News Roundup

A second brain death examination in patients older than 1 year is largely unecessary and may negatively affect organ donation, according to a report in the January 11 online Neurology. “In practice, observation time to a second neurologic examination was three times longer than the proposed guideline and associated with substantial intensive care unit costs and loss of viable organs,” researchers stated. The investigators reviewed data for 1,229 adult and 82 pediatric patients who had been pronounced brain-dead. No patients who were declared brain-dead regained brainstem function after repeat examination. The mean brain death declaration interval between the two examinations was 19.2 hours. Consent for organ donation decreased from 57% to 45% as the brain death declaration interval increased. However, refusal of organ donation increased from 23% to 36% as the brain death interval increased. A total of 166 patients (12%) sustained a cardiac arrest between the two examinations or after the second examination.

Most antiepileptic drugs (AEDs) were associated with an increased risk of nontraumatic fractures in patients 50 and older, according to a study in the January Archives of Neurology. A total of 15,792 persons with nontraumatic fractures of the wrist, hip, and vertebra were analyzed. Each patient was matched for age, sex, ethnicity, and comorbidity with as many as three controls (n = 47,289). Prior AED use among participants included carbamazepine, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproic acid, and vigabatrin. The researchers found a significant increase in fracture risk for most of the AEDs (carbamazepine, clonazepam, gabapentin, phenobarbital, and phenytoin). The adjusted odds ratios (ORs) ranged from 1.24 for clonazepam use to 1.91 for phenytoin use. Valproic acid (adjusted OR, 1.10) was the only AED not associated with an increased fracture risk. “Further studies are warranted to assess the risk of nontraumatic fractures with the newer AEDs and to determine the efficacy of osteoprotective medications in this population,” the researchers stated.

Although some pediatric patients with multiple sclerosis (MS) refractory to initial treatment may effectively switch between first-line disease-modifying therapies (DMTs), some may require second-line therapeutic interventions, per a report in the December 13, 2010, online Archives of Neurology. Researchers reviewed the records of 258 children with a confirmed diagnosis of MS and who had taken DMTs. Interferon beta and glatiramer acetate were the two most frequently used first-line DMTs. Overall, 144 children (55.8%) continued to receive one therapy, while 65 (25.2%) received two sequential therapies, 29 (11.2%) received three therapies, and 20 (7.8%) received four or more therapies during a mean observation period of 3.9 years. “Second-line DMT use was restricted to interferon beta and glatiramer acetate in 203 children (78.7%), whereas other treatments such as broad-spectrum chemotherapies (cyclophosphamide, mitoxantrone hydrochloride), natalizumab, corticosteroids (monthly), and daclizumab were used at some point during the observation period for disease management in 55 children (21.3%),” stated the investigators.

Transient pregnancy restless legs syndrome is a significant risk factor for developing a future chronic idiopathic restless legs syndrome form, and for a new transient symptomatology in a future pregnancy, according to a study in the December 7, 2010, Neurology. Seventy-four women who experienced restless legs syndrome during a previous pregnancy, and 133 who did not, were included in the study. The incidence of restless legs syndrome was 56% person/year in women who experienced the transient pregnancy restless legs syndrome form, versus 12.6% person/year in women who did not, with a significant fourfold increased risk of developing chronic restless legs syndrome in women who presented with restless legs syndrome in their previous pregnancy. “Considering further new pregnancies during the follow-up period, restless legs symptoms reappeared in 58% of the cases, while they emerged for the first time in only 3% of women who had never experienced restless legs syndrome,” stated the authors. 

The cancer drug paclitaxel may promote the regeneration of injured nerve cells in the CNS after spinal cord injury, according to a study in the online January 27 Science. Researchers found that the drug has a dual role in spinal cord repair in rodents, stabilizing the microtuble so that injured nerve cells regain their ability to grow and preventing the production of inhibitory substances in the scar tissue. Moderate microtubule stabilization decreased scar formation via various cellular mechanisms, including dampening of transforming growth factor-β signaling. “It prevented accumulation of chondroitin sulfate proteoglycans and rendered the lesion site permissive for axon regeneration of growth competent sensory neurons,” stated the investigators. “Microtubule stabilization also promoted growth of CNS axons of the Raphe-spinal tract and led to functional improvement.”

Among patients with acute ischemic stroke, blacks have a lower mortality than whites, which may be attributable to differences in receiving life-sustaining interventions and end-of-life care, researchers reported in the February 1 Annals of Internal Medicine. The findings are based on 5,319 black and 18,340 white patients 18 and older who were hospitalized with acute ischemic stroke. The overall in-hospital mortality rate was lower for black patients than for white patients (5.0% vs 7.4%), as was all-cause mortality at 30 days (6.1% vs 11.4%) and one year (16.5% vs 24.4%). After propensity score adjustment, black race was independently associated with lower in-hospital mortality (odds ratio [OR], 0.77) and all-cause mortality up to one year (OR, 0.86). “After adjustment for the probability of dying in the hospital, black patients with stroke were more likely to receive life-sustaining interventions (OR, 1.22) but less likely to be discharged to hospice (OR, 0.25),” the researchers concluded.

A second brain death examination in patients older than 1 year is largely unecessary and may negatively affect organ donation, according to a report in the January 11 online Neurology. “In practice, observation time to a second neurologic examination was three times longer than the proposed guideline and associated with substantial intensive care unit costs and loss of viable organs,” researchers stated. The investigators reviewed data for 1,229 adult and 82 pediatric patients who had been pronounced brain-dead. No patients who were declared brain-dead regained brainstem function after repeat examination. The mean brain death declaration interval between the two examinations was 19.2 hours. Consent for organ donation decreased from 57% to 45% as the brain death declaration interval increased. However, refusal of organ donation increased from 23% to 36% as the brain death interval increased. A total of 166 patients (12%) sustained a cardiac arrest between the two examinations or after the second examination.

Most antiepileptic drugs (AEDs) were associated with an increased risk of nontraumatic fractures in patients 50 and older, according to a study in the January Archives of Neurology. A total of 15,792 persons with nontraumatic fractures of the wrist, hip, and vertebra were analyzed. Each patient was matched for age, sex, ethnicity, and comorbidity with as many as three controls (n = 47,289). Prior AED use among participants included carbamazepine, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproic acid, and vigabatrin. The researchers found a significant increase in fracture risk for most of the AEDs (carbamazepine, clonazepam, gabapentin, phenobarbital, and phenytoin). The adjusted odds ratios (ORs) ranged from 1.24 for clonazepam use to 1.91 for phenytoin use. Valproic acid (adjusted OR, 1.10) was the only AED not associated with an increased fracture risk. “Further studies are warranted to assess the risk of nontraumatic fractures with the newer AEDs and to determine the efficacy of osteoprotective medications in this population,” the researchers stated.

Although some pediatric patients with multiple sclerosis (MS) refractory to initial treatment may effectively switch between first-line disease-modifying therapies (DMTs), some may require second-line therapeutic interventions, per a report in the December 13, 2010, online Archives of Neurology. Researchers reviewed the records of 258 children with a confirmed diagnosis of MS and who had taken DMTs. Interferon beta and glatiramer acetate were the two most frequently used first-line DMTs. Overall, 144 children (55.8%) continued to receive one therapy, while 65 (25.2%) received two sequential therapies, 29 (11.2%) received three therapies, and 20 (7.8%) received four or more therapies during a mean observation period of 3.9 years. “Second-line DMT use was restricted to interferon beta and glatiramer acetate in 203 children (78.7%), whereas other treatments such as broad-spectrum chemotherapies (cyclophosphamide, mitoxantrone hydrochloride), natalizumab, corticosteroids (monthly), and daclizumab were used at some point during the observation period for disease management in 55 children (21.3%),” stated the investigators.

Transient pregnancy restless legs syndrome is a significant risk factor for developing a future chronic idiopathic restless legs syndrome form, and for a new transient symptomatology in a future pregnancy, according to a study in the December 7, 2010, Neurology. Seventy-four women who experienced restless legs syndrome during a previous pregnancy, and 133 who did not, were included in the study. The incidence of restless legs syndrome was 56% person/year in women who experienced the transient pregnancy restless legs syndrome form, versus 12.6% person/year in women who did not, with a significant fourfold increased risk of developing chronic restless legs syndrome in women who presented with restless legs syndrome in their previous pregnancy. “Considering further new pregnancies during the follow-up period, restless legs symptoms reappeared in 58% of the cases, while they emerged for the first time in only 3% of women who had never experienced restless legs syndrome,” stated the authors. 

The cancer drug paclitaxel may promote the regeneration of injured nerve cells in the CNS after spinal cord injury, according to a study in the online January 27 Science. Researchers found that the drug has a dual role in spinal cord repair in rodents, stabilizing the microtuble so that injured nerve cells regain their ability to grow and preventing the production of inhibitory substances in the scar tissue. Moderate microtubule stabilization decreased scar formation via various cellular mechanisms, including dampening of transforming growth factor-β signaling. “It prevented accumulation of chondroitin sulfate proteoglycans and rendered the lesion site permissive for axon regeneration of growth competent sensory neurons,” stated the investigators. “Microtubule stabilization also promoted growth of CNS axons of the Raphe-spinal tract and led to functional improvement.”

Among patients with acute ischemic stroke, blacks have a lower mortality than whites, which may be attributable to differences in receiving life-sustaining interventions and end-of-life care, researchers reported in the February 1 Annals of Internal Medicine. The findings are based on 5,319 black and 18,340 white patients 18 and older who were hospitalized with acute ischemic stroke. The overall in-hospital mortality rate was lower for black patients than for white patients (5.0% vs 7.4%), as was all-cause mortality at 30 days (6.1% vs 11.4%) and one year (16.5% vs 24.4%). After propensity score adjustment, black race was independently associated with lower in-hospital mortality (odds ratio [OR], 0.77) and all-cause mortality up to one year (OR, 0.86). “After adjustment for the probability of dying in the hospital, black patients with stroke were more likely to receive life-sustaining interventions (OR, 1.22) but less likely to be discharged to hospice (OR, 0.25),” the researchers concluded.

A second brain death examination in patients older than 1 year is largely unecessary and may negatively affect organ donation, according to a report in the January 11 online Neurology. “In practice, observation time to a second neurologic examination was three times longer than the proposed guideline and associated with substantial intensive care unit costs and loss of viable organs,” researchers stated. The investigators reviewed data for 1,229 adult and 82 pediatric patients who had been pronounced brain-dead. No patients who were declared brain-dead regained brainstem function after repeat examination. The mean brain death declaration interval between the two examinations was 19.2 hours. Consent for organ donation decreased from 57% to 45% as the brain death declaration interval increased. However, refusal of organ donation increased from 23% to 36% as the brain death interval increased. A total of 166 patients (12%) sustained a cardiac arrest between the two examinations or after the second examination.

Most antiepileptic drugs (AEDs) were associated with an increased risk of nontraumatic fractures in patients 50 and older, according to a study in the January Archives of Neurology. A total of 15,792 persons with nontraumatic fractures of the wrist, hip, and vertebra were analyzed. Each patient was matched for age, sex, ethnicity, and comorbidity with as many as three controls (n = 47,289). Prior AED use among participants included carbamazepine, clonazepam, ethosuximide, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproic acid, and vigabatrin. The researchers found a significant increase in fracture risk for most of the AEDs (carbamazepine, clonazepam, gabapentin, phenobarbital, and phenytoin). The adjusted odds ratios (ORs) ranged from 1.24 for clonazepam use to 1.91 for phenytoin use. Valproic acid (adjusted OR, 1.10) was the only AED not associated with an increased fracture risk. “Further studies are warranted to assess the risk of nontraumatic fractures with the newer AEDs and to determine the efficacy of osteoprotective medications in this population,” the researchers stated.

Although some pediatric patients with multiple sclerosis (MS) refractory to initial treatment may effectively switch between first-line disease-modifying therapies (DMTs), some may require second-line therapeutic interventions, per a report in the December 13, 2010, online Archives of Neurology. Researchers reviewed the records of 258 children with a confirmed diagnosis of MS and who had taken DMTs. Interferon beta and glatiramer acetate were the two most frequently used first-line DMTs. Overall, 144 children (55.8%) continued to receive one therapy, while 65 (25.2%) received two sequential therapies, 29 (11.2%) received three therapies, and 20 (7.8%) received four or more therapies during a mean observation period of 3.9 years. “Second-line DMT use was restricted to interferon beta and glatiramer acetate in 203 children (78.7%), whereas other treatments such as broad-spectrum chemotherapies (cyclophosphamide, mitoxantrone hydrochloride), natalizumab, corticosteroids (monthly), and daclizumab were used at some point during the observation period for disease management in 55 children (21.3%),” stated the investigators.

Transient pregnancy restless legs syndrome is a significant risk factor for developing a future chronic idiopathic restless legs syndrome form, and for a new transient symptomatology in a future pregnancy, according to a study in the December 7, 2010, Neurology. Seventy-four women who experienced restless legs syndrome during a previous pregnancy, and 133 who did not, were included in the study. The incidence of restless legs syndrome was 56% person/year in women who experienced the transient pregnancy restless legs syndrome form, versus 12.6% person/year in women who did not, with a significant fourfold increased risk of developing chronic restless legs syndrome in women who presented with restless legs syndrome in their previous pregnancy. “Considering further new pregnancies during the follow-up period, restless legs symptoms reappeared in 58% of the cases, while they emerged for the first time in only 3% of women who had never experienced restless legs syndrome,” stated the authors. 

The cancer drug paclitaxel may promote the regeneration of injured nerve cells in the CNS after spinal cord injury, according to a study in the online January 27 Science. Researchers found that the drug has a dual role in spinal cord repair in rodents, stabilizing the microtuble so that injured nerve cells regain their ability to grow and preventing the production of inhibitory substances in the scar tissue. Moderate microtubule stabilization decreased scar formation via various cellular mechanisms, including dampening of transforming growth factor-β signaling. “It prevented accumulation of chondroitin sulfate proteoglycans and rendered the lesion site permissive for axon regeneration of growth competent sensory neurons,” stated the investigators. “Microtubule stabilization also promoted growth of CNS axons of the Raphe-spinal tract and led to functional improvement.”

Among patients with acute ischemic stroke, blacks have a lower mortality than whites, which may be attributable to differences in receiving life-sustaining interventions and end-of-life care, researchers reported in the February 1 Annals of Internal Medicine. The findings are based on 5,319 black and 18,340 white patients 18 and older who were hospitalized with acute ischemic stroke. The overall in-hospital mortality rate was lower for black patients than for white patients (5.0% vs 7.4%), as was all-cause mortality at 30 days (6.1% vs 11.4%) and one year (16.5% vs 24.4%). After propensity score adjustment, black race was independently associated with lower in-hospital mortality (odds ratio [OR], 0.77) and all-cause mortality up to one year (OR, 0.86). “After adjustment for the probability of dying in the hospital, black patients with stroke were more likely to receive life-sustaining interventions (OR, 1.22) but less likely to be discharged to hospice (OR, 0.25),” the researchers concluded.

High levels of high-density lipoprotein (HDL) appear to be associated with a reduced risk for Alzheimer’s disease in older adults, according to a report in the December 2010 issue of Archives of Neurology. Researchers studied 1,130 older adults with no history of dementia or cognitive impairment. During 4,469 person-years of follow-up, there were 101 new cases of Alzheimer’s disease, of which 89 were probable and 12 were possible. Higher levels of HDL cholesterol (>55 mg/dL) were associated with a decreased risk of both probable and possible Alzheimer’s disease compared with lower HDL cholesterol  levels, even after adjusting for age, sex, education, ethnic group, and APOE ε4 genotype.

NFKBIA gene deletion has been identified in up to one of every four cases of glioblastoma, according to a report published December 22, 2010, online ahead of print in the New England Journal of Medicine. The gene deletion contributes to tumor development, promotes resistance to therapy, and considerably worsens a patient’s prospects for survival. NFKBIA deletion triggers biochemical processes similar to those resulting from mutations in EGFR. Investigators analyzed several hundred tumor samples and found NFKBIA deletions in 25%. EGFR mutations were identified in about a third of the samples. But only 5% of samples had both gene aberrations; thus, the two defects taken together accounted for a majority of all glioblastomas. Patients with either the NFKBIA or EGFR abnormality had a significantly shorter survival, despite maximal therapy, than the remaining patients (about 40%) with neither gene defect.

African Americans and those with lower socioeconomic status appear to have more severe parkinsonism with greater levels of disability, according to findings published December 13, 2010, online ahead of print by Archives of Neurology. Researchers studied 1,159 patients with parkinsonism between 2003 and 2008. Of the participating patients, 93.4% were white, 6.1% were African American, 61.2% earned more than $50,000 annually, 62.7 completed college, and 79.2% had a diagnosis of Parkinson’s disease. When compared with white patients, those who were African American tended to have more severe parkinsonism and also greater disability. Lower income and lower education level were also associated with increased disease severity and disability. Disparities were also seen in treatment patterns. African Americans were prescribed fewer medications to treat parkinsonism at their first clinic visit, were less likely to receive newer dopaminergic medications, and more likely to receive antipsychotic medications.

Differential consumption of fish may contribute to the racial and geographic disparities in stroke, researchers reported in the December 22, 2010, Neurology. The findings are based on the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 21,675 US persons ages 45 and older, with oversampling from the southeastern Stroke Belt and Buckle and African Americans. A total of 5,022 (23%) participants consumed two or more servings per week of nonfried fi sh. Factors associated with inadequate intake of nonfried fish included living in the Stroke Belt (vs non-Belt) (odds ratio [OR], 0.83) and living in the Stroke Buckle (vs non-Belt) (OR, 0.89); factors associated with two or more servings per week of fried fi sh included being African American (vs white) (OR, 3.59), living in the Stroke Belt (vs non-Belt) (OR, 1.32), and living in the Stroke Buckle (vs non-Belt) (OR, 1.17).

Outcome in patients with acute ischemic stroke is significantly better in those who undergo thrombolysis, compared with those who do not, according to a report that was published in the November 23, 2010, online BMJ. A total of 29,228 patients were included in the analysis, which was adjusted for age and baseline severity, and the main outcome measure was functional outcomes at 90 days as measured by score on the modified Rankin Scale. “The median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group),” stated the investigators. “The distribution of scores on the modified Rankin Scale was better among all thrombolysis patients than controls (odds ratio 1.6)…. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.”

—Glenn S. Williams and Colby Stong 
 

High levels of high-density lipoprotein (HDL) appear to be associated with a reduced risk for Alzheimer’s disease in older adults, according to a report in the December 2010 issue of Archives of Neurology. Researchers studied 1,130 older adults with no history of dementia or cognitive impairment. During 4,469 person-years of follow-up, there were 101 new cases of Alzheimer’s disease, of which 89 were probable and 12 were possible. Higher levels of HDL cholesterol (>55 mg/dL) were associated with a decreased risk of both probable and possible Alzheimer’s disease compared with lower HDL cholesterol  levels, even after adjusting for age, sex, education, ethnic group, and APOE ε4 genotype.

NFKBIA gene deletion has been identified in up to one of every four cases of glioblastoma, according to a report published December 22, 2010, online ahead of print in the New England Journal of Medicine. The gene deletion contributes to tumor development, promotes resistance to therapy, and considerably worsens a patient’s prospects for survival. NFKBIA deletion triggers biochemical processes similar to those resulting from mutations in EGFR. Investigators analyzed several hundred tumor samples and found NFKBIA deletions in 25%. EGFR mutations were identified in about a third of the samples. But only 5% of samples had both gene aberrations; thus, the two defects taken together accounted for a majority of all glioblastomas. Patients with either the NFKBIA or EGFR abnormality had a significantly shorter survival, despite maximal therapy, than the remaining patients (about 40%) with neither gene defect.

African Americans and those with lower socioeconomic status appear to have more severe parkinsonism with greater levels of disability, according to findings published December 13, 2010, online ahead of print by Archives of Neurology. Researchers studied 1,159 patients with parkinsonism between 2003 and 2008. Of the participating patients, 93.4% were white, 6.1% were African American, 61.2% earned more than $50,000 annually, 62.7 completed college, and 79.2% had a diagnosis of Parkinson’s disease. When compared with white patients, those who were African American tended to have more severe parkinsonism and also greater disability. Lower income and lower education level were also associated with increased disease severity and disability. Disparities were also seen in treatment patterns. African Americans were prescribed fewer medications to treat parkinsonism at their first clinic visit, were less likely to receive newer dopaminergic medications, and more likely to receive antipsychotic medications.

Differential consumption of fish may contribute to the racial and geographic disparities in stroke, researchers reported in the December 22, 2010, Neurology. The findings are based on the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 21,675 US persons ages 45 and older, with oversampling from the southeastern Stroke Belt and Buckle and African Americans. A total of 5,022 (23%) participants consumed two or more servings per week of nonfried fi sh. Factors associated with inadequate intake of nonfried fish included living in the Stroke Belt (vs non-Belt) (odds ratio [OR], 0.83) and living in the Stroke Buckle (vs non-Belt) (OR, 0.89); factors associated with two or more servings per week of fried fi sh included being African American (vs white) (OR, 3.59), living in the Stroke Belt (vs non-Belt) (OR, 1.32), and living in the Stroke Buckle (vs non-Belt) (OR, 1.17).

Outcome in patients with acute ischemic stroke is significantly better in those who undergo thrombolysis, compared with those who do not, according to a report that was published in the November 23, 2010, online BMJ. A total of 29,228 patients were included in the analysis, which was adjusted for age and baseline severity, and the main outcome measure was functional outcomes at 90 days as measured by score on the modified Rankin Scale. “The median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group),” stated the investigators. “The distribution of scores on the modified Rankin Scale was better among all thrombolysis patients than controls (odds ratio 1.6)…. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.”

—Glenn S. Williams and Colby Stong 
 

High levels of high-density lipoprotein (HDL) appear to be associated with a reduced risk for Alzheimer’s disease in older adults, according to a report in the December 2010 issue of Archives of Neurology. Researchers studied 1,130 older adults with no history of dementia or cognitive impairment. During 4,469 person-years of follow-up, there were 101 new cases of Alzheimer’s disease, of which 89 were probable and 12 were possible. Higher levels of HDL cholesterol (>55 mg/dL) were associated with a decreased risk of both probable and possible Alzheimer’s disease compared with lower HDL cholesterol  levels, even after adjusting for age, sex, education, ethnic group, and APOE ε4 genotype.

NFKBIA gene deletion has been identified in up to one of every four cases of glioblastoma, according to a report published December 22, 2010, online ahead of print in the New England Journal of Medicine. The gene deletion contributes to tumor development, promotes resistance to therapy, and considerably worsens a patient’s prospects for survival. NFKBIA deletion triggers biochemical processes similar to those resulting from mutations in EGFR. Investigators analyzed several hundred tumor samples and found NFKBIA deletions in 25%. EGFR mutations were identified in about a third of the samples. But only 5% of samples had both gene aberrations; thus, the two defects taken together accounted for a majority of all glioblastomas. Patients with either the NFKBIA or EGFR abnormality had a significantly shorter survival, despite maximal therapy, than the remaining patients (about 40%) with neither gene defect.

African Americans and those with lower socioeconomic status appear to have more severe parkinsonism with greater levels of disability, according to findings published December 13, 2010, online ahead of print by Archives of Neurology. Researchers studied 1,159 patients with parkinsonism between 2003 and 2008. Of the participating patients, 93.4% were white, 6.1% were African American, 61.2% earned more than $50,000 annually, 62.7 completed college, and 79.2% had a diagnosis of Parkinson’s disease. When compared with white patients, those who were African American tended to have more severe parkinsonism and also greater disability. Lower income and lower education level were also associated with increased disease severity and disability. Disparities were also seen in treatment patterns. African Americans were prescribed fewer medications to treat parkinsonism at their first clinic visit, were less likely to receive newer dopaminergic medications, and more likely to receive antipsychotic medications.

Differential consumption of fish may contribute to the racial and geographic disparities in stroke, researchers reported in the December 22, 2010, Neurology. The findings are based on the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, which included 21,675 US persons ages 45 and older, with oversampling from the southeastern Stroke Belt and Buckle and African Americans. A total of 5,022 (23%) participants consumed two or more servings per week of nonfried fi sh. Factors associated with inadequate intake of nonfried fish included living in the Stroke Belt (vs non-Belt) (odds ratio [OR], 0.83) and living in the Stroke Buckle (vs non-Belt) (OR, 0.89); factors associated with two or more servings per week of fried fi sh included being African American (vs white) (OR, 3.59), living in the Stroke Belt (vs non-Belt) (OR, 1.32), and living in the Stroke Buckle (vs non-Belt) (OR, 1.17).

Outcome in patients with acute ischemic stroke is significantly better in those who undergo thrombolysis, compared with those who do not, according to a report that was published in the November 23, 2010, online BMJ. A total of 29,228 patients were included in the analysis, which was adjusted for age and baseline severity, and the main outcome measure was functional outcomes at 90 days as measured by score on the modified Rankin Scale. “The median severity at baseline was the same for patients who underwent thrombolysis and controls (median baseline stroke scale score: 12 for each group),” stated the investigators. “The distribution of scores on the modified Rankin Scale was better among all thrombolysis patients than controls (odds ratio 1.6)…. Increasing age is associated with poorer outcome but the association between thrombolysis treatment and improved outcome is maintained in very elderly people. Age alone should not be a barrier to treatment.”

—Glenn S. Williams and Colby Stong 
 

Out-of-hospital administration of hypertonic fluids following severe traumatic brain injury (TBI) offers no additional benefits over normal saline in patients who are not in hypovolemic shock, according to a report in the October 6 JAMA. In a double-blind, randomized, placebo-controlled multi-center trial of patients 15 and older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less, subjects received a single 250-mL bolus of either hypertonic saline with dextran (7.5% saline/6% dextran 70), hypertonic saline (7.5% saline), or normal saline (0.9% saline). Six-month data, which were available for 1,087 of the 1,282 patients enrolled in the study, showed no difference in neurologic outcome and no significant differences in disability by treatment group. Survival rates at 28 days were 74.3% in the hypertonic/dextran group, 75.7% in the hypertonic group, and 75.1% with normal saline.

Out-of-hospital administration of hypertonic fluids following severe traumatic brain injury (TBI) offers no additional benefits over normal saline in patients who are not in hypovolemic shock, according to a report in the October 6 JAMA. In a double-blind, randomized, placebo-controlled multi-center trial of patients 15 and older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less, subjects received a single 250-mL bolus of either hypertonic saline with dextran (7.5% saline/6% dextran 70), hypertonic saline (7.5% saline), or normal saline (0.9% saline). Six-month data, which were available for 1,087 of the 1,282 patients enrolled in the study, showed no difference in neurologic outcome and no significant differences in disability by treatment group. Survival rates at 28 days were 74.3% in the hypertonic/dextran group, 75.7% in the hypertonic group, and 75.1% with normal saline.

Out-of-hospital administration of hypertonic fluids following severe traumatic brain injury (TBI) offers no additional benefits over normal saline in patients who are not in hypovolemic shock, according to a report in the October 6 JAMA. In a double-blind, randomized, placebo-controlled multi-center trial of patients 15 and older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less, subjects received a single 250-mL bolus of either hypertonic saline with dextran (7.5% saline/6% dextran 70), hypertonic saline (7.5% saline), or normal saline (0.9% saline). Six-month data, which were available for 1,087 of the 1,282 patients enrolled in the study, showed no difference in neurologic outcome and no significant differences in disability by treatment group. Survival rates at 28 days were 74.3% in the hypertonic/dextran group, 75.7% in the hypertonic group, and 75.1% with normal saline.

Baseline levels of bioavailable testosterone in older men can predict a lower risk of developing Alzheimer’s disease, researchers reported in the October Journal of Alzheimer’s Disease. The study of 153 community-dwelling Chinese older men without dementia at baseline compared the effects of serum total testosterone, bioavailable testosterone, and sex hormone binding globulin on the risk of subsequent Alzheimer’s disease. At one-year follow-up, 10 subjects had been diagnosed with Alzheimer’s disease. After the investigators adjusted for age, education, BMI, fasting plasma glucose, and serum HDL cholesterol levels, logistic regression analysis determined independent predictors of the disease, including baseline serum bioavailable testosterone levels (adjusted relative risk [RR], 0.22), systolic blood pressure (RR, 1.04), and apolipoprotein ε4 genotype (RR, 5.04).

Exposure to multiple antiepileptic drugs (AEDs), older age, and lower education levels are important predictors of infertility in women with epilepsy, per research in the October 12 Neurology. The study followed 375 women with epilepsy who enrolled in the Kerala Registry of Epilepsy and Pregnancy in India during their preconception examination. The majority of subjects became pregnant within two years; however, 38.4% of the women remained infertile. Infertility rates were lowest for those with no exposure to AEDs and higher for those with exposure to AEDs. “Those exposed to phenobarbital had significant risk of infertility, but no such trend was observed with valproate or other drugs,” the researchers noted. Use of three or more AEDs was associated with a 2.91 odds ratio of infertility.

One oral dose of 200 mg to 400 mg of ibuprofen is an effective treatment for acute migraine headaches, according to a review of nine studies published October 6 in the Cochrane Database of Systematic Reviews. The analysis included 4,373 participants and 5,223 migraine attacks and compared ibuprofen with placebo or other active comparators. Two hours after taking 400 mg of ibuprofen, one in four subjects reported that their pain level went from moderate or severe to no pain, and about half of subjects reported that their pain level diminished to no greater than mild. One in 10 subjects taking placebo were pain free at two hours, while one in four subjects taking placebo reported pain levels no greater than mild. Adverse events reported in patients taking ibuprofen were mild, transient, and similar to those of subjects taking placebo.

Botox (onabotulinumtoxinA) has received FDA approval as a prophylactic treatment for headaches among adult patients with chronic migraine. The treatment is indicated for use in adult patients who experience 15 or more headache days per month that last four hours a day or longer. According to manufacturer Allergan (Irvine, California), when injected at labeled doses and in the recommended locations in the head and neck, Botox can prevent migraine headaches for up to three months, depending on the patient. It is the first clinically studied prophylactic treatment to be approved specifically for patients with chronic migraine.

Brain changes evident on neuroimaging may detect subclinical changes in patients with idiopathic rapid-eye-movement sleep behavior disorder (IRBD) before clinical manifestations of parkinsonism, per research in the October Lancet Neurology. In a prospective study of 43 patients with IRBD, investigators assessed dopamine transporters uptake using 123I-FP-CIT SPECT and echogenicity of the substantia nigra using transcranial sonography. A total of 27 subjects (63%) had reduced 123I-FP-CIT binding or substantial nigra hyperechogenicity at baseline. At follow-up 2.5 years later, eight of these individuals (30%) had been diagnosed with a neurodegenerative disorder (five with Parkinson’s disease, two with dementia with Lewy bodies, and one with multiple system atrophy). All subjects with normal neuroimaging results at baseline did not develop a neurodegenerative disorder by follow-up.

Insulin resistance is a marker of increased risk of ischemic stroke, as reported in the October Archives of Neurology. In a prospective, population-based cohort study of 1,509 nondiabetic participants of the Northern Manhattan Study, researchers measured insulin sensitivity as expressed by the homeostasis model assessment of insulin resistance (HOMA-IR). Mean HOMA-IR was 2.3, and the highest quartile was at least 2.8. During a follow-up of 8.5 years, vascular events occurred in 180 subjects, with 46 ischemic strokes, 45 myocardial infarctions, and a total of 121 deaths due to vascular causes. Having a HOMA-IR in the highest quartile significantly predicted ischemic stroke risk, but not other vascular events. The researchers noted that this effect was independent of sex, race/ethnicity, traditional vascular risk factors, and components of metabolic syndrome.

Carotid artery stenting was associated with an increased risk of both periprocedural and intermediate to long-term outcomes but also with reductions in periprocedural myocardial infarction and cranial nerve injury, according to a large, comprehensive meta-analysis in the October 11 online Archives of Neurology. The analysis combined data from 13 randomized clinical trials, with a total of 7,477 participants, and found that stenting was associated with a 65% increase in death or stroke and 67% increase in any stroke. Stenting was associated with a 55% reduced risk of myocardial infarction and with an 85% reduction in risk of cranial nerve injury. “Strategies are urgently needed to identify patients who are best served by carotid artery stenting versus carotid endarterectomy,” the authors concluded.

—Rebecca K. Abma

Baseline levels of bioavailable testosterone in older men can predict a lower risk of developing Alzheimer’s disease, researchers reported in the October Journal of Alzheimer’s Disease. The study of 153 community-dwelling Chinese older men without dementia at baseline compared the effects of serum total testosterone, bioavailable testosterone, and sex hormone binding globulin on the risk of subsequent Alzheimer’s disease. At one-year follow-up, 10 subjects had been diagnosed with Alzheimer’s disease. After the investigators adjusted for age, education, BMI, fasting plasma glucose, and serum HDL cholesterol levels, logistic regression analysis determined independent predictors of the disease, including baseline serum bioavailable testosterone levels (adjusted relative risk [RR], 0.22), systolic blood pressure (RR, 1.04), and apolipoprotein ε4 genotype (RR, 5.04).

Exposure to multiple antiepileptic drugs (AEDs), older age, and lower education levels are important predictors of infertility in women with epilepsy, per research in the October 12 Neurology. The study followed 375 women with epilepsy who enrolled in the Kerala Registry of Epilepsy and Pregnancy in India during their preconception examination. The majority of subjects became pregnant within two years; however, 38.4% of the women remained infertile. Infertility rates were lowest for those with no exposure to AEDs and higher for those with exposure to AEDs. “Those exposed to phenobarbital had significant risk of infertility, but no such trend was observed with valproate or other drugs,” the researchers noted. Use of three or more AEDs was associated with a 2.91 odds ratio of infertility.

One oral dose of 200 mg to 400 mg of ibuprofen is an effective treatment for acute migraine headaches, according to a review of nine studies published October 6 in the Cochrane Database of Systematic Reviews. The analysis included 4,373 participants and 5,223 migraine attacks and compared ibuprofen with placebo or other active comparators. Two hours after taking 400 mg of ibuprofen, one in four subjects reported that their pain level went from moderate or severe to no pain, and about half of subjects reported that their pain level diminished to no greater than mild. One in 10 subjects taking placebo were pain free at two hours, while one in four subjects taking placebo reported pain levels no greater than mild. Adverse events reported in patients taking ibuprofen were mild, transient, and similar to those of subjects taking placebo.

Botox (onabotulinumtoxinA) has received FDA approval as a prophylactic treatment for headaches among adult patients with chronic migraine. The treatment is indicated for use in adult patients who experience 15 or more headache days per month that last four hours a day or longer. According to manufacturer Allergan (Irvine, California), when injected at labeled doses and in the recommended locations in the head and neck, Botox can prevent migraine headaches for up to three months, depending on the patient. It is the first clinically studied prophylactic treatment to be approved specifically for patients with chronic migraine.

Brain changes evident on neuroimaging may detect subclinical changes in patients with idiopathic rapid-eye-movement sleep behavior disorder (IRBD) before clinical manifestations of parkinsonism, per research in the October Lancet Neurology. In a prospective study of 43 patients with IRBD, investigators assessed dopamine transporters uptake using 123I-FP-CIT SPECT and echogenicity of the substantia nigra using transcranial sonography. A total of 27 subjects (63%) had reduced 123I-FP-CIT binding or substantial nigra hyperechogenicity at baseline. At follow-up 2.5 years later, eight of these individuals (30%) had been diagnosed with a neurodegenerative disorder (five with Parkinson’s disease, two with dementia with Lewy bodies, and one with multiple system atrophy). All subjects with normal neuroimaging results at baseline did not develop a neurodegenerative disorder by follow-up.

Insulin resistance is a marker of increased risk of ischemic stroke, as reported in the October Archives of Neurology. In a prospective, population-based cohort study of 1,509 nondiabetic participants of the Northern Manhattan Study, researchers measured insulin sensitivity as expressed by the homeostasis model assessment of insulin resistance (HOMA-IR). Mean HOMA-IR was 2.3, and the highest quartile was at least 2.8. During a follow-up of 8.5 years, vascular events occurred in 180 subjects, with 46 ischemic strokes, 45 myocardial infarctions, and a total of 121 deaths due to vascular causes. Having a HOMA-IR in the highest quartile significantly predicted ischemic stroke risk, but not other vascular events. The researchers noted that this effect was independent of sex, race/ethnicity, traditional vascular risk factors, and components of metabolic syndrome.

Carotid artery stenting was associated with an increased risk of both periprocedural and intermediate to long-term outcomes but also with reductions in periprocedural myocardial infarction and cranial nerve injury, according to a large, comprehensive meta-analysis in the October 11 online Archives of Neurology. The analysis combined data from 13 randomized clinical trials, with a total of 7,477 participants, and found that stenting was associated with a 65% increase in death or stroke and 67% increase in any stroke. Stenting was associated with a 55% reduced risk of myocardial infarction and with an 85% reduction in risk of cranial nerve injury. “Strategies are urgently needed to identify patients who are best served by carotid artery stenting versus carotid endarterectomy,” the authors concluded.

—Rebecca K. Abma

Baseline levels of bioavailable testosterone in older men can predict a lower risk of developing Alzheimer’s disease, researchers reported in the October Journal of Alzheimer’s Disease. The study of 153 community-dwelling Chinese older men without dementia at baseline compared the effects of serum total testosterone, bioavailable testosterone, and sex hormone binding globulin on the risk of subsequent Alzheimer’s disease. At one-year follow-up, 10 subjects had been diagnosed with Alzheimer’s disease. After the investigators adjusted for age, education, BMI, fasting plasma glucose, and serum HDL cholesterol levels, logistic regression analysis determined independent predictors of the disease, including baseline serum bioavailable testosterone levels (adjusted relative risk [RR], 0.22), systolic blood pressure (RR, 1.04), and apolipoprotein ε4 genotype (RR, 5.04).

Exposure to multiple antiepileptic drugs (AEDs), older age, and lower education levels are important predictors of infertility in women with epilepsy, per research in the October 12 Neurology. The study followed 375 women with epilepsy who enrolled in the Kerala Registry of Epilepsy and Pregnancy in India during their preconception examination. The majority of subjects became pregnant within two years; however, 38.4% of the women remained infertile. Infertility rates were lowest for those with no exposure to AEDs and higher for those with exposure to AEDs. “Those exposed to phenobarbital had significant risk of infertility, but no such trend was observed with valproate or other drugs,” the researchers noted. Use of three or more AEDs was associated with a 2.91 odds ratio of infertility.

One oral dose of 200 mg to 400 mg of ibuprofen is an effective treatment for acute migraine headaches, according to a review of nine studies published October 6 in the Cochrane Database of Systematic Reviews. The analysis included 4,373 participants and 5,223 migraine attacks and compared ibuprofen with placebo or other active comparators. Two hours after taking 400 mg of ibuprofen, one in four subjects reported that their pain level went from moderate or severe to no pain, and about half of subjects reported that their pain level diminished to no greater than mild. One in 10 subjects taking placebo were pain free at two hours, while one in four subjects taking placebo reported pain levels no greater than mild. Adverse events reported in patients taking ibuprofen were mild, transient, and similar to those of subjects taking placebo.

Botox (onabotulinumtoxinA) has received FDA approval as a prophylactic treatment for headaches among adult patients with chronic migraine. The treatment is indicated for use in adult patients who experience 15 or more headache days per month that last four hours a day or longer. According to manufacturer Allergan (Irvine, California), when injected at labeled doses and in the recommended locations in the head and neck, Botox can prevent migraine headaches for up to three months, depending on the patient. It is the first clinically studied prophylactic treatment to be approved specifically for patients with chronic migraine.

Brain changes evident on neuroimaging may detect subclinical changes in patients with idiopathic rapid-eye-movement sleep behavior disorder (IRBD) before clinical manifestations of parkinsonism, per research in the October Lancet Neurology. In a prospective study of 43 patients with IRBD, investigators assessed dopamine transporters uptake using 123I-FP-CIT SPECT and echogenicity of the substantia nigra using transcranial sonography. A total of 27 subjects (63%) had reduced 123I-FP-CIT binding or substantial nigra hyperechogenicity at baseline. At follow-up 2.5 years later, eight of these individuals (30%) had been diagnosed with a neurodegenerative disorder (five with Parkinson’s disease, two with dementia with Lewy bodies, and one with multiple system atrophy). All subjects with normal neuroimaging results at baseline did not develop a neurodegenerative disorder by follow-up.

Insulin resistance is a marker of increased risk of ischemic stroke, as reported in the October Archives of Neurology. In a prospective, population-based cohort study of 1,509 nondiabetic participants of the Northern Manhattan Study, researchers measured insulin sensitivity as expressed by the homeostasis model assessment of insulin resistance (HOMA-IR). Mean HOMA-IR was 2.3, and the highest quartile was at least 2.8. During a follow-up of 8.5 years, vascular events occurred in 180 subjects, with 46 ischemic strokes, 45 myocardial infarctions, and a total of 121 deaths due to vascular causes. Having a HOMA-IR in the highest quartile significantly predicted ischemic stroke risk, but not other vascular events. The researchers noted that this effect was independent of sex, race/ethnicity, traditional vascular risk factors, and components of metabolic syndrome.

Carotid artery stenting was associated with an increased risk of both periprocedural and intermediate to long-term outcomes but also with reductions in periprocedural myocardial infarction and cranial nerve injury, according to a large, comprehensive meta-analysis in the October 11 online Archives of Neurology. The analysis combined data from 13 randomized clinical trials, with a total of 7,477 participants, and found that stenting was associated with a 65% increase in death or stroke and 67% increase in any stroke. Stenting was associated with a 55% reduced risk of myocardial infarction and with an 85% reduction in risk of cranial nerve injury. “Strategies are urgently needed to identify patients who are best served by carotid artery stenting versus carotid endarterectomy,” the authors concluded.

—Rebecca K. Abma

Mild cognitive impairment (MCI) may affect more men than women. A study published in the September 7 Neurology found that MCI was 1.5 times higher in men, compared with women. For the study, part of the Mayo Clinic Study of Aging, 2,050 people between the ages of 70 and 89 in Olmstead County, Minnesota, were interviewed about memory and tested on memory and thinking skills. Nearly 14% of the participants had MCI, about 10% had dementia, and 76% had normal memory and thinking skills. MCI was detected in 19% of men, compared with 14% of women. Study participants who had a low level of education or were never married also had a higher rate of MCI. “The finding that the frequency of MCI is greater in men was unexpected, since the frequency of Alzheimer’s disease is actually greater in women. It warrants further study,” said study author Ronald Petersen, MD, PhD.
Family members and close friends are more sensitive to early signs of Alzheimer’s dementia than traditional screening tests, according to a study published online September 7 in the journal Brain. Data from the two-minute Ascertain Dementia 8 (AD8) questionnaire, which uses an informant to evaluate cognitive changes and difficulties with activities of daily living, were collected for 257 individuals, who were also tested using the Mini Mental State Examination (MMSE). Study subjects were also evaluated for biomarkers using spinal fluid assays and amyloid imaging. Results showed that the AD8’s results corresponded with biomarker results more consistently than did the MMSE’s results. “The AD8 gives us a brief and very low-cost alternative that takes a few minutes of the informant’s time to screen for dementia and thus identify those individuals who need follow-up evaluations to determine if there truly are signs of Alzheimer’s disease,” said lead investigator John C. Morris, MD.

Mild memory loss is not a part of normal aging, according to a study in the September 15 Neurology. Investigators reported that even the very early, mild changes in memory that are much more common in old age than dementia are caused by the same brain lesions associated with Alzheimer’s disease and other dementias. As part of Rush University’s Religious Orders Study, more than 350 nuns, priests, and brothers completed up to 13 years of annual cognitive testing. Postmortem brains were examined for neurofibrillary tangles, cerebral infarction, and Lewy bodies. The last four to five years of life showed a very rapid decline; preceding years showed a much more gradual decline that would be described as normal aging. Pathologic lesions were related to the rapid decline. Pathology was very strongly predictive of the mild changes in cognitive function. Higher tangle density adversely affected all forms of cognition at all trajectory points. Both Lewy bodies and stroke approximately doubled the rate of gradual memory decline.

Aerobic fitness may relate to the structure and function of the preadolescent brain, according to findings published in the October 28 Brain Research. Among 49 children ages 9 and 10, those who were more physically fit tended to have a bigger hippocampus and perform better on memory tests than their less-fit peers. Researchers used MRI to investigate whether higher- and lower-fit 9- and 10-year-olds showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was positively associated with performance in the relational but not the item memory task. Bilateral hippocampal volume was found to mediate the relationship between fitness level (VO2 max) and relational memory.

The 2009 pandemic influenza A (H1N1) caused a higher rate of neurologic complications in children than the seasonal flu, according to a report in the September Annals of Neurology. Children younger than 19 who were hospitalized with H1N1 and neurologic complications between April 1 and November 20, 2009, were included in a retrospective study. The comparison group comprised records of children hospitalized with seasonal flu and neurologic complications from July 1, 2004, to June 30, 2008. A total of 303 children with 2009 H1N1 were identified, of whom 18 experienced neurologic complications. About 80% of these patients had an underlying medical condition (66% neurologic). The most common neurologic symptoms were seizures (67%) and encephalopathy (50%). The comparison group included 234 children, 16 of whom experienced neurologic complications. Only 25% of the comparison group had underlying medical conditions.

Results of a multicenter, prospective, randomized, blinded feasibility trial indicate that occipital nerve stimulation shows promise for treating medically refractory chronic migraine. In the Occipital Nerve Stimulation for the Treatment of Intractable Migraine (ONSTIM) study, eligible patients received an occipital nerve block. Responders were then randomized to adjustable stimulation, preset stimulation, or medical management. Seventy-five of 110 subjects were assigned to a treatment group. Complete diary data were available for 66. Response was defined as a 50% or greater reduction in the number of headache days per month or a 3-point or greater drop in average overall pain intensity compared with baseline. Three-month responder rates were 39% for adjustable stimulation, 6% for preset stimulation, and 0% for medical management. Study results were published September 29 in an online ahead of print edition of Cephalalgia.

IV aspirin is safe, effective, and useful for the treatment of severe headache, per a report in the September 21 Neurology. “IV lysine acetylsalicylate (aspirin) has been shown to be effective in the treatment of acute migraine attacks, but little is known about its effectiveness and safety in patients hospitalized for management of severe headache, typically arising from abrupt withdrawal of other acute attack medications,” researchers wrote. The study of 168 patients in a tertiary referral setting found improvements in pain scores, with a decrease of three or more points on a 10-point scale in more than 25% of cases. Side effect rates were also low (5.9%), and there were no serious adverse events.

Men who experience insomnia with short sleep duration have an increased risk of death, according to research in the September 1 Sleep. The longitudinal study of 1,741 men and women from central Pennsylvania found that men with insomnia who sleep for less than six hours have a fourfold increased risk of death when compared with those with normal sleep, “a risk that has been underestimated,” investigators reported. Insomnia was determined by complaint of sleep difficulty lasting one year or more, and short sleep duration was defined as less than six hours. Patients were seen in the sleep laboratory, and researchers tracked participants for 10 years (males) or 14 years (female). Mortality rates were 21% for men and 5% for women. Men with diabetes or hypertension had an even greater risk than men without these comorbidities. However, in women, mortality was not associated with insomnia or sleep duration.

IV dexamethasone reduces the number of unfavorable outcomes in patients with pneumococcal meningitis, researchers reported in the September 29 Neurology. The Dutch study compared outcomes of 357 episodes of the illness between 2006 and 2009, when 84% of patients received dexamethasone with or before the first dose of antibiotics, to 352 similar cases between 1998 and 2002, when 3% received dexamethasone. Outcomes were based on the 5-point Glasgow Outcome Scale, where a discharge score of 1 to 4 points was deemed unfavorable. Unfavorable outcomes decreased from 50% in the earlier cohort to 39%; rates of hearing loss dropped from 22% to 12%; and death rates declined from 30% to 20%. “The prognosis of pneumococcal meningitis on a national level has substantially improved after the introduction of adjunctive dexamethasone therapy,” the investigators reported.

The FDA approved Gilenya (fingolimod) 0.5 mg daily as a first-line treatment for relapsing forms of multiple sclerosis (MS). The approval makes Gilenya the first oral treatment for relapsing forms of MS. In clinical studies, fingolimod reduced relapses by 52% at one year, compared with interferon beta-1a. A two-year, placebo-controlled study showed that fingolimod significantly reduced the risk of disability progression. The oral therapy, which is marketed by Novartis Pharmaceuticals Corporation, is the first in a new class of drugs called sphingosine 1-phosphate receptor modulators. While fingolimod’s exact mechanism of action is unknown, it is thought to work by reducing the immune system’s attack on the CNS by retaining lymphocytes in the lymph nodes.

Age at disease onset is one of many clues to life expectancy for patients with Parkinson’s disease, according to a report that was published in the October 5 Neurology. Results of a 12-year study that included 230 patients indicate that the average time from symptom onset to death was 16 years. The average age at death was 81. The risk of earlier death was increased about 1.4 times for every 10-year increase in age at symptom onset. Patients with psychotic symptoms were also 1.5 times more likely to die sooner, compared with those without such symptoms. For patients with dementia symptoms, odds of dying earlier were nearly two times higher compared with patients with no memory problems. Men were 1.6 times more likely to die earlier, compared with women. Patients who scored worst on movement tests also had a higher risk of earlier death, compared with those with the highest scores.

A new understanding of the interaction between c-Abl and parkin offers a new target for neuroprotective therapies in Parkinson’s disease, according to research published in the September 7 online issue of theProceedings of the National Academy of Sciences. The over-activation of the c-Abl protein may shut down the brain-protective effects of parkin’s ubiquitin E3 ligase and contribute to a buildup of toxic proteins in the brain that enables the progression of sporadic Parkinson’s disease. The cancer drug imatinib is a c-Abl family kinase inhibitor, and investigators hope that it may help to maintain parkin’s normal protective functions. “The testing of these already approved, well-tolerated drugs for a new use—as a neuroprotective treatment for Parkinson’s disease—is a potentially exciting therapeutic arc that should be pursued,” the investigators reported.

—Glenn S. Williams and Rebecca K. Abma

Mild cognitive impairment (MCI) may affect more men than women. A study published in the September 7 Neurology found that MCI was 1.5 times higher in men, compared with women. For the study, part of the Mayo Clinic Study of Aging, 2,050 people between the ages of 70 and 89 in Olmstead County, Minnesota, were interviewed about memory and tested on memory and thinking skills. Nearly 14% of the participants had MCI, about 10% had dementia, and 76% had normal memory and thinking skills. MCI was detected in 19% of men, compared with 14% of women. Study participants who had a low level of education or were never married also had a higher rate of MCI. “The finding that the frequency of MCI is greater in men was unexpected, since the frequency of Alzheimer’s disease is actually greater in women. It warrants further study,” said study author Ronald Petersen, MD, PhD.
Family members and close friends are more sensitive to early signs of Alzheimer’s dementia than traditional screening tests, according to a study published online September 7 in the journal Brain. Data from the two-minute Ascertain Dementia 8 (AD8) questionnaire, which uses an informant to evaluate cognitive changes and difficulties with activities of daily living, were collected for 257 individuals, who were also tested using the Mini Mental State Examination (MMSE). Study subjects were also evaluated for biomarkers using spinal fluid assays and amyloid imaging. Results showed that the AD8’s results corresponded with biomarker results more consistently than did the MMSE’s results. “The AD8 gives us a brief and very low-cost alternative that takes a few minutes of the informant’s time to screen for dementia and thus identify those individuals who need follow-up evaluations to determine if there truly are signs of Alzheimer’s disease,” said lead investigator John C. Morris, MD.

Mild memory loss is not a part of normal aging, according to a study in the September 15 Neurology. Investigators reported that even the very early, mild changes in memory that are much more common in old age than dementia are caused by the same brain lesions associated with Alzheimer’s disease and other dementias. As part of Rush University’s Religious Orders Study, more than 350 nuns, priests, and brothers completed up to 13 years of annual cognitive testing. Postmortem brains were examined for neurofibrillary tangles, cerebral infarction, and Lewy bodies. The last four to five years of life showed a very rapid decline; preceding years showed a much more gradual decline that would be described as normal aging. Pathologic lesions were related to the rapid decline. Pathology was very strongly predictive of the mild changes in cognitive function. Higher tangle density adversely affected all forms of cognition at all trajectory points. Both Lewy bodies and stroke approximately doubled the rate of gradual memory decline.

Aerobic fitness may relate to the structure and function of the preadolescent brain, according to findings published in the October 28 Brain Research. Among 49 children ages 9 and 10, those who were more physically fit tended to have a bigger hippocampus and perform better on memory tests than their less-fit peers. Researchers used MRI to investigate whether higher- and lower-fit 9- and 10-year-olds showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was positively associated with performance in the relational but not the item memory task. Bilateral hippocampal volume was found to mediate the relationship between fitness level (VO2 max) and relational memory.

The 2009 pandemic influenza A (H1N1) caused a higher rate of neurologic complications in children than the seasonal flu, according to a report in the September Annals of Neurology. Children younger than 19 who were hospitalized with H1N1 and neurologic complications between April 1 and November 20, 2009, were included in a retrospective study. The comparison group comprised records of children hospitalized with seasonal flu and neurologic complications from July 1, 2004, to June 30, 2008. A total of 303 children with 2009 H1N1 were identified, of whom 18 experienced neurologic complications. About 80% of these patients had an underlying medical condition (66% neurologic). The most common neurologic symptoms were seizures (67%) and encephalopathy (50%). The comparison group included 234 children, 16 of whom experienced neurologic complications. Only 25% of the comparison group had underlying medical conditions.

Results of a multicenter, prospective, randomized, blinded feasibility trial indicate that occipital nerve stimulation shows promise for treating medically refractory chronic migraine. In the Occipital Nerve Stimulation for the Treatment of Intractable Migraine (ONSTIM) study, eligible patients received an occipital nerve block. Responders were then randomized to adjustable stimulation, preset stimulation, or medical management. Seventy-five of 110 subjects were assigned to a treatment group. Complete diary data were available for 66. Response was defined as a 50% or greater reduction in the number of headache days per month or a 3-point or greater drop in average overall pain intensity compared with baseline. Three-month responder rates were 39% for adjustable stimulation, 6% for preset stimulation, and 0% for medical management. Study results were published September 29 in an online ahead of print edition of Cephalalgia.

IV aspirin is safe, effective, and useful for the treatment of severe headache, per a report in the September 21 Neurology. “IV lysine acetylsalicylate (aspirin) has been shown to be effective in the treatment of acute migraine attacks, but little is known about its effectiveness and safety in patients hospitalized for management of severe headache, typically arising from abrupt withdrawal of other acute attack medications,” researchers wrote. The study of 168 patients in a tertiary referral setting found improvements in pain scores, with a decrease of three or more points on a 10-point scale in more than 25% of cases. Side effect rates were also low (5.9%), and there were no serious adverse events.

Men who experience insomnia with short sleep duration have an increased risk of death, according to research in the September 1 Sleep. The longitudinal study of 1,741 men and women from central Pennsylvania found that men with insomnia who sleep for less than six hours have a fourfold increased risk of death when compared with those with normal sleep, “a risk that has been underestimated,” investigators reported. Insomnia was determined by complaint of sleep difficulty lasting one year or more, and short sleep duration was defined as less than six hours. Patients were seen in the sleep laboratory, and researchers tracked participants for 10 years (males) or 14 years (female). Mortality rates were 21% for men and 5% for women. Men with diabetes or hypertension had an even greater risk than men without these comorbidities. However, in women, mortality was not associated with insomnia or sleep duration.

IV dexamethasone reduces the number of unfavorable outcomes in patients with pneumococcal meningitis, researchers reported in the September 29 Neurology. The Dutch study compared outcomes of 357 episodes of the illness between 2006 and 2009, when 84% of patients received dexamethasone with or before the first dose of antibiotics, to 352 similar cases between 1998 and 2002, when 3% received dexamethasone. Outcomes were based on the 5-point Glasgow Outcome Scale, where a discharge score of 1 to 4 points was deemed unfavorable. Unfavorable outcomes decreased from 50% in the earlier cohort to 39%; rates of hearing loss dropped from 22% to 12%; and death rates declined from 30% to 20%. “The prognosis of pneumococcal meningitis on a national level has substantially improved after the introduction of adjunctive dexamethasone therapy,” the investigators reported.

The FDA approved Gilenya (fingolimod) 0.5 mg daily as a first-line treatment for relapsing forms of multiple sclerosis (MS). The approval makes Gilenya the first oral treatment for relapsing forms of MS. In clinical studies, fingolimod reduced relapses by 52% at one year, compared with interferon beta-1a. A two-year, placebo-controlled study showed that fingolimod significantly reduced the risk of disability progression. The oral therapy, which is marketed by Novartis Pharmaceuticals Corporation, is the first in a new class of drugs called sphingosine 1-phosphate receptor modulators. While fingolimod’s exact mechanism of action is unknown, it is thought to work by reducing the immune system’s attack on the CNS by retaining lymphocytes in the lymph nodes.

Age at disease onset is one of many clues to life expectancy for patients with Parkinson’s disease, according to a report that was published in the October 5 Neurology. Results of a 12-year study that included 230 patients indicate that the average time from symptom onset to death was 16 years. The average age at death was 81. The risk of earlier death was increased about 1.4 times for every 10-year increase in age at symptom onset. Patients with psychotic symptoms were also 1.5 times more likely to die sooner, compared with those without such symptoms. For patients with dementia symptoms, odds of dying earlier were nearly two times higher compared with patients with no memory problems. Men were 1.6 times more likely to die earlier, compared with women. Patients who scored worst on movement tests also had a higher risk of earlier death, compared with those with the highest scores.

A new understanding of the interaction between c-Abl and parkin offers a new target for neuroprotective therapies in Parkinson’s disease, according to research published in the September 7 online issue of theProceedings of the National Academy of Sciences. The over-activation of the c-Abl protein may shut down the brain-protective effects of parkin’s ubiquitin E3 ligase and contribute to a buildup of toxic proteins in the brain that enables the progression of sporadic Parkinson’s disease. The cancer drug imatinib is a c-Abl family kinase inhibitor, and investigators hope that it may help to maintain parkin’s normal protective functions. “The testing of these already approved, well-tolerated drugs for a new use—as a neuroprotective treatment for Parkinson’s disease—is a potentially exciting therapeutic arc that should be pursued,” the investigators reported.

—Glenn S. Williams and Rebecca K. Abma

Mild cognitive impairment (MCI) may affect more men than women. A study published in the September 7 Neurology found that MCI was 1.5 times higher in men, compared with women. For the study, part of the Mayo Clinic Study of Aging, 2,050 people between the ages of 70 and 89 in Olmstead County, Minnesota, were interviewed about memory and tested on memory and thinking skills. Nearly 14% of the participants had MCI, about 10% had dementia, and 76% had normal memory and thinking skills. MCI was detected in 19% of men, compared with 14% of women. Study participants who had a low level of education or were never married also had a higher rate of MCI. “The finding that the frequency of MCI is greater in men was unexpected, since the frequency of Alzheimer’s disease is actually greater in women. It warrants further study,” said study author Ronald Petersen, MD, PhD.
Family members and close friends are more sensitive to early signs of Alzheimer’s dementia than traditional screening tests, according to a study published online September 7 in the journal Brain. Data from the two-minute Ascertain Dementia 8 (AD8) questionnaire, which uses an informant to evaluate cognitive changes and difficulties with activities of daily living, were collected for 257 individuals, who were also tested using the Mini Mental State Examination (MMSE). Study subjects were also evaluated for biomarkers using spinal fluid assays and amyloid imaging. Results showed that the AD8’s results corresponded with biomarker results more consistently than did the MMSE’s results. “The AD8 gives us a brief and very low-cost alternative that takes a few minutes of the informant’s time to screen for dementia and thus identify those individuals who need follow-up evaluations to determine if there truly are signs of Alzheimer’s disease,” said lead investigator John C. Morris, MD.

Mild memory loss is not a part of normal aging, according to a study in the September 15 Neurology. Investigators reported that even the very early, mild changes in memory that are much more common in old age than dementia are caused by the same brain lesions associated with Alzheimer’s disease and other dementias. As part of Rush University’s Religious Orders Study, more than 350 nuns, priests, and brothers completed up to 13 years of annual cognitive testing. Postmortem brains were examined for neurofibrillary tangles, cerebral infarction, and Lewy bodies. The last four to five years of life showed a very rapid decline; preceding years showed a much more gradual decline that would be described as normal aging. Pathologic lesions were related to the rapid decline. Pathology was very strongly predictive of the mild changes in cognitive function. Higher tangle density adversely affected all forms of cognition at all trajectory points. Both Lewy bodies and stroke approximately doubled the rate of gradual memory decline.

Aerobic fitness may relate to the structure and function of the preadolescent brain, according to findings published in the October 28 Brain Research. Among 49 children ages 9 and 10, those who were more physically fit tended to have a bigger hippocampus and perform better on memory tests than their less-fit peers. Researchers used MRI to investigate whether higher- and lower-fit 9- and 10-year-olds showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was positively associated with performance in the relational but not the item memory task. Bilateral hippocampal volume was found to mediate the relationship between fitness level (VO2 max) and relational memory.

The 2009 pandemic influenza A (H1N1) caused a higher rate of neurologic complications in children than the seasonal flu, according to a report in the September Annals of Neurology. Children younger than 19 who were hospitalized with H1N1 and neurologic complications between April 1 and November 20, 2009, were included in a retrospective study. The comparison group comprised records of children hospitalized with seasonal flu and neurologic complications from July 1, 2004, to June 30, 2008. A total of 303 children with 2009 H1N1 were identified, of whom 18 experienced neurologic complications. About 80% of these patients had an underlying medical condition (66% neurologic). The most common neurologic symptoms were seizures (67%) and encephalopathy (50%). The comparison group included 234 children, 16 of whom experienced neurologic complications. Only 25% of the comparison group had underlying medical conditions.

Results of a multicenter, prospective, randomized, blinded feasibility trial indicate that occipital nerve stimulation shows promise for treating medically refractory chronic migraine. In the Occipital Nerve Stimulation for the Treatment of Intractable Migraine (ONSTIM) study, eligible patients received an occipital nerve block. Responders were then randomized to adjustable stimulation, preset stimulation, or medical management. Seventy-five of 110 subjects were assigned to a treatment group. Complete diary data were available for 66. Response was defined as a 50% or greater reduction in the number of headache days per month or a 3-point or greater drop in average overall pain intensity compared with baseline. Three-month responder rates were 39% for adjustable stimulation, 6% for preset stimulation, and 0% for medical management. Study results were published September 29 in an online ahead of print edition of Cephalalgia.

IV aspirin is safe, effective, and useful for the treatment of severe headache, per a report in the September 21 Neurology. “IV lysine acetylsalicylate (aspirin) has been shown to be effective in the treatment of acute migraine attacks, but little is known about its effectiveness and safety in patients hospitalized for management of severe headache, typically arising from abrupt withdrawal of other acute attack medications,” researchers wrote. The study of 168 patients in a tertiary referral setting found improvements in pain scores, with a decrease of three or more points on a 10-point scale in more than 25% of cases. Side effect rates were also low (5.9%), and there were no serious adverse events.

Men who experience insomnia with short sleep duration have an increased risk of death, according to research in the September 1 Sleep. The longitudinal study of 1,741 men and women from central Pennsylvania found that men with insomnia who sleep for less than six hours have a fourfold increased risk of death when compared with those with normal sleep, “a risk that has been underestimated,” investigators reported. Insomnia was determined by complaint of sleep difficulty lasting one year or more, and short sleep duration was defined as less than six hours. Patients were seen in the sleep laboratory, and researchers tracked participants for 10 years (males) or 14 years (female). Mortality rates were 21% for men and 5% for women. Men with diabetes or hypertension had an even greater risk than men without these comorbidities. However, in women, mortality was not associated with insomnia or sleep duration.

IV dexamethasone reduces the number of unfavorable outcomes in patients with pneumococcal meningitis, researchers reported in the September 29 Neurology. The Dutch study compared outcomes of 357 episodes of the illness between 2006 and 2009, when 84% of patients received dexamethasone with or before the first dose of antibiotics, to 352 similar cases between 1998 and 2002, when 3% received dexamethasone. Outcomes were based on the 5-point Glasgow Outcome Scale, where a discharge score of 1 to 4 points was deemed unfavorable. Unfavorable outcomes decreased from 50% in the earlier cohort to 39%; rates of hearing loss dropped from 22% to 12%; and death rates declined from 30% to 20%. “The prognosis of pneumococcal meningitis on a national level has substantially improved after the introduction of adjunctive dexamethasone therapy,” the investigators reported.

The FDA approved Gilenya (fingolimod) 0.5 mg daily as a first-line treatment for relapsing forms of multiple sclerosis (MS). The approval makes Gilenya the first oral treatment for relapsing forms of MS. In clinical studies, fingolimod reduced relapses by 52% at one year, compared with interferon beta-1a. A two-year, placebo-controlled study showed that fingolimod significantly reduced the risk of disability progression. The oral therapy, which is marketed by Novartis Pharmaceuticals Corporation, is the first in a new class of drugs called sphingosine 1-phosphate receptor modulators. While fingolimod’s exact mechanism of action is unknown, it is thought to work by reducing the immune system’s attack on the CNS by retaining lymphocytes in the lymph nodes.

Age at disease onset is one of many clues to life expectancy for patients with Parkinson’s disease, according to a report that was published in the October 5 Neurology. Results of a 12-year study that included 230 patients indicate that the average time from symptom onset to death was 16 years. The average age at death was 81. The risk of earlier death was increased about 1.4 times for every 10-year increase in age at symptom onset. Patients with psychotic symptoms were also 1.5 times more likely to die sooner, compared with those without such symptoms. For patients with dementia symptoms, odds of dying earlier were nearly two times higher compared with patients with no memory problems. Men were 1.6 times more likely to die earlier, compared with women. Patients who scored worst on movement tests also had a higher risk of earlier death, compared with those with the highest scores.

A new understanding of the interaction between c-Abl and parkin offers a new target for neuroprotective therapies in Parkinson’s disease, according to research published in the September 7 online issue of theProceedings of the National Academy of Sciences. The over-activation of the c-Abl protein may shut down the brain-protective effects of parkin’s ubiquitin E3 ligase and contribute to a buildup of toxic proteins in the brain that enables the progression of sporadic Parkinson’s disease. The cancer drug imatinib is a c-Abl family kinase inhibitor, and investigators hope that it may help to maintain parkin’s normal protective functions. “The testing of these already approved, well-tolerated drugs for a new use—as a neuroprotective treatment for Parkinson’s disease—is a potentially exciting therapeutic arc that should be pursued,” the investigators reported.

—Glenn S. Williams and Rebecca K. Abma

Patients with Alzheimer’s disease who underwent repetitive transcranial magnetic stimulation (rTMS) showed improved sentence comprehension compared to baseline, according to a study published in the June 23 online Journal of Neurology, Neurosurgery, and Psychiatry. Researchers randomly assigned 10 patients to either a four-week rTMS protocol or two-week sham treatment followed by two weeks of real rTMS and found a significant difference between the two groups in terms of the percentage of correct responses of auditory sentence comprehension. “Only real treatment induced an improvement in performance with respect to baseline or placebo,” the investigators noted. “Moreover, both groups showed a lasting effect on the improved performance eight weeks after the end of treatment.” The researchers concluded that, in conjunction with other therapeutic interventions, rhythmic rTMS may offer a novel approach to treating Alzheimer’s-related language dysfunction.

Depression is associated with an increased risk of dementia and Alzheimer’s disease, researchers from the Framingham Heart Study reported in the July 6 Neurology. At baseline, 13.2% of the cohort (n = 949) scored 16 or greater on the Center for Epidemiologic Studies Depression Scale (CES-D). During the 17-year follow-up, 21.6% of participants who were depressed at baseline developed dementia, compared with 16.6% of those who were not depressed. “Depressed participants had more than a 50% increased risk for dementia and Alzheimer’s disease,” the investigators noted. “For each 10-point increase on the CES-D, there was a significant increase in the risk of dementia.”

In patients with mild cognitive impairment, baseline fluorodeoxyglucose (FDG)-PET scans and episodic memory performance predict conversion to Alzheimer’s disease better than CSF levels of hyperphosphorylated tau (p-tau181p) and Ab1-42, per research published in Neurology online ahead of print June 30. Using data from the Alzheimer’s Disease Neuroimaging Initiative, investigators evaluated the prognostic accuracy of genetic, CSF, neuroimaging, and cognitive measures for predicting disease progression. The study found that 17.2% of subjects annually converted from mild cognitive impairment to Alzheimer’s disease. Subjects with abnormal baseline results on both FDG-PET and episodic memory were 11.7 times more likely to progress to Alzheimer’s disease than were those with normal results. “Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention,” the researchers concluded.

A new oral formulation of the antiepileptic drug Vimpat (lacosamide) (C-V) is available as an add-on treatment of partial-onset seizures in patients with epilepsy who are 17 and older. “There are many people for whom swallowing pills is difficult, and the oral solution, which can be substituted milligram for milligram to the oral tablet, will be helpful for adults with swallowing difficulties,” said Ilo E. Leppik, MD, Director of the Epilepsy Research and Education Program, University of Minnesota, in Minneapolis. “This will be particularly useful for elderly in nursing homes who may have gastric tubes in place.” Vimpat is also available in oral tablets and IV injections. The new 10-mg/mL oral formulation is a strawberry-flavored liquid and should be stored at room temperature. Vimpat is manufactured by UCB in Brussels.

Use of the antiepileptic drug (AED) valproic acid in the first trimester of pregnancy greatly increases the risk of birth defects, reported a study in the June 10 New England Journal of Medicine. Researchers combined data from eight cohort studies totaling 1,565 pregnancies exposed to valproic acid and found 118 instances of major malformations. The investigators identified 14 birth defects significantly more common in pregnancies with first-trimester exposure to the AED, and then performed a case–controlled study based on 98,075 live births, stillbirths, or terminations with malformations registered in a European AED database. Using two control groups—those with malformations not previously linked to valproic acid and those with chromosomal abnormalities—the investigators determined that six of the 14 malformations were significantly associated with use of valproic acid monotherapy: spina bifida (odds ratio [OR], 12.7), atrial septal defect (OR, 2.5), cleft palate (OR, 5.2), hypospadias (OR, 4.8), polydactyly (OR, 2.2), and craniosynostosis (OR, 6.8).

High consumption of alcoholic beverages, smoking, and a lack of physical activity were significantly associated with migraine and tension-type headaches in high school students, researchers reported in the June 7 online ahead of print Headache . A total of 1,260 adolescents filled out questionnaires regarding their intake of food and beverages (including coffee, alcohol, and nonalcoholic drinks), smoking habits, and physical activity. Students who drank more alcohol were 3.4 times more likely to have headaches than those who did not. Likewise, those who drank coffee had 2.4 times greater odds of headaches, while those who smoked cigarettes had a 2.7 higher likelihood of headaches. “Diet and lifestyle are seen as factors which influence headache in adults,” the researchers noted. “However, population-based studies on this issue in adolescents are rare.” No link was found between headaches and skipping meals or insufficient fluid intake.

Disease-specific and balance- and mobility-related measures can accurately predict which patients with Parkinson’s disease are at greater risk of falls, according to a study published online ahead of print June 23 in Neurology. In a study of 101 subjects with early-stage Parkinson’s disease, investigators administered a battery of neurologic and functional tests, including Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk, which includes visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway assessments. In the six months following assessment, 48% of subjects reported at least one fall, while 24% of subjects reported more than one fall. The multivariate model revealed that the most accurate fall predictor was a combination of the Unified Parkinson’s Disease Rating Scale total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction.

A link between genetic variants, pesticide exposure, and Parkinson’s disease was reported in the June Archives of Neurology. Researchers tested for two ABCB1 polymorphisms associated with altered P-glycoprotein function in 207 subjects with Parkinson’s disease who were enrolled in the French health system for agricultural workers and 482 matched controls. Study participants also filled out questionnaires about their pesticide use, and subjects who used pesticides professionally were interviewed by an occupational health physician. Parkinson’s disease was not associated with the genetic variants in the full cohort; however, when separated by sex (101 male cases, 234 controls), investigators found a 3.5-fold higher incidence of organochlorine exposure in men with the variant G2677 (A, T) alleles. Among patients only, researchers noted an association between carrying two of the variant alleles and organochlorine exposure (odds ratio, 5.4), as well as with the cumulative lifetime number of hours of exposure.

Poststroke complications can shorten a patient’s optimum health span by about two years, per a study in the July 1 online Stroke. Using three-month outcome data from 1,233 patients with acute ischemic stroke in South Korea, researchers calculated the disability-adjusted life-year (DALY) loss from the stroke itself and then analyzed additional DALY lost from complications. Complications were reported in 34% of patients, with 20.8% of patients experiencing neurologic complications and 24.0% experiencing medical complications. The average DALY lost due to index stroke was 3.82. Patients with one complication lost an additional 1.52 DALY, while those with two or more complications lost an additional 2.69 DALY. “DALY analysis quantifies the burden of poststroke complications with a uniform metric potentially useful for healthy system planners,” the researchers stated.

—Rebecca K. Abma

Patients with Alzheimer’s disease who underwent repetitive transcranial magnetic stimulation (rTMS) showed improved sentence comprehension compared to baseline, according to a study published in the June 23 online Journal of Neurology, Neurosurgery, and Psychiatry. Researchers randomly assigned 10 patients to either a four-week rTMS protocol or two-week sham treatment followed by two weeks of real rTMS and found a significant difference between the two groups in terms of the percentage of correct responses of auditory sentence comprehension. “Only real treatment induced an improvement in performance with respect to baseline or placebo,” the investigators noted. “Moreover, both groups showed a lasting effect on the improved performance eight weeks after the end of treatment.” The researchers concluded that, in conjunction with other therapeutic interventions, rhythmic rTMS may offer a novel approach to treating Alzheimer’s-related language dysfunction.

Depression is associated with an increased risk of dementia and Alzheimer’s disease, researchers from the Framingham Heart Study reported in the July 6 Neurology. At baseline, 13.2% of the cohort (n = 949) scored 16 or greater on the Center for Epidemiologic Studies Depression Scale (CES-D). During the 17-year follow-up, 21.6% of participants who were depressed at baseline developed dementia, compared with 16.6% of those who were not depressed. “Depressed participants had more than a 50% increased risk for dementia and Alzheimer’s disease,” the investigators noted. “For each 10-point increase on the CES-D, there was a significant increase in the risk of dementia.”

In patients with mild cognitive impairment, baseline fluorodeoxyglucose (FDG)-PET scans and episodic memory performance predict conversion to Alzheimer’s disease better than CSF levels of hyperphosphorylated tau (p-tau181p) and Ab1-42, per research published in Neurology online ahead of print June 30. Using data from the Alzheimer’s Disease Neuroimaging Initiative, investigators evaluated the prognostic accuracy of genetic, CSF, neuroimaging, and cognitive measures for predicting disease progression. The study found that 17.2% of subjects annually converted from mild cognitive impairment to Alzheimer’s disease. Subjects with abnormal baseline results on both FDG-PET and episodic memory were 11.7 times more likely to progress to Alzheimer’s disease than were those with normal results. “Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention,” the researchers concluded.

A new oral formulation of the antiepileptic drug Vimpat (lacosamide) (C-V) is available as an add-on treatment of partial-onset seizures in patients with epilepsy who are 17 and older. “There are many people for whom swallowing pills is difficult, and the oral solution, which can be substituted milligram for milligram to the oral tablet, will be helpful for adults with swallowing difficulties,” said Ilo E. Leppik, MD, Director of the Epilepsy Research and Education Program, University of Minnesota, in Minneapolis. “This will be particularly useful for elderly in nursing homes who may have gastric tubes in place.” Vimpat is also available in oral tablets and IV injections. The new 10-mg/mL oral formulation is a strawberry-flavored liquid and should be stored at room temperature. Vimpat is manufactured by UCB in Brussels.

Use of the antiepileptic drug (AED) valproic acid in the first trimester of pregnancy greatly increases the risk of birth defects, reported a study in the June 10 New England Journal of Medicine. Researchers combined data from eight cohort studies totaling 1,565 pregnancies exposed to valproic acid and found 118 instances of major malformations. The investigators identified 14 birth defects significantly more common in pregnancies with first-trimester exposure to the AED, and then performed a case–controlled study based on 98,075 live births, stillbirths, or terminations with malformations registered in a European AED database. Using two control groups—those with malformations not previously linked to valproic acid and those with chromosomal abnormalities—the investigators determined that six of the 14 malformations were significantly associated with use of valproic acid monotherapy: spina bifida (odds ratio [OR], 12.7), atrial septal defect (OR, 2.5), cleft palate (OR, 5.2), hypospadias (OR, 4.8), polydactyly (OR, 2.2), and craniosynostosis (OR, 6.8).

High consumption of alcoholic beverages, smoking, and a lack of physical activity were significantly associated with migraine and tension-type headaches in high school students, researchers reported in the June 7 online ahead of print Headache . A total of 1,260 adolescents filled out questionnaires regarding their intake of food and beverages (including coffee, alcohol, and nonalcoholic drinks), smoking habits, and physical activity. Students who drank more alcohol were 3.4 times more likely to have headaches than those who did not. Likewise, those who drank coffee had 2.4 times greater odds of headaches, while those who smoked cigarettes had a 2.7 higher likelihood of headaches. “Diet and lifestyle are seen as factors which influence headache in adults,” the researchers noted. “However, population-based studies on this issue in adolescents are rare.” No link was found between headaches and skipping meals or insufficient fluid intake.

Disease-specific and balance- and mobility-related measures can accurately predict which patients with Parkinson’s disease are at greater risk of falls, according to a study published online ahead of print June 23 in Neurology. In a study of 101 subjects with early-stage Parkinson’s disease, investigators administered a battery of neurologic and functional tests, including Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk, which includes visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway assessments. In the six months following assessment, 48% of subjects reported at least one fall, while 24% of subjects reported more than one fall. The multivariate model revealed that the most accurate fall predictor was a combination of the Unified Parkinson’s Disease Rating Scale total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction.

A link between genetic variants, pesticide exposure, and Parkinson’s disease was reported in the June Archives of Neurology. Researchers tested for two ABCB1 polymorphisms associated with altered P-glycoprotein function in 207 subjects with Parkinson’s disease who were enrolled in the French health system for agricultural workers and 482 matched controls. Study participants also filled out questionnaires about their pesticide use, and subjects who used pesticides professionally were interviewed by an occupational health physician. Parkinson’s disease was not associated with the genetic variants in the full cohort; however, when separated by sex (101 male cases, 234 controls), investigators found a 3.5-fold higher incidence of organochlorine exposure in men with the variant G2677 (A, T) alleles. Among patients only, researchers noted an association between carrying two of the variant alleles and organochlorine exposure (odds ratio, 5.4), as well as with the cumulative lifetime number of hours of exposure.

Poststroke complications can shorten a patient’s optimum health span by about two years, per a study in the July 1 online Stroke. Using three-month outcome data from 1,233 patients with acute ischemic stroke in South Korea, researchers calculated the disability-adjusted life-year (DALY) loss from the stroke itself and then analyzed additional DALY lost from complications. Complications were reported in 34% of patients, with 20.8% of patients experiencing neurologic complications and 24.0% experiencing medical complications. The average DALY lost due to index stroke was 3.82. Patients with one complication lost an additional 1.52 DALY, while those with two or more complications lost an additional 2.69 DALY. “DALY analysis quantifies the burden of poststroke complications with a uniform metric potentially useful for healthy system planners,” the researchers stated.

—Rebecca K. Abma

Patients with Alzheimer’s disease who underwent repetitive transcranial magnetic stimulation (rTMS) showed improved sentence comprehension compared to baseline, according to a study published in the June 23 online Journal of Neurology, Neurosurgery, and Psychiatry. Researchers randomly assigned 10 patients to either a four-week rTMS protocol or two-week sham treatment followed by two weeks of real rTMS and found a significant difference between the two groups in terms of the percentage of correct responses of auditory sentence comprehension. “Only real treatment induced an improvement in performance with respect to baseline or placebo,” the investigators noted. “Moreover, both groups showed a lasting effect on the improved performance eight weeks after the end of treatment.” The researchers concluded that, in conjunction with other therapeutic interventions, rhythmic rTMS may offer a novel approach to treating Alzheimer’s-related language dysfunction.

Depression is associated with an increased risk of dementia and Alzheimer’s disease, researchers from the Framingham Heart Study reported in the July 6 Neurology. At baseline, 13.2% of the cohort (n = 949) scored 16 or greater on the Center for Epidemiologic Studies Depression Scale (CES-D). During the 17-year follow-up, 21.6% of participants who were depressed at baseline developed dementia, compared with 16.6% of those who were not depressed. “Depressed participants had more than a 50% increased risk for dementia and Alzheimer’s disease,” the investigators noted. “For each 10-point increase on the CES-D, there was a significant increase in the risk of dementia.”

In patients with mild cognitive impairment, baseline fluorodeoxyglucose (FDG)-PET scans and episodic memory performance predict conversion to Alzheimer’s disease better than CSF levels of hyperphosphorylated tau (p-tau181p) and Ab1-42, per research published in Neurology online ahead of print June 30. Using data from the Alzheimer’s Disease Neuroimaging Initiative, investigators evaluated the prognostic accuracy of genetic, CSF, neuroimaging, and cognitive measures for predicting disease progression. The study found that 17.2% of subjects annually converted from mild cognitive impairment to Alzheimer’s disease. Subjects with abnormal baseline results on both FDG-PET and episodic memory were 11.7 times more likely to progress to Alzheimer’s disease than were those with normal results. “Complementary information provided by these biomarkers may aid in future selection of patients for clinical trials or identification of patients likely to benefit from a therapeutic intervention,” the researchers concluded.

A new oral formulation of the antiepileptic drug Vimpat (lacosamide) (C-V) is available as an add-on treatment of partial-onset seizures in patients with epilepsy who are 17 and older. “There are many people for whom swallowing pills is difficult, and the oral solution, which can be substituted milligram for milligram to the oral tablet, will be helpful for adults with swallowing difficulties,” said Ilo E. Leppik, MD, Director of the Epilepsy Research and Education Program, University of Minnesota, in Minneapolis. “This will be particularly useful for elderly in nursing homes who may have gastric tubes in place.” Vimpat is also available in oral tablets and IV injections. The new 10-mg/mL oral formulation is a strawberry-flavored liquid and should be stored at room temperature. Vimpat is manufactured by UCB in Brussels.

Use of the antiepileptic drug (AED) valproic acid in the first trimester of pregnancy greatly increases the risk of birth defects, reported a study in the June 10 New England Journal of Medicine. Researchers combined data from eight cohort studies totaling 1,565 pregnancies exposed to valproic acid and found 118 instances of major malformations. The investigators identified 14 birth defects significantly more common in pregnancies with first-trimester exposure to the AED, and then performed a case–controlled study based on 98,075 live births, stillbirths, or terminations with malformations registered in a European AED database. Using two control groups—those with malformations not previously linked to valproic acid and those with chromosomal abnormalities—the investigators determined that six of the 14 malformations were significantly associated with use of valproic acid monotherapy: spina bifida (odds ratio [OR], 12.7), atrial septal defect (OR, 2.5), cleft palate (OR, 5.2), hypospadias (OR, 4.8), polydactyly (OR, 2.2), and craniosynostosis (OR, 6.8).

High consumption of alcoholic beverages, smoking, and a lack of physical activity were significantly associated with migraine and tension-type headaches in high school students, researchers reported in the June 7 online ahead of print Headache . A total of 1,260 adolescents filled out questionnaires regarding their intake of food and beverages (including coffee, alcohol, and nonalcoholic drinks), smoking habits, and physical activity. Students who drank more alcohol were 3.4 times more likely to have headaches than those who did not. Likewise, those who drank coffee had 2.4 times greater odds of headaches, while those who smoked cigarettes had a 2.7 higher likelihood of headaches. “Diet and lifestyle are seen as factors which influence headache in adults,” the researchers noted. “However, population-based studies on this issue in adolescents are rare.” No link was found between headaches and skipping meals or insufficient fluid intake.

Disease-specific and balance- and mobility-related measures can accurately predict which patients with Parkinson’s disease are at greater risk of falls, according to a study published online ahead of print June 23 in Neurology. In a study of 101 subjects with early-stage Parkinson’s disease, investigators administered a battery of neurologic and functional tests, including Tinetti, Berg, Timed Up and Go, Functional Reach, and the Physiological Profile Assessment of Falls Risk, which includes visual function, proprioception, strength, cutaneous sensitivity, reaction time, and postural sway assessments. In the six months following assessment, 48% of subjects reported at least one fall, while 24% of subjects reported more than one fall. The multivariate model revealed that the most accurate fall predictor was a combination of the Unified Parkinson’s Disease Rating Scale total score, total freezing of gait score, occurrence of symptomatic postural orthostasis, Tinetti total score, and extent of postural sway in the anterior-posterior direction.

A link between genetic variants, pesticide exposure, and Parkinson’s disease was reported in the June Archives of Neurology. Researchers tested for two ABCB1 polymorphisms associated with altered P-glycoprotein function in 207 subjects with Parkinson’s disease who were enrolled in the French health system for agricultural workers and 482 matched controls. Study participants also filled out questionnaires about their pesticide use, and subjects who used pesticides professionally were interviewed by an occupational health physician. Parkinson’s disease was not associated with the genetic variants in the full cohort; however, when separated by sex (101 male cases, 234 controls), investigators found a 3.5-fold higher incidence of organochlorine exposure in men with the variant G2677 (A, T) alleles. Among patients only, researchers noted an association between carrying two of the variant alleles and organochlorine exposure (odds ratio, 5.4), as well as with the cumulative lifetime number of hours of exposure.

Poststroke complications can shorten a patient’s optimum health span by about two years, per a study in the July 1 online Stroke. Using three-month outcome data from 1,233 patients with acute ischemic stroke in South Korea, researchers calculated the disability-adjusted life-year (DALY) loss from the stroke itself and then analyzed additional DALY lost from complications. Complications were reported in 34% of patients, with 20.8% of patients experiencing neurologic complications and 24.0% experiencing medical complications. The average DALY lost due to index stroke was 3.82. Patients with one complication lost an additional 1.52 DALY, while those with two or more complications lost an additional 2.69 DALY. “DALY analysis quantifies the burden of poststroke complications with a uniform metric potentially useful for healthy system planners,” the researchers stated.

—Rebecca K. Abma

Alzheimer's Disease/Dementia
A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Amyotrophic Lateral Sclerosis
Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS
protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

Epilepsy
The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless Legs Syndrome
Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Stroke/Cerebrovascular Disease
Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Tourette Syndrome
Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

Traumatic Brain Injury
In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

Alzheimer's Disease/Dementia
A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Amyotrophic Lateral Sclerosis
Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS
protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

Epilepsy
The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless Legs Syndrome
Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Stroke/Cerebrovascular Disease
Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Tourette Syndrome
Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

Traumatic Brain Injury
In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

Alzheimer's Disease/Dementia
A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Amyotrophic Lateral Sclerosis
Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS
protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

Epilepsy
The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless Legs Syndrome
Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Stroke/Cerebrovascular Disease
Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Tourette Syndrome
Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

Traumatic Brain Injury
In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

 —Rebecca K. Abma and Colby Stong

A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

 —Rebecca K. Abma and Colby Stong

A person whose spouse has dementia is six times more likely to develop incident dementia than are subjects whose spouses are dementia-free, researchers reported in the May Journal of the American Geriatrics Society. The findings are based on 1,221 married couples (ages 65 and older) from Cache County, Utah. Incident dementia was diagnosed in 255 participants, per DSM-III-Revised criteria. In sex-specific analyses, husbands had a higher risk of dementia (hazard rate ratio [HRR], 11.9) than wives (HRR, 3.7). “The finding of a six times greater risk of dementia in persons so exposed than in married men and women whose spouse had not developed dementia remained after adjustment for age, sex, education, socioeconomic status, and apolipoprotein E genotype, all of which were (as expected) associated with dementia risk,” the investigators reported.

Amyloid-beta, which forms plaques in the brains of patients with Alzheimer’s disease, also accumulates in the eyes of persons with Down syndrome, per a study in the May 20 PLoS One. The optical lenses of patients with Down syndrome have a “characteristic pattern of supranuclear opacification accompanied by accelerated supranuclear amyloid-beta accumulation, co-localizing amyloid pathology, and fiber cell cytoplasmic amyloid-beta aggregates identical to the lens pathology identified in Alzheimer’s disease,” researchers reported. “These results establish the genetic etiology of the distinctive lens phenotype in Down syndrome and identify the molecular origin and pathogenic mechanism by which lens pathology is expressed in this common chromosomal disorder,” the researchers concluded. “Moreover, these findings confirm increased amyloid-beta accumulation as a key pathogenic determinant linking lens and brain pathology in both Down syndrome and Alzheimer’s disease.”

Researchers have found a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), according to a study in the June Annals of Neurology. The investigators performed immunostaining on the postmortem spinal cords of 78 ALS cases, including 52 with sporadic ALS, 10 with ALS with dementia, and 16 with familial ALS. Postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also analyzed. The researchers observed FUS-immunoreactive inclusions in spinal anterior horn neurons in all sporadic and familial cases, except for those with SOD1 mutations. “Our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying sporadic ALS, non-SOD1 familial ALS, ALS/dementia, and related disorders,” reported the study authors.

The pertussis vaccine may trigger an earlier onset of Dravet syndrome—a severe form of epilepsy—in children with a mutation of the sodium channel gene SCN1A, per a study that was published in the June Lancet Neurology. In the vaccination-proximate group (12 subjects with seizure onset the day of or the day after vaccination) of the retrospective study, the average age of seizure onset was 18.4 weeks. In the vaccination-distant group (25 subjects with seizure onset two or more days after vaccination and three subjects with onset before vaccination), the average age of disease onset was 26.2 weeks. Subjects with the SCN1A mutation are “destined to develop the disease,” the investigators noted. “Vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome,” the authors concluded.

Restless legs syndrome (RLS) aggregates in families with a familial rate of 77%, a sibling relative risk of 3.6, and an offspring relative risk of 1.8, according to research in the May Archives of Neurology. Following 249 RLS probands and their families from Quebec in a sleep center for 15 years, researchers conducted diagnostic interviews via telephone and found that 671 cases matched the diagnostic criteria for familial RLS, comprising 192 probands and 479 affected family members. “RLS significantly aggregated in families with variable phenotypic expressivity, and the siblings of severely affected individuals have an increased risk of developing the disease,” the researchers wrote.

Results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the May 26 online New England Journal of Medicine. Initially presented at the 2010 International Stroke Conference (Neurology Reviews, “Carotid Stenting Versus Surgery for Stroke Prevention,” April, page 1), the study of 2,502 patients with symptomatic or asymptomatic carotid-artery stenosis found that the risk of stroke, myocardial infarction, or death among patients with symptomatic or asymptomatic carotid stenosis was statistically similar for patients undergoing carotid-artery stenting or carotid endarterectomy (7.2% and 6.8%, respectively). However, during the periprocedural period, stenting patients had a higher risk of stroke (hazard ratio, 1.50), while endarterectomy patients had a 2.3% rate of myocardial infarction compared to a 1.1% rate for stenting.

The use of transdermal hormone replacement therapy (HRT) containing low doses of estrogen does not seem to increase the risk of stroke, and thus may be safer than oral tablets of HRT, researchers reported in the June 3 online BMJ. The researchers matched 15,710 women (ages 50 to 79) who had a stroke with 59,958 controls. The rate of stroke in the cohort was 2.85 per 1,000 per year, and the adjusted rate ratio (RR) of stroke associated with current use of transdermal HRT was 0.95 relative to no use. “The risk of stroke was not increased with use of low estrogen dose patches (RR, 0.81) compared with no use, whereas the risk was increased with high dose patches (RR, 1.89),” the study authors reported. “Current users of oral HRT had a higher rate of stroke than nonusers (RR, 1.28) with both low dose and high dose.”

The risk of cerebrovasular disease is higher in individuals with elevated blood pressure or fluctuations in blood pressure than those with low blood pressure or fewer fluctuations, a study in the May Archives of Neurology reported. In a community-based epidemiologic study of older adults living in the Washington Heights-Inwood section of Manhattan, researchers measured white matter hyperintensity and the presence of brain infarctions in a group of 686 nondemented older adults whose blood pressure was measured during three visits 24 months apart and who underwent structural MRIs. Participants with the lowest white matter hyperintensity volume had the lowest mean/lowest blood pressure, and those with the highest white matter hyperintensity volume had the highest mean/highest blood pressure. “Given that cerebrovascular disease is associated with disability, these findings suggest that interventions should focus on long-term fluctuating blood pressure and elevated blood pressure,” investigators concluded.

Histaminergic neurotransmission may play a role in the mechanism and modulation of Tourette syndrome and tics, researchers reported in the May 20 New England Journal of Medicine. “Despite a strong genetic contribution, inheritance is complex and risk alleles have proven difficult to identify,” the investigators noted. “We have characterized a highly unusual two-generation pedigree in which Tourette syndrome is segregated in an autosomal dominant fashion.” The researchers identified “a rare functional mutation in the HDC gene encoding L-histamine decarboxylase, the rate-limiting enzyme in histamine biosynthesis.” They added that “the links between histaminergic neurotransmission and tics, suggested by our genetic findings, are further supported by previous studies of pharmacologic agents that target the presynaptic autoreceptor H3R.”

In patients with traumatic brain injury (TBI), reduced evening melatonin production may indicate disruption to circadian regulation of melatonin synthesis and lead to sleep disturbance, as reported in the May 25 Neurology. In an observational study of 23 patients with TBI and 23 age- and gender-matched healthy volunteers, researchers found two factors contributing to sleep disturbances in patients with TBI—reduced sleep quality due to elevated depression and anxiety and increased slow wave sleep due to mechanical brain damage. “Patients with TBI reported higher anxiety and depressive symptoms and sleep disturbance than controls,” the investigators wrote. “Patients with TBI showed decreased sleep efficiency and increased wake after sleep onset.” In addition, TBI subjects had lower levels of evening melatonin production associated with REM sleep.

 —Rebecca K. Abma and Colby Stong

Bilateral deep brain stimulation (DBS) of the anterior nuclei of the thalamus reduced the frequency of seizures in patients with refractory epilepsy, according to a study published in the March 18 online Epilepsia. The two-year, multicenter Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial included 110 patients with medically refractory partial seizures. In the initial three-month, double-blind segment, participants were randomized to either receive stimulation or no stimulation. At the three-month mark, the group that received stimulation reported a 29% greater reduction in seizures than the control group. For the remainder of the study, all patients received the treatment. At the two-year mark, there was a 56% median reduction in seizure frequency. Fourteen patients were seizure-free for at least six months, and researchers reported modest complication rates.

Long-term smoking has a greater effect in reducing the risk of Parkinson’s disease than the amount of cigarettes smoked per day, according to a study in the March 16 Neurology. Researchers compared the relative importance of smoking duration versus intensity in 305,468 participants of the NIH-AARP Diet and Health Cohort, 1,662 of whom were later diagnosed with Parkinson’s disease. Using multivariate logistic regression models, the investigators found that current smokers had a 0.56 odds ratio (OR) of Parkinson’s disease, compared with those who never smoked, and former smokers had an OR of 0.78. When the researchers stratified current and former smokers by number of years smoked, they found the highest Parkinson’s risk among those who smoked for fewer than 10 years (OR, 0.96) and the lowest risk among those who smoked for 30 or more years (OR, 0.59). The typical number of cigarettes smoked per day, in contrast, appeared to have no impact on risk.

The FDA has approved Botox (onabotulinumtoxin A) to treat spasticity in the flexor muscles of the elbow, wrist, and fingers in adults, a condition that is common after stroke or traumatic brain injury, or with the progression of multiple sclerosis. Botox works by temporarily blocking the connections between nerves and muscles, resulting in a temporary paralysis of the spastic muscle. “Muscles affected by spasticity have increased stiffness and tightness, which may lead to pain, difficulties with hygiene and other activities of daily living, and may affect how a patient looks,” noted Russell Katz, MD, Director of the Division of Neurology Products at the FDA’s Center for Drug Evaluation and Research in Silver Spring, Maryland. “In clinical trials, treatment with Botox was found to be beneficial to patients with upper limb spasticity. Botox is manufactured by Allergan Inc, of Irvine, California.

Cardiorespiratory fitness can preserve neuronal integrity in patients with multiple sclerosis, according to a study published in the February Brain Research. Investigators analyzed the relationship between physical fitness and brain tissue health and found that higher fitness levels correlated with preserved gray matter volumes and white matter tract integrity, both of which are associated with faster processing speed. Statistical mapping showed an association between greater gray matter volume in midline cortical structures and higher levels of fitness, and fitness levels also correlated with fractional anisotropy in the left thalamic radiation and right anterior corona radiata. “Taken together, these results suggest that fitness exerts a prophylactic influence on the structural decline observed early on, preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability,” researchers noted.

The FDA has approved once-daily Mirapex ER (pramipexole dihydrochloride) extended-release tablets for the treatment of early idiopathic Parkinson’s disease. A randomized, double-blind, placebo-controlled multicenter trial of more than 400 patients found that treatment with extended-release pramipexole offered clinically significant improvement compared with placebo. The extended-release tablets also offered similar benefits to the currently available immediate-release formulation, which needs to be taken three times a day. “This new, once daily treatment has a more convenient dosing schedule, offering greater flexibility as someone with early Parkinson’s disease plans his or her day,” noted Robert Hauser, MD, Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida College of Medicine. Mirapex is distributed by Boehringer Ingelheim Pharmaceuticals, based in Ridgefield, Connecticut.

Recent immigrants to Ontario, Canada, have a lower risk of premature acute stroke than long-term residents, according to a population-matched cohort study in the February 9 Neurology. Researchers identified 965,829 new immigrants, defined as new recipients of universal public health insurance, and matched subjects to 3,272,393 long-term residents by year of birth, sex, and location. In a median six-year follow-up period, 6,216 strokes were reported. This translated to an incidence rate of 1.69 per 10,000 person-years among new residents and 2.56 per 10,000 person-years among long-term residents. After adjusting for age, income, residency, history of hypertension, diabetes mellitus, smoking, and number of insurance claims, the investigators found that the hazard ratio for stroke was 0.69. Risks for both ischemic and hemorrhagic strokes were similar.

Bilateral deep brain stimulation (DBS) of the anterior nuclei of the thalamus reduced the frequency of seizures in patients with refractory epilepsy, according to a study published in the March 18 online Epilepsia. The two-year, multicenter Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial included 110 patients with medically refractory partial seizures. In the initial three-month, double-blind segment, participants were randomized to either receive stimulation or no stimulation. At the three-month mark, the group that received stimulation reported a 29% greater reduction in seizures than the control group. For the remainder of the study, all patients received the treatment. At the two-year mark, there was a 56% median reduction in seizure frequency. Fourteen patients were seizure-free for at least six months, and researchers reported modest complication rates.

Long-term smoking has a greater effect in reducing the risk of Parkinson’s disease than the amount of cigarettes smoked per day, according to a study in the March 16 Neurology. Researchers compared the relative importance of smoking duration versus intensity in 305,468 participants of the NIH-AARP Diet and Health Cohort, 1,662 of whom were later diagnosed with Parkinson’s disease. Using multivariate logistic regression models, the investigators found that current smokers had a 0.56 odds ratio (OR) of Parkinson’s disease, compared with those who never smoked, and former smokers had an OR of 0.78. When the researchers stratified current and former smokers by number of years smoked, they found the highest Parkinson’s risk among those who smoked for fewer than 10 years (OR, 0.96) and the lowest risk among those who smoked for 30 or more years (OR, 0.59). The typical number of cigarettes smoked per day, in contrast, appeared to have no impact on risk.

The FDA has approved Botox (onabotulinumtoxin A) to treat spasticity in the flexor muscles of the elbow, wrist, and fingers in adults, a condition that is common after stroke or traumatic brain injury, or with the progression of multiple sclerosis. Botox works by temporarily blocking the connections between nerves and muscles, resulting in a temporary paralysis of the spastic muscle. “Muscles affected by spasticity have increased stiffness and tightness, which may lead to pain, difficulties with hygiene and other activities of daily living, and may affect how a patient looks,” noted Russell Katz, MD, Director of the Division of Neurology Products at the FDA’s Center for Drug Evaluation and Research in Silver Spring, Maryland. “In clinical trials, treatment with Botox was found to be beneficial to patients with upper limb spasticity. Botox is manufactured by Allergan Inc, of Irvine, California.

Cardiorespiratory fitness can preserve neuronal integrity in patients with multiple sclerosis, according to a study published in the February Brain Research. Investigators analyzed the relationship between physical fitness and brain tissue health and found that higher fitness levels correlated with preserved gray matter volumes and white matter tract integrity, both of which are associated with faster processing speed. Statistical mapping showed an association between greater gray matter volume in midline cortical structures and higher levels of fitness, and fitness levels also correlated with fractional anisotropy in the left thalamic radiation and right anterior corona radiata. “Taken together, these results suggest that fitness exerts a prophylactic influence on the structural decline observed early on, preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability,” researchers noted.

The FDA has approved once-daily Mirapex ER (pramipexole dihydrochloride) extended-release tablets for the treatment of early idiopathic Parkinson’s disease. A randomized, double-blind, placebo-controlled multicenter trial of more than 400 patients found that treatment with extended-release pramipexole offered clinically significant improvement compared with placebo. The extended-release tablets also offered similar benefits to the currently available immediate-release formulation, which needs to be taken three times a day. “This new, once daily treatment has a more convenient dosing schedule, offering greater flexibility as someone with early Parkinson’s disease plans his or her day,” noted Robert Hauser, MD, Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida College of Medicine. Mirapex is distributed by Boehringer Ingelheim Pharmaceuticals, based in Ridgefield, Connecticut.

Recent immigrants to Ontario, Canada, have a lower risk of premature acute stroke than long-term residents, according to a population-matched cohort study in the February 9 Neurology. Researchers identified 965,829 new immigrants, defined as new recipients of universal public health insurance, and matched subjects to 3,272,393 long-term residents by year of birth, sex, and location. In a median six-year follow-up period, 6,216 strokes were reported. This translated to an incidence rate of 1.69 per 10,000 person-years among new residents and 2.56 per 10,000 person-years among long-term residents. After adjusting for age, income, residency, history of hypertension, diabetes mellitus, smoking, and number of insurance claims, the investigators found that the hazard ratio for stroke was 0.69. Risks for both ischemic and hemorrhagic strokes were similar.

Bilateral deep brain stimulation (DBS) of the anterior nuclei of the thalamus reduced the frequency of seizures in patients with refractory epilepsy, according to a study published in the March 18 online Epilepsia. The two-year, multicenter Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial included 110 patients with medically refractory partial seizures. In the initial three-month, double-blind segment, participants were randomized to either receive stimulation or no stimulation. At the three-month mark, the group that received stimulation reported a 29% greater reduction in seizures than the control group. For the remainder of the study, all patients received the treatment. At the two-year mark, there was a 56% median reduction in seizure frequency. Fourteen patients were seizure-free for at least six months, and researchers reported modest complication rates.

Long-term smoking has a greater effect in reducing the risk of Parkinson’s disease than the amount of cigarettes smoked per day, according to a study in the March 16 Neurology. Researchers compared the relative importance of smoking duration versus intensity in 305,468 participants of the NIH-AARP Diet and Health Cohort, 1,662 of whom were later diagnosed with Parkinson’s disease. Using multivariate logistic regression models, the investigators found that current smokers had a 0.56 odds ratio (OR) of Parkinson’s disease, compared with those who never smoked, and former smokers had an OR of 0.78. When the researchers stratified current and former smokers by number of years smoked, they found the highest Parkinson’s risk among those who smoked for fewer than 10 years (OR, 0.96) and the lowest risk among those who smoked for 30 or more years (OR, 0.59). The typical number of cigarettes smoked per day, in contrast, appeared to have no impact on risk.

The FDA has approved Botox (onabotulinumtoxin A) to treat spasticity in the flexor muscles of the elbow, wrist, and fingers in adults, a condition that is common after stroke or traumatic brain injury, or with the progression of multiple sclerosis. Botox works by temporarily blocking the connections between nerves and muscles, resulting in a temporary paralysis of the spastic muscle. “Muscles affected by spasticity have increased stiffness and tightness, which may lead to pain, difficulties with hygiene and other activities of daily living, and may affect how a patient looks,” noted Russell Katz, MD, Director of the Division of Neurology Products at the FDA’s Center for Drug Evaluation and Research in Silver Spring, Maryland. “In clinical trials, treatment with Botox was found to be beneficial to patients with upper limb spasticity. Botox is manufactured by Allergan Inc, of Irvine, California.

Cardiorespiratory fitness can preserve neuronal integrity in patients with multiple sclerosis, according to a study published in the February Brain Research. Investigators analyzed the relationship between physical fitness and brain tissue health and found that higher fitness levels correlated with preserved gray matter volumes and white matter tract integrity, both of which are associated with faster processing speed. Statistical mapping showed an association between greater gray matter volume in midline cortical structures and higher levels of fitness, and fitness levels also correlated with fractional anisotropy in the left thalamic radiation and right anterior corona radiata. “Taken together, these results suggest that fitness exerts a prophylactic influence on the structural decline observed early on, preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability,” researchers noted.

The FDA has approved once-daily Mirapex ER (pramipexole dihydrochloride) extended-release tablets for the treatment of early idiopathic Parkinson’s disease. A randomized, double-blind, placebo-controlled multicenter trial of more than 400 patients found that treatment with extended-release pramipexole offered clinically significant improvement compared with placebo. The extended-release tablets also offered similar benefits to the currently available immediate-release formulation, which needs to be taken three times a day. “This new, once daily treatment has a more convenient dosing schedule, offering greater flexibility as someone with early Parkinson’s disease plans his or her day,” noted Robert Hauser, MD, Director of the Parkinson’s Disease and Movement Disorders Center at the University of South Florida College of Medicine. Mirapex is distributed by Boehringer Ingelheim Pharmaceuticals, based in Ridgefield, Connecticut.

Recent immigrants to Ontario, Canada, have a lower risk of premature acute stroke than long-term residents, according to a population-matched cohort study in the February 9 Neurology. Researchers identified 965,829 new immigrants, defined as new recipients of universal public health insurance, and matched subjects to 3,272,393 long-term residents by year of birth, sex, and location. In a median six-year follow-up period, 6,216 strokes were reported. This translated to an incidence rate of 1.69 per 10,000 person-years among new residents and 2.56 per 10,000 person-years among long-term residents. After adjusting for age, income, residency, history of hypertension, diabetes mellitus, smoking, and number of insurance claims, the investigators found that the hazard ratio for stroke was 0.69. Risks for both ischemic and hemorrhagic strokes were similar.