User login
CDC releases guidelines for pediatric mTBI
and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
A growing realization that mTBI can have persistent and significant deleterious effects has informed medical and public attitudes toward concussion in children, which now results in almost 1 million annual ED visits.
Progress at the laboratory bench has elucidated much of the neurometabolic cascade that occurs with the insult of mTBI, and has allowed researchers to document the path of brain healing after injury. Neuroimaging now can go beyond static images to trace neural networks and detect previously unseen and subtle functional deficits engendered by mTBI.
In particular, 21st century magnetic resonance imaging (MRI) has shown increased sensitivity over CT alone. In the TRACK-TBI study, over one in four patients whose CTs were read as normal had MRI findings consistent with trauma-induced pathology. Both multimodal MRI and serum biomarkers show promise, although more research regarding their utility is needed, particularly in the case of proteomic biomarkers.
Still, high-quality studies of pediatric mTBI are scant, and translation of burgeoning research into clinical practice is severely impeded by the numerous knowledge gaps that exist in the field.
Dr. Lumba-Brown and her colleagues have synthesized research that supports a neurobiopsychosocial model of mTBI in children that comes into play most prominently in the postacute phase, when non–injury-related factors such as demographics, socioeconomic status, and premorbid psychological conditions are strong mediators of the recovery trajectory.
With children as with adults, scant research guides the path forward for treatment and recovery from mTBI. For children, clinicians are still grappling with issues surrounding return to full participation in the academic and recreational activities of the school environment.
Data from two currently active studies should help light the way forward, however. The TRACK-TBI study, funded by the National Institutes of Health, will include almost 200 children among its 2,700 enrollees who have sustained all levels of TBI.
The Concussion Assessment, Research, and Education (CARE) Consortium is funded jointly by the National College Athletic Association and the Department of Defense. Between student athletes and military cadets, over 40,000 individuals are now part of the study.
The two studies’ testing modalities and methodologies align, offering the opportunity for a powerful pooled analysis that includes civilians, athletes, and those in the military.
Until then, these guidelines provide a way forward to an individualized approach to the best care for a child with mTBI.
Michael McCrea, PhD, is professor of neurology and neurosurgery, and director of brain injury research at the Medical College of Wisconsin, Milwaukee. Geoff Manley, MD, PhD, is professor of neurologic surgery at the University of California, San Francisco. Neither author reported conflicts of interest. These remarks were drawn from an editorial accompanying the guidelines and systematic review (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2846).
and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
and should base management and prognostication on clinical decision-making tools and symptom rating scales, according to new practice guidelines issued by a working group of the Centers for Disease Control and Prevention (JAMA Pediatrics. 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2853.
The guidelines were released simultaneously with a systematic review, conducted by the same authors, of the existing literature regarding pediatric mTBI (JAMA Pediatrics 2018 Sep 4. doi: 10.1001/jamapediatrics.2018.2847). As the evaluators sorted through the literature to find high-quality studies for this population, the funnel rapidly narrowed: From an initial pool of over 15,000 studies conducted between 1990 and 2015, findings from just 75 studies were eventually included in the systematic review.
The review’s findings formed the basis for the guidelines and allowed Angela Lumba-Brown, MD, a pediatric emergency medicine physician at Stanford (Calif.) University, and her coauthors to ascribe a level of confidence in the inference from study data for a given recommendation. Recommendations also are categorized by strength and accordingly indicate that clinicians “should” or “may” follow them. Exceptions are carved out for practices, such as the use of hypertonic 3% saline solution for acute headache in the ED, that should not be used outside research settings.
In the end, the guidelines cover 19 main topics, sorted into guidance regarding the diagnosis, prognosis, and management and treatment of mTBI in children.
Diagnosis
The recommendations regarding mTBI diagnosis center around determining which children are at risk for significant intracranial injury (ICI). The guidelines recommend, with moderate confidence, that clinicians usually should not obtain a head CT for children with mTBI. Validated clinical decision rules should be used for risk stratification to determine which children can safely avoid imaging and which children should be considered for head CT, wrote Dr. Lumba-Brown and her coauthors. Magnetic resonance imaging is not recommended for initial evaluation of mTBI, nor should skull radiographs be ordered in the absence of clinical suspicion for skull fracture.
From the systematic review, Dr. Lumba-Brown and her colleagues found that several risk factors taken together may mean that significant ICI is more likely. These include patient age younger than 2 years; any vomiting, loss of consciousness, or amnesia; a severe mechanism of injury, severe or worsening headache, or nonfrontal scalp hematoma; a Glasgow Coma Scale (GCS) score of less than 15; and clinical suspicion for skull fracture. Clinicians should give consideration to the risks of ionizing radiation to the head, and balance this against their assessment of risk for severe – and perhaps actionable – injury.
A validated symptom rating scale, used in an age-appropriate way, should be used as part of the evaluation of children with mTBI. For children aged 6 and older, the Graded Symptom Checklist is an appropriate tool within 2 days after injury, while the Post Concussion Symptom Scale as part of computerized neurocognitive testing can differentiate which high school athletes have mTBI when used within 4 days of injury, according to the guidelines, which also identify other validated symptom rating scales.
The guidelines authors recommend, with high confidence, that serum biomarkers should not be used outside of research settings in the diagnosis of mTBI in children at present.
Prognosis
Families should be counseled that symptoms mostly resolve within 1-3 months for up to 80% of children with mTBI, but families also should know that “each child’s recovery from mTBI is unique and will follow its own trajectory,” wrote Dr. Lumba-Brown and her coauthors, in a moderate-strength recommendation.
Some factors have been associated with slower recovery from mTBI, and either upon evaluation for mTBI or in routine sports examinations, families should be told about this potential if risk factors are present, said the guidelines, although the evidence supporting the associations is of “varying strength,” wrote Dr. Lumba-Brown and her coauthors. Children with previous mTBIs and those with a history of premorbid neurologic and psychiatric problems, learning problems, or family and social stress all may have delayed recovery. For children with ICI, lower cognitive ability also is associated with delayed recovery.
Demographic factors such as lower socioeconomic status and being of Hispanic ethnicity also may increase the risk for delayed mTBI recovery. Older children and adolescents may recover more slowly. Those with more severe initial presentation and more symptoms in the immediate post-mTBI phase also may have a slower recovery course, said Dr. Lumba-Brown and her coauthors.
A validated prediction rule can be used in the ED to gather information about these discrete risk factors to guide family counseling, according to the guidelines, which note that research has found that “an empirically derived set of risk factors predicted the risk of persistent post-concussion symptoms at 28 days” for children seen in the ED with mTBI.
During the recovery phase, a combination of tools should be used to track recovery from mTBI; these can include validated symptom scales, validated cognitive testing, reaction time measures, and, in adolescent athletes, balance testing. Using a combination of tools is a valuable strategy, the researchers wrote. “No single assessment tool is strongly predictive of outcome in children with mTBI,” they noted.
When prognosis is poor, or recovery is not proceeding as expected, clinicians should have a low threshold for initiating other interventions and referrals.
Management and treatment
Although the guideline authors acknowledged significant knowledge gaps in all areas of pediatric mTBI diagnosis and management, evidence is especially scant for best practices for treatment, rest, and return to play and school after a child sustains mTBI, said Dr. Lumba-Brown and her coauthors.
However, families should be given information about warning signs for serious head injury and how to monitor symptoms, as well as information about mTBI and the expected recovery course. Other forward-looking instructions should cover the importance of preventing new head injuries, managing the gradual return to normal cognitive and physical activities, and clear instructions regarding return to school and recreational activities. The guideline authors made a strong recommendation to provide this information, with high confidence in the data.
However, little strong evidence points the way to a clear set of criteria for when children are ready for school, play, and athletic participation. These decisions must be customized to the individual child, and decision making, particularly about return to school and academic activities, should be a collaborative affair, with schools, clinicians, and families all communicating to make sure the pace of return to normal life is keeping pace with the child’s recovery. “Because postconcussive symptoms resolve at different rates in different children after mTBI, individualization of return-to-school programming is necessary,” wrote Dr. Lumba-Brown and her coauthors.
The guideline authors cite evidence that “suggests that early rest (within the first 3 days) may be beneficial but that inactivity beyond this period for most children may worsen their self-reported symptoms.”
Psychosocial support may be beneficial for certain children, wrote the researchers, drawing on evidence showing that such support is beneficial in frank TBI, and is probably beneficial in mTBI.
Active rehabilitation as tolerated is recommended after an initial period of rest, with exertion kept to a level that does not exacerbate symptoms. Children should not participate in contact activities until symptoms are fully resolved.
A posttraumatic headache that is severe or worsens in the ED should prompt consideration of emergent neuroimaging, according to the guidelines. In the postacute phase, however, children can have nonopioid analgesia, although parents should know about such risks as rebound headache. When chronic headache follows a mTBI, the guidelines recommend that clinicians refer patients for a multidisciplinary evaluation that can assess the many factors – including analgesic overuse – that can be contributors.
Drawing on the larger body of adult TBI research, the authors recommend that insufficient or disordered sleep be addressed, because “the maintenance of appropriate sleep and the management of disrupted sleep may be a critical target of treatment for the child with mTBI.”
Children who suffer a mTBI may experience cognitive dysfunction as a direct result of injury to the brain or secondary to the effects of other symptoms such as sleep disruptions, headache pain, fatigue, or low tolerance of frustration. Clinicians may want to perform or refer their patients for a neuropsychological evaluation to determine what is causing the cognitive dysfunction, the authors said.
Dr. Lumba-Brown and her coauthors, who formed the CDC’s Pediatric Mild Traumatic Brain Injury Guideline Workgroup, also recommended that clinicians use the term “mild traumatic brain injury” to describe head injuries that cause confusion or disorientation, without loss of consciousness, or loss of consciousness of up to 30 minutes or less, or posttraumatic amnesia of less than 24 hours duration, and that are associated with a GCS of 13-15 by 30 minutes after injury or at the time of initial medical assessment. This practice, they said, may reduce the risk of misinterpretation by medical professionals and the public that can occur when the terms “mTBI,” “concussion,” and “minor head injury” all may refer to the same injury.
The CDC has developed a suite of materials to assist both health care providers and the public in guideline implementation. The agency also is using its HEADS UP campaign to publicize the guidelines and related materials, and plans ongoing evaluation of the guidelines and implementation materials.
Many study authors, including Dr. Lumba-Brown, had relationships with medical device or pharmaceutical companies. The systematic review and guideline development were funded by the CDC.
FROM JAMA PEDIATRICS
New and Noteworthy Information—September 2018
Intrathecal Baclofen Reduces Pain in Poststroke Spasticity
Intrathecal baclofen (ITB) therapy improves pain and quality of life in patients with poststroke spasticity, according to a study published August 14 in Stroke. Patients with poststroke spasticity in two or more extremities and an Ashworth Scale score of 3 or higher in two or more affected lower extremity muscle groups were randomized to ITB or conventional medical management. At six months, ITB effectively reduced Numeric Pain Rating Scale scores for actual and least spasticity-related pain and improved quality of life, compared with medical management. In addition, 73% of patients given ITB therapy reported satisfaction with spasticity reduction at month six, versus 48% of patients given medical management. The researchers found no statistically significant differences between groups in reduction of worst pain.
Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018 Aug 14 [Epub ahead of print].
FDA Approves Diacomit for Seizures Associated With Dravet Syndrome
The FDA has approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients age 2 and older who are taking clobazam. Diacomit will be available in 250-mg and 500-mg capsules and in fruit-flavored powder packets for oral suspension. In two studies of patients between ages 3 and 17 with Dravet syndrome, patients were randomized to Diacomit or placebo, along with their previous treatment with clobazam and valproate. In Study 1, 71% of patients in the Diacomit group were 50% responders versus 5% in the placebo group. In Study 2, 67% of patients treated with Diacomit were 50% responders versus 9.1% of controls. Diacomit is marketed by Biocodex, which is headquartered in Gentilly, France.
Retinal Thinning Is Associated With Dopaminergic Cell Loss
Retinal thinning is linked to the loss of brain cells in Parkinson’s disease, according to a study published online ahead of print August 15 in Neurology. Researchers examined 49 participants (average age, 69) who had been diagnosed with Parkinson’s disease an average of two years earlier, but who had not yet started medication. Participants were compared with 54 healthy controls who were matched for age. Participants underwent a complete eye exam and high-resolution eye scans. Patients with Parkinson’s disease had retinal layer thinning in the temporal and inferior 2.22-mm sectors. The thickness of these layers in the inferior 2.22-mm sector correlated negatively with Hoehn and Yahr stage. Retinal thinning was associated with dopaminergic loss in the left substantia nigra.
Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. 2018 Aug 15 [Epub ahead of print].
Contact Sports Linked to Vascular Risk Factors and Depression
Athletes with a history of playing professional contact sports have more vascular risk factors and higher depression scores, according to a study published online ahead of print August 3 in the Journal of Head Trauma Rehabilitation. This case–control study included 21 retired National Football League and National Hockey League players and 21 age-matched noncontact athlete controls. The investigators assessed participants for mild cognitive impairment (MCI) and measured depression using the Beck Depression Inventory-II (BDI). Eight contact sport athletes and three noncontact athletes met criteria for MCI. Contact sport athletes’ scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher BDI scores.
Baker JG, Leddy JJ, Hinds AL, et al. An exploratory study of mild cognitive impairment of retired professional contact sport athletes. J Head Trauma Rehabil. 2018 Aug 3 [Epub ahead of print].
Managing Vegetative and Minimally Conscious States
The American Academy of Neurology; the American Congress of Rehabilitative Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research have published a practice guideline on the diagnosis and ongoing medical and rehabilitative care of patients in a vegetative or minimally conscious state caused by brain injury. The guideline was published online ahead of print August 8 in Neurology. The authors based their recommendations on a systematic review of the evidence using a modified Delphi consensus process. Clinicians should advise families that for adults, a minimally conscious state and traumatic etiology are associated with more favorable outcomes, according to the guideline. Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults, but no tests improve prognostic accuracy in children, said the authors.
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Aug 8 [Epub ahead of print].
FDA Approves Onpattro
The FDA has approved Onpattro (patisiran) lipid complex injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The approval of Onpattro was based on results from a randomized, double-blind, placebo-controlled phase III study. Of 225 patients, 148 were randomized to Onpattro infusion once every three weeks for 18 months. The other participants were randomized to placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms, compared with participants receiving placebo infusions. Patients receiving Onpattro also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living. Alnylam Pharmaceuticals, which markets Onpattro, is headquartered in Cambridge, Massachusetts.
Ophthalmic Conditions May Indicate Increased Risk of Alzheimer’s Disease
People with recent diagnoses of glaucoma, established age-related macular degeneration, and recent and established diabetic retinopathy may have increased risk of Alzheimer’s disease, according to a study published online ahead of print August 2 in Alzheimer’s & Dementia. The investigators included 3,877 participants selected randomly from the Adult Changes in Thought study in their analysis. Participants were age 65 or older and did not have Alzheimer’s disease at the time of enrollment. During the five-year study, a committee of dementia experts diagnosed Alzheimer’s disease in 792 people. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40% to 50% greater risk of developing Alzheimer’s disease, compared with people without these eye conditions. Cataract diagnosis was not a risk factor for Alzheimer’s disease.
Lee CS, Larson EB, Gibbons LE, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2018 Aug 2 [Epub ahead of print].
Insulin Resistance in Nondiabetics With Parkinson’s Disease
Insulin resistance is prevalent in Parkinson’s disease and correlates with BMI, according to a study published in the August issue of the Journal of Parkinson’s Disease. The investigators included 154 nondiabetic patients with Parkinson’s disease in the study. Participants were tested for fasting insulin, fasting glucose, and hemoglobin A1c (HbA1c) and underwent a battery of clinical tests. Investigators recorded participants’ Parkinson’s disease medications, height, weight, and other demographic features. Ninety (58.4%) participants had abnormal insulin resistance. Insulin resistance was more prevalent in overweight and obese participants than in participants with a normal weight. BMI was the only significant predictor of insulin resistance. Insulin resistance did not correlate with cognition, functioning, or nonmotor symptoms.
Hogg E, Athreya K, Basile C, et al. High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Parkinsons Dis. 2018;8(2):259-265.
FDA Approves Galafold for Fabry Disease in Adults
The FDA has approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is available in a 123-mg capsule. The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. Patients treated with Galafold over six months had a greater reduction in globotriaosylceramide in blood vessels of the kidneys, compared with patients taking placebo. Investigators studied the safety of Galafold in four clinical trials. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation, urinary tract infection, nausea, and fever. Amicus Therapeutics, which markets the capsules, is headquartered in Cranbury, New Jersey.
Binge Drinking Increases Cardiovascular Risk in Men
Young adults who frequently binge drink are more likely to have higher blood pressure, higher cholesterol, and higher blood sugar at a younger age than nonbinge drinkers, according to a study published June 27 in the Journal of the American Heart Association. Researchers analyzed data from the US National Health and Nutrition Examination Survey for 4,710 adults from ages 18 to 45. After controlling for diet and physical activity, men who binge drank as many as 12 times per year, compared with nonbinge drinkers, had higher systolic blood pressure (121.8 mm Hg vs 117.5 mm Hg) and total cholesterol (215.5 mg/dL vs 207.8 mg/dL). Binge drinking did not affect systolic blood pressure or total cholesterol in women. The effects of binge drinking on glucose parameters in men and women varied.
Piano MR, Burke L, Kang M, Phillips SA. Effects of repeated binge drinking on blood pressure levels and other cardiovascular health metrics in young adults: National Health and Nutrition Examination Survey, 2011-2014. J Am Heart Assoc. 2018;7(13).
Brain SPECT Predicts Brain Aging and Psychiatric Disorders
Brain SPECT predicts chronologic age, and brain aging varies as a function of common psychiatric disorders, according to a study published online ahead of print August 3 in the Journal of Alzheimer’s Disease. A psychiatric cohort of 31,227 participants underwent brain SPECT at rest and during a concentration task for a total of 62,454 scans. Analysis of variance identified the mean age trends over the population’s age range (ie, nine months to 105 years). Researchers studied 128 brain regions to predict the chronologic age of each participant. Older age predicted from the scan, compared with actual chronologic age, was considered accelerated aging. Childhood, adolescence, and late life were associated with variations in perfusion. Alcohol use, cannabis use, anxiety, bipolar disorder, schizophrenia, and ADHD were associated with increased brain aging.
Amen DG, Egan S, Meysami S, et al. Patterns of regional cerebral blood flow as a function of age throughout the lifespan. J Alzheimers Dis. 2018 Aug 3 [Epub ahead of print].
Folic Acid May Prevent Language Delays Associated With AED Exposure
Folic acid use early in pregnancy may prevent language delay associated with in utero antiepileptic drug (AED) exposure, according to a study published online ahead of print August 1 in Neurology. The study included 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy. For children with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratios for language delay in AED-exposed children, compared with controls, were 3.9 at 18 months and 4.7 at 36 months. When mothers took folic acid, the corresponding odds ratios for language delay were 1.7 and 1.7, respectively. The effect of folic acid supplementation on language delay in AED-exposed children was significant only when supplementation began four weeks before pregnancy and continued until the end of the first trimester.
Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018 Aug 1 [Epub ahead of print].
—Kimberly Williams
Intrathecal Baclofen Reduces Pain in Poststroke Spasticity
Intrathecal baclofen (ITB) therapy improves pain and quality of life in patients with poststroke spasticity, according to a study published August 14 in Stroke. Patients with poststroke spasticity in two or more extremities and an Ashworth Scale score of 3 or higher in two or more affected lower extremity muscle groups were randomized to ITB or conventional medical management. At six months, ITB effectively reduced Numeric Pain Rating Scale scores for actual and least spasticity-related pain and improved quality of life, compared with medical management. In addition, 73% of patients given ITB therapy reported satisfaction with spasticity reduction at month six, versus 48% of patients given medical management. The researchers found no statistically significant differences between groups in reduction of worst pain.
Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018 Aug 14 [Epub ahead of print].
FDA Approves Diacomit for Seizures Associated With Dravet Syndrome
The FDA has approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients age 2 and older who are taking clobazam. Diacomit will be available in 250-mg and 500-mg capsules and in fruit-flavored powder packets for oral suspension. In two studies of patients between ages 3 and 17 with Dravet syndrome, patients were randomized to Diacomit or placebo, along with their previous treatment with clobazam and valproate. In Study 1, 71% of patients in the Diacomit group were 50% responders versus 5% in the placebo group. In Study 2, 67% of patients treated with Diacomit were 50% responders versus 9.1% of controls. Diacomit is marketed by Biocodex, which is headquartered in Gentilly, France.
Retinal Thinning Is Associated With Dopaminergic Cell Loss
Retinal thinning is linked to the loss of brain cells in Parkinson’s disease, according to a study published online ahead of print August 15 in Neurology. Researchers examined 49 participants (average age, 69) who had been diagnosed with Parkinson’s disease an average of two years earlier, but who had not yet started medication. Participants were compared with 54 healthy controls who were matched for age. Participants underwent a complete eye exam and high-resolution eye scans. Patients with Parkinson’s disease had retinal layer thinning in the temporal and inferior 2.22-mm sectors. The thickness of these layers in the inferior 2.22-mm sector correlated negatively with Hoehn and Yahr stage. Retinal thinning was associated with dopaminergic loss in the left substantia nigra.
Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. 2018 Aug 15 [Epub ahead of print].
Contact Sports Linked to Vascular Risk Factors and Depression
Athletes with a history of playing professional contact sports have more vascular risk factors and higher depression scores, according to a study published online ahead of print August 3 in the Journal of Head Trauma Rehabilitation. This case–control study included 21 retired National Football League and National Hockey League players and 21 age-matched noncontact athlete controls. The investigators assessed participants for mild cognitive impairment (MCI) and measured depression using the Beck Depression Inventory-II (BDI). Eight contact sport athletes and three noncontact athletes met criteria for MCI. Contact sport athletes’ scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher BDI scores.
Baker JG, Leddy JJ, Hinds AL, et al. An exploratory study of mild cognitive impairment of retired professional contact sport athletes. J Head Trauma Rehabil. 2018 Aug 3 [Epub ahead of print].
Managing Vegetative and Minimally Conscious States
The American Academy of Neurology; the American Congress of Rehabilitative Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research have published a practice guideline on the diagnosis and ongoing medical and rehabilitative care of patients in a vegetative or minimally conscious state caused by brain injury. The guideline was published online ahead of print August 8 in Neurology. The authors based their recommendations on a systematic review of the evidence using a modified Delphi consensus process. Clinicians should advise families that for adults, a minimally conscious state and traumatic etiology are associated with more favorable outcomes, according to the guideline. Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults, but no tests improve prognostic accuracy in children, said the authors.
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Aug 8 [Epub ahead of print].
FDA Approves Onpattro
The FDA has approved Onpattro (patisiran) lipid complex injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The approval of Onpattro was based on results from a randomized, double-blind, placebo-controlled phase III study. Of 225 patients, 148 were randomized to Onpattro infusion once every three weeks for 18 months. The other participants were randomized to placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms, compared with participants receiving placebo infusions. Patients receiving Onpattro also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living. Alnylam Pharmaceuticals, which markets Onpattro, is headquartered in Cambridge, Massachusetts.
Ophthalmic Conditions May Indicate Increased Risk of Alzheimer’s Disease
People with recent diagnoses of glaucoma, established age-related macular degeneration, and recent and established diabetic retinopathy may have increased risk of Alzheimer’s disease, according to a study published online ahead of print August 2 in Alzheimer’s & Dementia. The investigators included 3,877 participants selected randomly from the Adult Changes in Thought study in their analysis. Participants were age 65 or older and did not have Alzheimer’s disease at the time of enrollment. During the five-year study, a committee of dementia experts diagnosed Alzheimer’s disease in 792 people. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40% to 50% greater risk of developing Alzheimer’s disease, compared with people without these eye conditions. Cataract diagnosis was not a risk factor for Alzheimer’s disease.
Lee CS, Larson EB, Gibbons LE, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2018 Aug 2 [Epub ahead of print].
Insulin Resistance in Nondiabetics With Parkinson’s Disease
Insulin resistance is prevalent in Parkinson’s disease and correlates with BMI, according to a study published in the August issue of the Journal of Parkinson’s Disease. The investigators included 154 nondiabetic patients with Parkinson’s disease in the study. Participants were tested for fasting insulin, fasting glucose, and hemoglobin A1c (HbA1c) and underwent a battery of clinical tests. Investigators recorded participants’ Parkinson’s disease medications, height, weight, and other demographic features. Ninety (58.4%) participants had abnormal insulin resistance. Insulin resistance was more prevalent in overweight and obese participants than in participants with a normal weight. BMI was the only significant predictor of insulin resistance. Insulin resistance did not correlate with cognition, functioning, or nonmotor symptoms.
Hogg E, Athreya K, Basile C, et al. High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Parkinsons Dis. 2018;8(2):259-265.
FDA Approves Galafold for Fabry Disease in Adults
The FDA has approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is available in a 123-mg capsule. The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. Patients treated with Galafold over six months had a greater reduction in globotriaosylceramide in blood vessels of the kidneys, compared with patients taking placebo. Investigators studied the safety of Galafold in four clinical trials. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation, urinary tract infection, nausea, and fever. Amicus Therapeutics, which markets the capsules, is headquartered in Cranbury, New Jersey.
Binge Drinking Increases Cardiovascular Risk in Men
Young adults who frequently binge drink are more likely to have higher blood pressure, higher cholesterol, and higher blood sugar at a younger age than nonbinge drinkers, according to a study published June 27 in the Journal of the American Heart Association. Researchers analyzed data from the US National Health and Nutrition Examination Survey for 4,710 adults from ages 18 to 45. After controlling for diet and physical activity, men who binge drank as many as 12 times per year, compared with nonbinge drinkers, had higher systolic blood pressure (121.8 mm Hg vs 117.5 mm Hg) and total cholesterol (215.5 mg/dL vs 207.8 mg/dL). Binge drinking did not affect systolic blood pressure or total cholesterol in women. The effects of binge drinking on glucose parameters in men and women varied.
Piano MR, Burke L, Kang M, Phillips SA. Effects of repeated binge drinking on blood pressure levels and other cardiovascular health metrics in young adults: National Health and Nutrition Examination Survey, 2011-2014. J Am Heart Assoc. 2018;7(13).
Brain SPECT Predicts Brain Aging and Psychiatric Disorders
Brain SPECT predicts chronologic age, and brain aging varies as a function of common psychiatric disorders, according to a study published online ahead of print August 3 in the Journal of Alzheimer’s Disease. A psychiatric cohort of 31,227 participants underwent brain SPECT at rest and during a concentration task for a total of 62,454 scans. Analysis of variance identified the mean age trends over the population’s age range (ie, nine months to 105 years). Researchers studied 128 brain regions to predict the chronologic age of each participant. Older age predicted from the scan, compared with actual chronologic age, was considered accelerated aging. Childhood, adolescence, and late life were associated with variations in perfusion. Alcohol use, cannabis use, anxiety, bipolar disorder, schizophrenia, and ADHD were associated with increased brain aging.
Amen DG, Egan S, Meysami S, et al. Patterns of regional cerebral blood flow as a function of age throughout the lifespan. J Alzheimers Dis. 2018 Aug 3 [Epub ahead of print].
Folic Acid May Prevent Language Delays Associated With AED Exposure
Folic acid use early in pregnancy may prevent language delay associated with in utero antiepileptic drug (AED) exposure, according to a study published online ahead of print August 1 in Neurology. The study included 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy. For children with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratios for language delay in AED-exposed children, compared with controls, were 3.9 at 18 months and 4.7 at 36 months. When mothers took folic acid, the corresponding odds ratios for language delay were 1.7 and 1.7, respectively. The effect of folic acid supplementation on language delay in AED-exposed children was significant only when supplementation began four weeks before pregnancy and continued until the end of the first trimester.
Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018 Aug 1 [Epub ahead of print].
—Kimberly Williams
Intrathecal Baclofen Reduces Pain in Poststroke Spasticity
Intrathecal baclofen (ITB) therapy improves pain and quality of life in patients with poststroke spasticity, according to a study published August 14 in Stroke. Patients with poststroke spasticity in two or more extremities and an Ashworth Scale score of 3 or higher in two or more affected lower extremity muscle groups were randomized to ITB or conventional medical management. At six months, ITB effectively reduced Numeric Pain Rating Scale scores for actual and least spasticity-related pain and improved quality of life, compared with medical management. In addition, 73% of patients given ITB therapy reported satisfaction with spasticity reduction at month six, versus 48% of patients given medical management. The researchers found no statistically significant differences between groups in reduction of worst pain.
Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018 Aug 14 [Epub ahead of print].
FDA Approves Diacomit for Seizures Associated With Dravet Syndrome
The FDA has approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients age 2 and older who are taking clobazam. Diacomit will be available in 250-mg and 500-mg capsules and in fruit-flavored powder packets for oral suspension. In two studies of patients between ages 3 and 17 with Dravet syndrome, patients were randomized to Diacomit or placebo, along with their previous treatment with clobazam and valproate. In Study 1, 71% of patients in the Diacomit group were 50% responders versus 5% in the placebo group. In Study 2, 67% of patients treated with Diacomit were 50% responders versus 9.1% of controls. Diacomit is marketed by Biocodex, which is headquartered in Gentilly, France.
Retinal Thinning Is Associated With Dopaminergic Cell Loss
Retinal thinning is linked to the loss of brain cells in Parkinson’s disease, according to a study published online ahead of print August 15 in Neurology. Researchers examined 49 participants (average age, 69) who had been diagnosed with Parkinson’s disease an average of two years earlier, but who had not yet started medication. Participants were compared with 54 healthy controls who were matched for age. Participants underwent a complete eye exam and high-resolution eye scans. Patients with Parkinson’s disease had retinal layer thinning in the temporal and inferior 2.22-mm sectors. The thickness of these layers in the inferior 2.22-mm sector correlated negatively with Hoehn and Yahr stage. Retinal thinning was associated with dopaminergic loss in the left substantia nigra.
Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. 2018 Aug 15 [Epub ahead of print].
Contact Sports Linked to Vascular Risk Factors and Depression
Athletes with a history of playing professional contact sports have more vascular risk factors and higher depression scores, according to a study published online ahead of print August 3 in the Journal of Head Trauma Rehabilitation. This case–control study included 21 retired National Football League and National Hockey League players and 21 age-matched noncontact athlete controls. The investigators assessed participants for mild cognitive impairment (MCI) and measured depression using the Beck Depression Inventory-II (BDI). Eight contact sport athletes and three noncontact athletes met criteria for MCI. Contact sport athletes’ scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher BDI scores.
Baker JG, Leddy JJ, Hinds AL, et al. An exploratory study of mild cognitive impairment of retired professional contact sport athletes. J Head Trauma Rehabil. 2018 Aug 3 [Epub ahead of print].
Managing Vegetative and Minimally Conscious States
The American Academy of Neurology; the American Congress of Rehabilitative Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research have published a practice guideline on the diagnosis and ongoing medical and rehabilitative care of patients in a vegetative or minimally conscious state caused by brain injury. The guideline was published online ahead of print August 8 in Neurology. The authors based their recommendations on a systematic review of the evidence using a modified Delphi consensus process. Clinicians should advise families that for adults, a minimally conscious state and traumatic etiology are associated with more favorable outcomes, according to the guideline. Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults, but no tests improve prognostic accuracy in children, said the authors.
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Aug 8 [Epub ahead of print].
FDA Approves Onpattro
The FDA has approved Onpattro (patisiran) lipid complex injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The approval of Onpattro was based on results from a randomized, double-blind, placebo-controlled phase III study. Of 225 patients, 148 were randomized to Onpattro infusion once every three weeks for 18 months. The other participants were randomized to placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms, compared with participants receiving placebo infusions. Patients receiving Onpattro also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living. Alnylam Pharmaceuticals, which markets Onpattro, is headquartered in Cambridge, Massachusetts.
Ophthalmic Conditions May Indicate Increased Risk of Alzheimer’s Disease
People with recent diagnoses of glaucoma, established age-related macular degeneration, and recent and established diabetic retinopathy may have increased risk of Alzheimer’s disease, according to a study published online ahead of print August 2 in Alzheimer’s & Dementia. The investigators included 3,877 participants selected randomly from the Adult Changes in Thought study in their analysis. Participants were age 65 or older and did not have Alzheimer’s disease at the time of enrollment. During the five-year study, a committee of dementia experts diagnosed Alzheimer’s disease in 792 people. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40% to 50% greater risk of developing Alzheimer’s disease, compared with people without these eye conditions. Cataract diagnosis was not a risk factor for Alzheimer’s disease.
Lee CS, Larson EB, Gibbons LE, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2018 Aug 2 [Epub ahead of print].
Insulin Resistance in Nondiabetics With Parkinson’s Disease
Insulin resistance is prevalent in Parkinson’s disease and correlates with BMI, according to a study published in the August issue of the Journal of Parkinson’s Disease. The investigators included 154 nondiabetic patients with Parkinson’s disease in the study. Participants were tested for fasting insulin, fasting glucose, and hemoglobin A1c (HbA1c) and underwent a battery of clinical tests. Investigators recorded participants’ Parkinson’s disease medications, height, weight, and other demographic features. Ninety (58.4%) participants had abnormal insulin resistance. Insulin resistance was more prevalent in overweight and obese participants than in participants with a normal weight. BMI was the only significant predictor of insulin resistance. Insulin resistance did not correlate with cognition, functioning, or nonmotor symptoms.
Hogg E, Athreya K, Basile C, et al. High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Parkinsons Dis. 2018;8(2):259-265.
FDA Approves Galafold for Fabry Disease in Adults
The FDA has approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is available in a 123-mg capsule. The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. Patients treated with Galafold over six months had a greater reduction in globotriaosylceramide in blood vessels of the kidneys, compared with patients taking placebo. Investigators studied the safety of Galafold in four clinical trials. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation, urinary tract infection, nausea, and fever. Amicus Therapeutics, which markets the capsules, is headquartered in Cranbury, New Jersey.
Binge Drinking Increases Cardiovascular Risk in Men
Young adults who frequently binge drink are more likely to have higher blood pressure, higher cholesterol, and higher blood sugar at a younger age than nonbinge drinkers, according to a study published June 27 in the Journal of the American Heart Association. Researchers analyzed data from the US National Health and Nutrition Examination Survey for 4,710 adults from ages 18 to 45. After controlling for diet and physical activity, men who binge drank as many as 12 times per year, compared with nonbinge drinkers, had higher systolic blood pressure (121.8 mm Hg vs 117.5 mm Hg) and total cholesterol (215.5 mg/dL vs 207.8 mg/dL). Binge drinking did not affect systolic blood pressure or total cholesterol in women. The effects of binge drinking on glucose parameters in men and women varied.
Piano MR, Burke L, Kang M, Phillips SA. Effects of repeated binge drinking on blood pressure levels and other cardiovascular health metrics in young adults: National Health and Nutrition Examination Survey, 2011-2014. J Am Heart Assoc. 2018;7(13).
Brain SPECT Predicts Brain Aging and Psychiatric Disorders
Brain SPECT predicts chronologic age, and brain aging varies as a function of common psychiatric disorders, according to a study published online ahead of print August 3 in the Journal of Alzheimer’s Disease. A psychiatric cohort of 31,227 participants underwent brain SPECT at rest and during a concentration task for a total of 62,454 scans. Analysis of variance identified the mean age trends over the population’s age range (ie, nine months to 105 years). Researchers studied 128 brain regions to predict the chronologic age of each participant. Older age predicted from the scan, compared with actual chronologic age, was considered accelerated aging. Childhood, adolescence, and late life were associated with variations in perfusion. Alcohol use, cannabis use, anxiety, bipolar disorder, schizophrenia, and ADHD were associated with increased brain aging.
Amen DG, Egan S, Meysami S, et al. Patterns of regional cerebral blood flow as a function of age throughout the lifespan. J Alzheimers Dis. 2018 Aug 3 [Epub ahead of print].
Folic Acid May Prevent Language Delays Associated With AED Exposure
Folic acid use early in pregnancy may prevent language delay associated with in utero antiepileptic drug (AED) exposure, according to a study published online ahead of print August 1 in Neurology. The study included 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy. For children with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratios for language delay in AED-exposed children, compared with controls, were 3.9 at 18 months and 4.7 at 36 months. When mothers took folic acid, the corresponding odds ratios for language delay were 1.7 and 1.7, respectively. The effect of folic acid supplementation on language delay in AED-exposed children was significant only when supplementation began four weeks before pregnancy and continued until the end of the first trimester.
Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018 Aug 1 [Epub ahead of print].
—Kimberly Williams
High autonomic dysfunction distinguishes persistent posttraumatic headache
SAN FRANCISCO – Symptoms of autonomic dysfunction are significantly greater in patients with persistent posttraumatic headache than in migraine, raising the welcome possibility that this characteristic might serve to reliably differentiate the two disorders, Levi Howard, MD, said at the annual meeting of the American Headache Society.
“Interestingly enough, in looking at other studies evaluating dysautonomia, the [autonomic dysfunction scores] in our persistent posttraumatic headache group were on a par with scores previously reported for patients with diseases such as small-fiber polyneuropathy and postural orthostatic tachycardia syndrome,” observed Dr. Howard, an active duty military physician assigned to obtain neurology training at the Mayo Clinic Arizona in Phoenix.
“This brings up two questions: Do autonomic symptoms contribute to accurate classification of persistent posttraumatic headache versus migraine? And if we treat this autonomic dysfunction, does the headache also improve? In our clinical observation, this appears to be the case,” he continued.
Right now, posttraumatic headache (PTH) is defined on the basis of its temporal relationship to head injury. At this time, PTH has no defining clinical characteristics, although most often it has a phenotype that meets diagnostic criteria for migraine.
However, Dr. Howard and his coinvestigators have observed anecdotally in clinical practice that persistent PTH – defined as PTH lasting longer than 3 months – is often accompanied by orthostatic intolerance. This observation, coupled with reports in multiple prior studies that dysautonomia is common in patients with mild traumatic brain injury (TBI) and postconcussion syndrome, prompted Dr. Howard and his coworkers to conduct a cross-sectional cohort study. It included 56 patients with persistent PTH due to mild TBI, 30 patients with migraine, and 36 healthy controls. Most of the persistent PTH group were military veterans with mild TBI due to blast injuries.
All subjects were assessed for autonomic dysfunction using the well-validated COMPASS-31 questionnaire. This instrument assesses six domains of autonomic function: orthostatic intolerance, bladder, gastrointestinal, vasomotor, secretomotor, and pupillomotor.
Scores in each of the six domains were numerically higher in the persistent PTH group, with the differences achieving statistical significance in the orthostatic intolerance and bladder domains.
Of note, the migraine group had a greater headache burden, with a mean 23-year headache history, compared with 10.56 years in the persistent PTH group. The migraine patients also averaged 21.1 headache days per month, versus 16.2 in the persistent PTH group. Yet the investigators found no strong association between autonomic dysfunction and headache burden as reflected in headache duration or headache days per month.
The study was funded by the Department of Defense. Dr. Howard reported having no financial conflicts of interest.
SOURCE: Howard L et al. AHS 2018, Abstract FHM03.
SAN FRANCISCO – Symptoms of autonomic dysfunction are significantly greater in patients with persistent posttraumatic headache than in migraine, raising the welcome possibility that this characteristic might serve to reliably differentiate the two disorders, Levi Howard, MD, said at the annual meeting of the American Headache Society.
“Interestingly enough, in looking at other studies evaluating dysautonomia, the [autonomic dysfunction scores] in our persistent posttraumatic headache group were on a par with scores previously reported for patients with diseases such as small-fiber polyneuropathy and postural orthostatic tachycardia syndrome,” observed Dr. Howard, an active duty military physician assigned to obtain neurology training at the Mayo Clinic Arizona in Phoenix.
“This brings up two questions: Do autonomic symptoms contribute to accurate classification of persistent posttraumatic headache versus migraine? And if we treat this autonomic dysfunction, does the headache also improve? In our clinical observation, this appears to be the case,” he continued.
Right now, posttraumatic headache (PTH) is defined on the basis of its temporal relationship to head injury. At this time, PTH has no defining clinical characteristics, although most often it has a phenotype that meets diagnostic criteria for migraine.
However, Dr. Howard and his coinvestigators have observed anecdotally in clinical practice that persistent PTH – defined as PTH lasting longer than 3 months – is often accompanied by orthostatic intolerance. This observation, coupled with reports in multiple prior studies that dysautonomia is common in patients with mild traumatic brain injury (TBI) and postconcussion syndrome, prompted Dr. Howard and his coworkers to conduct a cross-sectional cohort study. It included 56 patients with persistent PTH due to mild TBI, 30 patients with migraine, and 36 healthy controls. Most of the persistent PTH group were military veterans with mild TBI due to blast injuries.
All subjects were assessed for autonomic dysfunction using the well-validated COMPASS-31 questionnaire. This instrument assesses six domains of autonomic function: orthostatic intolerance, bladder, gastrointestinal, vasomotor, secretomotor, and pupillomotor.
Scores in each of the six domains were numerically higher in the persistent PTH group, with the differences achieving statistical significance in the orthostatic intolerance and bladder domains.
Of note, the migraine group had a greater headache burden, with a mean 23-year headache history, compared with 10.56 years in the persistent PTH group. The migraine patients also averaged 21.1 headache days per month, versus 16.2 in the persistent PTH group. Yet the investigators found no strong association between autonomic dysfunction and headache burden as reflected in headache duration or headache days per month.
The study was funded by the Department of Defense. Dr. Howard reported having no financial conflicts of interest.
SOURCE: Howard L et al. AHS 2018, Abstract FHM03.
SAN FRANCISCO – Symptoms of autonomic dysfunction are significantly greater in patients with persistent posttraumatic headache than in migraine, raising the welcome possibility that this characteristic might serve to reliably differentiate the two disorders, Levi Howard, MD, said at the annual meeting of the American Headache Society.
“Interestingly enough, in looking at other studies evaluating dysautonomia, the [autonomic dysfunction scores] in our persistent posttraumatic headache group were on a par with scores previously reported for patients with diseases such as small-fiber polyneuropathy and postural orthostatic tachycardia syndrome,” observed Dr. Howard, an active duty military physician assigned to obtain neurology training at the Mayo Clinic Arizona in Phoenix.
“This brings up two questions: Do autonomic symptoms contribute to accurate classification of persistent posttraumatic headache versus migraine? And if we treat this autonomic dysfunction, does the headache also improve? In our clinical observation, this appears to be the case,” he continued.
Right now, posttraumatic headache (PTH) is defined on the basis of its temporal relationship to head injury. At this time, PTH has no defining clinical characteristics, although most often it has a phenotype that meets diagnostic criteria for migraine.
However, Dr. Howard and his coinvestigators have observed anecdotally in clinical practice that persistent PTH – defined as PTH lasting longer than 3 months – is often accompanied by orthostatic intolerance. This observation, coupled with reports in multiple prior studies that dysautonomia is common in patients with mild traumatic brain injury (TBI) and postconcussion syndrome, prompted Dr. Howard and his coworkers to conduct a cross-sectional cohort study. It included 56 patients with persistent PTH due to mild TBI, 30 patients with migraine, and 36 healthy controls. Most of the persistent PTH group were military veterans with mild TBI due to blast injuries.
All subjects were assessed for autonomic dysfunction using the well-validated COMPASS-31 questionnaire. This instrument assesses six domains of autonomic function: orthostatic intolerance, bladder, gastrointestinal, vasomotor, secretomotor, and pupillomotor.
Scores in each of the six domains were numerically higher in the persistent PTH group, with the differences achieving statistical significance in the orthostatic intolerance and bladder domains.
Of note, the migraine group had a greater headache burden, with a mean 23-year headache history, compared with 10.56 years in the persistent PTH group. The migraine patients also averaged 21.1 headache days per month, versus 16.2 in the persistent PTH group. Yet the investigators found no strong association between autonomic dysfunction and headache burden as reflected in headache duration or headache days per month.
The study was funded by the Department of Defense. Dr. Howard reported having no financial conflicts of interest.
SOURCE: Howard L et al. AHS 2018, Abstract FHM03.
REPORTING FROM THE AHS ANNUAL MEETING
Key clinical point: New evidence that patients with persistent posttraumatic headache have high levels of autonomic dysfunction could open the door to novel treatments.
Major finding: Scores on the COMPASS-31 questionnaire, a measure of autonomic dysfunction, averaged 37.22 in patients with persistent posttraumatic headache, indicative of significantly greater impairment than the 27.15 in migraine patients and 11.67 in healthy controls.
Study details: This cross-sectional cohort study included 56 patients with persistent posttraumatic headache, 30 with migraine, and 36 healthy controls.
Disclosures: The study was sponsored by the Department of Defense and presented by an active duty military physician.
Source: Howard L et al. AHS 2018, Abstract FHM03
AAN and others update practice guidelines for prolonged disorders of consciousness
An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.
“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”
The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”
In the guidelines, the committee made the following recommendations:
- Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
- Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
- Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
- Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
- Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
- In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
- Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).
In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.
In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”
Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.
“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.
Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.
The American Academy of Neurology Guideline on Disorders of Consciousness should be lauded for its focus on rehabilitation of this population, but it misses an opportunity to address “the broader ethical implications for patient care and institutional reform,” Joseph J. Fins, MD, and James L. Bernat, MD, wrote in a related editorial.
The authors commended the guidelines for recommending a change in reclassifying permanent vegetative state (VS) as “chronic vegetative state” but noted that the designation may be too broad, considering it encompasses patients who were misdiagnosed, patients who improved after treatment, patients with cognitive-motor disassociation, and patients who have undergone late improvements to achieve some level of consciousness. Defining these patients to clarify their prognoses will be important in determining which patients with VS are able to make late improvements, they said.
“While this redesignation seems warranted on clinical and epidemiologic grounds, it will create repercussions beyond the house of medicine given that the right to refuse life-sustaining treatment initially was predicated upon the irreversibility of the VS,” the authors wrote.
Dr. Fins and Dr. Bernat also acknowledged the seemingly contradictory recommendation of systematizing the care of patients with prolonged disorders of consciousness given that the infrastructure to provide this care is unavailable and unaffordable for many patients.
“Now that the Guideline has stipulated benchmarks for practice, practitioners and institutions need to meet this standard of care, and payers must ensure that these services are covered. It is acceptable neither to plead ignorance of these conditions nor to assert that nothing can be done to help ameliorate the burden of severe brain injury,” the authors wrote. “Given the utility of greater specialized care in diagnosis, treatment, and rehabilitation, and the equal importance of avoiding medical complications that can impede recovery, our society must provide the infrastructure and resources needed to offer quality care.”
Dr. Fins is with the division of medical ethics and the Consortium for the Advanced Study of Brain Injury at Cornell University, New York. Dr. Bernat is with the departments of neurology and medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. They receive royalties from several published books that are relevant to the content of the guidelines.
The American Academy of Neurology Guideline on Disorders of Consciousness should be lauded for its focus on rehabilitation of this population, but it misses an opportunity to address “the broader ethical implications for patient care and institutional reform,” Joseph J. Fins, MD, and James L. Bernat, MD, wrote in a related editorial.
The authors commended the guidelines for recommending a change in reclassifying permanent vegetative state (VS) as “chronic vegetative state” but noted that the designation may be too broad, considering it encompasses patients who were misdiagnosed, patients who improved after treatment, patients with cognitive-motor disassociation, and patients who have undergone late improvements to achieve some level of consciousness. Defining these patients to clarify their prognoses will be important in determining which patients with VS are able to make late improvements, they said.
“While this redesignation seems warranted on clinical and epidemiologic grounds, it will create repercussions beyond the house of medicine given that the right to refuse life-sustaining treatment initially was predicated upon the irreversibility of the VS,” the authors wrote.
Dr. Fins and Dr. Bernat also acknowledged the seemingly contradictory recommendation of systematizing the care of patients with prolonged disorders of consciousness given that the infrastructure to provide this care is unavailable and unaffordable for many patients.
“Now that the Guideline has stipulated benchmarks for practice, practitioners and institutions need to meet this standard of care, and payers must ensure that these services are covered. It is acceptable neither to plead ignorance of these conditions nor to assert that nothing can be done to help ameliorate the burden of severe brain injury,” the authors wrote. “Given the utility of greater specialized care in diagnosis, treatment, and rehabilitation, and the equal importance of avoiding medical complications that can impede recovery, our society must provide the infrastructure and resources needed to offer quality care.”
Dr. Fins is with the division of medical ethics and the Consortium for the Advanced Study of Brain Injury at Cornell University, New York. Dr. Bernat is with the departments of neurology and medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. They receive royalties from several published books that are relevant to the content of the guidelines.
The American Academy of Neurology Guideline on Disorders of Consciousness should be lauded for its focus on rehabilitation of this population, but it misses an opportunity to address “the broader ethical implications for patient care and institutional reform,” Joseph J. Fins, MD, and James L. Bernat, MD, wrote in a related editorial.
The authors commended the guidelines for recommending a change in reclassifying permanent vegetative state (VS) as “chronic vegetative state” but noted that the designation may be too broad, considering it encompasses patients who were misdiagnosed, patients who improved after treatment, patients with cognitive-motor disassociation, and patients who have undergone late improvements to achieve some level of consciousness. Defining these patients to clarify their prognoses will be important in determining which patients with VS are able to make late improvements, they said.
“While this redesignation seems warranted on clinical and epidemiologic grounds, it will create repercussions beyond the house of medicine given that the right to refuse life-sustaining treatment initially was predicated upon the irreversibility of the VS,” the authors wrote.
Dr. Fins and Dr. Bernat also acknowledged the seemingly contradictory recommendation of systematizing the care of patients with prolonged disorders of consciousness given that the infrastructure to provide this care is unavailable and unaffordable for many patients.
“Now that the Guideline has stipulated benchmarks for practice, practitioners and institutions need to meet this standard of care, and payers must ensure that these services are covered. It is acceptable neither to plead ignorance of these conditions nor to assert that nothing can be done to help ameliorate the burden of severe brain injury,” the authors wrote. “Given the utility of greater specialized care in diagnosis, treatment, and rehabilitation, and the equal importance of avoiding medical complications that can impede recovery, our society must provide the infrastructure and resources needed to offer quality care.”
Dr. Fins is with the division of medical ethics and the Consortium for the Advanced Study of Brain Injury at Cornell University, New York. Dr. Bernat is with the departments of neurology and medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. They receive royalties from several published books that are relevant to the content of the guidelines.
An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.
“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”
The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”
In the guidelines, the committee made the following recommendations:
- Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
- Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
- Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
- Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
- Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
- In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
- Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).
In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.
In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”
Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.
“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.
Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.
An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.
“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”
The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”
In the guidelines, the committee made the following recommendations:
- Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
- Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
- Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
- Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
- Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
- In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
- Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).
In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.
In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”
Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.
“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.
Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.
FROM NEUROLOGY
TBI linked to increased suicide risk
Traumatic brain injury might be associated with an increased risk of suicide, according to results published Aug. 14 in JAMA.
In a retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide, patients with medical contact for traumatic brain injury (TBI) had increased suicide risk, compared with the general population (adjusted incidence rate ratio [IRR] = 1.90; 95% confidence interval, 1.83-1.97).
Patients were aged 10 years or older, and follow-up was conducted from Jan. 1, 1980, until date of death, emigration from Denmark, or Dec. 31, 2014, whichever came first. Data were obtained from national registries, including the Danish Civil Registration System, the Database for Integrated Labour Market Research, the National Hospital Register, the Psychiatric Central Research Register, and the Cause of Death Register. Associations between the separate registries were possible because of unique identification numbers assigned to every resident of Denmark, wrote Trine Madsen, PhD, of the Danish Research Institute of Suicide Prevention at the Mental Health Centre Copenhagen, Capital Region of Denmark, and her coauthors.
TBI was recorded in the National Patient Register and was categorized into three types of injury: mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injury with evidence of structural brain injury). The number of medical contacts for distinct TBI events, accumulated number of days in hospital treatment, age at first TBI, and time since last medical contact for TBI also were assessed.
Data on psychiatric illness and nonfatal self-harm were obtained from the Psychiatric Central Research Register, because of their association with suicide. Data for deaths by suicide were obtained from the Cause of Death Register. Demographic data collected from other registries included sex, age, marital status, cohabitation status, education, and socioeconomic status. IRRs were calculated using adjusted Poisson regression models.
Of 7,418,391 residents of Denmark included in the follow-up period from 1980 to 2014; 567,823 had a TBI diagnosis. Dr. Madsen and her coauthors also found that 423,502 patients (5.7%) were diagnosed with mild TBI, 24,221 (0.3%) with skull fracture, and 120,100 (1.6%) with severe TBI. A total of 34,529 died by suicide.
Of those who died by suicide, 3,536 (10.2%) had a previous TBI diagnosis (2,701 with mild TBI, 174 with skull fracture, and 661 with severe TBI). The absolute rate of suicide in individuals with hospital contact for TBI was 40.6 per 100,000 person-years (95% CI, 39.2-41.9), compared with 19.9 per 100,000 person-years (95% CI, 19.7-20.1) in those with no hospital contact for TBI.
The fully adjusted analysis showed an IRR of 1.90 (95% CI, 1.83-1.97), as well as an increased risk of suicide by TBI severity. The absolute rate for mild TBI was 38.6 per 100,000 person-years (95% CI, 37.1-40.0) with an IRR of 1.81 (95% CI, 1.74-1.88); 42.4 per 100,000 person-years for skull fracture (95% CI, 36.1-48.7) with an IRR of 2.01 (95% CI, 1.73-2.34, P less than .001), and 50.8 per 100,000 person-years for severe TBI (95% CI, 46.9-54.6) with an IRR of 2.38 (95% CI, 2.20-2.58, P less than .001), compared with individuals with no TBI, the authors wrote.
Patients with a first medical contact between 16 and 20 years of age had the highest suicide risk, compared with individuals with no TBI (IRR, 3.01; 95% CI, 2.74-3.30). In addition, individuals who were diagnosed with a psychiatric illness after TBI had a higher risk of suicide than that of those with TBI only (IRR, 4.90; 95% CI, 4.55-5.29; P less than .001), as did those who had engaged in self-harm after TBI (IRR, 7.54; 95% CI, 6.91-8.22; P less than .001). Patients diagnosed with a psychological illness before their TBI had a higher risk of suicide than did those with TBI only (IRR, 2.32; 95% CI, 2.10-2.55; P less than .001), as did those who had engaged self-harm before TBI (IRR, 2.85; 95% CI, 2.53-3.19; P less than .001), the authors noted.
Dr. Madsen and her coauthors cited several limitations. One is that information was not available on which treatment patients with TBIs received. This information “would have been useful to estimate whether different treatment regimens or subsequent follow-up would have reduced the suicide risk,” they wrote.
“Traumatic brain injury is a major public health problem that has many serious consequences, including suicide,” Dr. Madsen and her colleagues wrote. Since falls and traffic accidents account for the largest share of TBIs, helmet use may be a useful protective measure, particularly for injuries related to bicycling and falls that occur at work, the researchers wrote.
“The high prevalence of TBI globally emphasizes the importance for preventing TBI in order to ameliorate its sequelae, such as increased suicide risk,” they concluded.
The study was funded in part by the Mental Health Services Capital Region Denmark and the Lundbeck Foundation. No other disclosures were reported.
SOURCE: Madsen T et al. JAMA. 2018 Aug 14;320(6):580-8.
The results of this study “add to a growing body of evidence pointing to traumatic brain injury (TBI) as an important risk factor for suicide,” Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, wrote in an editorial published with the study (JAMA. 2018 Aug 14;320:[6]:554-6).
The study also stimulates key questions for research, Dr. Goldstein and Dr. Diaz-Arrastia wrote. “How exactly do TBIs increase suicide risk?” they wrote. “What are the substrates and processes that causally link TBI, a highly heterogeneous condition, to a singular catastrophic outcome? The answers are undoubtedly multifactorial and complex.”
Nevertheless, they wrote, the study provides important insights into the “underappreciated relationship” between TBI and suicide, including evidence of a clinical “triad”: TBI history, recent injury, and more numerous post-injury medical contacts for TBI – that may serve as “red flags” for increased suicide risk. “Notably, the results of this study indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”
Dr. Goldstein is affiliated with the department of psychiatry at Boston University and reported no conflicts of interest. Dr. Diaz-Arrastia is affiliated with the department of neurology at the University of Pennsylvania, Philadelphia, and also reported no conflicts of interest.
The results of this study “add to a growing body of evidence pointing to traumatic brain injury (TBI) as an important risk factor for suicide,” Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, wrote in an editorial published with the study (JAMA. 2018 Aug 14;320:[6]:554-6).
The study also stimulates key questions for research, Dr. Goldstein and Dr. Diaz-Arrastia wrote. “How exactly do TBIs increase suicide risk?” they wrote. “What are the substrates and processes that causally link TBI, a highly heterogeneous condition, to a singular catastrophic outcome? The answers are undoubtedly multifactorial and complex.”
Nevertheless, they wrote, the study provides important insights into the “underappreciated relationship” between TBI and suicide, including evidence of a clinical “triad”: TBI history, recent injury, and more numerous post-injury medical contacts for TBI – that may serve as “red flags” for increased suicide risk. “Notably, the results of this study indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”
Dr. Goldstein is affiliated with the department of psychiatry at Boston University and reported no conflicts of interest. Dr. Diaz-Arrastia is affiliated with the department of neurology at the University of Pennsylvania, Philadelphia, and also reported no conflicts of interest.
The results of this study “add to a growing body of evidence pointing to traumatic brain injury (TBI) as an important risk factor for suicide,” Lee Goldstein, MD, PhD, and Ramon Diaz-Arrastia, MD, PhD, wrote in an editorial published with the study (JAMA. 2018 Aug 14;320:[6]:554-6).
The study also stimulates key questions for research, Dr. Goldstein and Dr. Diaz-Arrastia wrote. “How exactly do TBIs increase suicide risk?” they wrote. “What are the substrates and processes that causally link TBI, a highly heterogeneous condition, to a singular catastrophic outcome? The answers are undoubtedly multifactorial and complex.”
Nevertheless, they wrote, the study provides important insights into the “underappreciated relationship” between TBI and suicide, including evidence of a clinical “triad”: TBI history, recent injury, and more numerous post-injury medical contacts for TBI – that may serve as “red flags” for increased suicide risk. “Notably, the results of this study indicate that increased suicide risk is relevant across all TBI severity levels, including the far more common mild injuries. Clinicians, health care professionals, and mental health practitioners must take notice of this important information.”
Dr. Goldstein is affiliated with the department of psychiatry at Boston University and reported no conflicts of interest. Dr. Diaz-Arrastia is affiliated with the department of neurology at the University of Pennsylvania, Philadelphia, and also reported no conflicts of interest.
Traumatic brain injury might be associated with an increased risk of suicide, according to results published Aug. 14 in JAMA.
In a retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide, patients with medical contact for traumatic brain injury (TBI) had increased suicide risk, compared with the general population (adjusted incidence rate ratio [IRR] = 1.90; 95% confidence interval, 1.83-1.97).
Patients were aged 10 years or older, and follow-up was conducted from Jan. 1, 1980, until date of death, emigration from Denmark, or Dec. 31, 2014, whichever came first. Data were obtained from national registries, including the Danish Civil Registration System, the Database for Integrated Labour Market Research, the National Hospital Register, the Psychiatric Central Research Register, and the Cause of Death Register. Associations between the separate registries were possible because of unique identification numbers assigned to every resident of Denmark, wrote Trine Madsen, PhD, of the Danish Research Institute of Suicide Prevention at the Mental Health Centre Copenhagen, Capital Region of Denmark, and her coauthors.
TBI was recorded in the National Patient Register and was categorized into three types of injury: mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injury with evidence of structural brain injury). The number of medical contacts for distinct TBI events, accumulated number of days in hospital treatment, age at first TBI, and time since last medical contact for TBI also were assessed.
Data on psychiatric illness and nonfatal self-harm were obtained from the Psychiatric Central Research Register, because of their association with suicide. Data for deaths by suicide were obtained from the Cause of Death Register. Demographic data collected from other registries included sex, age, marital status, cohabitation status, education, and socioeconomic status. IRRs were calculated using adjusted Poisson regression models.
Of 7,418,391 residents of Denmark included in the follow-up period from 1980 to 2014; 567,823 had a TBI diagnosis. Dr. Madsen and her coauthors also found that 423,502 patients (5.7%) were diagnosed with mild TBI, 24,221 (0.3%) with skull fracture, and 120,100 (1.6%) with severe TBI. A total of 34,529 died by suicide.
Of those who died by suicide, 3,536 (10.2%) had a previous TBI diagnosis (2,701 with mild TBI, 174 with skull fracture, and 661 with severe TBI). The absolute rate of suicide in individuals with hospital contact for TBI was 40.6 per 100,000 person-years (95% CI, 39.2-41.9), compared with 19.9 per 100,000 person-years (95% CI, 19.7-20.1) in those with no hospital contact for TBI.
The fully adjusted analysis showed an IRR of 1.90 (95% CI, 1.83-1.97), as well as an increased risk of suicide by TBI severity. The absolute rate for mild TBI was 38.6 per 100,000 person-years (95% CI, 37.1-40.0) with an IRR of 1.81 (95% CI, 1.74-1.88); 42.4 per 100,000 person-years for skull fracture (95% CI, 36.1-48.7) with an IRR of 2.01 (95% CI, 1.73-2.34, P less than .001), and 50.8 per 100,000 person-years for severe TBI (95% CI, 46.9-54.6) with an IRR of 2.38 (95% CI, 2.20-2.58, P less than .001), compared with individuals with no TBI, the authors wrote.
Patients with a first medical contact between 16 and 20 years of age had the highest suicide risk, compared with individuals with no TBI (IRR, 3.01; 95% CI, 2.74-3.30). In addition, individuals who were diagnosed with a psychiatric illness after TBI had a higher risk of suicide than that of those with TBI only (IRR, 4.90; 95% CI, 4.55-5.29; P less than .001), as did those who had engaged in self-harm after TBI (IRR, 7.54; 95% CI, 6.91-8.22; P less than .001). Patients diagnosed with a psychological illness before their TBI had a higher risk of suicide than did those with TBI only (IRR, 2.32; 95% CI, 2.10-2.55; P less than .001), as did those who had engaged self-harm before TBI (IRR, 2.85; 95% CI, 2.53-3.19; P less than .001), the authors noted.
Dr. Madsen and her coauthors cited several limitations. One is that information was not available on which treatment patients with TBIs received. This information “would have been useful to estimate whether different treatment regimens or subsequent follow-up would have reduced the suicide risk,” they wrote.
“Traumatic brain injury is a major public health problem that has many serious consequences, including suicide,” Dr. Madsen and her colleagues wrote. Since falls and traffic accidents account for the largest share of TBIs, helmet use may be a useful protective measure, particularly for injuries related to bicycling and falls that occur at work, the researchers wrote.
“The high prevalence of TBI globally emphasizes the importance for preventing TBI in order to ameliorate its sequelae, such as increased suicide risk,” they concluded.
The study was funded in part by the Mental Health Services Capital Region Denmark and the Lundbeck Foundation. No other disclosures were reported.
SOURCE: Madsen T et al. JAMA. 2018 Aug 14;320(6):580-8.
Traumatic brain injury might be associated with an increased risk of suicide, according to results published Aug. 14 in JAMA.
In a retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide, patients with medical contact for traumatic brain injury (TBI) had increased suicide risk, compared with the general population (adjusted incidence rate ratio [IRR] = 1.90; 95% confidence interval, 1.83-1.97).
Patients were aged 10 years or older, and follow-up was conducted from Jan. 1, 1980, until date of death, emigration from Denmark, or Dec. 31, 2014, whichever came first. Data were obtained from national registries, including the Danish Civil Registration System, the Database for Integrated Labour Market Research, the National Hospital Register, the Psychiatric Central Research Register, and the Cause of Death Register. Associations between the separate registries were possible because of unique identification numbers assigned to every resident of Denmark, wrote Trine Madsen, PhD, of the Danish Research Institute of Suicide Prevention at the Mental Health Centre Copenhagen, Capital Region of Denmark, and her coauthors.
TBI was recorded in the National Patient Register and was categorized into three types of injury: mild TBI (concussion), skull fracture without documented TBI, and severe TBI (head injury with evidence of structural brain injury). The number of medical contacts for distinct TBI events, accumulated number of days in hospital treatment, age at first TBI, and time since last medical contact for TBI also were assessed.
Data on psychiatric illness and nonfatal self-harm were obtained from the Psychiatric Central Research Register, because of their association with suicide. Data for deaths by suicide were obtained from the Cause of Death Register. Demographic data collected from other registries included sex, age, marital status, cohabitation status, education, and socioeconomic status. IRRs were calculated using adjusted Poisson regression models.
Of 7,418,391 residents of Denmark included in the follow-up period from 1980 to 2014; 567,823 had a TBI diagnosis. Dr. Madsen and her coauthors also found that 423,502 patients (5.7%) were diagnosed with mild TBI, 24,221 (0.3%) with skull fracture, and 120,100 (1.6%) with severe TBI. A total of 34,529 died by suicide.
Of those who died by suicide, 3,536 (10.2%) had a previous TBI diagnosis (2,701 with mild TBI, 174 with skull fracture, and 661 with severe TBI). The absolute rate of suicide in individuals with hospital contact for TBI was 40.6 per 100,000 person-years (95% CI, 39.2-41.9), compared with 19.9 per 100,000 person-years (95% CI, 19.7-20.1) in those with no hospital contact for TBI.
The fully adjusted analysis showed an IRR of 1.90 (95% CI, 1.83-1.97), as well as an increased risk of suicide by TBI severity. The absolute rate for mild TBI was 38.6 per 100,000 person-years (95% CI, 37.1-40.0) with an IRR of 1.81 (95% CI, 1.74-1.88); 42.4 per 100,000 person-years for skull fracture (95% CI, 36.1-48.7) with an IRR of 2.01 (95% CI, 1.73-2.34, P less than .001), and 50.8 per 100,000 person-years for severe TBI (95% CI, 46.9-54.6) with an IRR of 2.38 (95% CI, 2.20-2.58, P less than .001), compared with individuals with no TBI, the authors wrote.
Patients with a first medical contact between 16 and 20 years of age had the highest suicide risk, compared with individuals with no TBI (IRR, 3.01; 95% CI, 2.74-3.30). In addition, individuals who were diagnosed with a psychiatric illness after TBI had a higher risk of suicide than that of those with TBI only (IRR, 4.90; 95% CI, 4.55-5.29; P less than .001), as did those who had engaged in self-harm after TBI (IRR, 7.54; 95% CI, 6.91-8.22; P less than .001). Patients diagnosed with a psychological illness before their TBI had a higher risk of suicide than did those with TBI only (IRR, 2.32; 95% CI, 2.10-2.55; P less than .001), as did those who had engaged self-harm before TBI (IRR, 2.85; 95% CI, 2.53-3.19; P less than .001), the authors noted.
Dr. Madsen and her coauthors cited several limitations. One is that information was not available on which treatment patients with TBIs received. This information “would have been useful to estimate whether different treatment regimens or subsequent follow-up would have reduced the suicide risk,” they wrote.
“Traumatic brain injury is a major public health problem that has many serious consequences, including suicide,” Dr. Madsen and her colleagues wrote. Since falls and traffic accidents account for the largest share of TBIs, helmet use may be a useful protective measure, particularly for injuries related to bicycling and falls that occur at work, the researchers wrote.
“The high prevalence of TBI globally emphasizes the importance for preventing TBI in order to ameliorate its sequelae, such as increased suicide risk,” they concluded.
The study was funded in part by the Mental Health Services Capital Region Denmark and the Lundbeck Foundation. No other disclosures were reported.
SOURCE: Madsen T et al. JAMA. 2018 Aug 14;320(6):580-8.
FROM JAMA
Key clinical point: Helmet use might be a useful protective measure against TBI, particularly for injuries related to bicycling and falls that occur at work.
Major finding: Patients with medical contact for TBI had increased suicide risk, compared with the general population (adjusted incidence rate ratio =1.90; 95% confidence interval, 1.83-1.97).
Study details: A retrospective cohort study of 7,418,391 Danish individuals, including 34,529 who died by suicide between 1980 and 2014.
Disclosures: The study was funded in part by the Mental Health Services Capital Region Denmark and the Lundbeck Foundation. No other disclosures were reported.
Source: Madsen T et al. JAMA. 2018 Aug 14;320:(6):580-8.
New and Noteworthy Information—August 2018
Practice Effects May Influence MCI Detection
Failing to account for practice effects may lead to underdiagnosis of mild cognitive impairment (MCI), according to a study published May 14 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. In an approximately six-year follow-up of the Vietnam Era Twin Study of Aging, researchers retested the cognitive function of 995 late-middle-aged men. In addition, the researchers tested 170 age-matched study replacements for the first time. The investigators used group differences to calculate practice effects after controlling for attrition effects and generated MCI diagnoses from practice-adjusted scores. There were significant practice effects on most cognitive domains, even though participants’ uncorrected scores may have declined. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%.
Elman JA, Jak AJ, Panizzon MS, et al. Underdiagnosis of mild cognitive impairment: a consequence of ignoring practice effects. Alzheimers Dement (Amst). 2018;10:372-381.
Brain Iron Levels Predict Disability in Patients With MS
Iron levels in the brains of patients with multiple sclerosis (MS) measured using quantitative susceptibility mapping (QSM) may help identify people at a higher risk of physical disability, according to a study published online ahead of print July 17 in Radiology. In this prospective study, 600 participants with MS and 250 age- and sex-matched healthy controls were imaged with 3.0-T MRI. The researchers assessed QSM and MRI volumetric differences between study groups and associations with clinical outcomes using analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex. Compared with controls, participants with MS had lower thalamic susceptibility and higher susceptibility of basal ganglia. Lower thalamic susceptibility was associated with longer disease duration, greater disability, and secondary-progressive disease course.
Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Jul 17 [Epub ahead of print].
Concussion and ADHD May Increase Depression and Anxiety
Athletes with attention deficit hyperactivity disorder (ADHD) may be at greater risk of persistent anxiety and depression after a concussion, compared with athletes without ADHD, according to a study presented at the American Academy of Neurology’s Sports Concussion Conference. The study included 979 NCAA Division I college athletes. Researchers gathered information on ADHD diagnosis and history of concussion, and athletes completed questionnaires measuring anxiety and depression symptoms before the start of their sporting seasons. The investigators divided athletes into four groups—those with ADHD who had had a concussion, those with ADHD who had not had a concussion, those without ADHD who had had a concussion, and those without a history of concussion or ADHD. Athletes with ADHD and concussion had significantly higher anxiety and depression scores, compared with the other groups.
Late-Life Blood Pressure Is Associated With Brain Lesions
Higher average late-life systolic blood pressure and diastolic blood pressure are associated with an increasing number of brain infarcts, including gross and microinfarcts, according to a study published online ahead of print July 11 in Neurology. In addition, faster decline in systolic blood pressure increases the likelihood of an infarct. This clinical-pathologic study included data from 1,288 people who participated in prospective, community-based cohort studies of aging with similar designs and data collection. Blood pressure measurements were obtained annually. Participants were followed for an average of eight years, and the average age at death was 89. The mean standardized person-specific systolic blood pressure was 134 mm Hg and diastolic blood pressure was 71 mm Hg. Alzheimer’s disease pathology analyses found that systolic blood pressure was associated with the number of tangles but not plaques or other pathology.
Arvanitakis Z, Capuano AW, Lamar M, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018 Jul 11 [Epub ahead of print].
Is t-PA Beneficial for Minor Stroke?
Among patients with mild acute ischemic stroke, treatment with alteplase does not increase the likelihood of favorable functional outcome at 90 days, compared with treatment with aspirin, according to a study published July 10 in JAMA. The PRISMS trial, a phase IIIb, double-blind, double-placebo, randomized clinical trial, compared alteplase with aspirin for the treatment of emergent stroke. The study enrolled patients with NIH Stroke Scale scores of 0 to 5 and deficits that were not clearly disabling. Eligible patients were able to receive treatment within three hours of onset. Participants were randomized to receive IV alteplase (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin (325 mg) with IV placebo (n = 157). At 90 days, 78.2% of patients in the alteplase group and 81.5% of patients in the aspirin group had a favorable outcome (ie, a modified Rankin Scale score of 0 or 1). The trial originally was designed to enroll 948 patients but was ended early because of slow enrollment. The early study termination precludes definitive conclusions, the investigators said.
Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018 Jul 10;320(2):156-166.
FDA Approves Xeomin for Adults With Sialorrhea
The FDA has approved the supplemental Biologics License Application for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea in adult patients. The approval was based on a phase III, randomized, double-blind, placebo-controlled, multicenter trial that included 184 patients. The coprimary end points of change in unstimulated salivary flow rate and Global Impression of Change Scale at week four as compared with baseline significantly improved for participants administered 100 U incobotulinumtoxinA versus placebo. The overall frequency of adverse events was similar between placebo and treatment groups with no new or unexpected adverse events reported. Participants in the study received placebo, incobotulinumtoxinA 75 U, or incobotulinumtoxinA 100 U. Merz North America, which markets Xeomin, is headquartered in Raleigh, North Carolina.
Does Exposure to Organic Solvents Heighten the Risk of MS?
People who are exposed to organic solvents and carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at greater risk of the disease than people who have only the exposure to solvents or the MS risk genes, according to a study published online ahead of print July 3 in Neurology. Using a Swedish population-based case–control study of 2,042 incident cases of MS and 2,947 controls, investigators compared the occurrence of MS in participants with different genotypes, smoking habits, and exposures to organic solvents such as paint and varnish. A potential interaction between exposure to organic solvents and MS risk human leukocyte antigen genes was evaluated by calculating the attributable proportion due to interaction. The MS genes and exposure to solvents combined were responsible for an estimated 60% of the risk of developing MS.
Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: interaction with MS risk HLA genes. Neurology. 2018 Jul 3 [Epub ahead of print].
Epidiolex Approved for the Treatment of Seizures
The FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It also is the first FDA approval of a drug for the treatment of patients with Dravet syndrome. The drug’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Taken with other medications, cannabidiol reduced the frequency of seizures, compared with placebo. Epidiolex must be dispensed with a patient medication guide that describes the drug’s uses and risks. GW Pharmaceuticals, located in the United Kingdom, markets Epidiolex.
FDA Approves Nuplazid Capsule Formulation and 10-mg Tablet
The FDA approved a new capsule dose formulation and tablet strength of Nuplazid (pimavanserin), a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. The 34-mg capsule formulation provides the recommended once daily dose in one capsule, versus the current administration of two 17-mg tablets. The 10-mg tablet provides a lower dosage strength for patients who are concomitantly receiving strong cytochrome 3A4 inhibitors, which can inhibit the metabolism of Nuplazid. The drug is a nondopaminergic, selective serotonin inverse agonist preferentially targeting 5-HT2A receptors. Acadia Pharmaceuticals, which markets the therapy, is headquartered in San Diego.
Mild Sleep Problems May Elevate Blood Pressure in Women
Mild sleep problems such as trouble falling asleep are associated with increased blood pressure and vascular inflammation in women, according to a study published June 9 in the Journal of the American Heart Association. Researchers examined blood pressure and sleep habits in 323 women in the ongoing American Heart Association Go Red for Women Strategically Focused Research Network. Investigators assessed participant’s sleep quality, obstructive sleep apnea risk, and insomnia severity. In a subset of women, sleep duration was assessed using actigraphy, and endothelial inflammation was assessed directly in harvested endothelial cells. Systolic blood pressure was associated with poor sleep quality. Poor sleep quality, insomnia, and longer sleep onset latency were associated with endothelial inflammation.
Aggarwal B, Makarem N, Shah R, et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12):e008590.
DBS May Slow Tremor Progression in Early Parkinson’s Disease
Deep brain stimulation (DBS) in the early stage of Parkinson’s disease may slow tremor progression, according to a study published online ahead of print June 29 in Neurology. The prospective pilot trial enrolled patients with Parkinson’s disease who were ages 50 to 75, had been treated with Parkinson’s disease medications for six months to four years, and had no history of dyskinesia or other motor fluctuations. Participants were randomized to receive optimal drug therapy (ODT) or DBS and ODT. At baseline and six, 12, 18, and 24 months, all patients stopped all Parkinson’s disease therapy for one week. Unified Parkinson’s Disease Rating Scale-III scores were compared between the ODT and DBS and ODT groups (n = 28). Rest tremor slopes from baseline to 24 months favored DBS plus ODT off and on therapy, compared with ODT alone.
Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jun 29 [Epub ahead of print].
—Kimberly Williams
Practice Effects May Influence MCI Detection
Failing to account for practice effects may lead to underdiagnosis of mild cognitive impairment (MCI), according to a study published May 14 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. In an approximately six-year follow-up of the Vietnam Era Twin Study of Aging, researchers retested the cognitive function of 995 late-middle-aged men. In addition, the researchers tested 170 age-matched study replacements for the first time. The investigators used group differences to calculate practice effects after controlling for attrition effects and generated MCI diagnoses from practice-adjusted scores. There were significant practice effects on most cognitive domains, even though participants’ uncorrected scores may have declined. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%.
Elman JA, Jak AJ, Panizzon MS, et al. Underdiagnosis of mild cognitive impairment: a consequence of ignoring practice effects. Alzheimers Dement (Amst). 2018;10:372-381.
Brain Iron Levels Predict Disability in Patients With MS
Iron levels in the brains of patients with multiple sclerosis (MS) measured using quantitative susceptibility mapping (QSM) may help identify people at a higher risk of physical disability, according to a study published online ahead of print July 17 in Radiology. In this prospective study, 600 participants with MS and 250 age- and sex-matched healthy controls were imaged with 3.0-T MRI. The researchers assessed QSM and MRI volumetric differences between study groups and associations with clinical outcomes using analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex. Compared with controls, participants with MS had lower thalamic susceptibility and higher susceptibility of basal ganglia. Lower thalamic susceptibility was associated with longer disease duration, greater disability, and secondary-progressive disease course.
Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Jul 17 [Epub ahead of print].
Concussion and ADHD May Increase Depression and Anxiety
Athletes with attention deficit hyperactivity disorder (ADHD) may be at greater risk of persistent anxiety and depression after a concussion, compared with athletes without ADHD, according to a study presented at the American Academy of Neurology’s Sports Concussion Conference. The study included 979 NCAA Division I college athletes. Researchers gathered information on ADHD diagnosis and history of concussion, and athletes completed questionnaires measuring anxiety and depression symptoms before the start of their sporting seasons. The investigators divided athletes into four groups—those with ADHD who had had a concussion, those with ADHD who had not had a concussion, those without ADHD who had had a concussion, and those without a history of concussion or ADHD. Athletes with ADHD and concussion had significantly higher anxiety and depression scores, compared with the other groups.
Late-Life Blood Pressure Is Associated With Brain Lesions
Higher average late-life systolic blood pressure and diastolic blood pressure are associated with an increasing number of brain infarcts, including gross and microinfarcts, according to a study published online ahead of print July 11 in Neurology. In addition, faster decline in systolic blood pressure increases the likelihood of an infarct. This clinical-pathologic study included data from 1,288 people who participated in prospective, community-based cohort studies of aging with similar designs and data collection. Blood pressure measurements were obtained annually. Participants were followed for an average of eight years, and the average age at death was 89. The mean standardized person-specific systolic blood pressure was 134 mm Hg and diastolic blood pressure was 71 mm Hg. Alzheimer’s disease pathology analyses found that systolic blood pressure was associated with the number of tangles but not plaques or other pathology.
Arvanitakis Z, Capuano AW, Lamar M, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018 Jul 11 [Epub ahead of print].
Is t-PA Beneficial for Minor Stroke?
Among patients with mild acute ischemic stroke, treatment with alteplase does not increase the likelihood of favorable functional outcome at 90 days, compared with treatment with aspirin, according to a study published July 10 in JAMA. The PRISMS trial, a phase IIIb, double-blind, double-placebo, randomized clinical trial, compared alteplase with aspirin for the treatment of emergent stroke. The study enrolled patients with NIH Stroke Scale scores of 0 to 5 and deficits that were not clearly disabling. Eligible patients were able to receive treatment within three hours of onset. Participants were randomized to receive IV alteplase (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin (325 mg) with IV placebo (n = 157). At 90 days, 78.2% of patients in the alteplase group and 81.5% of patients in the aspirin group had a favorable outcome (ie, a modified Rankin Scale score of 0 or 1). The trial originally was designed to enroll 948 patients but was ended early because of slow enrollment. The early study termination precludes definitive conclusions, the investigators said.
Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018 Jul 10;320(2):156-166.
FDA Approves Xeomin for Adults With Sialorrhea
The FDA has approved the supplemental Biologics License Application for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea in adult patients. The approval was based on a phase III, randomized, double-blind, placebo-controlled, multicenter trial that included 184 patients. The coprimary end points of change in unstimulated salivary flow rate and Global Impression of Change Scale at week four as compared with baseline significantly improved for participants administered 100 U incobotulinumtoxinA versus placebo. The overall frequency of adverse events was similar between placebo and treatment groups with no new or unexpected adverse events reported. Participants in the study received placebo, incobotulinumtoxinA 75 U, or incobotulinumtoxinA 100 U. Merz North America, which markets Xeomin, is headquartered in Raleigh, North Carolina.
Does Exposure to Organic Solvents Heighten the Risk of MS?
People who are exposed to organic solvents and carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at greater risk of the disease than people who have only the exposure to solvents or the MS risk genes, according to a study published online ahead of print July 3 in Neurology. Using a Swedish population-based case–control study of 2,042 incident cases of MS and 2,947 controls, investigators compared the occurrence of MS in participants with different genotypes, smoking habits, and exposures to organic solvents such as paint and varnish. A potential interaction between exposure to organic solvents and MS risk human leukocyte antigen genes was evaluated by calculating the attributable proportion due to interaction. The MS genes and exposure to solvents combined were responsible for an estimated 60% of the risk of developing MS.
Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: interaction with MS risk HLA genes. Neurology. 2018 Jul 3 [Epub ahead of print].
Epidiolex Approved for the Treatment of Seizures
The FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It also is the first FDA approval of a drug for the treatment of patients with Dravet syndrome. The drug’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Taken with other medications, cannabidiol reduced the frequency of seizures, compared with placebo. Epidiolex must be dispensed with a patient medication guide that describes the drug’s uses and risks. GW Pharmaceuticals, located in the United Kingdom, markets Epidiolex.
FDA Approves Nuplazid Capsule Formulation and 10-mg Tablet
The FDA approved a new capsule dose formulation and tablet strength of Nuplazid (pimavanserin), a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. The 34-mg capsule formulation provides the recommended once daily dose in one capsule, versus the current administration of two 17-mg tablets. The 10-mg tablet provides a lower dosage strength for patients who are concomitantly receiving strong cytochrome 3A4 inhibitors, which can inhibit the metabolism of Nuplazid. The drug is a nondopaminergic, selective serotonin inverse agonist preferentially targeting 5-HT2A receptors. Acadia Pharmaceuticals, which markets the therapy, is headquartered in San Diego.
Mild Sleep Problems May Elevate Blood Pressure in Women
Mild sleep problems such as trouble falling asleep are associated with increased blood pressure and vascular inflammation in women, according to a study published June 9 in the Journal of the American Heart Association. Researchers examined blood pressure and sleep habits in 323 women in the ongoing American Heart Association Go Red for Women Strategically Focused Research Network. Investigators assessed participant’s sleep quality, obstructive sleep apnea risk, and insomnia severity. In a subset of women, sleep duration was assessed using actigraphy, and endothelial inflammation was assessed directly in harvested endothelial cells. Systolic blood pressure was associated with poor sleep quality. Poor sleep quality, insomnia, and longer sleep onset latency were associated with endothelial inflammation.
Aggarwal B, Makarem N, Shah R, et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12):e008590.
DBS May Slow Tremor Progression in Early Parkinson’s Disease
Deep brain stimulation (DBS) in the early stage of Parkinson’s disease may slow tremor progression, according to a study published online ahead of print June 29 in Neurology. The prospective pilot trial enrolled patients with Parkinson’s disease who were ages 50 to 75, had been treated with Parkinson’s disease medications for six months to four years, and had no history of dyskinesia or other motor fluctuations. Participants were randomized to receive optimal drug therapy (ODT) or DBS and ODT. At baseline and six, 12, 18, and 24 months, all patients stopped all Parkinson’s disease therapy for one week. Unified Parkinson’s Disease Rating Scale-III scores were compared between the ODT and DBS and ODT groups (n = 28). Rest tremor slopes from baseline to 24 months favored DBS plus ODT off and on therapy, compared with ODT alone.
Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jun 29 [Epub ahead of print].
—Kimberly Williams
Practice Effects May Influence MCI Detection
Failing to account for practice effects may lead to underdiagnosis of mild cognitive impairment (MCI), according to a study published May 14 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. In an approximately six-year follow-up of the Vietnam Era Twin Study of Aging, researchers retested the cognitive function of 995 late-middle-aged men. In addition, the researchers tested 170 age-matched study replacements for the first time. The investigators used group differences to calculate practice effects after controlling for attrition effects and generated MCI diagnoses from practice-adjusted scores. There were significant practice effects on most cognitive domains, even though participants’ uncorrected scores may have declined. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%.
Elman JA, Jak AJ, Panizzon MS, et al. Underdiagnosis of mild cognitive impairment: a consequence of ignoring practice effects. Alzheimers Dement (Amst). 2018;10:372-381.
Brain Iron Levels Predict Disability in Patients With MS
Iron levels in the brains of patients with multiple sclerosis (MS) measured using quantitative susceptibility mapping (QSM) may help identify people at a higher risk of physical disability, according to a study published online ahead of print July 17 in Radiology. In this prospective study, 600 participants with MS and 250 age- and sex-matched healthy controls were imaged with 3.0-T MRI. The researchers assessed QSM and MRI volumetric differences between study groups and associations with clinical outcomes using analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex. Compared with controls, participants with MS had lower thalamic susceptibility and higher susceptibility of basal ganglia. Lower thalamic susceptibility was associated with longer disease duration, greater disability, and secondary-progressive disease course.
Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Jul 17 [Epub ahead of print].
Concussion and ADHD May Increase Depression and Anxiety
Athletes with attention deficit hyperactivity disorder (ADHD) may be at greater risk of persistent anxiety and depression after a concussion, compared with athletes without ADHD, according to a study presented at the American Academy of Neurology’s Sports Concussion Conference. The study included 979 NCAA Division I college athletes. Researchers gathered information on ADHD diagnosis and history of concussion, and athletes completed questionnaires measuring anxiety and depression symptoms before the start of their sporting seasons. The investigators divided athletes into four groups—those with ADHD who had had a concussion, those with ADHD who had not had a concussion, those without ADHD who had had a concussion, and those without a history of concussion or ADHD. Athletes with ADHD and concussion had significantly higher anxiety and depression scores, compared with the other groups.
Late-Life Blood Pressure Is Associated With Brain Lesions
Higher average late-life systolic blood pressure and diastolic blood pressure are associated with an increasing number of brain infarcts, including gross and microinfarcts, according to a study published online ahead of print July 11 in Neurology. In addition, faster decline in systolic blood pressure increases the likelihood of an infarct. This clinical-pathologic study included data from 1,288 people who participated in prospective, community-based cohort studies of aging with similar designs and data collection. Blood pressure measurements were obtained annually. Participants were followed for an average of eight years, and the average age at death was 89. The mean standardized person-specific systolic blood pressure was 134 mm Hg and diastolic blood pressure was 71 mm Hg. Alzheimer’s disease pathology analyses found that systolic blood pressure was associated with the number of tangles but not plaques or other pathology.
Arvanitakis Z, Capuano AW, Lamar M, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018 Jul 11 [Epub ahead of print].
Is t-PA Beneficial for Minor Stroke?
Among patients with mild acute ischemic stroke, treatment with alteplase does not increase the likelihood of favorable functional outcome at 90 days, compared with treatment with aspirin, according to a study published July 10 in JAMA. The PRISMS trial, a phase IIIb, double-blind, double-placebo, randomized clinical trial, compared alteplase with aspirin for the treatment of emergent stroke. The study enrolled patients with NIH Stroke Scale scores of 0 to 5 and deficits that were not clearly disabling. Eligible patients were able to receive treatment within three hours of onset. Participants were randomized to receive IV alteplase (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin (325 mg) with IV placebo (n = 157). At 90 days, 78.2% of patients in the alteplase group and 81.5% of patients in the aspirin group had a favorable outcome (ie, a modified Rankin Scale score of 0 or 1). The trial originally was designed to enroll 948 patients but was ended early because of slow enrollment. The early study termination precludes definitive conclusions, the investigators said.
Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018 Jul 10;320(2):156-166.
FDA Approves Xeomin for Adults With Sialorrhea
The FDA has approved the supplemental Biologics License Application for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea in adult patients. The approval was based on a phase III, randomized, double-blind, placebo-controlled, multicenter trial that included 184 patients. The coprimary end points of change in unstimulated salivary flow rate and Global Impression of Change Scale at week four as compared with baseline significantly improved for participants administered 100 U incobotulinumtoxinA versus placebo. The overall frequency of adverse events was similar between placebo and treatment groups with no new or unexpected adverse events reported. Participants in the study received placebo, incobotulinumtoxinA 75 U, or incobotulinumtoxinA 100 U. Merz North America, which markets Xeomin, is headquartered in Raleigh, North Carolina.
Does Exposure to Organic Solvents Heighten the Risk of MS?
People who are exposed to organic solvents and carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at greater risk of the disease than people who have only the exposure to solvents or the MS risk genes, according to a study published online ahead of print July 3 in Neurology. Using a Swedish population-based case–control study of 2,042 incident cases of MS and 2,947 controls, investigators compared the occurrence of MS in participants with different genotypes, smoking habits, and exposures to organic solvents such as paint and varnish. A potential interaction between exposure to organic solvents and MS risk human leukocyte antigen genes was evaluated by calculating the attributable proportion due to interaction. The MS genes and exposure to solvents combined were responsible for an estimated 60% of the risk of developing MS.
Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: interaction with MS risk HLA genes. Neurology. 2018 Jul 3 [Epub ahead of print].
Epidiolex Approved for the Treatment of Seizures
The FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It also is the first FDA approval of a drug for the treatment of patients with Dravet syndrome. The drug’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Taken with other medications, cannabidiol reduced the frequency of seizures, compared with placebo. Epidiolex must be dispensed with a patient medication guide that describes the drug’s uses and risks. GW Pharmaceuticals, located in the United Kingdom, markets Epidiolex.
FDA Approves Nuplazid Capsule Formulation and 10-mg Tablet
The FDA approved a new capsule dose formulation and tablet strength of Nuplazid (pimavanserin), a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. The 34-mg capsule formulation provides the recommended once daily dose in one capsule, versus the current administration of two 17-mg tablets. The 10-mg tablet provides a lower dosage strength for patients who are concomitantly receiving strong cytochrome 3A4 inhibitors, which can inhibit the metabolism of Nuplazid. The drug is a nondopaminergic, selective serotonin inverse agonist preferentially targeting 5-HT2A receptors. Acadia Pharmaceuticals, which markets the therapy, is headquartered in San Diego.
Mild Sleep Problems May Elevate Blood Pressure in Women
Mild sleep problems such as trouble falling asleep are associated with increased blood pressure and vascular inflammation in women, according to a study published June 9 in the Journal of the American Heart Association. Researchers examined blood pressure and sleep habits in 323 women in the ongoing American Heart Association Go Red for Women Strategically Focused Research Network. Investigators assessed participant’s sleep quality, obstructive sleep apnea risk, and insomnia severity. In a subset of women, sleep duration was assessed using actigraphy, and endothelial inflammation was assessed directly in harvested endothelial cells. Systolic blood pressure was associated with poor sleep quality. Poor sleep quality, insomnia, and longer sleep onset latency were associated with endothelial inflammation.
Aggarwal B, Makarem N, Shah R, et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12):e008590.
DBS May Slow Tremor Progression in Early Parkinson’s Disease
Deep brain stimulation (DBS) in the early stage of Parkinson’s disease may slow tremor progression, according to a study published online ahead of print June 29 in Neurology. The prospective pilot trial enrolled patients with Parkinson’s disease who were ages 50 to 75, had been treated with Parkinson’s disease medications for six months to four years, and had no history of dyskinesia or other motor fluctuations. Participants were randomized to receive optimal drug therapy (ODT) or DBS and ODT. At baseline and six, 12, 18, and 24 months, all patients stopped all Parkinson’s disease therapy for one week. Unified Parkinson’s Disease Rating Scale-III scores were compared between the ODT and DBS and ODT groups (n = 28). Rest tremor slopes from baseline to 24 months favored DBS plus ODT off and on therapy, compared with ODT alone.
Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jun 29 [Epub ahead of print].
—Kimberly Williams
New and Noteworthy Information—July 2018
Adequate Sleep Associated With Lower Dementia Risk
Short and long daily sleep duration are risk factors for dementia and death in adults age 60 and older, according to a study published online ahead of print June 6 in the Journal of the American Geriatrics Society. In a prospective cohort study, researchers followed 1,517 adults without dementia for 10 years. Self-reported daily sleep durations were grouped into five categories. The association between daily sleep duration and risk of dementia and death was determined using Cox proportional hazards models. During follow-up, 294 participants developed dementia, and 282 died. Age- and sex-adjusted incidence rates of dementia and all-cause mortality were significantly greater in subjects who slept less than 5.0 hours/day or 10.0 or more hours/day than in people who slept from 5.0 to 6.9 hours/day.
Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018 Jun 6 [Epub ahead of print].
Rivaroxaban Not Superior to Aspirin for Stroke Prevention
Rivaroxaban is not superior to aspirin in the prevention of recurrent stroke, according to a study published June 7 in the New England Journal of Medicine. Researchers compared the efficacy and safety of rivaroxaban at a daily dose of 15 mg with aspirin at a daily dose of 100 mg for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism. The primary outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis. At 459 sites, 3,609 patients were randomly assigned to receive rivaroxaban, and 3,604 were randomized to aspirin. Recurrent ischemic stroke occurred in 172 patients in the rivaroxaban group and in 160 in the aspirin group.
Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201.
Disintegrating Brain Lesions May Indicate Worsening MS
Atrophied lesion volume may indicate increasing disability in patients with multiple sclerosis (MS), according to a study published online ahead of print June 1 in the Journal of Neuroimaging. A total of 192 patients with clinically isolated syndrome or MS received 3T MRI at baseline and at five years. Investigators quantified lesions at baseline and calculated new and enlarging lesion volumes during the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived CSF partial volume maps. The researchers evaluated correlations between these measures and disability, as measured by the Expanded Disability Status Scale (EDSS). Atrophied lesion volume was different between MS subtypes and exceeded new lesion volume accumulation in progressive MS. Atrophied lesion volume was the only significant correlate of EDSS change.
Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Jun 1 [Epub ahead of print].
Do Migraineurs Seek Behavioral Treatment After a Referral?
A significant number of migraineurs are not using effective behavioral treatments for migraine, according to a study published online ahead of print June 5 in Pain Medicine. In a prospective cohort study, researchers tracked 234 patients with migraine who presented to an academic headache center and referred 69 of them for behavioral treatment with an appropriately trained therapist. Fifty-three of the referred patients completed a follow-up interview within three months of their initial appointment and were included in the analysis. Of the patients referred for behavioral treatment, 30 made an appointment. Investigators found no differences between people who started behavioral therapy and people who did not. Study authors did find that people who had previously seen a psychologist for migraine were more likely to initiate therapy.
Minen MT, Azarchi S, Sobolev R, et al. Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: a prospective observational study. Pain Med. 2018 Jun 5 [Epub ahead of print].
TIA Associated With Increased Five-Year Risk of Stroke
People with transient ischemic attack (TIA) are at risk for a cardiovascular event in the following five years, according to a study published June 7 in the New England Journal of Medicine. Researchers evaluated patients who had had a TIA within seven days before enrollment in a registry of TIA clinics. Of 61 sites, 42 had follow-up data on more than 50% of their enrolled patients at five years. The study’s primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes, with an emphasis on events that occurred in the second through fifth years. At five years, stroke had occurred in 345 of the 3,847 patients included in the follow-up study, and 149 of them had a stroke during the second through fifth years of follow-up.
Amarenco P, Lavallée PC, Monteiro Tavares L, et al. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378(23):2182-2190.
Follow-Up Care for TBI Is Not Delivered Adequately
Follow-up care for patients with traumatic brain injury (TBI) is not delivered optimally, according to a study published May 25 in JAMA Network Open. In a cohort study, researchers surveyed 831 participants in the Transforming Research and Clinical Knowledge in TBI initiative about their care after hospital discharge. Follow-up care was defined as providing TBI-related educational materials at discharge, calling patients within two weeks after release, seeing a healthcare provider within two weeks, and seeing a healthcare provider within three months. Approximately 42% of participants reported receiving TBI-related educational material at discharge, and 44% reported seeing a physician or other medical practitioner within three months after injury. Of patients with a positive finding on CT, 39% had not seen a medical practitioner at three months after injury.
Seabury SA, Gaudette E, Goldman DP, et al. Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Network Open. 2018;1(1):e180210.
Researchers Examine Mortality Rate of Pediatric Stroke
In-hospital mortality occurs in 2.6% of children with arterial ischemic stroke, according to a study published in the May issue of Pediatrics. The retrospective study included 915 infants younger than 1 month and 2,273 children age 1 month to 18 years with stroke at 87 hospitals in 24 countries. Death during hospitalization and cause of death were ascertained from medical records. A total of 14 neonates and 70 children died during hospitalization. Of 48 cases with reported causes of death, 31 were stroke-related. Remaining deaths were attributed to medical disease. In multivariable analysis, congenital heart disease, posterior plus anterior circulation stroke, and stroke presentation without seizures were associated with in-hospital mortality for neonates. Hispanic ethnicity, congenital heart disease, and posterior plus anterior circulation stroke were associated with in-hospital mortality for children.
Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality after pediatric arterial ischemic stroke. Pediatrics. 2018;141(5).
FDA Approves zEEG Dry Electrode Headset
The FDA has approved the zEEG dry electrode EEG headset for clinical use. The zEEG headset is backed by a cloud platform that allows users to upload data instantly, provides tools for analysis, and enables remote interpretation by neurologists. A clinical study found that the zEEG headset provided EEG signal quality that was comparable to that of an approved, traditional EEG system. In two study cohorts, a total of 30 patients were studied for time periods of as long as two hours, and the zEEG device performed at least as well as the reference device, based on predefined acceptance criteria. Study results will be published in the coming months. Zeto, headquartered in Santa Clara, California, markets the device.
South Asian Americans Have High Cardiovascular Mortality
South Asians living in the United States have higher mortality from heart conditions caused by atherosclerosis, such as heart attack and stroke, according to a study published online ahead of print May 24 in Circulation. Investigators reviewed the literature relevant to South Asian populations’ demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies. South Asians have higher proportional mortality rates from atherosclerotic cardiovascular disease, compared with other Asian groups, largely because of the lower risk observed in East Asian populations. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially factors related to insulin resistance. The authors found no unique risk factors in this population.
Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018 May 24 [Epub ahead of print].
How Much Exercise Improves Cognition in Older Adults?
Exercising for at least 52 hours over six months is associated with improved cognitive performance in older adults with and without cognitive impairment, according to a study published online ahead of print May 30 in Neurology. Researchers reviewed data for 98 randomized, controlled exercise trials including 11,061 participants with an average age of 73. About 59% of the participants were healthy adults, 26% had mild cognitive impairment, and 15% had dementia. Researchers collected data on exercise session length, intensity, weekly frequency, and amount of exercise over time. Aerobic exercise was the most common form of exercise. In healthy people and people with cognitive impairment, longer term exposure to exercise, at least 52 hours conducted over an average of about six months, improved the brain’s processing speed.
Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurology. 2018 May 30 [Epub ahead of print].
Blood Biomarkers Detect Subconcussive Head Trauma
Blood biomarkers can detect the neurologic injury associated with repetitive subconcussive head trauma, according to a study published online ahead of print May 29 in the Journal of Neurosurgery. A total of 35 National Collegiate Athletic Association football players underwent blood sampling throughout the 2016 football season. Samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light. Athletes were categorized as starters or nonstarters, and the investigators assessed between-group differences and time-course differences. In nonstarters, plasma concentrations of tau decreased over the season. Starters had lower plasma concentrations of tau. Plasma concentrations of tau could not be used to distinguish between starters and nonstarters. Serum concentrations of neurofilament light increased as head impacts increased, specifically in starters. Serum neurofilament light distinguished starters from nonstarters.
Oliver JM, Anzalone AJ, Stone JD, et al. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29 [Epub ahead of print].
Model Estimates Risk of Alzheimer’s Disease Dementia
Most people with preclinical Alzheimer’s disease will not develop dementia during their lifetimes, according to a study published online ahead of print May 7 in Alzheimer’s & Dementia. Researchers used a multistate model for Alzheimer’s disease along with US death rates to estimate lifetime and 10-year risks of Alzheimer’s disease dementia. Lifetime risks of Alzheimer’s disease dementia vary by age, gender, and preclinical or clinical disease state. A 70-year-old male with amyloid but no signs of neurodegeneration and no memory loss has a lifetime risk of 19.9%. The lifetime risks for a female with amyloidosis are 8.4% at age 90 and 29.3% at age 65. People younger than 85 with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of Alzheimer’s disease dementia greater than 50%.
Brookmeyer R, Abdalla N. Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018 May 7 [Epub ahead of print].
Depression Is Associated With Brain and Memory Outcomes
In a sample of mostly Caribbean Hispanic, stroke-free older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts, according to a study published online ahead of print May 9 in Neurology. Researchers analyzed data from the Northern Manhattan Study. A total of 1,111 participants underwent baseline evaluations of depressive symptoms, MRI markers, and cognitive function. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographics, vascular risk factors, behavioral factors, and antidepressant medications. Furthermore, greater depressive symptoms were associated with smaller cerebral parenchymal fraction and increased odds of subclinical brain infarcts, after adjustment for sociodemographics, behavioral factors, and vascular risk factors.
Al Hazzouri AZ, Caunca MR, Nobrega JC. Greater depressive symptoms, cognition, and markers of brain aging. Neurology. 2018 May 9 [Epub ahead of print].
—Kimberly Williams
Adequate Sleep Associated With Lower Dementia Risk
Short and long daily sleep duration are risk factors for dementia and death in adults age 60 and older, according to a study published online ahead of print June 6 in the Journal of the American Geriatrics Society. In a prospective cohort study, researchers followed 1,517 adults without dementia for 10 years. Self-reported daily sleep durations were grouped into five categories. The association between daily sleep duration and risk of dementia and death was determined using Cox proportional hazards models. During follow-up, 294 participants developed dementia, and 282 died. Age- and sex-adjusted incidence rates of dementia and all-cause mortality were significantly greater in subjects who slept less than 5.0 hours/day or 10.0 or more hours/day than in people who slept from 5.0 to 6.9 hours/day.
Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018 Jun 6 [Epub ahead of print].
Rivaroxaban Not Superior to Aspirin for Stroke Prevention
Rivaroxaban is not superior to aspirin in the prevention of recurrent stroke, according to a study published June 7 in the New England Journal of Medicine. Researchers compared the efficacy and safety of rivaroxaban at a daily dose of 15 mg with aspirin at a daily dose of 100 mg for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism. The primary outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis. At 459 sites, 3,609 patients were randomly assigned to receive rivaroxaban, and 3,604 were randomized to aspirin. Recurrent ischemic stroke occurred in 172 patients in the rivaroxaban group and in 160 in the aspirin group.
Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201.
Disintegrating Brain Lesions May Indicate Worsening MS
Atrophied lesion volume may indicate increasing disability in patients with multiple sclerosis (MS), according to a study published online ahead of print June 1 in the Journal of Neuroimaging. A total of 192 patients with clinically isolated syndrome or MS received 3T MRI at baseline and at five years. Investigators quantified lesions at baseline and calculated new and enlarging lesion volumes during the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived CSF partial volume maps. The researchers evaluated correlations between these measures and disability, as measured by the Expanded Disability Status Scale (EDSS). Atrophied lesion volume was different between MS subtypes and exceeded new lesion volume accumulation in progressive MS. Atrophied lesion volume was the only significant correlate of EDSS change.
Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Jun 1 [Epub ahead of print].
Do Migraineurs Seek Behavioral Treatment After a Referral?
A significant number of migraineurs are not using effective behavioral treatments for migraine, according to a study published online ahead of print June 5 in Pain Medicine. In a prospective cohort study, researchers tracked 234 patients with migraine who presented to an academic headache center and referred 69 of them for behavioral treatment with an appropriately trained therapist. Fifty-three of the referred patients completed a follow-up interview within three months of their initial appointment and were included in the analysis. Of the patients referred for behavioral treatment, 30 made an appointment. Investigators found no differences between people who started behavioral therapy and people who did not. Study authors did find that people who had previously seen a psychologist for migraine were more likely to initiate therapy.
Minen MT, Azarchi S, Sobolev R, et al. Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: a prospective observational study. Pain Med. 2018 Jun 5 [Epub ahead of print].
TIA Associated With Increased Five-Year Risk of Stroke
People with transient ischemic attack (TIA) are at risk for a cardiovascular event in the following five years, according to a study published June 7 in the New England Journal of Medicine. Researchers evaluated patients who had had a TIA within seven days before enrollment in a registry of TIA clinics. Of 61 sites, 42 had follow-up data on more than 50% of their enrolled patients at five years. The study’s primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes, with an emphasis on events that occurred in the second through fifth years. At five years, stroke had occurred in 345 of the 3,847 patients included in the follow-up study, and 149 of them had a stroke during the second through fifth years of follow-up.
Amarenco P, Lavallée PC, Monteiro Tavares L, et al. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378(23):2182-2190.
Follow-Up Care for TBI Is Not Delivered Adequately
Follow-up care for patients with traumatic brain injury (TBI) is not delivered optimally, according to a study published May 25 in JAMA Network Open. In a cohort study, researchers surveyed 831 participants in the Transforming Research and Clinical Knowledge in TBI initiative about their care after hospital discharge. Follow-up care was defined as providing TBI-related educational materials at discharge, calling patients within two weeks after release, seeing a healthcare provider within two weeks, and seeing a healthcare provider within three months. Approximately 42% of participants reported receiving TBI-related educational material at discharge, and 44% reported seeing a physician or other medical practitioner within three months after injury. Of patients with a positive finding on CT, 39% had not seen a medical practitioner at three months after injury.
Seabury SA, Gaudette E, Goldman DP, et al. Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Network Open. 2018;1(1):e180210.
Researchers Examine Mortality Rate of Pediatric Stroke
In-hospital mortality occurs in 2.6% of children with arterial ischemic stroke, according to a study published in the May issue of Pediatrics. The retrospective study included 915 infants younger than 1 month and 2,273 children age 1 month to 18 years with stroke at 87 hospitals in 24 countries. Death during hospitalization and cause of death were ascertained from medical records. A total of 14 neonates and 70 children died during hospitalization. Of 48 cases with reported causes of death, 31 were stroke-related. Remaining deaths were attributed to medical disease. In multivariable analysis, congenital heart disease, posterior plus anterior circulation stroke, and stroke presentation without seizures were associated with in-hospital mortality for neonates. Hispanic ethnicity, congenital heart disease, and posterior plus anterior circulation stroke were associated with in-hospital mortality for children.
Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality after pediatric arterial ischemic stroke. Pediatrics. 2018;141(5).
FDA Approves zEEG Dry Electrode Headset
The FDA has approved the zEEG dry electrode EEG headset for clinical use. The zEEG headset is backed by a cloud platform that allows users to upload data instantly, provides tools for analysis, and enables remote interpretation by neurologists. A clinical study found that the zEEG headset provided EEG signal quality that was comparable to that of an approved, traditional EEG system. In two study cohorts, a total of 30 patients were studied for time periods of as long as two hours, and the zEEG device performed at least as well as the reference device, based on predefined acceptance criteria. Study results will be published in the coming months. Zeto, headquartered in Santa Clara, California, markets the device.
South Asian Americans Have High Cardiovascular Mortality
South Asians living in the United States have higher mortality from heart conditions caused by atherosclerosis, such as heart attack and stroke, according to a study published online ahead of print May 24 in Circulation. Investigators reviewed the literature relevant to South Asian populations’ demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies. South Asians have higher proportional mortality rates from atherosclerotic cardiovascular disease, compared with other Asian groups, largely because of the lower risk observed in East Asian populations. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially factors related to insulin resistance. The authors found no unique risk factors in this population.
Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018 May 24 [Epub ahead of print].
How Much Exercise Improves Cognition in Older Adults?
Exercising for at least 52 hours over six months is associated with improved cognitive performance in older adults with and without cognitive impairment, according to a study published online ahead of print May 30 in Neurology. Researchers reviewed data for 98 randomized, controlled exercise trials including 11,061 participants with an average age of 73. About 59% of the participants were healthy adults, 26% had mild cognitive impairment, and 15% had dementia. Researchers collected data on exercise session length, intensity, weekly frequency, and amount of exercise over time. Aerobic exercise was the most common form of exercise. In healthy people and people with cognitive impairment, longer term exposure to exercise, at least 52 hours conducted over an average of about six months, improved the brain’s processing speed.
Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurology. 2018 May 30 [Epub ahead of print].
Blood Biomarkers Detect Subconcussive Head Trauma
Blood biomarkers can detect the neurologic injury associated with repetitive subconcussive head trauma, according to a study published online ahead of print May 29 in the Journal of Neurosurgery. A total of 35 National Collegiate Athletic Association football players underwent blood sampling throughout the 2016 football season. Samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light. Athletes were categorized as starters or nonstarters, and the investigators assessed between-group differences and time-course differences. In nonstarters, plasma concentrations of tau decreased over the season. Starters had lower plasma concentrations of tau. Plasma concentrations of tau could not be used to distinguish between starters and nonstarters. Serum concentrations of neurofilament light increased as head impacts increased, specifically in starters. Serum neurofilament light distinguished starters from nonstarters.
Oliver JM, Anzalone AJ, Stone JD, et al. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29 [Epub ahead of print].
Model Estimates Risk of Alzheimer’s Disease Dementia
Most people with preclinical Alzheimer’s disease will not develop dementia during their lifetimes, according to a study published online ahead of print May 7 in Alzheimer’s & Dementia. Researchers used a multistate model for Alzheimer’s disease along with US death rates to estimate lifetime and 10-year risks of Alzheimer’s disease dementia. Lifetime risks of Alzheimer’s disease dementia vary by age, gender, and preclinical or clinical disease state. A 70-year-old male with amyloid but no signs of neurodegeneration and no memory loss has a lifetime risk of 19.9%. The lifetime risks for a female with amyloidosis are 8.4% at age 90 and 29.3% at age 65. People younger than 85 with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of Alzheimer’s disease dementia greater than 50%.
Brookmeyer R, Abdalla N. Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018 May 7 [Epub ahead of print].
Depression Is Associated With Brain and Memory Outcomes
In a sample of mostly Caribbean Hispanic, stroke-free older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts, according to a study published online ahead of print May 9 in Neurology. Researchers analyzed data from the Northern Manhattan Study. A total of 1,111 participants underwent baseline evaluations of depressive symptoms, MRI markers, and cognitive function. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographics, vascular risk factors, behavioral factors, and antidepressant medications. Furthermore, greater depressive symptoms were associated with smaller cerebral parenchymal fraction and increased odds of subclinical brain infarcts, after adjustment for sociodemographics, behavioral factors, and vascular risk factors.
Al Hazzouri AZ, Caunca MR, Nobrega JC. Greater depressive symptoms, cognition, and markers of brain aging. Neurology. 2018 May 9 [Epub ahead of print].
—Kimberly Williams
Adequate Sleep Associated With Lower Dementia Risk
Short and long daily sleep duration are risk factors for dementia and death in adults age 60 and older, according to a study published online ahead of print June 6 in the Journal of the American Geriatrics Society. In a prospective cohort study, researchers followed 1,517 adults without dementia for 10 years. Self-reported daily sleep durations were grouped into five categories. The association between daily sleep duration and risk of dementia and death was determined using Cox proportional hazards models. During follow-up, 294 participants developed dementia, and 282 died. Age- and sex-adjusted incidence rates of dementia and all-cause mortality were significantly greater in subjects who slept less than 5.0 hours/day or 10.0 or more hours/day than in people who slept from 5.0 to 6.9 hours/day.
Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018 Jun 6 [Epub ahead of print].
Rivaroxaban Not Superior to Aspirin for Stroke Prevention
Rivaroxaban is not superior to aspirin in the prevention of recurrent stroke, according to a study published June 7 in the New England Journal of Medicine. Researchers compared the efficacy and safety of rivaroxaban at a daily dose of 15 mg with aspirin at a daily dose of 100 mg for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism. The primary outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis. At 459 sites, 3,609 patients were randomly assigned to receive rivaroxaban, and 3,604 were randomized to aspirin. Recurrent ischemic stroke occurred in 172 patients in the rivaroxaban group and in 160 in the aspirin group.
Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201.
Disintegrating Brain Lesions May Indicate Worsening MS
Atrophied lesion volume may indicate increasing disability in patients with multiple sclerosis (MS), according to a study published online ahead of print June 1 in the Journal of Neuroimaging. A total of 192 patients with clinically isolated syndrome or MS received 3T MRI at baseline and at five years. Investigators quantified lesions at baseline and calculated new and enlarging lesion volumes during the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived CSF partial volume maps. The researchers evaluated correlations between these measures and disability, as measured by the Expanded Disability Status Scale (EDSS). Atrophied lesion volume was different between MS subtypes and exceeded new lesion volume accumulation in progressive MS. Atrophied lesion volume was the only significant correlate of EDSS change.
Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Jun 1 [Epub ahead of print].
Do Migraineurs Seek Behavioral Treatment After a Referral?
A significant number of migraineurs are not using effective behavioral treatments for migraine, according to a study published online ahead of print June 5 in Pain Medicine. In a prospective cohort study, researchers tracked 234 patients with migraine who presented to an academic headache center and referred 69 of them for behavioral treatment with an appropriately trained therapist. Fifty-three of the referred patients completed a follow-up interview within three months of their initial appointment and were included in the analysis. Of the patients referred for behavioral treatment, 30 made an appointment. Investigators found no differences between people who started behavioral therapy and people who did not. Study authors did find that people who had previously seen a psychologist for migraine were more likely to initiate therapy.
Minen MT, Azarchi S, Sobolev R, et al. Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: a prospective observational study. Pain Med. 2018 Jun 5 [Epub ahead of print].
TIA Associated With Increased Five-Year Risk of Stroke
People with transient ischemic attack (TIA) are at risk for a cardiovascular event in the following five years, according to a study published June 7 in the New England Journal of Medicine. Researchers evaluated patients who had had a TIA within seven days before enrollment in a registry of TIA clinics. Of 61 sites, 42 had follow-up data on more than 50% of their enrolled patients at five years. The study’s primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes, with an emphasis on events that occurred in the second through fifth years. At five years, stroke had occurred in 345 of the 3,847 patients included in the follow-up study, and 149 of them had a stroke during the second through fifth years of follow-up.
Amarenco P, Lavallée PC, Monteiro Tavares L, et al. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378(23):2182-2190.
Follow-Up Care for TBI Is Not Delivered Adequately
Follow-up care for patients with traumatic brain injury (TBI) is not delivered optimally, according to a study published May 25 in JAMA Network Open. In a cohort study, researchers surveyed 831 participants in the Transforming Research and Clinical Knowledge in TBI initiative about their care after hospital discharge. Follow-up care was defined as providing TBI-related educational materials at discharge, calling patients within two weeks after release, seeing a healthcare provider within two weeks, and seeing a healthcare provider within three months. Approximately 42% of participants reported receiving TBI-related educational material at discharge, and 44% reported seeing a physician or other medical practitioner within three months after injury. Of patients with a positive finding on CT, 39% had not seen a medical practitioner at three months after injury.
Seabury SA, Gaudette E, Goldman DP, et al. Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Network Open. 2018;1(1):e180210.
Researchers Examine Mortality Rate of Pediatric Stroke
In-hospital mortality occurs in 2.6% of children with arterial ischemic stroke, according to a study published in the May issue of Pediatrics. The retrospective study included 915 infants younger than 1 month and 2,273 children age 1 month to 18 years with stroke at 87 hospitals in 24 countries. Death during hospitalization and cause of death were ascertained from medical records. A total of 14 neonates and 70 children died during hospitalization. Of 48 cases with reported causes of death, 31 were stroke-related. Remaining deaths were attributed to medical disease. In multivariable analysis, congenital heart disease, posterior plus anterior circulation stroke, and stroke presentation without seizures were associated with in-hospital mortality for neonates. Hispanic ethnicity, congenital heart disease, and posterior plus anterior circulation stroke were associated with in-hospital mortality for children.
Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality after pediatric arterial ischemic stroke. Pediatrics. 2018;141(5).
FDA Approves zEEG Dry Electrode Headset
The FDA has approved the zEEG dry electrode EEG headset for clinical use. The zEEG headset is backed by a cloud platform that allows users to upload data instantly, provides tools for analysis, and enables remote interpretation by neurologists. A clinical study found that the zEEG headset provided EEG signal quality that was comparable to that of an approved, traditional EEG system. In two study cohorts, a total of 30 patients were studied for time periods of as long as two hours, and the zEEG device performed at least as well as the reference device, based on predefined acceptance criteria. Study results will be published in the coming months. Zeto, headquartered in Santa Clara, California, markets the device.
South Asian Americans Have High Cardiovascular Mortality
South Asians living in the United States have higher mortality from heart conditions caused by atherosclerosis, such as heart attack and stroke, according to a study published online ahead of print May 24 in Circulation. Investigators reviewed the literature relevant to South Asian populations’ demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies. South Asians have higher proportional mortality rates from atherosclerotic cardiovascular disease, compared with other Asian groups, largely because of the lower risk observed in East Asian populations. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially factors related to insulin resistance. The authors found no unique risk factors in this population.
Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018 May 24 [Epub ahead of print].
How Much Exercise Improves Cognition in Older Adults?
Exercising for at least 52 hours over six months is associated with improved cognitive performance in older adults with and without cognitive impairment, according to a study published online ahead of print May 30 in Neurology. Researchers reviewed data for 98 randomized, controlled exercise trials including 11,061 participants with an average age of 73. About 59% of the participants were healthy adults, 26% had mild cognitive impairment, and 15% had dementia. Researchers collected data on exercise session length, intensity, weekly frequency, and amount of exercise over time. Aerobic exercise was the most common form of exercise. In healthy people and people with cognitive impairment, longer term exposure to exercise, at least 52 hours conducted over an average of about six months, improved the brain’s processing speed.
Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurology. 2018 May 30 [Epub ahead of print].
Blood Biomarkers Detect Subconcussive Head Trauma
Blood biomarkers can detect the neurologic injury associated with repetitive subconcussive head trauma, according to a study published online ahead of print May 29 in the Journal of Neurosurgery. A total of 35 National Collegiate Athletic Association football players underwent blood sampling throughout the 2016 football season. Samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light. Athletes were categorized as starters or nonstarters, and the investigators assessed between-group differences and time-course differences. In nonstarters, plasma concentrations of tau decreased over the season. Starters had lower plasma concentrations of tau. Plasma concentrations of tau could not be used to distinguish between starters and nonstarters. Serum concentrations of neurofilament light increased as head impacts increased, specifically in starters. Serum neurofilament light distinguished starters from nonstarters.
Oliver JM, Anzalone AJ, Stone JD, et al. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29 [Epub ahead of print].
Model Estimates Risk of Alzheimer’s Disease Dementia
Most people with preclinical Alzheimer’s disease will not develop dementia during their lifetimes, according to a study published online ahead of print May 7 in Alzheimer’s & Dementia. Researchers used a multistate model for Alzheimer’s disease along with US death rates to estimate lifetime and 10-year risks of Alzheimer’s disease dementia. Lifetime risks of Alzheimer’s disease dementia vary by age, gender, and preclinical or clinical disease state. A 70-year-old male with amyloid but no signs of neurodegeneration and no memory loss has a lifetime risk of 19.9%. The lifetime risks for a female with amyloidosis are 8.4% at age 90 and 29.3% at age 65. People younger than 85 with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of Alzheimer’s disease dementia greater than 50%.
Brookmeyer R, Abdalla N. Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018 May 7 [Epub ahead of print].
Depression Is Associated With Brain and Memory Outcomes
In a sample of mostly Caribbean Hispanic, stroke-free older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts, according to a study published online ahead of print May 9 in Neurology. Researchers analyzed data from the Northern Manhattan Study. A total of 1,111 participants underwent baseline evaluations of depressive symptoms, MRI markers, and cognitive function. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographics, vascular risk factors, behavioral factors, and antidepressant medications. Furthermore, greater depressive symptoms were associated with smaller cerebral parenchymal fraction and increased odds of subclinical brain infarcts, after adjustment for sociodemographics, behavioral factors, and vascular risk factors.
Al Hazzouri AZ, Caunca MR, Nobrega JC. Greater depressive symptoms, cognition, and markers of brain aging. Neurology. 2018 May 9 [Epub ahead of print].
—Kimberly Williams
The fragile gray mass between your ears
He’s almost 10 years younger than me.
He’d been in the hospital for 3 weeks. The ICU room had been decorated, as many families do, with pictures of his life. His wedding. His kids. He and his wife dressed as Darth Vader and Princess Leia for a Halloween party. A few religious items.
He was off sedation. EEG didn’t show any seizures. Head CT just showed the extensive damage from his head injury. The neurosurgeons can evacuate clots and decrease intracranial pressure, but they can’t repair brain tissue.
His wife was long past the point of shock when I met with her. After 3 weeks, she understood what the new normal was and how the lives of both herself and their kids would never be the same. She held his hand at the bedside as we talked, asked me a few pointed questions, and then thanked me for coming in to see him.
For me, it was just another day on call. I walked back to the nurses station, got some coffee from the galley, and sat down to dictate a note. There are always other patients to see on the coverage list.
But it still reminds you.
The brain doesn’t weigh much, just 2-3 pounds; it’s about the size of your fists put together.
But it’s everything that we are, both as individuals and as a species. All that humanity has achieved, good and bad, came from the brain.
The rest of him was in good shape. A healthy guy in his 40s. Probably in better condition than me. But with his brain irreparably damaged, none of that meant anything.
Even after almost 20 years of doing this work, this sort of thing still reminds me how lucky I, and most of us, are – and to be grateful for what I have.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
He’s almost 10 years younger than me.
He’d been in the hospital for 3 weeks. The ICU room had been decorated, as many families do, with pictures of his life. His wedding. His kids. He and his wife dressed as Darth Vader and Princess Leia for a Halloween party. A few religious items.
He was off sedation. EEG didn’t show any seizures. Head CT just showed the extensive damage from his head injury. The neurosurgeons can evacuate clots and decrease intracranial pressure, but they can’t repair brain tissue.
His wife was long past the point of shock when I met with her. After 3 weeks, she understood what the new normal was and how the lives of both herself and their kids would never be the same. She held his hand at the bedside as we talked, asked me a few pointed questions, and then thanked me for coming in to see him.
For me, it was just another day on call. I walked back to the nurses station, got some coffee from the galley, and sat down to dictate a note. There are always other patients to see on the coverage list.
But it still reminds you.
The brain doesn’t weigh much, just 2-3 pounds; it’s about the size of your fists put together.
But it’s everything that we are, both as individuals and as a species. All that humanity has achieved, good and bad, came from the brain.
The rest of him was in good shape. A healthy guy in his 40s. Probably in better condition than me. But with his brain irreparably damaged, none of that meant anything.
Even after almost 20 years of doing this work, this sort of thing still reminds me how lucky I, and most of us, are – and to be grateful for what I have.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
He’s almost 10 years younger than me.
He’d been in the hospital for 3 weeks. The ICU room had been decorated, as many families do, with pictures of his life. His wedding. His kids. He and his wife dressed as Darth Vader and Princess Leia for a Halloween party. A few religious items.
He was off sedation. EEG didn’t show any seizures. Head CT just showed the extensive damage from his head injury. The neurosurgeons can evacuate clots and decrease intracranial pressure, but they can’t repair brain tissue.
His wife was long past the point of shock when I met with her. After 3 weeks, she understood what the new normal was and how the lives of both herself and their kids would never be the same. She held his hand at the bedside as we talked, asked me a few pointed questions, and then thanked me for coming in to see him.
For me, it was just another day on call. I walked back to the nurses station, got some coffee from the galley, and sat down to dictate a note. There are always other patients to see on the coverage list.
But it still reminds you.
The brain doesn’t weigh much, just 2-3 pounds; it’s about the size of your fists put together.
But it’s everything that we are, both as individuals and as a species. All that humanity has achieved, good and bad, came from the brain.
The rest of him was in good shape. A healthy guy in his 40s. Probably in better condition than me. But with his brain irreparably damaged, none of that meant anything.
Even after almost 20 years of doing this work, this sort of thing still reminds me how lucky I, and most of us, are – and to be grateful for what I have.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
New and Noteworthy Information—June 2018
CSF Predicts Progression of MS
CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.
Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.
APOE Plays a Greater Role in Women Than in Men
There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.
Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
Is Tenecteplase Better Than Alteplase Before Thrombectomy?
When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.
Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
Lifestyle Factors at Midlife Could Influence Dementia Risk
Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.
Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
Epilepsy Does Not Affect Women’s Fertility
In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Amon
Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
Sauna Bathing Reduces Stroke Risk
Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.
Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].
—Kimberly Williams
and Glenn Williams
CSF Predicts Progression of MS
CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.
Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.
APOE Plays a Greater Role in Women Than in Men
There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.
Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
Is Tenecteplase Better Than Alteplase Before Thrombectomy?
When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.
Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
Lifestyle Factors at Midlife Could Influence Dementia Risk
Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.
Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
Epilepsy Does Not Affect Women’s Fertility
In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Amon
Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
Sauna Bathing Reduces Stroke Risk
Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.
Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].
—Kimberly Williams
and Glenn Williams
CSF Predicts Progression of MS
CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.
Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].
First Anti-CGRP Monoclonal Antibody Gains FDA Approval
The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.
APOE Plays a Greater Role in Women Than in Men
There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.
Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].
FDA Issues Warning About Lamictal
The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.
Is Tenecteplase Better Than Alteplase Before Thrombectomy?
When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.
Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.
FDA Approves Gilenya for Pediatric Use
The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.
Lifestyle Factors at Midlife Could Influence Dementia Risk
Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.
Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.
DBS Device Approved for Refractory Epilepsy
The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.
Epilepsy Does Not Affect Women’s Fertility
In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Amon
Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].
FDA Approves Treatment for CIDP
The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.
Sauna Bathing Reduces Stroke Risk
Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.
Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].
—Kimberly Williams
and Glenn Williams
New and Noteworthy Information—May 2018
Starting School Later Improves Sleep Time
Delaying school start time can provide sustained benefits for sleep duration, daytime alertness, and mental well-being, according to a study published online ahead of print April 10 in Sleep. The study included 375 girls in grades 7 to 10 from a secondary school for girls. The school delayed its start time from 7:30 to 8:15 in the morning. Self-reports of sleep timing, sleepiness, and well-being were obtained at baseline before the delay and at approximately one and nine months after the delay. After one month, bedtimes on school nights were delayed by nine minutes, while rise times were delayed by 31.6 minutes, resulting in an increase in time in bed of 23.2 minutes. After nine months, the increase in time in bed was sustained, and total sleep time increased by 10 minutes.
Lo JC, Lee SM, Lee XK, et al. Sustained benefits of delaying school start time on adolescent sleep and well-being. Sleep. 2018 Apr 10 [Epub ahead of print].
Stroke Affects Social, Cognitive, and Psychologic Outcomes
Patients with ischemic stroke report symptoms in multiple domains that increase to variable degrees at higher levels of disability, according to a study published online ahead of print March 28 in Neurology. The observational cohort included 1,195 patients who completed Quality of Life in Neurological Disorders or the Patient-Reported Outcomes Measurement Information System scales as part of routine care. Participants were questioned about their physical function, satisfaction with social roles, fatigue, anxiety, depression, pain interference, and sleep disturbance. Researchers also measured participants’ level of disability. Among people with stroke, scores were considerably worse than those in the general population in every area except sleep and depression. About 58% of people with stroke had scores related to satisfaction with social roles that were meaningfully worse than those of the general population.
Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018 Mar 28 [Epub ahead of print].
ALS Genetic Variant Also a Risk Factor for Frontotemporal Dementia
One of the newly identified genetic variants associated with amyotrophic lateral sclerosis (ALS) also is a risk factor for frontotemporal dementia (FTD), according to a study published online ahead of print April 9 in JAMA Neurology. Researchers pooled data from previous genome-wide association studies that included genetic data from 124,876 participants. The studies included healthy controls and participants with ALS, Alzheimer’s disease, Parkinson’s disease, FTD, corticobasal degeneration, and progressive supranuclear palsy. Investigators found that a variation in a region of DNA containing the gene for tau protein was associated with elevated risk for ALS. In addition, study authors found significant genetic overlap between ALS and FTD at known ALS loci rs13302855, rs3849942, and rs4239633. They also found a genetic variation at rs538622 that is associated with ALS and FTD and affects BNIP1 production in the brain.
Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].
Intervention Promotes Stroke Preparedness
Hip-Hop Stroke (HHS) is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities, according to a study published in the April issue of Stroke. HHS is a three-hour, culturally tailored, theory-based, multimedia stroke literacy intervention that empowers schoolchildren to share stroke information with parents. Researchers recruited 3,070 fourth- through sixth-graders and 1,144 parents from 22 schools into a cluster-randomized trial. Schools were randomized to the HHS intervention or attentional control (ie, nutrition classes). Main outcome measures were stroke knowledge and preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% of controls and 2% of the intervention group demonstrated optimal stroke preparedness at baseline, increasing to 57% immediately after the program in the intervention group.
Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving community stroke preparedness in the HHS (Hip-Hop Stroke) randomized clinical trial. Stroke. 2018;49(4):972-979.
Risk of Unnatural Death Is Increased in Epilepsy
People with epilepsy are at increased risk of mortality from suicide and accidents, according to a study published online ahead of print April 9 in JAMA Neurology. Researchers examined the Clinical Practice Research Datalink (CPRD) and the Secure Anonymized Information Linkage (SAIL) databank, which are linked to hospitalization and mortality records. They matched people with epilepsy on age, sex, and general practice with as many as 20 controls. In all, 44,678 people in the CPRD and 14,051 individuals in the SAIL databank were identified in the prevalent epilepsy cohorts. Furthermore, 891,429 participants from the CPRD and 279,365 people from the SAIL databank were identified as controls. People with epilepsy were significantly more likely to die of an unnatural cause, unintentional injury, poisoning, or suicide, compared with controls.
Gorton HC, Webb RT, Carr MJ, et al. Risk of unnatural mortality in people with epilepsy. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].
Method to Assess Consciousness May Improve Care
The Glasgow Coma Scale-Pupil (GCS-P) score provides a way to rapidly assess levels of consciousness in people with head injuries and could improve patient care, according to a study published online ahead of print April 10 in the Journal of Neurosurgery. Investigators obtained patient-level information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality by reviewing data from the Corticosteroid Randomization After Significant Head Injury study and the International Mission for Prognosis and Clinical Trials database. GCS score and pupil response were independently related to patient outcome. Adding information about pupil response to the GCS score improved the information. The performance of the GCS-P was similar to that of methods for evaluating traumatic brain damage.
Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Apr 10 [Epub ahead of print].
Biomarkers of Dementia Risk Identified
Researchers have identified novel biomarkers of risk for future dementia, according to a study published online ahead of print February 28 in Alzheimer’s & Dementia. Investigators analyzed metabolites in blood samples drawn from 22,623 people enrolled in eight prospective cohorts. Over 246,698 person-years, they detected 995 cases of incident dementia and 745 cases of incident Alzheimer’s disease. Isoleucine, leucine, valine, creatinine, and two VLDL-specific lipoprotein lipid subclasses were associated with lower dementia risk. One HDL and one VLDL lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids also were associated with decreased Alzheimer’s disease risk, and the concentration of cholesterol esters relative to total lipids in large HDL was associated with increased Alzheimer’s disease risk.
Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimers Dement. 2018 Feb 28 [Epub ahead of print].
Smartphone App Helps Doctors Track Parkinson’s Disease Symptoms
A smartphone app generates a score that reflects symptom severity in patients with Parkinson’s disease, according to a study published online ahead of print March 26 in JAMA Neurology. This observational study assessed people with Parkinson’s disease who remotely completed voice, finger tapping, gait, balance, and reaction time tasks on the app. Researchers generated a mobile Parkinson’s disease score (mPDS) of 0 to 100 that objectively weighed features derived from each smartphone activity. The mPDS was based on 6,148 smartphone activity assessments from 129 individuals. Gait features contributed most to the total mPDS (33.4%). The mPDS detected symptom fluctuations with a mean intraday change of 13.9 points. The mPDS improved by a mean of 16.3 points in response to dopaminergic therapy.
Zhan A, Mohan S, Tarolli C, et al. Using smartphones and machine learning to quantify Parkinson disease severity: the mobile Parkinson disease score. JAMA Neurol. 2018 Mar 26 [Epub ahead of print].
Age at Natural Menopause Linked to Memory
Entering menopause at a later age may benefit memory in women years later, according to a study published online ahead of print April 11 in Neurology. Researchers used data from 1,315 participants in the Medical Research Council National Survey of Health and Development with known age at period cessation and as many as four assessments of verbal memory and processing speed at ages 43, 53, between 60 and 64, and 69. Investigators fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, BMI, smoking, occupational class, education, and childhood cognitive ability. Verbal memory increased with later age at natural menopause and with later age at surgical menopause. The association between age at natural menopause and verbal memory remained significant after data adjustment.
Kuh D, Cooper R, Moore A, et al. Age at menopause and lifetime cognition: findings from a British birth cohort study. Neurology. 2018 Apr 11 [Epub ahead of print].
Single-Pulse TMS Decreases Migraine Frequency
Single-pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a study published online ahead of print March 4 in Cephalalgia. Researchers examined data from the eNeura SpringTMS Post-Market Observational US Study of Migraine, a multicenter, prospective, open-label, observational study. A total of 263 patients with migraine completed a one-month baseline headache diary, followed by three months of preventive (four pulses bid) and acute treatment (three pulses repeated as many as three times per attack). In all, 220 participants were eligible based on their number of headache days. The device was assigned to 217 subjects, and 132 were included in the intention-to-treat full-analysis set. Treatment reduced mean monthly headache days by 2.75. The most common adverse events were tingling, lightheadedness, and tinnitus.
Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 Mar 4 [Epub ahead of print].
Short Sleep Increases Risk of Obesity in the Young
Short sleep duration is a risk factor for obesity in infants, children, and adolescents, according to a study published online ahead of print February 1 in Sleep. Researchers reviewed the results of 42 population studies that included 75,499 infants, children, and adolescents ages 0 to 18. Sleep duration was assessed through methods such as questionnaires and wearable technology. The investigators classified participants as short sleepers or regular sleepers. Short sleepers were defined as having less sleep than the reference category for their age. Participants were followed up for a median of three years, and changes in BMI and incidence of overweight status and obesity were recorded. At all ages, short sleepers gained more weight and were 58% more likely to become overweight or obese.
Miller MA, Kruisbrink M, Wallace J, et al. Sleep duration and incidence of obesity in infants, children and adolescents: a systematic review and meta-analysis of prospective studies. Sleep. 2018 Feb 1 [Epub ahead of print].
—Kimberly Williams
Starting School Later Improves Sleep Time
Delaying school start time can provide sustained benefits for sleep duration, daytime alertness, and mental well-being, according to a study published online ahead of print April 10 in Sleep. The study included 375 girls in grades 7 to 10 from a secondary school for girls. The school delayed its start time from 7:30 to 8:15 in the morning. Self-reports of sleep timing, sleepiness, and well-being were obtained at baseline before the delay and at approximately one and nine months after the delay. After one month, bedtimes on school nights were delayed by nine minutes, while rise times were delayed by 31.6 minutes, resulting in an increase in time in bed of 23.2 minutes. After nine months, the increase in time in bed was sustained, and total sleep time increased by 10 minutes.
Lo JC, Lee SM, Lee XK, et al. Sustained benefits of delaying school start time on adolescent sleep and well-being. Sleep. 2018 Apr 10 [Epub ahead of print].
Stroke Affects Social, Cognitive, and Psychologic Outcomes
Patients with ischemic stroke report symptoms in multiple domains that increase to variable degrees at higher levels of disability, according to a study published online ahead of print March 28 in Neurology. The observational cohort included 1,195 patients who completed Quality of Life in Neurological Disorders or the Patient-Reported Outcomes Measurement Information System scales as part of routine care. Participants were questioned about their physical function, satisfaction with social roles, fatigue, anxiety, depression, pain interference, and sleep disturbance. Researchers also measured participants’ level of disability. Among people with stroke, scores were considerably worse than those in the general population in every area except sleep and depression. About 58% of people with stroke had scores related to satisfaction with social roles that were meaningfully worse than those of the general population.
Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018 Mar 28 [Epub ahead of print].
ALS Genetic Variant Also a Risk Factor for Frontotemporal Dementia
One of the newly identified genetic variants associated with amyotrophic lateral sclerosis (ALS) also is a risk factor for frontotemporal dementia (FTD), according to a study published online ahead of print April 9 in JAMA Neurology. Researchers pooled data from previous genome-wide association studies that included genetic data from 124,876 participants. The studies included healthy controls and participants with ALS, Alzheimer’s disease, Parkinson’s disease, FTD, corticobasal degeneration, and progressive supranuclear palsy. Investigators found that a variation in a region of DNA containing the gene for tau protein was associated with elevated risk for ALS. In addition, study authors found significant genetic overlap between ALS and FTD at known ALS loci rs13302855, rs3849942, and rs4239633. They also found a genetic variation at rs538622 that is associated with ALS and FTD and affects BNIP1 production in the brain.
Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].
Intervention Promotes Stroke Preparedness
Hip-Hop Stroke (HHS) is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities, according to a study published in the April issue of Stroke. HHS is a three-hour, culturally tailored, theory-based, multimedia stroke literacy intervention that empowers schoolchildren to share stroke information with parents. Researchers recruited 3,070 fourth- through sixth-graders and 1,144 parents from 22 schools into a cluster-randomized trial. Schools were randomized to the HHS intervention or attentional control (ie, nutrition classes). Main outcome measures were stroke knowledge and preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% of controls and 2% of the intervention group demonstrated optimal stroke preparedness at baseline, increasing to 57% immediately after the program in the intervention group.
Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving community stroke preparedness in the HHS (Hip-Hop Stroke) randomized clinical trial. Stroke. 2018;49(4):972-979.
Risk of Unnatural Death Is Increased in Epilepsy
People with epilepsy are at increased risk of mortality from suicide and accidents, according to a study published online ahead of print April 9 in JAMA Neurology. Researchers examined the Clinical Practice Research Datalink (CPRD) and the Secure Anonymized Information Linkage (SAIL) databank, which are linked to hospitalization and mortality records. They matched people with epilepsy on age, sex, and general practice with as many as 20 controls. In all, 44,678 people in the CPRD and 14,051 individuals in the SAIL databank were identified in the prevalent epilepsy cohorts. Furthermore, 891,429 participants from the CPRD and 279,365 people from the SAIL databank were identified as controls. People with epilepsy were significantly more likely to die of an unnatural cause, unintentional injury, poisoning, or suicide, compared with controls.
Gorton HC, Webb RT, Carr MJ, et al. Risk of unnatural mortality in people with epilepsy. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].
Method to Assess Consciousness May Improve Care
The Glasgow Coma Scale-Pupil (GCS-P) score provides a way to rapidly assess levels of consciousness in people with head injuries and could improve patient care, according to a study published online ahead of print April 10 in the Journal of Neurosurgery. Investigators obtained patient-level information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality by reviewing data from the Corticosteroid Randomization After Significant Head Injury study and the International Mission for Prognosis and Clinical Trials database. GCS score and pupil response were independently related to patient outcome. Adding information about pupil response to the GCS score improved the information. The performance of the GCS-P was similar to that of methods for evaluating traumatic brain damage.
Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Apr 10 [Epub ahead of print].
Biomarkers of Dementia Risk Identified
Researchers have identified novel biomarkers of risk for future dementia, according to a study published online ahead of print February 28 in Alzheimer’s & Dementia. Investigators analyzed metabolites in blood samples drawn from 22,623 people enrolled in eight prospective cohorts. Over 246,698 person-years, they detected 995 cases of incident dementia and 745 cases of incident Alzheimer’s disease. Isoleucine, leucine, valine, creatinine, and two VLDL-specific lipoprotein lipid subclasses were associated with lower dementia risk. One HDL and one VLDL lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids also were associated with decreased Alzheimer’s disease risk, and the concentration of cholesterol esters relative to total lipids in large HDL was associated with increased Alzheimer’s disease risk.
Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimers Dement. 2018 Feb 28 [Epub ahead of print].
Smartphone App Helps Doctors Track Parkinson’s Disease Symptoms
A smartphone app generates a score that reflects symptom severity in patients with Parkinson’s disease, according to a study published online ahead of print March 26 in JAMA Neurology. This observational study assessed people with Parkinson’s disease who remotely completed voice, finger tapping, gait, balance, and reaction time tasks on the app. Researchers generated a mobile Parkinson’s disease score (mPDS) of 0 to 100 that objectively weighed features derived from each smartphone activity. The mPDS was based on 6,148 smartphone activity assessments from 129 individuals. Gait features contributed most to the total mPDS (33.4%). The mPDS detected symptom fluctuations with a mean intraday change of 13.9 points. The mPDS improved by a mean of 16.3 points in response to dopaminergic therapy.
Zhan A, Mohan S, Tarolli C, et al. Using smartphones and machine learning to quantify Parkinson disease severity: the mobile Parkinson disease score. JAMA Neurol. 2018 Mar 26 [Epub ahead of print].
Age at Natural Menopause Linked to Memory
Entering menopause at a later age may benefit memory in women years later, according to a study published online ahead of print April 11 in Neurology. Researchers used data from 1,315 participants in the Medical Research Council National Survey of Health and Development with known age at period cessation and as many as four assessments of verbal memory and processing speed at ages 43, 53, between 60 and 64, and 69. Investigators fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, BMI, smoking, occupational class, education, and childhood cognitive ability. Verbal memory increased with later age at natural menopause and with later age at surgical menopause. The association between age at natural menopause and verbal memory remained significant after data adjustment.
Kuh D, Cooper R, Moore A, et al. Age at menopause and lifetime cognition: findings from a British birth cohort study. Neurology. 2018 Apr 11 [Epub ahead of print].
Single-Pulse TMS Decreases Migraine Frequency
Single-pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a study published online ahead of print March 4 in Cephalalgia. Researchers examined data from the eNeura SpringTMS Post-Market Observational US Study of Migraine, a multicenter, prospective, open-label, observational study. A total of 263 patients with migraine completed a one-month baseline headache diary, followed by three months of preventive (four pulses bid) and acute treatment (three pulses repeated as many as three times per attack). In all, 220 participants were eligible based on their number of headache days. The device was assigned to 217 subjects, and 132 were included in the intention-to-treat full-analysis set. Treatment reduced mean monthly headache days by 2.75. The most common adverse events were tingling, lightheadedness, and tinnitus.
Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 Mar 4 [Epub ahead of print].
Short Sleep Increases Risk of Obesity in the Young
Short sleep duration is a risk factor for obesity in infants, children, and adolescents, according to a study published online ahead of print February 1 in Sleep. Researchers reviewed the results of 42 population studies that included 75,499 infants, children, and adolescents ages 0 to 18. Sleep duration was assessed through methods such as questionnaires and wearable technology. The investigators classified participants as short sleepers or regular sleepers. Short sleepers were defined as having less sleep than the reference category for their age. Participants were followed up for a median of three years, and changes in BMI and incidence of overweight status and obesity were recorded. At all ages, short sleepers gained more weight and were 58% more likely to become overweight or obese.
Miller MA, Kruisbrink M, Wallace J, et al. Sleep duration and incidence of obesity in infants, children and adolescents: a systematic review and meta-analysis of prospective studies. Sleep. 2018 Feb 1 [Epub ahead of print].
—Kimberly Williams
Starting School Later Improves Sleep Time
Delaying school start time can provide sustained benefits for sleep duration, daytime alertness, and mental well-being, according to a study published online ahead of print April 10 in Sleep. The study included 375 girls in grades 7 to 10 from a secondary school for girls. The school delayed its start time from 7:30 to 8:15 in the morning. Self-reports of sleep timing, sleepiness, and well-being were obtained at baseline before the delay and at approximately one and nine months after the delay. After one month, bedtimes on school nights were delayed by nine minutes, while rise times were delayed by 31.6 minutes, resulting in an increase in time in bed of 23.2 minutes. After nine months, the increase in time in bed was sustained, and total sleep time increased by 10 minutes.
Lo JC, Lee SM, Lee XK, et al. Sustained benefits of delaying school start time on adolescent sleep and well-being. Sleep. 2018 Apr 10 [Epub ahead of print].
Stroke Affects Social, Cognitive, and Psychologic Outcomes
Patients with ischemic stroke report symptoms in multiple domains that increase to variable degrees at higher levels of disability, according to a study published online ahead of print March 28 in Neurology. The observational cohort included 1,195 patients who completed Quality of Life in Neurological Disorders or the Patient-Reported Outcomes Measurement Information System scales as part of routine care. Participants were questioned about their physical function, satisfaction with social roles, fatigue, anxiety, depression, pain interference, and sleep disturbance. Researchers also measured participants’ level of disability. Among people with stroke, scores were considerably worse than those in the general population in every area except sleep and depression. About 58% of people with stroke had scores related to satisfaction with social roles that were meaningfully worse than those of the general population.
Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018 Mar 28 [Epub ahead of print].
ALS Genetic Variant Also a Risk Factor for Frontotemporal Dementia
One of the newly identified genetic variants associated with amyotrophic lateral sclerosis (ALS) also is a risk factor for frontotemporal dementia (FTD), according to a study published online ahead of print April 9 in JAMA Neurology. Researchers pooled data from previous genome-wide association studies that included genetic data from 124,876 participants. The studies included healthy controls and participants with ALS, Alzheimer’s disease, Parkinson’s disease, FTD, corticobasal degeneration, and progressive supranuclear palsy. Investigators found that a variation in a region of DNA containing the gene for tau protein was associated with elevated risk for ALS. In addition, study authors found significant genetic overlap between ALS and FTD at known ALS loci rs13302855, rs3849942, and rs4239633. They also found a genetic variation at rs538622 that is associated with ALS and FTD and affects BNIP1 production in the brain.
Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].
Intervention Promotes Stroke Preparedness
Hip-Hop Stroke (HHS) is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities, according to a study published in the April issue of Stroke. HHS is a three-hour, culturally tailored, theory-based, multimedia stroke literacy intervention that empowers schoolchildren to share stroke information with parents. Researchers recruited 3,070 fourth- through sixth-graders and 1,144 parents from 22 schools into a cluster-randomized trial. Schools were randomized to the HHS intervention or attentional control (ie, nutrition classes). Main outcome measures were stroke knowledge and preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% of controls and 2% of the intervention group demonstrated optimal stroke preparedness at baseline, increasing to 57% immediately after the program in the intervention group.
Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving community stroke preparedness in the HHS (Hip-Hop Stroke) randomized clinical trial. Stroke. 2018;49(4):972-979.
Risk of Unnatural Death Is Increased in Epilepsy
People with epilepsy are at increased risk of mortality from suicide and accidents, according to a study published online ahead of print April 9 in JAMA Neurology. Researchers examined the Clinical Practice Research Datalink (CPRD) and the Secure Anonymized Information Linkage (SAIL) databank, which are linked to hospitalization and mortality records. They matched people with epilepsy on age, sex, and general practice with as many as 20 controls. In all, 44,678 people in the CPRD and 14,051 individuals in the SAIL databank were identified in the prevalent epilepsy cohorts. Furthermore, 891,429 participants from the CPRD and 279,365 people from the SAIL databank were identified as controls. People with epilepsy were significantly more likely to die of an unnatural cause, unintentional injury, poisoning, or suicide, compared with controls.
Gorton HC, Webb RT, Carr MJ, et al. Risk of unnatural mortality in people with epilepsy. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].
Method to Assess Consciousness May Improve Care
The Glasgow Coma Scale-Pupil (GCS-P) score provides a way to rapidly assess levels of consciousness in people with head injuries and could improve patient care, according to a study published online ahead of print April 10 in the Journal of Neurosurgery. Investigators obtained patient-level information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality by reviewing data from the Corticosteroid Randomization After Significant Head Injury study and the International Mission for Prognosis and Clinical Trials database. GCS score and pupil response were independently related to patient outcome. Adding information about pupil response to the GCS score improved the information. The performance of the GCS-P was similar to that of methods for evaluating traumatic brain damage.
Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Apr 10 [Epub ahead of print].
Biomarkers of Dementia Risk Identified
Researchers have identified novel biomarkers of risk for future dementia, according to a study published online ahead of print February 28 in Alzheimer’s & Dementia. Investigators analyzed metabolites in blood samples drawn from 22,623 people enrolled in eight prospective cohorts. Over 246,698 person-years, they detected 995 cases of incident dementia and 745 cases of incident Alzheimer’s disease. Isoleucine, leucine, valine, creatinine, and two VLDL-specific lipoprotein lipid subclasses were associated with lower dementia risk. One HDL and one VLDL lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids also were associated with decreased Alzheimer’s disease risk, and the concentration of cholesterol esters relative to total lipids in large HDL was associated with increased Alzheimer’s disease risk.
Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimers Dement. 2018 Feb 28 [Epub ahead of print].
Smartphone App Helps Doctors Track Parkinson’s Disease Symptoms
A smartphone app generates a score that reflects symptom severity in patients with Parkinson’s disease, according to a study published online ahead of print March 26 in JAMA Neurology. This observational study assessed people with Parkinson’s disease who remotely completed voice, finger tapping, gait, balance, and reaction time tasks on the app. Researchers generated a mobile Parkinson’s disease score (mPDS) of 0 to 100 that objectively weighed features derived from each smartphone activity. The mPDS was based on 6,148 smartphone activity assessments from 129 individuals. Gait features contributed most to the total mPDS (33.4%). The mPDS detected symptom fluctuations with a mean intraday change of 13.9 points. The mPDS improved by a mean of 16.3 points in response to dopaminergic therapy.
Zhan A, Mohan S, Tarolli C, et al. Using smartphones and machine learning to quantify Parkinson disease severity: the mobile Parkinson disease score. JAMA Neurol. 2018 Mar 26 [Epub ahead of print].
Age at Natural Menopause Linked to Memory
Entering menopause at a later age may benefit memory in women years later, according to a study published online ahead of print April 11 in Neurology. Researchers used data from 1,315 participants in the Medical Research Council National Survey of Health and Development with known age at period cessation and as many as four assessments of verbal memory and processing speed at ages 43, 53, between 60 and 64, and 69. Investigators fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, BMI, smoking, occupational class, education, and childhood cognitive ability. Verbal memory increased with later age at natural menopause and with later age at surgical menopause. The association between age at natural menopause and verbal memory remained significant after data adjustment.
Kuh D, Cooper R, Moore A, et al. Age at menopause and lifetime cognition: findings from a British birth cohort study. Neurology. 2018 Apr 11 [Epub ahead of print].
Single-Pulse TMS Decreases Migraine Frequency
Single-pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a study published online ahead of print March 4 in Cephalalgia. Researchers examined data from the eNeura SpringTMS Post-Market Observational US Study of Migraine, a multicenter, prospective, open-label, observational study. A total of 263 patients with migraine completed a one-month baseline headache diary, followed by three months of preventive (four pulses bid) and acute treatment (three pulses repeated as many as three times per attack). In all, 220 participants were eligible based on their number of headache days. The device was assigned to 217 subjects, and 132 were included in the intention-to-treat full-analysis set. Treatment reduced mean monthly headache days by 2.75. The most common adverse events were tingling, lightheadedness, and tinnitus.
Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 Mar 4 [Epub ahead of print].
Short Sleep Increases Risk of Obesity in the Young
Short sleep duration is a risk factor for obesity in infants, children, and adolescents, according to a study published online ahead of print February 1 in Sleep. Researchers reviewed the results of 42 population studies that included 75,499 infants, children, and adolescents ages 0 to 18. Sleep duration was assessed through methods such as questionnaires and wearable technology. The investigators classified participants as short sleepers or regular sleepers. Short sleepers were defined as having less sleep than the reference category for their age. Participants were followed up for a median of three years, and changes in BMI and incidence of overweight status and obesity were recorded. At all ages, short sleepers gained more weight and were 58% more likely to become overweight or obese.
Miller MA, Kruisbrink M, Wallace J, et al. Sleep duration and incidence of obesity in infants, children and adolescents: a systematic review and meta-analysis of prospective studies. Sleep. 2018 Feb 1 [Epub ahead of print].
—Kimberly Williams