FDA for primary progressive MS. The efficacy of Ocrevus for the treatment of relapsing-remitting MS was shown in two clinical trials including 1,656 participants treated for 96 weeks. In both studies, patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability, compared with patients receiving interferon beta-1a. In a study of 732 participants with primary progressive MS treated for at least 120 weeks, participants receiving Ocrevus had a longer time to the worsening of disability, compared with participants receiving placebo. Common side effects include infusion-related reactions and upper respiratory tract infection. Genentech markets Ocrevus.
Unemployed men and women and reemployed men have an increased risk of hemorrhagic and ischemic stroke and mortality, according to a study published online ahead of print April 6 in Stroke. This prospective study included 21,902 men and 19,826 women, ages 40 to 59, from nine public health centers across Japan. Participants were followed up from 1990–1993 to the end of 2009–2014. During the follow-up period, 973 incident strokes and 275 deaths from stroke occurred in men, as well as 460 strokes and 131 deaths from stroke in women. Compared with continuously employed subjects, the multivariable hazard ratio (HR) for total stroke incidence was 1.58 in unemployed men and 1.51 in unemployed women. HR for total stroke mortality was 2.22 in men and 2.48 in women.
In people with uncomplicated childhood-onset epilepsy and five-year terminal remission, young adult social outcomes are comparable to those of sibling controls, according to a study published online ahead of print April 4 in Epilepsia. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, which included 361 individuals with epilepsy and 173 controls. Social outcomes for cases with uncomplicated epilepsy with five or more years’ terminal remission were comparable to those of controls. Cases with uncomplicated epilepsy and less than five years of seizure freedom were more likely to be less productive and not to have a driver’s license. Complicated cases with epilepsy and less than five years of seizure freedom had worse outcomes across multiple domains, including not graduating high school.
Deep brain stimulation of the ventralis oralis internus and centromedian-parafascicular thalamus is an effective and relatively safe treatment for severe, refractory Tourette syndrome, according to a study published online ahead of print April 7 in the Journal of Neurosurgery. Researchers retrospectively reviewed outcomes in 13 patients with refractory Tourette syndrome who underwent medial thalamic deep brain stimulation for seven years. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale. Patients showed an average decrease of 37% in total tic severity at their first postoperative visit. During their most recent visit, patient scores decreased from preoperative scores by an average of 50%, which was statistically significant. Device-related complications occurred in two patients, necessitating additional surgeries.
The FDA has approved Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia. Ingrezza is a selective vesicular monoamine transporter 2 inhibitor. The approval of Ingrezza was based on data from the Kinect 3 study, a phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study comparing once-daily Ingrezza (80 mg and 40 mg) to placebo over six weeks in patients with schizophrenia, schizoaffective disorder, or mood disorder. The mean change from baseline to week six in the AIMS dyskinesia total score was –3.2 for patients receiving 80 mg/day of Ingrezza, compared with –0.1 for controls. Ingrezza also was generally well tolerated, with somnolence as the only adverse event occurring at a rate of 5% or greater and twice the rate associated with placebo. Neurocrine Biosciences markets Ingrezza.
Benzodiazepine use is associated with an increased risk of pneumonia among patients with Alzheimer’s disease, according to a study published April 10 in CMAJ. Researchers obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland between 2005 and 2011 from the Medication use and Alzheimer’s disease cohort. Incident users of benzodiazepines and nonbenzodiazepines were identified using a one-year washout period and matched with nonusers through propensity scores. Among 49,484 eligible participants with Alzheimer’s disease, 5,232 taking benzodiazepines and 3,269 taking nonbenzodiazepines were matched 1:1 with people not taking these drugs. Benzodiazepine and nonbenzodiazepine use was associated with a 22% increased risk of pneumonia. When analyzed separately, benzodiazepine use was significantly associated with a 28% increased risk of pneumonia, but nonbenzodiazepine use was not.
Hospitalization rates for acute ischemic stroke in young adults are increasing, along with the prevalence of traditional stroke risk factors, according to a study published online ahead of print April 10 in JAMA Neurology. Hospitalization data from the National Inpatient Sample from 1995 through 2012 were used to analyze acute stroke hospitalization rates among people ages 18 to 64. The 2003–2004 set included 362,339 hospitalizations, and the 2011–2012 set included 421,815 hospitalizations. Acute ischemic stroke hospitalization rates increased significantly for men and women, and for certain racial and ethnic groups, among younger adults ages 18 to 54. The prevalence of stroke risk factors among people hospitalized for acute ischemic stroke continued to increase from 2003–2004 through 2011–2012 for men and women ages 18 to 64.
A polygenic hazard score may help quantify individual differences in age-specific genetic risk for Alzheimer’s disease, according to a study published March 21 in PLOS Medicine. The investigators reviewed single-nucleotide polymorphisms associated with Alzheimer’s disease risk. Using a Cox proportional hazard model, they calculated polygenic hazard scores for participants in the Alzheimer’s Disease Genetics Consortium and tested them in two independent cohorts. People in the top polygenic hazard score quartile developed Alzheimer’s disease at a considerably lower age and had the highest yearly Alzheimer’s disease incidence rate. Among people who did not have the APOE ε3 allele, polygenic hazard score modified the age of expected onset by more than 10 years between the lowest and highest deciles. In independent cohorts, the polygenic hazard score strongly predicted age of Alzheimer’s disease onset.
Generalized anxiety disorder (GAD) is associated with migraine, according to a study published in the March issue of Headache. Researchers performed a secondary data analysis of the 2012 Canadian Community Health Survey-Mental Health. The first subsample included people with and without migraine. The second subsample was restricted to people with migraine. Six percent of people with migraine had had GAD in the previous year, compared with 2.1% of people without migraine. The adjusted odds of previous year GAD were 2.5 times higher among people with migraine than among people without. In the sample containing only migraineurs, the factors associated with higher odds of 12-month GAD included having a university degree, having low income, being without a confidant, and being male.
The rates of childhood epilepsy increase with maternal overweight or obesity in a dose-response manner, according to a study published online ahead of print April 3 in JAMA Neurology. Researchers conducted a population-based cohort study of 1,441,623 live single births at 22 or more gestational weeks in Sweden from January 1, 1997, to December 31, 2011. The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women to 12.4 per 10,000 child-years among women with grade III obesity. Risk of epilepsy increased by 11% in children of overweight mothers, compared with children of normal-weight mothers. Grade I obesity was associated with a 20% increased risk, grade II obesity was associated with a 30% increased risk, and grade III obesity was associated with an 82% increased risk.
The FDA has approved a label expansion for Trokendi XR (topiramate) to include migraine prophylaxis in adults and adolescents age 12 and older. Trokendi XR is a once-daily extended release formulation. The drug previously was approved as initial monotherapy and adjunctive therapy in patients age 6 and older with partial onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients age 6 and older with seizures associated with Lennox-Gastaut syndrome. Trokendi XR is available in 25-mg, 50-mg, 100-mg, and 200-mg capsules. The drug may cause sudden decrease in vision, secondary angle closure glaucoma, or decreased sweating. Approximately one in 500 people who take Trokendi XR may have suicidal thoughts. Supernus Pharmaceuticals markets Trokendi XR.
The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Austedo was previously referred to by the name SD-809 and was granted Orphan Drug Designation by the FDA. Austedo is the second product approved for Huntington’s disease. The approval was based on phase III results in a randomized, double-blind, placebo-controlled, multicenter trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period, compared with approximately 1.9 units in the placebo group. At the week 13 follow-up visit (one week after discontinuation of the study drug), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline levels. Teva Pharmaceutical Industries markets Austedo.
—Kimberly Williams
New and Noteworthy Information—April 2017
More than 80% of patients with stroke and a history of atrial fibrillation received inadequate or no anticoagulation therapy before the stroke, despite the drugs’ proven record of reducing stroke risk, according to a study published March 14 in JAMA. This retrospective observational study included 94,474 patients with acute ischemic stroke and a known history of atrial fibrillation enrolled in the Get With the Guidelines-Stroke program registry. Approximately 16% of patients with atrial fibrillation had received the recommended anticoagulation medication prior to having a stroke. In addition, 84% of patients were not treated according to the guidelines prior to stroke. Thirty percent of patients were not taking any antithrombotic treatment, 40% were taking an antiplatelet drug, and 13.5% of patients were taking a subtherapeutic dose of warfarin.
Microwave measurements can enable rapid detection of intracranial bleeding in traumatic brain injuries, according to a study published online ahead of print March 13 in the Journal of Neurotrauma. The study compared 20 patients hospitalized for surgery of chronic subdural hematoma with 20 healthy volunteers. The patients were examined with microwave measurements that were compared with CT scans. The researchers assessed whether these measurements, together with a diagnostic algorithm, could distinguish between groups. The accuracy of the diagnostic algorithm was assessed using a leave-one-out analysis. At 100% sensitivity, the algorithm’s specificity was 75%. “The result indicates that the microwave measurements can be useful in ambulances and in other care settings,” said the researchers. Further studies of patients with acute head injury are ongoing.
People with epilepsy use cannabis products when antiepileptic drug side-effects are intolerable and their epilepsy is uncontrolled, according to Australian survey results published online ahead of print February 24 in Epilepsy & Behavior. The Epilepsy Action Australia survey consisted of 39 questions assessing demographics; clinical factors, including diagnosis and seizure types; and experiences with and opinions of cannabis use in epilepsy. In all, 976 responses met the inclusion criteria. Approximately 15% of adults with epilepsy and 13% of parents and guardians of children with epilepsy were currently using or had previously used cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after using cannabis products.
Interhemispheric transfer time may help predict which children will take longer to recover from a traumatic brain injury (TBI), according to a study published online ahead of print March 15 in Neurology. Researchers studied 21 children with moderate to severe TBI at two to five months post injury and at 13 to 19 months post injury. Twenty well-matched healthy control children also were studied. Investigators assessed corpus callosum function through interhemispheric transfer time, and related it to diffusion-weighted MRI measures of white matter microstructure. Children with TBI and normal interhemispheric transfer time did not differ significantly from healthy controls in white matter organization in the chronic phase or between the two evaluations. Children with TBI and slow interhemispheric transfer time had low and progressively declining white matter organization, compared with controls.
Dietary factors are associated with approximately half of deaths from heart disease, stroke, and type 2 diabetes, according to a study published March 7 in JAMA. Researchers used data from the National Health and Nutrition Examination Surveys, estimated associations of diet and disease from studies and clinical trials, and estimated disease-specific national mortality from the National Center for Health Statistics. The authors focused on the consumption of 10 foods and nutrients associated with cardiometabolic diseases. The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium intake, low nut and seed intake, high processed meat intake, low seafood omega-3 fat intake, low vegetable intake, low fruit intake, and high sugar-sweetened beverage intake. Declines in cardiometabolic deaths were associated with increased consumption of polyunsaturated fats.
Monoamine oxidase type B (MAO-B) inhibitors may reduce clinical decline in Parkinson’s disease, according to a study published March 6 in the Journal of Parkinson’s Disease. Researchers performed a secondary analysis of the NET-PD LS1 trial. They used a linear mixed model to explore the association between the cumulative duration of MAO-B inhibitor exposure and the Global Outcome, which included five clinical measures. The investigators found a significant association between longer duration of MAO-B inhibitor exposure and slower clinical decline. Each additional year of MAO-B inhibitor exposure reduced the annual clinical decline by approximately 20%. Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for the Activities of Daily Living scale, ambulatory capacity, and the modified Rankin scale.
Topological data analysis has identified a multivariate phenotype associated with unfavorable outcome at three and six months after mild traumatic brain injury (TBI), according to a study published online ahead of print March 3 in PLOS ONE. The Transforming Research and Clinical Knowledge in TBI Pilot multicenter study included 586 patients with acute TBI and collected diverse common data elements from them. Researchers applied topology-based data-driven discovery to identify subgroups of patients. The analysis identified a multivariate phenotype with high rates of posttraumatic stress disorder that was enriched for PARP1, ANKK1, and COMT. Machine learning methods such as topological data analysis may provide a robust method for patient stratification and treatment planning that targets identified biomarkers in future clinical trials in patients with TBI, said the investigators.
In patients ages 18 to 45 with ischemic stroke, migraine, especially migraine without aura, is consistently associated with cervical artery dissection (CEAD), according to a study published online ahead of print March 6 in JAMA Neurology. In all, 2,485 patients enrolled in the multicenter Italian Project on Stroke in Young Adults study that was conducted between January 1, 2000, and June 30, 2015. Of the people included in the study, 13.4% had CEAD ischemic stroke and 86.6% had non-CEAD ischemic stroke. Migraine was more common in the CEAD ischemic stroke group, mainly because of migraine without aura. Compared with migraine with aura, migraine without aura was independently associated with CEAD ischemic stroke. The strength of this association was higher in men and in patients age 39 or younger.
Data are insufficient to support a recommendation of cognitive training in the treatment of patients with dementia, according to a study published in the Journal of Alzheimer’s Disease. Researchers systematically reviewed the current evidence from randomized controlled trials to determine whether cognitive training improves or stabilizes cognition or everyday functioning in patients with mild and moderate Alzheimer’s disease. The investigators examined 31 randomized controlled trials with cognitive training as either the primary intervention or part of a broader cognitive or multicomponent intervention. A positive effect was reported in 24 trials, mainly on global cognition and training-specific tasks. The trials yielded little evidence of improved everyday functioning, however. Future randomized controlled trials with appropriate classification and specification of cognitive interventions are needed to confirm the latter’s benefit, said the authors.
Patients who infer a correlation between data collected on wearable sleep-tracking devices and daytime fatigue may begin a perfectionistic quest for ideal sleep to optimize daytime function, according to a case series published February 15 in the Journal of Clinical Sleep Medicine. Many patients believe that the devices are more reliable than they are. A male patient went to bed feeling the pressure of ensuring that the tracker would display eight hours of sleep the next day. He thus had self-induced anxiety that made achieving sound sleep more difficult. A female patient complained about feeling unrefreshed when awakening after what she perceived had been a poor night’s sleep. Polysomnography revealed that the woman had had deep sleep, but the woman dismissed the finding in favor of her device’s data.
Changes in brain connectivity at the time of mild traumatic brain injury (mTBI) may predict cognitive and behavioral performance at six months, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Seventy-five patients with mTBI were recruited into a pilot study and compared with 47 matched healthy subjects. Resting-state functional MRI data were acquired and processed using probabilistic independent component analysis. The investigators found alterations in the spatial maps of the resting-state networks between patients with mTBI and healthy controls in networks involved in behavioral and cognition processes. These alterations predicted outcomes at six months post injury in patients with mTBI. Compared with controls, patients with mTBI and lesions and those with mTBI without lesions had different patterns of reduced network interactions.
Patients with the BChE-K genotype who receive donepezil for mild cognitive impairment (MCI) may have faster cognitive decline, according to a study published in the January issue of the Journal of Alzheimer’s Disease. Researchers examined the association between BChE-K genotype and changes in cognitive function using data collected during a study of people with amnestic MCI who were treated with vitamin E, donepezil, or placebo. They found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores, compared with the common allele. BChE-K homozygous people treated with donepezil had faster decline on MMSE score and faster rise in CDR-SB score, compared with untreated BChE-K homozygous individuals.
The FDA has approved Xadago (safinamide) tablets as an add-on treatment for patients with Parkinson’s disease who are taking levodopa–carbidopa and experiencing off episodes. In a clinical trial of 645 participants with Parkinson’s disease taking levodopa and experiencing off time, participants who received Xadago had more on time without troublesome dyskinesia, compared with controls. The increase in on time was accompanied by a reduction in off time and better scores on a measure of motor function assessed during on time. Patients with severe liver problems and those who take dextromethorphan should not take Xadago. Patients who take a monoamine oxidase inhibitor or St. John’s wort also should not take Xadago. The most common adverse reactions observed in patients taking Xadago were uncontrolled involuntary movement, falls, nausea, and insomnia.
—Kimberly Williams
More than 80% of patients with stroke and a history of atrial fibrillation received inadequate or no anticoagulation therapy before the stroke, despite the drugs’ proven record of reducing stroke risk, according to a study published March 14 in JAMA. This retrospective observational study included 94,474 patients with acute ischemic stroke and a known history of atrial fibrillation enrolled in the Get With the Guidelines-Stroke program registry. Approximately 16% of patients with atrial fibrillation had received the recommended anticoagulation medication prior to having a stroke. In addition, 84% of patients were not treated according to the guidelines prior to stroke. Thirty percent of patients were not taking any antithrombotic treatment, 40% were taking an antiplatelet drug, and 13.5% of patients were taking a subtherapeutic dose of warfarin.
Microwave measurements can enable rapid detection of intracranial bleeding in traumatic brain injuries, according to a study published online ahead of print March 13 in the Journal of Neurotrauma. The study compared 20 patients hospitalized for surgery of chronic subdural hematoma with 20 healthy volunteers. The patients were examined with microwave measurements that were compared with CT scans. The researchers assessed whether these measurements, together with a diagnostic algorithm, could distinguish between groups. The accuracy of the diagnostic algorithm was assessed using a leave-one-out analysis. At 100% sensitivity, the algorithm’s specificity was 75%. “The result indicates that the microwave measurements can be useful in ambulances and in other care settings,” said the researchers. Further studies of patients with acute head injury are ongoing.
People with epilepsy use cannabis products when antiepileptic drug side-effects are intolerable and their epilepsy is uncontrolled, according to Australian survey results published online ahead of print February 24 in Epilepsy & Behavior. The Epilepsy Action Australia survey consisted of 39 questions assessing demographics; clinical factors, including diagnosis and seizure types; and experiences with and opinions of cannabis use in epilepsy. In all, 976 responses met the inclusion criteria. Approximately 15% of adults with epilepsy and 13% of parents and guardians of children with epilepsy were currently using or had previously used cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after using cannabis products.
Interhemispheric transfer time may help predict which children will take longer to recover from a traumatic brain injury (TBI), according to a study published online ahead of print March 15 in Neurology. Researchers studied 21 children with moderate to severe TBI at two to five months post injury and at 13 to 19 months post injury. Twenty well-matched healthy control children also were studied. Investigators assessed corpus callosum function through interhemispheric transfer time, and related it to diffusion-weighted MRI measures of white matter microstructure. Children with TBI and normal interhemispheric transfer time did not differ significantly from healthy controls in white matter organization in the chronic phase or between the two evaluations. Children with TBI and slow interhemispheric transfer time had low and progressively declining white matter organization, compared with controls.
Dietary factors are associated with approximately half of deaths from heart disease, stroke, and type 2 diabetes, according to a study published March 7 in JAMA. Researchers used data from the National Health and Nutrition Examination Surveys, estimated associations of diet and disease from studies and clinical trials, and estimated disease-specific national mortality from the National Center for Health Statistics. The authors focused on the consumption of 10 foods and nutrients associated with cardiometabolic diseases. The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium intake, low nut and seed intake, high processed meat intake, low seafood omega-3 fat intake, low vegetable intake, low fruit intake, and high sugar-sweetened beverage intake. Declines in cardiometabolic deaths were associated with increased consumption of polyunsaturated fats.
Monoamine oxidase type B (MAO-B) inhibitors may reduce clinical decline in Parkinson’s disease, according to a study published March 6 in the Journal of Parkinson’s Disease. Researchers performed a secondary analysis of the NET-PD LS1 trial. They used a linear mixed model to explore the association between the cumulative duration of MAO-B inhibitor exposure and the Global Outcome, which included five clinical measures. The investigators found a significant association between longer duration of MAO-B inhibitor exposure and slower clinical decline. Each additional year of MAO-B inhibitor exposure reduced the annual clinical decline by approximately 20%. Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for the Activities of Daily Living scale, ambulatory capacity, and the modified Rankin scale.
Topological data analysis has identified a multivariate phenotype associated with unfavorable outcome at three and six months after mild traumatic brain injury (TBI), according to a study published online ahead of print March 3 in PLOS ONE. The Transforming Research and Clinical Knowledge in TBI Pilot multicenter study included 586 patients with acute TBI and collected diverse common data elements from them. Researchers applied topology-based data-driven discovery to identify subgroups of patients. The analysis identified a multivariate phenotype with high rates of posttraumatic stress disorder that was enriched for PARP1, ANKK1, and COMT. Machine learning methods such as topological data analysis may provide a robust method for patient stratification and treatment planning that targets identified biomarkers in future clinical trials in patients with TBI, said the investigators.
In patients ages 18 to 45 with ischemic stroke, migraine, especially migraine without aura, is consistently associated with cervical artery dissection (CEAD), according to a study published online ahead of print March 6 in JAMA Neurology. In all, 2,485 patients enrolled in the multicenter Italian Project on Stroke in Young Adults study that was conducted between January 1, 2000, and June 30, 2015. Of the people included in the study, 13.4% had CEAD ischemic stroke and 86.6% had non-CEAD ischemic stroke. Migraine was more common in the CEAD ischemic stroke group, mainly because of migraine without aura. Compared with migraine with aura, migraine without aura was independently associated with CEAD ischemic stroke. The strength of this association was higher in men and in patients age 39 or younger.
Data are insufficient to support a recommendation of cognitive training in the treatment of patients with dementia, according to a study published in the Journal of Alzheimer’s Disease. Researchers systematically reviewed the current evidence from randomized controlled trials to determine whether cognitive training improves or stabilizes cognition or everyday functioning in patients with mild and moderate Alzheimer’s disease. The investigators examined 31 randomized controlled trials with cognitive training as either the primary intervention or part of a broader cognitive or multicomponent intervention. A positive effect was reported in 24 trials, mainly on global cognition and training-specific tasks. The trials yielded little evidence of improved everyday functioning, however. Future randomized controlled trials with appropriate classification and specification of cognitive interventions are needed to confirm the latter’s benefit, said the authors.
Patients who infer a correlation between data collected on wearable sleep-tracking devices and daytime fatigue may begin a perfectionistic quest for ideal sleep to optimize daytime function, according to a case series published February 15 in the Journal of Clinical Sleep Medicine. Many patients believe that the devices are more reliable than they are. A male patient went to bed feeling the pressure of ensuring that the tracker would display eight hours of sleep the next day. He thus had self-induced anxiety that made achieving sound sleep more difficult. A female patient complained about feeling unrefreshed when awakening after what she perceived had been a poor night’s sleep. Polysomnography revealed that the woman had had deep sleep, but the woman dismissed the finding in favor of her device’s data.
Changes in brain connectivity at the time of mild traumatic brain injury (mTBI) may predict cognitive and behavioral performance at six months, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Seventy-five patients with mTBI were recruited into a pilot study and compared with 47 matched healthy subjects. Resting-state functional MRI data were acquired and processed using probabilistic independent component analysis. The investigators found alterations in the spatial maps of the resting-state networks between patients with mTBI and healthy controls in networks involved in behavioral and cognition processes. These alterations predicted outcomes at six months post injury in patients with mTBI. Compared with controls, patients with mTBI and lesions and those with mTBI without lesions had different patterns of reduced network interactions.
Patients with the BChE-K genotype who receive donepezil for mild cognitive impairment (MCI) may have faster cognitive decline, according to a study published in the January issue of the Journal of Alzheimer’s Disease. Researchers examined the association between BChE-K genotype and changes in cognitive function using data collected during a study of people with amnestic MCI who were treated with vitamin E, donepezil, or placebo. They found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores, compared with the common allele. BChE-K homozygous people treated with donepezil had faster decline on MMSE score and faster rise in CDR-SB score, compared with untreated BChE-K homozygous individuals.
The FDA has approved Xadago (safinamide) tablets as an add-on treatment for patients with Parkinson’s disease who are taking levodopa–carbidopa and experiencing off episodes. In a clinical trial of 645 participants with Parkinson’s disease taking levodopa and experiencing off time, participants who received Xadago had more on time without troublesome dyskinesia, compared with controls. The increase in on time was accompanied by a reduction in off time and better scores on a measure of motor function assessed during on time. Patients with severe liver problems and those who take dextromethorphan should not take Xadago. Patients who take a monoamine oxidase inhibitor or St. John’s wort also should not take Xadago. The most common adverse reactions observed in patients taking Xadago were uncontrolled involuntary movement, falls, nausea, and insomnia.
—Kimberly Williams
More than 80% of patients with stroke and a history of atrial fibrillation received inadequate or no anticoagulation therapy before the stroke, despite the drugs’ proven record of reducing stroke risk, according to a study published March 14 in JAMA. This retrospective observational study included 94,474 patients with acute ischemic stroke and a known history of atrial fibrillation enrolled in the Get With the Guidelines-Stroke program registry. Approximately 16% of patients with atrial fibrillation had received the recommended anticoagulation medication prior to having a stroke. In addition, 84% of patients were not treated according to the guidelines prior to stroke. Thirty percent of patients were not taking any antithrombotic treatment, 40% were taking an antiplatelet drug, and 13.5% of patients were taking a subtherapeutic dose of warfarin.
Microwave measurements can enable rapid detection of intracranial bleeding in traumatic brain injuries, according to a study published online ahead of print March 13 in the Journal of Neurotrauma. The study compared 20 patients hospitalized for surgery of chronic subdural hematoma with 20 healthy volunteers. The patients were examined with microwave measurements that were compared with CT scans. The researchers assessed whether these measurements, together with a diagnostic algorithm, could distinguish between groups. The accuracy of the diagnostic algorithm was assessed using a leave-one-out analysis. At 100% sensitivity, the algorithm’s specificity was 75%. “The result indicates that the microwave measurements can be useful in ambulances and in other care settings,” said the researchers. Further studies of patients with acute head injury are ongoing.
People with epilepsy use cannabis products when antiepileptic drug side-effects are intolerable and their epilepsy is uncontrolled, according to Australian survey results published online ahead of print February 24 in Epilepsy & Behavior. The Epilepsy Action Australia survey consisted of 39 questions assessing demographics; clinical factors, including diagnosis and seizure types; and experiences with and opinions of cannabis use in epilepsy. In all, 976 responses met the inclusion criteria. Approximately 15% of adults with epilepsy and 13% of parents and guardians of children with epilepsy were currently using or had previously used cannabis products to treat epilepsy. Of those with a history of cannabis product use, 90% of adults and 71% of parents reported success in reducing seizure frequency after using cannabis products.
Interhemispheric transfer time may help predict which children will take longer to recover from a traumatic brain injury (TBI), according to a study published online ahead of print March 15 in Neurology. Researchers studied 21 children with moderate to severe TBI at two to five months post injury and at 13 to 19 months post injury. Twenty well-matched healthy control children also were studied. Investigators assessed corpus callosum function through interhemispheric transfer time, and related it to diffusion-weighted MRI measures of white matter microstructure. Children with TBI and normal interhemispheric transfer time did not differ significantly from healthy controls in white matter organization in the chronic phase or between the two evaluations. Children with TBI and slow interhemispheric transfer time had low and progressively declining white matter organization, compared with controls.
Dietary factors are associated with approximately half of deaths from heart disease, stroke, and type 2 diabetes, according to a study published March 7 in JAMA. Researchers used data from the National Health and Nutrition Examination Surveys, estimated associations of diet and disease from studies and clinical trials, and estimated disease-specific national mortality from the National Center for Health Statistics. The authors focused on the consumption of 10 foods and nutrients associated with cardiometabolic diseases. The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium intake, low nut and seed intake, high processed meat intake, low seafood omega-3 fat intake, low vegetable intake, low fruit intake, and high sugar-sweetened beverage intake. Declines in cardiometabolic deaths were associated with increased consumption of polyunsaturated fats.
Monoamine oxidase type B (MAO-B) inhibitors may reduce clinical decline in Parkinson’s disease, according to a study published March 6 in the Journal of Parkinson’s Disease. Researchers performed a secondary analysis of the NET-PD LS1 trial. They used a linear mixed model to explore the association between the cumulative duration of MAO-B inhibitor exposure and the Global Outcome, which included five clinical measures. The investigators found a significant association between longer duration of MAO-B inhibitor exposure and slower clinical decline. Each additional year of MAO-B inhibitor exposure reduced the annual clinical decline by approximately 20%. Significant associations between duration of MAO-B inhibitor exposure and less progression were observed for the Activities of Daily Living scale, ambulatory capacity, and the modified Rankin scale.
Topological data analysis has identified a multivariate phenotype associated with unfavorable outcome at three and six months after mild traumatic brain injury (TBI), according to a study published online ahead of print March 3 in PLOS ONE. The Transforming Research and Clinical Knowledge in TBI Pilot multicenter study included 586 patients with acute TBI and collected diverse common data elements from them. Researchers applied topology-based data-driven discovery to identify subgroups of patients. The analysis identified a multivariate phenotype with high rates of posttraumatic stress disorder that was enriched for PARP1, ANKK1, and COMT. Machine learning methods such as topological data analysis may provide a robust method for patient stratification and treatment planning that targets identified biomarkers in future clinical trials in patients with TBI, said the investigators.
In patients ages 18 to 45 with ischemic stroke, migraine, especially migraine without aura, is consistently associated with cervical artery dissection (CEAD), according to a study published online ahead of print March 6 in JAMA Neurology. In all, 2,485 patients enrolled in the multicenter Italian Project on Stroke in Young Adults study that was conducted between January 1, 2000, and June 30, 2015. Of the people included in the study, 13.4% had CEAD ischemic stroke and 86.6% had non-CEAD ischemic stroke. Migraine was more common in the CEAD ischemic stroke group, mainly because of migraine without aura. Compared with migraine with aura, migraine without aura was independently associated with CEAD ischemic stroke. The strength of this association was higher in men and in patients age 39 or younger.
Data are insufficient to support a recommendation of cognitive training in the treatment of patients with dementia, according to a study published in the Journal of Alzheimer’s Disease. Researchers systematically reviewed the current evidence from randomized controlled trials to determine whether cognitive training improves or stabilizes cognition or everyday functioning in patients with mild and moderate Alzheimer’s disease. The investigators examined 31 randomized controlled trials with cognitive training as either the primary intervention or part of a broader cognitive or multicomponent intervention. A positive effect was reported in 24 trials, mainly on global cognition and training-specific tasks. The trials yielded little evidence of improved everyday functioning, however. Future randomized controlled trials with appropriate classification and specification of cognitive interventions are needed to confirm the latter’s benefit, said the authors.
Patients who infer a correlation between data collected on wearable sleep-tracking devices and daytime fatigue may begin a perfectionistic quest for ideal sleep to optimize daytime function, according to a case series published February 15 in the Journal of Clinical Sleep Medicine. Many patients believe that the devices are more reliable than they are. A male patient went to bed feeling the pressure of ensuring that the tracker would display eight hours of sleep the next day. He thus had self-induced anxiety that made achieving sound sleep more difficult. A female patient complained about feeling unrefreshed when awakening after what she perceived had been a poor night’s sleep. Polysomnography revealed that the woman had had deep sleep, but the woman dismissed the finding in favor of her device’s data.
Changes in brain connectivity at the time of mild traumatic brain injury (mTBI) may predict cognitive and behavioral performance at six months, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Seventy-five patients with mTBI were recruited into a pilot study and compared with 47 matched healthy subjects. Resting-state functional MRI data were acquired and processed using probabilistic independent component analysis. The investigators found alterations in the spatial maps of the resting-state networks between patients with mTBI and healthy controls in networks involved in behavioral and cognition processes. These alterations predicted outcomes at six months post injury in patients with mTBI. Compared with controls, patients with mTBI and lesions and those with mTBI without lesions had different patterns of reduced network interactions.
Patients with the BChE-K genotype who receive donepezil for mild cognitive impairment (MCI) may have faster cognitive decline, according to a study published in the January issue of the Journal of Alzheimer’s Disease. Researchers examined the association between BChE-K genotype and changes in cognitive function using data collected during a study of people with amnestic MCI who were treated with vitamin E, donepezil, or placebo. They found significant interactions between BChE-K genotype and the duration of donepezil treatment, with increased changes in Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores, compared with the common allele. BChE-K homozygous people treated with donepezil had faster decline on MMSE score and faster rise in CDR-SB score, compared with untreated BChE-K homozygous individuals.
The FDA has approved Xadago (safinamide) tablets as an add-on treatment for patients with Parkinson’s disease who are taking levodopa–carbidopa and experiencing off episodes. In a clinical trial of 645 participants with Parkinson’s disease taking levodopa and experiencing off time, participants who received Xadago had more on time without troublesome dyskinesia, compared with controls. The increase in on time was accompanied by a reduction in off time and better scores on a measure of motor function assessed during on time. Patients with severe liver problems and those who take dextromethorphan should not take Xadago. Patients who take a monoamine oxidase inhibitor or St. John’s wort also should not take Xadago. The most common adverse reactions observed in patients taking Xadago were uncontrolled involuntary movement, falls, nausea, and insomnia.
—Kimberly Williams