New and Noteworthy Information—July 2016

There is a strong, inverse association between midlife cardiorespiratory fitness and stroke risk in later life, independent of the baseline and antecedent burden of risk factors, according to a study published online ahead of print June 9 in Stroke. Researchers studied 19,815 individuals who received Medicare coverage from 1999 to 2009. Cardiorespiratory fitness estimated at baseline was analyzed as a continuous variable and according to age- and sex-specific quintiles. Associations between midlife cardiorespiratory fitness and stroke hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. The investigators observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife cardiorespiratory fitness was associated with a lower risk of stroke hospitalization.

Incident dementia early after intracerebral hemorrhage is strongly associated with hematoma size and location, according to a study published online ahead of print June 13 in JAMA Neurology. A longitudinal study enrolled patients with intracerebral hemorrhage from January 1, 2006, to December 31, 2013. In all, 738 participants ages 18 or older, without pre-intracerebral hemorrhage dementia, who presented to a tertiary care academic institution with primary intracerebral hemorrhage were included in the study. A total of 140 patients developed dementia within six months. Larger hematoma size and lobar location of intracerebral hemorrhage were associated with early post-intracerebral hemorrhage dementia, but not with delayed post-intracerebral hemorrhage dementia. Educational level, incident mood symptoms, and white matter disease were associated with delayed, but not early, post-intracerebral hemorrhage dementia.

The FDA is investigating the risk of serious burns and potential permanent scarring from the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch for migraine. The patch delivers a dose of medicine in a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Since the introduction of the patch, many patients have reported injury to the skin where the patch was worn. The reports include descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin. Patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact a health care professional. Teva Pharmaceuticals has suspended the sale, marketing, and distribution of the patch.

More than 90% of the global stroke burden is attributable to modifiable risk factors, including air pollution, and controlling behavioral and metabolic risk factors could avert more than 75% of the global stroke burden, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers used data on stroke-related disability-adjusted life-years, risk factors, and population-attributable fraction from the Global Burden of Disease Study 2013 to estimate the burden of stroke by age and sex in 188 countries. Approximately 74% of the global stroke burden was attributable to behavioral factors. Clusters of metabolic factors (72%) and environmental factors (33%) were the second and third largest contributors to disability-adjusted life-years, respectively. About 29% of the burden of stroke was attributed to air pollution.

Abnormally high fractional anisotropy (FA) on diffusion tensor imaging (DTI) is associated with better outcomes after mild traumatic brain injury (mTBI), according to a study published online ahead of print June 9 in the American Journal of Neuroradiology. DTI was performed on 39 subjects with mTBI within 16 days of injury and on 40 controls. In all, 26 subjects with mTBI returned for follow-up at one year. Among these subjects, high FA in the left frontal lobe and left temporal lobe was associated with better attention. High FA in the left and right cerebelli was associated with improved somatic postconcussion symptoms. High FA in the right thalamus was associated with improved emotional postconcussion symptoms. Abnormally high FA may be an imaging correlate of postinjury compensatory processes, said the investigators.

Among patients with multiple sclerosis (MS), obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function, attention, processing speed, and working memory, according to a study published online ahead of print May 3 in Sleep. Thirty-eight participants underwent MS-specific cognitive testing and in-laboratory overnight polysomnography. In adjusted linear regression models, the oxygen desaturation index and minimum oxygen saturation were significantly associated with performance on multiple Minimal Assessment of Cognitive Function in MS measures. Apnea severity measures accounted for between 11% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation and total sleep time also showed significant associations with a component of the California Verbal Learning Test-II, explaining 18% and 27% of the variance in performance, respectively.

The differences in stroke mortality between African Americans and Caucasians are largely related to differences in stroke incidence, according to a study published online ahead of print June 2 in Stroke. Researchers assessed the difference between African American and Caucasian stroke mortality for 29,681 participants in the Reasons for Geographic and Racial Differences in Stroke cohort. They found that African Americans are four times more likely to die of stroke at age 45 than Caucasians because stroke incidence is greater among African Americans. By age 85, however, the difference in stroke mortality is no longer present. More should be done to reduce the disparity in stroke mortality between African Americans and Caucasians, and interventions should focus on prevention of stroke among African Americans, according to the investigators.

A mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, according to a study published online ahead of print June 6 in Nature Genetics. Researchers first investigated a family with 15 members who had typical symptoms of Parkinson's disease. They used DNA samples to perform a genome-wide analysis on 65 of the family's members, including 13 with Parkinson's disease, to find a common mutation that could explain the prevalence of Parkinson's disease. The study authors identified TMEM230 as the gene with a disease-causing mutation and found that TMEM230 encodes a protein that extends across the membrane of tiny sacs inside synaptic vesicles. The research team also found mutations in TMEM230 in cases of Parkinson's disease in additional families in North America and China.

People with blast exposure have a pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and between gray and white matter, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers analyzed brain specimens from five military service members with chronic blast exposure, three with acute blast exposure, five with chronic impact traumatic brain injury, five with exposure to opiates, and three control cases with no known neurologic disorders. All five cases with chronic blast exposure showed prominent astroglial scarring involving the subpial glial plate, penetrating cortical blood vessels, gray-white matter junctions, and structures lining the ventricles. Cases of acute blast exposure showed early astroglial scarring in the same brain regions. Cases of chronic blast exposure had an antemortem diagnosis of posttraumatic stress disorder.

A combination of dextromethorphan and quinidine is an effective and well-tolerated treatment for pseudobulbar affect secondary to dementia, stroke, or traumatic brain injury, according to a study published June 9 in BMC Neurology. The study included 367 participants with this disorder. Participants in this open-label, multicenter, 90-day trial received dextromethorphan and quinidine twice daily. The mean Center for Neurologic Study-Lability Scale score improved from 20.4 at baseline to 12.8 at the 90-day final visit. Reduction in pseudobulbar affect episode count was 72.3% at the 90-day final visit, compared with baseline. Scores on Clinical Global Impression of Change and Patient Global Impression of Change indicated that 76.6% and 72.4% of participants, respectively, showed much or very much improvement in symptoms of pseudobulbar affect.

—Kimberly Williams

There is a strong, inverse association between midlife cardiorespiratory fitness and stroke risk in later life, independent of the baseline and antecedent burden of risk factors, according to a study published online ahead of print June 9 in Stroke. Researchers studied 19,815 individuals who received Medicare coverage from 1999 to 2009. Cardiorespiratory fitness estimated at baseline was analyzed as a continuous variable and according to age- and sex-specific quintiles. Associations between midlife cardiorespiratory fitness and stroke hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. The investigators observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife cardiorespiratory fitness was associated with a lower risk of stroke hospitalization.

Incident dementia early after intracerebral hemorrhage is strongly associated with hematoma size and location, according to a study published online ahead of print June 13 in JAMA Neurology. A longitudinal study enrolled patients with intracerebral hemorrhage from January 1, 2006, to December 31, 2013. In all, 738 participants ages 18 or older, without pre-intracerebral hemorrhage dementia, who presented to a tertiary care academic institution with primary intracerebral hemorrhage were included in the study. A total of 140 patients developed dementia within six months. Larger hematoma size and lobar location of intracerebral hemorrhage were associated with early post-intracerebral hemorrhage dementia, but not with delayed post-intracerebral hemorrhage dementia. Educational level, incident mood symptoms, and white matter disease were associated with delayed, but not early, post-intracerebral hemorrhage dementia.

The FDA is investigating the risk of serious burns and potential permanent scarring from the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch for migraine. The patch delivers a dose of medicine in a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Since the introduction of the patch, many patients have reported injury to the skin where the patch was worn. The reports include descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin. Patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact a health care professional. Teva Pharmaceuticals has suspended the sale, marketing, and distribution of the patch.

More than 90% of the global stroke burden is attributable to modifiable risk factors, including air pollution, and controlling behavioral and metabolic risk factors could avert more than 75% of the global stroke burden, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers used data on stroke-related disability-adjusted life-years, risk factors, and population-attributable fraction from the Global Burden of Disease Study 2013 to estimate the burden of stroke by age and sex in 188 countries. Approximately 74% of the global stroke burden was attributable to behavioral factors. Clusters of metabolic factors (72%) and environmental factors (33%) were the second and third largest contributors to disability-adjusted life-years, respectively. About 29% of the burden of stroke was attributed to air pollution.

Abnormally high fractional anisotropy (FA) on diffusion tensor imaging (DTI) is associated with better outcomes after mild traumatic brain injury (mTBI), according to a study published online ahead of print June 9 in the American Journal of Neuroradiology. DTI was performed on 39 subjects with mTBI within 16 days of injury and on 40 controls. In all, 26 subjects with mTBI returned for follow-up at one year. Among these subjects, high FA in the left frontal lobe and left temporal lobe was associated with better attention. High FA in the left and right cerebelli was associated with improved somatic postconcussion symptoms. High FA in the right thalamus was associated with improved emotional postconcussion symptoms. Abnormally high FA may be an imaging correlate of postinjury compensatory processes, said the investigators.

Among patients with multiple sclerosis (MS), obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function, attention, processing speed, and working memory, according to a study published online ahead of print May 3 in Sleep. Thirty-eight participants underwent MS-specific cognitive testing and in-laboratory overnight polysomnography. In adjusted linear regression models, the oxygen desaturation index and minimum oxygen saturation were significantly associated with performance on multiple Minimal Assessment of Cognitive Function in MS measures. Apnea severity measures accounted for between 11% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation and total sleep time also showed significant associations with a component of the California Verbal Learning Test-II, explaining 18% and 27% of the variance in performance, respectively.

The differences in stroke mortality between African Americans and Caucasians are largely related to differences in stroke incidence, according to a study published online ahead of print June 2 in Stroke. Researchers assessed the difference between African American and Caucasian stroke mortality for 29,681 participants in the Reasons for Geographic and Racial Differences in Stroke cohort. They found that African Americans are four times more likely to die of stroke at age 45 than Caucasians because stroke incidence is greater among African Americans. By age 85, however, the difference in stroke mortality is no longer present. More should be done to reduce the disparity in stroke mortality between African Americans and Caucasians, and interventions should focus on prevention of stroke among African Americans, according to the investigators.

A mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, according to a study published online ahead of print June 6 in Nature Genetics. Researchers first investigated a family with 15 members who had typical symptoms of Parkinson's disease. They used DNA samples to perform a genome-wide analysis on 65 of the family's members, including 13 with Parkinson's disease, to find a common mutation that could explain the prevalence of Parkinson's disease. The study authors identified TMEM230 as the gene with a disease-causing mutation and found that TMEM230 encodes a protein that extends across the membrane of tiny sacs inside synaptic vesicles. The research team also found mutations in TMEM230 in cases of Parkinson's disease in additional families in North America and China.

People with blast exposure have a pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and between gray and white matter, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers analyzed brain specimens from five military service members with chronic blast exposure, three with acute blast exposure, five with chronic impact traumatic brain injury, five with exposure to opiates, and three control cases with no known neurologic disorders. All five cases with chronic blast exposure showed prominent astroglial scarring involving the subpial glial plate, penetrating cortical blood vessels, gray-white matter junctions, and structures lining the ventricles. Cases of acute blast exposure showed early astroglial scarring in the same brain regions. Cases of chronic blast exposure had an antemortem diagnosis of posttraumatic stress disorder.

A combination of dextromethorphan and quinidine is an effective and well-tolerated treatment for pseudobulbar affect secondary to dementia, stroke, or traumatic brain injury, according to a study published June 9 in BMC Neurology. The study included 367 participants with this disorder. Participants in this open-label, multicenter, 90-day trial received dextromethorphan and quinidine twice daily. The mean Center for Neurologic Study-Lability Scale score improved from 20.4 at baseline to 12.8 at the 90-day final visit. Reduction in pseudobulbar affect episode count was 72.3% at the 90-day final visit, compared with baseline. Scores on Clinical Global Impression of Change and Patient Global Impression of Change indicated that 76.6% and 72.4% of participants, respectively, showed much or very much improvement in symptoms of pseudobulbar affect.

—Kimberly Williams

There is a strong, inverse association between midlife cardiorespiratory fitness and stroke risk in later life, independent of the baseline and antecedent burden of risk factors, according to a study published online ahead of print June 9 in Stroke. Researchers studied 19,815 individuals who received Medicare coverage from 1999 to 2009. Cardiorespiratory fitness estimated at baseline was analyzed as a continuous variable and according to age- and sex-specific quintiles. Associations between midlife cardiorespiratory fitness and stroke hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. The investigators observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife cardiorespiratory fitness was associated with a lower risk of stroke hospitalization.

Incident dementia early after intracerebral hemorrhage is strongly associated with hematoma size and location, according to a study published online ahead of print June 13 in JAMA Neurology. A longitudinal study enrolled patients with intracerebral hemorrhage from January 1, 2006, to December 31, 2013. In all, 738 participants ages 18 or older, without pre-intracerebral hemorrhage dementia, who presented to a tertiary care academic institution with primary intracerebral hemorrhage were included in the study. A total of 140 patients developed dementia within six months. Larger hematoma size and lobar location of intracerebral hemorrhage were associated with early post-intracerebral hemorrhage dementia, but not with delayed post-intracerebral hemorrhage dementia. Educational level, incident mood symptoms, and white matter disease were associated with delayed, but not early, post-intracerebral hemorrhage dementia.

The FDA is investigating the risk of serious burns and potential permanent scarring from the use of the Zecuity (sumatriptan iontophoretic transdermal system) patch for migraine. The patch delivers a dose of medicine in a single-use, battery-powered patch that is wrapped around the upper arm or thigh. Since the introduction of the patch, many patients have reported injury to the skin where the patch was worn. The reports include descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin. Patients who experience moderate to severe pain at the patch site should immediately remove the patch to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact a health care professional. Teva Pharmaceuticals has suspended the sale, marketing, and distribution of the patch.

More than 90% of the global stroke burden is attributable to modifiable risk factors, including air pollution, and controlling behavioral and metabolic risk factors could avert more than 75% of the global stroke burden, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers used data on stroke-related disability-adjusted life-years, risk factors, and population-attributable fraction from the Global Burden of Disease Study 2013 to estimate the burden of stroke by age and sex in 188 countries. Approximately 74% of the global stroke burden was attributable to behavioral factors. Clusters of metabolic factors (72%) and environmental factors (33%) were the second and third largest contributors to disability-adjusted life-years, respectively. About 29% of the burden of stroke was attributed to air pollution.

Abnormally high fractional anisotropy (FA) on diffusion tensor imaging (DTI) is associated with better outcomes after mild traumatic brain injury (mTBI), according to a study published online ahead of print June 9 in the American Journal of Neuroradiology. DTI was performed on 39 subjects with mTBI within 16 days of injury and on 40 controls. In all, 26 subjects with mTBI returned for follow-up at one year. Among these subjects, high FA in the left frontal lobe and left temporal lobe was associated with better attention. High FA in the left and right cerebelli was associated with improved somatic postconcussion symptoms. High FA in the right thalamus was associated with improved emotional postconcussion symptoms. Abnormally high FA may be an imaging correlate of postinjury compensatory processes, said the investigators.

Among patients with multiple sclerosis (MS), obstructive sleep apnea and sleep disturbance are significantly associated with diminished visual memory, verbal memory, executive function, attention, processing speed, and working memory, according to a study published online ahead of print May 3 in Sleep. Thirty-eight participants underwent MS-specific cognitive testing and in-laboratory overnight polysomnography. In adjusted linear regression models, the oxygen desaturation index and minimum oxygen saturation were significantly associated with performance on multiple Minimal Assessment of Cognitive Function in MS measures. Apnea severity measures accounted for between 11% and 23% of the variance in cognitive test performance. Polysomnographic measures of sleep fragmentation and total sleep time also showed significant associations with a component of the California Verbal Learning Test-II, explaining 18% and 27% of the variance in performance, respectively.

The differences in stroke mortality between African Americans and Caucasians are largely related to differences in stroke incidence, according to a study published online ahead of print June 2 in Stroke. Researchers assessed the difference between African American and Caucasian stroke mortality for 29,681 participants in the Reasons for Geographic and Racial Differences in Stroke cohort. They found that African Americans are four times more likely to die of stroke at age 45 than Caucasians because stroke incidence is greater among African Americans. By age 85, however, the difference in stroke mortality is no longer present. More should be done to reduce the disparity in stroke mortality between African Americans and Caucasians, and interventions should focus on prevention of stroke among African Americans, according to the investigators.

A mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, according to a study published online ahead of print June 6 in Nature Genetics. Researchers first investigated a family with 15 members who had typical symptoms of Parkinson's disease. They used DNA samples to perform a genome-wide analysis on 65 of the family's members, including 13 with Parkinson's disease, to find a common mutation that could explain the prevalence of Parkinson's disease. The study authors identified TMEM230 as the gene with a disease-causing mutation and found that TMEM230 encodes a protein that extends across the membrane of tiny sacs inside synaptic vesicles. The research team also found mutations in TMEM230 in cases of Parkinson's disease in additional families in North America and China.

People with blast exposure have a pattern of interface astroglial scarring at boundaries between brain parenchyma and fluids, and between gray and white matter, according to a study published online ahead of print June 9 in the Lancet Neurology. Researchers analyzed brain specimens from five military service members with chronic blast exposure, three with acute blast exposure, five with chronic impact traumatic brain injury, five with exposure to opiates, and three control cases with no known neurologic disorders. All five cases with chronic blast exposure showed prominent astroglial scarring involving the subpial glial plate, penetrating cortical blood vessels, gray-white matter junctions, and structures lining the ventricles. Cases of acute blast exposure showed early astroglial scarring in the same brain regions. Cases of chronic blast exposure had an antemortem diagnosis of posttraumatic stress disorder.

A combination of dextromethorphan and quinidine is an effective and well-tolerated treatment for pseudobulbar affect secondary to dementia, stroke, or traumatic brain injury, according to a study published June 9 in BMC Neurology. The study included 367 participants with this disorder. Participants in this open-label, multicenter, 90-day trial received dextromethorphan and quinidine twice daily. The mean Center for Neurologic Study-Lability Scale score improved from 20.4 at baseline to 12.8 at the 90-day final visit. Reduction in pseudobulbar affect episode count was 72.3% at the 90-day final visit, compared with baseline. Scores on Clinical Global Impression of Change and Patient Global Impression of Change indicated that 76.6% and 72.4% of participants, respectively, showed much or very much improvement in symptoms of pseudobulbar affect.

—Kimberly Williams