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New and Noteworthy Information—March 2017
Serum levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were unable to distinguish between patients with mild traumatic brain injury (mTBI) and patients with orthopedic trauma, according to a study published online ahead of print January 27 in the Journal of Neurotrauma. The results cast doubt on the value of these proposed biomarkers in diagnosing mTBI, the researchers said. Serum UCH-L1 and GFAP were longitudinally measured in 73 patients with acute orthopedic injury and in 93 patients with CT-negative mTBI when they arrived at the hospital and one, two, three, and seven days after admission, as well as at a follow-up visit between three and 10 months after injury. Levels of GFAP were higher in patients with orthopedic trauma than in patients with mTBI on arrival, but subsequent levels did not differ between groups. Levels of UCH-L1 did not significantly differ between the groups.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation without maintenance therapy is effective for inducing long-term sustained remission of active relapsing-remitting multiple sclerosis at five years, according to a study published online ahead of print February 1 in Neurology. Twenty-five participants were evaluated for transplant, and 24 participants underwent high-dose immunosuppressive therapy and hematopoietic cell transplantation. Median follow-up was 62 months. Event-free survival (ie, survival without disability progression, relapse, or new lesions on MRI) was 69.2%. Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3%, 86.9%, and 86.3%, respectively. Adverse events were consistent with toxic effects associated with high-dose immunosuppressive therapy and hematopoietic cell transplantation, including cytopenia and infection. Neurologic disability improved among participants who survived and completed the study, with a median change in Expanded Disability Status Scale score of -0.5.
Estimated glomerular filtration rate on admission is an important predictor of poststroke short-term outcomes, according to a cohort study published in the February issue of Stroke. Investigators analyzed data from 232,236 patients with ischemic stroke in Get With The Guidelines-Stroke. Patients were age 65 or older. In all, 11.8% of patients died during hospitalization or were discharged to hospice, and 38.6% were discharged home. Renal dysfunction was independently associated with an increased risk of in-hospital mortality that was highest among those with an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 without dialysis (odds ratio, 2.52). In addition, receiving dialysis and having an estimated glomerular filtration rate of less than 29 mL/min/1.73 m2 were associated with lower odds of being discharged home.
Habitual sleep duration in monozygotic twins may be associated with distinct patterns of differential gene expression and pathway enrichment that affect immune response, according to a study published in the January issue of Sleep. Investigators selected 11 healthy monozygotic twin pairs (82% female; mean age, 42.7) based on subjective sleep duration discordance and then monitored participants' habitual sleep duration with two weeks of wrist actigraphy. Peripheral blood leukocyte RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. The mean 24-hour sleep duration of the total sample was 439.2 minutes. Mean within-pair sleep duration difference per 24 hours was 64.4 minutes. The researchers observed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with upregulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Genes that were downregulated with short sleep were highly enriched in immunoinfammatory pathways, as well as developmental programs, coagulation cascade, and cell adhesion.
A brain-computer interface that can decipher the thoughts of people who are unable to communicate may help people with completely locked-in syndrome, according to a study published January 31 in PLOS Biology. Researchers studied a brain-computer interface in four patients with advanced amyotrophic lateral sclerosis and completely locked-in syndrome. Patients responded to "yes" or "no" questions by thinking their answers. The noninvasive brain-computer interface assessed changes in frontocentral cortical oxygenation, measured using functional near-infrared spectroscopy, to determine patients' answers. Patients communicated with an above-chance-level correct response rate over 70%. EEG oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication.
Using a new noninvasive fMRI method, physicians may be able to predict who is more likely to continue experiencing symptoms months or years after concussion, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Investigators recruited 75 patients with mild traumatic brain injury (mTBI) and 47 healthy subjects as part of the prospective, multicenter Transforming Research and Clinical Knowledge in TBI pilot study. Researchers compared the functional connectivity of the resting-state networks between patients and controls, and group differences in the interactions between resting-state networks. They assessed patients' cognitive and behavioral performance at six months post injury. Spatial maps of resting-state networks involved in behavioral and cognitive processes differed between patients with mTBI and healthy controls, and these differences were predictive of patients' outcomes at six months post injury.
Among patients with Alzheimer's disease, lifelong bilingualism correlates with functional modulations in crucial neural networks, suggesting neural reserve and compensatory mechanisms, according to a study published online ahead of print January 30 in the Proceedings of the National Academy of Sciences. Eighty-five patients with Alzheimer's disease (45 German-Italian bilingual speakers and 40 monolingual speakers) matched for disease duration were included in this study. Bilingual individuals were on average five years older than people who did not speak another language. Consistent with models of cognitive reserve, cerebral hypometabolism was more severe in the group of bilingual individuals with Alzheimer's disease. Metabolic connectivity analyses supported a neuroprotective effect of bilingualism by showing increased connectivity in the executive control and the default mode networks in bilingual patients, compared with monolingual patients.
The Huntington's Disease Society of America (HDSA), in conjunction with the FDA, conducted two surveys to gather the perspectives of patients with Huntington's disease and juvenile Huntington's disease and their caregivers. Findings from the surveys were published online ahead of print January 24 in the Journal of Huntington's Disease. One survey covered disease symptoms that matter most to people with Huntington's disease, and the other covered current approaches to treatment. The surveys received a total of 3,631 responses. "The frequency and impact of symptoms appear to be felt more by caregivers than individuals with Huntington's Disease, especially when it comes to loss of abilities," said lead investigator George J. Yohrling, PhD, Senior Director of Mission and Scientific Affairs for the HDSA. "There was also a large difference in the perception of symptom frequency between caregivers and individuals with Huntington's disease."
Intentional and unintentional head impacts are independently associated with moderate to severe CNS symptoms in adult amateur soccer players, according to a study published online ahead of print February 1 in Neurology. Soccer players completed an online questionnaire about how often they played soccer during the previous two weeks, how many times they had unintentional head impacts, how many times they headed the ball, and the frequency and severity of CNS symptoms. A total of 222 players completed 470 questionnaires. Heading-related symptoms were reported in 20% of the questionnaires. Heading in the highest quartile was significantly associated with CNS symptoms when controlling for unintentional head impacts. People with unintentional head impacts were at increased risk for CNS symptoms when controlling for heading.
Meditation or music listening may significantly enhance subjective memory function and objective cognitive performance in adults with subjective cognitive decline, according to a study published February 3 in the Journal of Alzheimer's Disease. A total of 60 participants with subjective cognitive decline were randomized to a Kirtan Kriya meditation program or a music listening program. The researchers asked participants to practice 12 minutes each day for three months, then at their discretion for the ensuing three months. At baseline, three months, and six months, researchers measured memory and cognitive functioning. Fifty-three participants completed the study. Both groups showed marked and significant improvements at three months in memory and cognitive performance. At six months, overall gains were maintained or improved, with effect sizes ranging from medium to large.
Yoga and aerobic exercise interventions do not significantly reduce objectively measured sleep disturbances among midlife women who are experiencing hot flashes, according to a study published January 15 in the Journal of Clinical Sleep Medicine. Researchers conducted secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. In the trial, 186 late transition and postmenopausal women ages 40 to 62 with hot flashes were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity. Changes in the actigraphic sleep outcomes from baseline to weeks 11 to 12 were small and did not differ between groups. An exploratory analysis suggested that women with poor self-reported sleep quality at baseline potentially had improved sleep stability following yoga.
Longitudinal data provide strong evidence of cognitive aging in midlife women, with substantial within-woman declines in processing speed and memory, according to a study published January 3 in PLoS One. Researchers used data from 2,124 participants from the Study of Women's Health Across the Nation. Participants completed annual tests of processing speed, verbal episodic memory, and working memory. Average age at baseline was 54. There were 7,185 cognitive assessments with a median follow-up time of 6.5 years. In mixed effects regression, adjusted for practice effects, retention, menopause symptoms, and covariates, scores on two of four cognition tests declined. Mean decline in cognitive speed was 0.28 per year or 4.9% in 10 years, and mean decline in verbal episodic memory (delayed testing) was 0.02 per year or 2% in 10 years.
The FDA has approved Emflaza (deflazacort) for the treatment of Duchenne muscular dystrophy in patients age 5 and older. The corticosteroid is available in an immediate-release tablet formulation (6 mg, 18 mg, 30 mg, and 36 mg) as well as an oral suspension formulation (22.75 mg/mL). In a multicenter, randomized, double-blind, placebo-controlled study of 196 male pediatric patients, patients who received deflazacort had improved muscle strength at 12 weeks, compared with patients who received placebo. Through the 52-week study, an overall stability in average muscle strength was maintained in patients who received deflazacort. Results on several timed measures of patient function (eg, time to stand from supine, time to climb four stairs, and time to walk or run 30 feet) also numerically favored deflazacort 0.9 mg/kg/day at week 12. Marathon Pharmaceuticals, headquartered in Northbrook, Illinois, markets Emflaza.
—Kimberly Williams
Serum levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were unable to distinguish between patients with mild traumatic brain injury (mTBI) and patients with orthopedic trauma, according to a study published online ahead of print January 27 in the Journal of Neurotrauma. The results cast doubt on the value of these proposed biomarkers in diagnosing mTBI, the researchers said. Serum UCH-L1 and GFAP were longitudinally measured in 73 patients with acute orthopedic injury and in 93 patients with CT-negative mTBI when they arrived at the hospital and one, two, three, and seven days after admission, as well as at a follow-up visit between three and 10 months after injury. Levels of GFAP were higher in patients with orthopedic trauma than in patients with mTBI on arrival, but subsequent levels did not differ between groups. Levels of UCH-L1 did not significantly differ between the groups.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation without maintenance therapy is effective for inducing long-term sustained remission of active relapsing-remitting multiple sclerosis at five years, according to a study published online ahead of print February 1 in Neurology. Twenty-five participants were evaluated for transplant, and 24 participants underwent high-dose immunosuppressive therapy and hematopoietic cell transplantation. Median follow-up was 62 months. Event-free survival (ie, survival without disability progression, relapse, or new lesions on MRI) was 69.2%. Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3%, 86.9%, and 86.3%, respectively. Adverse events were consistent with toxic effects associated with high-dose immunosuppressive therapy and hematopoietic cell transplantation, including cytopenia and infection. Neurologic disability improved among participants who survived and completed the study, with a median change in Expanded Disability Status Scale score of -0.5.
Estimated glomerular filtration rate on admission is an important predictor of poststroke short-term outcomes, according to a cohort study published in the February issue of Stroke. Investigators analyzed data from 232,236 patients with ischemic stroke in Get With The Guidelines-Stroke. Patients were age 65 or older. In all, 11.8% of patients died during hospitalization or were discharged to hospice, and 38.6% were discharged home. Renal dysfunction was independently associated with an increased risk of in-hospital mortality that was highest among those with an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 without dialysis (odds ratio, 2.52). In addition, receiving dialysis and having an estimated glomerular filtration rate of less than 29 mL/min/1.73 m2 were associated with lower odds of being discharged home.
Habitual sleep duration in monozygotic twins may be associated with distinct patterns of differential gene expression and pathway enrichment that affect immune response, according to a study published in the January issue of Sleep. Investigators selected 11 healthy monozygotic twin pairs (82% female; mean age, 42.7) based on subjective sleep duration discordance and then monitored participants' habitual sleep duration with two weeks of wrist actigraphy. Peripheral blood leukocyte RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. The mean 24-hour sleep duration of the total sample was 439.2 minutes. Mean within-pair sleep duration difference per 24 hours was 64.4 minutes. The researchers observed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with upregulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Genes that were downregulated with short sleep were highly enriched in immunoinfammatory pathways, as well as developmental programs, coagulation cascade, and cell adhesion.
A brain-computer interface that can decipher the thoughts of people who are unable to communicate may help people with completely locked-in syndrome, according to a study published January 31 in PLOS Biology. Researchers studied a brain-computer interface in four patients with advanced amyotrophic lateral sclerosis and completely locked-in syndrome. Patients responded to "yes" or "no" questions by thinking their answers. The noninvasive brain-computer interface assessed changes in frontocentral cortical oxygenation, measured using functional near-infrared spectroscopy, to determine patients' answers. Patients communicated with an above-chance-level correct response rate over 70%. EEG oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication.
Using a new noninvasive fMRI method, physicians may be able to predict who is more likely to continue experiencing symptoms months or years after concussion, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Investigators recruited 75 patients with mild traumatic brain injury (mTBI) and 47 healthy subjects as part of the prospective, multicenter Transforming Research and Clinical Knowledge in TBI pilot study. Researchers compared the functional connectivity of the resting-state networks between patients and controls, and group differences in the interactions between resting-state networks. They assessed patients' cognitive and behavioral performance at six months post injury. Spatial maps of resting-state networks involved in behavioral and cognitive processes differed between patients with mTBI and healthy controls, and these differences were predictive of patients' outcomes at six months post injury.
Among patients with Alzheimer's disease, lifelong bilingualism correlates with functional modulations in crucial neural networks, suggesting neural reserve and compensatory mechanisms, according to a study published online ahead of print January 30 in the Proceedings of the National Academy of Sciences. Eighty-five patients with Alzheimer's disease (45 German-Italian bilingual speakers and 40 monolingual speakers) matched for disease duration were included in this study. Bilingual individuals were on average five years older than people who did not speak another language. Consistent with models of cognitive reserve, cerebral hypometabolism was more severe in the group of bilingual individuals with Alzheimer's disease. Metabolic connectivity analyses supported a neuroprotective effect of bilingualism by showing increased connectivity in the executive control and the default mode networks in bilingual patients, compared with monolingual patients.
The Huntington's Disease Society of America (HDSA), in conjunction with the FDA, conducted two surveys to gather the perspectives of patients with Huntington's disease and juvenile Huntington's disease and their caregivers. Findings from the surveys were published online ahead of print January 24 in the Journal of Huntington's Disease. One survey covered disease symptoms that matter most to people with Huntington's disease, and the other covered current approaches to treatment. The surveys received a total of 3,631 responses. "The frequency and impact of symptoms appear to be felt more by caregivers than individuals with Huntington's Disease, especially when it comes to loss of abilities," said lead investigator George J. Yohrling, PhD, Senior Director of Mission and Scientific Affairs for the HDSA. "There was also a large difference in the perception of symptom frequency between caregivers and individuals with Huntington's disease."
Intentional and unintentional head impacts are independently associated with moderate to severe CNS symptoms in adult amateur soccer players, according to a study published online ahead of print February 1 in Neurology. Soccer players completed an online questionnaire about how often they played soccer during the previous two weeks, how many times they had unintentional head impacts, how many times they headed the ball, and the frequency and severity of CNS symptoms. A total of 222 players completed 470 questionnaires. Heading-related symptoms were reported in 20% of the questionnaires. Heading in the highest quartile was significantly associated with CNS symptoms when controlling for unintentional head impacts. People with unintentional head impacts were at increased risk for CNS symptoms when controlling for heading.
Meditation or music listening may significantly enhance subjective memory function and objective cognitive performance in adults with subjective cognitive decline, according to a study published February 3 in the Journal of Alzheimer's Disease. A total of 60 participants with subjective cognitive decline were randomized to a Kirtan Kriya meditation program or a music listening program. The researchers asked participants to practice 12 minutes each day for three months, then at their discretion for the ensuing three months. At baseline, three months, and six months, researchers measured memory and cognitive functioning. Fifty-three participants completed the study. Both groups showed marked and significant improvements at three months in memory and cognitive performance. At six months, overall gains were maintained or improved, with effect sizes ranging from medium to large.
Yoga and aerobic exercise interventions do not significantly reduce objectively measured sleep disturbances among midlife women who are experiencing hot flashes, according to a study published January 15 in the Journal of Clinical Sleep Medicine. Researchers conducted secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. In the trial, 186 late transition and postmenopausal women ages 40 to 62 with hot flashes were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity. Changes in the actigraphic sleep outcomes from baseline to weeks 11 to 12 were small and did not differ between groups. An exploratory analysis suggested that women with poor self-reported sleep quality at baseline potentially had improved sleep stability following yoga.
Longitudinal data provide strong evidence of cognitive aging in midlife women, with substantial within-woman declines in processing speed and memory, according to a study published January 3 in PLoS One. Researchers used data from 2,124 participants from the Study of Women's Health Across the Nation. Participants completed annual tests of processing speed, verbal episodic memory, and working memory. Average age at baseline was 54. There were 7,185 cognitive assessments with a median follow-up time of 6.5 years. In mixed effects regression, adjusted for practice effects, retention, menopause symptoms, and covariates, scores on two of four cognition tests declined. Mean decline in cognitive speed was 0.28 per year or 4.9% in 10 years, and mean decline in verbal episodic memory (delayed testing) was 0.02 per year or 2% in 10 years.
The FDA has approved Emflaza (deflazacort) for the treatment of Duchenne muscular dystrophy in patients age 5 and older. The corticosteroid is available in an immediate-release tablet formulation (6 mg, 18 mg, 30 mg, and 36 mg) as well as an oral suspension formulation (22.75 mg/mL). In a multicenter, randomized, double-blind, placebo-controlled study of 196 male pediatric patients, patients who received deflazacort had improved muscle strength at 12 weeks, compared with patients who received placebo. Through the 52-week study, an overall stability in average muscle strength was maintained in patients who received deflazacort. Results on several timed measures of patient function (eg, time to stand from supine, time to climb four stairs, and time to walk or run 30 feet) also numerically favored deflazacort 0.9 mg/kg/day at week 12. Marathon Pharmaceuticals, headquartered in Northbrook, Illinois, markets Emflaza.
—Kimberly Williams
Serum levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were unable to distinguish between patients with mild traumatic brain injury (mTBI) and patients with orthopedic trauma, according to a study published online ahead of print January 27 in the Journal of Neurotrauma. The results cast doubt on the value of these proposed biomarkers in diagnosing mTBI, the researchers said. Serum UCH-L1 and GFAP were longitudinally measured in 73 patients with acute orthopedic injury and in 93 patients with CT-negative mTBI when they arrived at the hospital and one, two, three, and seven days after admission, as well as at a follow-up visit between three and 10 months after injury. Levels of GFAP were higher in patients with orthopedic trauma than in patients with mTBI on arrival, but subsequent levels did not differ between groups. Levels of UCH-L1 did not significantly differ between the groups.
High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation without maintenance therapy is effective for inducing long-term sustained remission of active relapsing-remitting multiple sclerosis at five years, according to a study published online ahead of print February 1 in Neurology. Twenty-five participants were evaluated for transplant, and 24 participants underwent high-dose immunosuppressive therapy and hematopoietic cell transplantation. Median follow-up was 62 months. Event-free survival (ie, survival without disability progression, relapse, or new lesions on MRI) was 69.2%. Progression-free survival, clinical relapse-free survival, and MRI activity-free survival were 91.3%, 86.9%, and 86.3%, respectively. Adverse events were consistent with toxic effects associated with high-dose immunosuppressive therapy and hematopoietic cell transplantation, including cytopenia and infection. Neurologic disability improved among participants who survived and completed the study, with a median change in Expanded Disability Status Scale score of -0.5.
Estimated glomerular filtration rate on admission is an important predictor of poststroke short-term outcomes, according to a cohort study published in the February issue of Stroke. Investigators analyzed data from 232,236 patients with ischemic stroke in Get With The Guidelines-Stroke. Patients were age 65 or older. In all, 11.8% of patients died during hospitalization or were discharged to hospice, and 38.6% were discharged home. Renal dysfunction was independently associated with an increased risk of in-hospital mortality that was highest among those with an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 without dialysis (odds ratio, 2.52). In addition, receiving dialysis and having an estimated glomerular filtration rate of less than 29 mL/min/1.73 m2 were associated with lower odds of being discharged home.
Habitual sleep duration in monozygotic twins may be associated with distinct patterns of differential gene expression and pathway enrichment that affect immune response, according to a study published in the January issue of Sleep. Investigators selected 11 healthy monozygotic twin pairs (82% female; mean age, 42.7) based on subjective sleep duration discordance and then monitored participants' habitual sleep duration with two weeks of wrist actigraphy. Peripheral blood leukocyte RNA from fasting blood samples was obtained on the final day of actigraphic measurement and hybridized to Illumina humanHT-12 microarrays. The mean 24-hour sleep duration of the total sample was 439.2 minutes. Mean within-pair sleep duration difference per 24 hours was 64.4 minutes. The researchers observed distinctive pathway enrichment based on sleep duration differences. Habitual short sleep was associated with upregulation of genes involved in transcription, ribosome, translation, and oxidative phosphorylation. Genes that were downregulated with short sleep were highly enriched in immunoinfammatory pathways, as well as developmental programs, coagulation cascade, and cell adhesion.
A brain-computer interface that can decipher the thoughts of people who are unable to communicate may help people with completely locked-in syndrome, according to a study published January 31 in PLOS Biology. Researchers studied a brain-computer interface in four patients with advanced amyotrophic lateral sclerosis and completely locked-in syndrome. Patients responded to "yes" or "no" questions by thinking their answers. The noninvasive brain-computer interface assessed changes in frontocentral cortical oxygenation, measured using functional near-infrared spectroscopy, to determine patients' answers. Patients communicated with an above-chance-level correct response rate over 70%. EEG oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication.
Using a new noninvasive fMRI method, physicians may be able to predict who is more likely to continue experiencing symptoms months or years after concussion, according to a study published online ahead of print January 13 in the Journal of Neurotrauma. Investigators recruited 75 patients with mild traumatic brain injury (mTBI) and 47 healthy subjects as part of the prospective, multicenter Transforming Research and Clinical Knowledge in TBI pilot study. Researchers compared the functional connectivity of the resting-state networks between patients and controls, and group differences in the interactions between resting-state networks. They assessed patients' cognitive and behavioral performance at six months post injury. Spatial maps of resting-state networks involved in behavioral and cognitive processes differed between patients with mTBI and healthy controls, and these differences were predictive of patients' outcomes at six months post injury.
Among patients with Alzheimer's disease, lifelong bilingualism correlates with functional modulations in crucial neural networks, suggesting neural reserve and compensatory mechanisms, according to a study published online ahead of print January 30 in the Proceedings of the National Academy of Sciences. Eighty-five patients with Alzheimer's disease (45 German-Italian bilingual speakers and 40 monolingual speakers) matched for disease duration were included in this study. Bilingual individuals were on average five years older than people who did not speak another language. Consistent with models of cognitive reserve, cerebral hypometabolism was more severe in the group of bilingual individuals with Alzheimer's disease. Metabolic connectivity analyses supported a neuroprotective effect of bilingualism by showing increased connectivity in the executive control and the default mode networks in bilingual patients, compared with monolingual patients.
The Huntington's Disease Society of America (HDSA), in conjunction with the FDA, conducted two surveys to gather the perspectives of patients with Huntington's disease and juvenile Huntington's disease and their caregivers. Findings from the surveys were published online ahead of print January 24 in the Journal of Huntington's Disease. One survey covered disease symptoms that matter most to people with Huntington's disease, and the other covered current approaches to treatment. The surveys received a total of 3,631 responses. "The frequency and impact of symptoms appear to be felt more by caregivers than individuals with Huntington's Disease, especially when it comes to loss of abilities," said lead investigator George J. Yohrling, PhD, Senior Director of Mission and Scientific Affairs for the HDSA. "There was also a large difference in the perception of symptom frequency between caregivers and individuals with Huntington's disease."
Intentional and unintentional head impacts are independently associated with moderate to severe CNS symptoms in adult amateur soccer players, according to a study published online ahead of print February 1 in Neurology. Soccer players completed an online questionnaire about how often they played soccer during the previous two weeks, how many times they had unintentional head impacts, how many times they headed the ball, and the frequency and severity of CNS symptoms. A total of 222 players completed 470 questionnaires. Heading-related symptoms were reported in 20% of the questionnaires. Heading in the highest quartile was significantly associated with CNS symptoms when controlling for unintentional head impacts. People with unintentional head impacts were at increased risk for CNS symptoms when controlling for heading.
Meditation or music listening may significantly enhance subjective memory function and objective cognitive performance in adults with subjective cognitive decline, according to a study published February 3 in the Journal of Alzheimer's Disease. A total of 60 participants with subjective cognitive decline were randomized to a Kirtan Kriya meditation program or a music listening program. The researchers asked participants to practice 12 minutes each day for three months, then at their discretion for the ensuing three months. At baseline, three months, and six months, researchers measured memory and cognitive functioning. Fifty-three participants completed the study. Both groups showed marked and significant improvements at three months in memory and cognitive performance. At six months, overall gains were maintained or improved, with effect sizes ranging from medium to large.
Yoga and aerobic exercise interventions do not significantly reduce objectively measured sleep disturbances among midlife women who are experiencing hot flashes, according to a study published January 15 in the Journal of Clinical Sleep Medicine. Researchers conducted secondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health network. In the trial, 186 late transition and postmenopausal women ages 40 to 62 with hot flashes were randomized to 12 weeks of yoga, supervised aerobic exercise, or usual activity. Changes in the actigraphic sleep outcomes from baseline to weeks 11 to 12 were small and did not differ between groups. An exploratory analysis suggested that women with poor self-reported sleep quality at baseline potentially had improved sleep stability following yoga.
Longitudinal data provide strong evidence of cognitive aging in midlife women, with substantial within-woman declines in processing speed and memory, according to a study published January 3 in PLoS One. Researchers used data from 2,124 participants from the Study of Women's Health Across the Nation. Participants completed annual tests of processing speed, verbal episodic memory, and working memory. Average age at baseline was 54. There were 7,185 cognitive assessments with a median follow-up time of 6.5 years. In mixed effects regression, adjusted for practice effects, retention, menopause symptoms, and covariates, scores on two of four cognition tests declined. Mean decline in cognitive speed was 0.28 per year or 4.9% in 10 years, and mean decline in verbal episodic memory (delayed testing) was 0.02 per year or 2% in 10 years.
The FDA has approved Emflaza (deflazacort) for the treatment of Duchenne muscular dystrophy in patients age 5 and older. The corticosteroid is available in an immediate-release tablet formulation (6 mg, 18 mg, 30 mg, and 36 mg) as well as an oral suspension formulation (22.75 mg/mL). In a multicenter, randomized, double-blind, placebo-controlled study of 196 male pediatric patients, patients who received deflazacort had improved muscle strength at 12 weeks, compared with patients who received placebo. Through the 52-week study, an overall stability in average muscle strength was maintained in patients who received deflazacort. Results on several timed measures of patient function (eg, time to stand from supine, time to climb four stairs, and time to walk or run 30 feet) also numerically favored deflazacort 0.9 mg/kg/day at week 12. Marathon Pharmaceuticals, headquartered in Northbrook, Illinois, markets Emflaza.
—Kimberly Williams
New and Noteworthy Information—February 2017
Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.
Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.
People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.
—Kimberly Williams
Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.
Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.
People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.
—Kimberly Williams
Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.
Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.
People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.
—Kimberly Williams
New and Noteworthy Information—January 2017
Students who played varsity high school football between 1956 and 1970 do not have an increased risk of neurodegenerative diseases, compared with athletes engaged in other varsity sports, according to a study published online ahead of print December 12, 2016, in Mayo Clinic Proceedings. Researchers identified 296 male varsity football players in public high schools in Rochester, Minnesota, and 190 male varsity swimmers, wrestlers, and basketball players. Using records from the Rochester Epidemiology Project, investigators ascertained the incidence of late-life neurodegenerative diseases. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared with other athletes, football players did not have an increased risk of neurodegenerative disease overall, nor an increased risk of dementia, parkinsonism, or amyotrophic lateral sclerosis.
Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, according to a study published online ahead of print December 5, 2016, in the Journal of Alzheimer's Disease. Researchers examined data from the MEDALZ study for 70,718 people who were newly diagnosed with Alzheimer's disease in Finland from 2005 to 2011. Death, excluding death from cancer, was extracted from the Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics using Cox proportional hazard models. The absolute difference in mortality rate was 4.58 deaths per 100 person-years. The risk of mortality was increased from the first days of antipsychotic use and attenuated gradually. Antipsychotic polypharmacy was associated with an almost doubled risk of mortality, compared with monotherapy.
A disruption of structural connections in a brain network contributes to cognitive deficits in patients with Parkinson's disease, according to a study published online ahead of print December 7, 2016, in Radiology. The structural brain connectomes of 170 patients with Parkinson's disease and 41 healthy controls were obtained with deterministic diffusion-tensor tractography. Patients with Parkinson's disease and mild cognitive impairment (MCI) had global network alterations, compared with controls and patients with Parkinson's disease without MCI. Relative to controls, patients with Parkinson's disease and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy in the right hemisphere and a subnetwork with increased mean diffusivity involving similar regions bilaterally. Compared with patients with Parkinson's disease without MCI, people with Parkinson's disease and MCI had networks with decreased fractional anisotropy.
A proposed diagnostic algorithm for sporadic Creutzfeldt-Jakob disease combines CSF and olfactory mucosa real-time quaking-induced conversion testing to provide approximately 100% sensitivity and specificity in the clinical phase of the disease, according to a study published online ahead of print December 12, 2016, in JAMA Neurology. Among the 86 patients included in this analysis, 61 patients with sporadic Creutzfeldt-Jakob disease had positive real-time quaking-induced conversion findings using olfactory mucosa, CSF samples, or both, for an overall real-time quaking-induced conversion sensitivity of 100%. All patients with a final diagnosis of nonprion disease had negative real-time quaking-induced conversion findings, for 100% specificity. Of eight symptomatic patients with various mutations causing Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker syndrome, six had positive and two had negative real-time quaking-induced conversion findings, for a sensitivity of 75%.
CSF autotaxin may be a useful biomarker of dysmetabolism for examining risk for and outcomes of Alzheimer's disease, according to research published December 1, 2016, in the Journal of Alzheimer's Disease. Investigators studied 287 participants in the Alzheimer's Disease Neuroimaging Initiative, including 86 cognitively normal participants, 135 participants with mild cognitive impairment (MCI), and 66 participants with Alzheimer's disease. Autotaxin levels were significantly higher in patients with MCI and those with Alzheimer's disease. Each point increase in log-based autotaxin corresponded to a 3.5- to 5-times higher likelihood of having MCI and Alzheimer's disease, respectively. Higher autotaxin in Alzheimer's disease predicted hypometabolism in the medial temporal lobe and prefrontal cortex, and worse performance on executive function and memory factors. Autotaxin was associated with decreased cortical thickness in prefrontal cortex areas.
Marital history is significantly associated with survival after stroke, according to a study published December 14, 2016, in the Journal of the American Heart Association. Data from a nationally representative sample of 2,351 older adults who experienced a stroke were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among people who were never married, remarried, divorced, and widowed, relative to those who remained continuously married. Researchers also found that having multiple marital losses was especially detrimental to survival, regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiologic risk factors.
Prefrontal brain activity levels during a cognitively demanding walking condition predict falls in high-functioning senior citizens, according to a study published online ahead of print December 7, 2016, in Neurology. Researchers examined 166 people with a mean age of 75 with functional near-infrared spectroscopy during motor, cognitive, and combined motor and cognitive tasks. Incident falls were prospectively assessed during a 50-month study period. During a mean follow-up of 33.9 months, 116 falls occurred. Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls. Neither behavioral outcomes on the dual task nor brain activation patterns on the single tasks predicted falls in this high-functioning sample. The results remained robust after accounting for multiple confounders, cognitive status, slow gait, previous falls, and frailty.
Localized brain injury and repair, indicated by higher translocator protein 18 kDa signal and white matter changes, may be associated with National Football League (NFL) play, according to a study published online ahead of print November 28, 2016, in JAMA Neurology. This cross-sectional, case-control study included young active or former NFL players recruited from across the United States and 16 age-, sex-, highest educational level-, and BMI-matched control participants. Researchers used [11C]DPA-713 PET data and other imaging data from 12 active or former NFL players and 11 matched control participants. The NFL players showed higher total distribution volume in eight of 12 brain regions examined. Investigators also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players, compared with 15 control participants.
Exposure to maternal rheumatoid arthritis is associated with an increased risk of childhood epilepsy, while exposure to paternal rheumatoid arthritis is not, according to a study published December 13, 2016, in Neurology. Researchers performed a nationwide cohort study of 1,917,723 people that were born between 1977 and 2008. Compared with unexposed children, children exposed to maternal rheumatoid arthritis had an increased risk of early and late childhood epilepsy, while children exposed to maternal rheumatoid arthritis had no increased risk of epilepsy in adolescence and adulthood. Paternal rheumatoid arthritis was not associated with an overall risk of epilepsy in the offspring or at any age. Children exposed to maternal rheumatoid arthritis in utero had a more pronounced increased risk of early childhood epilepsy than children of mothers who were diagnosed with rheumatoid arthritis after childbirth.
Having surgery may be linked to developing Guillain-Barré syndrome for people with cancer or autoimmune disorders, according to a study published online ahead of print November 23, 2016, in Neurology Clinical Practice. Researchers retrospectively reviewed consecutive patients diagnosed with Guillain-Barré syndrome within eight weeks of a surgical procedure between January 1995 and June 2014. Of the 208 people treated for Guillain-Barré syndrome, 31 people developed the syndrome within eight weeks of having a surgical procedure. People who had had cancer within the previous six months were seven times more likely to develop Guillain-Barré syndrome after surgery than people who had not had cancer. People who had pre-existing autoimmune disorders were five times more likely to develop Guillain-Barré syndrome after surgery than those without autoimmune disorders.
Patients with Parkinson's disease and orthostatic hypotension have transient, posture-mediated changes in cognition, according to a study published online ahead of print November 30, 2016, in Neurology. To investigate the relation between orthostatic hypotension and posture-mediated cognitive impairment in Parkinson disease, researchers used a cross-sectional and within-group design. Participants included 18 patients with Parkinson's disease and orthostatic hypotension, 19 patients with Parkinson's disease but without orthostatic hypotension, and 18 healthy controls. Participants underwent neuropsychologic tests in the supine and upright-tilted positions. When relative performances were compared with each other, postural changes had no significant impact on participants with Parkinson's disease but without orthostatic hypotension, compared with the control group. Participants with Parkinson's disease and orthostatic hypotension, however, were more susceptible to posture-related impairment on several tests.
Low concentrations of neonatal vitamin D are associated with an increased risk of multiple sclerosis (MS), according to a study published online ahead of print November 30, 2016, in Neurology. Researchers conducted a matched case-control study. Dried blood spots samples from 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, one to two controls with the same sex and birth date were retrieved from the Biobank. Lower levels of 25-hydroxyvitamin D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile and lowest among those in the top quintile of 25-hydroxyvitamin D, with an odds ratio for top versus bottom of 0.53.
Children exposed to valproate in the womb are at an increased risk of having a malformation at birth, and the dose of valproate that the child is exposed to determines the level of risk, according to a study published November 7, 2016, in the Cochrane Database of Systematic Reviews. Researchers analyzed 50 studies, with 31 contributing to a meta-analysis. Children exposed to valproate were at a higher risk of malformation, compared with children born to women without epilepsy and to women with untreated epilepsy. Investigators found significantly higher rates of specific malformations associating phenobarbital exposure with cardiac malformations and valproate exposure with neural tube, cardiac, orofacial, craniofacial, skeletal, and limb malformations, compared with other antiepileptic drugs. Dose of exposure mediated the risk of malformation following valproate exposure.
—Kimberly Williams
Students who played varsity high school football between 1956 and 1970 do not have an increased risk of neurodegenerative diseases, compared with athletes engaged in other varsity sports, according to a study published online ahead of print December 12, 2016, in Mayo Clinic Proceedings. Researchers identified 296 male varsity football players in public high schools in Rochester, Minnesota, and 190 male varsity swimmers, wrestlers, and basketball players. Using records from the Rochester Epidemiology Project, investigators ascertained the incidence of late-life neurodegenerative diseases. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared with other athletes, football players did not have an increased risk of neurodegenerative disease overall, nor an increased risk of dementia, parkinsonism, or amyotrophic lateral sclerosis.
Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, according to a study published online ahead of print December 5, 2016, in the Journal of Alzheimer's Disease. Researchers examined data from the MEDALZ study for 70,718 people who were newly diagnosed with Alzheimer's disease in Finland from 2005 to 2011. Death, excluding death from cancer, was extracted from the Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics using Cox proportional hazard models. The absolute difference in mortality rate was 4.58 deaths per 100 person-years. The risk of mortality was increased from the first days of antipsychotic use and attenuated gradually. Antipsychotic polypharmacy was associated with an almost doubled risk of mortality, compared with monotherapy.
A disruption of structural connections in a brain network contributes to cognitive deficits in patients with Parkinson's disease, according to a study published online ahead of print December 7, 2016, in Radiology. The structural brain connectomes of 170 patients with Parkinson's disease and 41 healthy controls were obtained with deterministic diffusion-tensor tractography. Patients with Parkinson's disease and mild cognitive impairment (MCI) had global network alterations, compared with controls and patients with Parkinson's disease without MCI. Relative to controls, patients with Parkinson's disease and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy in the right hemisphere and a subnetwork with increased mean diffusivity involving similar regions bilaterally. Compared with patients with Parkinson's disease without MCI, people with Parkinson's disease and MCI had networks with decreased fractional anisotropy.
A proposed diagnostic algorithm for sporadic Creutzfeldt-Jakob disease combines CSF and olfactory mucosa real-time quaking-induced conversion testing to provide approximately 100% sensitivity and specificity in the clinical phase of the disease, according to a study published online ahead of print December 12, 2016, in JAMA Neurology. Among the 86 patients included in this analysis, 61 patients with sporadic Creutzfeldt-Jakob disease had positive real-time quaking-induced conversion findings using olfactory mucosa, CSF samples, or both, for an overall real-time quaking-induced conversion sensitivity of 100%. All patients with a final diagnosis of nonprion disease had negative real-time quaking-induced conversion findings, for 100% specificity. Of eight symptomatic patients with various mutations causing Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker syndrome, six had positive and two had negative real-time quaking-induced conversion findings, for a sensitivity of 75%.
CSF autotaxin may be a useful biomarker of dysmetabolism for examining risk for and outcomes of Alzheimer's disease, according to research published December 1, 2016, in the Journal of Alzheimer's Disease. Investigators studied 287 participants in the Alzheimer's Disease Neuroimaging Initiative, including 86 cognitively normal participants, 135 participants with mild cognitive impairment (MCI), and 66 participants with Alzheimer's disease. Autotaxin levels were significantly higher in patients with MCI and those with Alzheimer's disease. Each point increase in log-based autotaxin corresponded to a 3.5- to 5-times higher likelihood of having MCI and Alzheimer's disease, respectively. Higher autotaxin in Alzheimer's disease predicted hypometabolism in the medial temporal lobe and prefrontal cortex, and worse performance on executive function and memory factors. Autotaxin was associated with decreased cortical thickness in prefrontal cortex areas.
Marital history is significantly associated with survival after stroke, according to a study published December 14, 2016, in the Journal of the American Heart Association. Data from a nationally representative sample of 2,351 older adults who experienced a stroke were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among people who were never married, remarried, divorced, and widowed, relative to those who remained continuously married. Researchers also found that having multiple marital losses was especially detrimental to survival, regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiologic risk factors.
Prefrontal brain activity levels during a cognitively demanding walking condition predict falls in high-functioning senior citizens, according to a study published online ahead of print December 7, 2016, in Neurology. Researchers examined 166 people with a mean age of 75 with functional near-infrared spectroscopy during motor, cognitive, and combined motor and cognitive tasks. Incident falls were prospectively assessed during a 50-month study period. During a mean follow-up of 33.9 months, 116 falls occurred. Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls. Neither behavioral outcomes on the dual task nor brain activation patterns on the single tasks predicted falls in this high-functioning sample. The results remained robust after accounting for multiple confounders, cognitive status, slow gait, previous falls, and frailty.
Localized brain injury and repair, indicated by higher translocator protein 18 kDa signal and white matter changes, may be associated with National Football League (NFL) play, according to a study published online ahead of print November 28, 2016, in JAMA Neurology. This cross-sectional, case-control study included young active or former NFL players recruited from across the United States and 16 age-, sex-, highest educational level-, and BMI-matched control participants. Researchers used [11C]DPA-713 PET data and other imaging data from 12 active or former NFL players and 11 matched control participants. The NFL players showed higher total distribution volume in eight of 12 brain regions examined. Investigators also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players, compared with 15 control participants.
Exposure to maternal rheumatoid arthritis is associated with an increased risk of childhood epilepsy, while exposure to paternal rheumatoid arthritis is not, according to a study published December 13, 2016, in Neurology. Researchers performed a nationwide cohort study of 1,917,723 people that were born between 1977 and 2008. Compared with unexposed children, children exposed to maternal rheumatoid arthritis had an increased risk of early and late childhood epilepsy, while children exposed to maternal rheumatoid arthritis had no increased risk of epilepsy in adolescence and adulthood. Paternal rheumatoid arthritis was not associated with an overall risk of epilepsy in the offspring or at any age. Children exposed to maternal rheumatoid arthritis in utero had a more pronounced increased risk of early childhood epilepsy than children of mothers who were diagnosed with rheumatoid arthritis after childbirth.
Having surgery may be linked to developing Guillain-Barré syndrome for people with cancer or autoimmune disorders, according to a study published online ahead of print November 23, 2016, in Neurology Clinical Practice. Researchers retrospectively reviewed consecutive patients diagnosed with Guillain-Barré syndrome within eight weeks of a surgical procedure between January 1995 and June 2014. Of the 208 people treated for Guillain-Barré syndrome, 31 people developed the syndrome within eight weeks of having a surgical procedure. People who had had cancer within the previous six months were seven times more likely to develop Guillain-Barré syndrome after surgery than people who had not had cancer. People who had pre-existing autoimmune disorders were five times more likely to develop Guillain-Barré syndrome after surgery than those without autoimmune disorders.
Patients with Parkinson's disease and orthostatic hypotension have transient, posture-mediated changes in cognition, according to a study published online ahead of print November 30, 2016, in Neurology. To investigate the relation between orthostatic hypotension and posture-mediated cognitive impairment in Parkinson disease, researchers used a cross-sectional and within-group design. Participants included 18 patients with Parkinson's disease and orthostatic hypotension, 19 patients with Parkinson's disease but without orthostatic hypotension, and 18 healthy controls. Participants underwent neuropsychologic tests in the supine and upright-tilted positions. When relative performances were compared with each other, postural changes had no significant impact on participants with Parkinson's disease but without orthostatic hypotension, compared with the control group. Participants with Parkinson's disease and orthostatic hypotension, however, were more susceptible to posture-related impairment on several tests.
Low concentrations of neonatal vitamin D are associated with an increased risk of multiple sclerosis (MS), according to a study published online ahead of print November 30, 2016, in Neurology. Researchers conducted a matched case-control study. Dried blood spots samples from 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, one to two controls with the same sex and birth date were retrieved from the Biobank. Lower levels of 25-hydroxyvitamin D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile and lowest among those in the top quintile of 25-hydroxyvitamin D, with an odds ratio for top versus bottom of 0.53.
Children exposed to valproate in the womb are at an increased risk of having a malformation at birth, and the dose of valproate that the child is exposed to determines the level of risk, according to a study published November 7, 2016, in the Cochrane Database of Systematic Reviews. Researchers analyzed 50 studies, with 31 contributing to a meta-analysis. Children exposed to valproate were at a higher risk of malformation, compared with children born to women without epilepsy and to women with untreated epilepsy. Investigators found significantly higher rates of specific malformations associating phenobarbital exposure with cardiac malformations and valproate exposure with neural tube, cardiac, orofacial, craniofacial, skeletal, and limb malformations, compared with other antiepileptic drugs. Dose of exposure mediated the risk of malformation following valproate exposure.
—Kimberly Williams
Students who played varsity high school football between 1956 and 1970 do not have an increased risk of neurodegenerative diseases, compared with athletes engaged in other varsity sports, according to a study published online ahead of print December 12, 2016, in Mayo Clinic Proceedings. Researchers identified 296 male varsity football players in public high schools in Rochester, Minnesota, and 190 male varsity swimmers, wrestlers, and basketball players. Using records from the Rochester Epidemiology Project, investigators ascertained the incidence of late-life neurodegenerative diseases. Football players had an increased risk of medically documented head trauma, especially if they played football for more than one year. Compared with other athletes, football players did not have an increased risk of neurodegenerative disease overall, nor an increased risk of dementia, parkinsonism, or amyotrophic lateral sclerosis.
Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, according to a study published online ahead of print December 5, 2016, in the Journal of Alzheimer's Disease. Researchers examined data from the MEDALZ study for 70,718 people who were newly diagnosed with Alzheimer's disease in Finland from 2005 to 2011. Death, excluding death from cancer, was extracted from the Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics using Cox proportional hazard models. The absolute difference in mortality rate was 4.58 deaths per 100 person-years. The risk of mortality was increased from the first days of antipsychotic use and attenuated gradually. Antipsychotic polypharmacy was associated with an almost doubled risk of mortality, compared with monotherapy.
A disruption of structural connections in a brain network contributes to cognitive deficits in patients with Parkinson's disease, according to a study published online ahead of print December 7, 2016, in Radiology. The structural brain connectomes of 170 patients with Parkinson's disease and 41 healthy controls were obtained with deterministic diffusion-tensor tractography. Patients with Parkinson's disease and mild cognitive impairment (MCI) had global network alterations, compared with controls and patients with Parkinson's disease without MCI. Relative to controls, patients with Parkinson's disease and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy in the right hemisphere and a subnetwork with increased mean diffusivity involving similar regions bilaterally. Compared with patients with Parkinson's disease without MCI, people with Parkinson's disease and MCI had networks with decreased fractional anisotropy.
A proposed diagnostic algorithm for sporadic Creutzfeldt-Jakob disease combines CSF and olfactory mucosa real-time quaking-induced conversion testing to provide approximately 100% sensitivity and specificity in the clinical phase of the disease, according to a study published online ahead of print December 12, 2016, in JAMA Neurology. Among the 86 patients included in this analysis, 61 patients with sporadic Creutzfeldt-Jakob disease had positive real-time quaking-induced conversion findings using olfactory mucosa, CSF samples, or both, for an overall real-time quaking-induced conversion sensitivity of 100%. All patients with a final diagnosis of nonprion disease had negative real-time quaking-induced conversion findings, for 100% specificity. Of eight symptomatic patients with various mutations causing Creutzfeldt-Jakob disease or Gerstmann-Sträussler-Scheinker syndrome, six had positive and two had negative real-time quaking-induced conversion findings, for a sensitivity of 75%.
CSF autotaxin may be a useful biomarker of dysmetabolism for examining risk for and outcomes of Alzheimer's disease, according to research published December 1, 2016, in the Journal of Alzheimer's Disease. Investigators studied 287 participants in the Alzheimer's Disease Neuroimaging Initiative, including 86 cognitively normal participants, 135 participants with mild cognitive impairment (MCI), and 66 participants with Alzheimer's disease. Autotaxin levels were significantly higher in patients with MCI and those with Alzheimer's disease. Each point increase in log-based autotaxin corresponded to a 3.5- to 5-times higher likelihood of having MCI and Alzheimer's disease, respectively. Higher autotaxin in Alzheimer's disease predicted hypometabolism in the medial temporal lobe and prefrontal cortex, and worse performance on executive function and memory factors. Autotaxin was associated with decreased cortical thickness in prefrontal cortex areas.
Marital history is significantly associated with survival after stroke, according to a study published December 14, 2016, in the Journal of the American Heart Association. Data from a nationally representative sample of 2,351 older adults who experienced a stroke were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among people who were never married, remarried, divorced, and widowed, relative to those who remained continuously married. Researchers also found that having multiple marital losses was especially detrimental to survival, regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiologic risk factors.
Prefrontal brain activity levels during a cognitively demanding walking condition predict falls in high-functioning senior citizens, according to a study published online ahead of print December 7, 2016, in Neurology. Researchers examined 166 people with a mean age of 75 with functional near-infrared spectroscopy during motor, cognitive, and combined motor and cognitive tasks. Incident falls were prospectively assessed during a 50-month study period. During a mean follow-up of 33.9 months, 116 falls occurred. Higher levels of prefrontal cortical activation during the dual-task walking condition predicted falls. Neither behavioral outcomes on the dual task nor brain activation patterns on the single tasks predicted falls in this high-functioning sample. The results remained robust after accounting for multiple confounders, cognitive status, slow gait, previous falls, and frailty.
Localized brain injury and repair, indicated by higher translocator protein 18 kDa signal and white matter changes, may be associated with National Football League (NFL) play, according to a study published online ahead of print November 28, 2016, in JAMA Neurology. This cross-sectional, case-control study included young active or former NFL players recruited from across the United States and 16 age-, sex-, highest educational level-, and BMI-matched control participants. Researchers used [11C]DPA-713 PET data and other imaging data from 12 active or former NFL players and 11 matched control participants. The NFL players showed higher total distribution volume in eight of 12 brain regions examined. Investigators also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players, compared with 15 control participants.
Exposure to maternal rheumatoid arthritis is associated with an increased risk of childhood epilepsy, while exposure to paternal rheumatoid arthritis is not, according to a study published December 13, 2016, in Neurology. Researchers performed a nationwide cohort study of 1,917,723 people that were born between 1977 and 2008. Compared with unexposed children, children exposed to maternal rheumatoid arthritis had an increased risk of early and late childhood epilepsy, while children exposed to maternal rheumatoid arthritis had no increased risk of epilepsy in adolescence and adulthood. Paternal rheumatoid arthritis was not associated with an overall risk of epilepsy in the offspring or at any age. Children exposed to maternal rheumatoid arthritis in utero had a more pronounced increased risk of early childhood epilepsy than children of mothers who were diagnosed with rheumatoid arthritis after childbirth.
Having surgery may be linked to developing Guillain-Barré syndrome for people with cancer or autoimmune disorders, according to a study published online ahead of print November 23, 2016, in Neurology Clinical Practice. Researchers retrospectively reviewed consecutive patients diagnosed with Guillain-Barré syndrome within eight weeks of a surgical procedure between January 1995 and June 2014. Of the 208 people treated for Guillain-Barré syndrome, 31 people developed the syndrome within eight weeks of having a surgical procedure. People who had had cancer within the previous six months were seven times more likely to develop Guillain-Barré syndrome after surgery than people who had not had cancer. People who had pre-existing autoimmune disorders were five times more likely to develop Guillain-Barré syndrome after surgery than those without autoimmune disorders.
Patients with Parkinson's disease and orthostatic hypotension have transient, posture-mediated changes in cognition, according to a study published online ahead of print November 30, 2016, in Neurology. To investigate the relation between orthostatic hypotension and posture-mediated cognitive impairment in Parkinson disease, researchers used a cross-sectional and within-group design. Participants included 18 patients with Parkinson's disease and orthostatic hypotension, 19 patients with Parkinson's disease but without orthostatic hypotension, and 18 healthy controls. Participants underwent neuropsychologic tests in the supine and upright-tilted positions. When relative performances were compared with each other, postural changes had no significant impact on participants with Parkinson's disease but without orthostatic hypotension, compared with the control group. Participants with Parkinson's disease and orthostatic hypotension, however, were more susceptible to posture-related impairment on several tests.
Low concentrations of neonatal vitamin D are associated with an increased risk of multiple sclerosis (MS), according to a study published online ahead of print November 30, 2016, in Neurology. Researchers conducted a matched case-control study. Dried blood spots samples from 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, one to two controls with the same sex and birth date were retrieved from the Biobank. Lower levels of 25-hydroxyvitamin D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile and lowest among those in the top quintile of 25-hydroxyvitamin D, with an odds ratio for top versus bottom of 0.53.
Children exposed to valproate in the womb are at an increased risk of having a malformation at birth, and the dose of valproate that the child is exposed to determines the level of risk, according to a study published November 7, 2016, in the Cochrane Database of Systematic Reviews. Researchers analyzed 50 studies, with 31 contributing to a meta-analysis. Children exposed to valproate were at a higher risk of malformation, compared with children born to women without epilepsy and to women with untreated epilepsy. Investigators found significantly higher rates of specific malformations associating phenobarbital exposure with cardiac malformations and valproate exposure with neural tube, cardiac, orofacial, craniofacial, skeletal, and limb malformations, compared with other antiepileptic drugs. Dose of exposure mediated the risk of malformation following valproate exposure.
—Kimberly Williams
New and Noteworthy Information—December 2016
Economic background does not affect the clinical course or long-term seizure outcome of childhood epilepsy, according to a study in Nova Scotia, Canada, published online ahead of print November 4 in Epilepsia. Researchers examined data for 421 patients with childhood epilepsy and 10 or more years of follow-up. Overall, 33% of families had poor income, 38% had adequate income, and 30% were well-off. Terminal remission occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off populations. Intractable epilepsy, status epilepticus, number of antiepileptic drugs used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes, however.
A genetic variant near melatonin receptor 1A (MTNR1A) may be associated with job-related exhaustion in shift workers, according to a study published online ahead of print October 10 in Sleep. Researchers assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey and performed a genome-wide association study. Job-related exhaustion was associated with the rs12506228 variation, located downstream of MTNR1A, in shift workers included in the Finnish national Health 2000 survey. The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and with changes in DNA methylation in the 5' regulatory region of MTNR1A. The risk variant may lead to reduced melatonin signaling in the brain.
In healthy postmenopausal women, reproductive life events related to sex hormones are positively related to aspects of cognition in later life, according to a study published November 7 in the Journal of the American Geriatrics Society. Researchers evaluated 830 menopausal women using a cognitive battery and a structured reproductive history questionnaire. On multivariable modeling, age at menarche of 13 or older was inversely associated with global cognition. Having a last pregnancy after age 35 was positively associated with verbal memory. Use of hormonal contraceptives was positively associated with global cognition and verbal memory. The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition and executive function.
Physical fitness, BMI, IQ, and stress resilience in young adulthood may be associated with the development of amyotrophic lateral sclerosis (ALS) at an early age, according to a study published in the October issue of the European Journal of Neurology. Data on physical fitness, BMI, IQ, and stress resilience were collected from 1,838,376 Swedish men ages 17 to 20 at conscription from 1968 to 2010. During follow-up, 439 participants developed ALS. People with physical fitness above the highest tertile had a higher risk of ALS before age 45. People with BMI greater than or equal to 25 had a lower risk of ALS at all ages. Individuals with IQ above the highest tertile had a significantly increased risk of ALS at an age of 56 and older.
Short sleep is associated with greater intake of sugared caffeinated sodas, according to a study published online ahead of print November 9 in Sleep Health. Using data from the 2005 to 2012 National Health and Nutrition Examination Survey, researchers examined self-reported sleep duration and beverage intake from two 24-hour dietary recalls among 18,779 adults. Adults who slept for seven to eight hours each night were considered the reference group. In fully adjusted models, people who slept for five hours or less had 21% higher sugar-sweetened beverage consumption. When analyzed by beverage type, this difference was attributed to caffeinated sugary beverages. Longer sleepers consumed fewer servings of coffee and water. There were no associations between self-reported sleep duration and consumption of 100% juice, tea, or diet drinks.
Treadmill training plus virtual reality reduces fall rates, compared with treadmill training alone, according to a study published September 17 in the Lancet. Adults ages 60 to 90 with motor and cognitive deficits and a high risk of falls were randomly assigned to receive six weeks of treadmill training plus virtual reality or treadmill training alone. Data from 282 participants were included in the prespecified, modified intention-to-treat analysis. In the six months after training, the incident rate of falls was significantly lower in the treadmill-training-plus-virtual-reality group than it had been before training. The incident rate did not decrease significantly in the treadmill-training-alone group. Six months after training, the incident rate of falls was also significantly lower in the treadmill-training-plus-virtual-reality group than in the treadmill-training group.
Current research does not support specific recommendations for treating hypertension to preserve cognition, according to a scientific statement by the American Heart Association published online ahead of print October 10 in Hypertension. A panel of experts reviewed the literature on hypertension, the treatment of hypertension, and the relationship between hypertension and cognition, and summarized the available data. They found that hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. They found strong evidence of a negative influence of mid-life hypertension on late-life cognitive function, but the cognitive effect of late-life hypertension is unclear. Observational studies indicate that high blood pressure damages the brain's blood vessels, leading to reduced blood flow to brain cells.
Manual-based cognitive behavioral therapy for insomnia delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia, according to a study published in the September issue of the Journal of the American Geriatrics Society. Researchers studied veterans age 60 or older who met diagnostic criteria for insomnia of three months' duration or longer. Nonclinician sleep coaches delivered five sessions of manual-based cognitive behavioral therapy for insomnia, including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, with weekly telephone behavioral sleep medicine supervision. Controls received sleep education. Intervention subjects had greater improvement than controls between baseline and post-treatment, baseline and six months, and baseline and 12 months in sleep onset latency, total wake time, sleep efficiency, Pittsburgh Sleep Quality Index, and Insomnia Severity Index.
Antioxidants, carotenes, fruits, and vegetables are associated with higher amyotrophic lateral sclerosis (ALS) function at baseline, according to a study published online ahead of print October 24 in JAMA Neurology. A cross-sectional baseline analysis of the ALS Multicenter Cohort Study of Oxidative Stress was conducted at 16 ALS clinics throughout the United States. Baseline data were available on 302 patients (124 women) with ALS (median age, 63.2). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALS Functional Rating Scale-Revised (ALSFRS-R) scores or percentage forced vital capacity. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores and percentage forced vital capacity.
Fluselenamyl detects amyloid clumps better than current FDA-approved compounds, according to a study published online ahead of print November 2 in Scientific Reports. To determine whether fluselenamyl can detect amyloid beta plaques in the brain, researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and from people of similar ages who had died of other causes (ie, controls). Fluselenamyl labeled diffuse and fibrillar plaques in brain sections of patients with Alzheimer's disease, but did not interact with biomarker proteins of other neurodegenerative diseases, thereby indicating specificity for detecting amyloid beta in Alzheimer's disease. Overall, fluselenamyl demonstrated potent binding affinity to autopsy-confirmed Alzheimer's disease homogenates. The binding affinity was superior to that of [18F]-AV-45, [18F]-florbetaben, and [18F]-flutemetamol.
Preserved hippocampal volumes are associated with increased risk of probable dementia with Lewy bodies, rather than Alzheimer's disease, in patients with mild cognitive impairment (MCI), according to a study published online ahead of print November 2 in Neurology. In the study, 160 people with MCI underwent MRI to measure hippocampal size. During a median follow-up of two years, 38% of people developed Alzheimer's disease, and 13% of people developed probable dementia with Lewy bodies. The people who had no hippocampal shrinkage were 5.8 times more likely to develop probable dementia with Lewy bodies than people who had hippocampal atrophy. Approximately 85% of people who developed dementia with Lewy bodies had a normal hippocampal volume. Furthermore, 61% of people who developed Alzheimer's disease had hippocampal atrophy.
Use of a media device at bedtime is significantly associated with inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, according to a systematic review published online ahead of print October 31 in JAMA Pediatrics. Researchers examined published studies of school-age children between ages six and 19 with information about portable screen-based media devices and sleep outcomes. The final analysis included 125,198 children with an average age of 14.5. Children who had access to, but did not use, media devices at night were more likely to have inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. Teachers, health care professionals, and parents should cooperate to minimize device access at bedtime, according to the researchers. Future studies should evaluate devices' influence on sleep hygiene, they added.
The FDA has approved the Amplatzer Patent Foramen Ovale (PFO) Occluder device, which reduces the risk of stroke in patients who previously had a stroke believed to be caused by a blood clot that passed through a PFO. The Amplatzer PFO Occluder is inserted through a catheter that is placed in a leg vein and advanced to the heart. In a randomized study, 499 participants ages 18 to 60 were treated with the Amplatzer PFO Occluder and blood-thinning medications and compared with 481 participants treated with blood-thinning medications alone. There was a 50% reduction in the rate of new strokes in participants using the Amplatzer PFO Occluder and blood-thinning medications, compared with participants taking medications alone. St. Jude Medical, headquartered in Plymouth, Minnesota, markets the Amplatzer PFO Occluder.
—Kimberly Williams
Economic background does not affect the clinical course or long-term seizure outcome of childhood epilepsy, according to a study in Nova Scotia, Canada, published online ahead of print November 4 in Epilepsia. Researchers examined data for 421 patients with childhood epilepsy and 10 or more years of follow-up. Overall, 33% of families had poor income, 38% had adequate income, and 30% were well-off. Terminal remission occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off populations. Intractable epilepsy, status epilepticus, number of antiepileptic drugs used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes, however.
A genetic variant near melatonin receptor 1A (MTNR1A) may be associated with job-related exhaustion in shift workers, according to a study published online ahead of print October 10 in Sleep. Researchers assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey and performed a genome-wide association study. Job-related exhaustion was associated with the rs12506228 variation, located downstream of MTNR1A, in shift workers included in the Finnish national Health 2000 survey. The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and with changes in DNA methylation in the 5' regulatory region of MTNR1A. The risk variant may lead to reduced melatonin signaling in the brain.
In healthy postmenopausal women, reproductive life events related to sex hormones are positively related to aspects of cognition in later life, according to a study published November 7 in the Journal of the American Geriatrics Society. Researchers evaluated 830 menopausal women using a cognitive battery and a structured reproductive history questionnaire. On multivariable modeling, age at menarche of 13 or older was inversely associated with global cognition. Having a last pregnancy after age 35 was positively associated with verbal memory. Use of hormonal contraceptives was positively associated with global cognition and verbal memory. The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition and executive function.
Physical fitness, BMI, IQ, and stress resilience in young adulthood may be associated with the development of amyotrophic lateral sclerosis (ALS) at an early age, according to a study published in the October issue of the European Journal of Neurology. Data on physical fitness, BMI, IQ, and stress resilience were collected from 1,838,376 Swedish men ages 17 to 20 at conscription from 1968 to 2010. During follow-up, 439 participants developed ALS. People with physical fitness above the highest tertile had a higher risk of ALS before age 45. People with BMI greater than or equal to 25 had a lower risk of ALS at all ages. Individuals with IQ above the highest tertile had a significantly increased risk of ALS at an age of 56 and older.
Short sleep is associated with greater intake of sugared caffeinated sodas, according to a study published online ahead of print November 9 in Sleep Health. Using data from the 2005 to 2012 National Health and Nutrition Examination Survey, researchers examined self-reported sleep duration and beverage intake from two 24-hour dietary recalls among 18,779 adults. Adults who slept for seven to eight hours each night were considered the reference group. In fully adjusted models, people who slept for five hours or less had 21% higher sugar-sweetened beverage consumption. When analyzed by beverage type, this difference was attributed to caffeinated sugary beverages. Longer sleepers consumed fewer servings of coffee and water. There were no associations between self-reported sleep duration and consumption of 100% juice, tea, or diet drinks.
Treadmill training plus virtual reality reduces fall rates, compared with treadmill training alone, according to a study published September 17 in the Lancet. Adults ages 60 to 90 with motor and cognitive deficits and a high risk of falls were randomly assigned to receive six weeks of treadmill training plus virtual reality or treadmill training alone. Data from 282 participants were included in the prespecified, modified intention-to-treat analysis. In the six months after training, the incident rate of falls was significantly lower in the treadmill-training-plus-virtual-reality group than it had been before training. The incident rate did not decrease significantly in the treadmill-training-alone group. Six months after training, the incident rate of falls was also significantly lower in the treadmill-training-plus-virtual-reality group than in the treadmill-training group.
Current research does not support specific recommendations for treating hypertension to preserve cognition, according to a scientific statement by the American Heart Association published online ahead of print October 10 in Hypertension. A panel of experts reviewed the literature on hypertension, the treatment of hypertension, and the relationship between hypertension and cognition, and summarized the available data. They found that hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. They found strong evidence of a negative influence of mid-life hypertension on late-life cognitive function, but the cognitive effect of late-life hypertension is unclear. Observational studies indicate that high blood pressure damages the brain's blood vessels, leading to reduced blood flow to brain cells.
Manual-based cognitive behavioral therapy for insomnia delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia, according to a study published in the September issue of the Journal of the American Geriatrics Society. Researchers studied veterans age 60 or older who met diagnostic criteria for insomnia of three months' duration or longer. Nonclinician sleep coaches delivered five sessions of manual-based cognitive behavioral therapy for insomnia, including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, with weekly telephone behavioral sleep medicine supervision. Controls received sleep education. Intervention subjects had greater improvement than controls between baseline and post-treatment, baseline and six months, and baseline and 12 months in sleep onset latency, total wake time, sleep efficiency, Pittsburgh Sleep Quality Index, and Insomnia Severity Index.
Antioxidants, carotenes, fruits, and vegetables are associated with higher amyotrophic lateral sclerosis (ALS) function at baseline, according to a study published online ahead of print October 24 in JAMA Neurology. A cross-sectional baseline analysis of the ALS Multicenter Cohort Study of Oxidative Stress was conducted at 16 ALS clinics throughout the United States. Baseline data were available on 302 patients (124 women) with ALS (median age, 63.2). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALS Functional Rating Scale-Revised (ALSFRS-R) scores or percentage forced vital capacity. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores and percentage forced vital capacity.
Fluselenamyl detects amyloid clumps better than current FDA-approved compounds, according to a study published online ahead of print November 2 in Scientific Reports. To determine whether fluselenamyl can detect amyloid beta plaques in the brain, researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and from people of similar ages who had died of other causes (ie, controls). Fluselenamyl labeled diffuse and fibrillar plaques in brain sections of patients with Alzheimer's disease, but did not interact with biomarker proteins of other neurodegenerative diseases, thereby indicating specificity for detecting amyloid beta in Alzheimer's disease. Overall, fluselenamyl demonstrated potent binding affinity to autopsy-confirmed Alzheimer's disease homogenates. The binding affinity was superior to that of [18F]-AV-45, [18F]-florbetaben, and [18F]-flutemetamol.
Preserved hippocampal volumes are associated with increased risk of probable dementia with Lewy bodies, rather than Alzheimer's disease, in patients with mild cognitive impairment (MCI), according to a study published online ahead of print November 2 in Neurology. In the study, 160 people with MCI underwent MRI to measure hippocampal size. During a median follow-up of two years, 38% of people developed Alzheimer's disease, and 13% of people developed probable dementia with Lewy bodies. The people who had no hippocampal shrinkage were 5.8 times more likely to develop probable dementia with Lewy bodies than people who had hippocampal atrophy. Approximately 85% of people who developed dementia with Lewy bodies had a normal hippocampal volume. Furthermore, 61% of people who developed Alzheimer's disease had hippocampal atrophy.
Use of a media device at bedtime is significantly associated with inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, according to a systematic review published online ahead of print October 31 in JAMA Pediatrics. Researchers examined published studies of school-age children between ages six and 19 with information about portable screen-based media devices and sleep outcomes. The final analysis included 125,198 children with an average age of 14.5. Children who had access to, but did not use, media devices at night were more likely to have inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. Teachers, health care professionals, and parents should cooperate to minimize device access at bedtime, according to the researchers. Future studies should evaluate devices' influence on sleep hygiene, they added.
The FDA has approved the Amplatzer Patent Foramen Ovale (PFO) Occluder device, which reduces the risk of stroke in patients who previously had a stroke believed to be caused by a blood clot that passed through a PFO. The Amplatzer PFO Occluder is inserted through a catheter that is placed in a leg vein and advanced to the heart. In a randomized study, 499 participants ages 18 to 60 were treated with the Amplatzer PFO Occluder and blood-thinning medications and compared with 481 participants treated with blood-thinning medications alone. There was a 50% reduction in the rate of new strokes in participants using the Amplatzer PFO Occluder and blood-thinning medications, compared with participants taking medications alone. St. Jude Medical, headquartered in Plymouth, Minnesota, markets the Amplatzer PFO Occluder.
—Kimberly Williams
Economic background does not affect the clinical course or long-term seizure outcome of childhood epilepsy, according to a study in Nova Scotia, Canada, published online ahead of print November 4 in Epilepsia. Researchers examined data for 421 patients with childhood epilepsy and 10 or more years of follow-up. Overall, 33% of families had poor income, 38% had adequate income, and 30% were well-off. Terminal remission occurred in 65% of the poor, 61% of the adequate, and 61% of the well-off populations. Intractable epilepsy, status epilepticus, number of antiepileptic drugs used, and the number of generalized tonic-clonic or focal with secondary generalization seizures through the clinical course was the same in all groups. Neither paternal nor maternal education was associated with remission. Poor children had significantly more adverse social outcomes, however.
A genetic variant near melatonin receptor 1A (MTNR1A) may be associated with job-related exhaustion in shift workers, according to a study published online ahead of print October 10 in Sleep. Researchers assessed intolerance to shift work with job-related exhaustion symptoms in shift workers using the emotional exhaustion subscale of the Maslach Burnout Inventory-General Survey and performed a genome-wide association study. Job-related exhaustion was associated with the rs12506228 variation, located downstream of MTNR1A, in shift workers included in the Finnish national Health 2000 survey. The risk allele was also associated with reduced in silico gene expression levels of MTNR1A in brain tissue and with changes in DNA methylation in the 5' regulatory region of MTNR1A. The risk variant may lead to reduced melatonin signaling in the brain.
In healthy postmenopausal women, reproductive life events related to sex hormones are positively related to aspects of cognition in later life, according to a study published November 7 in the Journal of the American Geriatrics Society. Researchers evaluated 830 menopausal women using a cognitive battery and a structured reproductive history questionnaire. On multivariable modeling, age at menarche of 13 or older was inversely associated with global cognition. Having a last pregnancy after age 35 was positively associated with verbal memory. Use of hormonal contraceptives was positively associated with global cognition and verbal memory. The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition and executive function.
Physical fitness, BMI, IQ, and stress resilience in young adulthood may be associated with the development of amyotrophic lateral sclerosis (ALS) at an early age, according to a study published in the October issue of the European Journal of Neurology. Data on physical fitness, BMI, IQ, and stress resilience were collected from 1,838,376 Swedish men ages 17 to 20 at conscription from 1968 to 2010. During follow-up, 439 participants developed ALS. People with physical fitness above the highest tertile had a higher risk of ALS before age 45. People with BMI greater than or equal to 25 had a lower risk of ALS at all ages. Individuals with IQ above the highest tertile had a significantly increased risk of ALS at an age of 56 and older.
Short sleep is associated with greater intake of sugared caffeinated sodas, according to a study published online ahead of print November 9 in Sleep Health. Using data from the 2005 to 2012 National Health and Nutrition Examination Survey, researchers examined self-reported sleep duration and beverage intake from two 24-hour dietary recalls among 18,779 adults. Adults who slept for seven to eight hours each night were considered the reference group. In fully adjusted models, people who slept for five hours or less had 21% higher sugar-sweetened beverage consumption. When analyzed by beverage type, this difference was attributed to caffeinated sugary beverages. Longer sleepers consumed fewer servings of coffee and water. There were no associations between self-reported sleep duration and consumption of 100% juice, tea, or diet drinks.
Treadmill training plus virtual reality reduces fall rates, compared with treadmill training alone, according to a study published September 17 in the Lancet. Adults ages 60 to 90 with motor and cognitive deficits and a high risk of falls were randomly assigned to receive six weeks of treadmill training plus virtual reality or treadmill training alone. Data from 282 participants were included in the prespecified, modified intention-to-treat analysis. In the six months after training, the incident rate of falls was significantly lower in the treadmill-training-plus-virtual-reality group than it had been before training. The incident rate did not decrease significantly in the treadmill-training-alone group. Six months after training, the incident rate of falls was also significantly lower in the treadmill-training-plus-virtual-reality group than in the treadmill-training group.
Current research does not support specific recommendations for treating hypertension to preserve cognition, according to a scientific statement by the American Heart Association published online ahead of print October 10 in Hypertension. A panel of experts reviewed the literature on hypertension, the treatment of hypertension, and the relationship between hypertension and cognition, and summarized the available data. They found that hypertension disrupts the structure and function of cerebral blood vessels, leads to ischemic damage of white matter regions critical for cognitive function, and may promote Alzheimer pathology. They found strong evidence of a negative influence of mid-life hypertension on late-life cognitive function, but the cognitive effect of late-life hypertension is unclear. Observational studies indicate that high blood pressure damages the brain's blood vessels, leading to reduced blood flow to brain cells.
Manual-based cognitive behavioral therapy for insomnia delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia, according to a study published in the September issue of the Journal of the American Geriatrics Society. Researchers studied veterans age 60 or older who met diagnostic criteria for insomnia of three months' duration or longer. Nonclinician sleep coaches delivered five sessions of manual-based cognitive behavioral therapy for insomnia, including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy, with weekly telephone behavioral sleep medicine supervision. Controls received sleep education. Intervention subjects had greater improvement than controls between baseline and post-treatment, baseline and six months, and baseline and 12 months in sleep onset latency, total wake time, sleep efficiency, Pittsburgh Sleep Quality Index, and Insomnia Severity Index.
Antioxidants, carotenes, fruits, and vegetables are associated with higher amyotrophic lateral sclerosis (ALS) function at baseline, according to a study published online ahead of print October 24 in JAMA Neurology. A cross-sectional baseline analysis of the ALS Multicenter Cohort Study of Oxidative Stress was conducted at 16 ALS clinics throughout the United States. Baseline data were available on 302 patients (124 women) with ALS (median age, 63.2). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALS Functional Rating Scale-Revised (ALSFRS-R) scores or percentage forced vital capacity. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores and percentage forced vital capacity.
Fluselenamyl detects amyloid clumps better than current FDA-approved compounds, according to a study published online ahead of print November 2 in Scientific Reports. To determine whether fluselenamyl can detect amyloid beta plaques in the brain, researchers used the compound to stain brain slices from people who had died of Alzheimer's disease and from people of similar ages who had died of other causes (ie, controls). Fluselenamyl labeled diffuse and fibrillar plaques in brain sections of patients with Alzheimer's disease, but did not interact with biomarker proteins of other neurodegenerative diseases, thereby indicating specificity for detecting amyloid beta in Alzheimer's disease. Overall, fluselenamyl demonstrated potent binding affinity to autopsy-confirmed Alzheimer's disease homogenates. The binding affinity was superior to that of [18F]-AV-45, [18F]-florbetaben, and [18F]-flutemetamol.
Preserved hippocampal volumes are associated with increased risk of probable dementia with Lewy bodies, rather than Alzheimer's disease, in patients with mild cognitive impairment (MCI), according to a study published online ahead of print November 2 in Neurology. In the study, 160 people with MCI underwent MRI to measure hippocampal size. During a median follow-up of two years, 38% of people developed Alzheimer's disease, and 13% of people developed probable dementia with Lewy bodies. The people who had no hippocampal shrinkage were 5.8 times more likely to develop probable dementia with Lewy bodies than people who had hippocampal atrophy. Approximately 85% of people who developed dementia with Lewy bodies had a normal hippocampal volume. Furthermore, 61% of people who developed Alzheimer's disease had hippocampal atrophy.
Use of a media device at bedtime is significantly associated with inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness, according to a systematic review published online ahead of print October 31 in JAMA Pediatrics. Researchers examined published studies of school-age children between ages six and 19 with information about portable screen-based media devices and sleep outcomes. The final analysis included 125,198 children with an average age of 14.5. Children who had access to, but did not use, media devices at night were more likely to have inadequate sleep quantity, poor sleep quality, and excessive daytime sleepiness. Teachers, health care professionals, and parents should cooperate to minimize device access at bedtime, according to the researchers. Future studies should evaluate devices' influence on sleep hygiene, they added.
The FDA has approved the Amplatzer Patent Foramen Ovale (PFO) Occluder device, which reduces the risk of stroke in patients who previously had a stroke believed to be caused by a blood clot that passed through a PFO. The Amplatzer PFO Occluder is inserted through a catheter that is placed in a leg vein and advanced to the heart. In a randomized study, 499 participants ages 18 to 60 were treated with the Amplatzer PFO Occluder and blood-thinning medications and compared with 481 participants treated with blood-thinning medications alone. There was a 50% reduction in the rate of new strokes in participants using the Amplatzer PFO Occluder and blood-thinning medications, compared with participants taking medications alone. St. Jude Medical, headquartered in Plymouth, Minnesota, markets the Amplatzer PFO Occluder.
—Kimberly Williams
New and Noteworthy Information—November 2016
Exercise may be associated with a small benefit for elderly people who have memory and thinking problems, according to a study published online ahead of print October 19 in Neurology. Researchers studied 70 adults randomized to six months of aerobic exercise training or usual care plus education on cognitive and everyday function. The aerobic exercise training group had significantly improved Alzheimer's Disease Assessment Scale-Cognitive subscale performance, compared with controls. This difference was not significant at six-month follow-up, however. There were no significant between-group differences at intervention completion and at the six-month follow-up in Executive Interview or Alzheimer's Disease Cooperative Study-Activities of Daily Living performance. Examination of secondary measures showed between-group differences at intervention completion favoring the exercise training program group in six-minute walk distance and in diastolic blood pressure.
The FDA has approved Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv has received orphan drug designation for this indication and will be the first available IV formulation of carbamazepine. The drug is intended for people with partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns, or other partial or generalized seizures. Carnexiv is not indicated for the treatment of absence seizures. People taking Carnexiv should not discontinue the drug abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs and symptoms. In addition, Carnexiv should not be used in patients with moderate or severe renal impairment. The drug is marketed by Lundbeck, which is headquartered in Deerfield, Illinois.
Chiropractic spinal manipulative therapy (CSMT) is no more effective than placebo for migraine, according to a study published online ahead of print October 2 in the European Journal of Neurology. Investigators randomized 104 migraineurs with at least one migraine attack per month to CSMT, sham chiropractic, or usual pharmacologic management for 17 months. Migraine days were significantly reduced within all three groups from baseline to post treatment. The effect continued in the CSMT and placebo groups at all follow-up time points, but the control group returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT group than in the control group toward the end of follow-up.
Video monitoring facilitates nocturnal surveillance of patients with epilepsy, but the costs are high, according to a study published online ahead of print September 30 in Epilepsia. For six months, researchers asked caregivers at an epilepsy unit to specify whether an acoustic detection system, bed motion sensor, or video monitoring alerted them to seizures and whether the alerts led to interventions. They identified 1,208 seizures in 37 people. Four people had no nocturnal seizures, and 33% of seizures were seen only on video. In 14% of seizures, including 10% of seizures seen only on video, an intervention was made. The extra costs of monitoring were 7,035 euro per seizure seen only on video and leading to an intervention. The results underscore the need for reliable seizure-detection devices, said the authors.
A higher level of physical activity may not reduce a woman's risk of multiple sclerosis (MS), according to a study published online ahead of print September 28 in Neurology. Researchers calculated total metabolic equivalent hours of physical activity per week for women participating in the Nurses' Health Study (NHS) and NHS II. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. The investigators analyzed the data with Cox proportional hazards models. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS. This trend was not present in six-year lagged analyses, however. In NHS II, total early life activity at ages 12 to 22 was not associated with MS.
Youth with primary hypertension have significantly worse performance on neurocognitive testing, compared with normotensive controls, according to a study published online ahead of print September 27 in the Journal of Pediatrics.Seventy-five children with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. The participants completed general intelligence, attention, memory, executive function, and processing speed tests. Parents rated participants' executive function and sleep disordered breathing. The study groups were well matched. Hypertension was independently associated with worse memory, attention, and executive function, compared with normotension. Results indicated a significant interaction between disordered sleep and hypertension on ratings of executive function. Hypertension heightened the association between increased disordered sleep and worse executive function.
Headache disorders may be associated with an increased risk for the development of new-onset hypothyroidism, according to a study published online ahead of print September 27 in Headache. This longitudinal retrospective cohort study used data from 8,412 participants enrolled in the Fernald Medical Monitoring Program. Participants underwent physical examinations and thyroid function testing every three years during the 20-year program. The primary outcome measure was new-onset hypothyroidism, defined as the initiation of thyroid replacement therapy or thyroid-stimulating hormone test value greater than or equal to 10 without thyroid medication. Headache disorders were present in about 26% of the participants, and new-onset hypothyroidism developed in approximately 7% of participants. The hazard ratio for the development of new-onset hypothyroidism was 1.21 for people with headache disorders.
People with epilepsy can face various psychosocial adversities and extensively report feeling discriminated against, compared with the general population, according to a study published online ahead of print September 16 in Epilepsia. The Adult Psychiatric Morbidity Survey 2007 included comprehensive interviews with 7,403 people. Overall, people with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems than the general population without epilepsy. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events.
Short episodes of atrial tachycardia or fibrillation are not associated with increased risk of clinical events, compared with absence of these episodes, according to a study published October 18 in Circulation. The Registry of Atrial Tachycardia and Atrial Fibrillation Episodes enrolled 5,379 patients with pacemakers or implantable cardioverter defibrillators. There were 478 hospitalizations among 342 patients for clinical events. Study authors adjudicated 37,531 electrograms. Patients with clinical events were more likely than those without them to have long atrial tachycardia or fibrillation. Only short episodes of atrial tachycardia or fibrillation were documented in 9% of patients with pacemakers and in 16% of patients with implantable cardioverter defibrillators. Patients with clinical events were no more likely than those without them to have short atrial tachycardia or fibrillation.
A brain signature identifies patients with fibromyalgia with 93% accuracy, according to a study published online ahead of print August 31 in Pain. Researchers examined 37 patients with fibromyalgia and 35 matched healthy controls. They analyzed participants' functional MRI responses to painful pressure and nonpainful multisensory stimulation. Investigators used machine-learning techniques to identify a brain-based fibromyalgia signature. When exposed to the same painful stimuli, patients with fibromyalgia had greater Neurologic Pain Signature responses. Furthermore, a new pain-related classifier revealed augmented responses in sensory integration and self-referential regions in fibromyalgia, and reduced responses in the lateral frontal cortex. Combined activity in the Neurologic Pain Signature, fibromyalgia pain, and multisensory patterns classified patients vs. controls with 92% sensitivity and 94% specificity in individuals who were not part of the study sample.
Children have measurable brain changes after a single season of youth football, even when they do not sustain a concussion, according to a study published online ahead of print October 24 in Radiology. Head impact data were recorded using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure. Twenty-five male participants were evaluated for seasonal fractional anisotropy changes in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. There were statistically significant linear relationships between risk-weighted cumulative exposure and decreased fractional anisotropy in the whole, core, and terminals of the left inferior fronto-occipital fasciculus. A trend toward statistical significance in the right superior longitudinal fasciculus was observed. Decrease in fractional anisotropy of the right superior longitudinal fasciculus terminal was significantly correlated with risk-weighted cumulative exposure.
Zika virus contributes to the development of Guillain-Barré syndrome, according to a study published online ahead of print October 5 in the New England Journal of Medicine. From November 2015 through March 2016, clusters of cases of Guillain-Barré syndrome were observed during an outbreak of Zika virus in Colombia. Researchers characterized the clinical features of 68 patients with Guillain-Barré syndrome during the outbreak and investigated their relationship with Zika virus infection. In all, 97% of patients had symptoms compatible with Zika virus infection before the onset of Guillain-Barré syndrome. Among the 42 patients who had samples tested for Zika virus infection, the results were positive in 40%. Most of the positive results were in urine samples, although three samples of CSF were also positive.
Among patients with amnestic mild cognitive impairment (aMCI), women have better verbal memory than men despite similar levels of brain hypometabolism, according to a study published online ahead of print October 5 in Neurology. In the Alzheimer's Disease Neuroimaging Initiative, 390 controls, 672 participants with aMCI, and 254 people with Alzheimer's disease dementia completed the Rey Auditory Verbal Learning Test and [18F]-fluorodeoxyglucose-PET. Female sex, higher temporal lobe glucose metabolic rates (TLGluMR), and the interaction of the two factors were associated with better verbal memory. The female advantage in verbal memory was greatest in people with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group.
—Kimberly Williams
Exercise may be associated with a small benefit for elderly people who have memory and thinking problems, according to a study published online ahead of print October 19 in Neurology. Researchers studied 70 adults randomized to six months of aerobic exercise training or usual care plus education on cognitive and everyday function. The aerobic exercise training group had significantly improved Alzheimer's Disease Assessment Scale-Cognitive subscale performance, compared with controls. This difference was not significant at six-month follow-up, however. There were no significant between-group differences at intervention completion and at the six-month follow-up in Executive Interview or Alzheimer's Disease Cooperative Study-Activities of Daily Living performance. Examination of secondary measures showed between-group differences at intervention completion favoring the exercise training program group in six-minute walk distance and in diastolic blood pressure.
The FDA has approved Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv has received orphan drug designation for this indication and will be the first available IV formulation of carbamazepine. The drug is intended for people with partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns, or other partial or generalized seizures. Carnexiv is not indicated for the treatment of absence seizures. People taking Carnexiv should not discontinue the drug abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs and symptoms. In addition, Carnexiv should not be used in patients with moderate or severe renal impairment. The drug is marketed by Lundbeck, which is headquartered in Deerfield, Illinois.
Chiropractic spinal manipulative therapy (CSMT) is no more effective than placebo for migraine, according to a study published online ahead of print October 2 in the European Journal of Neurology. Investigators randomized 104 migraineurs with at least one migraine attack per month to CSMT, sham chiropractic, or usual pharmacologic management for 17 months. Migraine days were significantly reduced within all three groups from baseline to post treatment. The effect continued in the CSMT and placebo groups at all follow-up time points, but the control group returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT group than in the control group toward the end of follow-up.
Video monitoring facilitates nocturnal surveillance of patients with epilepsy, but the costs are high, according to a study published online ahead of print September 30 in Epilepsia. For six months, researchers asked caregivers at an epilepsy unit to specify whether an acoustic detection system, bed motion sensor, or video monitoring alerted them to seizures and whether the alerts led to interventions. They identified 1,208 seizures in 37 people. Four people had no nocturnal seizures, and 33% of seizures were seen only on video. In 14% of seizures, including 10% of seizures seen only on video, an intervention was made. The extra costs of monitoring were 7,035 euro per seizure seen only on video and leading to an intervention. The results underscore the need for reliable seizure-detection devices, said the authors.
A higher level of physical activity may not reduce a woman's risk of multiple sclerosis (MS), according to a study published online ahead of print September 28 in Neurology. Researchers calculated total metabolic equivalent hours of physical activity per week for women participating in the Nurses' Health Study (NHS) and NHS II. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. The investigators analyzed the data with Cox proportional hazards models. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS. This trend was not present in six-year lagged analyses, however. In NHS II, total early life activity at ages 12 to 22 was not associated with MS.
Youth with primary hypertension have significantly worse performance on neurocognitive testing, compared with normotensive controls, according to a study published online ahead of print September 27 in the Journal of Pediatrics.Seventy-five children with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. The participants completed general intelligence, attention, memory, executive function, and processing speed tests. Parents rated participants' executive function and sleep disordered breathing. The study groups were well matched. Hypertension was independently associated with worse memory, attention, and executive function, compared with normotension. Results indicated a significant interaction between disordered sleep and hypertension on ratings of executive function. Hypertension heightened the association between increased disordered sleep and worse executive function.
Headache disorders may be associated with an increased risk for the development of new-onset hypothyroidism, according to a study published online ahead of print September 27 in Headache. This longitudinal retrospective cohort study used data from 8,412 participants enrolled in the Fernald Medical Monitoring Program. Participants underwent physical examinations and thyroid function testing every three years during the 20-year program. The primary outcome measure was new-onset hypothyroidism, defined as the initiation of thyroid replacement therapy or thyroid-stimulating hormone test value greater than or equal to 10 without thyroid medication. Headache disorders were present in about 26% of the participants, and new-onset hypothyroidism developed in approximately 7% of participants. The hazard ratio for the development of new-onset hypothyroidism was 1.21 for people with headache disorders.
People with epilepsy can face various psychosocial adversities and extensively report feeling discriminated against, compared with the general population, according to a study published online ahead of print September 16 in Epilepsia. The Adult Psychiatric Morbidity Survey 2007 included comprehensive interviews with 7,403 people. Overall, people with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems than the general population without epilepsy. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events.
Short episodes of atrial tachycardia or fibrillation are not associated with increased risk of clinical events, compared with absence of these episodes, according to a study published October 18 in Circulation. The Registry of Atrial Tachycardia and Atrial Fibrillation Episodes enrolled 5,379 patients with pacemakers or implantable cardioverter defibrillators. There were 478 hospitalizations among 342 patients for clinical events. Study authors adjudicated 37,531 electrograms. Patients with clinical events were more likely than those without them to have long atrial tachycardia or fibrillation. Only short episodes of atrial tachycardia or fibrillation were documented in 9% of patients with pacemakers and in 16% of patients with implantable cardioverter defibrillators. Patients with clinical events were no more likely than those without them to have short atrial tachycardia or fibrillation.
A brain signature identifies patients with fibromyalgia with 93% accuracy, according to a study published online ahead of print August 31 in Pain. Researchers examined 37 patients with fibromyalgia and 35 matched healthy controls. They analyzed participants' functional MRI responses to painful pressure and nonpainful multisensory stimulation. Investigators used machine-learning techniques to identify a brain-based fibromyalgia signature. When exposed to the same painful stimuli, patients with fibromyalgia had greater Neurologic Pain Signature responses. Furthermore, a new pain-related classifier revealed augmented responses in sensory integration and self-referential regions in fibromyalgia, and reduced responses in the lateral frontal cortex. Combined activity in the Neurologic Pain Signature, fibromyalgia pain, and multisensory patterns classified patients vs. controls with 92% sensitivity and 94% specificity in individuals who were not part of the study sample.
Children have measurable brain changes after a single season of youth football, even when they do not sustain a concussion, according to a study published online ahead of print October 24 in Radiology. Head impact data were recorded using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure. Twenty-five male participants were evaluated for seasonal fractional anisotropy changes in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. There were statistically significant linear relationships between risk-weighted cumulative exposure and decreased fractional anisotropy in the whole, core, and terminals of the left inferior fronto-occipital fasciculus. A trend toward statistical significance in the right superior longitudinal fasciculus was observed. Decrease in fractional anisotropy of the right superior longitudinal fasciculus terminal was significantly correlated with risk-weighted cumulative exposure.
Zika virus contributes to the development of Guillain-Barré syndrome, according to a study published online ahead of print October 5 in the New England Journal of Medicine. From November 2015 through March 2016, clusters of cases of Guillain-Barré syndrome were observed during an outbreak of Zika virus in Colombia. Researchers characterized the clinical features of 68 patients with Guillain-Barré syndrome during the outbreak and investigated their relationship with Zika virus infection. In all, 97% of patients had symptoms compatible with Zika virus infection before the onset of Guillain-Barré syndrome. Among the 42 patients who had samples tested for Zika virus infection, the results were positive in 40%. Most of the positive results were in urine samples, although three samples of CSF were also positive.
Among patients with amnestic mild cognitive impairment (aMCI), women have better verbal memory than men despite similar levels of brain hypometabolism, according to a study published online ahead of print October 5 in Neurology. In the Alzheimer's Disease Neuroimaging Initiative, 390 controls, 672 participants with aMCI, and 254 people with Alzheimer's disease dementia completed the Rey Auditory Verbal Learning Test and [18F]-fluorodeoxyglucose-PET. Female sex, higher temporal lobe glucose metabolic rates (TLGluMR), and the interaction of the two factors were associated with better verbal memory. The female advantage in verbal memory was greatest in people with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group.
—Kimberly Williams
Exercise may be associated with a small benefit for elderly people who have memory and thinking problems, according to a study published online ahead of print October 19 in Neurology. Researchers studied 70 adults randomized to six months of aerobic exercise training or usual care plus education on cognitive and everyday function. The aerobic exercise training group had significantly improved Alzheimer's Disease Assessment Scale-Cognitive subscale performance, compared with controls. This difference was not significant at six-month follow-up, however. There were no significant between-group differences at intervention completion and at the six-month follow-up in Executive Interview or Alzheimer's Disease Cooperative Study-Activities of Daily Living performance. Examination of secondary measures showed between-group differences at intervention completion favoring the exercise training program group in six-minute walk distance and in diastolic blood pressure.
The FDA has approved Carnexiv (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv has received orphan drug designation for this indication and will be the first available IV formulation of carbamazepine. The drug is intended for people with partial seizures with complex symptomatology, generalized tonic-clonic seizures, mixed seizure patterns, or other partial or generalized seizures. Carnexiv is not indicated for the treatment of absence seizures. People taking Carnexiv should not discontinue the drug abruptly because of the risk of seizures, status epilepticus, and other withdrawal signs and symptoms. In addition, Carnexiv should not be used in patients with moderate or severe renal impairment. The drug is marketed by Lundbeck, which is headquartered in Deerfield, Illinois.
Chiropractic spinal manipulative therapy (CSMT) is no more effective than placebo for migraine, according to a study published online ahead of print October 2 in the European Journal of Neurology. Investigators randomized 104 migraineurs with at least one migraine attack per month to CSMT, sham chiropractic, or usual pharmacologic management for 17 months. Migraine days were significantly reduced within all three groups from baseline to post treatment. The effect continued in the CSMT and placebo groups at all follow-up time points, but the control group returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT group than in the control group toward the end of follow-up.
Video monitoring facilitates nocturnal surveillance of patients with epilepsy, but the costs are high, according to a study published online ahead of print September 30 in Epilepsia. For six months, researchers asked caregivers at an epilepsy unit to specify whether an acoustic detection system, bed motion sensor, or video monitoring alerted them to seizures and whether the alerts led to interventions. They identified 1,208 seizures in 37 people. Four people had no nocturnal seizures, and 33% of seizures were seen only on video. In 14% of seizures, including 10% of seizures seen only on video, an intervention was made. The extra costs of monitoring were 7,035 euro per seizure seen only on video and leading to an intervention. The results underscore the need for reliable seizure-detection devices, said the authors.
A higher level of physical activity may not reduce a woman's risk of multiple sclerosis (MS), according to a study published online ahead of print September 28 in Neurology. Researchers calculated total metabolic equivalent hours of physical activity per week for women participating in the Nurses' Health Study (NHS) and NHS II. There were 341 confirmed MS cases with first symptoms after baseline. Participants also reported early-life activity. The investigators analyzed the data with Cox proportional hazards models. Compared with women in the lowest baseline physical activity quartile, women in the highest quartile had a 27% reduced rate of MS. This trend was not present in six-year lagged analyses, however. In NHS II, total early life activity at ages 12 to 22 was not associated with MS.
Youth with primary hypertension have significantly worse performance on neurocognitive testing, compared with normotensive controls, according to a study published online ahead of print September 27 in the Journal of Pediatrics.Seventy-five children with newly diagnosed, untreated hypertension and 75 frequency-matched normotensive controls had baseline neurocognitive testing as part of a prospective multicenter study of cognition in primary hypertension. The participants completed general intelligence, attention, memory, executive function, and processing speed tests. Parents rated participants' executive function and sleep disordered breathing. The study groups were well matched. Hypertension was independently associated with worse memory, attention, and executive function, compared with normotension. Results indicated a significant interaction between disordered sleep and hypertension on ratings of executive function. Hypertension heightened the association between increased disordered sleep and worse executive function.
Headache disorders may be associated with an increased risk for the development of new-onset hypothyroidism, according to a study published online ahead of print September 27 in Headache. This longitudinal retrospective cohort study used data from 8,412 participants enrolled in the Fernald Medical Monitoring Program. Participants underwent physical examinations and thyroid function testing every three years during the 20-year program. The primary outcome measure was new-onset hypothyroidism, defined as the initiation of thyroid replacement therapy or thyroid-stimulating hormone test value greater than or equal to 10 without thyroid medication. Headache disorders were present in about 26% of the participants, and new-onset hypothyroidism developed in approximately 7% of participants. The hazard ratio for the development of new-onset hypothyroidism was 1.21 for people with headache disorders.
People with epilepsy can face various psychosocial adversities and extensively report feeling discriminated against, compared with the general population, according to a study published online ahead of print September 16 in Epilepsia. The Adult Psychiatric Morbidity Survey 2007 included comprehensive interviews with 7,403 people. Overall, people with epilepsy were sevenfold more likely to have reported experiencing discrimination due to health problems than the general population without epilepsy. People with epilepsy also had greater odds of experiencing domestic violence and sexual abuse than the general population, although these associations were also found in people with other chronic conditions. There was less evidence of an association between epilepsy and a history of physical abuse or having a greater burden of other stressful life events.
Short episodes of atrial tachycardia or fibrillation are not associated with increased risk of clinical events, compared with absence of these episodes, according to a study published October 18 in Circulation. The Registry of Atrial Tachycardia and Atrial Fibrillation Episodes enrolled 5,379 patients with pacemakers or implantable cardioverter defibrillators. There were 478 hospitalizations among 342 patients for clinical events. Study authors adjudicated 37,531 electrograms. Patients with clinical events were more likely than those without them to have long atrial tachycardia or fibrillation. Only short episodes of atrial tachycardia or fibrillation were documented in 9% of patients with pacemakers and in 16% of patients with implantable cardioverter defibrillators. Patients with clinical events were no more likely than those without them to have short atrial tachycardia or fibrillation.
A brain signature identifies patients with fibromyalgia with 93% accuracy, according to a study published online ahead of print August 31 in Pain. Researchers examined 37 patients with fibromyalgia and 35 matched healthy controls. They analyzed participants' functional MRI responses to painful pressure and nonpainful multisensory stimulation. Investigators used machine-learning techniques to identify a brain-based fibromyalgia signature. When exposed to the same painful stimuli, patients with fibromyalgia had greater Neurologic Pain Signature responses. Furthermore, a new pain-related classifier revealed augmented responses in sensory integration and self-referential regions in fibromyalgia, and reduced responses in the lateral frontal cortex. Combined activity in the Neurologic Pain Signature, fibromyalgia pain, and multisensory patterns classified patients vs. controls with 92% sensitivity and 94% specificity in individuals who were not part of the study sample.
Children have measurable brain changes after a single season of youth football, even when they do not sustain a concussion, according to a study published online ahead of print October 24 in Radiology. Head impact data were recorded using the Head Impact Telemetry system and quantified as the combined-probability risk-weighted cumulative exposure. Twenty-five male participants were evaluated for seasonal fractional anisotropy changes in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus. There were statistically significant linear relationships between risk-weighted cumulative exposure and decreased fractional anisotropy in the whole, core, and terminals of the left inferior fronto-occipital fasciculus. A trend toward statistical significance in the right superior longitudinal fasciculus was observed. Decrease in fractional anisotropy of the right superior longitudinal fasciculus terminal was significantly correlated with risk-weighted cumulative exposure.
Zika virus contributes to the development of Guillain-Barré syndrome, according to a study published online ahead of print October 5 in the New England Journal of Medicine. From November 2015 through March 2016, clusters of cases of Guillain-Barré syndrome were observed during an outbreak of Zika virus in Colombia. Researchers characterized the clinical features of 68 patients with Guillain-Barré syndrome during the outbreak and investigated their relationship with Zika virus infection. In all, 97% of patients had symptoms compatible with Zika virus infection before the onset of Guillain-Barré syndrome. Among the 42 patients who had samples tested for Zika virus infection, the results were positive in 40%. Most of the positive results were in urine samples, although three samples of CSF were also positive.
Among patients with amnestic mild cognitive impairment (aMCI), women have better verbal memory than men despite similar levels of brain hypometabolism, according to a study published online ahead of print October 5 in Neurology. In the Alzheimer's Disease Neuroimaging Initiative, 390 controls, 672 participants with aMCI, and 254 people with Alzheimer's disease dementia completed the Rey Auditory Verbal Learning Test and [18F]-fluorodeoxyglucose-PET. Female sex, higher temporal lobe glucose metabolic rates (TLGluMR), and the interaction of the two factors were associated with better verbal memory. The female advantage in verbal memory was greatest in people with moderate to high TLGluMR and minimal or absent among individuals with lower TLGluMR. Diagnosis-stratified analyses revealed that this interaction was driven by the aMCI group.
—Kimberly Williams
New and Noteworthy Information—October 2016
Resective surgery for epilepsy is cost-effective in the medium term, according to a study published online ahead of print September 5 in Epilepsia. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed for more than five years in 15 French centers. During the second year of follow-up, the proportion of patients who had been completely seizure-free for the previous 12 months was 69.0% among participants who underwent surgery and 12.3% in the medical group. The respective rates of seizure freedom were 76.8% and 21% during the fifth year. Direct costs became significantly lower in the surgical group during the third year after surgery as a result of decreased antiepileptic drug use. Surgery became cost-effective between nine and 10 years after surgery.
The NIH Toolbox Cognitive Battery can assess important dimensions of cognition in persons with intellectual disabilities, and several tests may be useful for tracking response to interventions, according to a study published September 6 in the Journal of Neurodevelopmental Disorders. In separate pilot studies of patients with fragile X syndrome, Down syndrome, and idiopathic intellectual disabilities, researchers used the web-based NIH Toolbox Cognitive Battery to measure processing speed, executive function, episodic memory, word and letter reading, receptive vocabulary, and working memory. The test's feasibility was good to excellent for people above mental age 4 for all tests except list sorting. Test-retest stability was good to excellent. More extensive psychometric studies are needed to determine the battery's true utility as a set of outcome measures, said the researchers.
Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric sports-related concussion, according to a study published online ahead of print September 13 in the Journal of Neurosurgery: Pediatrics. Researchers conducted a retrospective chart review of 106 pediatric patients with sports-related concussion who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Treadmill testing confirmed physiologic recovery in 96.9% of 65 patients tested, allowing successful return to play in 93.8% of patients. Of the 41 patients with physiologic post-concussion disorder who had complete follow-up and were treated with tailored submaximal exercise, 90.2% were classified as clinically improved and 80.5% successfully returned to sporting activities.
Exposure to MRI during the first trimester of pregnancy, compared with nonexposure, is not associated with increased risk of harm to the fetus or in early childhood, according to a study published September 6 in JAMA. Gadolinium MRI, however, was associated with an increased risk of rheumatologic, inflammatory, or infiltrative skin conditions, and stillbirth or neonatal death. The study included 1,424,105 deliveries. Researchers compared first-trimester MRI exposure to no MRI exposure. The adjusted relative risk of stillbirth, congenital anomalies, neoplasm, or vision or hearing loss for first-trimester MRI was not significantly higher, compared with no MRI exposure. Comparing gadolinium MRI with no MRI, the adjusted hazard ratio of any rheumatologic, inflammatory, or infiltrative skin condition for first-trimester MRI was 1.36, for an adjusted risk difference of 45.3 per 1,000 person-years.
In women in the United Kingdom, higher BMI is associated with increased risk of ischemic stroke, but decreased risk of hemorrhagic stroke, according to a study published online ahead of print September 7 in Neurology. Researchers recruited 1.3 million previously stroke-free women from the UK between 1996 and 2001 and followed them by record linkage for hospital admissions and deaths. Increased BMI was associated with an increased risk of ischemic stroke, but a decreased risk of hemorrhagic stroke. The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different, but were not significantly different for intracerebral hemorrhage and subarachnoid hemorrhage. Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic stroke than hemorrhagic stroke, with most evidence before this study coming from Asian populations.
Data confirm the relevance of complement biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease, according to a study published September 6 in the Journal of Alzheimer's Disease. Results also indicate the value of multiparameter models for disease prediction and stratification. Researchers studied 292 people to measure five complement proteins and four activation products in plasma from donors with MCI, those with Alzheimer's disease, and healthy controls. Only clusterin differed significantly between control and Alzheimer's disease plasma. Overall, a model combining clusterin with relevant covariables was highly predictive of disease. Clusterin, factor I, and terminal complement complex were significantly different between individuals with MCI who had converted to dementia one year later compared with nonconverters. A model combining these three analytes with informative covariables was highly predictive of conversion.
Prenatal exposure to levetiracetam or topiramate may not impair a child's thinking skills, according to a study published online ahead of print August 31 in Neurology. For this cross-sectional observational study, researchers followed women enrolled in the UK Epilepsy and Pregnancy Register. The women received monotherapy levetiracetam, topiramate, or valproate, or took no therapy. Physicians conducted assessor-blinded neuropsychologic assessments of the women's children between ages 5 and 9. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in children's cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing the dose of valproate was associated with poorer full-scale IQ, verbal abilities, nonverbal abilities, and expressive language ability. The evidence base for newer antiepileptic drugs is limited, said the authors.
At six months, decompressive craniectomy in patients with traumatic brain injury (TBI) and refractory intracranial hypertension results in lower mortality and higher rates of vegetative state and severe disability, compared with medical care, according to a study published online ahead of print September 7 in the New England Journal of Medicine. Researchers randomly assigned 408 patients, ages 10 to 65, with TBI and refractory elevated intracranial pressure to undergo decompressive craniectomy or receive ongoing medical care. At six months, approximately 27% of patients who received a craniectomy had died, compared with 49% of patients who received medical management. Patients who survived after a craniectomy were more likely to be dependent on others for care. At 12 months, mortality was 30% among surgical patients and 52% among medical patients.
Contralaterally controlled functional electrical stimulation (CCFES) improves hand dexterity after stroke more than cyclic neuromuscular electrical stimulation (cNMES) does, according to a study published online ahead of print September 8 in Stroke. Researchers enrolled 80 patients with stroke and chronic moderate to severe upper extremity hemiparesis in the study. Participants were randomized to receive 10 sessions per week of CCFES- or cNMES-assisted hand-opening exercise at home, along with 20 sessions of functional task practice in the laboratory for 12 weeks. At six months post treatment, the CCFES group had an improvement of 4.6 on the Box and Block Test, compared with an improvement of 1.8 for the cNMES group. Fugl-Meyer performance and Arm Motor Abilities Test performance did not differ between groups, however.
Antipsychotic use is associated with higher risk of pneumonia, regardless of the choice of drug, according to a study published online ahead of print June 11 in Chest. Researchers investigated whether incident antipsychotic use or specific antipsychotics are related to higher risk of hospitalization or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons who received a clinically verified diagnosis of Alzheimer's disease in Finland from 2005 to 2011. A matched comparison cohort without Alzheimer's disease was used to compare the magnitude of risk. Antipsychotic use was associated with higher risk of pneumonia in the Alzheimer's disease cohort and with somewhat higher risk in the comparison cohort. No major differences were observed between the most commonly used antipsychotics.
The FDA has allowed the marketing of two Trevo clot-retrieval devices as an initial therapy to reduce paralysis, speech difficulties, and other disabilities following ischemic stroke. The agency evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device and t-PA and medical management with 249 patients who received only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent at three months after stroke, compared with 19% of patients who were not treated with the Trevo device. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug, which needs to be given within three hours of symptom onset, said the FDA. Concentric Medical, headquartered in Mountain View, California, markets Trevo.
Class I evidence suggests that for boys with Duchenne muscular dystrophy, daily use of deflazacort or prednisone is effective in preserving muscle strength over a 12-week period, according to a study published online ahead of print August 26 in Neurology. This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated the muscle strength of 196 boys ages 5 to 15 with Duchenne muscular dystrophy during a 52-week period. Participants received deflazacort, prednisone, or placebo for 12 weeks. At week 13, patients continued active treatment or switched from placebo to active treatment. All treatment groups demonstrated significant improvement in muscle strength, compared with placebo, at 12 weeks. Participants taking prednisone had significantly more weight gain than other participants at 12 weeks and at 52 weeks.
The FDA has granted tentative approval to Supernus Pharmaceuticals's Supplemental New Drug Application (sNDA) requesting a label expansion for Trokendi XR (topiramate) to include prophylaxis of migraine headache in adults. The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval, but is subject to the pediatric exclusivity, which expires on March 28, 2017. Final approval may not be made effective until this exclusivity period has expired. The FDA also has granted final approval to expand the label for Trokendi XR for monotherapy treatment of partial onset seizures to include adults and pediatric patients age six and older, rather than age 10 and older. Supernus Pharmaceuticals is headquartered in Rockville, Maryland.
—Kimberly Williams
Resective surgery for epilepsy is cost-effective in the medium term, according to a study published online ahead of print September 5 in Epilepsia. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed for more than five years in 15 French centers. During the second year of follow-up, the proportion of patients who had been completely seizure-free for the previous 12 months was 69.0% among participants who underwent surgery and 12.3% in the medical group. The respective rates of seizure freedom were 76.8% and 21% during the fifth year. Direct costs became significantly lower in the surgical group during the third year after surgery as a result of decreased antiepileptic drug use. Surgery became cost-effective between nine and 10 years after surgery.
The NIH Toolbox Cognitive Battery can assess important dimensions of cognition in persons with intellectual disabilities, and several tests may be useful for tracking response to interventions, according to a study published September 6 in the Journal of Neurodevelopmental Disorders. In separate pilot studies of patients with fragile X syndrome, Down syndrome, and idiopathic intellectual disabilities, researchers used the web-based NIH Toolbox Cognitive Battery to measure processing speed, executive function, episodic memory, word and letter reading, receptive vocabulary, and working memory. The test's feasibility was good to excellent for people above mental age 4 for all tests except list sorting. Test-retest stability was good to excellent. More extensive psychometric studies are needed to determine the battery's true utility as a set of outcome measures, said the researchers.
Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric sports-related concussion, according to a study published online ahead of print September 13 in the Journal of Neurosurgery: Pediatrics. Researchers conducted a retrospective chart review of 106 pediatric patients with sports-related concussion who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Treadmill testing confirmed physiologic recovery in 96.9% of 65 patients tested, allowing successful return to play in 93.8% of patients. Of the 41 patients with physiologic post-concussion disorder who had complete follow-up and were treated with tailored submaximal exercise, 90.2% were classified as clinically improved and 80.5% successfully returned to sporting activities.
Exposure to MRI during the first trimester of pregnancy, compared with nonexposure, is not associated with increased risk of harm to the fetus or in early childhood, according to a study published September 6 in JAMA. Gadolinium MRI, however, was associated with an increased risk of rheumatologic, inflammatory, or infiltrative skin conditions, and stillbirth or neonatal death. The study included 1,424,105 deliveries. Researchers compared first-trimester MRI exposure to no MRI exposure. The adjusted relative risk of stillbirth, congenital anomalies, neoplasm, or vision or hearing loss for first-trimester MRI was not significantly higher, compared with no MRI exposure. Comparing gadolinium MRI with no MRI, the adjusted hazard ratio of any rheumatologic, inflammatory, or infiltrative skin condition for first-trimester MRI was 1.36, for an adjusted risk difference of 45.3 per 1,000 person-years.
In women in the United Kingdom, higher BMI is associated with increased risk of ischemic stroke, but decreased risk of hemorrhagic stroke, according to a study published online ahead of print September 7 in Neurology. Researchers recruited 1.3 million previously stroke-free women from the UK between 1996 and 2001 and followed them by record linkage for hospital admissions and deaths. Increased BMI was associated with an increased risk of ischemic stroke, but a decreased risk of hemorrhagic stroke. The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different, but were not significantly different for intracerebral hemorrhage and subarachnoid hemorrhage. Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic stroke than hemorrhagic stroke, with most evidence before this study coming from Asian populations.
Data confirm the relevance of complement biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease, according to a study published September 6 in the Journal of Alzheimer's Disease. Results also indicate the value of multiparameter models for disease prediction and stratification. Researchers studied 292 people to measure five complement proteins and four activation products in plasma from donors with MCI, those with Alzheimer's disease, and healthy controls. Only clusterin differed significantly between control and Alzheimer's disease plasma. Overall, a model combining clusterin with relevant covariables was highly predictive of disease. Clusterin, factor I, and terminal complement complex were significantly different between individuals with MCI who had converted to dementia one year later compared with nonconverters. A model combining these three analytes with informative covariables was highly predictive of conversion.
Prenatal exposure to levetiracetam or topiramate may not impair a child's thinking skills, according to a study published online ahead of print August 31 in Neurology. For this cross-sectional observational study, researchers followed women enrolled in the UK Epilepsy and Pregnancy Register. The women received monotherapy levetiracetam, topiramate, or valproate, or took no therapy. Physicians conducted assessor-blinded neuropsychologic assessments of the women's children between ages 5 and 9. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in children's cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing the dose of valproate was associated with poorer full-scale IQ, verbal abilities, nonverbal abilities, and expressive language ability. The evidence base for newer antiepileptic drugs is limited, said the authors.
At six months, decompressive craniectomy in patients with traumatic brain injury (TBI) and refractory intracranial hypertension results in lower mortality and higher rates of vegetative state and severe disability, compared with medical care, according to a study published online ahead of print September 7 in the New England Journal of Medicine. Researchers randomly assigned 408 patients, ages 10 to 65, with TBI and refractory elevated intracranial pressure to undergo decompressive craniectomy or receive ongoing medical care. At six months, approximately 27% of patients who received a craniectomy had died, compared with 49% of patients who received medical management. Patients who survived after a craniectomy were more likely to be dependent on others for care. At 12 months, mortality was 30% among surgical patients and 52% among medical patients.
Contralaterally controlled functional electrical stimulation (CCFES) improves hand dexterity after stroke more than cyclic neuromuscular electrical stimulation (cNMES) does, according to a study published online ahead of print September 8 in Stroke. Researchers enrolled 80 patients with stroke and chronic moderate to severe upper extremity hemiparesis in the study. Participants were randomized to receive 10 sessions per week of CCFES- or cNMES-assisted hand-opening exercise at home, along with 20 sessions of functional task practice in the laboratory for 12 weeks. At six months post treatment, the CCFES group had an improvement of 4.6 on the Box and Block Test, compared with an improvement of 1.8 for the cNMES group. Fugl-Meyer performance and Arm Motor Abilities Test performance did not differ between groups, however.
Antipsychotic use is associated with higher risk of pneumonia, regardless of the choice of drug, according to a study published online ahead of print June 11 in Chest. Researchers investigated whether incident antipsychotic use or specific antipsychotics are related to higher risk of hospitalization or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons who received a clinically verified diagnosis of Alzheimer's disease in Finland from 2005 to 2011. A matched comparison cohort without Alzheimer's disease was used to compare the magnitude of risk. Antipsychotic use was associated with higher risk of pneumonia in the Alzheimer's disease cohort and with somewhat higher risk in the comparison cohort. No major differences were observed between the most commonly used antipsychotics.
The FDA has allowed the marketing of two Trevo clot-retrieval devices as an initial therapy to reduce paralysis, speech difficulties, and other disabilities following ischemic stroke. The agency evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device and t-PA and medical management with 249 patients who received only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent at three months after stroke, compared with 19% of patients who were not treated with the Trevo device. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug, which needs to be given within three hours of symptom onset, said the FDA. Concentric Medical, headquartered in Mountain View, California, markets Trevo.
Class I evidence suggests that for boys with Duchenne muscular dystrophy, daily use of deflazacort or prednisone is effective in preserving muscle strength over a 12-week period, according to a study published online ahead of print August 26 in Neurology. This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated the muscle strength of 196 boys ages 5 to 15 with Duchenne muscular dystrophy during a 52-week period. Participants received deflazacort, prednisone, or placebo for 12 weeks. At week 13, patients continued active treatment or switched from placebo to active treatment. All treatment groups demonstrated significant improvement in muscle strength, compared with placebo, at 12 weeks. Participants taking prednisone had significantly more weight gain than other participants at 12 weeks and at 52 weeks.
The FDA has granted tentative approval to Supernus Pharmaceuticals's Supplemental New Drug Application (sNDA) requesting a label expansion for Trokendi XR (topiramate) to include prophylaxis of migraine headache in adults. The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval, but is subject to the pediatric exclusivity, which expires on March 28, 2017. Final approval may not be made effective until this exclusivity period has expired. The FDA also has granted final approval to expand the label for Trokendi XR for monotherapy treatment of partial onset seizures to include adults and pediatric patients age six and older, rather than age 10 and older. Supernus Pharmaceuticals is headquartered in Rockville, Maryland.
—Kimberly Williams
Resective surgery for epilepsy is cost-effective in the medium term, according to a study published online ahead of print September 5 in Epilepsia. A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed for more than five years in 15 French centers. During the second year of follow-up, the proportion of patients who had been completely seizure-free for the previous 12 months was 69.0% among participants who underwent surgery and 12.3% in the medical group. The respective rates of seizure freedom were 76.8% and 21% during the fifth year. Direct costs became significantly lower in the surgical group during the third year after surgery as a result of decreased antiepileptic drug use. Surgery became cost-effective between nine and 10 years after surgery.
The NIH Toolbox Cognitive Battery can assess important dimensions of cognition in persons with intellectual disabilities, and several tests may be useful for tracking response to interventions, according to a study published September 6 in the Journal of Neurodevelopmental Disorders. In separate pilot studies of patients with fragile X syndrome, Down syndrome, and idiopathic intellectual disabilities, researchers used the web-based NIH Toolbox Cognitive Battery to measure processing speed, executive function, episodic memory, word and letter reading, receptive vocabulary, and working memory. The test's feasibility was good to excellent for people above mental age 4 for all tests except list sorting. Test-retest stability was good to excellent. More extensive psychometric studies are needed to determine the battery's true utility as a set of outcome measures, said the researchers.
Graded aerobic treadmill testing is a safe, tolerable, and clinically valuable tool that can assist in the evaluation and management of pediatric sports-related concussion, according to a study published online ahead of print September 13 in the Journal of Neurosurgery: Pediatrics. Researchers conducted a retrospective chart review of 106 pediatric patients with sports-related concussion who were referred to a multidisciplinary pediatric concussion program and underwent graded aerobic treadmill testing between October 9, 2014, and February 11, 2016. Treadmill testing confirmed physiologic recovery in 96.9% of 65 patients tested, allowing successful return to play in 93.8% of patients. Of the 41 patients with physiologic post-concussion disorder who had complete follow-up and were treated with tailored submaximal exercise, 90.2% were classified as clinically improved and 80.5% successfully returned to sporting activities.
Exposure to MRI during the first trimester of pregnancy, compared with nonexposure, is not associated with increased risk of harm to the fetus or in early childhood, according to a study published September 6 in JAMA. Gadolinium MRI, however, was associated with an increased risk of rheumatologic, inflammatory, or infiltrative skin conditions, and stillbirth or neonatal death. The study included 1,424,105 deliveries. Researchers compared first-trimester MRI exposure to no MRI exposure. The adjusted relative risk of stillbirth, congenital anomalies, neoplasm, or vision or hearing loss for first-trimester MRI was not significantly higher, compared with no MRI exposure. Comparing gadolinium MRI with no MRI, the adjusted hazard ratio of any rheumatologic, inflammatory, or infiltrative skin condition for first-trimester MRI was 1.36, for an adjusted risk difference of 45.3 per 1,000 person-years.
In women in the United Kingdom, higher BMI is associated with increased risk of ischemic stroke, but decreased risk of hemorrhagic stroke, according to a study published online ahead of print September 7 in Neurology. Researchers recruited 1.3 million previously stroke-free women from the UK between 1996 and 2001 and followed them by record linkage for hospital admissions and deaths. Increased BMI was associated with an increased risk of ischemic stroke, but a decreased risk of hemorrhagic stroke. The BMI-associated trends for ischemic and hemorrhagic stroke were significantly different, but were not significantly different for intracerebral hemorrhage and subarachnoid hemorrhage. Published data from prospective studies showed consistently greater BMI-associated relative risks for ischemic stroke than hemorrhagic stroke, with most evidence before this study coming from Asian populations.
Data confirm the relevance of complement biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease, according to a study published September 6 in the Journal of Alzheimer's Disease. Results also indicate the value of multiparameter models for disease prediction and stratification. Researchers studied 292 people to measure five complement proteins and four activation products in plasma from donors with MCI, those with Alzheimer's disease, and healthy controls. Only clusterin differed significantly between control and Alzheimer's disease plasma. Overall, a model combining clusterin with relevant covariables was highly predictive of disease. Clusterin, factor I, and terminal complement complex were significantly different between individuals with MCI who had converted to dementia one year later compared with nonconverters. A model combining these three analytes with informative covariables was highly predictive of conversion.
Prenatal exposure to levetiracetam or topiramate may not impair a child's thinking skills, according to a study published online ahead of print August 31 in Neurology. For this cross-sectional observational study, researchers followed women enrolled in the UK Epilepsy and Pregnancy Register. The women received monotherapy levetiracetam, topiramate, or valproate, or took no therapy. Physicians conducted assessor-blinded neuropsychologic assessments of the women's children between ages 5 and 9. In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in children's cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing the dose of valproate was associated with poorer full-scale IQ, verbal abilities, nonverbal abilities, and expressive language ability. The evidence base for newer antiepileptic drugs is limited, said the authors.
At six months, decompressive craniectomy in patients with traumatic brain injury (TBI) and refractory intracranial hypertension results in lower mortality and higher rates of vegetative state and severe disability, compared with medical care, according to a study published online ahead of print September 7 in the New England Journal of Medicine. Researchers randomly assigned 408 patients, ages 10 to 65, with TBI and refractory elevated intracranial pressure to undergo decompressive craniectomy or receive ongoing medical care. At six months, approximately 27% of patients who received a craniectomy had died, compared with 49% of patients who received medical management. Patients who survived after a craniectomy were more likely to be dependent on others for care. At 12 months, mortality was 30% among surgical patients and 52% among medical patients.
Contralaterally controlled functional electrical stimulation (CCFES) improves hand dexterity after stroke more than cyclic neuromuscular electrical stimulation (cNMES) does, according to a study published online ahead of print September 8 in Stroke. Researchers enrolled 80 patients with stroke and chronic moderate to severe upper extremity hemiparesis in the study. Participants were randomized to receive 10 sessions per week of CCFES- or cNMES-assisted hand-opening exercise at home, along with 20 sessions of functional task practice in the laboratory for 12 weeks. At six months post treatment, the CCFES group had an improvement of 4.6 on the Box and Block Test, compared with an improvement of 1.8 for the cNMES group. Fugl-Meyer performance and Arm Motor Abilities Test performance did not differ between groups, however.
Antipsychotic use is associated with higher risk of pneumonia, regardless of the choice of drug, according to a study published online ahead of print June 11 in Chest. Researchers investigated whether incident antipsychotic use or specific antipsychotics are related to higher risk of hospitalization or death due to pneumonia in the MEDALZ cohort. The cohort includes all persons who received a clinically verified diagnosis of Alzheimer's disease in Finland from 2005 to 2011. A matched comparison cohort without Alzheimer's disease was used to compare the magnitude of risk. Antipsychotic use was associated with higher risk of pneumonia in the Alzheimer's disease cohort and with somewhat higher risk in the comparison cohort. No major differences were observed between the most commonly used antipsychotics.
The FDA has allowed the marketing of two Trevo clot-retrieval devices as an initial therapy to reduce paralysis, speech difficulties, and other disabilities following ischemic stroke. The agency evaluated data from a clinical trial comparing 96 randomly selected patients treated with the Trevo device and t-PA and medical management with 249 patients who received only t-PA and medical management. Twenty-nine percent of patients treated with the Trevo device were functionally independent at three months after stroke, compared with 19% of patients who were not treated with the Trevo device. These devices should be used within six hours of symptom onset and only following treatment with a clot-dissolving drug, which needs to be given within three hours of symptom onset, said the FDA. Concentric Medical, headquartered in Mountain View, California, markets Trevo.
Class I evidence suggests that for boys with Duchenne muscular dystrophy, daily use of deflazacort or prednisone is effective in preserving muscle strength over a 12-week period, according to a study published online ahead of print August 26 in Neurology. This phase III, double-blind, randomized, placebo-controlled, multicenter study evaluated the muscle strength of 196 boys ages 5 to 15 with Duchenne muscular dystrophy during a 52-week period. Participants received deflazacort, prednisone, or placebo for 12 weeks. At week 13, patients continued active treatment or switched from placebo to active treatment. All treatment groups demonstrated significant improvement in muscle strength, compared with placebo, at 12 weeks. Participants taking prednisone had significantly more weight gain than other participants at 12 weeks and at 52 weeks.
The FDA has granted tentative approval to Supernus Pharmaceuticals's Supplemental New Drug Application (sNDA) requesting a label expansion for Trokendi XR (topiramate) to include prophylaxis of migraine headache in adults. The approval of the sNDA is tentative because the FDA has determined that the drug meets all of the required quality, safety, and efficacy standards for approval, but is subject to the pediatric exclusivity, which expires on March 28, 2017. Final approval may not be made effective until this exclusivity period has expired. The FDA also has granted final approval to expand the label for Trokendi XR for monotherapy treatment of partial onset seizures to include adults and pediatric patients age six and older, rather than age 10 and older. Supernus Pharmaceuticals is headquartered in Rockville, Maryland.
—Kimberly Williams
New and Noteworthy Information—September 2016
Hospitalization of patients with stroke in primary stroke centers, compared with noncertified hospitals, is associated with decreased seven-day and 30-day case fatality, according to a study published online ahead of print July 25 in JAMA Internal Medicine. Among 865,184 elderly patients with stroke (mean age, 78.9; 55.5% female), 53.9% were treated in primary stroke centers. Admission to primary stroke centers was associated with 1.8% lower seven-day and 1.8% lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in primary stroke centers to save one life at 30 days. Overall, receiving treatment in primary stroke centers was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of care in primary stroke centers.
Obesity may increase the risk of neurodegeneration, according to a study published online ahead of print July 27 in Neurobiology of Aging. Participants were a population-based cohort of cognitively healthy adults recruited over a five-year period. In all, 527 subjects with an age range of 20 to 87 were included. Researchers performed a cross-sectional analysis of MRI-based brain structure and found a statistically significant interaction between age and BMI. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white matter volume, cortical thickness, and surface area. Cerebral white matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase in brain age of 10 years.
Thymectomy improves clinical outcomes over a three-year period in patients with nonthymomatous myasthenia gravis, according to a study published August 11 in the New England Journal of Medicine. Researchers randomized 126 patients to thymectomy plus alternate-day prednisone or alternate-day prednisone alone. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those who received prednisone alone. Patients in the thymectomy group also had a lower average requirement for alternate-day prednisone. Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine or were hospitalized for exacerbations. The number of patients with treatment-associated complications did not differ significantly between groups. However, patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications.
Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease, according to a study published online ahead of print August 17 in Neurology. This longitudinal population-based study included 700 women without dementia between ages 70 and 92. At baseline and at five-year follow-up, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan also was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Women treated with calcium supplements had a higher risk of developing dementia and the subtype of stroke-related dementia. Calcium supplementation was associated with the development of dementia in groups with a history of stroke or presence of white matter lesions, but not in groups without these conditions.
Exposure to bright light during the day may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light, according to a study published online ahead of print June 16 in Sleep Medicine. Following a constant bright light exposure over 6.5 hours, 14 participants read a novel either on a tablet or as a physical book for two hours. Evening concentrations of saliva melatonin were measured repeatedly. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated. Participants who had read the novel on a tablet in the first experimental session continued reading the same novel as a physical book, and vice versa. There were no differences in sleep parameters and presleep saliva melatonin levels between the tablet reading and physical book reading conditions.
Treatment immediately after clinically isolated syndrome (CIS) is more beneficial than delayed treatment, according to a study published online ahead of print August 10 in Neurology. Researchers randomized 278 people with CIS to interferon beta-1b or placebo. After two years or a diagnosis of multiple sclerosis (MS), patients receiving placebo could receive treatment. After 11 years, risk of clinically definite MS remained lower in the early-treatment arm, compared with the delayed-treatment arm, with longer time to first relapse and lower overall annualized relapse rate. Twenty-five patients converted to secondary progressive MS. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores. Health resource utilization was low in both groups.
Patients with anemia have increased mortality after stroke, according to a study published online ahead of print August 17 in the Journal of the American Heart Association. Researchers analyzed data from a cohort of 8,013 patients with stroke who were consecutively admitted over 11 years. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to one year following stroke. Elevated hemoglobin also was associated with increased mortality. In addition, investigators conducted a systematic review using various databases. When combined with the cohort from the current study, the pooled population had 29,943 patients with stroke. Anemia on admission was associated with an increased risk of mortality in ischemic stroke and hemorrhagic stroke.
Bedside EEG methods may indicate the level of awareness of patients in a vegetative state, according to a study published online ahead of print August 4 in Annals of Neurology. Fourteen patients with severe brain injuries were evaluated with an EEG vibrotactile attention task designed to identify a hierarchy of residual somatosensory and cognitive abilities. Each patient also was assessed with a clinical behavioral scale and two fMRI assessments of covert command following. Six patients produced only sensory responses, with no evidence of cognitive event-related potentials. Furthermore, eight patients demonstrated reliable bottom-up attention-orienting responses. No patient showed evidence of top-down attention. Only patients who followed commands, whether overtly with behavior or covertly with functional neuroimaging, also demonstrated event-related potential evidence of attentional orienting.
The PET tracer [18F]-AV-1451 may help identify the stages of the preclinical and clinical phases of Alzheimer's disease, according to a study published online ahead of print July 25 in JAMA Neurology. In all, 59 participants (64% male; mean age, 74) underwent PET imaging. The [18F]-AV-1451 standardized uptake value ratio (SUVR) in the hippocampus and Alzheimer's disease cortical signature regions distinguished participants with Alzheimer's disease from cognitively normal participants. A SUVR cutoff value of 1.19 from Alzheimer's disease cortical signature regions best distinguished these groups. Amyloid β-positivity was associated with an elevated [18F]-AV-1451 SUVR in Alzheimer's disease cortical signature regions, but not in the hippocampus. Amyloid β-positivity alone was not related to hippocampal volume or Alzheimer's disease signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with brain volumetric loss.
Symptom exacerbations after concussion are common among children and may not impede recovery, according to a study published online ahead of print August 1 in JAMA Pediatrics. Eligible participants were between ages 11 and 18 and had sustained a concussion that did not result in an abnormal CT scan or require hospital admission. The mean age of the 63 participants (34.9% girls) was 13.8. Symptom spikes occurred in 31.7% of the sample. An abrupt increase in mental activity from one day to the next increased the risk of a symptom spike. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period, but did not differ from the group without symptom spikes on cognition or balance 10 days following injury.
The FDA has approved the supplemental Biologics License Application from Ipsen Biopharmaceuticals for Dysport (abobotulinumtoxinA) for injection in the treatment of lower limb spasticity in pediatric patients age 2 and older. This approval is based on a phase III pivotal study of 235 pediatric patients ages 2 to 17 with lower limb spasticity because of cerebral palsy causing dynamic equinus foot deformity. Patients treated with Dysport showed statistically significant improvement in ankle plantar flexor muscle tone. Like all botulinum toxin products, Dysport has a boxed warning stating that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Ipsen Biopharmaceuticals is headquartered in Basking Ridge, New Jersey.
Lower BMI in late life is associated with greater cortical amyloid burden, according to a study published June 18 in the Journal of Alzheimer's Disease. The study entailed cross-sectional analyses that were completed using baseline data from the Harvard Aging Brain Study, which included 280 cognitively normal adults ages 62 to 90. Assessments included medical histories and physical exams, Pittsburgh compound B (PiB) PET amyloid imaging, and APOE4 genotyping. In the primary analysis, greater PiB retention was associated with lower BMI. In the secondary analyses, APOE4 carrier status and normal BMI, as opposed to overweight or obese BMI, were associated with greater PiB retention. The interaction between BMI and APOE4 also was significant. Future studies should seek to clarify the mechanism of this association, said the researchers.
Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome, according to a literature review published online ahead of print August 3 in Neurology. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in patients with transient ischemic attack or stroke are recommended in view of the high prevalence of SDB, said the researchers. Treatment of obstructive SDB with continuous positive airway pressure is recommended, given the strength of the evidence that supports the treatment's benefit. Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB, said the researchers. Experimental studies found that SWD may impair neuroplasticity and functional stroke recovery.
—Kimberly Williams
Hospitalization of patients with stroke in primary stroke centers, compared with noncertified hospitals, is associated with decreased seven-day and 30-day case fatality, according to a study published online ahead of print July 25 in JAMA Internal Medicine. Among 865,184 elderly patients with stroke (mean age, 78.9; 55.5% female), 53.9% were treated in primary stroke centers. Admission to primary stroke centers was associated with 1.8% lower seven-day and 1.8% lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in primary stroke centers to save one life at 30 days. Overall, receiving treatment in primary stroke centers was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of care in primary stroke centers.
Obesity may increase the risk of neurodegeneration, according to a study published online ahead of print July 27 in Neurobiology of Aging. Participants were a population-based cohort of cognitively healthy adults recruited over a five-year period. In all, 527 subjects with an age range of 20 to 87 were included. Researchers performed a cross-sectional analysis of MRI-based brain structure and found a statistically significant interaction between age and BMI. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white matter volume, cortical thickness, and surface area. Cerebral white matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase in brain age of 10 years.
Thymectomy improves clinical outcomes over a three-year period in patients with nonthymomatous myasthenia gravis, according to a study published August 11 in the New England Journal of Medicine. Researchers randomized 126 patients to thymectomy plus alternate-day prednisone or alternate-day prednisone alone. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those who received prednisone alone. Patients in the thymectomy group also had a lower average requirement for alternate-day prednisone. Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine or were hospitalized for exacerbations. The number of patients with treatment-associated complications did not differ significantly between groups. However, patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications.
Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease, according to a study published online ahead of print August 17 in Neurology. This longitudinal population-based study included 700 women without dementia between ages 70 and 92. At baseline and at five-year follow-up, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan also was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Women treated with calcium supplements had a higher risk of developing dementia and the subtype of stroke-related dementia. Calcium supplementation was associated with the development of dementia in groups with a history of stroke or presence of white matter lesions, but not in groups without these conditions.
Exposure to bright light during the day may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light, according to a study published online ahead of print June 16 in Sleep Medicine. Following a constant bright light exposure over 6.5 hours, 14 participants read a novel either on a tablet or as a physical book for two hours. Evening concentrations of saliva melatonin were measured repeatedly. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated. Participants who had read the novel on a tablet in the first experimental session continued reading the same novel as a physical book, and vice versa. There were no differences in sleep parameters and presleep saliva melatonin levels between the tablet reading and physical book reading conditions.
Treatment immediately after clinically isolated syndrome (CIS) is more beneficial than delayed treatment, according to a study published online ahead of print August 10 in Neurology. Researchers randomized 278 people with CIS to interferon beta-1b or placebo. After two years or a diagnosis of multiple sclerosis (MS), patients receiving placebo could receive treatment. After 11 years, risk of clinically definite MS remained lower in the early-treatment arm, compared with the delayed-treatment arm, with longer time to first relapse and lower overall annualized relapse rate. Twenty-five patients converted to secondary progressive MS. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores. Health resource utilization was low in both groups.
Patients with anemia have increased mortality after stroke, according to a study published online ahead of print August 17 in the Journal of the American Heart Association. Researchers analyzed data from a cohort of 8,013 patients with stroke who were consecutively admitted over 11 years. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to one year following stroke. Elevated hemoglobin also was associated with increased mortality. In addition, investigators conducted a systematic review using various databases. When combined with the cohort from the current study, the pooled population had 29,943 patients with stroke. Anemia on admission was associated with an increased risk of mortality in ischemic stroke and hemorrhagic stroke.
Bedside EEG methods may indicate the level of awareness of patients in a vegetative state, according to a study published online ahead of print August 4 in Annals of Neurology. Fourteen patients with severe brain injuries were evaluated with an EEG vibrotactile attention task designed to identify a hierarchy of residual somatosensory and cognitive abilities. Each patient also was assessed with a clinical behavioral scale and two fMRI assessments of covert command following. Six patients produced only sensory responses, with no evidence of cognitive event-related potentials. Furthermore, eight patients demonstrated reliable bottom-up attention-orienting responses. No patient showed evidence of top-down attention. Only patients who followed commands, whether overtly with behavior or covertly with functional neuroimaging, also demonstrated event-related potential evidence of attentional orienting.
The PET tracer [18F]-AV-1451 may help identify the stages of the preclinical and clinical phases of Alzheimer's disease, according to a study published online ahead of print July 25 in JAMA Neurology. In all, 59 participants (64% male; mean age, 74) underwent PET imaging. The [18F]-AV-1451 standardized uptake value ratio (SUVR) in the hippocampus and Alzheimer's disease cortical signature regions distinguished participants with Alzheimer's disease from cognitively normal participants. A SUVR cutoff value of 1.19 from Alzheimer's disease cortical signature regions best distinguished these groups. Amyloid β-positivity was associated with an elevated [18F]-AV-1451 SUVR in Alzheimer's disease cortical signature regions, but not in the hippocampus. Amyloid β-positivity alone was not related to hippocampal volume or Alzheimer's disease signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with brain volumetric loss.
Symptom exacerbations after concussion are common among children and may not impede recovery, according to a study published online ahead of print August 1 in JAMA Pediatrics. Eligible participants were between ages 11 and 18 and had sustained a concussion that did not result in an abnormal CT scan or require hospital admission. The mean age of the 63 participants (34.9% girls) was 13.8. Symptom spikes occurred in 31.7% of the sample. An abrupt increase in mental activity from one day to the next increased the risk of a symptom spike. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period, but did not differ from the group without symptom spikes on cognition or balance 10 days following injury.
The FDA has approved the supplemental Biologics License Application from Ipsen Biopharmaceuticals for Dysport (abobotulinumtoxinA) for injection in the treatment of lower limb spasticity in pediatric patients age 2 and older. This approval is based on a phase III pivotal study of 235 pediatric patients ages 2 to 17 with lower limb spasticity because of cerebral palsy causing dynamic equinus foot deformity. Patients treated with Dysport showed statistically significant improvement in ankle plantar flexor muscle tone. Like all botulinum toxin products, Dysport has a boxed warning stating that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Ipsen Biopharmaceuticals is headquartered in Basking Ridge, New Jersey.
Lower BMI in late life is associated with greater cortical amyloid burden, according to a study published June 18 in the Journal of Alzheimer's Disease. The study entailed cross-sectional analyses that were completed using baseline data from the Harvard Aging Brain Study, which included 280 cognitively normal adults ages 62 to 90. Assessments included medical histories and physical exams, Pittsburgh compound B (PiB) PET amyloid imaging, and APOE4 genotyping. In the primary analysis, greater PiB retention was associated with lower BMI. In the secondary analyses, APOE4 carrier status and normal BMI, as opposed to overweight or obese BMI, were associated with greater PiB retention. The interaction between BMI and APOE4 also was significant. Future studies should seek to clarify the mechanism of this association, said the researchers.
Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome, according to a literature review published online ahead of print August 3 in Neurology. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in patients with transient ischemic attack or stroke are recommended in view of the high prevalence of SDB, said the researchers. Treatment of obstructive SDB with continuous positive airway pressure is recommended, given the strength of the evidence that supports the treatment's benefit. Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB, said the researchers. Experimental studies found that SWD may impair neuroplasticity and functional stroke recovery.
—Kimberly Williams
Hospitalization of patients with stroke in primary stroke centers, compared with noncertified hospitals, is associated with decreased seven-day and 30-day case fatality, according to a study published online ahead of print July 25 in JAMA Internal Medicine. Among 865,184 elderly patients with stroke (mean age, 78.9; 55.5% female), 53.9% were treated in primary stroke centers. Admission to primary stroke centers was associated with 1.8% lower seven-day and 1.8% lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in primary stroke centers to save one life at 30 days. Overall, receiving treatment in primary stroke centers was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of care in primary stroke centers.
Obesity may increase the risk of neurodegeneration, according to a study published online ahead of print July 27 in Neurobiology of Aging. Participants were a population-based cohort of cognitively healthy adults recruited over a five-year period. In all, 527 subjects with an age range of 20 to 87 were included. Researchers performed a cross-sectional analysis of MRI-based brain structure and found a statistically significant interaction between age and BMI. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white matter volume, cortical thickness, and surface area. Cerebral white matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase in brain age of 10 years.
Thymectomy improves clinical outcomes over a three-year period in patients with nonthymomatous myasthenia gravis, according to a study published August 11 in the New England Journal of Medicine. Researchers randomized 126 patients to thymectomy plus alternate-day prednisone or alternate-day prednisone alone. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those who received prednisone alone. Patients in the thymectomy group also had a lower average requirement for alternate-day prednisone. Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine or were hospitalized for exacerbations. The number of patients with treatment-associated complications did not differ significantly between groups. However, patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications.
Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease, according to a study published online ahead of print August 17 in Neurology. This longitudinal population-based study included 700 women without dementia between ages 70 and 92. At baseline and at five-year follow-up, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan also was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Women treated with calcium supplements had a higher risk of developing dementia and the subtype of stroke-related dementia. Calcium supplementation was associated with the development of dementia in groups with a history of stroke or presence of white matter lesions, but not in groups without these conditions.
Exposure to bright light during the day may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light, according to a study published online ahead of print June 16 in Sleep Medicine. Following a constant bright light exposure over 6.5 hours, 14 participants read a novel either on a tablet or as a physical book for two hours. Evening concentrations of saliva melatonin were measured repeatedly. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated. Participants who had read the novel on a tablet in the first experimental session continued reading the same novel as a physical book, and vice versa. There were no differences in sleep parameters and presleep saliva melatonin levels between the tablet reading and physical book reading conditions.
Treatment immediately after clinically isolated syndrome (CIS) is more beneficial than delayed treatment, according to a study published online ahead of print August 10 in Neurology. Researchers randomized 278 people with CIS to interferon beta-1b or placebo. After two years or a diagnosis of multiple sclerosis (MS), patients receiving placebo could receive treatment. After 11 years, risk of clinically definite MS remained lower in the early-treatment arm, compared with the delayed-treatment arm, with longer time to first relapse and lower overall annualized relapse rate. Twenty-five patients converted to secondary progressive MS. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores. Health resource utilization was low in both groups.
Patients with anemia have increased mortality after stroke, according to a study published online ahead of print August 17 in the Journal of the American Heart Association. Researchers analyzed data from a cohort of 8,013 patients with stroke who were consecutively admitted over 11 years. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to one year following stroke. Elevated hemoglobin also was associated with increased mortality. In addition, investigators conducted a systematic review using various databases. When combined with the cohort from the current study, the pooled population had 29,943 patients with stroke. Anemia on admission was associated with an increased risk of mortality in ischemic stroke and hemorrhagic stroke.
Bedside EEG methods may indicate the level of awareness of patients in a vegetative state, according to a study published online ahead of print August 4 in Annals of Neurology. Fourteen patients with severe brain injuries were evaluated with an EEG vibrotactile attention task designed to identify a hierarchy of residual somatosensory and cognitive abilities. Each patient also was assessed with a clinical behavioral scale and two fMRI assessments of covert command following. Six patients produced only sensory responses, with no evidence of cognitive event-related potentials. Furthermore, eight patients demonstrated reliable bottom-up attention-orienting responses. No patient showed evidence of top-down attention. Only patients who followed commands, whether overtly with behavior or covertly with functional neuroimaging, also demonstrated event-related potential evidence of attentional orienting.
The PET tracer [18F]-AV-1451 may help identify the stages of the preclinical and clinical phases of Alzheimer's disease, according to a study published online ahead of print July 25 in JAMA Neurology. In all, 59 participants (64% male; mean age, 74) underwent PET imaging. The [18F]-AV-1451 standardized uptake value ratio (SUVR) in the hippocampus and Alzheimer's disease cortical signature regions distinguished participants with Alzheimer's disease from cognitively normal participants. A SUVR cutoff value of 1.19 from Alzheimer's disease cortical signature regions best distinguished these groups. Amyloid β-positivity was associated with an elevated [18F]-AV-1451 SUVR in Alzheimer's disease cortical signature regions, but not in the hippocampus. Amyloid β-positivity alone was not related to hippocampal volume or Alzheimer's disease signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with brain volumetric loss.
Symptom exacerbations after concussion are common among children and may not impede recovery, according to a study published online ahead of print August 1 in JAMA Pediatrics. Eligible participants were between ages 11 and 18 and had sustained a concussion that did not result in an abnormal CT scan or require hospital admission. The mean age of the 63 participants (34.9% girls) was 13.8. Symptom spikes occurred in 31.7% of the sample. An abrupt increase in mental activity from one day to the next increased the risk of a symptom spike. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period, but did not differ from the group without symptom spikes on cognition or balance 10 days following injury.
The FDA has approved the supplemental Biologics License Application from Ipsen Biopharmaceuticals for Dysport (abobotulinumtoxinA) for injection in the treatment of lower limb spasticity in pediatric patients age 2 and older. This approval is based on a phase III pivotal study of 235 pediatric patients ages 2 to 17 with lower limb spasticity because of cerebral palsy causing dynamic equinus foot deformity. Patients treated with Dysport showed statistically significant improvement in ankle plantar flexor muscle tone. Like all botulinum toxin products, Dysport has a boxed warning stating that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Ipsen Biopharmaceuticals is headquartered in Basking Ridge, New Jersey.
Lower BMI in late life is associated with greater cortical amyloid burden, according to a study published June 18 in the Journal of Alzheimer's Disease. The study entailed cross-sectional analyses that were completed using baseline data from the Harvard Aging Brain Study, which included 280 cognitively normal adults ages 62 to 90. Assessments included medical histories and physical exams, Pittsburgh compound B (PiB) PET amyloid imaging, and APOE4 genotyping. In the primary analysis, greater PiB retention was associated with lower BMI. In the secondary analyses, APOE4 carrier status and normal BMI, as opposed to overweight or obese BMI, were associated with greater PiB retention. The interaction between BMI and APOE4 also was significant. Future studies should seek to clarify the mechanism of this association, said the researchers.
Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome, according to a literature review published online ahead of print August 3 in Neurology. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in patients with transient ischemic attack or stroke are recommended in view of the high prevalence of SDB, said the researchers. Treatment of obstructive SDB with continuous positive airway pressure is recommended, given the strength of the evidence that supports the treatment's benefit. Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB, said the researchers. Experimental studies found that SWD may impair neuroplasticity and functional stroke recovery.
—Kimberly Williams
New and Noteworthy Information—August 2016
People with epilepsy are at increased risk of autism spectrum disorder, especially if epilepsy appears in childhood, according to a study published July 12 in Neurology. Researchers used the Swedish Patient Register to identify 85,201 individuals with epilepsy, their siblings, and their offspring. Each person with epilepsy was compared with five controls matched for age, sex, calendar period, and county. Patients' siblings and offspring were compared with siblings and offspring of controls. During follow-up, 1.6% of people with epilepsy and 0.2% of controls were diagnosed with autism spectrum disorder. People with epilepsy were at increased risk of future autism spectrum disorder, with the highest risk seen in individuals diagnosed with epilepsy in childhood. Siblings and offspring of patients were at increased risk of autism spectrum disorder, compared with controls.
Among patients with chorea associated with Huntington's disease, deutetrabenazine, compared with placebo, results in improved motor signs at 12 weeks, according to a study published July 5 in JAMA. For this study, 90 adults (mean age, 53.7; 44.4% women) with Huntington's disease and a baseline total maximal chorea score of eight or higher were enrolled from August 2013 to August 2014. Participants were randomized to receive deutetrabenazine or placebo. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 to 7.7, whereas in the placebo group, scores improved from 13.2 to 11.3. In the deutetrabenazine group, the mean 36-Item Short Form physical functioning subscale scores decreased from 47.5 to 47.4, whereas in the placebo group, scores decreased from 43.2 to 39.9.
The estimated suicide rate among people with epilepsy in a large US population exceeds that in the general population, according to a study published online ahead of print June 30 in Epilepsy & Behavior. Among people age 10 and older, researchers identified 972 suicide cases with epilepsy and 81,529 suicide cases without epilepsy in 17 states from 2003 through 2011. Investigators estimated their suicide rates, evaluated suicide risk among people with epilepsy, and investigated suicide risk factors specific to epilepsy by comparing those with and without epilepsy. The estimated annual suicide mortality rate among people with epilepsy was 22% higher than that in the general population. Overall, compared with people without epilepsy, those with epilepsy were more likely to have died from suicide and were twice as likely to poison themselves.
Low-dose methylene blue increases functional MRI (fMRI) activity during sustained attention and short-term memory tasks and enhances memory retrieval, according to a study published online ahead of print June 28 in Radiology. Twenty-six people ages 22 to 62 were enrolled. Researchers performed fMRI imaging with a psychomotor vigilance task and delayed match-to-sample tasks before and one hour after administration of low-dose methylene blue or placebo. Cerebrovascular reactivity effects were measured with the carbon dioxide challenge. Multiple comparison correction also was applied. Administration of methylene blue increased response in the bilateral insular cortex during the psychomotor vigilance task and fMRI response during the short-term memory task involving the prefrontal, parietal, and occipital cortex. Methylene blue also was associated with a 7% increase in correct responses during memory retrieval.
Traumatic brain injury (TBI) with loss of consciousness is associated with an increased risk for clinical and neuropathologic findings of Parkinson's disease, but not Alzheimer's disease, according to a study published online ahead of print July 11 in JAMA Neurology. Researchers retrospectively analyzed data from three prospective cohort studies that included annual or biennial cognitive and clinical testing to identify incident cases of dementia and Alzheimer's disease. Of 7,130 participants, 865 reported a history of TBI with loss of consciousness. In 45,190 person-years of follow-up, 1,537 incident cases of dementia and 117 of Parkinson's disease were identified. No association was found between TBI with loss of consciousness and incident dementia or Alzheimer's disease. TBI with loss of consciousness was associated with incident Parkinson's disease, progression of parkinsonian signs, Lewy bodies, and microinfarcts.
Genetically elevated BMI is associated with risk of multiple sclerosis (MS), which suggests a causal role for obesity in MS etiology, according to an article published June 28 in PLOS Medicine. Researchers used summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the International MS Genetics Consortium (IMSGC). The effect of each single-nucleotide polymorphism (SNP) on MS was weighted by its effect on BMI. Seventy SNPs had genome-wide significance for BMI in GIANT and were investigated for their association with MS risk in the IMSGC. It was found that increased BMI influences MS susceptibility, where a one-standard-deviation increase in genetically determined BMI increased odds of MS by 41%. Sensitivity analyses, including MR-Egger regression, and the weighted median approach provided no evidence of pleiotropic effects.
The FDA has accepted the Biologics License Application for Ocrevus (ocrelizumab) for the treatment of relapsing multiple sclerosis and primary progressive multiple sclerosis. The agency granted the application Priority Review Designation with a targeted action date of December 28, 2016. The Ocrevus Marketing Authorization Application has also been validated by the European Medicines Agency. The Ocrevus marketing applications are based on results from three phase III studies that met primary and key secondary end points. Data from OPERA I and OPERA II in people with relapsing multiple sclerosis showed superior efficacy of Ocrevus in reducing annualized relapse rates and disability progression sustained for at least three and for at least six months, respectively, compared with interferon beta-1a. Genentech, which will manufacture the drug, is headquartered in South San Francisco, California.
Thirty-eight independent genomic regions are associated with migraine, according to a study published online ahead of print June 20 in Nature Genetics. The identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, which is consistent with a predominant theory of migraine that highlights vascular etiologies. To identify new genomic loci associated with susceptibility to migraine, researchers carried out a genetic study of migraine on 59,674 subjects with migraine and 316,078 controls who participated in 22 genome-wide association studies. Investigators identified 44 independent single-nucleotide polymorphisms significantly associated with migraine risk that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that is the first to be identified on chromosome X. The findings may promote the development of personalized treatments for migraine.
Long-term risks of recurrent stroke and poststroke dementia remain high after stroke and are substantially influenced by prestroke risk factors, emphasizing the need for optimizing primary prevention, according to a study published online ahead of print July 14 in Stroke. Researchers monitored 1,237 patients with first-ever stroke and 4,928 stroke-free participants, matched by age, sex, examination round, and stroke date, for the occurrence of stroke or dementia. Beyond one year after stroke, patients retained a threefold increased risk of recurrent stroke and an almost twofold increased risk of dementia, compared with people without stroke. In all, 39% of recurrent strokes and 10% of poststroke dementia cases were attributable to prestroke cardiovascular risk factors. These percentages were similar for first-ever stroke and dementia in the matched stroke-free population.
Molecular evidence indicates that nilotinib significantly increases brain dopamine and reduces toxic proteins linked to disease progression in patients with Parkinson's disease or dementia with Lewy bodies, according to a phase I study published July 11 in the Journal of Parkinson's Disease. Twelve participants were randomized to 150 mg/day or 300 mg/day of oral nilotinib for 24 weeks. The CSF levels of homovanillic acid were significantly increased between baseline and 24 weeks of treatment. The researchers found that nilotinib is safe and well tolerated for people with advanced Parkinson's disease. In addition, nilotinib is detectable in the CSF and engages the target ABL1. Improvements in motor and cognitive function suggest that nilotinib may have clinical benefits. Nilotinib should be evaluated in larger randomized trials, said the researchers.
The FDA has approved ExAblate Neuro, the first focused ultrasound device to treat essential tremor in patients who have not responded to medication. ExAblate Neuro uses MRI to deliver focused ultrasound to destroy brain tissue in a small area thought to be responsible for causing tremors. Of 76 patients with essential tremor, 56 randomly received the ExAblate Neuro treatment in one study. Patients in the control group were able to cross over into the treatment group three months later. Patients treated with ExAblate Neuro showed a nearly 50% improvement in tremor and motor function three months after treatment, compared with their baseline scores. To determine whether ExAblate Neuro treatment is appropriate, patients should first have MRI and CT scans. InSightec, the device's manufacturer, is headquartered in Tirat Carmel, Israel.
The driving ability of patients with mild cognitive impairment (MCI) and Alzheimer's disease is related to their degree of cognitive impairment, according to a systematic review published May 11 in the Journal of Alzheimer's Disease. Researchers investigated the predictive utility of cognitive tests and domains, and the areas and degree of driving impairment in patients with MCI and Alzheimer's disease. Effect sizes were derived and analyzed in a random effects model. Executive function, attention, visuospatial function, and global cognition significantly predicted driving performance. Trail Making Test Part B and Maze test were the best single predictors of driving performance. Patients with very mild Alzheimer's disease and mild Alzheimer's disease were more likely to fail an on-road test than healthy control drivers, with failure rates of 13.6%, 33.3%, and 1.6%, respectively.
Functional brain scans may help predict recovery and guide treatment after stroke, according to a study published online ahead of print July 11 in the Proceedings of the National Academy of Sciences. Researchers investigated whether functional connectivity MRI (fcMRI) could provide useful information for assessing stroke damage. They used fcMRI to assess communication between brain areas in 132 patients with stroke and 31 people without stroke. The technology allowed the authors to identify large disruptions in brain communication that occurred as a result of stroke. Each participant also underwent a battery of neuropsychologic tests. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains.
—Kimberly Williams
People with epilepsy are at increased risk of autism spectrum disorder, especially if epilepsy appears in childhood, according to a study published July 12 in Neurology. Researchers used the Swedish Patient Register to identify 85,201 individuals with epilepsy, their siblings, and their offspring. Each person with epilepsy was compared with five controls matched for age, sex, calendar period, and county. Patients' siblings and offspring were compared with siblings and offspring of controls. During follow-up, 1.6% of people with epilepsy and 0.2% of controls were diagnosed with autism spectrum disorder. People with epilepsy were at increased risk of future autism spectrum disorder, with the highest risk seen in individuals diagnosed with epilepsy in childhood. Siblings and offspring of patients were at increased risk of autism spectrum disorder, compared with controls.
Among patients with chorea associated with Huntington's disease, deutetrabenazine, compared with placebo, results in improved motor signs at 12 weeks, according to a study published July 5 in JAMA. For this study, 90 adults (mean age, 53.7; 44.4% women) with Huntington's disease and a baseline total maximal chorea score of eight or higher were enrolled from August 2013 to August 2014. Participants were randomized to receive deutetrabenazine or placebo. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 to 7.7, whereas in the placebo group, scores improved from 13.2 to 11.3. In the deutetrabenazine group, the mean 36-Item Short Form physical functioning subscale scores decreased from 47.5 to 47.4, whereas in the placebo group, scores decreased from 43.2 to 39.9.
The estimated suicide rate among people with epilepsy in a large US population exceeds that in the general population, according to a study published online ahead of print June 30 in Epilepsy & Behavior. Among people age 10 and older, researchers identified 972 suicide cases with epilepsy and 81,529 suicide cases without epilepsy in 17 states from 2003 through 2011. Investigators estimated their suicide rates, evaluated suicide risk among people with epilepsy, and investigated suicide risk factors specific to epilepsy by comparing those with and without epilepsy. The estimated annual suicide mortality rate among people with epilepsy was 22% higher than that in the general population. Overall, compared with people without epilepsy, those with epilepsy were more likely to have died from suicide and were twice as likely to poison themselves.
Low-dose methylene blue increases functional MRI (fMRI) activity during sustained attention and short-term memory tasks and enhances memory retrieval, according to a study published online ahead of print June 28 in Radiology. Twenty-six people ages 22 to 62 were enrolled. Researchers performed fMRI imaging with a psychomotor vigilance task and delayed match-to-sample tasks before and one hour after administration of low-dose methylene blue or placebo. Cerebrovascular reactivity effects were measured with the carbon dioxide challenge. Multiple comparison correction also was applied. Administration of methylene blue increased response in the bilateral insular cortex during the psychomotor vigilance task and fMRI response during the short-term memory task involving the prefrontal, parietal, and occipital cortex. Methylene blue also was associated with a 7% increase in correct responses during memory retrieval.
Traumatic brain injury (TBI) with loss of consciousness is associated with an increased risk for clinical and neuropathologic findings of Parkinson's disease, but not Alzheimer's disease, according to a study published online ahead of print July 11 in JAMA Neurology. Researchers retrospectively analyzed data from three prospective cohort studies that included annual or biennial cognitive and clinical testing to identify incident cases of dementia and Alzheimer's disease. Of 7,130 participants, 865 reported a history of TBI with loss of consciousness. In 45,190 person-years of follow-up, 1,537 incident cases of dementia and 117 of Parkinson's disease were identified. No association was found between TBI with loss of consciousness and incident dementia or Alzheimer's disease. TBI with loss of consciousness was associated with incident Parkinson's disease, progression of parkinsonian signs, Lewy bodies, and microinfarcts.
Genetically elevated BMI is associated with risk of multiple sclerosis (MS), which suggests a causal role for obesity in MS etiology, according to an article published June 28 in PLOS Medicine. Researchers used summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the International MS Genetics Consortium (IMSGC). The effect of each single-nucleotide polymorphism (SNP) on MS was weighted by its effect on BMI. Seventy SNPs had genome-wide significance for BMI in GIANT and were investigated for their association with MS risk in the IMSGC. It was found that increased BMI influences MS susceptibility, where a one-standard-deviation increase in genetically determined BMI increased odds of MS by 41%. Sensitivity analyses, including MR-Egger regression, and the weighted median approach provided no evidence of pleiotropic effects.
The FDA has accepted the Biologics License Application for Ocrevus (ocrelizumab) for the treatment of relapsing multiple sclerosis and primary progressive multiple sclerosis. The agency granted the application Priority Review Designation with a targeted action date of December 28, 2016. The Ocrevus Marketing Authorization Application has also been validated by the European Medicines Agency. The Ocrevus marketing applications are based on results from three phase III studies that met primary and key secondary end points. Data from OPERA I and OPERA II in people with relapsing multiple sclerosis showed superior efficacy of Ocrevus in reducing annualized relapse rates and disability progression sustained for at least three and for at least six months, respectively, compared with interferon beta-1a. Genentech, which will manufacture the drug, is headquartered in South San Francisco, California.
Thirty-eight independent genomic regions are associated with migraine, according to a study published online ahead of print June 20 in Nature Genetics. The identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, which is consistent with a predominant theory of migraine that highlights vascular etiologies. To identify new genomic loci associated with susceptibility to migraine, researchers carried out a genetic study of migraine on 59,674 subjects with migraine and 316,078 controls who participated in 22 genome-wide association studies. Investigators identified 44 independent single-nucleotide polymorphisms significantly associated with migraine risk that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that is the first to be identified on chromosome X. The findings may promote the development of personalized treatments for migraine.
Long-term risks of recurrent stroke and poststroke dementia remain high after stroke and are substantially influenced by prestroke risk factors, emphasizing the need for optimizing primary prevention, according to a study published online ahead of print July 14 in Stroke. Researchers monitored 1,237 patients with first-ever stroke and 4,928 stroke-free participants, matched by age, sex, examination round, and stroke date, for the occurrence of stroke or dementia. Beyond one year after stroke, patients retained a threefold increased risk of recurrent stroke and an almost twofold increased risk of dementia, compared with people without stroke. In all, 39% of recurrent strokes and 10% of poststroke dementia cases were attributable to prestroke cardiovascular risk factors. These percentages were similar for first-ever stroke and dementia in the matched stroke-free population.
Molecular evidence indicates that nilotinib significantly increases brain dopamine and reduces toxic proteins linked to disease progression in patients with Parkinson's disease or dementia with Lewy bodies, according to a phase I study published July 11 in the Journal of Parkinson's Disease. Twelve participants were randomized to 150 mg/day or 300 mg/day of oral nilotinib for 24 weeks. The CSF levels of homovanillic acid were significantly increased between baseline and 24 weeks of treatment. The researchers found that nilotinib is safe and well tolerated for people with advanced Parkinson's disease. In addition, nilotinib is detectable in the CSF and engages the target ABL1. Improvements in motor and cognitive function suggest that nilotinib may have clinical benefits. Nilotinib should be evaluated in larger randomized trials, said the researchers.
The FDA has approved ExAblate Neuro, the first focused ultrasound device to treat essential tremor in patients who have not responded to medication. ExAblate Neuro uses MRI to deliver focused ultrasound to destroy brain tissue in a small area thought to be responsible for causing tremors. Of 76 patients with essential tremor, 56 randomly received the ExAblate Neuro treatment in one study. Patients in the control group were able to cross over into the treatment group three months later. Patients treated with ExAblate Neuro showed a nearly 50% improvement in tremor and motor function three months after treatment, compared with their baseline scores. To determine whether ExAblate Neuro treatment is appropriate, patients should first have MRI and CT scans. InSightec, the device's manufacturer, is headquartered in Tirat Carmel, Israel.
The driving ability of patients with mild cognitive impairment (MCI) and Alzheimer's disease is related to their degree of cognitive impairment, according to a systematic review published May 11 in the Journal of Alzheimer's Disease. Researchers investigated the predictive utility of cognitive tests and domains, and the areas and degree of driving impairment in patients with MCI and Alzheimer's disease. Effect sizes were derived and analyzed in a random effects model. Executive function, attention, visuospatial function, and global cognition significantly predicted driving performance. Trail Making Test Part B and Maze test were the best single predictors of driving performance. Patients with very mild Alzheimer's disease and mild Alzheimer's disease were more likely to fail an on-road test than healthy control drivers, with failure rates of 13.6%, 33.3%, and 1.6%, respectively.
Functional brain scans may help predict recovery and guide treatment after stroke, according to a study published online ahead of print July 11 in the Proceedings of the National Academy of Sciences. Researchers investigated whether functional connectivity MRI (fcMRI) could provide useful information for assessing stroke damage. They used fcMRI to assess communication between brain areas in 132 patients with stroke and 31 people without stroke. The technology allowed the authors to identify large disruptions in brain communication that occurred as a result of stroke. Each participant also underwent a battery of neuropsychologic tests. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains.
—Kimberly Williams
People with epilepsy are at increased risk of autism spectrum disorder, especially if epilepsy appears in childhood, according to a study published July 12 in Neurology. Researchers used the Swedish Patient Register to identify 85,201 individuals with epilepsy, their siblings, and their offspring. Each person with epilepsy was compared with five controls matched for age, sex, calendar period, and county. Patients' siblings and offspring were compared with siblings and offspring of controls. During follow-up, 1.6% of people with epilepsy and 0.2% of controls were diagnosed with autism spectrum disorder. People with epilepsy were at increased risk of future autism spectrum disorder, with the highest risk seen in individuals diagnosed with epilepsy in childhood. Siblings and offspring of patients were at increased risk of autism spectrum disorder, compared with controls.
Among patients with chorea associated with Huntington's disease, deutetrabenazine, compared with placebo, results in improved motor signs at 12 weeks, according to a study published July 5 in JAMA. For this study, 90 adults (mean age, 53.7; 44.4% women) with Huntington's disease and a baseline total maximal chorea score of eight or higher were enrolled from August 2013 to August 2014. Participants were randomized to receive deutetrabenazine or placebo. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 to 7.7, whereas in the placebo group, scores improved from 13.2 to 11.3. In the deutetrabenazine group, the mean 36-Item Short Form physical functioning subscale scores decreased from 47.5 to 47.4, whereas in the placebo group, scores decreased from 43.2 to 39.9.
The estimated suicide rate among people with epilepsy in a large US population exceeds that in the general population, according to a study published online ahead of print June 30 in Epilepsy & Behavior. Among people age 10 and older, researchers identified 972 suicide cases with epilepsy and 81,529 suicide cases without epilepsy in 17 states from 2003 through 2011. Investigators estimated their suicide rates, evaluated suicide risk among people with epilepsy, and investigated suicide risk factors specific to epilepsy by comparing those with and without epilepsy. The estimated annual suicide mortality rate among people with epilepsy was 22% higher than that in the general population. Overall, compared with people without epilepsy, those with epilepsy were more likely to have died from suicide and were twice as likely to poison themselves.
Low-dose methylene blue increases functional MRI (fMRI) activity during sustained attention and short-term memory tasks and enhances memory retrieval, according to a study published online ahead of print June 28 in Radiology. Twenty-six people ages 22 to 62 were enrolled. Researchers performed fMRI imaging with a psychomotor vigilance task and delayed match-to-sample tasks before and one hour after administration of low-dose methylene blue or placebo. Cerebrovascular reactivity effects were measured with the carbon dioxide challenge. Multiple comparison correction also was applied. Administration of methylene blue increased response in the bilateral insular cortex during the psychomotor vigilance task and fMRI response during the short-term memory task involving the prefrontal, parietal, and occipital cortex. Methylene blue also was associated with a 7% increase in correct responses during memory retrieval.
Traumatic brain injury (TBI) with loss of consciousness is associated with an increased risk for clinical and neuropathologic findings of Parkinson's disease, but not Alzheimer's disease, according to a study published online ahead of print July 11 in JAMA Neurology. Researchers retrospectively analyzed data from three prospective cohort studies that included annual or biennial cognitive and clinical testing to identify incident cases of dementia and Alzheimer's disease. Of 7,130 participants, 865 reported a history of TBI with loss of consciousness. In 45,190 person-years of follow-up, 1,537 incident cases of dementia and 117 of Parkinson's disease were identified. No association was found between TBI with loss of consciousness and incident dementia or Alzheimer's disease. TBI with loss of consciousness was associated with incident Parkinson's disease, progression of parkinsonian signs, Lewy bodies, and microinfarcts.
Genetically elevated BMI is associated with risk of multiple sclerosis (MS), which suggests a causal role for obesity in MS etiology, according to an article published June 28 in PLOS Medicine. Researchers used summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the International MS Genetics Consortium (IMSGC). The effect of each single-nucleotide polymorphism (SNP) on MS was weighted by its effect on BMI. Seventy SNPs had genome-wide significance for BMI in GIANT and were investigated for their association with MS risk in the IMSGC. It was found that increased BMI influences MS susceptibility, where a one-standard-deviation increase in genetically determined BMI increased odds of MS by 41%. Sensitivity analyses, including MR-Egger regression, and the weighted median approach provided no evidence of pleiotropic effects.
The FDA has accepted the Biologics License Application for Ocrevus (ocrelizumab) for the treatment of relapsing multiple sclerosis and primary progressive multiple sclerosis. The agency granted the application Priority Review Designation with a targeted action date of December 28, 2016. The Ocrevus Marketing Authorization Application has also been validated by the European Medicines Agency. The Ocrevus marketing applications are based on results from three phase III studies that met primary and key secondary end points. Data from OPERA I and OPERA II in people with relapsing multiple sclerosis showed superior efficacy of Ocrevus in reducing annualized relapse rates and disability progression sustained for at least three and for at least six months, respectively, compared with interferon beta-1a. Genentech, which will manufacture the drug, is headquartered in South San Francisco, California.
Thirty-eight independent genomic regions are associated with migraine, according to a study published online ahead of print June 20 in Nature Genetics. The identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, which is consistent with a predominant theory of migraine that highlights vascular etiologies. To identify new genomic loci associated with susceptibility to migraine, researchers carried out a genetic study of migraine on 59,674 subjects with migraine and 316,078 controls who participated in 22 genome-wide association studies. Investigators identified 44 independent single-nucleotide polymorphisms significantly associated with migraine risk that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that is the first to be identified on chromosome X. The findings may promote the development of personalized treatments for migraine.
Long-term risks of recurrent stroke and poststroke dementia remain high after stroke and are substantially influenced by prestroke risk factors, emphasizing the need for optimizing primary prevention, according to a study published online ahead of print July 14 in Stroke. Researchers monitored 1,237 patients with first-ever stroke and 4,928 stroke-free participants, matched by age, sex, examination round, and stroke date, for the occurrence of stroke or dementia. Beyond one year after stroke, patients retained a threefold increased risk of recurrent stroke and an almost twofold increased risk of dementia, compared with people without stroke. In all, 39% of recurrent strokes and 10% of poststroke dementia cases were attributable to prestroke cardiovascular risk factors. These percentages were similar for first-ever stroke and dementia in the matched stroke-free population.
Molecular evidence indicates that nilotinib significantly increases brain dopamine and reduces toxic proteins linked to disease progression in patients with Parkinson's disease or dementia with Lewy bodies, according to a phase I study published July 11 in the Journal of Parkinson's Disease. Twelve participants were randomized to 150 mg/day or 300 mg/day of oral nilotinib for 24 weeks. The CSF levels of homovanillic acid were significantly increased between baseline and 24 weeks of treatment. The researchers found that nilotinib is safe and well tolerated for people with advanced Parkinson's disease. In addition, nilotinib is detectable in the CSF and engages the target ABL1. Improvements in motor and cognitive function suggest that nilotinib may have clinical benefits. Nilotinib should be evaluated in larger randomized trials, said the researchers.
The FDA has approved ExAblate Neuro, the first focused ultrasound device to treat essential tremor in patients who have not responded to medication. ExAblate Neuro uses MRI to deliver focused ultrasound to destroy brain tissue in a small area thought to be responsible for causing tremors. Of 76 patients with essential tremor, 56 randomly received the ExAblate Neuro treatment in one study. Patients in the control group were able to cross over into the treatment group three months later. Patients treated with ExAblate Neuro showed a nearly 50% improvement in tremor and motor function three months after treatment, compared with their baseline scores. To determine whether ExAblate Neuro treatment is appropriate, patients should first have MRI and CT scans. InSightec, the device's manufacturer, is headquartered in Tirat Carmel, Israel.
The driving ability of patients with mild cognitive impairment (MCI) and Alzheimer's disease is related to their degree of cognitive impairment, according to a systematic review published May 11 in the Journal of Alzheimer's Disease. Researchers investigated the predictive utility of cognitive tests and domains, and the areas and degree of driving impairment in patients with MCI and Alzheimer's disease. Effect sizes were derived and analyzed in a random effects model. Executive function, attention, visuospatial function, and global cognition significantly predicted driving performance. Trail Making Test Part B and Maze test were the best single predictors of driving performance. Patients with very mild Alzheimer's disease and mild Alzheimer's disease were more likely to fail an on-road test than healthy control drivers, with failure rates of 13.6%, 33.3%, and 1.6%, respectively.
Functional brain scans may help predict recovery and guide treatment after stroke, according to a study published online ahead of print July 11 in the Proceedings of the National Academy of Sciences. Researchers investigated whether functional connectivity MRI (fcMRI) could provide useful information for assessing stroke damage. They used fcMRI to assess communication between brain areas in 132 patients with stroke and 31 people without stroke. The technology allowed the authors to identify large disruptions in brain communication that occurred as a result of stroke. Each participant also underwent a battery of neuropsychologic tests. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains.
—Kimberly Williams
New and Noteworthy Information—July 2016
There is a strong, inverse association between midlife cardiorespiratory fitness and stroke risk in later life, independent of the baseline and antecedent burden of risk factors, according to a study published online ahead of print June 9 in Stroke. Researchers studied 19,815 individuals who received Medicare coverage from 1999 to 2009. Cardiorespiratory fitness estimated at baseline was analyzed as a continuous variable and according to age- and sex-specific quintiles. Associations between midlife cardiorespiratory fitness and stroke hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. The investigators observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife cardiorespiratory fitness was associated with a lower risk of stroke hospitalization.
Incident dementia early after intracerebral hemorrhage is strongly associated with hematoma size and location, according to a study published online ahead of print June 13 in JAMA Neurology. A longitudinal study enrolled patients with intracerebral hemorrhage from January 1, 2006, to December 31, 2013. In all, 738 participants ages 18 or older, without pre-intracerebral hemorrhage dementia, who presented to a tertiary care academic institution with primary intracerebral hemorrhage were included in the study. A total of 140 patients developed dementia within six months. Larger hematoma size and lobar location of intracerebral hemorrhage were associated with early post-intracerebral hemorrhage dementia, but not with delayed post-intracerebral hemorrhage dementia. Educational level, incident mood symptoms, and white matter disease were associated with delayed, but not early, post-intracerebral hemorrhage dementia.
The FDA is investigating the risk of serious burns and potential permanent scarring from the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch for migraine. The patch delivers a dose of medicine in a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Since the introduction of the patch, many patients have reported injury to the skin where the patch was worn. The reports include descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin. Patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact a health care professional. Teva Pharmaceuticals has suspended the sale, marketing, and distribution of the patch.
More than 90% of the global stroke burden is attributable to modifiable risk factors, including air pollution, and controlling behavioral and metabolic risk factors could avert more than 75% of the global stroke burden, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers used data on stroke-related disability-adjusted life-years, risk factors, and population-attributable fraction from the Global Burden of Disease Study 2013 to estimate the burden of stroke by age and sex in 188 countries. Approximately 74% of the global stroke burden was attributable to behavioral factors. Clusters of metabolic factors (72%) and environmental factors (33%) were the second and third largest contributors to disability-adjusted life-years, respectively. About 29% of the burden of stroke was attributed to air pollution.
Abnormally high fractional anisotropy (FA) on diffusion tensor imaging (DTI) is associated with better outcomes after mild traumatic brain injury (mTBI), according to a study published online ahead of print June 9 in the American Journal of Neuroradiology. DTI was performed on 39 subjects with mTBI within 16 days of injury and on 40 controls. In all, 26 subjects with mTBI returned for follow-up at one year. Among these subjects, high FA in the left frontal lobe and left temporal lobe was associated with better attention. High FA in the left and right cerebelli was associated with improved somatic postconcussion symptoms. High FA in the right thalamus was associated with improved emotional postconcussion symptoms. Abnormally high FA may be an imaging correlate of postinjury compensatory processes, said the investigators.
Among patients with multiple sclerosis (MS), obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function, attention, processing speed, and working memory, according to a study published online ahead of print May 3 in Sleep. Thirty-eight participants underwent MS-specific cognitive testing and in-laboratory overnight polysomnography. In adjusted linear regression models, the oxygen desaturation index and minimum oxygen saturation were significantly associated with performance on multiple Minimal Assessment of Cognitive Function in MS measures. Apnea severity measures accounted for between 11% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation and total sleep time also showed significant associations with a component of the California Verbal Learning Test-II, explaining 18% and 27% of the variance in performance, respectively.
The differences in stroke mortality between African Americans and Caucasians are largely related to differences in stroke incidence, according to a study published online ahead of print June 2 in Stroke. Researchers assessed the difference between African American and Caucasian stroke mortality for 29,681 participants in the Reasons for Geographic and Racial Differences in Stroke cohort. They found that African Americans are four times more likely to die of stroke at age 45 than Caucasians because stroke incidence is greater among African Americans. By age 85, however, the difference in stroke mortality is no longer present. More should be done to reduce the disparity in stroke mortality between African Americans and Caucasians, and interventions should focus on prevention of stroke among African Americans, according to the investigators.
A mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, according to a study published online ahead of print June 6 in Nature Genetics. Researchers first investigated a family with 15 members who had typical symptoms of Parkinson's disease. They used DNA samples to perform a genome-wide analysis on 65 of the family's members, including 13 with Parkinson's disease, to find a common mutation that could explain the prevalence of Parkinson's disease. The study authors identified TMEM230 as the gene with a disease-causing mutation and found that TMEM230 encodes a protein that extends across the membrane of tiny sacs inside synaptic vesicles. The research team also found mutations in TMEM230 in cases of Parkinson's disease in additional families in North America and China.
People with blast exposure have a pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and between gray and white matter, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers analyzed brain specimens from five military service members with chronic blast exposure, three with acute blast exposure, five with chronic impact traumatic brain injury, five with exposure to opiates, and three control cases with no known neurologic disorders. All five cases with chronic blast exposure showed prominent astroglial scarring involving the subpial glial plate, penetrating cortical blood vessels, gray-white matter junctions, and structures lining the ventricles. Cases of acute blast exposure showed early astroglial scarring in the same brain regions. Cases of chronic blast exposure had an antemortem diagnosis of posttraumatic stress disorder.
A combination of dextromethorphan and quinidine is an effective and well-tolerated treatment for pseudobulbar affect secondary to dementia, stroke, or traumatic brain injury, according to a study published June 9 in BMC Neurology. The study included 367 participants with this disorder. Participants in this open-label, multicenter, 90-day trial received dextromethorphan and quinidine twice daily. The mean Center for Neurologic Study-Lability Scale score improved from 20.4 at baseline to 12.8 at the 90-day final visit. Reduction in pseudobulbar affect episode count was 72.3% at the 90-day final visit, compared with baseline. Scores on Clinical Global Impression of Change and Patient Global Impression of Change indicated that 76.6% and 72.4% of participants, respectively, showed much or very much improvement in symptoms of pseudobulbar affect.
—Kimberly Williams
There is a strong, inverse association between midlife cardiorespiratory fitness and stroke risk in later life, independent of the baseline and antecedent burden of risk factors, according to a study published online ahead of print June 9 in Stroke. Researchers studied 19,815 individuals who received Medicare coverage from 1999 to 2009. Cardiorespiratory fitness estimated at baseline was analyzed as a continuous variable and according to age- and sex-specific quintiles. Associations between midlife cardiorespiratory fitness and stroke hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. The investigators observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife cardiorespiratory fitness was associated with a lower risk of stroke hospitalization.
Incident dementia early after intracerebral hemorrhage is strongly associated with hematoma size and location, according to a study published online ahead of print June 13 in JAMA Neurology. A longitudinal study enrolled patients with intracerebral hemorrhage from January 1, 2006, to December 31, 2013. In all, 738 participants ages 18 or older, without pre-intracerebral hemorrhage dementia, who presented to a tertiary care academic institution with primary intracerebral hemorrhage were included in the study. A total of 140 patients developed dementia within six months. Larger hematoma size and lobar location of intracerebral hemorrhage were associated with early post-intracerebral hemorrhage dementia, but not with delayed post-intracerebral hemorrhage dementia. Educational level, incident mood symptoms, and white matter disease were associated with delayed, but not early, post-intracerebral hemorrhage dementia.
The FDA is investigating the risk of serious burns and potential permanent scarring from the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch for migraine. The patch delivers a dose of medicine in a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Since the introduction of the patch, many patients have reported injury to the skin where the patch was worn. The reports include descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin. Patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact a health care professional. Teva Pharmaceuticals has suspended the sale, marketing, and distribution of the patch.
More than 90% of the global stroke burden is attributable to modifiable risk factors, including air pollution, and controlling behavioral and metabolic risk factors could avert more than 75% of the global stroke burden, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers used data on stroke-related disability-adjusted life-years, risk factors, and population-attributable fraction from the Global Burden of Disease Study 2013 to estimate the burden of stroke by age and sex in 188 countries. Approximately 74% of the global stroke burden was attributable to behavioral factors. Clusters of metabolic factors (72%) and environmental factors (33%) were the second and third largest contributors to disability-adjusted life-years, respectively. About 29% of the burden of stroke was attributed to air pollution.
Abnormally high fractional anisotropy (FA) on diffusion tensor imaging (DTI) is associated with better outcomes after mild traumatic brain injury (mTBI), according to a study published online ahead of print June 9 in the American Journal of Neuroradiology. DTI was performed on 39 subjects with mTBI within 16 days of injury and on 40 controls. In all, 26 subjects with mTBI returned for follow-up at one year. Among these subjects, high FA in the left frontal lobe and left temporal lobe was associated with better attention. High FA in the left and right cerebelli was associated with improved somatic postconcussion symptoms. High FA in the right thalamus was associated with improved emotional postconcussion symptoms. Abnormally high FA may be an imaging correlate of postinjury compensatory processes, said the investigators.
Among patients with multiple sclerosis (MS), obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function, attention, processing speed, and working memory, according to a study published online ahead of print May 3 in Sleep. Thirty-eight participants underwent MS-specific cognitive testing and in-laboratory overnight polysomnography. In adjusted linear regression models, the oxygen desaturation index and minimum oxygen saturation were significantly associated with performance on multiple Minimal Assessment of Cognitive Function in MS measures. Apnea severity measures accounted for between 11% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation and total sleep time also showed significant associations with a component of the California Verbal Learning Test-II, explaining 18% and 27% of the variance in performance, respectively.
The differences in stroke mortality between African Americans and Caucasians are largely related to differences in stroke incidence, according to a study published online ahead of print June 2 in Stroke. Researchers assessed the difference between African American and Caucasian stroke mortality for 29,681 participants in the Reasons for Geographic and Racial Differences in Stroke cohort. They found that African Americans are four times more likely to die of stroke at age 45 than Caucasians because stroke incidence is greater among African Americans. By age 85, however, the difference in stroke mortality is no longer present. More should be done to reduce the disparity in stroke mortality between African Americans and Caucasians, and interventions should focus on prevention of stroke among African Americans, according to the investigators.
A mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, according to a study published online ahead of print June 6 in Nature Genetics. Researchers first investigated a family with 15 members who had typical symptoms of Parkinson's disease. They used DNA samples to perform a genome-wide analysis on 65 of the family's members, including 13 with Parkinson's disease, to find a common mutation that could explain the prevalence of Parkinson's disease. The study authors identified TMEM230 as the gene with a disease-causing mutation and found that TMEM230 encodes a protein that extends across the membrane of tiny sacs inside synaptic vesicles. The research team also found mutations in TMEM230 in cases of Parkinson's disease in additional families in North America and China.
People with blast exposure have a pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and between gray and white matter, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers analyzed brain specimens from five military service members with chronic blast exposure, three with acute blast exposure, five with chronic impact traumatic brain injury, five with exposure to opiates, and three control cases with no known neurologic disorders. All five cases with chronic blast exposure showed prominent astroglial scarring involving the subpial glial plate, penetrating cortical blood vessels, gray-white matter junctions, and structures lining the ventricles. Cases of acute blast exposure showed early astroglial scarring in the same brain regions. Cases of chronic blast exposure had an antemortem diagnosis of posttraumatic stress disorder.
A combination of dextromethorphan and quinidine is an effective and well-tolerated treatment for pseudobulbar affect secondary to dementia, stroke, or traumatic brain injury, according to a study published June 9 in BMC Neurology. The study included 367 participants with this disorder. Participants in this open-label, multicenter, 90-day trial received dextromethorphan and quinidine twice daily. The mean Center for Neurologic Study-Lability Scale score improved from 20.4 at baseline to 12.8 at the 90-day final visit. Reduction in pseudobulbar affect episode count was 72.3% at the 90-day final visit, compared with baseline. Scores on Clinical Global Impression of Change and Patient Global Impression of Change indicated that 76.6% and 72.4% of participants, respectively, showed much or very much improvement in symptoms of pseudobulbar affect.
—Kimberly Williams
There is a strong, inverse association between midlife cardiorespiratory fitness and stroke risk in later life, independent of the baseline and antecedent burden of risk factors, according to a study published online ahead of print June 9 in Stroke. Researchers studied 19,815 individuals who received Medicare coverage from 1999 to 2009. Cardiorespiratory fitness estimated at baseline was analyzed as a continuous variable and according to age- and sex-specific quintiles. Associations between midlife cardiorespiratory fitness and stroke hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. The investigators observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife cardiorespiratory fitness was associated with a lower risk of stroke hospitalization.
Incident dementia early after intracerebral hemorrhage is strongly associated with hematoma size and location, according to a study published online ahead of print June 13 in JAMA Neurology. A longitudinal study enrolled patients with intracerebral hemorrhage from January 1, 2006, to December 31, 2013. In all, 738 participants ages 18 or older, without pre-intracerebral hemorrhage dementia, who presented to a tertiary care academic institution with primary intracerebral hemorrhage were included in the study. A total of 140 patients developed dementia within six months. Larger hematoma size and lobar location of intracerebral hemorrhage were associated with early post-intracerebral hemorrhage dementia, but not with delayed post-intracerebral hemorrhage dementia. Educational level, incident mood symptoms, and white matter disease were associated with delayed, but not early, post-intracerebral hemorrhage dementia.
The FDA is investigating the risk of serious burns and potential permanent scarring from the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch for migraine. The patch delivers a dose of medicine in a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Since the introduction of the patch, many patients have reported injury to the skin where the patch was worn. The reports include descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin. Patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact a health care professional. Teva Pharmaceuticals has suspended the sale, marketing, and distribution of the patch.
More than 90% of the global stroke burden is attributable to modifiable risk factors, including air pollution, and controlling behavioral and metabolic risk factors could avert more than 75% of the global stroke burden, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers used data on stroke-related disability-adjusted life-years, risk factors, and population-attributable fraction from the Global Burden of Disease Study 2013 to estimate the burden of stroke by age and sex in 188 countries. Approximately 74% of the global stroke burden was attributable to behavioral factors. Clusters of metabolic factors (72%) and environmental factors (33%) were the second and third largest contributors to disability-adjusted life-years, respectively. About 29% of the burden of stroke was attributed to air pollution.
Abnormally high fractional anisotropy (FA) on diffusion tensor imaging (DTI) is associated with better outcomes after mild traumatic brain injury (mTBI), according to a study published online ahead of print June 9 in the American Journal of Neuroradiology. DTI was performed on 39 subjects with mTBI within 16 days of injury and on 40 controls. In all, 26 subjects with mTBI returned for follow-up at one year. Among these subjects, high FA in the left frontal lobe and left temporal lobe was associated with better attention. High FA in the left and right cerebelli was associated with improved somatic postconcussion symptoms. High FA in the right thalamus was associated with improved emotional postconcussion symptoms. Abnormally high FA may be an imaging correlate of postinjury compensatory processes, said the investigators.
Among patients with multiple sclerosis (MS), obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function, attention, processing speed, and working memory, according to a study published online ahead of print May 3 in Sleep. Thirty-eight participants underwent MS-specific cognitive testing and in-laboratory overnight polysomnography. In adjusted linear regression models, the oxygen desaturation index and minimum oxygen saturation were significantly associated with performance on multiple Minimal Assessment of Cognitive Function in MS measures. Apnea severity measures accounted for between 11% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation and total sleep time also showed significant associations with a component of the California Verbal Learning Test-II, explaining 18% and 27% of the variance in performance, respectively.
The differences in stroke mortality between African Americans and Caucasians are largely related to differences in stroke incidence, according to a study published online ahead of print June 2 in Stroke. Researchers assessed the difference between African American and Caucasian stroke mortality for 29,681 participants in the Reasons for Geographic and Racial Differences in Stroke cohort. They found that African Americans are four times more likely to die of stroke at age 45 than Caucasians because stroke incidence is greater among African Americans. By age 85, however, the difference in stroke mortality is no longer present. More should be done to reduce the disparity in stroke mortality between African Americans and Caucasians, and interventions should focus on prevention of stroke among African Americans, according to the investigators.
A mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, according to a study published online ahead of print June 6 in Nature Genetics. Researchers first investigated a family with 15 members who had typical symptoms of Parkinson's disease. They used DNA samples to perform a genome-wide analysis on 65 of the family's members, including 13 with Parkinson's disease, to find a common mutation that could explain the prevalence of Parkinson's disease. The study authors identified TMEM230 as the gene with a disease-causing mutation and found that TMEM230 encodes a protein that extends across the membrane of tiny sacs inside synaptic vesicles. The research team also found mutations in TMEM230 in cases of Parkinson's disease in additional families in North America and China.
People with blast exposure have a pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and between gray and white matter, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers analyzed brain specimens from five military service members with chronic blast exposure, three with acute blast exposure, five with chronic impact traumatic brain injury, five with exposure to opiates, and three control cases with no known neurologic disorders. All five cases with chronic blast exposure showed prominent astroglial scarring involving the subpial glial plate, penetrating cortical blood vessels, gray-white matter junctions, and structures lining the ventricles. Cases of acute blast exposure showed early astroglial scarring in the same brain regions. Cases of chronic blast exposure had an antemortem diagnosis of posttraumatic stress disorder.
A combination of dextromethorphan and quinidine is an effective and well-tolerated treatment for pseudobulbar affect secondary to dementia, stroke, or traumatic brain injury, according to a study published June 9 in BMC Neurology. The study included 367 participants with this disorder. Participants in this open-label, multicenter, 90-day trial received dextromethorphan and quinidine twice daily. The mean Center for Neurologic Study-Lability Scale score improved from 20.4 at baseline to 12.8 at the 90-day final visit. Reduction in pseudobulbar affect episode count was 72.3% at the 90-day final visit, compared with baseline. Scores on Clinical Global Impression of Change and Patient Global Impression of Change indicated that 76.6% and 72.4% of participants, respectively, showed much or very much improvement in symptoms of pseudobulbar affect.
—Kimberly Williams