Neurology

The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.

Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.

After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.

In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.

“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”

The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.

The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.

“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”

In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.

Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.

The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).

The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.

However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.

The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.

SOURCE: Sen S et al. Neurology. 2018;91:1-9.

This article was updated 12/12/18.

The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.

Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.

After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.

In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.

“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”

The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.

The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.

“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”

In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.

Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.

The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).

The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.

However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.

The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.

SOURCE: Sen S et al. Neurology. 2018;91:1-9.

This article was updated 12/12/18.

The presence of visual aura during migraine is associated with an increased risk of atrial fibrillation, a study in Neurology has found.

Researchers reported an analysis of data from the longitudinal, community-based Atherosclerosis Risk in Communities (ARIC) Study, which included 11,939 individuals with no history of atrial fibrillation or stroke. Of these, 426 experienced migraines with visual aura, 1,090 experienced migraines without aura, 1,018 experienced nonmigraine headache, and 9,405 experienced no headache.

After adjustment for age and sex, individuals who had migraine with visual aura showed a significant 46% increase in the risk of incident atrial fibrillation when compared with those who experienced migraine without aura and a 39% increased risk when compared with individuals who did not experience headache (P = .004). After adjustment for risk factors such as hypertension, smoking, coronary artery disease, and congestive heart failure, the hazard ratio of incident atrial fibrillation was 1.30 for migraineurs with aura, compared with people without headache. In addition, the hazard ratio of incident atrial fibrillation was 1.39 for migraineurs with aura, compared with migraineurs without aura.

In contrast, individuals who experienced migraines without aura did not show a significantly increased risk of atrial fibrillation.

“This finding has important clinical implications and may help us better understand the atrial fibrillation mediation of the migraine-stroke link,” wrote Souvik Sen, MD, MPH, a professor in the department of neurology at the University of South Carolina, Columbia, and his coauthors. “A randomized clinical trial may help ascertain whether patients with migraine with visual aura may benefit from atrial fibrillation detection and subsequent anticoagulation or antiplatelet therapy as a primary stroke prevention strategy.”

The study also showed a significant interaction with age and sex. While men who experienced migraine with aura had an 89% higher risk of atrial fibrillation, women with aura showed no increase in risk, compared with individuals who experienced no headache. Similarly, only individuals aged 60 years or older who experienced migraine with aura showed an increased risk of atrial fibrillation, while those younger than 60 years did not.

The authors noted that previous case reports have recorded the incidence of atrial fibrillation during a migraine attack. Autonomic dysfunction influences the pathophysiology of atrial fibrillation and migraine.

“Cardiac arrhythmia recordings have been shown to be present in ECGs of patients while experiencing migraine headaches as compared with migraine-free phases,” they wrote. “This hypothesis is further supported by atrial fibrillation ablation procedures that have shown tendencies to reduce migraine symptoms and frequencies.”

In regard to the role that migraine aura played in this, they speculated as to whether migraine aura could be the result of cardioembolic stroke that might have occurred because of the atrial fibrillation.

Overall, 167 patients had incident cardioembolic strokes, and researchers suggested strokes in 87% of these cases could be attributed to the atrial fibrillation that came before the stroke.

The stroke incidence rate also was around twice as high in individuals who experienced migraine with aura, compared with those who experienced migraine without aura (4.1 per 1,000 person-years vs. 2.07 per 1,000 person-years).

The study authors acknowledged that patent foramen ovale, which was not assessed in ARIC, is a possible confounder. Previous studies have showed that patent foramen ovale is more common in younger individuals with migraine and particularly in patients who experience migraine with aura.

However, they also noted that trials of patent foramen ovale closures as a treatment for migraine have not shown success in reducing migraine frequency and, therefore, argued against patent foramen ovale as being a major confounder.

The study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. One author declared grants from the National Institutes of health, one declared research support from Tian Medical, and one author is an associate editor for Neurology. No other conflicts of interest were declared.

SOURCE: Sen S et al. Neurology. 2018;91:1-9.

This article was updated 12/12/18.

Use of anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) may benefit children with more than 8 headache days each month, a high Pediatric Migraine Disability Assessment (PedMIDAS) score, and failure of other treatments; however, researchers cautioned that long-term safety outcomes for the treatment are not yet known, according to a recent set of recommendations published in the journal Headache.

Christina L. Szperka, MD, MSCE, of the division of neurology at the Children’s Hospital of Philadelphia and members of the Pediatric and Adolescent Headache special interest group of the American Headache Society discussed the topic of anti-CGRP mAbs at the 2018 Annual Scientific Meeting of the American Headache Society. They noted clinical outcomes for anti-CGRP mAbs in pediatric patients will likely not be available for several years and created a set of recommendations based on expert opinion of anti-CGRP mAb use in children and adolescents.

Their recommendations support using anti-CGRP mAbs for children with migraine if patients meet the following criteria: headache frequency exceeding 8 headache days per month; a PedMIDAS score of 30 or greater; failure of two or more therapies, such as pharmacologic, nonpharmacologic, or nutraceutical ones; and in patients who are past puberty.

The special interest group recommended against use of anti-CGRP mAbs in children and adolescents with recent meningitis, recent peripheral nerve injury, neurosurgery, or a central nervous system injury caused by a potentially compromised blood-brain barrier. Children and adolescents with immunodeficiency, receiving immunosuppressive medications, with structural heart defects, with pulmonary hypertension, with coronary artery disease, with cardiomyopathy, or at risk for stroke should also avoid use of anti-CGRP mAbs. Anti-CGRP mAbs are also potentially teratogenic and should not be used by adolescents or women who are pregnant, breastfeeding, or have a pregnancy wish.

Pediatric patients with significant osteoporosis or bone disease should be monitored when prescribed anti-CGRP mAbs, and the recommendations specified monitoring height and linear growth or waiting until after puberty to prescribe anti-CGRP mAbs. Although there is currently no evidence that use of anti-CGRP mAb requires pituitary hormone monitoring, the recommendations noted that weight and body mass index should also be observed.

“Pediatric and adolescent trials of anti-CGRP mAbs should be designed to maximize the chances of determining efficacy in these age groups and should focus on those who have not been successful with current multidisciplinary care,” Dr. Szperka and her colleagues wrote in the recommendations. “In the interim, the use of anti-CGRP mAbs for the treatment of headache disorders in children and adolescents may be considered in appropriate cases but should be done with close follow-up and attention to patient characteristics such as age, pubertal state, and medical comorbidities.”

Dr. Szperka receives grant support from Pfizer and Amgen and research funding from NIH. Other authors have reported grants, consulting fees, speaking fees, royalties, advisory board memberships, speaker’s bureau memberships and travel funds from Alder, Allergan, American Academy of Neurology, Amgen, Aralez, Avanir, Autonomic Technologies Inc., Biohaven, Cambridge University Press, Curelator, Depomed, Dr. Reddy’s Laboratories, Electrocore, eNeura, Genentech, Healint, Impax, JAMA Neurology, Journal Watch, Lilly, Massachusetts Medical Society, MedDay, MedicoLegal, Merck, NIH, Novartis, Oxford University Press, Quest Diagnostics, Scion, Supernus, Teva, Trigemina Inc., Upsher-Smith, UpToDate, Wolters Kluwer and Zosano.

SOURCE: Szperka CL et al. Headache. 2018. doi: 10.1111/head.13414.

Use of anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) may benefit children with more than 8 headache days each month, a high Pediatric Migraine Disability Assessment (PedMIDAS) score, and failure of other treatments; however, researchers cautioned that long-term safety outcomes for the treatment are not yet known, according to a recent set of recommendations published in the journal Headache.

Christina L. Szperka, MD, MSCE, of the division of neurology at the Children’s Hospital of Philadelphia and members of the Pediatric and Adolescent Headache special interest group of the American Headache Society discussed the topic of anti-CGRP mAbs at the 2018 Annual Scientific Meeting of the American Headache Society. They noted clinical outcomes for anti-CGRP mAbs in pediatric patients will likely not be available for several years and created a set of recommendations based on expert opinion of anti-CGRP mAb use in children and adolescents.

Their recommendations support using anti-CGRP mAbs for children with migraine if patients meet the following criteria: headache frequency exceeding 8 headache days per month; a PedMIDAS score of 30 or greater; failure of two or more therapies, such as pharmacologic, nonpharmacologic, or nutraceutical ones; and in patients who are past puberty.

The special interest group recommended against use of anti-CGRP mAbs in children and adolescents with recent meningitis, recent peripheral nerve injury, neurosurgery, or a central nervous system injury caused by a potentially compromised blood-brain barrier. Children and adolescents with immunodeficiency, receiving immunosuppressive medications, with structural heart defects, with pulmonary hypertension, with coronary artery disease, with cardiomyopathy, or at risk for stroke should also avoid use of anti-CGRP mAbs. Anti-CGRP mAbs are also potentially teratogenic and should not be used by adolescents or women who are pregnant, breastfeeding, or have a pregnancy wish.

Pediatric patients with significant osteoporosis or bone disease should be monitored when prescribed anti-CGRP mAbs, and the recommendations specified monitoring height and linear growth or waiting until after puberty to prescribe anti-CGRP mAbs. Although there is currently no evidence that use of anti-CGRP mAb requires pituitary hormone monitoring, the recommendations noted that weight and body mass index should also be observed.

“Pediatric and adolescent trials of anti-CGRP mAbs should be designed to maximize the chances of determining efficacy in these age groups and should focus on those who have not been successful with current multidisciplinary care,” Dr. Szperka and her colleagues wrote in the recommendations. “In the interim, the use of anti-CGRP mAbs for the treatment of headache disorders in children and adolescents may be considered in appropriate cases but should be done with close follow-up and attention to patient characteristics such as age, pubertal state, and medical comorbidities.”

Dr. Szperka receives grant support from Pfizer and Amgen and research funding from NIH. Other authors have reported grants, consulting fees, speaking fees, royalties, advisory board memberships, speaker’s bureau memberships and travel funds from Alder, Allergan, American Academy of Neurology, Amgen, Aralez, Avanir, Autonomic Technologies Inc., Biohaven, Cambridge University Press, Curelator, Depomed, Dr. Reddy’s Laboratories, Electrocore, eNeura, Genentech, Healint, Impax, JAMA Neurology, Journal Watch, Lilly, Massachusetts Medical Society, MedDay, MedicoLegal, Merck, NIH, Novartis, Oxford University Press, Quest Diagnostics, Scion, Supernus, Teva, Trigemina Inc., Upsher-Smith, UpToDate, Wolters Kluwer and Zosano.

SOURCE: Szperka CL et al. Headache. 2018. doi: 10.1111/head.13414.

Use of anti–calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) may benefit children with more than 8 headache days each month, a high Pediatric Migraine Disability Assessment (PedMIDAS) score, and failure of other treatments; however, researchers cautioned that long-term safety outcomes for the treatment are not yet known, according to a recent set of recommendations published in the journal Headache.

Christina L. Szperka, MD, MSCE, of the division of neurology at the Children’s Hospital of Philadelphia and members of the Pediatric and Adolescent Headache special interest group of the American Headache Society discussed the topic of anti-CGRP mAbs at the 2018 Annual Scientific Meeting of the American Headache Society. They noted clinical outcomes for anti-CGRP mAbs in pediatric patients will likely not be available for several years and created a set of recommendations based on expert opinion of anti-CGRP mAb use in children and adolescents.

Their recommendations support using anti-CGRP mAbs for children with migraine if patients meet the following criteria: headache frequency exceeding 8 headache days per month; a PedMIDAS score of 30 or greater; failure of two or more therapies, such as pharmacologic, nonpharmacologic, or nutraceutical ones; and in patients who are past puberty.

The special interest group recommended against use of anti-CGRP mAbs in children and adolescents with recent meningitis, recent peripheral nerve injury, neurosurgery, or a central nervous system injury caused by a potentially compromised blood-brain barrier. Children and adolescents with immunodeficiency, receiving immunosuppressive medications, with structural heart defects, with pulmonary hypertension, with coronary artery disease, with cardiomyopathy, or at risk for stroke should also avoid use of anti-CGRP mAbs. Anti-CGRP mAbs are also potentially teratogenic and should not be used by adolescents or women who are pregnant, breastfeeding, or have a pregnancy wish.

Pediatric patients with significant osteoporosis or bone disease should be monitored when prescribed anti-CGRP mAbs, and the recommendations specified monitoring height and linear growth or waiting until after puberty to prescribe anti-CGRP mAbs. Although there is currently no evidence that use of anti-CGRP mAb requires pituitary hormone monitoring, the recommendations noted that weight and body mass index should also be observed.

“Pediatric and adolescent trials of anti-CGRP mAbs should be designed to maximize the chances of determining efficacy in these age groups and should focus on those who have not been successful with current multidisciplinary care,” Dr. Szperka and her colleagues wrote in the recommendations. “In the interim, the use of anti-CGRP mAbs for the treatment of headache disorders in children and adolescents may be considered in appropriate cases but should be done with close follow-up and attention to patient characteristics such as age, pubertal state, and medical comorbidities.”

Dr. Szperka receives grant support from Pfizer and Amgen and research funding from NIH. Other authors have reported grants, consulting fees, speaking fees, royalties, advisory board memberships, speaker’s bureau memberships and travel funds from Alder, Allergan, American Academy of Neurology, Amgen, Aralez, Avanir, Autonomic Technologies Inc., Biohaven, Cambridge University Press, Curelator, Depomed, Dr. Reddy’s Laboratories, Electrocore, eNeura, Genentech, Healint, Impax, JAMA Neurology, Journal Watch, Lilly, Massachusetts Medical Society, MedDay, MedicoLegal, Merck, NIH, Novartis, Oxford University Press, Quest Diagnostics, Scion, Supernus, Teva, Trigemina Inc., Upsher-Smith, UpToDate, Wolters Kluwer and Zosano.

SOURCE: Szperka CL et al. Headache. 2018. doi: 10.1111/head.13414.

Children and adolescents who suffer sports-related concussion should engage in light activities for their minds and bodies, while being monitored and evaluated, according to a new clinical report from the American Academy of Pediatrics.

The update to the 2010 guidelines was needed to reflect the latest research “and it was necessary to provide this new information to guide pediatricians in evaluating and treating concussions they may see in their practice,” Mark Halstead, MD, of Washington University, St. Louis, said in an interview.

The biggest changes to the guidelines involve management of concussion, noted Dr. Halstead, who was a coauthor of the AAP clinical report. “The previous recommendation called for cognitive and physical rest, which unfortunately was interpreted as complete removal from all physical activity and limiting many other things including electronic use.

“Because of research that has been conducted since the original report, it has been shown that starting some light physical activity to increase heart rate, provided it does not worsen symptoms, can be beneficial in recovery. Also, the recommendation for complete removal of electronics and computer use has unfortunately created some issues with kids getting socially isolated,” he added.

James Boulette/iStockphoto

“For better or for worse, kids are connected through their electronic devices. Removing them, with no evidence that it worsens the concussion, essentially punishes kids for their injury. We also are trying to discourage prolonged removal of kids from school,” Dr. Halstead emphasized.

The new recommendations emphasize the unique nature of sports-related concussion (SRC) from one individual to another, and the need for individualized management.

Symptoms of SRC fall into five categories, according to the guidelines: somatic, vestibular, oculomotor, cognitive, and emotional/sleep. Pediatric health care providers should rule out more severe head injuries and recognize that concussion symptoms are nonspecific and may reflect preexisting conditions, such as migraine or headache disorders, learning disorders, ADHD, mental health conditions, or sleep disorders.

Use of assessments such as the Sport Concussion Management Tool (SCAT5 for 13 years and older or Child SCAT5 for 5-12 years) can help guide clinicians, but should not be used in isolation to diagnose a concussion, the guideline authors wrote.

Strategies for injury prevention are included in the guidelines as well, such as the use of appropriate headgear. As for management, computerized neurocognitive testing can play a role in decisions regarding return to play, but should not be used in isolation.

“The biggest thing we are lacking is an objective diagnostic test to determine the presence of a concussion or its resolution,” coauthor Kody A. Moffatt, MD, of Creighton University, Omaha, Nebraska, said in an interview.

“Mandatory baseline and postinjury computerized neurocognitive testing is not recommended,” he added.

Clinicians can best manage SRC with prompt recognition and diagnosis using the available tools, followed by relative rest and return to school, then noncontact physical activities, and eventually a return to sport if appropriate.

“Most concussions in children and adolescents will resolve within 4 weeks as long as there is not additional injury to the brain during that time,” Dr. Moffat said.

More research is needed in particular about concussions in elementary and middle school children, Dr. Halstead added.

In the meantime, the take-home message to pediatricians for managing SRC is one of common sense. “Extremes of removing all stimulus from a child is not likely to get them better sooner and research suggests may take them longer to get better,” Dr. Halstead noted. “That doesn’t mean they don’t have to reduce anything, as it is important to reduce physical activity and modify school workload while recovering but we should be avoiding the blanket recommendation to ‘stay home and do nothing until you are better’ approach to concussion management.”

Dr. Halstead and Dr. Moffatt reported no relevant financial conflicts to disclose; the same was true for the other report coauthors. There was no external funding for the report.

SOURCE: Halstead M et al. Pediatrics. 2018 Nov 12. doi: 10.1542/peds.2018-3074.

Children and adolescents who suffer sports-related concussion should engage in light activities for their minds and bodies, while being monitored and evaluated, according to a new clinical report from the American Academy of Pediatrics.

The update to the 2010 guidelines was needed to reflect the latest research “and it was necessary to provide this new information to guide pediatricians in evaluating and treating concussions they may see in their practice,” Mark Halstead, MD, of Washington University, St. Louis, said in an interview.

The biggest changes to the guidelines involve management of concussion, noted Dr. Halstead, who was a coauthor of the AAP clinical report. “The previous recommendation called for cognitive and physical rest, which unfortunately was interpreted as complete removal from all physical activity and limiting many other things including electronic use.

“Because of research that has been conducted since the original report, it has been shown that starting some light physical activity to increase heart rate, provided it does not worsen symptoms, can be beneficial in recovery. Also, the recommendation for complete removal of electronics and computer use has unfortunately created some issues with kids getting socially isolated,” he added.

James Boulette/iStockphoto

“For better or for worse, kids are connected through their electronic devices. Removing them, with no evidence that it worsens the concussion, essentially punishes kids for their injury. We also are trying to discourage prolonged removal of kids from school,” Dr. Halstead emphasized.

The new recommendations emphasize the unique nature of sports-related concussion (SRC) from one individual to another, and the need for individualized management.

Symptoms of SRC fall into five categories, according to the guidelines: somatic, vestibular, oculomotor, cognitive, and emotional/sleep. Pediatric health care providers should rule out more severe head injuries and recognize that concussion symptoms are nonspecific and may reflect preexisting conditions, such as migraine or headache disorders, learning disorders, ADHD, mental health conditions, or sleep disorders.

Use of assessments such as the Sport Concussion Management Tool (SCAT5 for 13 years and older or Child SCAT5 for 5-12 years) can help guide clinicians, but should not be used in isolation to diagnose a concussion, the guideline authors wrote.

Strategies for injury prevention are included in the guidelines as well, such as the use of appropriate headgear. As for management, computerized neurocognitive testing can play a role in decisions regarding return to play, but should not be used in isolation.

“The biggest thing we are lacking is an objective diagnostic test to determine the presence of a concussion or its resolution,” coauthor Kody A. Moffatt, MD, of Creighton University, Omaha, Nebraska, said in an interview.

“Mandatory baseline and postinjury computerized neurocognitive testing is not recommended,” he added.

Clinicians can best manage SRC with prompt recognition and diagnosis using the available tools, followed by relative rest and return to school, then noncontact physical activities, and eventually a return to sport if appropriate.

“Most concussions in children and adolescents will resolve within 4 weeks as long as there is not additional injury to the brain during that time,” Dr. Moffat said.

More research is needed in particular about concussions in elementary and middle school children, Dr. Halstead added.

In the meantime, the take-home message to pediatricians for managing SRC is one of common sense. “Extremes of removing all stimulus from a child is not likely to get them better sooner and research suggests may take them longer to get better,” Dr. Halstead noted. “That doesn’t mean they don’t have to reduce anything, as it is important to reduce physical activity and modify school workload while recovering but we should be avoiding the blanket recommendation to ‘stay home and do nothing until you are better’ approach to concussion management.”

Dr. Halstead and Dr. Moffatt reported no relevant financial conflicts to disclose; the same was true for the other report coauthors. There was no external funding for the report.

SOURCE: Halstead M et al. Pediatrics. 2018 Nov 12. doi: 10.1542/peds.2018-3074.

Children and adolescents who suffer sports-related concussion should engage in light activities for their minds and bodies, while being monitored and evaluated, according to a new clinical report from the American Academy of Pediatrics.

The update to the 2010 guidelines was needed to reflect the latest research “and it was necessary to provide this new information to guide pediatricians in evaluating and treating concussions they may see in their practice,” Mark Halstead, MD, of Washington University, St. Louis, said in an interview.

The biggest changes to the guidelines involve management of concussion, noted Dr. Halstead, who was a coauthor of the AAP clinical report. “The previous recommendation called for cognitive and physical rest, which unfortunately was interpreted as complete removal from all physical activity and limiting many other things including electronic use.

“Because of research that has been conducted since the original report, it has been shown that starting some light physical activity to increase heart rate, provided it does not worsen symptoms, can be beneficial in recovery. Also, the recommendation for complete removal of electronics and computer use has unfortunately created some issues with kids getting socially isolated,” he added.

James Boulette/iStockphoto

“For better or for worse, kids are connected through their electronic devices. Removing them, with no evidence that it worsens the concussion, essentially punishes kids for their injury. We also are trying to discourage prolonged removal of kids from school,” Dr. Halstead emphasized.

The new recommendations emphasize the unique nature of sports-related concussion (SRC) from one individual to another, and the need for individualized management.

Symptoms of SRC fall into five categories, according to the guidelines: somatic, vestibular, oculomotor, cognitive, and emotional/sleep. Pediatric health care providers should rule out more severe head injuries and recognize that concussion symptoms are nonspecific and may reflect preexisting conditions, such as migraine or headache disorders, learning disorders, ADHD, mental health conditions, or sleep disorders.

Use of assessments such as the Sport Concussion Management Tool (SCAT5 for 13 years and older or Child SCAT5 for 5-12 years) can help guide clinicians, but should not be used in isolation to diagnose a concussion, the guideline authors wrote.

Strategies for injury prevention are included in the guidelines as well, such as the use of appropriate headgear. As for management, computerized neurocognitive testing can play a role in decisions regarding return to play, but should not be used in isolation.

“The biggest thing we are lacking is an objective diagnostic test to determine the presence of a concussion or its resolution,” coauthor Kody A. Moffatt, MD, of Creighton University, Omaha, Nebraska, said in an interview.

“Mandatory baseline and postinjury computerized neurocognitive testing is not recommended,” he added.

Clinicians can best manage SRC with prompt recognition and diagnosis using the available tools, followed by relative rest and return to school, then noncontact physical activities, and eventually a return to sport if appropriate.

“Most concussions in children and adolescents will resolve within 4 weeks as long as there is not additional injury to the brain during that time,” Dr. Moffat said.

More research is needed in particular about concussions in elementary and middle school children, Dr. Halstead added.

In the meantime, the take-home message to pediatricians for managing SRC is one of common sense. “Extremes of removing all stimulus from a child is not likely to get them better sooner and research suggests may take them longer to get better,” Dr. Halstead noted. “That doesn’t mean they don’t have to reduce anything, as it is important to reduce physical activity and modify school workload while recovering but we should be avoiding the blanket recommendation to ‘stay home and do nothing until you are better’ approach to concussion management.”

Dr. Halstead and Dr. Moffatt reported no relevant financial conflicts to disclose; the same was true for the other report coauthors. There was no external funding for the report.

SOURCE: Halstead M et al. Pediatrics. 2018 Nov 12. doi: 10.1542/peds.2018-3074.

Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the Centers for Disease Control and Prevention.

Sasiistock/iStock/Getty Images Plus

The number of confirmed cases is triple that seen in 2017.

Nearly all of the patients (90%) were children aged 2-8 years, and 99% experienced a fever and /or respiratory illness 7-10 days before the onset of symptoms. But although the prodrome and seasonality of AFM suggest an infective process, only 54% of the patients tested positive for the virus, Nancy Messonnier, MD, said during a briefing held by CDC officials. The most common findings were the enteroviruses EV-A71 (29%) and EV-D68 (37%); other viruses were recovered in the remaining pathogen-positive cases.

It’s not at all clear that these were causative agents, said Dr. Messonnier, director of the National Center for Immunization and Respiratory Diseases.

“At this time of year lots of children have a fever and respiratory infections,” she said. AFM may be caused by one of the identified viruses, a still-undetected pathogen, or a pathogen hiding in untested tissue. “Or, it could be an infection that’s kicking off an immune process,” attacking gray matter in the spinal cord.

The reported increase in cases must be viewed cautiously, Dr. Messonnier said. Physicians are becoming more aware of AFM, so the spike could represent an increase in reporting as well as actual incidence.

It’s not clear why the disease manifests almost exclusively in children, Dr. Messonnier said. Nor do health officials have much of a grasp on AFM’s long-term sequelae.

“We know that patients can recover fully, but at least half don’t, and some of those have serious sequelae. Unfortunately, we have not been following every patient, so this is a gap in our knowledge.”

A newly created national task force will examine AFM’s long-term effects, Dr. Messonnier said. The task force will also look at mortality; health departments across the country will examine mortality records to identify any past deaths preceded by AFM-like symptoms.

“One of the reasons we have convened this task force is to think about this hypothesis [of an autoimmune syndrome]. We have not backed off on the idea of an infectious organism causing it, but we are thinking more broadly,” Dr. Messonnier said.

Some anti-immunization groups are blaming vaccines for the disease, noting that several childhood vaccines list encephalomyelitis and transverse myelitis as possible adverse events.

“We are investigating every one of the cases in this and prior years and have a list of hypotheses based on the epidemiology,” Dr. Messonnier said. “I would say toxins are low on that list. Many of the children may have been vaccinated [before developing AFM] and that is something we will look at, but for now we recommend that all children should be vaccinated” according to the recommended schedule.

Additional details were published on 80 of the cases. Patients’ mean age was 4 years; 59% were male. Symptoms suggesting a viral illness occurred in 99%; these included fever (81%), cough, rhinorrhea, and congestion (78%), and vomiting and diarrhea (38%).

AFM symptoms varied; 47% had only upper limb involvement, 9% only lower limb, 15% two or three upper, and 29% all four limbs. All the patients with confirmed AFM were hospitalized, and 59% treated in intensive care units. There were no deaths (MMWR. 2018;ePub:13 November. DOI: http://dx.doi.org/10.15585/mmwr.mm6745e1).

AFM remains extremely rare, Dr. Messonnier said. But physicians should be alert for any signs of sudden limb weakness in children and report those immediately. The workup should include questions about recent fever with or without respiratory or gastrointestinal symptoms. Prompt collection of viral testing samples (cerebrospinal fluid, serum, respiratory, and stool specimens) is critical.

Additional information for health care professionals is available on the CDC AFM web page.

msullivan@mdedge.com

Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the Centers for Disease Control and Prevention.

Sasiistock/iStock/Getty Images Plus

The number of confirmed cases is triple that seen in 2017.

Nearly all of the patients (90%) were children aged 2-8 years, and 99% experienced a fever and /or respiratory illness 7-10 days before the onset of symptoms. But although the prodrome and seasonality of AFM suggest an infective process, only 54% of the patients tested positive for the virus, Nancy Messonnier, MD, said during a briefing held by CDC officials. The most common findings were the enteroviruses EV-A71 (29%) and EV-D68 (37%); other viruses were recovered in the remaining pathogen-positive cases.

It’s not at all clear that these were causative agents, said Dr. Messonnier, director of the National Center for Immunization and Respiratory Diseases.

“At this time of year lots of children have a fever and respiratory infections,” she said. AFM may be caused by one of the identified viruses, a still-undetected pathogen, or a pathogen hiding in untested tissue. “Or, it could be an infection that’s kicking off an immune process,” attacking gray matter in the spinal cord.

The reported increase in cases must be viewed cautiously, Dr. Messonnier said. Physicians are becoming more aware of AFM, so the spike could represent an increase in reporting as well as actual incidence.

It’s not clear why the disease manifests almost exclusively in children, Dr. Messonnier said. Nor do health officials have much of a grasp on AFM’s long-term sequelae.

“We know that patients can recover fully, but at least half don’t, and some of those have serious sequelae. Unfortunately, we have not been following every patient, so this is a gap in our knowledge.”

A newly created national task force will examine AFM’s long-term effects, Dr. Messonnier said. The task force will also look at mortality; health departments across the country will examine mortality records to identify any past deaths preceded by AFM-like symptoms.

“One of the reasons we have convened this task force is to think about this hypothesis [of an autoimmune syndrome]. We have not backed off on the idea of an infectious organism causing it, but we are thinking more broadly,” Dr. Messonnier said.

Some anti-immunization groups are blaming vaccines for the disease, noting that several childhood vaccines list encephalomyelitis and transverse myelitis as possible adverse events.

“We are investigating every one of the cases in this and prior years and have a list of hypotheses based on the epidemiology,” Dr. Messonnier said. “I would say toxins are low on that list. Many of the children may have been vaccinated [before developing AFM] and that is something we will look at, but for now we recommend that all children should be vaccinated” according to the recommended schedule.

Additional details were published on 80 of the cases. Patients’ mean age was 4 years; 59% were male. Symptoms suggesting a viral illness occurred in 99%; these included fever (81%), cough, rhinorrhea, and congestion (78%), and vomiting and diarrhea (38%).

AFM symptoms varied; 47% had only upper limb involvement, 9% only lower limb, 15% two or three upper, and 29% all four limbs. All the patients with confirmed AFM were hospitalized, and 59% treated in intensive care units. There were no deaths (MMWR. 2018;ePub:13 November. DOI: http://dx.doi.org/10.15585/mmwr.mm6745e1).

AFM remains extremely rare, Dr. Messonnier said. But physicians should be alert for any signs of sudden limb weakness in children and report those immediately. The workup should include questions about recent fever with or without respiratory or gastrointestinal symptoms. Prompt collection of viral testing samples (cerebrospinal fluid, serum, respiratory, and stool specimens) is critical.

Additional information for health care professionals is available on the CDC AFM web page.

msullivan@mdedge.com

Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the Centers for Disease Control and Prevention.

Sasiistock/iStock/Getty Images Plus

The number of confirmed cases is triple that seen in 2017.

Nearly all of the patients (90%) were children aged 2-8 years, and 99% experienced a fever and /or respiratory illness 7-10 days before the onset of symptoms. But although the prodrome and seasonality of AFM suggest an infective process, only 54% of the patients tested positive for the virus, Nancy Messonnier, MD, said during a briefing held by CDC officials. The most common findings were the enteroviruses EV-A71 (29%) and EV-D68 (37%); other viruses were recovered in the remaining pathogen-positive cases.

It’s not at all clear that these were causative agents, said Dr. Messonnier, director of the National Center for Immunization and Respiratory Diseases.

“At this time of year lots of children have a fever and respiratory infections,” she said. AFM may be caused by one of the identified viruses, a still-undetected pathogen, or a pathogen hiding in untested tissue. “Or, it could be an infection that’s kicking off an immune process,” attacking gray matter in the spinal cord.

The reported increase in cases must be viewed cautiously, Dr. Messonnier said. Physicians are becoming more aware of AFM, so the spike could represent an increase in reporting as well as actual incidence.

It’s not clear why the disease manifests almost exclusively in children, Dr. Messonnier said. Nor do health officials have much of a grasp on AFM’s long-term sequelae.

“We know that patients can recover fully, but at least half don’t, and some of those have serious sequelae. Unfortunately, we have not been following every patient, so this is a gap in our knowledge.”

A newly created national task force will examine AFM’s long-term effects, Dr. Messonnier said. The task force will also look at mortality; health departments across the country will examine mortality records to identify any past deaths preceded by AFM-like symptoms.

“One of the reasons we have convened this task force is to think about this hypothesis [of an autoimmune syndrome]. We have not backed off on the idea of an infectious organism causing it, but we are thinking more broadly,” Dr. Messonnier said.

Some anti-immunization groups are blaming vaccines for the disease, noting that several childhood vaccines list encephalomyelitis and transverse myelitis as possible adverse events.

“We are investigating every one of the cases in this and prior years and have a list of hypotheses based on the epidemiology,” Dr. Messonnier said. “I would say toxins are low on that list. Many of the children may have been vaccinated [before developing AFM] and that is something we will look at, but for now we recommend that all children should be vaccinated” according to the recommended schedule.

Additional details were published on 80 of the cases. Patients’ mean age was 4 years; 59% were male. Symptoms suggesting a viral illness occurred in 99%; these included fever (81%), cough, rhinorrhea, and congestion (78%), and vomiting and diarrhea (38%).

AFM symptoms varied; 47% had only upper limb involvement, 9% only lower limb, 15% two or three upper, and 29% all four limbs. All the patients with confirmed AFM were hospitalized, and 59% treated in intensive care units. There were no deaths (MMWR. 2018;ePub:13 November. DOI: http://dx.doi.org/10.15585/mmwr.mm6745e1).

AFM remains extremely rare, Dr. Messonnier said. But physicians should be alert for any signs of sudden limb weakness in children and report those immediately. The workup should include questions about recent fever with or without respiratory or gastrointestinal symptoms. Prompt collection of viral testing samples (cerebrospinal fluid, serum, respiratory, and stool specimens) is critical.

Additional information for health care professionals is available on the CDC AFM web page.

msullivan@mdedge.com

Clinical question: Can an opiate-prescribing standard that favors oral and subcutaneous over intravenous administration reduce exposure to intravenous opiates for hospitalized adults?

Background: IV opiates, while effective for analgesia, may have a higher addictive potential because of the rapid and intermittent rises of peak concentrations. Subcutaneous and/or oral administration is a proven method of opioid delivery with similar bioavailability and efficacy of intravenous administration with more favorable pharmacokinetics.

Study design: Intervention-based quality improvement project.

Dr. Chowdury is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Can an opiate-prescribing standard that favors oral and subcutaneous over intravenous administration reduce exposure to intravenous opiates for hospitalized adults?

Background: IV opiates, while effective for analgesia, may have a higher addictive potential because of the rapid and intermittent rises of peak concentrations. Subcutaneous and/or oral administration is a proven method of opioid delivery with similar bioavailability and efficacy of intravenous administration with more favorable pharmacokinetics.

Study design: Intervention-based quality improvement project.

Dr. Chowdury is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Can an opiate-prescribing standard that favors oral and subcutaneous over intravenous administration reduce exposure to intravenous opiates for hospitalized adults?

Background: IV opiates, while effective for analgesia, may have a higher addictive potential because of the rapid and intermittent rises of peak concentrations. Subcutaneous and/or oral administration is a proven method of opioid delivery with similar bioavailability and efficacy of intravenous administration with more favorable pharmacokinetics.

Study design: Intervention-based quality improvement project.

Dr. Chowdury is an assistant professor in the division of hospital medicine, University of Colorado, Denver.

Risk of suicide was doubled in persons who experienced a concussion or mild traumatic brain injury (TBI) earlier in life, according to results of a meta-analysis of 17 studies representing nearly 7 million patients.

However, the absolute risk of suicide remained quite low, according to Michael Fralick, MD, of the University of Toronto, and co-investigators.

“Nearly all patients diagnosed with concussion and/or mild TBI did not die by suicide,” Dr. Fralick and colleagues said in their report on the study, which appears in JAMA Neurology.

Nevertheless, the meta-analysis illustrates evidence for an increased risk of suicide, suicide attempts, and suicidal ideation for persons with a history of these injuries, they said in the report.

The meta-analysis included 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies looking at the risk of suicide, suicide attempts, or suicidal ideation after a concussion or mild TBI. Those studies included a roughly 714,000 individuals with a concussion and/or TBI diagnosis, and 6,236,000 without a diagnosis.

For people diagnosed with at least one concussion and/or mild TBI, the risk of suicide was 2-fold higher (relative risk, 2.03; 95% CI, 1.47-2.80; P less than 0.001), according to the report.

The risk was “slightly stronger,” investigators said, when the analysis was limited to studies adjusting for factors associated with those brain injuries and with suicide (RR, 2.10; 95% CI, 1.40-3.13; P less than 0.01).

Four of the 5 cohort studies reported absolute risk of suicide, according to Dr. Fralick and coauthors. In one study with a median follow-up of 3.6 years, 0.50% of individuals with a concussion and/or TBI subsequently died of suicide, while similarly, 0.59% died in a study with 4.0 years of follow-up, 0.28% in a study with 9.3 years follow-up, and 0.49% in one with a 12.3 year median follow-up.

Most of the studies in the meta-analysis reported an increased risk of suicide attempt after concussion and/or mild TBI, according to Dr. Fralick and his collaborators, while the eight studies looking at suicidal ideation all reported heightened risk after those brain injuries.

The researchers acknowledged some limitations of their analysis. Recall bias could have led to an overestimation of the association between concussion and suicide risk, since suicide attempts may affect reporting of concussion history, they said.

Furthermore, most of the studies were retrospective, and did not include an active comparator group, such as individuals with non-neurologic injuries, they added.

“Until large prospective studies with sufficiently large durations of follow-up are available, we have to rely on the currently available data,” they said in the report.

Dr. Fralick and co-authors reported no conflict of interest disclosures related to the study.

SOURCE: Fralick M, et al. JAMA Neurol. 2018 Nov 12.

Risk of suicide was doubled in persons who experienced a concussion or mild traumatic brain injury (TBI) earlier in life, according to results of a meta-analysis of 17 studies representing nearly 7 million patients.

However, the absolute risk of suicide remained quite low, according to Michael Fralick, MD, of the University of Toronto, and co-investigators.

“Nearly all patients diagnosed with concussion and/or mild TBI did not die by suicide,” Dr. Fralick and colleagues said in their report on the study, which appears in JAMA Neurology.

Nevertheless, the meta-analysis illustrates evidence for an increased risk of suicide, suicide attempts, and suicidal ideation for persons with a history of these injuries, they said in the report.

The meta-analysis included 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies looking at the risk of suicide, suicide attempts, or suicidal ideation after a concussion or mild TBI. Those studies included a roughly 714,000 individuals with a concussion and/or TBI diagnosis, and 6,236,000 without a diagnosis.

For people diagnosed with at least one concussion and/or mild TBI, the risk of suicide was 2-fold higher (relative risk, 2.03; 95% CI, 1.47-2.80; P less than 0.001), according to the report.

The risk was “slightly stronger,” investigators said, when the analysis was limited to studies adjusting for factors associated with those brain injuries and with suicide (RR, 2.10; 95% CI, 1.40-3.13; P less than 0.01).

Four of the 5 cohort studies reported absolute risk of suicide, according to Dr. Fralick and coauthors. In one study with a median follow-up of 3.6 years, 0.50% of individuals with a concussion and/or TBI subsequently died of suicide, while similarly, 0.59% died in a study with 4.0 years of follow-up, 0.28% in a study with 9.3 years follow-up, and 0.49% in one with a 12.3 year median follow-up.

Most of the studies in the meta-analysis reported an increased risk of suicide attempt after concussion and/or mild TBI, according to Dr. Fralick and his collaborators, while the eight studies looking at suicidal ideation all reported heightened risk after those brain injuries.

The researchers acknowledged some limitations of their analysis. Recall bias could have led to an overestimation of the association between concussion and suicide risk, since suicide attempts may affect reporting of concussion history, they said.

Furthermore, most of the studies were retrospective, and did not include an active comparator group, such as individuals with non-neurologic injuries, they added.

“Until large prospective studies with sufficiently large durations of follow-up are available, we have to rely on the currently available data,” they said in the report.

Dr. Fralick and co-authors reported no conflict of interest disclosures related to the study.

SOURCE: Fralick M, et al. JAMA Neurol. 2018 Nov 12.

Risk of suicide was doubled in persons who experienced a concussion or mild traumatic brain injury (TBI) earlier in life, according to results of a meta-analysis of 17 studies representing nearly 7 million patients.

However, the absolute risk of suicide remained quite low, according to Michael Fralick, MD, of the University of Toronto, and co-investigators.

“Nearly all patients diagnosed with concussion and/or mild TBI did not die by suicide,” Dr. Fralick and colleagues said in their report on the study, which appears in JAMA Neurology.

Nevertheless, the meta-analysis illustrates evidence for an increased risk of suicide, suicide attempts, and suicidal ideation for persons with a history of these injuries, they said in the report.

The meta-analysis included 10 cohort studies, 5 cross-sectional studies, and 2 case-control studies looking at the risk of suicide, suicide attempts, or suicidal ideation after a concussion or mild TBI. Those studies included a roughly 714,000 individuals with a concussion and/or TBI diagnosis, and 6,236,000 without a diagnosis.

For people diagnosed with at least one concussion and/or mild TBI, the risk of suicide was 2-fold higher (relative risk, 2.03; 95% CI, 1.47-2.80; P less than 0.001), according to the report.

The risk was “slightly stronger,” investigators said, when the analysis was limited to studies adjusting for factors associated with those brain injuries and with suicide (RR, 2.10; 95% CI, 1.40-3.13; P less than 0.01).

Four of the 5 cohort studies reported absolute risk of suicide, according to Dr. Fralick and coauthors. In one study with a median follow-up of 3.6 years, 0.50% of individuals with a concussion and/or TBI subsequently died of suicide, while similarly, 0.59% died in a study with 4.0 years of follow-up, 0.28% in a study with 9.3 years follow-up, and 0.49% in one with a 12.3 year median follow-up.

Most of the studies in the meta-analysis reported an increased risk of suicide attempt after concussion and/or mild TBI, according to Dr. Fralick and his collaborators, while the eight studies looking at suicidal ideation all reported heightened risk after those brain injuries.

The researchers acknowledged some limitations of their analysis. Recall bias could have led to an overestimation of the association between concussion and suicide risk, since suicide attempts may affect reporting of concussion history, they said.

Furthermore, most of the studies were retrospective, and did not include an active comparator group, such as individuals with non-neurologic injuries, they added.

“Until large prospective studies with sufficiently large durations of follow-up are available, we have to rely on the currently available data,” they said in the report.

Dr. Fralick and co-authors reported no conflict of interest disclosures related to the study.

SOURCE: Fralick M, et al. JAMA Neurol. 2018 Nov 12.

Pediatric headache and migraine are associated with a variety of conditions including respiratory, gastrointestinal, neurologic, and mood disorders, according to findings published in the Journal of Pediatrics.

Marta Ortiz/iStock/Getty Images Plus

In a study of 9,329 pediatric patients from the Philadelphia Neurodevelopmental Cohort, at the University of Pennsylvania, children with any headache type were more likely to have cardiovascular (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) and gastrointestinal (OR, 1.2; 95% CI, 1.1-1.4) problems than did those without headache. In addition, they were more likely to have attention deficit hyperactivity disorder (OR, 1.2; 95% CI, 1.1-1.4), wrote Tarannum M. Lateef, MD, MPH, of the Center for Neuroscience and Behavioral Medicine at Children’s National Medical Center in Washington, and her coauthors.

Study participants were aged 8-21 years and were enrolled in the cohort from November 2009 to November 2011. Physical conditions were identified using EMRs and interviews and were later grouped together by general category.

Patients were asked about lifetime headache and migraine symptoms including sensitivity to light and noise, gastrointestinal symptoms, unilateral pain, throbbing and pulsation, and interference at school or work. Migraine was defined as headache accompanied by any three of these symptoms. Mental disorders were identified using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, reported Dr. Lateef and her associates.

Lifetime prevalence of any headache was 45.5%, and 22.6% for migraine. Migraine was more common in female patients (25.5%) than in male patients (19.4%).

Compared with nonmigraine headache patients, those with migraine more frequently had neurologic/central nervous system disorders (OR, 1.7; 95% CI, 1.4-2.0), developmental disorders (OR, 1.3; 95% CI, 1.1-1.6), respiratory problems (OR, 1.3; 95% CI, 1.1-1.6), anxiety (OR, 1.6; 95% CI, 1.3-2), mood disorders (OR, 2; 95% CI, 1.6-2.3), and behavioral disorders (OR, 1.3; 95% CI, 1.1-1.6).

The results suggest that “headache, particularly migraine, is associated with respiratory and other neurologic and developmental disorders, as well as with anxiety and mood disorders,” the authors wrote.

“Comorbidity may be an important index of heterogeneity … that can guide clinical management, genetic investigation, and future research on shared pathophysiology” with other disorders, they concluded.

No disclosures were reported.
 

SOURCE: Lateef T et al. J Pediatr. 2018 Oct 29. doi: 10.1016/j.jpeds.2018.09.033.

Pediatric headache and migraine are associated with a variety of conditions including respiratory, gastrointestinal, neurologic, and mood disorders, according to findings published in the Journal of Pediatrics.

Marta Ortiz/iStock/Getty Images Plus

In a study of 9,329 pediatric patients from the Philadelphia Neurodevelopmental Cohort, at the University of Pennsylvania, children with any headache type were more likely to have cardiovascular (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) and gastrointestinal (OR, 1.2; 95% CI, 1.1-1.4) problems than did those without headache. In addition, they were more likely to have attention deficit hyperactivity disorder (OR, 1.2; 95% CI, 1.1-1.4), wrote Tarannum M. Lateef, MD, MPH, of the Center for Neuroscience and Behavioral Medicine at Children’s National Medical Center in Washington, and her coauthors.

Study participants were aged 8-21 years and were enrolled in the cohort from November 2009 to November 2011. Physical conditions were identified using EMRs and interviews and were later grouped together by general category.

Patients were asked about lifetime headache and migraine symptoms including sensitivity to light and noise, gastrointestinal symptoms, unilateral pain, throbbing and pulsation, and interference at school or work. Migraine was defined as headache accompanied by any three of these symptoms. Mental disorders were identified using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, reported Dr. Lateef and her associates.

Lifetime prevalence of any headache was 45.5%, and 22.6% for migraine. Migraine was more common in female patients (25.5%) than in male patients (19.4%).

Compared with nonmigraine headache patients, those with migraine more frequently had neurologic/central nervous system disorders (OR, 1.7; 95% CI, 1.4-2.0), developmental disorders (OR, 1.3; 95% CI, 1.1-1.6), respiratory problems (OR, 1.3; 95% CI, 1.1-1.6), anxiety (OR, 1.6; 95% CI, 1.3-2), mood disorders (OR, 2; 95% CI, 1.6-2.3), and behavioral disorders (OR, 1.3; 95% CI, 1.1-1.6).

The results suggest that “headache, particularly migraine, is associated with respiratory and other neurologic and developmental disorders, as well as with anxiety and mood disorders,” the authors wrote.

“Comorbidity may be an important index of heterogeneity … that can guide clinical management, genetic investigation, and future research on shared pathophysiology” with other disorders, they concluded.

No disclosures were reported.
 

SOURCE: Lateef T et al. J Pediatr. 2018 Oct 29. doi: 10.1016/j.jpeds.2018.09.033.

Pediatric headache and migraine are associated with a variety of conditions including respiratory, gastrointestinal, neurologic, and mood disorders, according to findings published in the Journal of Pediatrics.

Marta Ortiz/iStock/Getty Images Plus

In a study of 9,329 pediatric patients from the Philadelphia Neurodevelopmental Cohort, at the University of Pennsylvania, children with any headache type were more likely to have cardiovascular (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) and gastrointestinal (OR, 1.2; 95% CI, 1.1-1.4) problems than did those without headache. In addition, they were more likely to have attention deficit hyperactivity disorder (OR, 1.2; 95% CI, 1.1-1.4), wrote Tarannum M. Lateef, MD, MPH, of the Center for Neuroscience and Behavioral Medicine at Children’s National Medical Center in Washington, and her coauthors.

Study participants were aged 8-21 years and were enrolled in the cohort from November 2009 to November 2011. Physical conditions were identified using EMRs and interviews and were later grouped together by general category.

Patients were asked about lifetime headache and migraine symptoms including sensitivity to light and noise, gastrointestinal symptoms, unilateral pain, throbbing and pulsation, and interference at school or work. Migraine was defined as headache accompanied by any three of these symptoms. Mental disorders were identified using an abbreviated version of the Kiddie-Schedule for Affective Disorders and Schizophrenia, reported Dr. Lateef and her associates.

Lifetime prevalence of any headache was 45.5%, and 22.6% for migraine. Migraine was more common in female patients (25.5%) than in male patients (19.4%).

Compared with nonmigraine headache patients, those with migraine more frequently had neurologic/central nervous system disorders (OR, 1.7; 95% CI, 1.4-2.0), developmental disorders (OR, 1.3; 95% CI, 1.1-1.6), respiratory problems (OR, 1.3; 95% CI, 1.1-1.6), anxiety (OR, 1.6; 95% CI, 1.3-2), mood disorders (OR, 2; 95% CI, 1.6-2.3), and behavioral disorders (OR, 1.3; 95% CI, 1.1-1.6).

The results suggest that “headache, particularly migraine, is associated with respiratory and other neurologic and developmental disorders, as well as with anxiety and mood disorders,” the authors wrote.

“Comorbidity may be an important index of heterogeneity … that can guide clinical management, genetic investigation, and future research on shared pathophysiology” with other disorders, they concluded.

No disclosures were reported.
 

SOURCE: Lateef T et al. J Pediatr. 2018 Oct 29. doi: 10.1016/j.jpeds.2018.09.033.

A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.

jpbcpa/Getty Images

The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.

Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.

All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).

In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).

Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).

The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.

The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.

The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.

Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).

Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.

When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.

The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.

SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.

A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.

jpbcpa/Getty Images

The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.

Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.

All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).

In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).

Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).

The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.

The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.

The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.

Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).

Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.

When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.

The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.

SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.

A series of three studies in college students showed that some serum markers are associated with concussion but the background level of the markers can vary considerably. There was no association between the markers and history of concussion, and they markers varied significantly by sex and race.

jpbcpa/Getty Images

The work, published in Neurology, suggests that there is hope for finding biomarkers for concussion, but much more work needs to be done.

Serum levels of amyloid beta 42 (Abeta42), total tau, and S100 calcium binding protein B (S100B) were associated with concussion, especially when tests were performed within 4 hours of the injury. However, the varying background levels indicate that these biomarkers are not yet ready for clinical application.

All three studies looked at serum levels of Abeta42, total tau, S100B, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), microtubule-associated protein 2 (MAP2), and 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase).

In the first study, researchers recruited 415 college athletes without a concussion (61% male, 40% white). The researchers took measurements outside of the athletes’ competitive sports season to maximize the odds that the levels would represent a true baseline. The median time between blood draw and the last risk of head impact was 80 days (mean, 98.4 days; interquartile range, 38-204 days).

Males had higher levels of UCH-L1 (Cohen d = 0.75; P less than .001) and S100B (Cohen d = 0.56; P less than .001), while females had higher levels of CNPase (Cohen d = 0.43; P less than .001). White subjects had higher levels of Abeta42 (Cohen d = .28; P = .005) and CNPase (Cohen d = 0.46; P less than .001). Black subjects had higher levels of UCH-L1 (Cohen d = 0.61; P less than .001) and S100 B (Cohen d = 1.1; P less than .001).

The measurements were not particularly reliable, with retests over 6- to 12-month periods yielding varying results such that none of the test/retest cutoff points reached the cutoff for acceptable reliability.

The second study was an observational cohort study of the same 415 subjects. The researchers assessed the self-reported concussion history and the cumulative exposure to collision sports with serum levels of the above biomarkers. The only relationship between a biomarker history and self-reported concussions was higher baseline Abeta42, but that had a small effect size (P = .005). Among football players, there was no association between approximate number of head impacts and any baseline biomarker.

The third study looked at 31 subjects who had experienced a sports-related concussion, 29 of whom had had both a baseline and a postconcussion blood draw, and compared them with nonconcussed, demographically matched athletes.

Of all the biomarkers studied, only levels of S100B rose following a concussion, with 67% of concussed subjects experiencing such a change (P = .003). When the researchers restricted the analysis to subjects who had a blood draw within 4 hours of the concussion, 88% of the tests showed an increase (P = .001). UCH-L1 also rose in 86% of subjects, but this change was not significant after adjustment for multiple comparisons (P greater than .007).

Compared with controls, concussed individuals had significantly higher levels of Abeta42, total tau, S100B, and GFAP. Of the concussed patients, 79.4% had Abeta42 levels higher than the median of controls, 67.6% had higher levels of total tau than the median of controls, and 83.3% had higher levels of S100B. Restriction of analysis to blood drawn within 4 hours of the injury yielded values of 81.3%, 75.0%, and 88.2%, respectively.

When limited to blood draws taken within 4 hours of injury, the researchers found fair diagnostic accuracy for measurements of Abeta42 (area under the curve, 0.75; 95% confidence interval, 0.59-0.91), total tau (AUC, 0.74; 95% CI, 0.58-0.90), and S100B (AUC, 0.75; 95% CI, 0.64-0.85). Abeta42 concentrations higher than 13.7 pg/mL were 75.0% sensitive and 82.4% specific to a sports-related concussion. Total tau concentrations higher than 1.7 pg/mL detected sports-related concussions at 75.0% sensitivity and 66.3% specificity, with acceptable diagnostic accuracy for white subjects (AUC, 0.82, 95% CI, 0.72-0.93). Also for white participants, S100B concentrations higher than 53 pg/mL predicted sports-related concussions with 83.3% sensitivity and 74.6% specificity.

The researchers found no associations between biomarkers and performance on clinical tests or time away from sports.

SOURCE: BM Asken et al. Neurology. 2018. doi: 10.1212/WNL.0000000000006613.

ATLANTA – In the fall of 2013, world-famous actor and comedian Robin Williams began to suffer symptoms from a disease he would never know the name of: Lewy body dementia.

Doug Brunk/MDedge News

“With our medical team’s care, for the next 10 months we chased symptoms, but they were so elusive,” Mr. Williams’ widow, Susan Schneider Williams, said during a keynote address at the annual meeting of the American Neurological Association. “One hallmark of LBD is that symptoms appear and disappear randomly. The game whack-a-mole comes to mind. As soon as you think you are about to figure out a symptom, it disappears, and another one pops up.”

Mr. Williams’ medical team included one general physician, one neurologist, one motor specialist, two psychiatrists, one hypnotherapist, one physical trainer, and assorted alternative specialists. “We had been celebrating our second wedding anniversary when Robin started having gut discomfort,” Ms. Williams recalled. “He was tested for diverticulitis [but] the results came back negative. The pain eventually subsided but what was alarming was Robin’s reaction to it. He had a sudden and sustained spike in fear and anxiety unlike anything I’d seen before. By that point, we’d been by each other’s side long enough that I knew his normal baseline moods, fears, and anxieties. This was totally out of character, and I wondered privately: ‘Is my husband a hypochondriac?’ What I know now is that he was exhibiting a notable hallmark of LBD: new onset anxiety, sustained.” Lewy body disease is characterized by more than 40 symptoms, she continued, “and Robin experienced nearly all of them. He was particularly debilitated by fear, anxiety, delusions, paranoia, and as I came to find out later, hallucinations.”

The medical team continued running all sorts of tests, but everything kept came back negative, except for a very high cortisol count. By the late spring of 2014, however, Mr. Williams was diagnosed with Parkinson’s disease. “I was relieved to find out we finally had an answer, but I could tell, Robin was not buying it,” said Ms. Williams, who is a California-based fine artist, author, and brain health advocate. “The motor specialist said it was early and mild and that he’d be feeling better once he adjusted to the medications, [that] he had another 10 good years.”

In an attempt to treat the Parkinson’s and what was assumed to be depression, his care plan involved adjusting Parkinson’s medications, combined with an antidepressant. His physician also recommended a visit to the Dan Anderson Renewal Center in Minnesota, “for enhanced 12-step work to augment his sobriety,” Ms. Williams said. “The hope was this might help with fear and anxiety. Robin was clean and sober for 8 continuous years when he passed. I watched how he gained spiritually in so many ways from all the work he’d been doing, but his brain biology was going in the exact opposite direction. He tried desperately to join the parts of his heart, mind, and spirit, but his brain was pulling him apart. I felt like I was watching my husband disintegrate before my eyes, and there was nothing anyone could do about it. There came a day when we were getting ready to go to one of our dear friend’s birthday party. I came and saw Robin as he lay on our bed, imprisoned by fear and anxiety. Through tears, he pleaded, ‘I just want to reboot my brain!’ I promised him, ‘I know, honey. I swear we’re going to get to the bottom of this.’ ”

The couple was about a week away from choosing which neurocognitive testing facility to go to for further evaluation when Mr. Williams took his own life in his Paradise Cay, Calif., home on Aug. 11, 2014. “Robin was exhausted from the terror coming from his brain,” Ms. Williams said. “He took [his own life] before it could take any more of him.”

dbrunk@mdedge.com

ATLANTA – In the fall of 2013, world-famous actor and comedian Robin Williams began to suffer symptoms from a disease he would never know the name of: Lewy body dementia.

Doug Brunk/MDedge News

“With our medical team’s care, for the next 10 months we chased symptoms, but they were so elusive,” Mr. Williams’ widow, Susan Schneider Williams, said during a keynote address at the annual meeting of the American Neurological Association. “One hallmark of LBD is that symptoms appear and disappear randomly. The game whack-a-mole comes to mind. As soon as you think you are about to figure out a symptom, it disappears, and another one pops up.”

Mr. Williams’ medical team included one general physician, one neurologist, one motor specialist, two psychiatrists, one hypnotherapist, one physical trainer, and assorted alternative specialists. “We had been celebrating our second wedding anniversary when Robin started having gut discomfort,” Ms. Williams recalled. “He was tested for diverticulitis [but] the results came back negative. The pain eventually subsided but what was alarming was Robin’s reaction to it. He had a sudden and sustained spike in fear and anxiety unlike anything I’d seen before. By that point, we’d been by each other’s side long enough that I knew his normal baseline moods, fears, and anxieties. This was totally out of character, and I wondered privately: ‘Is my husband a hypochondriac?’ What I know now is that he was exhibiting a notable hallmark of LBD: new onset anxiety, sustained.” Lewy body disease is characterized by more than 40 symptoms, she continued, “and Robin experienced nearly all of them. He was particularly debilitated by fear, anxiety, delusions, paranoia, and as I came to find out later, hallucinations.”

The medical team continued running all sorts of tests, but everything kept came back negative, except for a very high cortisol count. By the late spring of 2014, however, Mr. Williams was diagnosed with Parkinson’s disease. “I was relieved to find out we finally had an answer, but I could tell, Robin was not buying it,” said Ms. Williams, who is a California-based fine artist, author, and brain health advocate. “The motor specialist said it was early and mild and that he’d be feeling better once he adjusted to the medications, [that] he had another 10 good years.”

In an attempt to treat the Parkinson’s and what was assumed to be depression, his care plan involved adjusting Parkinson’s medications, combined with an antidepressant. His physician also recommended a visit to the Dan Anderson Renewal Center in Minnesota, “for enhanced 12-step work to augment his sobriety,” Ms. Williams said. “The hope was this might help with fear and anxiety. Robin was clean and sober for 8 continuous years when he passed. I watched how he gained spiritually in so many ways from all the work he’d been doing, but his brain biology was going in the exact opposite direction. He tried desperately to join the parts of his heart, mind, and spirit, but his brain was pulling him apart. I felt like I was watching my husband disintegrate before my eyes, and there was nothing anyone could do about it. There came a day when we were getting ready to go to one of our dear friend’s birthday party. I came and saw Robin as he lay on our bed, imprisoned by fear and anxiety. Through tears, he pleaded, ‘I just want to reboot my brain!’ I promised him, ‘I know, honey. I swear we’re going to get to the bottom of this.’ ”

The couple was about a week away from choosing which neurocognitive testing facility to go to for further evaluation when Mr. Williams took his own life in his Paradise Cay, Calif., home on Aug. 11, 2014. “Robin was exhausted from the terror coming from his brain,” Ms. Williams said. “He took [his own life] before it could take any more of him.”

dbrunk@mdedge.com

ATLANTA – In the fall of 2013, world-famous actor and comedian Robin Williams began to suffer symptoms from a disease he would never know the name of: Lewy body dementia.

Doug Brunk/MDedge News

“With our medical team’s care, for the next 10 months we chased symptoms, but they were so elusive,” Mr. Williams’ widow, Susan Schneider Williams, said during a keynote address at the annual meeting of the American Neurological Association. “One hallmark of LBD is that symptoms appear and disappear randomly. The game whack-a-mole comes to mind. As soon as you think you are about to figure out a symptom, it disappears, and another one pops up.”

Mr. Williams’ medical team included one general physician, one neurologist, one motor specialist, two psychiatrists, one hypnotherapist, one physical trainer, and assorted alternative specialists. “We had been celebrating our second wedding anniversary when Robin started having gut discomfort,” Ms. Williams recalled. “He was tested for diverticulitis [but] the results came back negative. The pain eventually subsided but what was alarming was Robin’s reaction to it. He had a sudden and sustained spike in fear and anxiety unlike anything I’d seen before. By that point, we’d been by each other’s side long enough that I knew his normal baseline moods, fears, and anxieties. This was totally out of character, and I wondered privately: ‘Is my husband a hypochondriac?’ What I know now is that he was exhibiting a notable hallmark of LBD: new onset anxiety, sustained.” Lewy body disease is characterized by more than 40 symptoms, she continued, “and Robin experienced nearly all of them. He was particularly debilitated by fear, anxiety, delusions, paranoia, and as I came to find out later, hallucinations.”

The medical team continued running all sorts of tests, but everything kept came back negative, except for a very high cortisol count. By the late spring of 2014, however, Mr. Williams was diagnosed with Parkinson’s disease. “I was relieved to find out we finally had an answer, but I could tell, Robin was not buying it,” said Ms. Williams, who is a California-based fine artist, author, and brain health advocate. “The motor specialist said it was early and mild and that he’d be feeling better once he adjusted to the medications, [that] he had another 10 good years.”

In an attempt to treat the Parkinson’s and what was assumed to be depression, his care plan involved adjusting Parkinson’s medications, combined with an antidepressant. His physician also recommended a visit to the Dan Anderson Renewal Center in Minnesota, “for enhanced 12-step work to augment his sobriety,” Ms. Williams said. “The hope was this might help with fear and anxiety. Robin was clean and sober for 8 continuous years when he passed. I watched how he gained spiritually in so many ways from all the work he’d been doing, but his brain biology was going in the exact opposite direction. He tried desperately to join the parts of his heart, mind, and spirit, but his brain was pulling him apart. I felt like I was watching my husband disintegrate before my eyes, and there was nothing anyone could do about it. There came a day when we were getting ready to go to one of our dear friend’s birthday party. I came and saw Robin as he lay on our bed, imprisoned by fear and anxiety. Through tears, he pleaded, ‘I just want to reboot my brain!’ I promised him, ‘I know, honey. I swear we’re going to get to the bottom of this.’ ”

The couple was about a week away from choosing which neurocognitive testing facility to go to for further evaluation when Mr. Williams took his own life in his Paradise Cay, Calif., home on Aug. 11, 2014. “Robin was exhausted from the terror coming from his brain,” Ms. Williams said. “He took [his own life] before it could take any more of him.”

dbrunk@mdedge.com

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.

SEATTLE – A novel extrasynaptic gamma-aminobutyric acid (GABA)–receptor agonist called OV-101 was safe and well-tolerated in adult and adolescent Angelman syndrome patients in a 12-week phase 2 trial. In a secondary analysis, the treatment appeared to improve sleep.

Jim Kling/MDedge News

Angelman syndrome is associated with a microdeletion on chromosome 15 encompassing the ubiquitin protein ligase E3a (UBE3A) gene. The resulting loss of expression of the UBE3A protein leads to increases in the uptake of GABA and reduces levels of extrasynaptic GABA. Patients with Angelman syndrome typically have motor dysfunction, often extreme: “These kids are very excitable, very active, and they have lots of trouble with sleep,” said Alex Kolevzon, MD, professor of psychiatry and pediatrics at the Icahn School of Medicine at Mount Sinai, in an interview.

Dr. Kolevzon presented the results at a poster session at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The study was conducted at 12 sites in the United States and 1 in Israel. Ovid Pharmaceuticals plans to apply to the Food and Drug Administration later this year for approval. There is no existing drug for Angelman syndrome, and the study provided good safety reassurance. “There were some side effects, but for the most part we considered them mild, and only four (out of 88 subjects) discontinued because of side effects,” said Dr. Kolevzon.

The researchers used actigraphy to gain a more objective measure of sleep in the study participants. They randomized 88 patients with Angelman syndrome (aged 13-49 years) to receive placebo in the morning and 15 mg of OV-101 at night, 10 mg OVID-101 in the morning and 15 mg OVID-101 at night, or placebo both in the morning and at night.

Pyrexia occurred in 24% of the group who received the active drug only at night, 3% of the group given the twice-daily dose, and 7% of the placebo group. Seizures occurred in 7% of the once-daily group and 10% of the twice-daily group; seizures were not noted in the placebo group.

The main efficacy outcome measure was the Clinical Global Impressions-9 (CGI-9) scale. The once-daily group had a significant benefit in the sleep domain at 12 weeks, compared with placebo (difference, –0.77; P = .0141), but the twice-daily group had only a trend toward improvement in sleep (difference, –0.45; P = .1407).

Both active therapy groups had significant improvement in CGI-9 measures after 12 weeks of treatment compared to placebo – the twice-daily group (P = .0206, Fisher’s Exact Test) and the once-daily group (P = .0006, mixed model repeated measures analysis).

The actigraphy analysis, conducted in the 45% of patients who could tolerate its use, found that, compared to placebo, the once-daily dosing group experienced an 25.7 minute improvement in latency to sleep onset (P = .0147), as well an approximately 50 minute reduction in sleep time during the day, and a 3.65% improvement in sleep efficiency.

OV-101 has the potential to treat other conditions as well. “Obviously there are a lot of neurodevelopmental disorders where you see dysregulation between the GABAergic and glutamergic systems. This is a drug that has a unique effect on the GABAergic system. It’s already being studied in Fragile X syndrome, where we see this same kind of dysregulation and excess excitation,” said Dr. Kolevzon.

Dr. Kolevzon is a consultant for several drug companies including Ovid Therapeutics.
 

SOURCE: AACAP 2018. New Research Poster 3.1.