News Roundup

Thrombolysis Benefits Patients With Stroke

In patients with acute stroke with an unknown time of onset, IV alteplase guided by a mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) in the region of ischemia results in a significantly better functional outcome and more intracranial hemorrhages at 90 days, compared with placebo, according to a study published August 16 in the New England Journal of Medicine. Researchers randomly assigned 254 participants to receive IV alteplase and 249 participants to receive placebo. Participants had an ischemic lesion on MRI diffusion-weighted imaging, but no parenchymal hyperintensity on FLAIR. A favorable outcome (ie, a score of 0 or 1 on the modified Rankin Scale at 90 days) occurred in 53.3% of the alteplase group versus 41.8% of the placebo group.

Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-622.

High Levels of Cortisol Linked to Impaired Memory

Middle-aged people with high levels of cortisol in their blood have impaired memory, compared with people with average levels of cortisol, according to a study published online ahead of print October 24 in Neurology. Researchers identified 2,231 people with an average age of 49 who did not have dementia. At the start of the study, each participant underwent a psychologic exam and assessments of memory and thinking skills. Participants’ memory and thinking skills were tested again at an average of eight years later. Participants also provided a blood sample. After adjusting for age, sex, smoking, and BMI, researchers found that people with high levels of cortisol had lower scores on tests of memory and thinking skills, compared with people with normal levels of cortisol.

Echouffo-Tcheugui JB, Conner SC, Himali JJ, et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology. 2018 Oct 24 [Epub ahead of print].

Is Nusinersen Effective If Initiated Later?

Patients with spinal muscular atrophy type 1 (SMA1) may benefit from nusinersen when the therapy is initiated after age 7 months, according to a study published online ahead of print August 29 in Neurology. In this study, 33 patients with SMA1 received intrathecal nusinersen injections. Researchers evaluated patients before treatment and at two months and six months after treatment. All patients were alive and continuing treatment at six months. Median progress on the modified Hammersmith Infant Neurologic Examination Part 2 score was 1.5 points after six months of treatment. The need for respiratory support significantly increased over time. The results are consistent with those of a phase III trial in which patients with SMA1 received nusinersen before age 7 months, the researchers said.

Aragon-Gawinska K, Seferian AM, Daron A, et al. Nusinersen in spinal muscular atrophy type 1 patients older than 7 months: a cohort study. Neurology. 2018 Aug 29 [Epub ahead of print].

Pre-Eclampsia Linked to Dementia in Late Life

Pre-eclampsia is associated with an increased risk of dementia, particularly vascular dementia, according to a study published October 17 in BMJ. The study cohort consisted of 1,178,005 Danish women with at least one live birth or stillbirth between 1978 and 2015. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late-onset disease than for early-onset disease. Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios moderately. Sensitivity analyses suggested that BMI was unlikely to explain the association with vascular dementia. In contrast, modest associations were observed for Alzheimer’s disease and other or unspecified dementia.

Basit S, Wohlfahrt J, Boyd HA. Pre-eclampsia and risk of dementia later in life: nationwide cohort study. BMJ. 2018;363:k4109.

Does Antiepileptic Drug Clearance Change During Pregnancy?

In pregnant women, antiepileptic drug (AED) clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate, according to a study published September 25 in Neurology. This prospective, observational study included 40 women with epilepsy who were planning to conceive or were fewer than 16 weeks pregnant and who chose to continue their AEDs during pregnancy. Drug clearance values were obtained by blood draw at baseline and during pregnancy. Mean maximal clearances were 1.71 times the baseline clearance for levetiracetam, 1.63 times the baseline clearance for oxcarbazepine, and 1.39 the baseline clearance for topiramate. In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower ratio to target concentration.

Voinescu PE, Park S, Chen LQ, et al. Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology. 2018;91(13):e1228-e1236.

Do Dextroamphetamine and Physical Therapy Improve Function After Stroke?

Compared with placebo, dextroamphetamine combined with physical therapy does not improve recovery of motor function after stroke, according to a study published online ahead of print August 27 in JAMA Neurology. This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits. A total of 64 participants were randomized to receive 10 mg of dextroamphetamine or placebo one hour before a one-hour physical therapy session every four days for six sessions, in addition to standard rehabilitation. The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to three months after stroke. Treatment was not associated with differences in the primary outcome, secondary measures, or subgroups based on stroke location or baseline severity.

Goldstein LB, Lennihan L, Rabadi MJ, et al. Effect of dextroamphetamine on poststroke motor recovery: a randomized clinical trial. JAMA Neurol. 2018 Aug 27 [Epub ahead of print].

FDA Approves Tegsedi for hATTR in Adults

The FDA has approved Tegsedi (inotersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults. The approval is based on data from the phase III randomized, double-blind, placebo-controlled, 15-month, international NEURO-TTR study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, Tegsedi demonstrated significant benefit, compared with placebo, in neuropathy and quality of life, as measured by the modified Neuropathy Impairment Score +7 and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy total score. Patients treated with Tegsedi experienced similar benefit regardless of subgroup, such as age, sex, race, region, Neuropathy Impairment Score, Val30Met mutation status, and disease stage. Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals that is headquartered in Boston, markets Tegsedi.

Data Review Evaluates Nusinersen’s Efficacy in SMA

A panel has reviewed the evidence for nusinersen treatment of spinal muscular atrophy (SMA). The results were published online ahead of print October 12 in Neurology. The authors systematically reviewed clinical trials of nusinersen in patients with SMA and assigned level of evidence statements. Among four published clinical trials identified, three were rated above Class IV. There is Class I evidence that in term infants with SMA and two copies of SMN2, treatment with nusinersen started in children younger than 7 months results in a better motor milestone response and higher rates of event-free survival than sham control. There is Class I evidence that in children aged 2 to 12 with SMA symptom onset after age 6 months, nusinersen yields greater improvement in motor function at 15 months than sham control.

Michelson D, Ciafaloni E, Ashwal S, et al. Evidence in focus: nusinersen use in spinal muscular atrophy: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Oct 12 [Epub ahead of print].

Aortic Stiffness Predicts Incident Dementia

Arterial stiffness can predict a person’s likelihood of developing dementia, according to a study published October 16 in the Journal of Alzheimer’s Disease. Researchers analyzed the association between arterial stiffness and dementia among 356 older adults with an average age of 78 who were part of the Cardiovascular Health Study Cognition Study. Eligible participants were dementia-free when the study began in 1998. Investigators tested participants’ aortic stiffness with carotid-femoral pulse wave velocity. Participants also underwent MRI of their brains to measure signs of subclinical brain disease. The researchers found that participants with high carotid-femoral pulse wave velocity readings were 60% more likely to develop dementia during the following 15 years, compared with people with lower carotid-femoral pulse wave velocity values.

Cui C, Sekikawa A, Kuller LH, et al. Aortic stiffness is associated with increased risk of incident dementia in older adults. J Alzheimers Dis. 2018;66(1):297-306.

Early MoCA Score Predicts Long-Term Outcome After Stroke

Early cognitive testing with the Montreal Cognitive Assessment (MoCA) predicts long-term cognitive outcome, functional outcome, and mortality after stroke, according to a study published online ahead of print October 17 in Neurology. In this international study, 274 people with stroke were administered MoCA within a week of stroke onset. Participants were divided into two groups: people with no problems with thinking and memory skills and people with cognitive impairment. People who had cognitive impairment within one week of stroke were seven times more likely to die during the three years of the study than people without cognitive impairment. Furthermore, the survival rate for people with cognitive impairment after three years was 83%, and the rate was 97% for people who did not have early cognitive impairment.

Zietemann V, Georgakis MK, Dondaine T, et al. Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke. Neurology. 2018 Oct 17 [Epub ahead of print].

Antiepileptic Drug Use Related to Increased Stroke Risk

In Alzheimer’s disease, antiepileptic drug (AED) use is related to an increased risk of stroke, according to a study published September 18 in the Journal of the American Heart Association. Investigators examined the Medication Use and Alzheimer’s Disease cohort, which included all Finnish people who received a clinically verified diagnosis of Alzheimer’s disease from 2005 to 2011. People with previous stroke were excluded. For each incident AED user, the investigators matched one nonuser according to sex, age, and time since Alzheimer’s disease diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse, AED use was associated with an increased risk of stroke, and the risk of stroke was strongest during the first 90 days of AED use (adjusted hazard ratio, 2.36).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic drug use and the risk of stroke among community-dwelling people with Alzheimer disease: A matched cohort study. J Am Heart Assoc. 2018;7(18):e009742.

Thrombolysis Benefits Patients With Stroke

In patients with acute stroke with an unknown time of onset, IV alteplase guided by a mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) in the region of ischemia results in a significantly better functional outcome and more intracranial hemorrhages at 90 days, compared with placebo, according to a study published August 16 in the New England Journal of Medicine. Researchers randomly assigned 254 participants to receive IV alteplase and 249 participants to receive placebo. Participants had an ischemic lesion on MRI diffusion-weighted imaging, but no parenchymal hyperintensity on FLAIR. A favorable outcome (ie, a score of 0 or 1 on the modified Rankin Scale at 90 days) occurred in 53.3% of the alteplase group versus 41.8% of the placebo group.

Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-622.

High Levels of Cortisol Linked to Impaired Memory

Middle-aged people with high levels of cortisol in their blood have impaired memory, compared with people with average levels of cortisol, according to a study published online ahead of print October 24 in Neurology. Researchers identified 2,231 people with an average age of 49 who did not have dementia. At the start of the study, each participant underwent a psychologic exam and assessments of memory and thinking skills. Participants’ memory and thinking skills were tested again at an average of eight years later. Participants also provided a blood sample. After adjusting for age, sex, smoking, and BMI, researchers found that people with high levels of cortisol had lower scores on tests of memory and thinking skills, compared with people with normal levels of cortisol.

Echouffo-Tcheugui JB, Conner SC, Himali JJ, et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology. 2018 Oct 24 [Epub ahead of print].

Is Nusinersen Effective If Initiated Later?

Patients with spinal muscular atrophy type 1 (SMA1) may benefit from nusinersen when the therapy is initiated after age 7 months, according to a study published online ahead of print August 29 in Neurology. In this study, 33 patients with SMA1 received intrathecal nusinersen injections. Researchers evaluated patients before treatment and at two months and six months after treatment. All patients were alive and continuing treatment at six months. Median progress on the modified Hammersmith Infant Neurologic Examination Part 2 score was 1.5 points after six months of treatment. The need for respiratory support significantly increased over time. The results are consistent with those of a phase III trial in which patients with SMA1 received nusinersen before age 7 months, the researchers said.

Aragon-Gawinska K, Seferian AM, Daron A, et al. Nusinersen in spinal muscular atrophy type 1 patients older than 7 months: a cohort study. Neurology. 2018 Aug 29 [Epub ahead of print].

Pre-Eclampsia Linked to Dementia in Late Life

Pre-eclampsia is associated with an increased risk of dementia, particularly vascular dementia, according to a study published October 17 in BMJ. The study cohort consisted of 1,178,005 Danish women with at least one live birth or stillbirth between 1978 and 2015. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late-onset disease than for early-onset disease. Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios moderately. Sensitivity analyses suggested that BMI was unlikely to explain the association with vascular dementia. In contrast, modest associations were observed for Alzheimer’s disease and other or unspecified dementia.

Basit S, Wohlfahrt J, Boyd HA. Pre-eclampsia and risk of dementia later in life: nationwide cohort study. BMJ. 2018;363:k4109.

Does Antiepileptic Drug Clearance Change During Pregnancy?

In pregnant women, antiepileptic drug (AED) clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate, according to a study published September 25 in Neurology. This prospective, observational study included 40 women with epilepsy who were planning to conceive or were fewer than 16 weeks pregnant and who chose to continue their AEDs during pregnancy. Drug clearance values were obtained by blood draw at baseline and during pregnancy. Mean maximal clearances were 1.71 times the baseline clearance for levetiracetam, 1.63 times the baseline clearance for oxcarbazepine, and 1.39 the baseline clearance for topiramate. In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower ratio to target concentration.

Voinescu PE, Park S, Chen LQ, et al. Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology. 2018;91(13):e1228-e1236.

Do Dextroamphetamine and Physical Therapy Improve Function After Stroke?

Compared with placebo, dextroamphetamine combined with physical therapy does not improve recovery of motor function after stroke, according to a study published online ahead of print August 27 in JAMA Neurology. This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits. A total of 64 participants were randomized to receive 10 mg of dextroamphetamine or placebo one hour before a one-hour physical therapy session every four days for six sessions, in addition to standard rehabilitation. The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to three months after stroke. Treatment was not associated with differences in the primary outcome, secondary measures, or subgroups based on stroke location or baseline severity.

Goldstein LB, Lennihan L, Rabadi MJ, et al. Effect of dextroamphetamine on poststroke motor recovery: a randomized clinical trial. JAMA Neurol. 2018 Aug 27 [Epub ahead of print].

FDA Approves Tegsedi for hATTR in Adults

The FDA has approved Tegsedi (inotersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults. The approval is based on data from the phase III randomized, double-blind, placebo-controlled, 15-month, international NEURO-TTR study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, Tegsedi demonstrated significant benefit, compared with placebo, in neuropathy and quality of life, as measured by the modified Neuropathy Impairment Score +7 and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy total score. Patients treated with Tegsedi experienced similar benefit regardless of subgroup, such as age, sex, race, region, Neuropathy Impairment Score, Val30Met mutation status, and disease stage. Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals that is headquartered in Boston, markets Tegsedi.

Data Review Evaluates Nusinersen’s Efficacy in SMA

A panel has reviewed the evidence for nusinersen treatment of spinal muscular atrophy (SMA). The results were published online ahead of print October 12 in Neurology. The authors systematically reviewed clinical trials of nusinersen in patients with SMA and assigned level of evidence statements. Among four published clinical trials identified, three were rated above Class IV. There is Class I evidence that in term infants with SMA and two copies of SMN2, treatment with nusinersen started in children younger than 7 months results in a better motor milestone response and higher rates of event-free survival than sham control. There is Class I evidence that in children aged 2 to 12 with SMA symptom onset after age 6 months, nusinersen yields greater improvement in motor function at 15 months than sham control.

Michelson D, Ciafaloni E, Ashwal S, et al. Evidence in focus: nusinersen use in spinal muscular atrophy: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Oct 12 [Epub ahead of print].

Aortic Stiffness Predicts Incident Dementia

Arterial stiffness can predict a person’s likelihood of developing dementia, according to a study published October 16 in the Journal of Alzheimer’s Disease. Researchers analyzed the association between arterial stiffness and dementia among 356 older adults with an average age of 78 who were part of the Cardiovascular Health Study Cognition Study. Eligible participants were dementia-free when the study began in 1998. Investigators tested participants’ aortic stiffness with carotid-femoral pulse wave velocity. Participants also underwent MRI of their brains to measure signs of subclinical brain disease. The researchers found that participants with high carotid-femoral pulse wave velocity readings were 60% more likely to develop dementia during the following 15 years, compared with people with lower carotid-femoral pulse wave velocity values.

Cui C, Sekikawa A, Kuller LH, et al. Aortic stiffness is associated with increased risk of incident dementia in older adults. J Alzheimers Dis. 2018;66(1):297-306.

Early MoCA Score Predicts Long-Term Outcome After Stroke

Early cognitive testing with the Montreal Cognitive Assessment (MoCA) predicts long-term cognitive outcome, functional outcome, and mortality after stroke, according to a study published online ahead of print October 17 in Neurology. In this international study, 274 people with stroke were administered MoCA within a week of stroke onset. Participants were divided into two groups: people with no problems with thinking and memory skills and people with cognitive impairment. People who had cognitive impairment within one week of stroke were seven times more likely to die during the three years of the study than people without cognitive impairment. Furthermore, the survival rate for people with cognitive impairment after three years was 83%, and the rate was 97% for people who did not have early cognitive impairment.

Zietemann V, Georgakis MK, Dondaine T, et al. Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke. Neurology. 2018 Oct 17 [Epub ahead of print].

Antiepileptic Drug Use Related to Increased Stroke Risk

In Alzheimer’s disease, antiepileptic drug (AED) use is related to an increased risk of stroke, according to a study published September 18 in the Journal of the American Heart Association. Investigators examined the Medication Use and Alzheimer’s Disease cohort, which included all Finnish people who received a clinically verified diagnosis of Alzheimer’s disease from 2005 to 2011. People with previous stroke were excluded. For each incident AED user, the investigators matched one nonuser according to sex, age, and time since Alzheimer’s disease diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse, AED use was associated with an increased risk of stroke, and the risk of stroke was strongest during the first 90 days of AED use (adjusted hazard ratio, 2.36).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic drug use and the risk of stroke among community-dwelling people with Alzheimer disease: A matched cohort study. J Am Heart Assoc. 2018;7(18):e009742.

Thrombolysis Benefits Patients With Stroke

In patients with acute stroke with an unknown time of onset, IV alteplase guided by a mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) in the region of ischemia results in a significantly better functional outcome and more intracranial hemorrhages at 90 days, compared with placebo, according to a study published August 16 in the New England Journal of Medicine. Researchers randomly assigned 254 participants to receive IV alteplase and 249 participants to receive placebo. Participants had an ischemic lesion on MRI diffusion-weighted imaging, but no parenchymal hyperintensity on FLAIR. A favorable outcome (ie, a score of 0 or 1 on the modified Rankin Scale at 90 days) occurred in 53.3% of the alteplase group versus 41.8% of the placebo group.

Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-622.

High Levels of Cortisol Linked to Impaired Memory

Middle-aged people with high levels of cortisol in their blood have impaired memory, compared with people with average levels of cortisol, according to a study published online ahead of print October 24 in Neurology. Researchers identified 2,231 people with an average age of 49 who did not have dementia. At the start of the study, each participant underwent a psychologic exam and assessments of memory and thinking skills. Participants’ memory and thinking skills were tested again at an average of eight years later. Participants also provided a blood sample. After adjusting for age, sex, smoking, and BMI, researchers found that people with high levels of cortisol had lower scores on tests of memory and thinking skills, compared with people with normal levels of cortisol.

Echouffo-Tcheugui JB, Conner SC, Himali JJ, et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology. 2018 Oct 24 [Epub ahead of print].

Is Nusinersen Effective If Initiated Later?

Patients with spinal muscular atrophy type 1 (SMA1) may benefit from nusinersen when the therapy is initiated after age 7 months, according to a study published online ahead of print August 29 in Neurology. In this study, 33 patients with SMA1 received intrathecal nusinersen injections. Researchers evaluated patients before treatment and at two months and six months after treatment. All patients were alive and continuing treatment at six months. Median progress on the modified Hammersmith Infant Neurologic Examination Part 2 score was 1.5 points after six months of treatment. The need for respiratory support significantly increased over time. The results are consistent with those of a phase III trial in which patients with SMA1 received nusinersen before age 7 months, the researchers said.

Aragon-Gawinska K, Seferian AM, Daron A, et al. Nusinersen in spinal muscular atrophy type 1 patients older than 7 months: a cohort study. Neurology. 2018 Aug 29 [Epub ahead of print].

Pre-Eclampsia Linked to Dementia in Late Life

Pre-eclampsia is associated with an increased risk of dementia, particularly vascular dementia, according to a study published October 17 in BMJ. The study cohort consisted of 1,178,005 Danish women with at least one live birth or stillbirth between 1978 and 2015. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late-onset disease than for early-onset disease. Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios moderately. Sensitivity analyses suggested that BMI was unlikely to explain the association with vascular dementia. In contrast, modest associations were observed for Alzheimer’s disease and other or unspecified dementia.

Basit S, Wohlfahrt J, Boyd HA. Pre-eclampsia and risk of dementia later in life: nationwide cohort study. BMJ. 2018;363:k4109.

Does Antiepileptic Drug Clearance Change During Pregnancy?

In pregnant women, antiepileptic drug (AED) clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate, according to a study published September 25 in Neurology. This prospective, observational study included 40 women with epilepsy who were planning to conceive or were fewer than 16 weeks pregnant and who chose to continue their AEDs during pregnancy. Drug clearance values were obtained by blood draw at baseline and during pregnancy. Mean maximal clearances were 1.71 times the baseline clearance for levetiracetam, 1.63 times the baseline clearance for oxcarbazepine, and 1.39 the baseline clearance for topiramate. In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower ratio to target concentration.

Voinescu PE, Park S, Chen LQ, et al. Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology. 2018;91(13):e1228-e1236.

Do Dextroamphetamine and Physical Therapy Improve Function After Stroke?

Compared with placebo, dextroamphetamine combined with physical therapy does not improve recovery of motor function after stroke, according to a study published online ahead of print August 27 in JAMA Neurology. This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits. A total of 64 participants were randomized to receive 10 mg of dextroamphetamine or placebo one hour before a one-hour physical therapy session every four days for six sessions, in addition to standard rehabilitation. The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to three months after stroke. Treatment was not associated with differences in the primary outcome, secondary measures, or subgroups based on stroke location or baseline severity.

Goldstein LB, Lennihan L, Rabadi MJ, et al. Effect of dextroamphetamine on poststroke motor recovery: a randomized clinical trial. JAMA Neurol. 2018 Aug 27 [Epub ahead of print].

FDA Approves Tegsedi for hATTR in Adults

The FDA has approved Tegsedi (inotersen) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults. The approval is based on data from the phase III randomized, double-blind, placebo-controlled, 15-month, international NEURO-TTR study in 172 patients with hATTR amyloidosis with symptoms of polyneuropathy. In NEURO-TTR, Tegsedi demonstrated significant benefit, compared with placebo, in neuropathy and quality of life, as measured by the modified Neuropathy Impairment Score +7 and the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy total score. Patients treated with Tegsedi experienced similar benefit regardless of subgroup, such as age, sex, race, region, Neuropathy Impairment Score, Val30Met mutation status, and disease stage. Akcea Therapeutics, an affiliate of Ionis Pharmaceuticals that is headquartered in Boston, markets Tegsedi.

Data Review Evaluates Nusinersen’s Efficacy in SMA

A panel has reviewed the evidence for nusinersen treatment of spinal muscular atrophy (SMA). The results were published online ahead of print October 12 in Neurology. The authors systematically reviewed clinical trials of nusinersen in patients with SMA and assigned level of evidence statements. Among four published clinical trials identified, three were rated above Class IV. There is Class I evidence that in term infants with SMA and two copies of SMN2, treatment with nusinersen started in children younger than 7 months results in a better motor milestone response and higher rates of event-free survival than sham control. There is Class I evidence that in children aged 2 to 12 with SMA symptom onset after age 6 months, nusinersen yields greater improvement in motor function at 15 months than sham control.

Michelson D, Ciafaloni E, Ashwal S, et al. Evidence in focus: nusinersen use in spinal muscular atrophy: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Oct 12 [Epub ahead of print].

Aortic Stiffness Predicts Incident Dementia

Arterial stiffness can predict a person’s likelihood of developing dementia, according to a study published October 16 in the Journal of Alzheimer’s Disease. Researchers analyzed the association between arterial stiffness and dementia among 356 older adults with an average age of 78 who were part of the Cardiovascular Health Study Cognition Study. Eligible participants were dementia-free when the study began in 1998. Investigators tested participants’ aortic stiffness with carotid-femoral pulse wave velocity. Participants also underwent MRI of their brains to measure signs of subclinical brain disease. The researchers found that participants with high carotid-femoral pulse wave velocity readings were 60% more likely to develop dementia during the following 15 years, compared with people with lower carotid-femoral pulse wave velocity values.

Cui C, Sekikawa A, Kuller LH, et al. Aortic stiffness is associated with increased risk of incident dementia in older adults. J Alzheimers Dis. 2018;66(1):297-306.

Early MoCA Score Predicts Long-Term Outcome After Stroke

Early cognitive testing with the Montreal Cognitive Assessment (MoCA) predicts long-term cognitive outcome, functional outcome, and mortality after stroke, according to a study published online ahead of print October 17 in Neurology. In this international study, 274 people with stroke were administered MoCA within a week of stroke onset. Participants were divided into two groups: people with no problems with thinking and memory skills and people with cognitive impairment. People who had cognitive impairment within one week of stroke were seven times more likely to die during the three years of the study than people without cognitive impairment. Furthermore, the survival rate for people with cognitive impairment after three years was 83%, and the rate was 97% for people who did not have early cognitive impairment.

Zietemann V, Georgakis MK, Dondaine T, et al. Early MoCA predicts long-term cognitive and functional outcome and mortality after stroke. Neurology. 2018 Oct 17 [Epub ahead of print].

Antiepileptic Drug Use Related to Increased Stroke Risk

In Alzheimer’s disease, antiepileptic drug (AED) use is related to an increased risk of stroke, according to a study published September 18 in the Journal of the American Heart Association. Investigators examined the Medication Use and Alzheimer’s Disease cohort, which included all Finnish people who received a clinically verified diagnosis of Alzheimer’s disease from 2005 to 2011. People with previous stroke were excluded. For each incident AED user, the investigators matched one nonuser according to sex, age, and time since Alzheimer’s disease diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse, AED use was associated with an increased risk of stroke, and the risk of stroke was strongest during the first 90 days of AED use (adjusted hazard ratio, 2.36).

Sarycheva T, Lavikainen P, Taipale H, et al. Antiepileptic drug use and the risk of stroke among community-dwelling people with Alzheimer disease: A matched cohort study. J Am Heart Assoc. 2018;7(18):e009742.

CPAP After Stroke May Improve Function

Treating sleep apnea after a stroke or transient ischemic attack (TIA) may improve speech impairment, neurologic symptoms, walking, and physical function, according to a study published August 15 in the Journal of the American Heart Association. To examine whether continuous positive airway pressure (CPAP) improves clinical outcomes among patients with stroke or TIA who have obstructive sleep apnea, researchers analyzed data from a trial that included 252 patients with stroke or TIA. Participants were randomized to intervention groups that received polysomnography soon after the stroke or TIA or to a control group. Among the 81 patients in the intervention groups with sleep apnea, more than 70% used CPAP during approximately one year of follow-up. In intention-to-treat analyses, changes in NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were similar across groups. In as-treated analyses among patients with sleep apnea, CPAP use was associated with improved NIHSS and mRS scores. In addition, 59% of intervention patients with sleep apnea had a final NIHSS score of 0 or 1 versus 38% of controls with sleep apnea.

Bravata DM, Sico J, Fragoso CAV, et al. Diagnosing and treating sleep apnea in patients with acute cerebrovascular disease. J Am Heart Assoc. 2018;7:e008841.

Intervention Reduces Cognitive Decline in Blacks With MCI

Among black patients with mild cognitive impairment (MCI), a behavioral intervention that aims to increase social, cognitive, and physical activity reduces the risk of memory decline, compared with supportive therapy, according to a study published online ahead of print September 10 in JAMA Neurology. Between June 2011 and October 2014, researchers enrolled 221 black participants with MCI (mean age, 75.8; 79% women) into a clinical trial. Participants were randomized to behavioral activation or supportive therapy (ie, an attention control treatment). The primary outcome was a decline of six or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised at six, 12, 18, and 24 months. The two-year incidence of memory decline was lower in the behavioral activation group than in the supportive therapy group (1.2% vs 9.3%). Behavioral activation reduced the risk of cognitive decline by 88%, compared with supportive therapy.

Rovner BW, Casten RJ, Hegel MT, Leiby B. Preventing cognitive decline in black individuals with mild cognitive impairment: a randomized clinical trial. JAMA Neurol. 2018 Sep 10 [Epub ahead of print].

Medical Marijuana May Treat Nerve Pain

Among patients with neuropathic pain, sublingual tetrahydrocannabinol (THC) significantly reduces pain versus placebo, according to a randomized, double-blind study published online ahead of print September 5 in Neurology. The trial included 15 men with chronic radicular nerve pain (average age, 33). Before and one hour after treatment with THC or placebo oil, participants rated their pain levels on a scale from zero to 100. At least one week later, they received the other treatment. The average pain level before treatment was 53. After taking THC, participants’ average pain level was 35, compared with an average pain level of 43 after taking placebo. Functional MRI showed that the drug’s analgesic effect correlated with reduced functional connectivity between brain areas involved in emotion and pain processing.

Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018 Sep 5 [Epub ahead of print].

For Which Clots Is t-PA Most Effective?

In patients with acute ischemic stroke, a more distal thrombus location, greater thrombus permeability, and longer time to assessment of recanalization are associated with recanalization of an arterial occlusion after administration of IV alteplase, according to a study published in the September 11 issue of JAMA. This multicenter prospective cohort study included 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on CT angiogram (CTA). In all, 275 participants received IV alteplase, 195 participants received IV alteplase plus endovascular thrombectomy, 48 participants received endovascular thrombectomy, and 57 participants received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes. Successful recanalization occurred at an unadjusted rate of 27.3%, including in 30.4% of patients who received IV alteplase and 13.3% who did not.

Menon BK, Al-Ajlan FS, Najm M, et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018;320(10):1017-1026.

FDA Approves Ajovy for Adults With Migraine

The FDA has approved Ajovy (fremanezumab-vfrm), a calcitonin gene-related peptide (CGRP) antagonist, for the preventive treatment of migraine in adults. Dosing options include 225 mg monthly administered as one subcutaneous injection or 675 mg quarterly administered as three subcutaneous injections. The injections can be administered by a healthcare professional or by a patient or caregiver. The treatment was evaluated in two phase III, placebo-controlled clinical trials that enrolled patients with migraine. The trials examined the therapy as a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse reactions were injection site reactions. Ajovy is a humanized monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor. Teva Pharmaceutical Industries, which markets Ajovy, is headquartered in Jerusalem.

Is Daytime Sleepiness Associated With an Alzheimer’s Disease Biomarker?

Excessive daytime sleepiness (EDS) is associated with more than 2.5 times the odds of β-amyloid (Aβ) deposition an average of 15.7 years later, according to a study published online ahead of print September 5 in Sleep. Researchers studied 124 participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-reported measures of EDS and napping at baseline and underwent 11C-Pittsburgh compound B-PET scans of the brain an average of 15.7 years later. Participants’ mean age was 60.1 at baseline; 24.4% had EDS, and 28.5% napped. In unadjusted analyses, compared with participants without EDS, people with EDS had more than three times the odds of being Aβ+ (ie, having a cortical distribution volume ratio of greater than 1.06) at follow-up. After adjusting for age, sex, education, and BMI, the odds ratio was 2.75.

Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018 Sep 5 [Epub ahead of print].

Sepsis Heightens Risk of Stroke and Heart Attack

Patients recovering from sepsis have a greater risk of myocardial infarction or stroke in the first four weeks after hospital discharge, compared with population and hospital controls, according to a study published September 10 in the Canadian Medical Association Journal. This retrospective population-based cohort study included 42,316 patients with sepsis identified from the National Health Insurance Research Database in Taiwan. In all, 831 patients with sepsis had a stroke and 184 had a myocardial infarction within 180 days of discharge from the hospital. Compared with population controls, the risk was highest in the first seven days after discharge (hazard ratio, 4.78). Compared with hospital controls, the risk was attenuated but remained elevated before day 36 after discharge (hazard ratio, 1.32).

Lai CC, Lee MG, Lee WC, et al. Susceptible period for cardiovascular complications in patients recovering from sepsis. CMAJ. 2018;190(36):E1062-E1069.

Ten-Year Risk Factors for Dementia

Age, sex, and APOE genotype identify high-risk groups for Alzheimer’s disease and dementia, according to a study published September 4 in the Canadian Medical Association Journal. The study looked at data from 104,537 people in Copenhagen. Participants completed a questionnaire and underwent physical examination and blood sampling at baseline. The researchers obtained diagnoses of dementia and cerebrovascular disease from the Danish National Patient Registry through November 10, 2014. The absolute 10-year risk of Alzheimer’s disease among 3,017 people who were carriers of the APOE ε44 genotype was 7% for women and 6% for men ages 60 to 69, 16% for women and 12% for men ages 70 to 79, and 24% for women and 19% for men ages 80 and older.

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041.

Is Job Stress Associated With Parkinson’s Disease Risk?

Occupational stress may increase Parkinson’s disease risk, according to a study published online ahead of print August 25 in Movement Disorders. Researchers conducted a population-based cohort study of 2,544,748 Swedes whose occupations had been reported in censuses. They identified incident Parkinson’s disease cases using Swedish national health registers and analyzed the data using Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. During a mean follow-up of 21.3 years, 21,544 incident Parkinson’s disease cases were identified. High job demands were associated with increased risk of Parkinson’s disease among men, most evidently in men with high levels of education. High levels of job control were associated with increased risk among people with low levels of education, and this association was stronger in women.

Sieurin J, Andel R, Tillander A, et al. Occupational stress and risk for Parkinson’s disease: a nationwide cohort study. Mov Disord. 2018 Aug 25 [Epub ahead of print].

FDA Approves Tiglutik for ALS

The FDA has approved Tiglutik (riluzole) oral suspension for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik is a thickened liquid taken twice daily by oral syringe. The approval of Tiglutik is based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. The recommended dosage is 50 mg/10 mL. The drug should be taken at least one hour before or two hours after a meal. In clinical studies, riluzole modulated glutamate neurotransmission by inhibiting glutamate release and postsynaptic glutamate receptor signaling. ITF Pharma, which markets the drug, is headquartered in Berwyn, Pennsylvania.

—Kimberly Williams

CPAP After Stroke May Improve Function

Treating sleep apnea after a stroke or transient ischemic attack (TIA) may improve speech impairment, neurologic symptoms, walking, and physical function, according to a study published August 15 in the Journal of the American Heart Association. To examine whether continuous positive airway pressure (CPAP) improves clinical outcomes among patients with stroke or TIA who have obstructive sleep apnea, researchers analyzed data from a trial that included 252 patients with stroke or TIA. Participants were randomized to intervention groups that received polysomnography soon after the stroke or TIA or to a control group. Among the 81 patients in the intervention groups with sleep apnea, more than 70% used CPAP during approximately one year of follow-up. In intention-to-treat analyses, changes in NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were similar across groups. In as-treated analyses among patients with sleep apnea, CPAP use was associated with improved NIHSS and mRS scores. In addition, 59% of intervention patients with sleep apnea had a final NIHSS score of 0 or 1 versus 38% of controls with sleep apnea.

Bravata DM, Sico J, Fragoso CAV, et al. Diagnosing and treating sleep apnea in patients with acute cerebrovascular disease. J Am Heart Assoc. 2018;7:e008841.

Intervention Reduces Cognitive Decline in Blacks With MCI

Among black patients with mild cognitive impairment (MCI), a behavioral intervention that aims to increase social, cognitive, and physical activity reduces the risk of memory decline, compared with supportive therapy, according to a study published online ahead of print September 10 in JAMA Neurology. Between June 2011 and October 2014, researchers enrolled 221 black participants with MCI (mean age, 75.8; 79% women) into a clinical trial. Participants were randomized to behavioral activation or supportive therapy (ie, an attention control treatment). The primary outcome was a decline of six or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised at six, 12, 18, and 24 months. The two-year incidence of memory decline was lower in the behavioral activation group than in the supportive therapy group (1.2% vs 9.3%). Behavioral activation reduced the risk of cognitive decline by 88%, compared with supportive therapy.

Rovner BW, Casten RJ, Hegel MT, Leiby B. Preventing cognitive decline in black individuals with mild cognitive impairment: a randomized clinical trial. JAMA Neurol. 2018 Sep 10 [Epub ahead of print].

Medical Marijuana May Treat Nerve Pain

Among patients with neuropathic pain, sublingual tetrahydrocannabinol (THC) significantly reduces pain versus placebo, according to a randomized, double-blind study published online ahead of print September 5 in Neurology. The trial included 15 men with chronic radicular nerve pain (average age, 33). Before and one hour after treatment with THC or placebo oil, participants rated their pain levels on a scale from zero to 100. At least one week later, they received the other treatment. The average pain level before treatment was 53. After taking THC, participants’ average pain level was 35, compared with an average pain level of 43 after taking placebo. Functional MRI showed that the drug’s analgesic effect correlated with reduced functional connectivity between brain areas involved in emotion and pain processing.

Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018 Sep 5 [Epub ahead of print].

For Which Clots Is t-PA Most Effective?

In patients with acute ischemic stroke, a more distal thrombus location, greater thrombus permeability, and longer time to assessment of recanalization are associated with recanalization of an arterial occlusion after administration of IV alteplase, according to a study published in the September 11 issue of JAMA. This multicenter prospective cohort study included 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on CT angiogram (CTA). In all, 275 participants received IV alteplase, 195 participants received IV alteplase plus endovascular thrombectomy, 48 participants received endovascular thrombectomy, and 57 participants received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes. Successful recanalization occurred at an unadjusted rate of 27.3%, including in 30.4% of patients who received IV alteplase and 13.3% who did not.

Menon BK, Al-Ajlan FS, Najm M, et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018;320(10):1017-1026.

FDA Approves Ajovy for Adults With Migraine

The FDA has approved Ajovy (fremanezumab-vfrm), a calcitonin gene-related peptide (CGRP) antagonist, for the preventive treatment of migraine in adults. Dosing options include 225 mg monthly administered as one subcutaneous injection or 675 mg quarterly administered as three subcutaneous injections. The injections can be administered by a healthcare professional or by a patient or caregiver. The treatment was evaluated in two phase III, placebo-controlled clinical trials that enrolled patients with migraine. The trials examined the therapy as a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse reactions were injection site reactions. Ajovy is a humanized monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor. Teva Pharmaceutical Industries, which markets Ajovy, is headquartered in Jerusalem.

Is Daytime Sleepiness Associated With an Alzheimer’s Disease Biomarker?

Excessive daytime sleepiness (EDS) is associated with more than 2.5 times the odds of β-amyloid (Aβ) deposition an average of 15.7 years later, according to a study published online ahead of print September 5 in Sleep. Researchers studied 124 participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-reported measures of EDS and napping at baseline and underwent 11C-Pittsburgh compound B-PET scans of the brain an average of 15.7 years later. Participants’ mean age was 60.1 at baseline; 24.4% had EDS, and 28.5% napped. In unadjusted analyses, compared with participants without EDS, people with EDS had more than three times the odds of being Aβ+ (ie, having a cortical distribution volume ratio of greater than 1.06) at follow-up. After adjusting for age, sex, education, and BMI, the odds ratio was 2.75.

Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018 Sep 5 [Epub ahead of print].

Sepsis Heightens Risk of Stroke and Heart Attack

Patients recovering from sepsis have a greater risk of myocardial infarction or stroke in the first four weeks after hospital discharge, compared with population and hospital controls, according to a study published September 10 in the Canadian Medical Association Journal. This retrospective population-based cohort study included 42,316 patients with sepsis identified from the National Health Insurance Research Database in Taiwan. In all, 831 patients with sepsis had a stroke and 184 had a myocardial infarction within 180 days of discharge from the hospital. Compared with population controls, the risk was highest in the first seven days after discharge (hazard ratio, 4.78). Compared with hospital controls, the risk was attenuated but remained elevated before day 36 after discharge (hazard ratio, 1.32).

Lai CC, Lee MG, Lee WC, et al. Susceptible period for cardiovascular complications in patients recovering from sepsis. CMAJ. 2018;190(36):E1062-E1069.

Ten-Year Risk Factors for Dementia

Age, sex, and APOE genotype identify high-risk groups for Alzheimer’s disease and dementia, according to a study published September 4 in the Canadian Medical Association Journal. The study looked at data from 104,537 people in Copenhagen. Participants completed a questionnaire and underwent physical examination and blood sampling at baseline. The researchers obtained diagnoses of dementia and cerebrovascular disease from the Danish National Patient Registry through November 10, 2014. The absolute 10-year risk of Alzheimer’s disease among 3,017 people who were carriers of the APOE ε44 genotype was 7% for women and 6% for men ages 60 to 69, 16% for women and 12% for men ages 70 to 79, and 24% for women and 19% for men ages 80 and older.

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041.

Is Job Stress Associated With Parkinson’s Disease Risk?

Occupational stress may increase Parkinson’s disease risk, according to a study published online ahead of print August 25 in Movement Disorders. Researchers conducted a population-based cohort study of 2,544,748 Swedes whose occupations had been reported in censuses. They identified incident Parkinson’s disease cases using Swedish national health registers and analyzed the data using Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. During a mean follow-up of 21.3 years, 21,544 incident Parkinson’s disease cases were identified. High job demands were associated with increased risk of Parkinson’s disease among men, most evidently in men with high levels of education. High levels of job control were associated with increased risk among people with low levels of education, and this association was stronger in women.

Sieurin J, Andel R, Tillander A, et al. Occupational stress and risk for Parkinson’s disease: a nationwide cohort study. Mov Disord. 2018 Aug 25 [Epub ahead of print].

FDA Approves Tiglutik for ALS

The FDA has approved Tiglutik (riluzole) oral suspension for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik is a thickened liquid taken twice daily by oral syringe. The approval of Tiglutik is based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. The recommended dosage is 50 mg/10 mL. The drug should be taken at least one hour before or two hours after a meal. In clinical studies, riluzole modulated glutamate neurotransmission by inhibiting glutamate release and postsynaptic glutamate receptor signaling. ITF Pharma, which markets the drug, is headquartered in Berwyn, Pennsylvania.

—Kimberly Williams

CPAP After Stroke May Improve Function

Treating sleep apnea after a stroke or transient ischemic attack (TIA) may improve speech impairment, neurologic symptoms, walking, and physical function, according to a study published August 15 in the Journal of the American Heart Association. To examine whether continuous positive airway pressure (CPAP) improves clinical outcomes among patients with stroke or TIA who have obstructive sleep apnea, researchers analyzed data from a trial that included 252 patients with stroke or TIA. Participants were randomized to intervention groups that received polysomnography soon after the stroke or TIA or to a control group. Among the 81 patients in the intervention groups with sleep apnea, more than 70% used CPAP during approximately one year of follow-up. In intention-to-treat analyses, changes in NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores were similar across groups. In as-treated analyses among patients with sleep apnea, CPAP use was associated with improved NIHSS and mRS scores. In addition, 59% of intervention patients with sleep apnea had a final NIHSS score of 0 or 1 versus 38% of controls with sleep apnea.

Bravata DM, Sico J, Fragoso CAV, et al. Diagnosing and treating sleep apnea in patients with acute cerebrovascular disease. J Am Heart Assoc. 2018;7:e008841.

Intervention Reduces Cognitive Decline in Blacks With MCI

Among black patients with mild cognitive impairment (MCI), a behavioral intervention that aims to increase social, cognitive, and physical activity reduces the risk of memory decline, compared with supportive therapy, according to a study published online ahead of print September 10 in JAMA Neurology. Between June 2011 and October 2014, researchers enrolled 221 black participants with MCI (mean age, 75.8; 79% women) into a clinical trial. Participants were randomized to behavioral activation or supportive therapy (ie, an attention control treatment). The primary outcome was a decline of six or more recalled words on the total recall score of the Hopkins Verbal Learning Test-Revised at six, 12, 18, and 24 months. The two-year incidence of memory decline was lower in the behavioral activation group than in the supportive therapy group (1.2% vs 9.3%). Behavioral activation reduced the risk of cognitive decline by 88%, compared with supportive therapy.

Rovner BW, Casten RJ, Hegel MT, Leiby B. Preventing cognitive decline in black individuals with mild cognitive impairment: a randomized clinical trial. JAMA Neurol. 2018 Sep 10 [Epub ahead of print].

Medical Marijuana May Treat Nerve Pain

Among patients with neuropathic pain, sublingual tetrahydrocannabinol (THC) significantly reduces pain versus placebo, according to a randomized, double-blind study published online ahead of print September 5 in Neurology. The trial included 15 men with chronic radicular nerve pain (average age, 33). Before and one hour after treatment with THC or placebo oil, participants rated their pain levels on a scale from zero to 100. At least one week later, they received the other treatment. The average pain level before treatment was 53. After taking THC, participants’ average pain level was 35, compared with an average pain level of 43 after taking placebo. Functional MRI showed that the drug’s analgesic effect correlated with reduced functional connectivity between brain areas involved in emotion and pain processing.

Weizman L, Dayan L, Brill S, et al. Cannabis analgesia in chronic neuropathic pain is associated with altered brain connectivity. Neurology. 2018 Sep 5 [Epub ahead of print].

For Which Clots Is t-PA Most Effective?

In patients with acute ischemic stroke, a more distal thrombus location, greater thrombus permeability, and longer time to assessment of recanalization are associated with recanalization of an arterial occlusion after administration of IV alteplase, according to a study published in the September 11 issue of JAMA. This multicenter prospective cohort study included 575 patients with acute ischemic stroke and intracranial arterial occlusion demonstrated on CT angiogram (CTA). In all, 275 participants received IV alteplase, 195 participants received IV alteplase plus endovascular thrombectomy, 48 participants received endovascular thrombectomy, and 57 participants received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes. Successful recanalization occurred at an unadjusted rate of 27.3%, including in 30.4% of patients who received IV alteplase and 13.3% who did not.

Menon BK, Al-Ajlan FS, Najm M, et al. Association of clinical, imaging, and thrombus characteristics with recanalization of visible intracranial occlusion in patients with acute ischemic stroke. JAMA. 2018;320(10):1017-1026.

FDA Approves Ajovy for Adults With Migraine

The FDA has approved Ajovy (fremanezumab-vfrm), a calcitonin gene-related peptide (CGRP) antagonist, for the preventive treatment of migraine in adults. Dosing options include 225 mg monthly administered as one subcutaneous injection or 675 mg quarterly administered as three subcutaneous injections. The injections can be administered by a healthcare professional or by a patient or caregiver. The treatment was evaluated in two phase III, placebo-controlled clinical trials that enrolled patients with migraine. The trials examined the therapy as a stand-alone preventive treatment and in combination with oral preventive treatments. Patients experienced a reduction in monthly migraine days during a 12-week period. The most common adverse reactions were injection site reactions. Ajovy is a humanized monoclonal antibody that binds to CGRP ligand and blocks its binding to the receptor. Teva Pharmaceutical Industries, which markets Ajovy, is headquartered in Jerusalem.

Is Daytime Sleepiness Associated With an Alzheimer’s Disease Biomarker?

Excessive daytime sleepiness (EDS) is associated with more than 2.5 times the odds of β-amyloid (Aβ) deposition an average of 15.7 years later, according to a study published online ahead of print September 5 in Sleep. Researchers studied 124 participants in the Baltimore Longitudinal Study of Aging Neuroimaging Substudy who completed self-reported measures of EDS and napping at baseline and underwent 11C-Pittsburgh compound B-PET scans of the brain an average of 15.7 years later. Participants’ mean age was 60.1 at baseline; 24.4% had EDS, and 28.5% napped. In unadjusted analyses, compared with participants without EDS, people with EDS had more than three times the odds of being Aβ+ (ie, having a cortical distribution volume ratio of greater than 1.06) at follow-up. After adjusting for age, sex, education, and BMI, the odds ratio was 2.75.

Spira AP, An Y, Wu MN, et al. Excessive daytime sleepiness and napping in cognitively normal adults: associations with subsequent amyloid deposition measured by PiB PET. Sleep. 2018 Sep 5 [Epub ahead of print].

Sepsis Heightens Risk of Stroke and Heart Attack

Patients recovering from sepsis have a greater risk of myocardial infarction or stroke in the first four weeks after hospital discharge, compared with population and hospital controls, according to a study published September 10 in the Canadian Medical Association Journal. This retrospective population-based cohort study included 42,316 patients with sepsis identified from the National Health Insurance Research Database in Taiwan. In all, 831 patients with sepsis had a stroke and 184 had a myocardial infarction within 180 days of discharge from the hospital. Compared with population controls, the risk was highest in the first seven days after discharge (hazard ratio, 4.78). Compared with hospital controls, the risk was attenuated but remained elevated before day 36 after discharge (hazard ratio, 1.32).

Lai CC, Lee MG, Lee WC, et al. Susceptible period for cardiovascular complications in patients recovering from sepsis. CMAJ. 2018;190(36):E1062-E1069.

Ten-Year Risk Factors for Dementia

Age, sex, and APOE genotype identify high-risk groups for Alzheimer’s disease and dementia, according to a study published September 4 in the Canadian Medical Association Journal. The study looked at data from 104,537 people in Copenhagen. Participants completed a questionnaire and underwent physical examination and blood sampling at baseline. The researchers obtained diagnoses of dementia and cerebrovascular disease from the Danish National Patient Registry through November 10, 2014. The absolute 10-year risk of Alzheimer’s disease among 3,017 people who were carriers of the APOE ε44 genotype was 7% for women and 6% for men ages 60 to 69, 16% for women and 12% for men ages 70 to 79, and 24% for women and 19% for men ages 80 and older.

Rasmussen KL, Tybjærg-Hansen A, Nordestgaard BG, Frikke-Schmidt R. Absolute 10-year risk of dementia by age, sex and APOE genotype: a population-based cohort study. CMAJ. 2018;190(35):E1033-E1041.

Is Job Stress Associated With Parkinson’s Disease Risk?

Occupational stress may increase Parkinson’s disease risk, according to a study published online ahead of print August 25 in Movement Disorders. Researchers conducted a population-based cohort study of 2,544,748 Swedes whose occupations had been reported in censuses. They identified incident Parkinson’s disease cases using Swedish national health registers and analyzed the data using Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking. During a mean follow-up of 21.3 years, 21,544 incident Parkinson’s disease cases were identified. High job demands were associated with increased risk of Parkinson’s disease among men, most evidently in men with high levels of education. High levels of job control were associated with increased risk among people with low levels of education, and this association was stronger in women.

Sieurin J, Andel R, Tillander A, et al. Occupational stress and risk for Parkinson’s disease: a nationwide cohort study. Mov Disord. 2018 Aug 25 [Epub ahead of print].

FDA Approves Tiglutik for ALS

The FDA has approved Tiglutik (riluzole) oral suspension for the treatment of amyotrophic lateral sclerosis (ALS). Tiglutik is a thickened liquid taken twice daily by oral syringe. The approval of Tiglutik is based on bioavailability studies comparing oral riluzole tablets to Tiglutik oral suspension. The most common side effects of Tiglutik are consistent with the established clinical profile of riluzole and include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain. The recommended dosage is 50 mg/10 mL. The drug should be taken at least one hour before or two hours after a meal. In clinical studies, riluzole modulated glutamate neurotransmission by inhibiting glutamate release and postsynaptic glutamate receptor signaling. ITF Pharma, which markets the drug, is headquartered in Berwyn, Pennsylvania.

—Kimberly Williams

Intrathecal Baclofen Reduces Pain in Poststroke Spasticity

Intrathecal baclofen (ITB) therapy improves pain and quality of life in patients with poststroke spasticity, according to a study published August 14 in Stroke. Patients with poststroke spasticity in two or more extremities and an Ashworth Scale score of 3 or higher in two or more affected lower extremity muscle groups were randomized to ITB or conventional medical management. At six months, ITB effectively reduced Numeric Pain Rating Scale scores for actual and least spasticity-related pain and improved quality of life, compared with medical management. In addition, 73% of patients given ITB therapy reported satisfaction with spasticity reduction at month six, versus 48% of patients given medical management. The researchers found no statistically significant differences between groups in reduction of worst pain.

Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018 Aug 14 [Epub ahead of print].

FDA Approves Diacomit for Seizures Associated With Dravet Syndrome

The FDA has approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients age 2 and older who are taking clobazam. Diacomit will be available in 250-mg and 500-mg capsules and in fruit-flavored powder packets for oral suspension. In two studies of patients between ages 3 and 17 with Dravet syndrome, patients were randomized to Diacomit or placebo, along with their previous treatment with clobazam and valproate. In Study 1, 71% of patients in the Diacomit group were 50% responders versus 5% in the placebo group. In Study 2, 67% of patients treated with Diacomit were 50% responders versus 9.1% of controls. Diacomit is marketed by Biocodex, which is headquartered in Gentilly, France.

Retinal Thinning Is Associated With Dopaminergic Cell Loss

Retinal thinning is linked to the loss of brain cells in Parkinson’s disease, according to a study published online ahead of print August 15 in Neurology. Researchers examined 49 participants (average age, 69) who had been diagnosed with Parkinson’s disease an average of two years earlier, but who had not yet started medication. Participants were compared with 54 healthy controls who were matched for age. Participants underwent a complete eye exam and high-resolution eye scans. Patients with Parkinson’s disease had retinal layer thinning in the temporal and inferior 2.22-mm sectors. The thickness of these layers in the inferior 2.22-mm sector correlated negatively with Hoehn and Yahr stage. Retinal thinning was associated with dopaminergic loss in the left substantia nigra.

Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. 2018 Aug 15 [Epub ahead of print].

Contact Sports Linked to Vascular Risk Factors and Depression

Athletes with a history of playing professional contact sports have more vascular risk factors and higher depression scores, according to a study published online ahead of print August 3 in the Journal of Head Trauma Rehabilitation. This case–control study included 21 retired National Football League and National Hockey League players and 21 age-matched noncontact athlete controls. The investigators assessed participants for mild cognitive impairment (MCI) and measured depression using the Beck Depression Inventory-II (BDI). Eight contact sport athletes and three noncontact athletes met criteria for MCI. Contact sport athletes’ scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher BDI scores.

Baker JG, Leddy JJ, Hinds AL, et al. An exploratory study of mild cognitive impairment of retired professional contact sport athletes. J Head Trauma Rehabil. 2018 Aug 3 [Epub ahead of print].

Managing Vegetative and Minimally Conscious States

The American Academy of Neurology; the American Congress of Rehabilitative Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research have published a practice guideline on the diagnosis and ongoing medical and rehabilitative care of patients in a vegetative or minimally conscious state caused by brain injury. The guideline was published online ahead of print August 8 in Neurology. The authors based their recommendations on a systematic review of the evidence using a modified Delphi consensus process. Clinicians should advise families that for adults, a minimally conscious state and traumatic etiology are associated with more favorable outcomes, according to the guideline. Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults, but no tests improve prognostic accuracy in children, said the authors.

Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Aug 8 [Epub ahead of print].

FDA Approves Onpattro

The FDA has approved Onpattro (patisiran) lipid complex injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The approval of Onpattro was based on results from a randomized, double-blind, placebo-controlled phase III study. Of 225 patients, 148 were randomized to Onpattro infusion once every three weeks for 18 months. The other participants were randomized to placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms, compared with participants receiving placebo infusions. Patients receiving Onpattro also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living. Alnylam Pharmaceuticals, which markets Onpattro, is headquartered in Cambridge, Massachusetts.

Ophthalmic Conditions May Indicate Increased Risk of Alzheimer’s Disease

People with recent diagnoses of glaucoma, established age-related macular degeneration, and recent and established diabetic retinopathy may have increased risk of Alzheimer’s disease, according to a study published online ahead of print August 2 in Alzheimer’s & Dementia. The investigators included 3,877 participants selected randomly from the Adult Changes in Thought study in their analysis. Participants were age 65 or older and did not have Alzheimer’s disease at the time of enrollment. During the five-year study, a committee of dementia experts diagnosed Alzheimer’s disease in 792 people. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40% to 50% greater risk of developing Alzheimer’s disease, compared with people without these eye conditions. Cataract diagnosis was not a risk factor for Alzheimer’s disease.

Lee CS, Larson EB, Gibbons LE, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2018 Aug 2 [Epub ahead of print].

Insulin Resistance in Nondiabetics With Parkinson’s Disease

Insulin resistance is prevalent in Parkinson’s disease and correlates with BMI, according to a study published in the August issue of the Journal of Parkinson’s Disease. The investigators included 154 nondiabetic patients with Parkinson’s disease in the study. Participants were tested for fasting insulin, fasting glucose, and hemoglobin A1c (HbA1c) and underwent a battery of clinical tests. Investigators recorded participants’ Parkinson’s disease medications, height, weight, and other demographic features. Ninety (58.4%) participants had abnormal insulin resistance. Insulin resistance was more prevalent in overweight and obese participants than in participants with a normal weight. BMI was the only significant predictor of insulin resistance. Insulin resistance did not correlate with cognition, functioning, or nonmotor symptoms.

Hogg E, Athreya K, Basile C, et al. High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Parkinsons Dis. 2018;8(2):259-265.

FDA Approves Galafold for Fabry Disease in Adults

The FDA has approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is available in a 123-mg capsule. The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. Patients treated with Galafold over six months had a greater reduction in globotriaosylceramide in blood vessels of the kidneys, compared with patients taking placebo. Investigators studied the safety of Galafold in four clinical trials. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation, urinary tract infection, nausea, and fever. Amicus Therapeutics, which markets the capsules, is headquartered in Cranbury, New Jersey.

Binge Drinking Increases Cardiovascular Risk in Men

Young adults who frequently binge drink are more likely to have higher blood pressure, higher cholesterol, and higher blood sugar at a younger age than nonbinge drinkers, according to a study published June 27 in the Journal of the American Heart Association. Researchers analyzed data from the US National Health and Nutrition Examination Survey for 4,710 adults from ages 18 to 45. After controlling for diet and physical activity, men who binge drank as many as 12 times per year, compared with nonbinge drinkers, had higher systolic blood pressure (121.8 mm Hg vs 117.5 mm Hg) and total cholesterol (215.5 mg/dL vs 207.8 mg/dL). Binge drinking did not affect systolic blood pressure or total cholesterol in women. The effects of binge drinking on glucose parameters in men and women varied.

Piano MR, Burke L, Kang M, Phillips SA. Effects of repeated binge drinking on blood pressure levels and other cardiovascular health metrics in young adults: National Health and Nutrition Examination Survey, 2011-2014. J Am Heart Assoc. 2018;7(13).

Brain SPECT Predicts Brain Aging and Psychiatric Disorders

Brain SPECT predicts chronologic age, and brain aging varies as a function of common psychiatric disorders, according to a study published online ahead of print August 3 in the Journal of Alzheimer’s Disease. A psychiatric cohort of 31,227 participants underwent brain SPECT at rest and during a concentration task for a total of 62,454 scans. Analysis of variance identified the mean age trends over the population’s age range (ie, nine months to 105 years). Researchers studied 128 brain regions to predict the chronologic age of each participant. Older age predicted from the scan, compared with actual chronologic age, was considered accelerated aging. Childhood, adolescence, and late life were associated with variations in perfusion. Alcohol use, cannabis use, anxiety, bipolar disorder, schizophrenia, and ADHD were associated with increased brain aging.

Amen DG, Egan S, Meysami S, et al. Patterns of regional cerebral blood flow as a function of age throughout the lifespan. J Alzheimers Dis. 2018 Aug 3 [Epub ahead of print].

Folic Acid May Prevent Language Delays Associated With AED Exposure

Folic acid use early in pregnancy may prevent language delay associated with in utero antiepileptic drug (AED) exposure, according to a study published online ahead of print August 1 in Neurology. The study included 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy. For children with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratios for language delay in AED-exposed children, compared with controls, were 3.9 at 18 months and 4.7 at 36 months. When mothers took folic acid, the corresponding odds ratios for language delay were 1.7 and 1.7, respectively. The effect of folic acid supplementation on language delay in AED-exposed children was significant only when supplementation began four weeks before pregnancy and continued until the end of the first trimester.

Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018 Aug 1 [Epub ahead of print].

—Kimberly Williams

Intrathecal Baclofen Reduces Pain in Poststroke Spasticity

Intrathecal baclofen (ITB) therapy improves pain and quality of life in patients with poststroke spasticity, according to a study published August 14 in Stroke. Patients with poststroke spasticity in two or more extremities and an Ashworth Scale score of 3 or higher in two or more affected lower extremity muscle groups were randomized to ITB or conventional medical management. At six months, ITB effectively reduced Numeric Pain Rating Scale scores for actual and least spasticity-related pain and improved quality of life, compared with medical management. In addition, 73% of patients given ITB therapy reported satisfaction with spasticity reduction at month six, versus 48% of patients given medical management. The researchers found no statistically significant differences between groups in reduction of worst pain.

Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018 Aug 14 [Epub ahead of print].

FDA Approves Diacomit for Seizures Associated With Dravet Syndrome

The FDA has approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients age 2 and older who are taking clobazam. Diacomit will be available in 250-mg and 500-mg capsules and in fruit-flavored powder packets for oral suspension. In two studies of patients between ages 3 and 17 with Dravet syndrome, patients were randomized to Diacomit or placebo, along with their previous treatment with clobazam and valproate. In Study 1, 71% of patients in the Diacomit group were 50% responders versus 5% in the placebo group. In Study 2, 67% of patients treated with Diacomit were 50% responders versus 9.1% of controls. Diacomit is marketed by Biocodex, which is headquartered in Gentilly, France.

Retinal Thinning Is Associated With Dopaminergic Cell Loss

Retinal thinning is linked to the loss of brain cells in Parkinson’s disease, according to a study published online ahead of print August 15 in Neurology. Researchers examined 49 participants (average age, 69) who had been diagnosed with Parkinson’s disease an average of two years earlier, but who had not yet started medication. Participants were compared with 54 healthy controls who were matched for age. Participants underwent a complete eye exam and high-resolution eye scans. Patients with Parkinson’s disease had retinal layer thinning in the temporal and inferior 2.22-mm sectors. The thickness of these layers in the inferior 2.22-mm sector correlated negatively with Hoehn and Yahr stage. Retinal thinning was associated with dopaminergic loss in the left substantia nigra.

Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. 2018 Aug 15 [Epub ahead of print].

Contact Sports Linked to Vascular Risk Factors and Depression

Athletes with a history of playing professional contact sports have more vascular risk factors and higher depression scores, according to a study published online ahead of print August 3 in the Journal of Head Trauma Rehabilitation. This case–control study included 21 retired National Football League and National Hockey League players and 21 age-matched noncontact athlete controls. The investigators assessed participants for mild cognitive impairment (MCI) and measured depression using the Beck Depression Inventory-II (BDI). Eight contact sport athletes and three noncontact athletes met criteria for MCI. Contact sport athletes’ scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher BDI scores.

Baker JG, Leddy JJ, Hinds AL, et al. An exploratory study of mild cognitive impairment of retired professional contact sport athletes. J Head Trauma Rehabil. 2018 Aug 3 [Epub ahead of print].

Managing Vegetative and Minimally Conscious States

The American Academy of Neurology; the American Congress of Rehabilitative Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research have published a practice guideline on the diagnosis and ongoing medical and rehabilitative care of patients in a vegetative or minimally conscious state caused by brain injury. The guideline was published online ahead of print August 8 in Neurology. The authors based their recommendations on a systematic review of the evidence using a modified Delphi consensus process. Clinicians should advise families that for adults, a minimally conscious state and traumatic etiology are associated with more favorable outcomes, according to the guideline. Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults, but no tests improve prognostic accuracy in children, said the authors.

Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Aug 8 [Epub ahead of print].

FDA Approves Onpattro

The FDA has approved Onpattro (patisiran) lipid complex injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The approval of Onpattro was based on results from a randomized, double-blind, placebo-controlled phase III study. Of 225 patients, 148 were randomized to Onpattro infusion once every three weeks for 18 months. The other participants were randomized to placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms, compared with participants receiving placebo infusions. Patients receiving Onpattro also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living. Alnylam Pharmaceuticals, which markets Onpattro, is headquartered in Cambridge, Massachusetts.

Ophthalmic Conditions May Indicate Increased Risk of Alzheimer’s Disease

People with recent diagnoses of glaucoma, established age-related macular degeneration, and recent and established diabetic retinopathy may have increased risk of Alzheimer’s disease, according to a study published online ahead of print August 2 in Alzheimer’s & Dementia. The investigators included 3,877 participants selected randomly from the Adult Changes in Thought study in their analysis. Participants were age 65 or older and did not have Alzheimer’s disease at the time of enrollment. During the five-year study, a committee of dementia experts diagnosed Alzheimer’s disease in 792 people. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40% to 50% greater risk of developing Alzheimer’s disease, compared with people without these eye conditions. Cataract diagnosis was not a risk factor for Alzheimer’s disease.

Lee CS, Larson EB, Gibbons LE, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2018 Aug 2 [Epub ahead of print].

Insulin Resistance in Nondiabetics With Parkinson’s Disease

Insulin resistance is prevalent in Parkinson’s disease and correlates with BMI, according to a study published in the August issue of the Journal of Parkinson’s Disease. The investigators included 154 nondiabetic patients with Parkinson’s disease in the study. Participants were tested for fasting insulin, fasting glucose, and hemoglobin A1c (HbA1c) and underwent a battery of clinical tests. Investigators recorded participants’ Parkinson’s disease medications, height, weight, and other demographic features. Ninety (58.4%) participants had abnormal insulin resistance. Insulin resistance was more prevalent in overweight and obese participants than in participants with a normal weight. BMI was the only significant predictor of insulin resistance. Insulin resistance did not correlate with cognition, functioning, or nonmotor symptoms.

Hogg E, Athreya K, Basile C, et al. High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Parkinsons Dis. 2018;8(2):259-265.

FDA Approves Galafold for Fabry Disease in Adults

The FDA has approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is available in a 123-mg capsule. The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. Patients treated with Galafold over six months had a greater reduction in globotriaosylceramide in blood vessels of the kidneys, compared with patients taking placebo. Investigators studied the safety of Galafold in four clinical trials. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation, urinary tract infection, nausea, and fever. Amicus Therapeutics, which markets the capsules, is headquartered in Cranbury, New Jersey.

Binge Drinking Increases Cardiovascular Risk in Men

Young adults who frequently binge drink are more likely to have higher blood pressure, higher cholesterol, and higher blood sugar at a younger age than nonbinge drinkers, according to a study published June 27 in the Journal of the American Heart Association. Researchers analyzed data from the US National Health and Nutrition Examination Survey for 4,710 adults from ages 18 to 45. After controlling for diet and physical activity, men who binge drank as many as 12 times per year, compared with nonbinge drinkers, had higher systolic blood pressure (121.8 mm Hg vs 117.5 mm Hg) and total cholesterol (215.5 mg/dL vs 207.8 mg/dL). Binge drinking did not affect systolic blood pressure or total cholesterol in women. The effects of binge drinking on glucose parameters in men and women varied.

Piano MR, Burke L, Kang M, Phillips SA. Effects of repeated binge drinking on blood pressure levels and other cardiovascular health metrics in young adults: National Health and Nutrition Examination Survey, 2011-2014. J Am Heart Assoc. 2018;7(13).

Brain SPECT Predicts Brain Aging and Psychiatric Disorders

Brain SPECT predicts chronologic age, and brain aging varies as a function of common psychiatric disorders, according to a study published online ahead of print August 3 in the Journal of Alzheimer’s Disease. A psychiatric cohort of 31,227 participants underwent brain SPECT at rest and during a concentration task for a total of 62,454 scans. Analysis of variance identified the mean age trends over the population’s age range (ie, nine months to 105 years). Researchers studied 128 brain regions to predict the chronologic age of each participant. Older age predicted from the scan, compared with actual chronologic age, was considered accelerated aging. Childhood, adolescence, and late life were associated with variations in perfusion. Alcohol use, cannabis use, anxiety, bipolar disorder, schizophrenia, and ADHD were associated with increased brain aging.

Amen DG, Egan S, Meysami S, et al. Patterns of regional cerebral blood flow as a function of age throughout the lifespan. J Alzheimers Dis. 2018 Aug 3 [Epub ahead of print].

Folic Acid May Prevent Language Delays Associated With AED Exposure

Folic acid use early in pregnancy may prevent language delay associated with in utero antiepileptic drug (AED) exposure, according to a study published online ahead of print August 1 in Neurology. The study included 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy. For children with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratios for language delay in AED-exposed children, compared with controls, were 3.9 at 18 months and 4.7 at 36 months. When mothers took folic acid, the corresponding odds ratios for language delay were 1.7 and 1.7, respectively. The effect of folic acid supplementation on language delay in AED-exposed children was significant only when supplementation began four weeks before pregnancy and continued until the end of the first trimester.

Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018 Aug 1 [Epub ahead of print].

—Kimberly Williams

Intrathecal Baclofen Reduces Pain in Poststroke Spasticity

Intrathecal baclofen (ITB) therapy improves pain and quality of life in patients with poststroke spasticity, according to a study published August 14 in Stroke. Patients with poststroke spasticity in two or more extremities and an Ashworth Scale score of 3 or higher in two or more affected lower extremity muscle groups were randomized to ITB or conventional medical management. At six months, ITB effectively reduced Numeric Pain Rating Scale scores for actual and least spasticity-related pain and improved quality of life, compared with medical management. In addition, 73% of patients given ITB therapy reported satisfaction with spasticity reduction at month six, versus 48% of patients given medical management. The researchers found no statistically significant differences between groups in reduction of worst pain.

Creamer M, Cloud G, Kossmehl P, et al. Effect of intrathecal baclofen on pain and quality of life in poststroke spasticity. Stroke. 2018 Aug 14 [Epub ahead of print].

FDA Approves Diacomit for Seizures Associated With Dravet Syndrome

The FDA has approved Diacomit (stiripentol) for the treatment of seizures associated with Dravet syndrome in patients age 2 and older who are taking clobazam. Diacomit will be available in 250-mg and 500-mg capsules and in fruit-flavored powder packets for oral suspension. In two studies of patients between ages 3 and 17 with Dravet syndrome, patients were randomized to Diacomit or placebo, along with their previous treatment with clobazam and valproate. In Study 1, 71% of patients in the Diacomit group were 50% responders versus 5% in the placebo group. In Study 2, 67% of patients treated with Diacomit were 50% responders versus 9.1% of controls. Diacomit is marketed by Biocodex, which is headquartered in Gentilly, France.

Retinal Thinning Is Associated With Dopaminergic Cell Loss

Retinal thinning is linked to the loss of brain cells in Parkinson’s disease, according to a study published online ahead of print August 15 in Neurology. Researchers examined 49 participants (average age, 69) who had been diagnosed with Parkinson’s disease an average of two years earlier, but who had not yet started medication. Participants were compared with 54 healthy controls who were matched for age. Participants underwent a complete eye exam and high-resolution eye scans. Patients with Parkinson’s disease had retinal layer thinning in the temporal and inferior 2.22-mm sectors. The thickness of these layers in the inferior 2.22-mm sector correlated negatively with Hoehn and Yahr stage. Retinal thinning was associated with dopaminergic loss in the left substantia nigra.

Ahn J, Lee JY, Kim TW, et al. Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson disease. Neurology. 2018 Aug 15 [Epub ahead of print].

Contact Sports Linked to Vascular Risk Factors and Depression

Athletes with a history of playing professional contact sports have more vascular risk factors and higher depression scores, according to a study published online ahead of print August 3 in the Journal of Head Trauma Rehabilitation. This case–control study included 21 retired National Football League and National Hockey League players and 21 age-matched noncontact athlete controls. The investigators assessed participants for mild cognitive impairment (MCI) and measured depression using the Beck Depression Inventory-II (BDI). Eight contact sport athletes and three noncontact athletes met criteria for MCI. Contact sport athletes’ scores were significantly worse on Letter Fluency and List B Immediate Recall. Contact athletes were more obese, had more vascular risk factors, and had higher BDI scores.

Baker JG, Leddy JJ, Hinds AL, et al. An exploratory study of mild cognitive impairment of retired professional contact sport athletes. J Head Trauma Rehabil. 2018 Aug 3 [Epub ahead of print].

Managing Vegetative and Minimally Conscious States

The American Academy of Neurology; the American Congress of Rehabilitative Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research have published a practice guideline on the diagnosis and ongoing medical and rehabilitative care of patients in a vegetative or minimally conscious state caused by brain injury. The guideline was published online ahead of print August 8 in Neurology. The authors based their recommendations on a systematic review of the evidence using a modified Delphi consensus process. Clinicians should advise families that for adults, a minimally conscious state and traumatic etiology are associated with more favorable outcomes, according to the guideline. Structural MRI, SPECT, and the Coma Recovery Scale-Revised can assist prognostication in adults, but no tests improve prognostic accuracy in children, said the authors.

Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018 Aug 8 [Epub ahead of print].

FDA Approves Onpattro

The FDA has approved Onpattro (patisiran) lipid complex injection for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. The approval of Onpattro was based on results from a randomized, double-blind, placebo-controlled phase III study. Of 225 patients, 148 were randomized to Onpattro infusion once every three weeks for 18 months. The other participants were randomized to placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy, including muscle strength, sensation, reflexes, and autonomic symptoms, compared with participants receiving placebo infusions. Patients receiving Onpattro also scored better on assessments of walking, nutritional status, and the ability to perform activities of daily living. Alnylam Pharmaceuticals, which markets Onpattro, is headquartered in Cambridge, Massachusetts.

Ophthalmic Conditions May Indicate Increased Risk of Alzheimer’s Disease

People with recent diagnoses of glaucoma, established age-related macular degeneration, and recent and established diabetic retinopathy may have increased risk of Alzheimer’s disease, according to a study published online ahead of print August 2 in Alzheimer’s & Dementia. The investigators included 3,877 participants selected randomly from the Adult Changes in Thought study in their analysis. Participants were age 65 or older and did not have Alzheimer’s disease at the time of enrollment. During the five-year study, a committee of dementia experts diagnosed Alzheimer’s disease in 792 people. Patients with age-related macular degeneration, diabetic retinopathy, or glaucoma were at 40% to 50% greater risk of developing Alzheimer’s disease, compared with people without these eye conditions. Cataract diagnosis was not a risk factor for Alzheimer’s disease.

Lee CS, Larson EB, Gibbons LE, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement. 2018 Aug 2 [Epub ahead of print].

Insulin Resistance in Nondiabetics With Parkinson’s Disease

Insulin resistance is prevalent in Parkinson’s disease and correlates with BMI, according to a study published in the August issue of the Journal of Parkinson’s Disease. The investigators included 154 nondiabetic patients with Parkinson’s disease in the study. Participants were tested for fasting insulin, fasting glucose, and hemoglobin A1c (HbA1c) and underwent a battery of clinical tests. Investigators recorded participants’ Parkinson’s disease medications, height, weight, and other demographic features. Ninety (58.4%) participants had abnormal insulin resistance. Insulin resistance was more prevalent in overweight and obese participants than in participants with a normal weight. BMI was the only significant predictor of insulin resistance. Insulin resistance did not correlate with cognition, functioning, or nonmotor symptoms.

Hogg E, Athreya K, Basile C, et al. High prevalence of undiagnosed insulin resistance in non-diabetic subjects with Parkinson’s disease. J Parkinsons Dis. 2018;8(2):259-265.

FDA Approves Galafold for Fabry Disease in Adults

The FDA has approved Galafold (migalastat), the first oral medication for the treatment of adults with Fabry disease. The drug is available in a 123-mg capsule. The efficacy of Galafold was demonstrated in a six-month, placebo-controlled clinical trial in 45 adults with Fabry disease. Patients treated with Galafold over six months had a greater reduction in globotriaosylceramide in blood vessels of the kidneys, compared with patients taking placebo. Investigators studied the safety of Galafold in four clinical trials. The most common adverse drug reactions in patients taking Galafold in clinical trials were headache, nasal and throat irritation, urinary tract infection, nausea, and fever. Amicus Therapeutics, which markets the capsules, is headquartered in Cranbury, New Jersey.

Binge Drinking Increases Cardiovascular Risk in Men

Young adults who frequently binge drink are more likely to have higher blood pressure, higher cholesterol, and higher blood sugar at a younger age than nonbinge drinkers, according to a study published June 27 in the Journal of the American Heart Association. Researchers analyzed data from the US National Health and Nutrition Examination Survey for 4,710 adults from ages 18 to 45. After controlling for diet and physical activity, men who binge drank as many as 12 times per year, compared with nonbinge drinkers, had higher systolic blood pressure (121.8 mm Hg vs 117.5 mm Hg) and total cholesterol (215.5 mg/dL vs 207.8 mg/dL). Binge drinking did not affect systolic blood pressure or total cholesterol in women. The effects of binge drinking on glucose parameters in men and women varied.

Piano MR, Burke L, Kang M, Phillips SA. Effects of repeated binge drinking on blood pressure levels and other cardiovascular health metrics in young adults: National Health and Nutrition Examination Survey, 2011-2014. J Am Heart Assoc. 2018;7(13).

Brain SPECT Predicts Brain Aging and Psychiatric Disorders

Brain SPECT predicts chronologic age, and brain aging varies as a function of common psychiatric disorders, according to a study published online ahead of print August 3 in the Journal of Alzheimer’s Disease. A psychiatric cohort of 31,227 participants underwent brain SPECT at rest and during a concentration task for a total of 62,454 scans. Analysis of variance identified the mean age trends over the population’s age range (ie, nine months to 105 years). Researchers studied 128 brain regions to predict the chronologic age of each participant. Older age predicted from the scan, compared with actual chronologic age, was considered accelerated aging. Childhood, adolescence, and late life were associated with variations in perfusion. Alcohol use, cannabis use, anxiety, bipolar disorder, schizophrenia, and ADHD were associated with increased brain aging.

Amen DG, Egan S, Meysami S, et al. Patterns of regional cerebral blood flow as a function of age throughout the lifespan. J Alzheimers Dis. 2018 Aug 3 [Epub ahead of print].

Folic Acid May Prevent Language Delays Associated With AED Exposure

Folic acid use early in pregnancy may prevent language delay associated with in utero antiepileptic drug (AED) exposure, according to a study published online ahead of print August 1 in Neurology. The study included 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy. For children with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratios for language delay in AED-exposed children, compared with controls, were 3.9 at 18 months and 4.7 at 36 months. When mothers took folic acid, the corresponding odds ratios for language delay were 1.7 and 1.7, respectively. The effect of folic acid supplementation on language delay in AED-exposed children was significant only when supplementation began four weeks before pregnancy and continued until the end of the first trimester.

Husebye ESN, Gilhus NE, Riedel B, et al. Verbal abilities in children of mothers with epilepsy: association to maternal folate status. Neurology. 2018 Aug 1 [Epub ahead of print].

—Kimberly Williams

Practice Effects May Influence MCI Detection

Failing to account for practice effects may lead to underdiagnosis of mild cognitive impairment (MCI), according to a study published May 14 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. In an approximately six-year follow-up of the Vietnam Era Twin Study of Aging, researchers retested the cognitive function of 995 late-middle-aged men. In addition, the researchers tested 170 age-matched study replacements for the first time. The investigators used group differences to calculate practice effects after controlling for attrition effects and generated MCI diagnoses from practice-adjusted scores. There were significant practice effects on most cognitive domains, even though participants’ uncorrected scores may have declined. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%.

Elman JA, Jak AJ, Panizzon MS, et al. Underdiagnosis of mild cognitive impairment: a consequence of ignoring practice effects. Alzheimers Dement (Amst). 2018;10:372-381.

Brain Iron Levels Predict Disability in Patients With MS

Iron levels in the brains of patients with multiple sclerosis (MS) measured using quantitative susceptibility mapping (QSM) may help identify people at a higher risk of physical disability, according to a study published online ahead of print July 17 in Radiology. In this prospective study, 600 participants with MS and 250 age- and sex-matched healthy controls were imaged with 3.0-T MRI. The researchers assessed QSM and MRI volumetric differences between study groups and associations with clinical outcomes using analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex. Compared with controls, participants with MS had lower thalamic susceptibility and higher susceptibility of basal ganglia. Lower thalamic susceptibility was associated with longer disease duration, greater disability, and secondary-progressive disease course.

Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Jul 17 [Epub ahead of print].

Concussion and ADHD May Increase Depression and Anxiety

Athletes with attention deficit hyperactivity disorder (ADHD) may be at greater risk of persistent anxiety and depression after a concussion, compared with athletes without ADHD, according to a study presented at the American Academy of Neurology’s Sports Concussion Conference. The study included 979 NCAA Division I college athletes. Researchers gathered information on ADHD diagnosis and history of concussion, and athletes completed questionnaires measuring anxiety and depression symptoms before the start of their sporting seasons. The investigators divided athletes into four groups—those with ADHD who had had a concussion, those with ADHD who had not had a concussion, those without ADHD who had had a concussion, and those without a history of concussion or ADHD. Athletes with ADHD and concussion had significantly higher anxiety and depression scores, compared with the other groups.

Late-Life Blood Pressure Is Associated With Brain Lesions

Higher average late-life systolic blood pressure and diastolic blood pressure are associated with an increasing number of brain infarcts, including gross and microinfarcts, according to a study published online ahead of print July 11 in Neurology. In addition, faster decline in systolic blood pressure increases the likelihood of an infarct. This clinical-pathologic study included data from 1,288 people who participated in prospective, community-based cohort studies of aging with similar designs and data collection. Blood pressure measurements were obtained annually. Participants were followed for an average of eight years, and the average age at death was 89. The mean standardized person-specific systolic blood pressure was 134 mm Hg and diastolic blood pressure was 71 mm Hg. Alzheimer’s disease pathology analyses found that systolic blood pressure was associated with the number of tangles but not plaques or other pathology.

Arvanitakis Z, Capuano AW, Lamar M, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018 Jul 11 [Epub ahead of print].

Is t-PA Beneficial for Minor Stroke?

Among patients with mild acute ischemic stroke, treatment with alteplase does not increase the likelihood of favorable functional outcome at 90 days, compared with treatment with aspirin, according to a study published July 10 in JAMA. The PRISMS trial, a phase IIIb, double-blind, double-placebo, randomized clinical trial, compared alteplase with aspirin for the treatment of emergent stroke. The study enrolled patients with NIH Stroke Scale scores of 0 to 5 and deficits that were not clearly disabling. Eligible patients were able to receive treatment within three hours of onset. Participants were randomized to receive IV alteplase (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin (325 mg) with IV placebo (n = 157). At 90 days, 78.2% of patients in the alteplase group and 81.5% of patients in the aspirin group had a favorable outcome (ie, a modified Rankin Scale score of 0 or 1). The trial originally was designed to enroll 948 patients but was ended early because of slow enrollment. The early study termination precludes definitive conclusions, the investigators said.

Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018 Jul 10;320(2):156-166.

FDA Approves Xeomin for Adults With Sialorrhea

The FDA has approved the supplemental Biologics License Application for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea in adult patients. The approval was based on a phase III, randomized, double-blind, placebo-controlled, multicenter trial that included 184 patients. The coprimary end points of change in unstimulated salivary flow rate and Global Impression of Change Scale at week four as compared with baseline significantly improved for participants administered 100 U incobotulinumtoxinA versus placebo. The overall frequency of adverse events was similar between placebo and treatment groups with no new or unexpected adverse events reported. Participants in the study received placebo, incobotulinumtoxinA 75 U, or incobotulinumtoxinA 100 U. Merz North America, which markets Xeomin, is headquartered in Raleigh, North Carolina.

Does Exposure to Organic Solvents Heighten the Risk of MS?

People who are exposed to organic solvents and carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at greater risk of the disease than people who have only the exposure to solvents or the MS risk genes, according to a study published online ahead of print July 3 in Neurology. Using a Swedish population-based case–control study of 2,042 incident cases of MS and 2,947 controls, investigators compared the occurrence of MS in participants with different genotypes, smoking habits, and exposures to organic solvents such as paint and varnish. A potential interaction between exposure to organic solvents and MS risk human leukocyte antigen genes was evaluated by calculating the attributable proportion due to interaction. The MS genes and exposure to solvents combined were responsible for an estimated 60% of the risk of developing MS.

Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: interaction with MS risk HLA genes. Neurology. 2018 Jul 3 [Epub ahead of print].

Epidiolex Approved for the Treatment of Seizures

The FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It also is the first FDA approval of a drug for the treatment of patients with Dravet syndrome. The drug’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Taken with other medications, cannabidiol reduced the frequency of seizures, compared with placebo. Epidiolex must be dispensed with a patient medication guide that describes the drug’s uses and risks. GW Pharmaceuticals, located in the United Kingdom, markets Epidiolex.

FDA Approves Nuplazid Capsule Formulation and 10-mg Tablet

The FDA approved a new capsule dose formulation and tablet strength of Nuplazid (pimavanserin), a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. The 34-mg capsule formulation provides the recommended once daily dose in one capsule, versus the current administration of two 17-mg tablets. The 10-mg tablet provides a lower dosage strength for patients who are concomitantly receiving strong cytochrome 3A4 inhibitors, which can inhibit the metabolism of Nuplazid. The drug is a nondopaminergic, selective serotonin inverse agonist preferentially targeting 5-HT_2A receptors. Acadia Pharmaceuticals, which markets the therapy, is headquartered in San Diego.

Mild Sleep Problems May Elevate Blood Pressure in Women

Mild sleep problems such as trouble falling asleep are associated with increased blood pressure and vascular inflammation in women, according to a study published June 9 in the Journal of the American Heart Association. Researchers examined blood pressure and sleep habits in 323 women in the ongoing American Heart Association Go Red for Women Strategically Focused Research Network. Investigators assessed participant’s sleep quality, obstructive sleep apnea risk, and insomnia severity. In a subset of women, sleep duration was assessed using actigraphy, and endothelial inflammation was assessed directly in harvested endothelial cells. Systolic blood pressure was associated with poor sleep quality. Poor sleep quality, insomnia, and longer sleep onset latency were associated with endothelial inflammation.

Aggarwal B, Makarem N, Shah R, et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12):e008590.

DBS May Slow Tremor Progression in Early Parkinson’s Disease

Deep brain stimulation (DBS) in the early stage of Parkinson’s disease may slow tremor progression, according to a study published online ahead of print June 29 in Neurology. The prospective pilot trial enrolled patients with Parkinson’s disease who were ages 50 to 75, had been treated with Parkinson’s disease medications for six months to four years, and had no history of dyskinesia or other motor fluctuations. Participants were randomized to receive optimal drug therapy (ODT) or DBS and ODT. At baseline and six, 12, 18, and 24 months, all patients stopped all Parkinson’s disease therapy for one week. Unified Parkinson’s Disease Rating Scale-III scores were compared between the ODT and DBS and ODT groups (n = 28). Rest tremor slopes from baseline to 24 months favored DBS plus ODT off and on therapy, compared with ODT alone.

Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jun 29 [Epub ahead of print].

—Kimberly Williams

Practice Effects May Influence MCI Detection

Failing to account for practice effects may lead to underdiagnosis of mild cognitive impairment (MCI), according to a study published May 14 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. In an approximately six-year follow-up of the Vietnam Era Twin Study of Aging, researchers retested the cognitive function of 995 late-middle-aged men. In addition, the researchers tested 170 age-matched study replacements for the first time. The investigators used group differences to calculate practice effects after controlling for attrition effects and generated MCI diagnoses from practice-adjusted scores. There were significant practice effects on most cognitive domains, even though participants’ uncorrected scores may have declined. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%.

Elman JA, Jak AJ, Panizzon MS, et al. Underdiagnosis of mild cognitive impairment: a consequence of ignoring practice effects. Alzheimers Dement (Amst). 2018;10:372-381.

Brain Iron Levels Predict Disability in Patients With MS

Iron levels in the brains of patients with multiple sclerosis (MS) measured using quantitative susceptibility mapping (QSM) may help identify people at a higher risk of physical disability, according to a study published online ahead of print July 17 in Radiology. In this prospective study, 600 participants with MS and 250 age- and sex-matched healthy controls were imaged with 3.0-T MRI. The researchers assessed QSM and MRI volumetric differences between study groups and associations with clinical outcomes using analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex. Compared with controls, participants with MS had lower thalamic susceptibility and higher susceptibility of basal ganglia. Lower thalamic susceptibility was associated with longer disease duration, greater disability, and secondary-progressive disease course.

Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Jul 17 [Epub ahead of print].

Concussion and ADHD May Increase Depression and Anxiety

Athletes with attention deficit hyperactivity disorder (ADHD) may be at greater risk of persistent anxiety and depression after a concussion, compared with athletes without ADHD, according to a study presented at the American Academy of Neurology’s Sports Concussion Conference. The study included 979 NCAA Division I college athletes. Researchers gathered information on ADHD diagnosis and history of concussion, and athletes completed questionnaires measuring anxiety and depression symptoms before the start of their sporting seasons. The investigators divided athletes into four groups—those with ADHD who had had a concussion, those with ADHD who had not had a concussion, those without ADHD who had had a concussion, and those without a history of concussion or ADHD. Athletes with ADHD and concussion had significantly higher anxiety and depression scores, compared with the other groups.

Late-Life Blood Pressure Is Associated With Brain Lesions

Higher average late-life systolic blood pressure and diastolic blood pressure are associated with an increasing number of brain infarcts, including gross and microinfarcts, according to a study published online ahead of print July 11 in Neurology. In addition, faster decline in systolic blood pressure increases the likelihood of an infarct. This clinical-pathologic study included data from 1,288 people who participated in prospective, community-based cohort studies of aging with similar designs and data collection. Blood pressure measurements were obtained annually. Participants were followed for an average of eight years, and the average age at death was 89. The mean standardized person-specific systolic blood pressure was 134 mm Hg and diastolic blood pressure was 71 mm Hg. Alzheimer’s disease pathology analyses found that systolic blood pressure was associated with the number of tangles but not plaques or other pathology.

Arvanitakis Z, Capuano AW, Lamar M, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018 Jul 11 [Epub ahead of print].

Is t-PA Beneficial for Minor Stroke?

Among patients with mild acute ischemic stroke, treatment with alteplase does not increase the likelihood of favorable functional outcome at 90 days, compared with treatment with aspirin, according to a study published July 10 in JAMA. The PRISMS trial, a phase IIIb, double-blind, double-placebo, randomized clinical trial, compared alteplase with aspirin for the treatment of emergent stroke. The study enrolled patients with NIH Stroke Scale scores of 0 to 5 and deficits that were not clearly disabling. Eligible patients were able to receive treatment within three hours of onset. Participants were randomized to receive IV alteplase (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin (325 mg) with IV placebo (n = 157). At 90 days, 78.2% of patients in the alteplase group and 81.5% of patients in the aspirin group had a favorable outcome (ie, a modified Rankin Scale score of 0 or 1). The trial originally was designed to enroll 948 patients but was ended early because of slow enrollment. The early study termination precludes definitive conclusions, the investigators said.

Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018 Jul 10;320(2):156-166.

FDA Approves Xeomin for Adults With Sialorrhea

The FDA has approved the supplemental Biologics License Application for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea in adult patients. The approval was based on a phase III, randomized, double-blind, placebo-controlled, multicenter trial that included 184 patients. The coprimary end points of change in unstimulated salivary flow rate and Global Impression of Change Scale at week four as compared with baseline significantly improved for participants administered 100 U incobotulinumtoxinA versus placebo. The overall frequency of adverse events was similar between placebo and treatment groups with no new or unexpected adverse events reported. Participants in the study received placebo, incobotulinumtoxinA 75 U, or incobotulinumtoxinA 100 U. Merz North America, which markets Xeomin, is headquartered in Raleigh, North Carolina.

Does Exposure to Organic Solvents Heighten the Risk of MS?

People who are exposed to organic solvents and carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at greater risk of the disease than people who have only the exposure to solvents or the MS risk genes, according to a study published online ahead of print July 3 in Neurology. Using a Swedish population-based case–control study of 2,042 incident cases of MS and 2,947 controls, investigators compared the occurrence of MS in participants with different genotypes, smoking habits, and exposures to organic solvents such as paint and varnish. A potential interaction between exposure to organic solvents and MS risk human leukocyte antigen genes was evaluated by calculating the attributable proportion due to interaction. The MS genes and exposure to solvents combined were responsible for an estimated 60% of the risk of developing MS.

Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: interaction with MS risk HLA genes. Neurology. 2018 Jul 3 [Epub ahead of print].

Epidiolex Approved for the Treatment of Seizures

The FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It also is the first FDA approval of a drug for the treatment of patients with Dravet syndrome. The drug’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Taken with other medications, cannabidiol reduced the frequency of seizures, compared with placebo. Epidiolex must be dispensed with a patient medication guide that describes the drug’s uses and risks. GW Pharmaceuticals, located in the United Kingdom, markets Epidiolex.

FDA Approves Nuplazid Capsule Formulation and 10-mg Tablet

The FDA approved a new capsule dose formulation and tablet strength of Nuplazid (pimavanserin), a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. The 34-mg capsule formulation provides the recommended once daily dose in one capsule, versus the current administration of two 17-mg tablets. The 10-mg tablet provides a lower dosage strength for patients who are concomitantly receiving strong cytochrome 3A4 inhibitors, which can inhibit the metabolism of Nuplazid. The drug is a nondopaminergic, selective serotonin inverse agonist preferentially targeting 5-HT_2A receptors. Acadia Pharmaceuticals, which markets the therapy, is headquartered in San Diego.

Mild Sleep Problems May Elevate Blood Pressure in Women

Mild sleep problems such as trouble falling asleep are associated with increased blood pressure and vascular inflammation in women, according to a study published June 9 in the Journal of the American Heart Association. Researchers examined blood pressure and sleep habits in 323 women in the ongoing American Heart Association Go Red for Women Strategically Focused Research Network. Investigators assessed participant’s sleep quality, obstructive sleep apnea risk, and insomnia severity. In a subset of women, sleep duration was assessed using actigraphy, and endothelial inflammation was assessed directly in harvested endothelial cells. Systolic blood pressure was associated with poor sleep quality. Poor sleep quality, insomnia, and longer sleep onset latency were associated with endothelial inflammation.

Aggarwal B, Makarem N, Shah R, et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12):e008590.

DBS May Slow Tremor Progression in Early Parkinson’s Disease

Deep brain stimulation (DBS) in the early stage of Parkinson’s disease may slow tremor progression, according to a study published online ahead of print June 29 in Neurology. The prospective pilot trial enrolled patients with Parkinson’s disease who were ages 50 to 75, had been treated with Parkinson’s disease medications for six months to four years, and had no history of dyskinesia or other motor fluctuations. Participants were randomized to receive optimal drug therapy (ODT) or DBS and ODT. At baseline and six, 12, 18, and 24 months, all patients stopped all Parkinson’s disease therapy for one week. Unified Parkinson’s Disease Rating Scale-III scores were compared between the ODT and DBS and ODT groups (n = 28). Rest tremor slopes from baseline to 24 months favored DBS plus ODT off and on therapy, compared with ODT alone.

Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jun 29 [Epub ahead of print].

—Kimberly Williams

Practice Effects May Influence MCI Detection

Failing to account for practice effects may lead to underdiagnosis of mild cognitive impairment (MCI), according to a study published May 14 in Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. In an approximately six-year follow-up of the Vietnam Era Twin Study of Aging, researchers retested the cognitive function of 995 late-middle-aged men. In addition, the researchers tested 170 age-matched study replacements for the first time. The investigators used group differences to calculate practice effects after controlling for attrition effects and generated MCI diagnoses from practice-adjusted scores. There were significant practice effects on most cognitive domains, even though participants’ uncorrected scores may have declined. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%.

Elman JA, Jak AJ, Panizzon MS, et al. Underdiagnosis of mild cognitive impairment: a consequence of ignoring practice effects. Alzheimers Dement (Amst). 2018;10:372-381.

Brain Iron Levels Predict Disability in Patients With MS

Iron levels in the brains of patients with multiple sclerosis (MS) measured using quantitative susceptibility mapping (QSM) may help identify people at a higher risk of physical disability, according to a study published online ahead of print July 17 in Radiology. In this prospective study, 600 participants with MS and 250 age- and sex-matched healthy controls were imaged with 3.0-T MRI. The researchers assessed QSM and MRI volumetric differences between study groups and associations with clinical outcomes using analysis of covariance, multivariable linear regression, and voxelwise analyses, controlling for age and sex. Compared with controls, participants with MS had lower thalamic susceptibility and higher susceptibility of basal ganglia. Lower thalamic susceptibility was associated with longer disease duration, greater disability, and secondary-progressive disease course.

Zivadinov R, Tavazzi E, Bergsland N, et al. Brain iron at quantitative MRI is associated with disability in multiple sclerosis. Radiology. 2018 Jul 17 [Epub ahead of print].

Concussion and ADHD May Increase Depression and Anxiety

Athletes with attention deficit hyperactivity disorder (ADHD) may be at greater risk of persistent anxiety and depression after a concussion, compared with athletes without ADHD, according to a study presented at the American Academy of Neurology’s Sports Concussion Conference. The study included 979 NCAA Division I college athletes. Researchers gathered information on ADHD diagnosis and history of concussion, and athletes completed questionnaires measuring anxiety and depression symptoms before the start of their sporting seasons. The investigators divided athletes into four groups—those with ADHD who had had a concussion, those with ADHD who had not had a concussion, those without ADHD who had had a concussion, and those without a history of concussion or ADHD. Athletes with ADHD and concussion had significantly higher anxiety and depression scores, compared with the other groups.

Late-Life Blood Pressure Is Associated With Brain Lesions

Higher average late-life systolic blood pressure and diastolic blood pressure are associated with an increasing number of brain infarcts, including gross and microinfarcts, according to a study published online ahead of print July 11 in Neurology. In addition, faster decline in systolic blood pressure increases the likelihood of an infarct. This clinical-pathologic study included data from 1,288 people who participated in prospective, community-based cohort studies of aging with similar designs and data collection. Blood pressure measurements were obtained annually. Participants were followed for an average of eight years, and the average age at death was 89. The mean standardized person-specific systolic blood pressure was 134 mm Hg and diastolic blood pressure was 71 mm Hg. Alzheimer’s disease pathology analyses found that systolic blood pressure was associated with the number of tangles but not plaques or other pathology.

Arvanitakis Z, Capuano AW, Lamar M, et al. Late-life blood pressure association with cerebrovascular and Alzheimer disease pathology. Neurology. 2018 Jul 11 [Epub ahead of print].

Is t-PA Beneficial for Minor Stroke?

Among patients with mild acute ischemic stroke, treatment with alteplase does not increase the likelihood of favorable functional outcome at 90 days, compared with treatment with aspirin, according to a study published July 10 in JAMA. The PRISMS trial, a phase IIIb, double-blind, double-placebo, randomized clinical trial, compared alteplase with aspirin for the treatment of emergent stroke. The study enrolled patients with NIH Stroke Scale scores of 0 to 5 and deficits that were not clearly disabling. Eligible patients were able to receive treatment within three hours of onset. Participants were randomized to receive IV alteplase (0.9 mg/kg) with oral placebo (n = 156) or oral aspirin (325 mg) with IV placebo (n = 157). At 90 days, 78.2% of patients in the alteplase group and 81.5% of patients in the aspirin group had a favorable outcome (ie, a modified Rankin Scale score of 0 or 1). The trial originally was designed to enroll 948 patients but was ended early because of slow enrollment. The early study termination precludes definitive conclusions, the investigators said.

Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA. 2018 Jul 10;320(2):156-166.

FDA Approves Xeomin for Adults With Sialorrhea

The FDA has approved the supplemental Biologics License Application for Xeomin (incobotulinumtoxinA) for the treatment of chronic sialorrhea in adult patients. The approval was based on a phase III, randomized, double-blind, placebo-controlled, multicenter trial that included 184 patients. The coprimary end points of change in unstimulated salivary flow rate and Global Impression of Change Scale at week four as compared with baseline significantly improved for participants administered 100 U incobotulinumtoxinA versus placebo. The overall frequency of adverse events was similar between placebo and treatment groups with no new or unexpected adverse events reported. Participants in the study received placebo, incobotulinumtoxinA 75 U, or incobotulinumtoxinA 100 U. Merz North America, which markets Xeomin, is headquartered in Raleigh, North Carolina.

Does Exposure to Organic Solvents Heighten the Risk of MS?

People who are exposed to organic solvents and carry genes that make them more susceptible to developing multiple sclerosis (MS) may be at greater risk of the disease than people who have only the exposure to solvents or the MS risk genes, according to a study published online ahead of print July 3 in Neurology. Using a Swedish population-based case–control study of 2,042 incident cases of MS and 2,947 controls, investigators compared the occurrence of MS in participants with different genotypes, smoking habits, and exposures to organic solvents such as paint and varnish. A potential interaction between exposure to organic solvents and MS risk human leukocyte antigen genes was evaluated by calculating the attributable proportion due to interaction. The MS genes and exposure to solvents combined were responsible for an estimated 60% of the risk of developing MS.

Hedström AK, Hössjer O, Katsoulis M, et al. Organic solvents and MS susceptibility: interaction with MS risk HLA genes. Neurology. 2018 Jul 3 [Epub ahead of print].

Epidiolex Approved for the Treatment of Seizures

The FDA approved Epidiolex (cannabidiol) oral solution for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients age 2 and older. Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana. It also is the first FDA approval of a drug for the treatment of patients with Dravet syndrome. The drug’s effectiveness was studied in three randomized, double-blind, placebo-controlled clinical trials that included 516 patients with Lennox-Gastaut syndrome or Dravet syndrome. Taken with other medications, cannabidiol reduced the frequency of seizures, compared with placebo. Epidiolex must be dispensed with a patient medication guide that describes the drug’s uses and risks. GW Pharmaceuticals, located in the United Kingdom, markets Epidiolex.

FDA Approves Nuplazid Capsule Formulation and 10-mg Tablet

The FDA approved a new capsule dose formulation and tablet strength of Nuplazid (pimavanserin), a treatment for hallucinations and delusions associated with Parkinson’s disease psychosis. The 34-mg capsule formulation provides the recommended once daily dose in one capsule, versus the current administration of two 17-mg tablets. The 10-mg tablet provides a lower dosage strength for patients who are concomitantly receiving strong cytochrome 3A4 inhibitors, which can inhibit the metabolism of Nuplazid. The drug is a nondopaminergic, selective serotonin inverse agonist preferentially targeting 5-HT_2A receptors. Acadia Pharmaceuticals, which markets the therapy, is headquartered in San Diego.

Mild Sleep Problems May Elevate Blood Pressure in Women

Mild sleep problems such as trouble falling asleep are associated with increased blood pressure and vascular inflammation in women, according to a study published June 9 in the Journal of the American Heart Association. Researchers examined blood pressure and sleep habits in 323 women in the ongoing American Heart Association Go Red for Women Strategically Focused Research Network. Investigators assessed participant’s sleep quality, obstructive sleep apnea risk, and insomnia severity. In a subset of women, sleep duration was assessed using actigraphy, and endothelial inflammation was assessed directly in harvested endothelial cells. Systolic blood pressure was associated with poor sleep quality. Poor sleep quality, insomnia, and longer sleep onset latency were associated with endothelial inflammation.

Aggarwal B, Makarem N, Shah R, et al. Effects of inadequate sleep on blood pressure and endothelial inflammation in women: findings from the American Heart Association Go Red for Women Strategically Focused Research Network. J Am Heart Assoc. 2018;7(12):e008590.

DBS May Slow Tremor Progression in Early Parkinson’s Disease

Deep brain stimulation (DBS) in the early stage of Parkinson’s disease may slow tremor progression, according to a study published online ahead of print June 29 in Neurology. The prospective pilot trial enrolled patients with Parkinson’s disease who were ages 50 to 75, had been treated with Parkinson’s disease medications for six months to four years, and had no history of dyskinesia or other motor fluctuations. Participants were randomized to receive optimal drug therapy (ODT) or DBS and ODT. At baseline and six, 12, 18, and 24 months, all patients stopped all Parkinson’s disease therapy for one week. Unified Parkinson’s Disease Rating Scale-III scores were compared between the ODT and DBS and ODT groups (n = 28). Rest tremor slopes from baseline to 24 months favored DBS plus ODT off and on therapy, compared with ODT alone.

Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jun 29 [Epub ahead of print].

—Kimberly Williams

Adequate Sleep Associated With Lower Dementia Risk

Short and long daily sleep duration are risk factors for dementia and death in adults age 60 and older, according to a study published online ahead of print June 6 in the Journal of the American Geriatrics Society. In a prospective cohort study, researchers followed 1,517 adults without dementia for 10 years. Self-reported daily sleep durations were grouped into five categories. The association between daily sleep duration and risk of dementia and death was determined using Cox proportional hazards models. During follow-up, 294 participants developed dementia, and 282 died. Age- and sex-adjusted incidence rates of dementia and all-cause mortality were significantly greater in subjects who slept less than 5.0 hours/day or 10.0 or more hours/day than in people who slept from 5.0 to 6.9 hours/day.

Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018 Jun 6 [Epub ahead of print].

Rivaroxaban Not Superior to Aspirin for Stroke Prevention

Rivaroxaban is not superior to aspirin in the prevention of recurrent stroke, according to a study published June 7 in the New England Journal of Medicine. Researchers compared the efficacy and safety of rivaroxaban at a daily dose of 15 mg with aspirin at a daily dose of 100 mg for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism. The primary outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis. At 459 sites, 3,609 patients were randomly assigned to receive rivaroxaban, and 3,604 were randomized to aspirin. Recurrent ischemic stroke occurred in 172 patients in the rivaroxaban group and in 160 in the aspirin group.

Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201.

Disintegrating Brain Lesions May Indicate Worsening MS

Atrophied lesion volume may indicate increasing disability in patients with multiple sclerosis (MS), according to a study published online ahead of print June 1 in the Journal of Neuroimaging. A total of 192 patients with clinically isolated syndrome or MS received 3T MRI at baseline and at five years. Investigators quantified lesions at baseline and calculated new and enlarging lesion volumes during the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived CSF partial volume maps. The researchers evaluated correlations between these measures and disability, as measured by the Expanded Disability Status Scale (EDSS). Atrophied lesion volume was different between MS subtypes and exceeded new lesion volume accumulation in progressive MS. Atrophied lesion volume was the only significant correlate of EDSS change.

Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Jun 1 [Epub ahead of print].

Do Migraineurs Seek Behavioral Treatment After a Referral?

A significant number of migraineurs are not using effective behavioral treatments for migraine, according to a study published online ahead of print June 5 in Pain Medicine. In a prospective cohort study, researchers tracked 234 patients with migraine who presented to an academic headache center and referred 69 of them for behavioral treatment with an appropriately trained therapist. Fifty-three of the referred patients completed a follow-up interview within three months of their initial appointment and were included in the analysis. Of the patients referred for behavioral treatment, 30 made an appointment. Investigators found no differences between people who started behavioral therapy and people who did not. Study authors did find that people who had previously seen a psychologist for migraine were more likely to initiate therapy.

Minen MT, Azarchi S, Sobolev R, et al. Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: a prospective observational study. Pain Med. 2018 Jun 5 [Epub ahead of print].

TIA Associated With Increased Five-Year Risk of Stroke

People with transient ischemic attack (TIA) are at risk for a cardiovascular event in the following five years, according to a study published June 7 in the New England Journal of Medicine. Researchers evaluated patients who had had a TIA within seven days before enrollment in a registry of TIA clinics. Of 61 sites, 42 had follow-up data on more than 50% of their enrolled patients at five years. The study’s primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes, with an emphasis on events that occurred in the second through fifth years. At five years, stroke had occurred in 345 of the 3,847 patients included in the follow-up study, and 149 of them had a stroke during the second through fifth years of follow-up.

Amarenco P, Lavallée PC, Monteiro Tavares L, et al. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378(23):2182-2190.

Follow-Up Care for TBI Is Not Delivered Adequately

Follow-up care for patients with traumatic brain injury (TBI) is not delivered optimally, according to a study published May 25 in JAMA Network Open. In a cohort study, researchers surveyed 831 participants in the Transforming Research and Clinical Knowledge in TBI initiative about their care after hospital discharge. Follow-up care was defined as providing TBI-related educational materials at discharge, calling patients within two weeks after release, seeing a healthcare provider within two weeks, and seeing a healthcare provider within three months. Approximately 42% of participants reported receiving TBI-related educational material at discharge, and 44% reported seeing a physician or other medical practitioner within three months after injury. Of patients with a positive finding on CT, 39% had not seen a medical practitioner at three months after injury.

Seabury SA, Gaudette E, Goldman DP, et al. Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Network Open. 2018;1(1):e180210.

Researchers Examine Mortality Rate of Pediatric Stroke

In-hospital mortality occurs in 2.6% of children with arterial ischemic stroke, according to a study published in the May issue of Pediatrics. The retrospective study included 915 infants younger than 1 month and 2,273 children age 1 month to 18 years with stroke at 87 hospitals in 24 countries. Death during hospitalization and cause of death were ascertained from medical records. A total of 14 neonates and 70 children died during hospitalization. Of 48 cases with reported causes of death, 31 were stroke-related. Remaining deaths were attributed to medical disease. In multivariable analysis, congenital heart disease, posterior plus anterior circulation stroke, and stroke presentation without seizures were associated with in-hospital mortality for neonates. Hispanic ethnicity, congenital heart disease, and posterior plus anterior circulation stroke were associated with in-hospital mortality for children.

Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality after pediatric arterial ischemic stroke. Pediatrics. 2018;141(5).

FDA Approves zEEG Dry Electrode Headset

The FDA has approved the zEEG dry electrode EEG headset for clinical use. The zEEG headset is backed by a cloud platform that allows users to upload data instantly, provides tools for analysis, and enables remote interpretation by neurologists. A clinical study found that the zEEG headset provided EEG signal quality that was comparable to that of an approved, traditional EEG system. In two study cohorts, a total of 30 patients were studied for time periods of as long as two hours, and the zEEG device performed at least as well as the reference device, based on predefined acceptance criteria. Study results will be published in the coming months. Zeto, headquartered in Santa Clara, California, markets the device.

South Asian Americans Have High Cardiovascular Mortality

South Asians living in the United States have higher mortality from heart conditions caused by atherosclerosis, such as heart attack and stroke, according to a study published online ahead of print May 24 in Circulation. Investigators reviewed the literature relevant to South Asian populations’ demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies. South Asians have higher proportional mortality rates from atherosclerotic cardiovascular disease, compared with other Asian groups, largely because of the lower risk observed in East Asian populations. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially factors related to insulin resistance. The authors found no unique risk factors in this population.

Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018 May 24 [Epub ahead of print].

How Much Exercise Improves Cognition in Older Adults?

Exercising for at least 52 hours over six months is associated with improved cognitive performance in older adults with and without cognitive impairment, according to a study published online ahead of print May 30 in Neurology. Researchers reviewed data for 98 randomized, controlled exercise trials including 11,061 participants with an average age of 73. About 59% of the participants were healthy adults, 26% had mild cognitive impairment, and 15% had dementia. Researchers collected data on exercise session length, intensity, weekly frequency, and amount of exercise over time. Aerobic exercise was the most common form of exercise. In healthy people and people with cognitive impairment, longer term exposure to exercise, at least 52 hours conducted over an average of about six months, improved the brain’s processing speed.

Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurology. 2018 May 30 [Epub ahead of print].

Blood Biomarkers Detect Subconcussive Head Trauma

Blood biomarkers can detect the neurologic injury associated with repetitive subconcussive head trauma, according to a study published online ahead of print May 29 in the Journal of Neurosurgery. A total of 35 National Collegiate Athletic Association football players underwent blood sampling throughout the 2016 football season. Samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light. Athletes were categorized as starters or nonstarters, and the investigators assessed between-group differences and time-course differences. In nonstarters, plasma concentrations of tau decreased over the season. Starters had lower plasma concentrations of tau. Plasma concentrations of tau could not be used to distinguish between starters and nonstarters. Serum concentrations of neurofilament light increased as head impacts increased, specifically in starters. Serum neurofilament light distinguished starters from nonstarters.

Oliver JM, Anzalone AJ, Stone JD, et al. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29 [Epub ahead of print].

Model Estimates Risk of Alzheimer’s Disease Dementia

Most people with preclinical Alzheimer’s disease will not develop dementia during their lifetimes, according to a study published online ahead of print May 7 in Alzheimer’s & Dementia. Researchers used a multistate model for Alzheimer’s disease along with US death rates to estimate lifetime and 10-year risks of Alzheimer’s disease dementia. Lifetime risks of Alzheimer’s disease dementia vary by age, gender, and preclinical or clinical disease state. A 70-year-old male with amyloid but no signs of neurodegeneration and no memory loss has a lifetime risk of 19.9%. The lifetime risks for a female with amyloidosis are 8.4% at age 90 and 29.3% at age 65. People younger than 85 with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of Alzheimer’s disease dementia greater than 50%.

Brookmeyer R, Abdalla N. Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018 May 7 [Epub ahead of print].

Depression Is Associated With Brain and Memory Outcomes

In a sample of mostly Caribbean Hispanic, stroke-free older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts, according to a study published online ahead of print May 9 in Neurology. Researchers analyzed data from the Northern Manhattan Study. A total of 1,111 participants underwent baseline evaluations of depressive symptoms, MRI markers, and cognitive function. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographics, vascular risk factors, behavioral factors, and antidepressant medications. Furthermore, greater depressive symptoms were associated with smaller cerebral parenchymal fraction and increased odds of subclinical brain infarcts, after adjustment for sociodemographics, behavioral factors, and vascular risk factors.

Al Hazzouri AZ, Caunca MR, Nobrega JC. Greater depressive symptoms, cognition, and markers of brain aging. Neurology. 2018 May 9 [Epub ahead of print].

—Kimberly Williams

Adequate Sleep Associated With Lower Dementia Risk

Short and long daily sleep duration are risk factors for dementia and death in adults age 60 and older, according to a study published online ahead of print June 6 in the Journal of the American Geriatrics Society. In a prospective cohort study, researchers followed 1,517 adults without dementia for 10 years. Self-reported daily sleep durations were grouped into five categories. The association between daily sleep duration and risk of dementia and death was determined using Cox proportional hazards models. During follow-up, 294 participants developed dementia, and 282 died. Age- and sex-adjusted incidence rates of dementia and all-cause mortality were significantly greater in subjects who slept less than 5.0 hours/day or 10.0 or more hours/day than in people who slept from 5.0 to 6.9 hours/day.

Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018 Jun 6 [Epub ahead of print].

Rivaroxaban Not Superior to Aspirin for Stroke Prevention

Rivaroxaban is not superior to aspirin in the prevention of recurrent stroke, according to a study published June 7 in the New England Journal of Medicine. Researchers compared the efficacy and safety of rivaroxaban at a daily dose of 15 mg with aspirin at a daily dose of 100 mg for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism. The primary outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis. At 459 sites, 3,609 patients were randomly assigned to receive rivaroxaban, and 3,604 were randomized to aspirin. Recurrent ischemic stroke occurred in 172 patients in the rivaroxaban group and in 160 in the aspirin group.

Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201.

Disintegrating Brain Lesions May Indicate Worsening MS

Atrophied lesion volume may indicate increasing disability in patients with multiple sclerosis (MS), according to a study published online ahead of print June 1 in the Journal of Neuroimaging. A total of 192 patients with clinically isolated syndrome or MS received 3T MRI at baseline and at five years. Investigators quantified lesions at baseline and calculated new and enlarging lesion volumes during the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived CSF partial volume maps. The researchers evaluated correlations between these measures and disability, as measured by the Expanded Disability Status Scale (EDSS). Atrophied lesion volume was different between MS subtypes and exceeded new lesion volume accumulation in progressive MS. Atrophied lesion volume was the only significant correlate of EDSS change.

Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Jun 1 [Epub ahead of print].

Do Migraineurs Seek Behavioral Treatment After a Referral?

A significant number of migraineurs are not using effective behavioral treatments for migraine, according to a study published online ahead of print June 5 in Pain Medicine. In a prospective cohort study, researchers tracked 234 patients with migraine who presented to an academic headache center and referred 69 of them for behavioral treatment with an appropriately trained therapist. Fifty-three of the referred patients completed a follow-up interview within three months of their initial appointment and were included in the analysis. Of the patients referred for behavioral treatment, 30 made an appointment. Investigators found no differences between people who started behavioral therapy and people who did not. Study authors did find that people who had previously seen a psychologist for migraine were more likely to initiate therapy.

Minen MT, Azarchi S, Sobolev R, et al. Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: a prospective observational study. Pain Med. 2018 Jun 5 [Epub ahead of print].

TIA Associated With Increased Five-Year Risk of Stroke

People with transient ischemic attack (TIA) are at risk for a cardiovascular event in the following five years, according to a study published June 7 in the New England Journal of Medicine. Researchers evaluated patients who had had a TIA within seven days before enrollment in a registry of TIA clinics. Of 61 sites, 42 had follow-up data on more than 50% of their enrolled patients at five years. The study’s primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes, with an emphasis on events that occurred in the second through fifth years. At five years, stroke had occurred in 345 of the 3,847 patients included in the follow-up study, and 149 of them had a stroke during the second through fifth years of follow-up.

Amarenco P, Lavallée PC, Monteiro Tavares L, et al. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378(23):2182-2190.

Follow-Up Care for TBI Is Not Delivered Adequately

Follow-up care for patients with traumatic brain injury (TBI) is not delivered optimally, according to a study published May 25 in JAMA Network Open. In a cohort study, researchers surveyed 831 participants in the Transforming Research and Clinical Knowledge in TBI initiative about their care after hospital discharge. Follow-up care was defined as providing TBI-related educational materials at discharge, calling patients within two weeks after release, seeing a healthcare provider within two weeks, and seeing a healthcare provider within three months. Approximately 42% of participants reported receiving TBI-related educational material at discharge, and 44% reported seeing a physician or other medical practitioner within three months after injury. Of patients with a positive finding on CT, 39% had not seen a medical practitioner at three months after injury.

Seabury SA, Gaudette E, Goldman DP, et al. Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Network Open. 2018;1(1):e180210.

Researchers Examine Mortality Rate of Pediatric Stroke

In-hospital mortality occurs in 2.6% of children with arterial ischemic stroke, according to a study published in the May issue of Pediatrics. The retrospective study included 915 infants younger than 1 month and 2,273 children age 1 month to 18 years with stroke at 87 hospitals in 24 countries. Death during hospitalization and cause of death were ascertained from medical records. A total of 14 neonates and 70 children died during hospitalization. Of 48 cases with reported causes of death, 31 were stroke-related. Remaining deaths were attributed to medical disease. In multivariable analysis, congenital heart disease, posterior plus anterior circulation stroke, and stroke presentation without seizures were associated with in-hospital mortality for neonates. Hispanic ethnicity, congenital heart disease, and posterior plus anterior circulation stroke were associated with in-hospital mortality for children.

Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality after pediatric arterial ischemic stroke. Pediatrics. 2018;141(5).

FDA Approves zEEG Dry Electrode Headset

The FDA has approved the zEEG dry electrode EEG headset for clinical use. The zEEG headset is backed by a cloud platform that allows users to upload data instantly, provides tools for analysis, and enables remote interpretation by neurologists. A clinical study found that the zEEG headset provided EEG signal quality that was comparable to that of an approved, traditional EEG system. In two study cohorts, a total of 30 patients were studied for time periods of as long as two hours, and the zEEG device performed at least as well as the reference device, based on predefined acceptance criteria. Study results will be published in the coming months. Zeto, headquartered in Santa Clara, California, markets the device.

South Asian Americans Have High Cardiovascular Mortality

South Asians living in the United States have higher mortality from heart conditions caused by atherosclerosis, such as heart attack and stroke, according to a study published online ahead of print May 24 in Circulation. Investigators reviewed the literature relevant to South Asian populations’ demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies. South Asians have higher proportional mortality rates from atherosclerotic cardiovascular disease, compared with other Asian groups, largely because of the lower risk observed in East Asian populations. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially factors related to insulin resistance. The authors found no unique risk factors in this population.

Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018 May 24 [Epub ahead of print].

How Much Exercise Improves Cognition in Older Adults?

Exercising for at least 52 hours over six months is associated with improved cognitive performance in older adults with and without cognitive impairment, according to a study published online ahead of print May 30 in Neurology. Researchers reviewed data for 98 randomized, controlled exercise trials including 11,061 participants with an average age of 73. About 59% of the participants were healthy adults, 26% had mild cognitive impairment, and 15% had dementia. Researchers collected data on exercise session length, intensity, weekly frequency, and amount of exercise over time. Aerobic exercise was the most common form of exercise. In healthy people and people with cognitive impairment, longer term exposure to exercise, at least 52 hours conducted over an average of about six months, improved the brain’s processing speed.

Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurology. 2018 May 30 [Epub ahead of print].

Blood Biomarkers Detect Subconcussive Head Trauma

Blood biomarkers can detect the neurologic injury associated with repetitive subconcussive head trauma, according to a study published online ahead of print May 29 in the Journal of Neurosurgery. A total of 35 National Collegiate Athletic Association football players underwent blood sampling throughout the 2016 football season. Samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light. Athletes were categorized as starters or nonstarters, and the investigators assessed between-group differences and time-course differences. In nonstarters, plasma concentrations of tau decreased over the season. Starters had lower plasma concentrations of tau. Plasma concentrations of tau could not be used to distinguish between starters and nonstarters. Serum concentrations of neurofilament light increased as head impacts increased, specifically in starters. Serum neurofilament light distinguished starters from nonstarters.

Oliver JM, Anzalone AJ, Stone JD, et al. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29 [Epub ahead of print].

Model Estimates Risk of Alzheimer’s Disease Dementia

Most people with preclinical Alzheimer’s disease will not develop dementia during their lifetimes, according to a study published online ahead of print May 7 in Alzheimer’s & Dementia. Researchers used a multistate model for Alzheimer’s disease along with US death rates to estimate lifetime and 10-year risks of Alzheimer’s disease dementia. Lifetime risks of Alzheimer’s disease dementia vary by age, gender, and preclinical or clinical disease state. A 70-year-old male with amyloid but no signs of neurodegeneration and no memory loss has a lifetime risk of 19.9%. The lifetime risks for a female with amyloidosis are 8.4% at age 90 and 29.3% at age 65. People younger than 85 with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of Alzheimer’s disease dementia greater than 50%.

Brookmeyer R, Abdalla N. Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018 May 7 [Epub ahead of print].

Depression Is Associated With Brain and Memory Outcomes

In a sample of mostly Caribbean Hispanic, stroke-free older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts, according to a study published online ahead of print May 9 in Neurology. Researchers analyzed data from the Northern Manhattan Study. A total of 1,111 participants underwent baseline evaluations of depressive symptoms, MRI markers, and cognitive function. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographics, vascular risk factors, behavioral factors, and antidepressant medications. Furthermore, greater depressive symptoms were associated with smaller cerebral parenchymal fraction and increased odds of subclinical brain infarcts, after adjustment for sociodemographics, behavioral factors, and vascular risk factors.

Al Hazzouri AZ, Caunca MR, Nobrega JC. Greater depressive symptoms, cognition, and markers of brain aging. Neurology. 2018 May 9 [Epub ahead of print].

—Kimberly Williams

Adequate Sleep Associated With Lower Dementia Risk

Short and long daily sleep duration are risk factors for dementia and death in adults age 60 and older, according to a study published online ahead of print June 6 in the Journal of the American Geriatrics Society. In a prospective cohort study, researchers followed 1,517 adults without dementia for 10 years. Self-reported daily sleep durations were grouped into five categories. The association between daily sleep duration and risk of dementia and death was determined using Cox proportional hazards models. During follow-up, 294 participants developed dementia, and 282 died. Age- and sex-adjusted incidence rates of dementia and all-cause mortality were significantly greater in subjects who slept less than 5.0 hours/day or 10.0 or more hours/day than in people who slept from 5.0 to 6.9 hours/day.

Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018 Jun 6 [Epub ahead of print].

Rivaroxaban Not Superior to Aspirin for Stroke Prevention

Rivaroxaban is not superior to aspirin in the prevention of recurrent stroke, according to a study published June 7 in the New England Journal of Medicine. Researchers compared the efficacy and safety of rivaroxaban at a daily dose of 15 mg with aspirin at a daily dose of 100 mg for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism. The primary outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis. At 459 sites, 3,609 patients were randomly assigned to receive rivaroxaban, and 3,604 were randomized to aspirin. Recurrent ischemic stroke occurred in 172 patients in the rivaroxaban group and in 160 in the aspirin group.

Hart RG, Sharma M, Mundl H, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201.

Disintegrating Brain Lesions May Indicate Worsening MS

Atrophied lesion volume may indicate increasing disability in patients with multiple sclerosis (MS), according to a study published online ahead of print June 1 in the Journal of Neuroimaging. A total of 192 patients with clinically isolated syndrome or MS received 3T MRI at baseline and at five years. Investigators quantified lesions at baseline and calculated new and enlarging lesion volumes during the study interval. Atrophied lesion volume was calculated by combining baseline lesion masks with follow-up SIENAX-derived CSF partial volume maps. The researchers evaluated correlations between these measures and disability, as measured by the Expanded Disability Status Scale (EDSS). Atrophied lesion volume was different between MS subtypes and exceeded new lesion volume accumulation in progressive MS. Atrophied lesion volume was the only significant correlate of EDSS change.

Dwyer MG, Bergsland N, Ramasamy DP, et al. Atrophied brain lesion volume: a new imaging biomarker in multiple sclerosis. J Neuroimaging. 2018 Jun 1 [Epub ahead of print].

Do Migraineurs Seek Behavioral Treatment After a Referral?

A significant number of migraineurs are not using effective behavioral treatments for migraine, according to a study published online ahead of print June 5 in Pain Medicine. In a prospective cohort study, researchers tracked 234 patients with migraine who presented to an academic headache center and referred 69 of them for behavioral treatment with an appropriately trained therapist. Fifty-three of the referred patients completed a follow-up interview within three months of their initial appointment and were included in the analysis. Of the patients referred for behavioral treatment, 30 made an appointment. Investigators found no differences between people who started behavioral therapy and people who did not. Study authors did find that people who had previously seen a psychologist for migraine were more likely to initiate therapy.

Minen MT, Azarchi S, Sobolev R, et al. Factors related to migraine patients’ decisions to initiate behavioral migraine treatment following a headache specialist’s recommendation: a prospective observational study. Pain Med. 2018 Jun 5 [Epub ahead of print].

TIA Associated With Increased Five-Year Risk of Stroke

People with transient ischemic attack (TIA) are at risk for a cardiovascular event in the following five years, according to a study published June 7 in the New England Journal of Medicine. Researchers evaluated patients who had had a TIA within seven days before enrollment in a registry of TIA clinics. Of 61 sites, 42 had follow-up data on more than 50% of their enrolled patients at five years. The study’s primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes, with an emphasis on events that occurred in the second through fifth years. At five years, stroke had occurred in 345 of the 3,847 patients included in the follow-up study, and 149 of them had a stroke during the second through fifth years of follow-up.

Amarenco P, Lavallée PC, Monteiro Tavares L, et al. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378(23):2182-2190.

Follow-Up Care for TBI Is Not Delivered Adequately

Follow-up care for patients with traumatic brain injury (TBI) is not delivered optimally, according to a study published May 25 in JAMA Network Open. In a cohort study, researchers surveyed 831 participants in the Transforming Research and Clinical Knowledge in TBI initiative about their care after hospital discharge. Follow-up care was defined as providing TBI-related educational materials at discharge, calling patients within two weeks after release, seeing a healthcare provider within two weeks, and seeing a healthcare provider within three months. Approximately 42% of participants reported receiving TBI-related educational material at discharge, and 44% reported seeing a physician or other medical practitioner within three months after injury. Of patients with a positive finding on CT, 39% had not seen a medical practitioner at three months after injury.

Seabury SA, Gaudette E, Goldman DP, et al. Assessment of follow-up care after emergency department presentation for mild traumatic brain injury and concussion: results from the TRACK-TBI study. JAMA Network Open. 2018;1(1):e180210.

Researchers Examine Mortality Rate of Pediatric Stroke

In-hospital mortality occurs in 2.6% of children with arterial ischemic stroke, according to a study published in the May issue of Pediatrics. The retrospective study included 915 infants younger than 1 month and 2,273 children age 1 month to 18 years with stroke at 87 hospitals in 24 countries. Death during hospitalization and cause of death were ascertained from medical records. A total of 14 neonates and 70 children died during hospitalization. Of 48 cases with reported causes of death, 31 were stroke-related. Remaining deaths were attributed to medical disease. In multivariable analysis, congenital heart disease, posterior plus anterior circulation stroke, and stroke presentation without seizures were associated with in-hospital mortality for neonates. Hispanic ethnicity, congenital heart disease, and posterior plus anterior circulation stroke were associated with in-hospital mortality for children.

Beslow LA, Dowling MM, Hassanein SMA, et al. Mortality after pediatric arterial ischemic stroke. Pediatrics. 2018;141(5).

FDA Approves zEEG Dry Electrode Headset

The FDA has approved the zEEG dry electrode EEG headset for clinical use. The zEEG headset is backed by a cloud platform that allows users to upload data instantly, provides tools for analysis, and enables remote interpretation by neurologists. A clinical study found that the zEEG headset provided EEG signal quality that was comparable to that of an approved, traditional EEG system. In two study cohorts, a total of 30 patients were studied for time periods of as long as two hours, and the zEEG device performed at least as well as the reference device, based on predefined acceptance criteria. Study results will be published in the coming months. Zeto, headquartered in Santa Clara, California, markets the device.

South Asian Americans Have High Cardiovascular Mortality

South Asians living in the United States have higher mortality from heart conditions caused by atherosclerosis, such as heart attack and stroke, according to a study published online ahead of print May 24 in Circulation. Investigators reviewed the literature relevant to South Asian populations’ demographics and risk factors, health behaviors, and interventions, including physical activity, diet, medications, and community strategies. South Asians have higher proportional mortality rates from atherosclerotic cardiovascular disease, compared with other Asian groups, largely because of the lower risk observed in East Asian populations. A majority of the risk in South Asians can be explained by the increased prevalence of known risk factors, especially factors related to insulin resistance. The authors found no unique risk factors in this population.

Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018 May 24 [Epub ahead of print].

How Much Exercise Improves Cognition in Older Adults?

Exercising for at least 52 hours over six months is associated with improved cognitive performance in older adults with and without cognitive impairment, according to a study published online ahead of print May 30 in Neurology. Researchers reviewed data for 98 randomized, controlled exercise trials including 11,061 participants with an average age of 73. About 59% of the participants were healthy adults, 26% had mild cognitive impairment, and 15% had dementia. Researchers collected data on exercise session length, intensity, weekly frequency, and amount of exercise over time. Aerobic exercise was the most common form of exercise. In healthy people and people with cognitive impairment, longer term exposure to exercise, at least 52 hours conducted over an average of about six months, improved the brain’s processing speed.

Gomes-Osman J, Cabral DF, Morris TP, et al. Exercise for cognitive brain health in aging. Neurology. 2018 May 30 [Epub ahead of print].

Blood Biomarkers Detect Subconcussive Head Trauma

Blood biomarkers can detect the neurologic injury associated with repetitive subconcussive head trauma, according to a study published online ahead of print May 29 in the Journal of Neurosurgery. A total of 35 National Collegiate Athletic Association football players underwent blood sampling throughout the 2016 football season. Samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light. Athletes were categorized as starters or nonstarters, and the investigators assessed between-group differences and time-course differences. In nonstarters, plasma concentrations of tau decreased over the season. Starters had lower plasma concentrations of tau. Plasma concentrations of tau could not be used to distinguish between starters and nonstarters. Serum concentrations of neurofilament light increased as head impacts increased, specifically in starters. Serum neurofilament light distinguished starters from nonstarters.

Oliver JM, Anzalone AJ, Stone JD, et al. Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season. J Neurosurg. 2018 May 29 [Epub ahead of print].

Model Estimates Risk of Alzheimer’s Disease Dementia

Most people with preclinical Alzheimer’s disease will not develop dementia during their lifetimes, according to a study published online ahead of print May 7 in Alzheimer’s & Dementia. Researchers used a multistate model for Alzheimer’s disease along with US death rates to estimate lifetime and 10-year risks of Alzheimer’s disease dementia. Lifetime risks of Alzheimer’s disease dementia vary by age, gender, and preclinical or clinical disease state. A 70-year-old male with amyloid but no signs of neurodegeneration and no memory loss has a lifetime risk of 19.9%. The lifetime risks for a female with amyloidosis are 8.4% at age 90 and 29.3% at age 65. People younger than 85 with mild cognitive impairment, amyloidosis, and neurodegeneration have lifetime risks of Alzheimer’s disease dementia greater than 50%.

Brookmeyer R, Abdalla N. Estimation of lifetime risks of Alzheimer’s disease dementia using biomarkers for preclinical disease. Alzheimers Dement. 2018 May 7 [Epub ahead of print].

Depression Is Associated With Brain and Memory Outcomes

In a sample of mostly Caribbean Hispanic, stroke-free older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts, according to a study published online ahead of print May 9 in Neurology. Researchers analyzed data from the Northern Manhattan Study. A total of 1,111 participants underwent baseline evaluations of depressive symptoms, MRI markers, and cognitive function. At baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographics, vascular risk factors, behavioral factors, and antidepressant medications. Furthermore, greater depressive symptoms were associated with smaller cerebral parenchymal fraction and increased odds of subclinical brain infarcts, after adjustment for sociodemographics, behavioral factors, and vascular risk factors.

Al Hazzouri AZ, Caunca MR, Nobrega JC. Greater depressive symptoms, cognition, and markers of brain aging. Neurology. 2018 May 9 [Epub ahead of print].

—Kimberly Williams

CSF Predicts Progression of MS

CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.

Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

APOE Plays a Greater Role in Women Than in Men

There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.

Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

Is Tenecteplase Better Than Alteplase Before Thrombectomy?

When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.

Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

Lifestyle Factors at Midlife Could Influence Dementia Risk

Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.

Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

Epilepsy Does Not Affect Women’s Fertility

In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Among women with epilepsy, 60.7% achieved pregnancy, compared with 60.2% among controls. Median time to pregnancy was similar between groups.

Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

Sauna Bathing Reduces Stroke Risk

Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.

Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].

—Kimberly Williams
and Glenn Williams

CSF Predicts Progression of MS

CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.

Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

APOE Plays a Greater Role in Women Than in Men

There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.

Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

Is Tenecteplase Better Than Alteplase Before Thrombectomy?

When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.

Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

Lifestyle Factors at Midlife Could Influence Dementia Risk

Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.

Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

Epilepsy Does Not Affect Women’s Fertility

In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Among women with epilepsy, 60.7% achieved pregnancy, compared with 60.2% among controls. Median time to pregnancy was similar between groups.

Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

Sauna Bathing Reduces Stroke Risk

Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.

Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].

—Kimberly Williams
and Glenn Williams

CSF Predicts Progression of MS

CSF can predict the future progression of multiple sclerosis (MS), according to a study published online ahead of print May 9 in the Journal of Neurology, Neurosurgery & Psychiatry. CSF and peripheral blood were obtained from patients with clinically isolated syndrome, relapsing-remitting MS, primary progressive MS, or other inflammatory or noninflammatory neurologic diseases who underwent elective diagnostic lumbar puncture. Patients without MS served as controls. CSF samples were analyzed for free and immunoglobulin-associated light chains on B cells and plasmablasts. Clinical follow-up duration was five years. There was an increased median CSF κ:λ free light chain in all groups except controls. This ratio predicted Expanded Disability Status Scale (EDSS) score progression at five years. Median EDSS score was lower among patients with high CSF κ:λ free light chain.

Rathbone E, Durant L, Kinsella J, et al. Cerebrospinal fluid immunoglobulin light chain ratios predict disease progression in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2018 May 9 [Epub ahead of print].

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

APOE Plays a Greater Role in Women Than in Men

There is a stronger association between APOE-ε4 and CSF tau levels among women than among men, according to a study published online ahead of print May 7 in JAMA Neurology. Investigators selected data from 10 longitudinal cohort studies of normal aging and Alzheimer’s disease. Biomarker analyses included CSF levels of β-amyloid 42, total tau, and phosphorylated tau. Of the 1,798 patients in the CSF biomarker cohort, 862 were women, 226 had Alzheimer’s disease, 1,690 were white, and the mean age was 70. Of the 5,109 patients in the autopsy cohort, 2,813 were women, 4,953 were white, and the mean age was 84. After correcting for multiple comparisons using the Bonferroni procedure, investigators observed a statistically significant interaction between APOE-ε4 and sex on CSF total tau and phosphorylated tau.

Hohman TJ, Dumitrescu L, Barnes LL. Sex-specific association of apolipoprotein E with cerebrospinal fluid levels of tau. JAMA Neurol. 2018 May 7 [Epub ahead of print].

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

Is Tenecteplase Better Than Alteplase Before Thrombectomy?

When administered before thrombectomy, tenecteplase is associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset, according to a study published April 26 in the New England Journal of Medicine. Researchers randomly assigned patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy to receive tenecteplase or alteplase within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the initial angiographic assessment. Of 202 patients enrolled, 101 were assigned to receive tenecteplase. The primary outcome occurred in 22% of the tenecteplase group and 10% of the alteplase group.

Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

Lifestyle Factors at Midlife Could Influence Dementia Risk

Demographic and lifestyle factors assessed in midlife could potentially modify the risk of dementia in late adulthood, according to a study published in the March issue of Journal of Alzheimer’s Disease. Researchers used data collected from 1979 until 1983 in the Framingham Heart Study Offspring cohort to examine associations between lifestyle factors in midlife and late-life dementia. They examined the data with decision tree classifier and random forests analysis. Investigators then evaluated model performance by computing area under receiver operating characteristic (ROC) curve. Age was strongly associated with dementia. The analysis also identified widowed status, lower BMI, and less sleep at midlife as risk factors for dementia. The areas under the ROC curves were 0.79 for the decision tree and 0.89 for the random forest model.

Li J, Ogrodnik M, Kolachalama VB, et al. Assessment of the mid-life demographic and lifestyle risk factors of dementia using data from the Framingham Heart Study Offspring Cohort. J Alzheimers Dis. 2018;63(3):1119-1127.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

Epilepsy Does Not Affect Women’s Fertility

In women without a history of infertility or related disorders, the likelihood of conceiving and having a live birth is no different between individuals with or without epilepsy, according to a study published online ahead of print April 30 in JAMA Neurology. Researchers examined data from the Women With Epilepsy: Pregnancy Outcomes and Deliveries study to compare fertility rates between women with and without epilepsy. The primary outcome was the proportion of women who achieved pregnancy within 12 months after enrollment. Of the 197 participants, 142 were white. Mean age was 31.9 among the 89 women with epilepsy and 31.1 among the 108 control women. Among women with epilepsy, 60.7% achieved pregnancy, compared with 60.2% among controls. Median time to pregnancy was similar between groups.

Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy. JAMA Neurol. 2018 Apr 30 [Epub ahead of print].

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

Sauna Bathing Reduces Stroke Risk

Frequent sauna bathing is associated with a reduced risk of stroke, according to a study published online ahead of print May 2 in Neurology. Researchers assessed baseline habits of sauna bathing in 1,628 adults between ages 53 and 74 (mean age, 62.7) without a known history of stroke. The following sauna bathing frequency groups were defined: once per week, two to three times per week, and four to seven times per week. During a median follow-up of 14.9 years, 155 incident stroke events were recorded. Compared with people who took one sauna bath per week, the risk of stroke was 14% lower among people with two to three sessions and 61% lower among people with four to seven sessions. Controlling for stroke risk factors did not alter the association.

Kunutsor SK, Khan H, Zaccardi F, et al. Sauna bathing reduces the risk of stroke in Finnish men and women: a prospective cohort study. Neurology. 2018 May 2 [Epub ahead of print].

—Kimberly Williams
and Glenn Williams

Starting School Later Improves Sleep Time

Delaying school start time can provide sustained benefits for sleep duration, daytime alertness, and mental well-being, according to a study published online ahead of print April 10 in Sleep. The study included 375 girls in grades 7 to 10 from a secondary school for girls. The school delayed its start time from 7:30 to 8:15 in the morning. Self-reports of sleep timing, sleepiness, and well-being were obtained at baseline before the delay and at approximately one and nine months after the delay. After one month, bedtimes on school nights were delayed by nine minutes, while rise times were delayed by 31.6 minutes, resulting in an increase in time in bed of 23.2 minutes. After nine months, the increase in time in bed was sustained, and total sleep time increased by 10 minutes.

Lo JC, Lee SM, Lee XK, et al. Sustained benefits of delaying school start time on adolescent sleep and well-being. Sleep. 2018 Apr 10 [Epub ahead of print].

Stroke Affects Social, Cognitive, and Psychologic Outcomes

Patients with ischemic stroke report symptoms in multiple domains that increase to variable degrees at higher levels of disability, according to a study published online ahead of print March 28 in Neurology. The observational cohort included 1,195 patients who completed Quality of Life in Neurological Disorders or the Patient-Reported Outcomes Measurement Information System scales as part of routine care. Participants were questioned about their physical function, satisfaction with social roles, fatigue, anxiety, depression, pain interference, and sleep disturbance. Researchers also measured participants’ level of disability. Among people with stroke, scores were considerably worse than those in the general population in every area except sleep and depression. About 58% of people with stroke had scores related to satisfaction with social roles that were meaningfully worse than those of the general population.

Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018 Mar 28 [Epub ahead of print].

ALS Genetic Variant Also a Risk Factor for Frontotemporal Dementia

One of the newly identified genetic variants associated with amyotrophic lateral sclerosis (ALS) also is a risk factor for frontotemporal dementia (FTD), according to a study published online ahead of print April 9 in JAMA Neurology. Researchers pooled data from previous genome-wide association studies that included genetic data from 124,876 participants. The studies included healthy controls and participants with ALS, Alzheimer’s disease, Parkinson’s disease, FTD, corticobasal degeneration, and progressive supranuclear palsy. Investigators found that a variation in a region of DNA containing the gene for tau protein was associated with elevated risk for ALS. In addition, study authors found significant genetic overlap between ALS and FTD at known ALS loci rs13302855, rs3849942, and rs4239633. They also found a genetic variation at rs538622 that is associated with ALS and FTD and affects BNIP1 production in the brain.

Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].

Intervention Promotes Stroke Preparedness

Hip-Hop Stroke (HHS) is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities, according to a study published in the April issue of Stroke. HHS is a three-hour, culturally tailored, theory-based, multimedia stroke literacy intervention that empowers schoolchildren to share stroke information with parents. Researchers recruited 3,070 fourth- through sixth-graders and 1,144 parents from 22 schools into a cluster-randomized trial. Schools were randomized to the HHS intervention or attentional control (ie, nutrition classes). Main outcome measures were stroke knowledge and preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% of controls and 2% of the intervention group demonstrated optimal stroke preparedness at baseline, increasing to 57% immediately after the program in the intervention group.

Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving community stroke preparedness in the HHS (Hip-Hop Stroke) randomized clinical trial. Stroke. 2018;49(4):972-979.

Risk of Unnatural Death Is Increased in Epilepsy

People with epilepsy are at increased risk of mortality from suicide and accidents, according to a study published online ahead of print April 9 in JAMA Neurology. Researchers examined the Clinical Practice Research Datalink (CPRD) and the Secure Anonymized Information Linkage (SAIL) databank, which are linked to hospitalization and mortality records. They matched people with epilepsy on age, sex, and general practice with as many as 20 controls. In all, 44,678 people in the CPRD and 14,051 individuals in the SAIL databank were identified in the prevalent epilepsy cohorts. Furthermore, 891,429 participants from the CPRD and 279,365 people from the SAIL databank were identified as controls. People with epilepsy were significantly more likely to die of an unnatural cause, unintentional injury, poisoning, or suicide, compared with controls.

Gorton HC, Webb RT, Carr MJ, et al. Risk of unnatural mortality in people with epilepsy. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].

Method to Assess Consciousness May Improve Care

The Glasgow Coma Scale-Pupil (GCS-P) score provides a way to rapidly assess levels of consciousness in people with head injuries and could improve patient care, according to a study published online ahead of print April 10 in the Journal of Neurosurgery. Investigators obtained patient-level information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality by reviewing data from the Corticosteroid Randomization After Significant Head Injury study and the International Mission for Prognosis and Clinical Trials database. GCS score and pupil response were independently related to patient outcome. Adding information about pupil response to the GCS score improved the information. The performance of the GCS-P was similar to that of methods for evaluating traumatic brain damage.

Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Apr 10 [Epub ahead of print].

Biomarkers of Dementia Risk Identified

Researchers have identified novel biomarkers of risk for future dementia, according to a study published online ahead of print February 28 in Alzheimer’s & Dementia. Investigators analyzed metabolites in blood samples drawn from 22,623 people enrolled in eight prospective cohorts. Over 246,698 person-years, they detected 995 cases of incident dementia and 745 cases of incident Alzheimer’s disease. Isoleucine, leucine, valine, creatinine, and two VLDL-specific lipoprotein lipid subclasses were associated with lower dementia risk. One HDL and one VLDL lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids also were associated with decreased Alzheimer’s disease risk, and the concentration of cholesterol esters relative to total lipids in large HDL was associated with increased Alzheimer’s disease risk.

Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimers Dement. 2018 Feb 28 [Epub ahead of print].

Smartphone App Helps Doctors Track Parkinson’s Disease Symptoms

A smartphone app generates a score that reflects symptom severity in patients with Parkinson’s disease, according to a study published online ahead of print March 26 in JAMA Neurology. This observational study assessed people with Parkinson’s disease who remotely completed voice, finger tapping, gait, balance, and reaction time tasks on the app. Researchers generated a mobile Parkinson’s disease score (mPDS) of 0 to 100 that objectively weighed features derived from each smartphone activity. The mPDS was based on 6,148 smartphone activity assessments from 129 individuals. Gait features contributed most to the total mPDS (33.4%). The mPDS detected symptom fluctuations with a mean intraday change of 13.9 points. The mPDS improved by a mean of 16.3 points in response to dopaminergic therapy.

Zhan A, Mohan S, Tarolli C, et al. Using smartphones and machine learning to quantify Parkinson disease severity: the mobile Parkinson disease score. JAMA Neurol. 2018 Mar 26 [Epub ahead of print].

Age at Natural Menopause Linked to Memory

Entering menopause at a later age may benefit memory in women years later, according to a study published online ahead of print April 11 in Neurology. Researchers used data from 1,315 participants in the Medical Research Council National Survey of Health and Development with known age at period cessation and as many as four assessments of verbal memory and processing speed at ages 43, 53, between 60 and 64, and 69. Investigators fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, BMI, smoking, occupational class, education, and childhood cognitive ability. Verbal memory increased with later age at natural menopause and with later age at surgical menopause. The association between age at natural menopause and verbal memory remained significant after data adjustment.

Kuh D, Cooper R, Moore A, et al. Age at menopause and lifetime cognition: findings from a British birth cohort study. Neurology. 2018 Apr 11 [Epub ahead of print].

Single-Pulse TMS Decreases Migraine Frequency

Single-pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a study published online ahead of print March 4 in Cephalalgia. Researchers examined data from the eNeura SpringTMS Post-Market Observational US Study of Migraine, a multicenter, prospective, open-label, observational study. A total of 263 patients with migraine completed a one-month baseline headache diary, followed by three months of preventive (four pulses bid) and acute treatment (three pulses repeated as many as three times per attack). In all, 220 participants were eligible based on their number of headache days. The device was assigned to 217 subjects, and 132 were included in the intention-to-treat full-analysis set. Treatment reduced mean monthly headache days by 2.75. The most common adverse events were tingling, lightheadedness, and tinnitus.

Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 Mar 4 [Epub ahead of print].

Short Sleep Increases Risk of Obesity in the Young

Short sleep duration is a risk factor for obesity in infants, children, and adolescents, according to a study published online ahead of print February 1 in Sleep. Researchers reviewed the results of 42 population studies that included 75,499 infants, children, and adolescents ages 0 to 18. Sleep duration was assessed through methods such as questionnaires and wearable technology. The investigators classified participants as short sleepers or regular sleepers. Short sleepers were defined as having less sleep than the reference category for their age. Participants were followed up for a median of three years, and changes in BMI and incidence of overweight status and obesity were recorded. At all ages, short sleepers gained more weight and were 58% more likely to become overweight or obese.

Miller MA, Kruisbrink M, Wallace J, et al. Sleep duration and incidence of obesity in infants, children and adolescents: a systematic review and meta-analysis of prospective studies. Sleep. 2018 Feb 1 [Epub ahead of print].

—Kimberly Williams

Starting School Later Improves Sleep Time

Delaying school start time can provide sustained benefits for sleep duration, daytime alertness, and mental well-being, according to a study published online ahead of print April 10 in Sleep. The study included 375 girls in grades 7 to 10 from a secondary school for girls. The school delayed its start time from 7:30 to 8:15 in the morning. Self-reports of sleep timing, sleepiness, and well-being were obtained at baseline before the delay and at approximately one and nine months after the delay. After one month, bedtimes on school nights were delayed by nine minutes, while rise times were delayed by 31.6 minutes, resulting in an increase in time in bed of 23.2 minutes. After nine months, the increase in time in bed was sustained, and total sleep time increased by 10 minutes.

Lo JC, Lee SM, Lee XK, et al. Sustained benefits of delaying school start time on adolescent sleep and well-being. Sleep. 2018 Apr 10 [Epub ahead of print].

Stroke Affects Social, Cognitive, and Psychologic Outcomes

Patients with ischemic stroke report symptoms in multiple domains that increase to variable degrees at higher levels of disability, according to a study published online ahead of print March 28 in Neurology. The observational cohort included 1,195 patients who completed Quality of Life in Neurological Disorders or the Patient-Reported Outcomes Measurement Information System scales as part of routine care. Participants were questioned about their physical function, satisfaction with social roles, fatigue, anxiety, depression, pain interference, and sleep disturbance. Researchers also measured participants’ level of disability. Among people with stroke, scores were considerably worse than those in the general population in every area except sleep and depression. About 58% of people with stroke had scores related to satisfaction with social roles that were meaningfully worse than those of the general population.

Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018 Mar 28 [Epub ahead of print].

ALS Genetic Variant Also a Risk Factor for Frontotemporal Dementia

One of the newly identified genetic variants associated with amyotrophic lateral sclerosis (ALS) also is a risk factor for frontotemporal dementia (FTD), according to a study published online ahead of print April 9 in JAMA Neurology. Researchers pooled data from previous genome-wide association studies that included genetic data from 124,876 participants. The studies included healthy controls and participants with ALS, Alzheimer’s disease, Parkinson’s disease, FTD, corticobasal degeneration, and progressive supranuclear palsy. Investigators found that a variation in a region of DNA containing the gene for tau protein was associated with elevated risk for ALS. In addition, study authors found significant genetic overlap between ALS and FTD at known ALS loci rs13302855, rs3849942, and rs4239633. They also found a genetic variation at rs538622 that is associated with ALS and FTD and affects BNIP1 production in the brain.

Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].

Intervention Promotes Stroke Preparedness

Hip-Hop Stroke (HHS) is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities, according to a study published in the April issue of Stroke. HHS is a three-hour, culturally tailored, theory-based, multimedia stroke literacy intervention that empowers schoolchildren to share stroke information with parents. Researchers recruited 3,070 fourth- through sixth-graders and 1,144 parents from 22 schools into a cluster-randomized trial. Schools were randomized to the HHS intervention or attentional control (ie, nutrition classes). Main outcome measures were stroke knowledge and preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% of controls and 2% of the intervention group demonstrated optimal stroke preparedness at baseline, increasing to 57% immediately after the program in the intervention group.

Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving community stroke preparedness in the HHS (Hip-Hop Stroke) randomized clinical trial. Stroke. 2018;49(4):972-979.

Risk of Unnatural Death Is Increased in Epilepsy

People with epilepsy are at increased risk of mortality from suicide and accidents, according to a study published online ahead of print April 9 in JAMA Neurology. Researchers examined the Clinical Practice Research Datalink (CPRD) and the Secure Anonymized Information Linkage (SAIL) databank, which are linked to hospitalization and mortality records. They matched people with epilepsy on age, sex, and general practice with as many as 20 controls. In all, 44,678 people in the CPRD and 14,051 individuals in the SAIL databank were identified in the prevalent epilepsy cohorts. Furthermore, 891,429 participants from the CPRD and 279,365 people from the SAIL databank were identified as controls. People with epilepsy were significantly more likely to die of an unnatural cause, unintentional injury, poisoning, or suicide, compared with controls.

Gorton HC, Webb RT, Carr MJ, et al. Risk of unnatural mortality in people with epilepsy. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].

Method to Assess Consciousness May Improve Care

The Glasgow Coma Scale-Pupil (GCS-P) score provides a way to rapidly assess levels of consciousness in people with head injuries and could improve patient care, according to a study published online ahead of print April 10 in the Journal of Neurosurgery. Investigators obtained patient-level information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality by reviewing data from the Corticosteroid Randomization After Significant Head Injury study and the International Mission for Prognosis and Clinical Trials database. GCS score and pupil response were independently related to patient outcome. Adding information about pupil response to the GCS score improved the information. The performance of the GCS-P was similar to that of methods for evaluating traumatic brain damage.

Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Apr 10 [Epub ahead of print].

Biomarkers of Dementia Risk Identified

Researchers have identified novel biomarkers of risk for future dementia, according to a study published online ahead of print February 28 in Alzheimer’s & Dementia. Investigators analyzed metabolites in blood samples drawn from 22,623 people enrolled in eight prospective cohorts. Over 246,698 person-years, they detected 995 cases of incident dementia and 745 cases of incident Alzheimer’s disease. Isoleucine, leucine, valine, creatinine, and two VLDL-specific lipoprotein lipid subclasses were associated with lower dementia risk. One HDL and one VLDL lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids also were associated with decreased Alzheimer’s disease risk, and the concentration of cholesterol esters relative to total lipids in large HDL was associated with increased Alzheimer’s disease risk.

Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimers Dement. 2018 Feb 28 [Epub ahead of print].

Smartphone App Helps Doctors Track Parkinson’s Disease Symptoms

A smartphone app generates a score that reflects symptom severity in patients with Parkinson’s disease, according to a study published online ahead of print March 26 in JAMA Neurology. This observational study assessed people with Parkinson’s disease who remotely completed voice, finger tapping, gait, balance, and reaction time tasks on the app. Researchers generated a mobile Parkinson’s disease score (mPDS) of 0 to 100 that objectively weighed features derived from each smartphone activity. The mPDS was based on 6,148 smartphone activity assessments from 129 individuals. Gait features contributed most to the total mPDS (33.4%). The mPDS detected symptom fluctuations with a mean intraday change of 13.9 points. The mPDS improved by a mean of 16.3 points in response to dopaminergic therapy.

Zhan A, Mohan S, Tarolli C, et al. Using smartphones and machine learning to quantify Parkinson disease severity: the mobile Parkinson disease score. JAMA Neurol. 2018 Mar 26 [Epub ahead of print].

Age at Natural Menopause Linked to Memory

Entering menopause at a later age may benefit memory in women years later, according to a study published online ahead of print April 11 in Neurology. Researchers used data from 1,315 participants in the Medical Research Council National Survey of Health and Development with known age at period cessation and as many as four assessments of verbal memory and processing speed at ages 43, 53, between 60 and 64, and 69. Investigators fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, BMI, smoking, occupational class, education, and childhood cognitive ability. Verbal memory increased with later age at natural menopause and with later age at surgical menopause. The association between age at natural menopause and verbal memory remained significant after data adjustment.

Kuh D, Cooper R, Moore A, et al. Age at menopause and lifetime cognition: findings from a British birth cohort study. Neurology. 2018 Apr 11 [Epub ahead of print].

Single-Pulse TMS Decreases Migraine Frequency

Single-pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a study published online ahead of print March 4 in Cephalalgia. Researchers examined data from the eNeura SpringTMS Post-Market Observational US Study of Migraine, a multicenter, prospective, open-label, observational study. A total of 263 patients with migraine completed a one-month baseline headache diary, followed by three months of preventive (four pulses bid) and acute treatment (three pulses repeated as many as three times per attack). In all, 220 participants were eligible based on their number of headache days. The device was assigned to 217 subjects, and 132 were included in the intention-to-treat full-analysis set. Treatment reduced mean monthly headache days by 2.75. The most common adverse events were tingling, lightheadedness, and tinnitus.

Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 Mar 4 [Epub ahead of print].

Short Sleep Increases Risk of Obesity in the Young

Short sleep duration is a risk factor for obesity in infants, children, and adolescents, according to a study published online ahead of print February 1 in Sleep. Researchers reviewed the results of 42 population studies that included 75,499 infants, children, and adolescents ages 0 to 18. Sleep duration was assessed through methods such as questionnaires and wearable technology. The investigators classified participants as short sleepers or regular sleepers. Short sleepers were defined as having less sleep than the reference category for their age. Participants were followed up for a median of three years, and changes in BMI and incidence of overweight status and obesity were recorded. At all ages, short sleepers gained more weight and were 58% more likely to become overweight or obese.

Miller MA, Kruisbrink M, Wallace J, et al. Sleep duration and incidence of obesity in infants, children and adolescents: a systematic review and meta-analysis of prospective studies. Sleep. 2018 Feb 1 [Epub ahead of print].

—Kimberly Williams

Starting School Later Improves Sleep Time

Delaying school start time can provide sustained benefits for sleep duration, daytime alertness, and mental well-being, according to a study published online ahead of print April 10 in Sleep. The study included 375 girls in grades 7 to 10 from a secondary school for girls. The school delayed its start time from 7:30 to 8:15 in the morning. Self-reports of sleep timing, sleepiness, and well-being were obtained at baseline before the delay and at approximately one and nine months after the delay. After one month, bedtimes on school nights were delayed by nine minutes, while rise times were delayed by 31.6 minutes, resulting in an increase in time in bed of 23.2 minutes. After nine months, the increase in time in bed was sustained, and total sleep time increased by 10 minutes.

Lo JC, Lee SM, Lee XK, et al. Sustained benefits of delaying school start time on adolescent sleep and well-being. Sleep. 2018 Apr 10 [Epub ahead of print].

Stroke Affects Social, Cognitive, and Psychologic Outcomes

Patients with ischemic stroke report symptoms in multiple domains that increase to variable degrees at higher levels of disability, according to a study published online ahead of print March 28 in Neurology. The observational cohort included 1,195 patients who completed Quality of Life in Neurological Disorders or the Patient-Reported Outcomes Measurement Information System scales as part of routine care. Participants were questioned about their physical function, satisfaction with social roles, fatigue, anxiety, depression, pain interference, and sleep disturbance. Researchers also measured participants’ level of disability. Among people with stroke, scores were considerably worse than those in the general population in every area except sleep and depression. About 58% of people with stroke had scores related to satisfaction with social roles that were meaningfully worse than those of the general population.

Katzan IL, Thompson NR, Uchino K, Lapin B. The most affected health domains after ischemic stroke. Neurology. 2018 Mar 28 [Epub ahead of print].

ALS Genetic Variant Also a Risk Factor for Frontotemporal Dementia

One of the newly identified genetic variants associated with amyotrophic lateral sclerosis (ALS) also is a risk factor for frontotemporal dementia (FTD), according to a study published online ahead of print April 9 in JAMA Neurology. Researchers pooled data from previous genome-wide association studies that included genetic data from 124,876 participants. The studies included healthy controls and participants with ALS, Alzheimer’s disease, Parkinson’s disease, FTD, corticobasal degeneration, and progressive supranuclear palsy. Investigators found that a variation in a region of DNA containing the gene for tau protein was associated with elevated risk for ALS. In addition, study authors found significant genetic overlap between ALS and FTD at known ALS loci rs13302855, rs3849942, and rs4239633. They also found a genetic variation at rs538622 that is associated with ALS and FTD and affects BNIP1 production in the brain.

Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].

Intervention Promotes Stroke Preparedness

Hip-Hop Stroke (HHS) is an effective, intergenerational model for increasing stroke preparedness among economically disadvantaged minorities, according to a study published in the April issue of Stroke. HHS is a three-hour, culturally tailored, theory-based, multimedia stroke literacy intervention that empowers schoolchildren to share stroke information with parents. Researchers recruited 3,070 fourth- through sixth-graders and 1,144 parents from 22 schools into a cluster-randomized trial. Schools were randomized to the HHS intervention or attentional control (ie, nutrition classes). Main outcome measures were stroke knowledge and preparedness of children and parents using validated surrogates. Among children, it was estimated that 1% of controls and 2% of the intervention group demonstrated optimal stroke preparedness at baseline, increasing to 57% immediately after the program in the intervention group.

Williams O, Leighton-Herrmann Quinn E, Teresi J, et al. Improving community stroke preparedness in the HHS (Hip-Hop Stroke) randomized clinical trial. Stroke. 2018;49(4):972-979.

Risk of Unnatural Death Is Increased in Epilepsy

People with epilepsy are at increased risk of mortality from suicide and accidents, according to a study published online ahead of print April 9 in JAMA Neurology. Researchers examined the Clinical Practice Research Datalink (CPRD) and the Secure Anonymized Information Linkage (SAIL) databank, which are linked to hospitalization and mortality records. They matched people with epilepsy on age, sex, and general practice with as many as 20 controls. In all, 44,678 people in the CPRD and 14,051 individuals in the SAIL databank were identified in the prevalent epilepsy cohorts. Furthermore, 891,429 participants from the CPRD and 279,365 people from the SAIL databank were identified as controls. People with epilepsy were significantly more likely to die of an unnatural cause, unintentional injury, poisoning, or suicide, compared with controls.

Gorton HC, Webb RT, Carr MJ, et al. Risk of unnatural mortality in people with epilepsy. JAMA Neurol. 2018 Apr 9 [Epub ahead of print].

Method to Assess Consciousness May Improve Care

The Glasgow Coma Scale-Pupil (GCS-P) score provides a way to rapidly assess levels of consciousness in people with head injuries and could improve patient care, according to a study published online ahead of print April 10 in the Journal of Neurosurgery. Investigators obtained patient-level information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality by reviewing data from the Corticosteroid Randomization After Significant Head Injury study and the International Mission for Prognosis and Clinical Trials database. GCS score and pupil response were independently related to patient outcome. Adding information about pupil response to the GCS score improved the information. The performance of the GCS-P was similar to that of methods for evaluating traumatic brain damage.

Brennan PM, Murray GD, Teasdale GM. Simplifying the use of prognostic information in traumatic brain injury. Part 1: The GCS-Pupils score: an extended index of clinical severity. J Neurosurg. 2018 Apr 10 [Epub ahead of print].

Biomarkers of Dementia Risk Identified

Researchers have identified novel biomarkers of risk for future dementia, according to a study published online ahead of print February 28 in Alzheimer’s & Dementia. Investigators analyzed metabolites in blood samples drawn from 22,623 people enrolled in eight prospective cohorts. Over 246,698 person-years, they detected 995 cases of incident dementia and 745 cases of incident Alzheimer’s disease. Isoleucine, leucine, valine, creatinine, and two VLDL-specific lipoprotein lipid subclasses were associated with lower dementia risk. One HDL and one VLDL lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids also were associated with decreased Alzheimer’s disease risk, and the concentration of cholesterol esters relative to total lipids in large HDL was associated with increased Alzheimer’s disease risk.

Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer’s disease: a prospective study in eight cohorts. Alzheimers Dement. 2018 Feb 28 [Epub ahead of print].

Smartphone App Helps Doctors Track Parkinson’s Disease Symptoms

A smartphone app generates a score that reflects symptom severity in patients with Parkinson’s disease, according to a study published online ahead of print March 26 in JAMA Neurology. This observational study assessed people with Parkinson’s disease who remotely completed voice, finger tapping, gait, balance, and reaction time tasks on the app. Researchers generated a mobile Parkinson’s disease score (mPDS) of 0 to 100 that objectively weighed features derived from each smartphone activity. The mPDS was based on 6,148 smartphone activity assessments from 129 individuals. Gait features contributed most to the total mPDS (33.4%). The mPDS detected symptom fluctuations with a mean intraday change of 13.9 points. The mPDS improved by a mean of 16.3 points in response to dopaminergic therapy.

Zhan A, Mohan S, Tarolli C, et al. Using smartphones and machine learning to quantify Parkinson disease severity: the mobile Parkinson disease score. JAMA Neurol. 2018 Mar 26 [Epub ahead of print].

Age at Natural Menopause Linked to Memory

Entering menopause at a later age may benefit memory in women years later, according to a study published online ahead of print April 11 in Neurology. Researchers used data from 1,315 participants in the Medical Research Council National Survey of Health and Development with known age at period cessation and as many as four assessments of verbal memory and processing speed at ages 43, 53, between 60 and 64, and 69. Investigators fitted multilevel models with linear and quadratic age terms, stratified by natural or surgical menopause, and adjusted for hormone replacement therapy, BMI, smoking, occupational class, education, and childhood cognitive ability. Verbal memory increased with later age at natural menopause and with later age at surgical menopause. The association between age at natural menopause and verbal memory remained significant after data adjustment.

Kuh D, Cooper R, Moore A, et al. Age at menopause and lifetime cognition: findings from a British birth cohort study. Neurology. 2018 Apr 11 [Epub ahead of print].

Single-Pulse TMS Decreases Migraine Frequency

Single-pulse transcranial magnetic stimulation (sTMS) may be an effective, well-tolerated treatment option for migraine prevention, according to a study published online ahead of print March 4 in Cephalalgia. Researchers examined data from the eNeura SpringTMS Post-Market Observational US Study of Migraine, a multicenter, prospective, open-label, observational study. A total of 263 patients with migraine completed a one-month baseline headache diary, followed by three months of preventive (four pulses bid) and acute treatment (three pulses repeated as many as three times per attack). In all, 220 participants were eligible based on their number of headache days. The device was assigned to 217 subjects, and 132 were included in the intention-to-treat full-analysis set. Treatment reduced mean monthly headache days by 2.75. The most common adverse events were tingling, lightheadedness, and tinnitus.

Starling AJ, Tepper SJ, Marmura MJ, et al. A multicenter, prospective, single arm, open label, observational study of sTMS for migraine prevention (ESPOUSE Study). Cephalalgia. 2018 Mar 4 [Epub ahead of print].

Short Sleep Increases Risk of Obesity in the Young

Short sleep duration is a risk factor for obesity in infants, children, and adolescents, according to a study published online ahead of print February 1 in Sleep. Researchers reviewed the results of 42 population studies that included 75,499 infants, children, and adolescents ages 0 to 18. Sleep duration was assessed through methods such as questionnaires and wearable technology. The investigators classified participants as short sleepers or regular sleepers. Short sleepers were defined as having less sleep than the reference category for their age. Participants were followed up for a median of three years, and changes in BMI and incidence of overweight status and obesity were recorded. At all ages, short sleepers gained more weight and were 58% more likely to become overweight or obese.

Miller MA, Kruisbrink M, Wallace J, et al. Sleep duration and incidence of obesity in infants, children and adolescents: a systematic review and meta-analysis of prospective studies. Sleep. 2018 Feb 1 [Epub ahead of print].

—Kimberly Williams

New Genetic Risk Factors for Stroke Determined

New genetic risk factors for stroke have been identified, thereby tripling the number of gene regions known to affect stroke risk, according to a study published online ahead of print March 12 in Nature Genetics. Researchers conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 with stroke) and discovered 22 new stroke risk loci, bringing the total to 32. In addition, the investigators found shared genetic variation with related vascular traits (eg, blood pressure, cardiac traits, and venous thromboembolism) at individual loci and using genetic risk scores and linkage-disequilibrium-score regression. Several loci had distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology. The researchers prioritized risk variants and genes through bioinformatics analyses using functional datasets.

Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018 Mar 12 [Epub ahead of print].

MS Medication Withdrawn Because of Safety Concerns

Citing concerns about safety, Biogen and AbbVie announced March 2 that they will be withdrawing daclizumab (Zinbryta) from worldwide markets. Daclizumab has known risks, so it was usually prescribed only for people with relapsing multiple sclerosis who had tried two or more other medications that had not worked well enough. Reports of inflammatory encephalitis and meningoencephalitis led the European Medicines Agency to initiate an Article 20 referral procedure. In such referrals, a medicine or class of medicines are scientifically assessed because of concerns over safety or quality. However, Biogen and AbbVie concluded that, because of the complex nature of these reports and how few patients were taking daclizumab, it would be difficult to characterize the nature of the medication’s harms and benefits, so the companies instead have decided to withdraw the medication from the market.

Many Elderly Patients With Epilepsy Receive Interacting Treatments

Many elderly patients with epilepsy receive combinations of nonepilepsy drugs (NEDs) and antiepileptic drugs (AEDs) that could interact, according to a study published February 7 in Epilepsia. Researchers retrospectively analyzed 2008–2010 Medicare claims for a random sample of beneficiaries age 67 and older. Prevalent cases had a diagnosis of epilepsy and took one or more AEDs. Incident cases had no seizure or epilepsy claim codes or AEDs in the preceding 365 days. Interacting pairs of AEDs and NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. Interacting drug pairs affected NED efficacy in 24.5% of incident cases and 39% of prevalent cases. Combinations affected AED efficacy in 20.4% of incident cases and 29.3% of prevalent cases.

Faught E, Szaflarski JP, Richman J, et al. Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk. Epilepsia. 2018;59(3):715-723.

Are Physically Fit Women at Reduced Risk for Dementia?

High cardiovascular fitness in midlife is associated with decreased risk of subsequent dementia, according to a study published online ahead of print March 14 in Neurology. Physicians examined a population-based sample of 1,462 women ages 38 to 60 in 1968. A subsample of 191 women with an average age of 50 took a maximal ergometer cycling test to measure their peak cardiovascular capacity. Over the following 44 years, participants were tested for dementia six times. By 2012, 44 of the women developed dementia. Approximately 5% of the highly fit women developed dementia, compared with 25% of moderately fit women, and 32% of the women with low fitness. The highly fit women were 88% less likely to develop dementia than the moderately fit women.

Hörder H, Johansson L, Guo X, et al. Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology. 2018 Mar 14 [Epub ahead of print].

Data on Geriatric TBI May Be Inadequate

Many older adults with traumatic brain injury (TBI) respond well to aggressive management and rehabilitation, which suggests that age and TBI severity alone are inadequate prognostic markers, according to a study published online ahead of print February 15 in the Journal of Neurotrauma. Researchers reviewed the literature on incident TBI sustained in older adulthood. They found few geriatric-specific TBI guidelines to assist with complex management decisions and concluded that TBI prognostic models do not perform optimally in this population. Major barriers in management of geriatric TBI include underrepresentation of older adults in TBI research, lack of systematic measurement of preinjury health that may predict outcome and response to treatment, and lack of geriatric-specific TBI common data elements. Investigators need to develop more age-inclusive TBI research protocols, said the authors.

Gardner RC, Dams-O’Connor K, Morrissey MR, Manley GT. Geriatric traumatic brain injury: epidemiology, outcomes, knowledge gaps, and future directions. J Neurotrauma. 2018 Feb 15 [Epub ahead of print].

TDCS Improves Gait in Parkinson’s Disease

Transcranial direct-current stimulation (TDCS) reduces freezing of gait and improves executive function and mobility, according to a study published online ahead of print February 13 in Movement Disorders. Researchers examined 20 patients with Parkinson’s disease and freezing of gait. The patients received 20 minutes of TDCS or sham treatment during three separate visits. TDCS targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously or primary motor cortex only. Participants completed the Timed Up and Go and Stroop tests before and after each stimulation session. Performance on the Timed Up and Go and Stroop tests improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after stimulation of the primary motor cortex alone or sham stimulation.

Dagan M, Herman T, Harrison R, et al. Multitarget transcranial direct current stimulation for freezing of gait in Parkinson’s disease. Mov Disord. 2018 Feb 13 [Epub ahead of print].

Patients With Major Stroke Need Realistic Planning

Doctors who care for patients with severe stroke should plan with patients and caregivers and discuss the possibility of death or survival with disability, according to a study published March 5 in the Canadian Medical Association Journal. Researchers recruited a purposive sample of people with total anterior circulation stroke at three stroke services and conducted serial, qualitative interviews with participants and their caregivers at six weeks, six months, and one year. Investigators also conducted a data-linkage study of all patients with anterior circulation stroke admitted to the three services over six months. About 57% of patients died within six months. Patients experienced immediate and persistent emotional distress and poor quality of life. Physicians should practice palliative care for these patients, but avoid using that term, said the authors.

Kendall M, Cowey E, Mead G, et al. Outcomes, experiences and palliative care in major stroke: a multicentre, mixed-method, longitudinal study. CMAJ. 2018;190(9):E238-E246.

Dengue Fever Is Associated With Increased Risk of Stroke

Dengue fever is associated with an increased risk of stroke in the first few months after diagnosis, according to a study published March 12 in Canadian Medical Association Journal. Using data from the Taiwan National Health Insurance Research Database, researchers examined 13,787 patients diagnosed with dengue fever between 2000 and 2012. The control cohort consisted of patients matched by demographic characteristics and stroke-related comorbidities who did not have dengue fever. The overall incidence rate of stroke was 5.33 per 1,000 person-years in the dengue fever cohort and 3.72 per 1,000 person-years in the control cohort. The adjusted hazard ratio of stroke was 1.16 in patients with dengue fever. The risk of stroke was 2.49 times higher in patients with dengue fever during the first two months after diagnosis, compared with controls.

Li HM, Huang YK, Su YC, Kao CH. Risk of stroke in patients with dengue fever: a population-based cohort study. CMAJ. 2018;190(10):E285-E290.

Do Survivors of Stroke Need Additional Help Taking Medication?

More than half of patients with stroke need help taking medication, according to a study published March 11 in BMJ Open. Approximately 600 community-dwelling patients with stroke responded to a five-item questionnaire about practical support that they need and receive. Approximately 56% of respondents got help with taking medication, and 11% needed additional help, including help with prescriptions and collection of medicines, getting medicines out of the packaging, and being reminded to take medicines. Being dependent on others was associated with experiencing more unmet needs with daily medicine taking. About 35% of respondents said that they had missed taking medicine in the previous 30 days. Younger patients with stroke were more likely to miss their medicines, possibly because they were less likely to receive help from a caregiver.

Jamison J, Ayerbe L, Di Tanna GL, et al. Evaluating practical support stroke survivors get with medicines and unmet needs in primary care: a survey. BMJ Open. 2018;8(3):e019874.

Sun Exposure Associated With Reduced Risk of MS

Living in areas with high ambient levels of ultraviolet-B light during childhood and the years before multiple sclerosis (MS) onset is associated with a lower MS risk, according to a study published online ahead of print March 7 in Neurology. Researchers identified 151 women with MS and 235 age-matched controls. The average age at MS onset was 40. All participants completed questionnaires about summer, winter, and lifetime sun exposure. Researchers separated the women into three groups representing low, moderate, and high ultraviolet-B ray exposure, based on their residence. Women who lived in sunnier climates with the highest exposure to ultraviolet-B rays had a 45% reduced risk of developing MS across all pre-MS onset age groups, when compared with participants living in areas with the lowest ultraviolet-B ray exposure.

Tremlett H, Zhu F, Ascherio A, Munger KL. Sun exposure over the life course and associations with multiple sclerosis. Neurology. 2018 Mar 7 [Epub ahead of print].

New Blood Pressure Guidelines May Not Benefit Everyone

The new blood pressure guidelines could harm certain patients, according to a study published online ahead of print March 2 in the Journal of the American College of Cardiology. Investigators examined the effect of 10-year cardiovascular disease (CVD) risk on primary outcome events and serious adverse events in the Systolic Pressure Intervention Trial, which was a basis for the new guidelines. They stratified patients by quartiles of risk and used Cox proportional hazards models to examine associations. From the first to fourth quartiles, the number needed to treat to prevent primary outcomes decreased from 91 to 38. The number needed to harm for all-cause serious adverse events increased from 62 to 250. Classifying patients by future risk could identify patients who would benefit from intensive treatment, said the authors.

Phillips RA, Xu J, Peterson LE, et al. Impact of cardiovascular risk on the relative benefit and harm of intensive treatment of hypertension. J Am Coll Cardiol. 2018 Mar 2 [Epub ahead of print].

—Kimberly Williams

New Genetic Risk Factors for Stroke Determined

New genetic risk factors for stroke have been identified, thereby tripling the number of gene regions known to affect stroke risk, according to a study published online ahead of print March 12 in Nature Genetics. Researchers conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 with stroke) and discovered 22 new stroke risk loci, bringing the total to 32. In addition, the investigators found shared genetic variation with related vascular traits (eg, blood pressure, cardiac traits, and venous thromboembolism) at individual loci and using genetic risk scores and linkage-disequilibrium-score regression. Several loci had distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology. The researchers prioritized risk variants and genes through bioinformatics analyses using functional datasets.

Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018 Mar 12 [Epub ahead of print].

MS Medication Withdrawn Because of Safety Concerns

Citing concerns about safety, Biogen and AbbVie announced March 2 that they will be withdrawing daclizumab (Zinbryta) from worldwide markets. Daclizumab has known risks, so it was usually prescribed only for people with relapsing multiple sclerosis who had tried two or more other medications that had not worked well enough. Reports of inflammatory encephalitis and meningoencephalitis led the European Medicines Agency to initiate an Article 20 referral procedure. In such referrals, a medicine or class of medicines are scientifically assessed because of concerns over safety or quality. However, Biogen and AbbVie concluded that, because of the complex nature of these reports and how few patients were taking daclizumab, it would be difficult to characterize the nature of the medication’s harms and benefits, so the companies instead have decided to withdraw the medication from the market.

Many Elderly Patients With Epilepsy Receive Interacting Treatments

Many elderly patients with epilepsy receive combinations of nonepilepsy drugs (NEDs) and antiepileptic drugs (AEDs) that could interact, according to a study published February 7 in Epilepsia. Researchers retrospectively analyzed 2008–2010 Medicare claims for a random sample of beneficiaries age 67 and older. Prevalent cases had a diagnosis of epilepsy and took one or more AEDs. Incident cases had no seizure or epilepsy claim codes or AEDs in the preceding 365 days. Interacting pairs of AEDs and NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. Interacting drug pairs affected NED efficacy in 24.5% of incident cases and 39% of prevalent cases. Combinations affected AED efficacy in 20.4% of incident cases and 29.3% of prevalent cases.

Faught E, Szaflarski JP, Richman J, et al. Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk. Epilepsia. 2018;59(3):715-723.

Are Physically Fit Women at Reduced Risk for Dementia?

High cardiovascular fitness in midlife is associated with decreased risk of subsequent dementia, according to a study published online ahead of print March 14 in Neurology. Physicians examined a population-based sample of 1,462 women ages 38 to 60 in 1968. A subsample of 191 women with an average age of 50 took a maximal ergometer cycling test to measure their peak cardiovascular capacity. Over the following 44 years, participants were tested for dementia six times. By 2012, 44 of the women developed dementia. Approximately 5% of the highly fit women developed dementia, compared with 25% of moderately fit women, and 32% of the women with low fitness. The highly fit women were 88% less likely to develop dementia than the moderately fit women.

Hörder H, Johansson L, Guo X, et al. Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology. 2018 Mar 14 [Epub ahead of print].

Data on Geriatric TBI May Be Inadequate

Many older adults with traumatic brain injury (TBI) respond well to aggressive management and rehabilitation, which suggests that age and TBI severity alone are inadequate prognostic markers, according to a study published online ahead of print February 15 in the Journal of Neurotrauma. Researchers reviewed the literature on incident TBI sustained in older adulthood. They found few geriatric-specific TBI guidelines to assist with complex management decisions and concluded that TBI prognostic models do not perform optimally in this population. Major barriers in management of geriatric TBI include underrepresentation of older adults in TBI research, lack of systematic measurement of preinjury health that may predict outcome and response to treatment, and lack of geriatric-specific TBI common data elements. Investigators need to develop more age-inclusive TBI research protocols, said the authors.

Gardner RC, Dams-O’Connor K, Morrissey MR, Manley GT. Geriatric traumatic brain injury: epidemiology, outcomes, knowledge gaps, and future directions. J Neurotrauma. 2018 Feb 15 [Epub ahead of print].

TDCS Improves Gait in Parkinson’s Disease

Transcranial direct-current stimulation (TDCS) reduces freezing of gait and improves executive function and mobility, according to a study published online ahead of print February 13 in Movement Disorders. Researchers examined 20 patients with Parkinson’s disease and freezing of gait. The patients received 20 minutes of TDCS or sham treatment during three separate visits. TDCS targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously or primary motor cortex only. Participants completed the Timed Up and Go and Stroop tests before and after each stimulation session. Performance on the Timed Up and Go and Stroop tests improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after stimulation of the primary motor cortex alone or sham stimulation.

Dagan M, Herman T, Harrison R, et al. Multitarget transcranial direct current stimulation for freezing of gait in Parkinson’s disease. Mov Disord. 2018 Feb 13 [Epub ahead of print].

Patients With Major Stroke Need Realistic Planning

Doctors who care for patients with severe stroke should plan with patients and caregivers and discuss the possibility of death or survival with disability, according to a study published March 5 in the Canadian Medical Association Journal. Researchers recruited a purposive sample of people with total anterior circulation stroke at three stroke services and conducted serial, qualitative interviews with participants and their caregivers at six weeks, six months, and one year. Investigators also conducted a data-linkage study of all patients with anterior circulation stroke admitted to the three services over six months. About 57% of patients died within six months. Patients experienced immediate and persistent emotional distress and poor quality of life. Physicians should practice palliative care for these patients, but avoid using that term, said the authors.

Kendall M, Cowey E, Mead G, et al. Outcomes, experiences and palliative care in major stroke: a multicentre, mixed-method, longitudinal study. CMAJ. 2018;190(9):E238-E246.

Dengue Fever Is Associated With Increased Risk of Stroke

Dengue fever is associated with an increased risk of stroke in the first few months after diagnosis, according to a study published March 12 in Canadian Medical Association Journal. Using data from the Taiwan National Health Insurance Research Database, researchers examined 13,787 patients diagnosed with dengue fever between 2000 and 2012. The control cohort consisted of patients matched by demographic characteristics and stroke-related comorbidities who did not have dengue fever. The overall incidence rate of stroke was 5.33 per 1,000 person-years in the dengue fever cohort and 3.72 per 1,000 person-years in the control cohort. The adjusted hazard ratio of stroke was 1.16 in patients with dengue fever. The risk of stroke was 2.49 times higher in patients with dengue fever during the first two months after diagnosis, compared with controls.

Li HM, Huang YK, Su YC, Kao CH. Risk of stroke in patients with dengue fever: a population-based cohort study. CMAJ. 2018;190(10):E285-E290.

Do Survivors of Stroke Need Additional Help Taking Medication?

More than half of patients with stroke need help taking medication, according to a study published March 11 in BMJ Open. Approximately 600 community-dwelling patients with stroke responded to a five-item questionnaire about practical support that they need and receive. Approximately 56% of respondents got help with taking medication, and 11% needed additional help, including help with prescriptions and collection of medicines, getting medicines out of the packaging, and being reminded to take medicines. Being dependent on others was associated with experiencing more unmet needs with daily medicine taking. About 35% of respondents said that they had missed taking medicine in the previous 30 days. Younger patients with stroke were more likely to miss their medicines, possibly because they were less likely to receive help from a caregiver.

Jamison J, Ayerbe L, Di Tanna GL, et al. Evaluating practical support stroke survivors get with medicines and unmet needs in primary care: a survey. BMJ Open. 2018;8(3):e019874.

Sun Exposure Associated With Reduced Risk of MS

Living in areas with high ambient levels of ultraviolet-B light during childhood and the years before multiple sclerosis (MS) onset is associated with a lower MS risk, according to a study published online ahead of print March 7 in Neurology. Researchers identified 151 women with MS and 235 age-matched controls. The average age at MS onset was 40. All participants completed questionnaires about summer, winter, and lifetime sun exposure. Researchers separated the women into three groups representing low, moderate, and high ultraviolet-B ray exposure, based on their residence. Women who lived in sunnier climates with the highest exposure to ultraviolet-B rays had a 45% reduced risk of developing MS across all pre-MS onset age groups, when compared with participants living in areas with the lowest ultraviolet-B ray exposure.

Tremlett H, Zhu F, Ascherio A, Munger KL. Sun exposure over the life course and associations with multiple sclerosis. Neurology. 2018 Mar 7 [Epub ahead of print].

New Blood Pressure Guidelines May Not Benefit Everyone

The new blood pressure guidelines could harm certain patients, according to a study published online ahead of print March 2 in the Journal of the American College of Cardiology. Investigators examined the effect of 10-year cardiovascular disease (CVD) risk on primary outcome events and serious adverse events in the Systolic Pressure Intervention Trial, which was a basis for the new guidelines. They stratified patients by quartiles of risk and used Cox proportional hazards models to examine associations. From the first to fourth quartiles, the number needed to treat to prevent primary outcomes decreased from 91 to 38. The number needed to harm for all-cause serious adverse events increased from 62 to 250. Classifying patients by future risk could identify patients who would benefit from intensive treatment, said the authors.

Phillips RA, Xu J, Peterson LE, et al. Impact of cardiovascular risk on the relative benefit and harm of intensive treatment of hypertension. J Am Coll Cardiol. 2018 Mar 2 [Epub ahead of print].

—Kimberly Williams

New Genetic Risk Factors for Stroke Determined

New genetic risk factors for stroke have been identified, thereby tripling the number of gene regions known to affect stroke risk, according to a study published online ahead of print March 12 in Nature Genetics. Researchers conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 with stroke) and discovered 22 new stroke risk loci, bringing the total to 32. In addition, the investigators found shared genetic variation with related vascular traits (eg, blood pressure, cardiac traits, and venous thromboembolism) at individual loci and using genetic risk scores and linkage-disequilibrium-score regression. Several loci had distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology. The researchers prioritized risk variants and genes through bioinformatics analyses using functional datasets.

Malik R, Chauhan G, Traylor M, et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat Genet. 2018 Mar 12 [Epub ahead of print].

MS Medication Withdrawn Because of Safety Concerns

Citing concerns about safety, Biogen and AbbVie announced March 2 that they will be withdrawing daclizumab (Zinbryta) from worldwide markets. Daclizumab has known risks, so it was usually prescribed only for people with relapsing multiple sclerosis who had tried two or more other medications that had not worked well enough. Reports of inflammatory encephalitis and meningoencephalitis led the European Medicines Agency to initiate an Article 20 referral procedure. In such referrals, a medicine or class of medicines are scientifically assessed because of concerns over safety or quality. However, Biogen and AbbVie concluded that, because of the complex nature of these reports and how few patients were taking daclizumab, it would be difficult to characterize the nature of the medication’s harms and benefits, so the companies instead have decided to withdraw the medication from the market.

Many Elderly Patients With Epilepsy Receive Interacting Treatments

Many elderly patients with epilepsy receive combinations of nonepilepsy drugs (NEDs) and antiepileptic drugs (AEDs) that could interact, according to a study published February 7 in Epilepsia. Researchers retrospectively analyzed 2008–2010 Medicare claims for a random sample of beneficiaries age 67 and older. Prevalent cases had a diagnosis of epilepsy and took one or more AEDs. Incident cases had no seizure or epilepsy claim codes or AEDs in the preceding 365 days. Interacting pairs of AEDs and NEDs were identified by literature review. Logistic regression models were used to examine factors affecting the likelihood of interaction risk. Interacting drug pairs affected NED efficacy in 24.5% of incident cases and 39% of prevalent cases. Combinations affected AED efficacy in 20.4% of incident cases and 29.3% of prevalent cases.

Faught E, Szaflarski JP, Richman J, et al. Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk. Epilepsia. 2018;59(3):715-723.

Are Physically Fit Women at Reduced Risk for Dementia?

High cardiovascular fitness in midlife is associated with decreased risk of subsequent dementia, according to a study published online ahead of print March 14 in Neurology. Physicians examined a population-based sample of 1,462 women ages 38 to 60 in 1968. A subsample of 191 women with an average age of 50 took a maximal ergometer cycling test to measure their peak cardiovascular capacity. Over the following 44 years, participants were tested for dementia six times. By 2012, 44 of the women developed dementia. Approximately 5% of the highly fit women developed dementia, compared with 25% of moderately fit women, and 32% of the women with low fitness. The highly fit women were 88% less likely to develop dementia than the moderately fit women.

Hörder H, Johansson L, Guo X, et al. Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology. 2018 Mar 14 [Epub ahead of print].

Data on Geriatric TBI May Be Inadequate

Many older adults with traumatic brain injury (TBI) respond well to aggressive management and rehabilitation, which suggests that age and TBI severity alone are inadequate prognostic markers, according to a study published online ahead of print February 15 in the Journal of Neurotrauma. Researchers reviewed the literature on incident TBI sustained in older adulthood. They found few geriatric-specific TBI guidelines to assist with complex management decisions and concluded that TBI prognostic models do not perform optimally in this population. Major barriers in management of geriatric TBI include underrepresentation of older adults in TBI research, lack of systematic measurement of preinjury health that may predict outcome and response to treatment, and lack of geriatric-specific TBI common data elements. Investigators need to develop more age-inclusive TBI research protocols, said the authors.

Gardner RC, Dams-O’Connor K, Morrissey MR, Manley GT. Geriatric traumatic brain injury: epidemiology, outcomes, knowledge gaps, and future directions. J Neurotrauma. 2018 Feb 15 [Epub ahead of print].

TDCS Improves Gait in Parkinson’s Disease

Transcranial direct-current stimulation (TDCS) reduces freezing of gait and improves executive function and mobility, according to a study published online ahead of print February 13 in Movement Disorders. Researchers examined 20 patients with Parkinson’s disease and freezing of gait. The patients received 20 minutes of TDCS or sham treatment during three separate visits. TDCS targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously or primary motor cortex only. Participants completed the Timed Up and Go and Stroop tests before and after each stimulation session. Performance on the Timed Up and Go and Stroop tests improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after stimulation of the primary motor cortex alone or sham stimulation.

Dagan M, Herman T, Harrison R, et al. Multitarget transcranial direct current stimulation for freezing of gait in Parkinson’s disease. Mov Disord. 2018 Feb 13 [Epub ahead of print].

Patients With Major Stroke Need Realistic Planning

Doctors who care for patients with severe stroke should plan with patients and caregivers and discuss the possibility of death or survival with disability, according to a study published March 5 in the Canadian Medical Association Journal. Researchers recruited a purposive sample of people with total anterior circulation stroke at three stroke services and conducted serial, qualitative interviews with participants and their caregivers at six weeks, six months, and one year. Investigators also conducted a data-linkage study of all patients with anterior circulation stroke admitted to the three services over six months. About 57% of patients died within six months. Patients experienced immediate and persistent emotional distress and poor quality of life. Physicians should practice palliative care for these patients, but avoid using that term, said the authors.

Kendall M, Cowey E, Mead G, et al. Outcomes, experiences and palliative care in major stroke: a multicentre, mixed-method, longitudinal study. CMAJ. 2018;190(9):E238-E246.

Dengue Fever Is Associated With Increased Risk of Stroke

Dengue fever is associated with an increased risk of stroke in the first few months after diagnosis, according to a study published March 12 in Canadian Medical Association Journal. Using data from the Taiwan National Health Insurance Research Database, researchers examined 13,787 patients diagnosed with dengue fever between 2000 and 2012. The control cohort consisted of patients matched by demographic characteristics and stroke-related comorbidities who did not have dengue fever. The overall incidence rate of stroke was 5.33 per 1,000 person-years in the dengue fever cohort and 3.72 per 1,000 person-years in the control cohort. The adjusted hazard ratio of stroke was 1.16 in patients with dengue fever. The risk of stroke was 2.49 times higher in patients with dengue fever during the first two months after diagnosis, compared with controls.

Li HM, Huang YK, Su YC, Kao CH. Risk of stroke in patients with dengue fever: a population-based cohort study. CMAJ. 2018;190(10):E285-E290.

Do Survivors of Stroke Need Additional Help Taking Medication?

More than half of patients with stroke need help taking medication, according to a study published March 11 in BMJ Open. Approximately 600 community-dwelling patients with stroke responded to a five-item questionnaire about practical support that they need and receive. Approximately 56% of respondents got help with taking medication, and 11% needed additional help, including help with prescriptions and collection of medicines, getting medicines out of the packaging, and being reminded to take medicines. Being dependent on others was associated with experiencing more unmet needs with daily medicine taking. About 35% of respondents said that they had missed taking medicine in the previous 30 days. Younger patients with stroke were more likely to miss their medicines, possibly because they were less likely to receive help from a caregiver.

Jamison J, Ayerbe L, Di Tanna GL, et al. Evaluating practical support stroke survivors get with medicines and unmet needs in primary care: a survey. BMJ Open. 2018;8(3):e019874.

Sun Exposure Associated With Reduced Risk of MS

Living in areas with high ambient levels of ultraviolet-B light during childhood and the years before multiple sclerosis (MS) onset is associated with a lower MS risk, according to a study published online ahead of print March 7 in Neurology. Researchers identified 151 women with MS and 235 age-matched controls. The average age at MS onset was 40. All participants completed questionnaires about summer, winter, and lifetime sun exposure. Researchers separated the women into three groups representing low, moderate, and high ultraviolet-B ray exposure, based on their residence. Women who lived in sunnier climates with the highest exposure to ultraviolet-B rays had a 45% reduced risk of developing MS across all pre-MS onset age groups, when compared with participants living in areas with the lowest ultraviolet-B ray exposure.

Tremlett H, Zhu F, Ascherio A, Munger KL. Sun exposure over the life course and associations with multiple sclerosis. Neurology. 2018 Mar 7 [Epub ahead of print].

New Blood Pressure Guidelines May Not Benefit Everyone

The new blood pressure guidelines could harm certain patients, according to a study published online ahead of print March 2 in the Journal of the American College of Cardiology. Investigators examined the effect of 10-year cardiovascular disease (CVD) risk on primary outcome events and serious adverse events in the Systolic Pressure Intervention Trial, which was a basis for the new guidelines. They stratified patients by quartiles of risk and used Cox proportional hazards models to examine associations. From the first to fourth quartiles, the number needed to treat to prevent primary outcomes decreased from 91 to 38. The number needed to harm for all-cause serious adverse events increased from 62 to 250. Classifying patients by future risk could identify patients who would benefit from intensive treatment, said the authors.

Phillips RA, Xu J, Peterson LE, et al. Impact of cardiovascular risk on the relative benefit and harm of intensive treatment of hypertension. J Am Coll Cardiol. 2018 Mar 2 [Epub ahead of print].

—Kimberly Williams

Short Stature in Children Linked to Future Stroke

Short stature at ages 7 to 13 is associated with increased risk of stroke in adulthood, according to a study published online ahead of print February 15 in Stroke. Data were examined for 311,009 schoolchildren born between 1930 and 1989. Cox proportional hazards regressions were performed to estimate hazard ratios. Among the participants, 10,412 were diagnosed with ischemic stroke, and 2,546 were diagnosed with intracerebral hemorrhage. Height at age 7 was inversely and significantly associated with ischemic stroke in both sexes and with intracerebral hemorrhage in men, but not in women. Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from ages 7 to 13 were observed for ischemic stroke or intracerebral hemorrhage.

Gjærde LK, Truelsen TC, Baker JL. Childhood stature and growth in relation to first ischemic stroke or intracerebral hemorrhage. Stroke. 2018 Feb 15 [Epub ahead of print].

FDA Expands Treatment Window for Trevo Device

The FDA has cleared the use of the Trevo clot-retrieval device to treat certain patients with stroke as long as 24 hours after symptom onset, thus expanding its indications. The device is cleared as an initial therapy for acute ischemic stroke to reduce paralysis, speech difficulties, and other disabilities. It is to be used in addition to t-PA. Trevo was previously cleared for use in patients six hours after symptom onset. The agency evaluated data from a clinical trial comparing 107 patients treated with Trevo and medical management with 99 patients receiving medical management alone. About 48% of patients treated with Trevo were functionally independent three months after stroke, compared with 13% of patients receiving medical management. Stryker, headquartered in Kalamazoo, Michigan, markets the device.

Positive Views on Aging May Reduce Dementia Risk

Older adults who gain positive beliefs about old age from their culture are less likely to develop dementia, according to a study published February 7 in PLoS One. The cohort included 4,765 Health and Retirement Study participants age 60 or older who were dementia-free at baseline. In the total sample, people with positive age beliefs at baseline were significantly less likely to develop dementia, after adjusting for relevant covariates. Among people with APOE ε4, participants with positive age beliefs were 49.8% less likely to develop dementia than people with negative age beliefs. The results of this study suggest that positive age beliefs, which are modifiable and reduce stress, can be protective, even for older individuals at high risk of dementia, said the investigators.

Levy BR, Slade MD, Pietrzak RH, Ferrucci L. Positive age beliefs protect against dementia even among elders with high-risk gene. PLoS One. 2018 Feb 7;13(2):e0191004.

Should Women Stop MS Treatment During Pregnancy?

Natalizumab exposure for as long as 12 weeks of gestation increases the risk of spontaneous abortion, compared with exposure to injectable treatments or no treatment, in women with multiple sclerosis (MS), according to a study published online ahead of print February 7 in Neurology. Data for all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab were collected and compared with data for pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with spontaneous abortion. The rate of spontaneous abortion was within the estimates for the general population, however, as was the rate of major congenital anomalies.

Portaccio E, Annovazzi P, Ghezzi A, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology. 2018 Feb 7 [Epub ahead of print].

Walking Ability After Stroke Improves With Arm Exercise

Arm exercise may improve walking ability after stroke, according to a study published online ahead of print December 6, 2017, in the Journal of Neurophysiology. Researchers worked with a group of older adults who had had a stroke between seven months and 17 years before the study. Participants underwent three 30-minute, moderate-intensity arm cycling training sessions each week for five weeks. Bilateral soleus stretch reflexes were elicited at rest and during 1-Hz arm cycling. Investigators measured physical abilities before and after arm training using several standardized scales and tests of physical function. Performance significantly improved on all walking tests and improved as much as 28% on the Timed Up and Go test. Several subjects had less tightness in their muscles after completing the arm cycling trial.

Kaupp C, Pearcey GE, Klarner T, et al. Rhythmic arm cycling training improves walking and neurophysiological integrity in chronic stroke-the arms can give legs a helping hand in rehabilitation. J Neurophysiol. 2017 Dec 6 [Epub ahead of print].

CSF May Indicate Parkinson’s Disease Phenotype

Lower CSF alpha-synuclein level is associated with diagnosis and motor phenotype in moderate and advanced Parkinson’s disease, according to a study published in the February issue of Movement Disorders. Researchers analyzed data from BioFIND, a cross-sectional, observational study that examines clinical and biomarker characteristics in moderate and advanced Parkinson’s disease and matched healthy controls. Investigators compared alpha-synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and Movement Disorders Society Unified Parkinson’s Disease Rating Scale, motor phenotype, Montreal Cognitive Assessment, and REM sleep behavior disorder questionnaire scores in Parkinson’s disease were examined. CSF alpha-synuclein level was lower in Parkinson’s disease versus controls. Plasma and saliva alpha-synuclein levels did not differ between Parkinson’s disease and controls, and alpha-synuclein did not significantly correlate among biofluids.

Goldman JG, Andrews H, Amara A, et al. Cerebrospinal fluid, plasma, and saliva in the BioFIND study: relationships among biomarkers and Parkinson’s disease features. Mov Disord. 2018;33(2):282-288.

Social Interaction May Improve Quality of Life in Dementia

Increasing the amount of social interaction for people with dementia living in care homes to one hour a week improves quality of life when combined with personalized care, according to a study published February 6 in PLoS Med. In all, 847 people with dementia in 69 care homes were included in this study, which compared a psychosocial intervention plus antipsychotic treatment review with standard treatment using an intention-to-treat analysis. The primary outcome was quality of life. Staff were trained in person-centered care, social interaction, and education in antipsychotic medications. A total of 553 participants completed the nine-month randomized controlled trial. The intervention significantly improved quality of life, agitation, and overall neuropsychiatric symptoms. Benefits were greatest in people with moderately severe dementia.

Ballard C, Corbett A, Orrell M, et al. Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial. PLoS Med. 2018 Feb 6;15(2):e1002500.

Adjunctive Cetirizine Reduces Relapses in Neuromyelitis Optica

In patients with neuromyelitis optica, adding cetirizine to standard therapy is safe and well tolerated and may reduce relapses, according to a study published online ahead of print February 2 in Neurology Neuroimmunology & Neuroinflammation. This pilot, open-label, add-on trial of cetirizine followed 16 patients with neuromyelitis optica taking 10 mg/day of oral cetirizine for one year in addition to their usual treatment. The primary end point was the annualized relapse rate while on the same disease-modifying therapy before starting cetirizine, compared with that while taking cetirizine. Participants were monitored for new neurologic episodes and potential adverse events related to the study drug. Annualized relapse rate was 0.4 before cetirizine treatment and 0.1 afterward. Cetirizine did not affect participants’ Expanded Disability Status Scale scores.

Katz Sand I, Fabian MT, Telford R, et al. Open-label, add-on trial of cetirizine for neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2018 Feb 2 [Epub ahead of print].

Stroke Risk Factors Specific to Women Identified

Investigators have identified stroke risk factors specific to women, according to a study published online ahead of print February 8 in Stroke. A literature review found risk factors in the three main categories of endogenous hormones, exogenous hormones, and pregnancy-related exposures. These factors include early age of menarche, early age at menopause, low levels of dehydroepiandrosterone, and taking oral estrogen or combined oral contraceptives. The risk factors are common, and not all women who have one or more of them will have a stroke. Clinicians should consider history of pregnancy complications, including gestational diabetes, pre-eclampsia, or hypertension during or immediately following pregnancy, when evaluating a patient for stroke risk, said the investigators. These women should be monitored carefully and told that they are at higher risk, they added.

Demel SL, Kittner S, Ley SH, et al. Stroke risk factors unique to women. Stroke. 2018 Feb 8 [Epub ahead of print].

FDA Clears Embrace for Monitoring Seizure Activity

The FDA has cleared the Embrace smart watch for detecting generalized tonic-clonic seizures. The device uses advanced machine learning and measures multiple indicators, including electrodermal activity. It also sends alerts to summon caregivers when it detects seizures. In a multisite clinical study, 135 patients with epilepsy were admitted to epilepsy monitoring units for continuous monitoring with video-EEG while they wore the device. A total of 6,530 hours of data were recorded over 272 days, including data for 40 generalized tonic-clonic seizures. The device’s algorithm detected 100% of the seizures. The trial used the gold standard of defining seizures as those clinically labelled by at least two out of three independent epileptologists, who examined the video-EEG data without seeing any data used by Embrace. The Embrace watch was approved in Europe in April 2017 as a medical device for seizure monitoring and alert. Empatica, which markets the watch, is located in Cambridge, Massachusetts.

FDA Approves Glatopa for Relapsing Forms of MS

The FDA has approved Glatopa (glatiramer acetate injection) 40 mg/mL, as a thrice-weekly generic treatment option for relapsing forms of multiple sclerosis (MS). Doses should be administered at 48-hour intervals. The treatment is intended to be fully substitutable for Copaxone. A 20-mg/mL formulation of the drug has been available since June 2015. Glatopa is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol. The most common adverse reactions with glatiramer acetate injection 40 mg/mL versus placebo are injection-site reactions such as erythema (22% vs 2%). The most common side effects of glatiramer acetate injection 20 mg/mL versus placebo are erythema, vasodilatation, rash, dyspnea, and chest pain. Sandoz, which markets Glatopa, is headquartered in Holzkirchen, Germany.

—Kimberly Williams

Short Stature in Children Linked to Future Stroke

Short stature at ages 7 to 13 is associated with increased risk of stroke in adulthood, according to a study published online ahead of print February 15 in Stroke. Data were examined for 311,009 schoolchildren born between 1930 and 1989. Cox proportional hazards regressions were performed to estimate hazard ratios. Among the participants, 10,412 were diagnosed with ischemic stroke, and 2,546 were diagnosed with intracerebral hemorrhage. Height at age 7 was inversely and significantly associated with ischemic stroke in both sexes and with intracerebral hemorrhage in men, but not in women. Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from ages 7 to 13 were observed for ischemic stroke or intracerebral hemorrhage.

Gjærde LK, Truelsen TC, Baker JL. Childhood stature and growth in relation to first ischemic stroke or intracerebral hemorrhage. Stroke. 2018 Feb 15 [Epub ahead of print].

FDA Expands Treatment Window for Trevo Device

The FDA has cleared the use of the Trevo clot-retrieval device to treat certain patients with stroke as long as 24 hours after symptom onset, thus expanding its indications. The device is cleared as an initial therapy for acute ischemic stroke to reduce paralysis, speech difficulties, and other disabilities. It is to be used in addition to t-PA. Trevo was previously cleared for use in patients six hours after symptom onset. The agency evaluated data from a clinical trial comparing 107 patients treated with Trevo and medical management with 99 patients receiving medical management alone. About 48% of patients treated with Trevo were functionally independent three months after stroke, compared with 13% of patients receiving medical management. Stryker, headquartered in Kalamazoo, Michigan, markets the device.

Positive Views on Aging May Reduce Dementia Risk

Older adults who gain positive beliefs about old age from their culture are less likely to develop dementia, according to a study published February 7 in PLoS One. The cohort included 4,765 Health and Retirement Study participants age 60 or older who were dementia-free at baseline. In the total sample, people with positive age beliefs at baseline were significantly less likely to develop dementia, after adjusting for relevant covariates. Among people with APOE ε4, participants with positive age beliefs were 49.8% less likely to develop dementia than people with negative age beliefs. The results of this study suggest that positive age beliefs, which are modifiable and reduce stress, can be protective, even for older individuals at high risk of dementia, said the investigators.

Levy BR, Slade MD, Pietrzak RH, Ferrucci L. Positive age beliefs protect against dementia even among elders with high-risk gene. PLoS One. 2018 Feb 7;13(2):e0191004.

Should Women Stop MS Treatment During Pregnancy?

Natalizumab exposure for as long as 12 weeks of gestation increases the risk of spontaneous abortion, compared with exposure to injectable treatments or no treatment, in women with multiple sclerosis (MS), according to a study published online ahead of print February 7 in Neurology. Data for all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab were collected and compared with data for pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with spontaneous abortion. The rate of spontaneous abortion was within the estimates for the general population, however, as was the rate of major congenital anomalies.

Portaccio E, Annovazzi P, Ghezzi A, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology. 2018 Feb 7 [Epub ahead of print].

Walking Ability After Stroke Improves With Arm Exercise

Arm exercise may improve walking ability after stroke, according to a study published online ahead of print December 6, 2017, in the Journal of Neurophysiology. Researchers worked with a group of older adults who had had a stroke between seven months and 17 years before the study. Participants underwent three 30-minute, moderate-intensity arm cycling training sessions each week for five weeks. Bilateral soleus stretch reflexes were elicited at rest and during 1-Hz arm cycling. Investigators measured physical abilities before and after arm training using several standardized scales and tests of physical function. Performance significantly improved on all walking tests and improved as much as 28% on the Timed Up and Go test. Several subjects had less tightness in their muscles after completing the arm cycling trial.

Kaupp C, Pearcey GE, Klarner T, et al. Rhythmic arm cycling training improves walking and neurophysiological integrity in chronic stroke-the arms can give legs a helping hand in rehabilitation. J Neurophysiol. 2017 Dec 6 [Epub ahead of print].

CSF May Indicate Parkinson’s Disease Phenotype

Lower CSF alpha-synuclein level is associated with diagnosis and motor phenotype in moderate and advanced Parkinson’s disease, according to a study published in the February issue of Movement Disorders. Researchers analyzed data from BioFIND, a cross-sectional, observational study that examines clinical and biomarker characteristics in moderate and advanced Parkinson’s disease and matched healthy controls. Investigators compared alpha-synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and Movement Disorders Society Unified Parkinson’s Disease Rating Scale, motor phenotype, Montreal Cognitive Assessment, and REM sleep behavior disorder questionnaire scores in Parkinson’s disease were examined. CSF alpha-synuclein level was lower in Parkinson’s disease versus controls. Plasma and saliva alpha-synuclein levels did not differ between Parkinson’s disease and controls, and alpha-synuclein did not significantly correlate among biofluids.

Goldman JG, Andrews H, Amara A, et al. Cerebrospinal fluid, plasma, and saliva in the BioFIND study: relationships among biomarkers and Parkinson’s disease features. Mov Disord. 2018;33(2):282-288.

Social Interaction May Improve Quality of Life in Dementia

Increasing the amount of social interaction for people with dementia living in care homes to one hour a week improves quality of life when combined with personalized care, according to a study published February 6 in PLoS Med. In all, 847 people with dementia in 69 care homes were included in this study, which compared a psychosocial intervention plus antipsychotic treatment review with standard treatment using an intention-to-treat analysis. The primary outcome was quality of life. Staff were trained in person-centered care, social interaction, and education in antipsychotic medications. A total of 553 participants completed the nine-month randomized controlled trial. The intervention significantly improved quality of life, agitation, and overall neuropsychiatric symptoms. Benefits were greatest in people with moderately severe dementia.

Ballard C, Corbett A, Orrell M, et al. Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial. PLoS Med. 2018 Feb 6;15(2):e1002500.

Adjunctive Cetirizine Reduces Relapses in Neuromyelitis Optica

In patients with neuromyelitis optica, adding cetirizine to standard therapy is safe and well tolerated and may reduce relapses, according to a study published online ahead of print February 2 in Neurology Neuroimmunology & Neuroinflammation. This pilot, open-label, add-on trial of cetirizine followed 16 patients with neuromyelitis optica taking 10 mg/day of oral cetirizine for one year in addition to their usual treatment. The primary end point was the annualized relapse rate while on the same disease-modifying therapy before starting cetirizine, compared with that while taking cetirizine. Participants were monitored for new neurologic episodes and potential adverse events related to the study drug. Annualized relapse rate was 0.4 before cetirizine treatment and 0.1 afterward. Cetirizine did not affect participants’ Expanded Disability Status Scale scores.

Katz Sand I, Fabian MT, Telford R, et al. Open-label, add-on trial of cetirizine for neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2018 Feb 2 [Epub ahead of print].

Stroke Risk Factors Specific to Women Identified

Investigators have identified stroke risk factors specific to women, according to a study published online ahead of print February 8 in Stroke. A literature review found risk factors in the three main categories of endogenous hormones, exogenous hormones, and pregnancy-related exposures. These factors include early age of menarche, early age at menopause, low levels of dehydroepiandrosterone, and taking oral estrogen or combined oral contraceptives. The risk factors are common, and not all women who have one or more of them will have a stroke. Clinicians should consider history of pregnancy complications, including gestational diabetes, pre-eclampsia, or hypertension during or immediately following pregnancy, when evaluating a patient for stroke risk, said the investigators. These women should be monitored carefully and told that they are at higher risk, they added.

Demel SL, Kittner S, Ley SH, et al. Stroke risk factors unique to women. Stroke. 2018 Feb 8 [Epub ahead of print].

FDA Clears Embrace for Monitoring Seizure Activity

The FDA has cleared the Embrace smart watch for detecting generalized tonic-clonic seizures. The device uses advanced machine learning and measures multiple indicators, including electrodermal activity. It also sends alerts to summon caregivers when it detects seizures. In a multisite clinical study, 135 patients with epilepsy were admitted to epilepsy monitoring units for continuous monitoring with video-EEG while they wore the device. A total of 6,530 hours of data were recorded over 272 days, including data for 40 generalized tonic-clonic seizures. The device’s algorithm detected 100% of the seizures. The trial used the gold standard of defining seizures as those clinically labelled by at least two out of three independent epileptologists, who examined the video-EEG data without seeing any data used by Embrace. The Embrace watch was approved in Europe in April 2017 as a medical device for seizure monitoring and alert. Empatica, which markets the watch, is located in Cambridge, Massachusetts.

FDA Approves Glatopa for Relapsing Forms of MS

The FDA has approved Glatopa (glatiramer acetate injection) 40 mg/mL, as a thrice-weekly generic treatment option for relapsing forms of multiple sclerosis (MS). Doses should be administered at 48-hour intervals. The treatment is intended to be fully substitutable for Copaxone. A 20-mg/mL formulation of the drug has been available since June 2015. Glatopa is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol. The most common adverse reactions with glatiramer acetate injection 40 mg/mL versus placebo are injection-site reactions such as erythema (22% vs 2%). The most common side effects of glatiramer acetate injection 20 mg/mL versus placebo are erythema, vasodilatation, rash, dyspnea, and chest pain. Sandoz, which markets Glatopa, is headquartered in Holzkirchen, Germany.

—Kimberly Williams

Short Stature in Children Linked to Future Stroke

Short stature at ages 7 to 13 is associated with increased risk of stroke in adulthood, according to a study published online ahead of print February 15 in Stroke. Data were examined for 311,009 schoolchildren born between 1930 and 1989. Cox proportional hazards regressions were performed to estimate hazard ratios. Among the participants, 10,412 were diagnosed with ischemic stroke, and 2,546 were diagnosed with intracerebral hemorrhage. Height at age 7 was inversely and significantly associated with ischemic stroke in both sexes and with intracerebral hemorrhage in men, but not in women. Associations were similar at older childhood ages and were stable throughout the study period. No statistically significant associations for growth from ages 7 to 13 were observed for ischemic stroke or intracerebral hemorrhage.

Gjærde LK, Truelsen TC, Baker JL. Childhood stature and growth in relation to first ischemic stroke or intracerebral hemorrhage. Stroke. 2018 Feb 15 [Epub ahead of print].

FDA Expands Treatment Window for Trevo Device

The FDA has cleared the use of the Trevo clot-retrieval device to treat certain patients with stroke as long as 24 hours after symptom onset, thus expanding its indications. The device is cleared as an initial therapy for acute ischemic stroke to reduce paralysis, speech difficulties, and other disabilities. It is to be used in addition to t-PA. Trevo was previously cleared for use in patients six hours after symptom onset. The agency evaluated data from a clinical trial comparing 107 patients treated with Trevo and medical management with 99 patients receiving medical management alone. About 48% of patients treated with Trevo were functionally independent three months after stroke, compared with 13% of patients receiving medical management. Stryker, headquartered in Kalamazoo, Michigan, markets the device.

Positive Views on Aging May Reduce Dementia Risk

Older adults who gain positive beliefs about old age from their culture are less likely to develop dementia, according to a study published February 7 in PLoS One. The cohort included 4,765 Health and Retirement Study participants age 60 or older who were dementia-free at baseline. In the total sample, people with positive age beliefs at baseline were significantly less likely to develop dementia, after adjusting for relevant covariates. Among people with APOE ε4, participants with positive age beliefs were 49.8% less likely to develop dementia than people with negative age beliefs. The results of this study suggest that positive age beliefs, which are modifiable and reduce stress, can be protective, even for older individuals at high risk of dementia, said the investigators.

Levy BR, Slade MD, Pietrzak RH, Ferrucci L. Positive age beliefs protect against dementia even among elders with high-risk gene. PLoS One. 2018 Feb 7;13(2):e0191004.

Should Women Stop MS Treatment During Pregnancy?

Natalizumab exposure for as long as 12 weeks of gestation increases the risk of spontaneous abortion, compared with exposure to injectable treatments or no treatment, in women with multiple sclerosis (MS), according to a study published online ahead of print February 7 in Neurology. Data for all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab were collected and compared with data for pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with spontaneous abortion. The rate of spontaneous abortion was within the estimates for the general population, however, as was the rate of major congenital anomalies.

Portaccio E, Annovazzi P, Ghezzi A, et al. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks. Neurology. 2018 Feb 7 [Epub ahead of print].

Walking Ability After Stroke Improves With Arm Exercise

Arm exercise may improve walking ability after stroke, according to a study published online ahead of print December 6, 2017, in the Journal of Neurophysiology. Researchers worked with a group of older adults who had had a stroke between seven months and 17 years before the study. Participants underwent three 30-minute, moderate-intensity arm cycling training sessions each week for five weeks. Bilateral soleus stretch reflexes were elicited at rest and during 1-Hz arm cycling. Investigators measured physical abilities before and after arm training using several standardized scales and tests of physical function. Performance significantly improved on all walking tests and improved as much as 28% on the Timed Up and Go test. Several subjects had less tightness in their muscles after completing the arm cycling trial.

Kaupp C, Pearcey GE, Klarner T, et al. Rhythmic arm cycling training improves walking and neurophysiological integrity in chronic stroke-the arms can give legs a helping hand in rehabilitation. J Neurophysiol. 2017 Dec 6 [Epub ahead of print].

CSF May Indicate Parkinson’s Disease Phenotype

Lower CSF alpha-synuclein level is associated with diagnosis and motor phenotype in moderate and advanced Parkinson’s disease, according to a study published in the February issue of Movement Disorders. Researchers analyzed data from BioFIND, a cross-sectional, observational study that examines clinical and biomarker characteristics in moderate and advanced Parkinson’s disease and matched healthy controls. Investigators compared alpha-synuclein concentrations across diagnosis, biofluids, and CSF biomarkers. Correlations of CSF biomarkers and Movement Disorders Society Unified Parkinson’s Disease Rating Scale, motor phenotype, Montreal Cognitive Assessment, and REM sleep behavior disorder questionnaire scores in Parkinson’s disease were examined. CSF alpha-synuclein level was lower in Parkinson’s disease versus controls. Plasma and saliva alpha-synuclein levels did not differ between Parkinson’s disease and controls, and alpha-synuclein did not significantly correlate among biofluids.

Goldman JG, Andrews H, Amara A, et al. Cerebrospinal fluid, plasma, and saliva in the BioFIND study: relationships among biomarkers and Parkinson’s disease features. Mov Disord. 2018;33(2):282-288.

Social Interaction May Improve Quality of Life in Dementia

Increasing the amount of social interaction for people with dementia living in care homes to one hour a week improves quality of life when combined with personalized care, according to a study published February 6 in PLoS Med. In all, 847 people with dementia in 69 care homes were included in this study, which compared a psychosocial intervention plus antipsychotic treatment review with standard treatment using an intention-to-treat analysis. The primary outcome was quality of life. Staff were trained in person-centered care, social interaction, and education in antipsychotic medications. A total of 553 participants completed the nine-month randomized controlled trial. The intervention significantly improved quality of life, agitation, and overall neuropsychiatric symptoms. Benefits were greatest in people with moderately severe dementia.

Ballard C, Corbett A, Orrell M, et al. Impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes: a cluster-randomised controlled trial. PLoS Med. 2018 Feb 6;15(2):e1002500.

Adjunctive Cetirizine Reduces Relapses in Neuromyelitis Optica

In patients with neuromyelitis optica, adding cetirizine to standard therapy is safe and well tolerated and may reduce relapses, according to a study published online ahead of print February 2 in Neurology Neuroimmunology & Neuroinflammation. This pilot, open-label, add-on trial of cetirizine followed 16 patients with neuromyelitis optica taking 10 mg/day of oral cetirizine for one year in addition to their usual treatment. The primary end point was the annualized relapse rate while on the same disease-modifying therapy before starting cetirizine, compared with that while taking cetirizine. Participants were monitored for new neurologic episodes and potential adverse events related to the study drug. Annualized relapse rate was 0.4 before cetirizine treatment and 0.1 afterward. Cetirizine did not affect participants’ Expanded Disability Status Scale scores.

Katz Sand I, Fabian MT, Telford R, et al. Open-label, add-on trial of cetirizine for neuromyelitis optica. Neurol Neuroimmunol Neuroinflamm. 2018 Feb 2 [Epub ahead of print].

Stroke Risk Factors Specific to Women Identified

Investigators have identified stroke risk factors specific to women, according to a study published online ahead of print February 8 in Stroke. A literature review found risk factors in the three main categories of endogenous hormones, exogenous hormones, and pregnancy-related exposures. These factors include early age of menarche, early age at menopause, low levels of dehydroepiandrosterone, and taking oral estrogen or combined oral contraceptives. The risk factors are common, and not all women who have one or more of them will have a stroke. Clinicians should consider history of pregnancy complications, including gestational diabetes, pre-eclampsia, or hypertension during or immediately following pregnancy, when evaluating a patient for stroke risk, said the investigators. These women should be monitored carefully and told that they are at higher risk, they added.

Demel SL, Kittner S, Ley SH, et al. Stroke risk factors unique to women. Stroke. 2018 Feb 8 [Epub ahead of print].

FDA Clears Embrace for Monitoring Seizure Activity

The FDA has cleared the Embrace smart watch for detecting generalized tonic-clonic seizures. The device uses advanced machine learning and measures multiple indicators, including electrodermal activity. It also sends alerts to summon caregivers when it detects seizures. In a multisite clinical study, 135 patients with epilepsy were admitted to epilepsy monitoring units for continuous monitoring with video-EEG while they wore the device. A total of 6,530 hours of data were recorded over 272 days, including data for 40 generalized tonic-clonic seizures. The device’s algorithm detected 100% of the seizures. The trial used the gold standard of defining seizures as those clinically labelled by at least two out of three independent epileptologists, who examined the video-EEG data without seeing any data used by Embrace. The Embrace watch was approved in Europe in April 2017 as a medical device for seizure monitoring and alert. Empatica, which markets the watch, is located in Cambridge, Massachusetts.

FDA Approves Glatopa for Relapsing Forms of MS

The FDA has approved Glatopa (glatiramer acetate injection) 40 mg/mL, as a thrice-weekly generic treatment option for relapsing forms of multiple sclerosis (MS). Doses should be administered at 48-hour intervals. The treatment is intended to be fully substitutable for Copaxone. A 20-mg/mL formulation of the drug has been available since June 2015. Glatopa is contraindicated in patients with known hypersensitivity to glatiramer acetate or mannitol. The most common adverse reactions with glatiramer acetate injection 40 mg/mL versus placebo are injection-site reactions such as erythema (22% vs 2%). The most common side effects of glatiramer acetate injection 20 mg/mL versus placebo are erythema, vasodilatation, rash, dyspnea, and chest pain. Sandoz, which markets Glatopa, is headquartered in Holzkirchen, Germany.

—Kimberly Williams

Device May Predict Seizure Risk

The NeuroPace RNS System may enable clinicians to identify when patients are at highest risk for seizures, thus allowing patients to plan around these events, according to a study published January 8 in Nature Communications. In 37 subjects with the implanted brain stimulation device, which detected interictal epileptiform activity (IEA) and seizures over years, researchers found that IEA oscillates with circadian and subject-specific multiday periods. Multiday periodicities, most commonly 20–30 days in duration, are robust and relatively stable for as long as 10 years in men and women. Investigators also found that seizures occur preferentially during the rising phase of multiday IEA rhythms. Combining phase information from circadian and multiday IEA rhythms could be a biomarker for determining relative seizure risk with a large effect size in most subjects.

Baud MO, Kleen JK, Mirro EA, et al. Multi-day rhythms modulate seizure risk in epilepsy. Nat Commun. 2018;9(1):88.

DBS May Improve Survival in Parkinson’s Disease

Deep brain stimulation (DBS) is associated with a modest survival advantage when compared with medical management alone, according to a study published in the December 2017 issue of Movement Disorders. Investigators conducted a retrospective analysis of Veterans Affairs and Medicare administrative data of veterans with Parkinson’s disease between 2007 and 2013. They used propensity-score matching to pair patients who received DBS with those who received medical management alone. Veterans with Parkinson’s disease who received DBS had a longer survival measured in days than veterans who did not undergo DBS (2,291 days vs 2,064 days). Mean age at death was similar for both groups (76.5 vs 75.9), and the most common cause of death was Parkinson’s disease. The study groups may have differed in ways that are not measured.

Weaver FM, Stroupe KT, Smith B, et al. Survival in patients with Parkinson’s disease after deep brain stimulation or medical management. Mov Disord. 2017;32(12):1756-1763.

Idalopirdine May Not Decrease Cognitive Loss in Alzheimer’s Disease

In patients with mild to moderate Alzheimer’s disease, the use of idalopirdine, compared with placebo, does not improve cognition over 24 weeks of treatment, according to a study published January 9 in JAMA. The study examined three randomized clinical trials with 2,525 patients age 50 or older with mild to moderate Alzheimer’s disease. The 24-week studies were conducted from October 2013 to January 2017. Six months of 10 mg/day, 30 mg/day, or 60 mg/day idalopirdine treatment added to cholinesterase inhibitor therapy did not improve cognition or decrease cognitive loss. There was no requirement for evidence of Alzheimer’s disease biomarker positivity for inclusion in the trials, however, which may have allowed some patients to be included without having Alzheimer’s disease pathology.

Atri A, Frölich L, Ballard C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: three randomized clinical trials. JAMA. 2018;319(2):130-142.

New Biomarker May Identify Huntington’s Disease

A potential biomarker for Huntington’s disease could mean a more effective way of evaluating treatments for this neurologic disease, according to a study published online ahead of print December 27, 2017, in Neurology. Researchers studied miRNA levels in CSF from 30 asymptomatic carriers of the mutation that causes Huntington’s disease. They also studied CSF from participants diagnosed with Huntington’s disease, and from healthy controls. In all, 2,081 miRNAs were detected, and six were significantly increased in asymptomatic carriers versus controls. When the researchers evaluated the miRNA levels in each of the three patient groups, they found that all six had a pattern of increasing abundance from control to low risk, and from low risk to medium risk. The miRNA levels increase years before symptoms arise.

Reed ER, Latourelle JC, Bockholt JH, et al. MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study. Neurology. 2017 Dec 27 [Epub ahead of print].

Higher Topiramate Dose May Increase Risk of Cleft Lip or Palate

Topiramate increases the risk of cleft lip or cleft palate in offspring in a dose-dependent manner, according to a study published online ahead of print December 27, 2017, in Neurology. Researchers examined Medicaid data and identified approximately 1.4 million women who gave birth to live babies over 10 years. They compared women who filled a prescription for topiramate during their first trimester with women who did not fill a prescription for any antiseizure drug and women who filled a prescription for lamotrigine. The risk of oral clefts at birth was 4.1 per 1,000 in infants born to women exposed to topiramate, compared with 1.1 per 1,000 in the group unexposed to antiseizure drugs, and 1.5 per 1,000 among women exposed to lamotrigine.

Hernandez-Diaz S, Huybrechts KF, Desai RJ, et al. Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology. 2017 Dec 27 [Epub ahead of print].

Genetic Factors That Contribute to Alzheimer’s Disease Identified

Researchers have identified several new genes responsible for Alzheimer’s disease, including genes leading to functional and structural changes in the brain and elevated levels of Alzheimer’s disease proteins in CSF, according to a study published online ahead of print December 20, 2017, in Alzheimer’s & Dementia. Researchers tested the association between Alzheimer’s disease-related brain MRI measures, logical memory test scores, and CSF levels of amyloid beta and tau with millions of single-nucleotide polymorphisms (SNPs) in 1,189 participants in the Alzheimer Disease Neuroimaging Initiative study. Among people with normal cognitive functioning, SRRM4 was associated with total tau, and MTUS1 was associated with hippocampal volume. In participants with mild cognitive impairment, SNPs near ZNF804B were associated with logical memory test of delayed recall scores.

Chung J, Wang X, Maruyama T, et al. Genome-wide association study of Alzheimer’s disease endophenotypes at prediagnosis stages. Alzheimers Dement. 2017 Dec 20 [Epub ahead of print].

Fish Consumption May Improve Intelligence and Sleep

Children who eat fish at least once per week sleep better and have higher IQ scores than children who consume fish less frequently or not at all, according to a study published December 21, 2017, in Scientific Reports. The study included a cohort of 541 children (54% boys) between ages 9 and 11. The children took an IQ test and completed a questionnaire about fish consumption in the previous month. Options ranged from “never” to “at least once per week.” Their parents also answered the standardized Children Sleep Habits Questionnaire. Children who reported eating fish weekly scored 4.8 points higher on the IQ exams than those who said they “seldom” or “never” consumed fish. In addition, increased fish consumption was associated with fewer sleep disturbances.

Liu J, Cui Y, Li L, et al. The mediating role of sleep in the fish consumption - cognitive functioning relationship: a cohort study. Sci Rep. 2017;7(1):17961.

Rating Scales Predict Discharge Destination in Stroke

Outcome measure scores strongly predict discharge destination among patients with stroke and provide an objective means of early discharge planning, according to a study published in the January issue of the Journal of Neurologic Physical Therapy. A systematic review indicated that for every one-point increase on the Functional Independence Measure, a patient was approximately 1.08 times more likely to be discharged home than to institutionalized care. Patients with stroke who performed above average were 12 times more likely to be discharged home. Patients who performed poorly were 3.4 times more likely to be discharged to institutionalized care than home, and skilled nursing facility admission was more likely than admission to an inpatient rehabilitation facility. Patients with average performance were 1.9 times more likely to be discharged to institutionalized care.

Thorpe ER, Garrett KB, Smith AM, et al. Outcome measure scores predict discharge destination in patients with acute and subacute stroke: a systematic review and series of meta-analyses. J Neurol Phys Ther. 2018;42(1):2-11.

Do Green Leafy Vegetables Slow Brain Aging?

Eating about one serving per day of green, leafy vegetables may be linked to a slower rate of brain aging, according to a study published online ahead of print December 20, 2017, in Neurology. Researchers followed 960 cognitively normal people with an average age of 81 for an average of 4.7 years. In a linear mixed model adjusted for age, sex, education, cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green, leafy vegetables was associated with slower cognitive decline. Participants in the highest quintile of vegetable intake were the equivalent of 11 years younger, compared with people who never ate vegetables. Higher intake of phylloquinone, lutein, nitrate, folate, kaempferol, and alpha-tocopherol were associated with slower cognitive decline.

Morris MC, Wang Y, Barnes LL, et al. Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study. Neurology. 2017 Dec 20 [Epub ahead of print].

Data Clarify the Genetic Profile of Dementia With Lewy Bodies

Research has increased understanding of the unique genetic profile of dementia with Lewy bodies. In a study published January 17 in Lancet Neurology, researchers genotyped 1,743 patients with dementia with Lewy bodies and 4,454 controls. APOE and GBA had the same associations with dementia with Lewy bodies as they do with Alzheimer’s disease and Parkinson’s disease, respectively. SNCA, which is associated with Parkinson’s disease, also was associated with dementia with Lewy bodies, but through a different part of the gene. Evidence suggested that CNTN1 is associated with dementia with Lewy bodies, but the result was not statistically significant. The authors estimated that the heritable component of the disorder is approximately 36%. Common genetic variability has a role in the disease, said the authors.

Guerreiro R, Ross OA, Kun-Rodrigues C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17(1):64-74.

Preterm Newborns Have Altered Cerebral Perfusion

Altered regional cortical blood flow (CBF) in infants born very preterm at term-equivalent age may reflect early brain dysmaturation despite the absence of cerebral cortical injury, according to a study published online ahead of print November 30, 2017 in the Journal of Pediatrics. In this prospective, cross-sectional study, researchers used noninvasive 3T arterial spin labeling MRI to quantify regional CBF in the cerebral cortex of 202 infants, 98 of whom were born preterm. Analyses were performed controlling for sex, gestational age, and age at MRI. Infants born preterm had greater global CBF and greater absolute regional CBF in all brain regions except the insula. Relative CBF in the insula, anterior cingulate cortex, and auditory cortex were decreased significantly in infants born preterm, compared with infants born at full term.

Bouyssi-Kobar M, Murnick J, Brossard-Racine M, et al. Altered cerebral perfusion in infants born preterm compared with infants born full term. J Pediatr. 2017 Nov 30 [Epub ahead of print].

—Kimberly Williams

Device May Predict Seizure Risk

The NeuroPace RNS System may enable clinicians to identify when patients are at highest risk for seizures, thus allowing patients to plan around these events, according to a study published January 8 in Nature Communications. In 37 subjects with the implanted brain stimulation device, which detected interictal epileptiform activity (IEA) and seizures over years, researchers found that IEA oscillates with circadian and subject-specific multiday periods. Multiday periodicities, most commonly 20–30 days in duration, are robust and relatively stable for as long as 10 years in men and women. Investigators also found that seizures occur preferentially during the rising phase of multiday IEA rhythms. Combining phase information from circadian and multiday IEA rhythms could be a biomarker for determining relative seizure risk with a large effect size in most subjects.

Baud MO, Kleen JK, Mirro EA, et al. Multi-day rhythms modulate seizure risk in epilepsy. Nat Commun. 2018;9(1):88.

DBS May Improve Survival in Parkinson’s Disease

Deep brain stimulation (DBS) is associated with a modest survival advantage when compared with medical management alone, according to a study published in the December 2017 issue of Movement Disorders. Investigators conducted a retrospective analysis of Veterans Affairs and Medicare administrative data of veterans with Parkinson’s disease between 2007 and 2013. They used propensity-score matching to pair patients who received DBS with those who received medical management alone. Veterans with Parkinson’s disease who received DBS had a longer survival measured in days than veterans who did not undergo DBS (2,291 days vs 2,064 days). Mean age at death was similar for both groups (76.5 vs 75.9), and the most common cause of death was Parkinson’s disease. The study groups may have differed in ways that are not measured.

Weaver FM, Stroupe KT, Smith B, et al. Survival in patients with Parkinson’s disease after deep brain stimulation or medical management. Mov Disord. 2017;32(12):1756-1763.

Idalopirdine May Not Decrease Cognitive Loss in Alzheimer’s Disease

In patients with mild to moderate Alzheimer’s disease, the use of idalopirdine, compared with placebo, does not improve cognition over 24 weeks of treatment, according to a study published January 9 in JAMA. The study examined three randomized clinical trials with 2,525 patients age 50 or older with mild to moderate Alzheimer’s disease. The 24-week studies were conducted from October 2013 to January 2017. Six months of 10 mg/day, 30 mg/day, or 60 mg/day idalopirdine treatment added to cholinesterase inhibitor therapy did not improve cognition or decrease cognitive loss. There was no requirement for evidence of Alzheimer’s disease biomarker positivity for inclusion in the trials, however, which may have allowed some patients to be included without having Alzheimer’s disease pathology.

Atri A, Frölich L, Ballard C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: three randomized clinical trials. JAMA. 2018;319(2):130-142.

New Biomarker May Identify Huntington’s Disease

A potential biomarker for Huntington’s disease could mean a more effective way of evaluating treatments for this neurologic disease, according to a study published online ahead of print December 27, 2017, in Neurology. Researchers studied miRNA levels in CSF from 30 asymptomatic carriers of the mutation that causes Huntington’s disease. They also studied CSF from participants diagnosed with Huntington’s disease, and from healthy controls. In all, 2,081 miRNAs were detected, and six were significantly increased in asymptomatic carriers versus controls. When the researchers evaluated the miRNA levels in each of the three patient groups, they found that all six had a pattern of increasing abundance from control to low risk, and from low risk to medium risk. The miRNA levels increase years before symptoms arise.

Reed ER, Latourelle JC, Bockholt JH, et al. MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study. Neurology. 2017 Dec 27 [Epub ahead of print].

Higher Topiramate Dose May Increase Risk of Cleft Lip or Palate

Topiramate increases the risk of cleft lip or cleft palate in offspring in a dose-dependent manner, according to a study published online ahead of print December 27, 2017, in Neurology. Researchers examined Medicaid data and identified approximately 1.4 million women who gave birth to live babies over 10 years. They compared women who filled a prescription for topiramate during their first trimester with women who did not fill a prescription for any antiseizure drug and women who filled a prescription for lamotrigine. The risk of oral clefts at birth was 4.1 per 1,000 in infants born to women exposed to topiramate, compared with 1.1 per 1,000 in the group unexposed to antiseizure drugs, and 1.5 per 1,000 among women exposed to lamotrigine.

Hernandez-Diaz S, Huybrechts KF, Desai RJ, et al. Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology. 2017 Dec 27 [Epub ahead of print].

Genetic Factors That Contribute to Alzheimer’s Disease Identified

Researchers have identified several new genes responsible for Alzheimer’s disease, including genes leading to functional and structural changes in the brain and elevated levels of Alzheimer’s disease proteins in CSF, according to a study published online ahead of print December 20, 2017, in Alzheimer’s & Dementia. Researchers tested the association between Alzheimer’s disease-related brain MRI measures, logical memory test scores, and CSF levels of amyloid beta and tau with millions of single-nucleotide polymorphisms (SNPs) in 1,189 participants in the Alzheimer Disease Neuroimaging Initiative study. Among people with normal cognitive functioning, SRRM4 was associated with total tau, and MTUS1 was associated with hippocampal volume. In participants with mild cognitive impairment, SNPs near ZNF804B were associated with logical memory test of delayed recall scores.

Chung J, Wang X, Maruyama T, et al. Genome-wide association study of Alzheimer’s disease endophenotypes at prediagnosis stages. Alzheimers Dement. 2017 Dec 20 [Epub ahead of print].

Fish Consumption May Improve Intelligence and Sleep

Children who eat fish at least once per week sleep better and have higher IQ scores than children who consume fish less frequently or not at all, according to a study published December 21, 2017, in Scientific Reports. The study included a cohort of 541 children (54% boys) between ages 9 and 11. The children took an IQ test and completed a questionnaire about fish consumption in the previous month. Options ranged from “never” to “at least once per week.” Their parents also answered the standardized Children Sleep Habits Questionnaire. Children who reported eating fish weekly scored 4.8 points higher on the IQ exams than those who said they “seldom” or “never” consumed fish. In addition, increased fish consumption was associated with fewer sleep disturbances.

Liu J, Cui Y, Li L, et al. The mediating role of sleep in the fish consumption - cognitive functioning relationship: a cohort study. Sci Rep. 2017;7(1):17961.

Rating Scales Predict Discharge Destination in Stroke

Outcome measure scores strongly predict discharge destination among patients with stroke and provide an objective means of early discharge planning, according to a study published in the January issue of the Journal of Neurologic Physical Therapy. A systematic review indicated that for every one-point increase on the Functional Independence Measure, a patient was approximately 1.08 times more likely to be discharged home than to institutionalized care. Patients with stroke who performed above average were 12 times more likely to be discharged home. Patients who performed poorly were 3.4 times more likely to be discharged to institutionalized care than home, and skilled nursing facility admission was more likely than admission to an inpatient rehabilitation facility. Patients with average performance were 1.9 times more likely to be discharged to institutionalized care.

Thorpe ER, Garrett KB, Smith AM, et al. Outcome measure scores predict discharge destination in patients with acute and subacute stroke: a systematic review and series of meta-analyses. J Neurol Phys Ther. 2018;42(1):2-11.

Do Green Leafy Vegetables Slow Brain Aging?

Eating about one serving per day of green, leafy vegetables may be linked to a slower rate of brain aging, according to a study published online ahead of print December 20, 2017, in Neurology. Researchers followed 960 cognitively normal people with an average age of 81 for an average of 4.7 years. In a linear mixed model adjusted for age, sex, education, cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green, leafy vegetables was associated with slower cognitive decline. Participants in the highest quintile of vegetable intake were the equivalent of 11 years younger, compared with people who never ate vegetables. Higher intake of phylloquinone, lutein, nitrate, folate, kaempferol, and alpha-tocopherol were associated with slower cognitive decline.

Morris MC, Wang Y, Barnes LL, et al. Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study. Neurology. 2017 Dec 20 [Epub ahead of print].

Data Clarify the Genetic Profile of Dementia With Lewy Bodies

Research has increased understanding of the unique genetic profile of dementia with Lewy bodies. In a study published January 17 in Lancet Neurology, researchers genotyped 1,743 patients with dementia with Lewy bodies and 4,454 controls. APOE and GBA had the same associations with dementia with Lewy bodies as they do with Alzheimer’s disease and Parkinson’s disease, respectively. SNCA, which is associated with Parkinson’s disease, also was associated with dementia with Lewy bodies, but through a different part of the gene. Evidence suggested that CNTN1 is associated with dementia with Lewy bodies, but the result was not statistically significant. The authors estimated that the heritable component of the disorder is approximately 36%. Common genetic variability has a role in the disease, said the authors.

Guerreiro R, Ross OA, Kun-Rodrigues C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17(1):64-74.

Preterm Newborns Have Altered Cerebral Perfusion

Altered regional cortical blood flow (CBF) in infants born very preterm at term-equivalent age may reflect early brain dysmaturation despite the absence of cerebral cortical injury, according to a study published online ahead of print November 30, 2017 in the Journal of Pediatrics. In this prospective, cross-sectional study, researchers used noninvasive 3T arterial spin labeling MRI to quantify regional CBF in the cerebral cortex of 202 infants, 98 of whom were born preterm. Analyses were performed controlling for sex, gestational age, and age at MRI. Infants born preterm had greater global CBF and greater absolute regional CBF in all brain regions except the insula. Relative CBF in the insula, anterior cingulate cortex, and auditory cortex were decreased significantly in infants born preterm, compared with infants born at full term.

Bouyssi-Kobar M, Murnick J, Brossard-Racine M, et al. Altered cerebral perfusion in infants born preterm compared with infants born full term. J Pediatr. 2017 Nov 30 [Epub ahead of print].

—Kimberly Williams

Device May Predict Seizure Risk

The NeuroPace RNS System may enable clinicians to identify when patients are at highest risk for seizures, thus allowing patients to plan around these events, according to a study published January 8 in Nature Communications. In 37 subjects with the implanted brain stimulation device, which detected interictal epileptiform activity (IEA) and seizures over years, researchers found that IEA oscillates with circadian and subject-specific multiday periods. Multiday periodicities, most commonly 20–30 days in duration, are robust and relatively stable for as long as 10 years in men and women. Investigators also found that seizures occur preferentially during the rising phase of multiday IEA rhythms. Combining phase information from circadian and multiday IEA rhythms could be a biomarker for determining relative seizure risk with a large effect size in most subjects.

Baud MO, Kleen JK, Mirro EA, et al. Multi-day rhythms modulate seizure risk in epilepsy. Nat Commun. 2018;9(1):88.

DBS May Improve Survival in Parkinson’s Disease

Deep brain stimulation (DBS) is associated with a modest survival advantage when compared with medical management alone, according to a study published in the December 2017 issue of Movement Disorders. Investigators conducted a retrospective analysis of Veterans Affairs and Medicare administrative data of veterans with Parkinson’s disease between 2007 and 2013. They used propensity-score matching to pair patients who received DBS with those who received medical management alone. Veterans with Parkinson’s disease who received DBS had a longer survival measured in days than veterans who did not undergo DBS (2,291 days vs 2,064 days). Mean age at death was similar for both groups (76.5 vs 75.9), and the most common cause of death was Parkinson’s disease. The study groups may have differed in ways that are not measured.

Weaver FM, Stroupe KT, Smith B, et al. Survival in patients with Parkinson’s disease after deep brain stimulation or medical management. Mov Disord. 2017;32(12):1756-1763.

Idalopirdine May Not Decrease Cognitive Loss in Alzheimer’s Disease

In patients with mild to moderate Alzheimer’s disease, the use of idalopirdine, compared with placebo, does not improve cognition over 24 weeks of treatment, according to a study published January 9 in JAMA. The study examined three randomized clinical trials with 2,525 patients age 50 or older with mild to moderate Alzheimer’s disease. The 24-week studies were conducted from October 2013 to January 2017. Six months of 10 mg/day, 30 mg/day, or 60 mg/day idalopirdine treatment added to cholinesterase inhibitor therapy did not improve cognition or decrease cognitive loss. There was no requirement for evidence of Alzheimer’s disease biomarker positivity for inclusion in the trials, however, which may have allowed some patients to be included without having Alzheimer’s disease pathology.

Atri A, Frölich L, Ballard C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on change in cognition in patients with Alzheimer disease: three randomized clinical trials. JAMA. 2018;319(2):130-142.

New Biomarker May Identify Huntington’s Disease

A potential biomarker for Huntington’s disease could mean a more effective way of evaluating treatments for this neurologic disease, according to a study published online ahead of print December 27, 2017, in Neurology. Researchers studied miRNA levels in CSF from 30 asymptomatic carriers of the mutation that causes Huntington’s disease. They also studied CSF from participants diagnosed with Huntington’s disease, and from healthy controls. In all, 2,081 miRNAs were detected, and six were significantly increased in asymptomatic carriers versus controls. When the researchers evaluated the miRNA levels in each of the three patient groups, they found that all six had a pattern of increasing abundance from control to low risk, and from low risk to medium risk. The miRNA levels increase years before symptoms arise.

Reed ER, Latourelle JC, Bockholt JH, et al. MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study. Neurology. 2017 Dec 27 [Epub ahead of print].

Higher Topiramate Dose May Increase Risk of Cleft Lip or Palate

Topiramate increases the risk of cleft lip or cleft palate in offspring in a dose-dependent manner, according to a study published online ahead of print December 27, 2017, in Neurology. Researchers examined Medicaid data and identified approximately 1.4 million women who gave birth to live babies over 10 years. They compared women who filled a prescription for topiramate during their first trimester with women who did not fill a prescription for any antiseizure drug and women who filled a prescription for lamotrigine. The risk of oral clefts at birth was 4.1 per 1,000 in infants born to women exposed to topiramate, compared with 1.1 per 1,000 in the group unexposed to antiseizure drugs, and 1.5 per 1,000 among women exposed to lamotrigine.

Hernandez-Diaz S, Huybrechts KF, Desai RJ, et al. Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology. 2017 Dec 27 [Epub ahead of print].

Genetic Factors That Contribute to Alzheimer’s Disease Identified

Researchers have identified several new genes responsible for Alzheimer’s disease, including genes leading to functional and structural changes in the brain and elevated levels of Alzheimer’s disease proteins in CSF, according to a study published online ahead of print December 20, 2017, in Alzheimer’s & Dementia. Researchers tested the association between Alzheimer’s disease-related brain MRI measures, logical memory test scores, and CSF levels of amyloid beta and tau with millions of single-nucleotide polymorphisms (SNPs) in 1,189 participants in the Alzheimer Disease Neuroimaging Initiative study. Among people with normal cognitive functioning, SRRM4 was associated with total tau, and MTUS1 was associated with hippocampal volume. In participants with mild cognitive impairment, SNPs near ZNF804B were associated with logical memory test of delayed recall scores.

Chung J, Wang X, Maruyama T, et al. Genome-wide association study of Alzheimer’s disease endophenotypes at prediagnosis stages. Alzheimers Dement. 2017 Dec 20 [Epub ahead of print].

Fish Consumption May Improve Intelligence and Sleep

Children who eat fish at least once per week sleep better and have higher IQ scores than children who consume fish less frequently or not at all, according to a study published December 21, 2017, in Scientific Reports. The study included a cohort of 541 children (54% boys) between ages 9 and 11. The children took an IQ test and completed a questionnaire about fish consumption in the previous month. Options ranged from “never” to “at least once per week.” Their parents also answered the standardized Children Sleep Habits Questionnaire. Children who reported eating fish weekly scored 4.8 points higher on the IQ exams than those who said they “seldom” or “never” consumed fish. In addition, increased fish consumption was associated with fewer sleep disturbances.

Liu J, Cui Y, Li L, et al. The mediating role of sleep in the fish consumption - cognitive functioning relationship: a cohort study. Sci Rep. 2017;7(1):17961.

Rating Scales Predict Discharge Destination in Stroke

Outcome measure scores strongly predict discharge destination among patients with stroke and provide an objective means of early discharge planning, according to a study published in the January issue of the Journal of Neurologic Physical Therapy. A systematic review indicated that for every one-point increase on the Functional Independence Measure, a patient was approximately 1.08 times more likely to be discharged home than to institutionalized care. Patients with stroke who performed above average were 12 times more likely to be discharged home. Patients who performed poorly were 3.4 times more likely to be discharged to institutionalized care than home, and skilled nursing facility admission was more likely than admission to an inpatient rehabilitation facility. Patients with average performance were 1.9 times more likely to be discharged to institutionalized care.

Thorpe ER, Garrett KB, Smith AM, et al. Outcome measure scores predict discharge destination in patients with acute and subacute stroke: a systematic review and series of meta-analyses. J Neurol Phys Ther. 2018;42(1):2-11.

Do Green Leafy Vegetables Slow Brain Aging?

Eating about one serving per day of green, leafy vegetables may be linked to a slower rate of brain aging, according to a study published online ahead of print December 20, 2017, in Neurology. Researchers followed 960 cognitively normal people with an average age of 81 for an average of 4.7 years. In a linear mixed model adjusted for age, sex, education, cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green, leafy vegetables was associated with slower cognitive decline. Participants in the highest quintile of vegetable intake were the equivalent of 11 years younger, compared with people who never ate vegetables. Higher intake of phylloquinone, lutein, nitrate, folate, kaempferol, and alpha-tocopherol were associated with slower cognitive decline.

Morris MC, Wang Y, Barnes LL, et al. Nutrients and bioactives in green leafy vegetables and cognitive decline: prospective study. Neurology. 2017 Dec 20 [Epub ahead of print].

Data Clarify the Genetic Profile of Dementia With Lewy Bodies

Research has increased understanding of the unique genetic profile of dementia with Lewy bodies. In a study published January 17 in Lancet Neurology, researchers genotyped 1,743 patients with dementia with Lewy bodies and 4,454 controls. APOE and GBA had the same associations with dementia with Lewy bodies as they do with Alzheimer’s disease and Parkinson’s disease, respectively. SNCA, which is associated with Parkinson’s disease, also was associated with dementia with Lewy bodies, but through a different part of the gene. Evidence suggested that CNTN1 is associated with dementia with Lewy bodies, but the result was not statistically significant. The authors estimated that the heritable component of the disorder is approximately 36%. Common genetic variability has a role in the disease, said the authors.

Guerreiro R, Ross OA, Kun-Rodrigues C, et al. Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study. Lancet Neurol. 2018;17(1):64-74.

Preterm Newborns Have Altered Cerebral Perfusion

Altered regional cortical blood flow (CBF) in infants born very preterm at term-equivalent age may reflect early brain dysmaturation despite the absence of cerebral cortical injury, according to a study published online ahead of print November 30, 2017 in the Journal of Pediatrics. In this prospective, cross-sectional study, researchers used noninvasive 3T arterial spin labeling MRI to quantify regional CBF in the cerebral cortex of 202 infants, 98 of whom were born preterm. Analyses were performed controlling for sex, gestational age, and age at MRI. Infants born preterm had greater global CBF and greater absolute regional CBF in all brain regions except the insula. Relative CBF in the insula, anterior cingulate cortex, and auditory cortex were decreased significantly in infants born preterm, compared with infants born at full term.

Bouyssi-Kobar M, Murnick J, Brossard-Racine M, et al. Altered cerebral perfusion in infants born preterm compared with infants born full term. J Pediatr. 2017 Nov 30 [Epub ahead of print].

—Kimberly Williams