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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.
