News Roundup

Mild traumatic brain injury (TBI) may be associated with increased cortical fractional anisotropy, but not with cortical or subcortical atrophy, according to research published online ahead of print November 20 in Neurology. Investigators evaluated 50 patients and 50 sex-, age-, and education-matched controls with a clinical and neuroimaging battery approximately 14 days after TBI. A total of 26 patients returned for follow-up four months after injury. Patients had increased fractional anisotropy in the bilateral superior frontal cortex during the semiacute phase of injury. Fractional anisotropy in the left superior frontal cortex remained elevated at four months after injury. The researchers found no significant differences between patients and matched controls on neuropsychologic testing or measures of gray matter atrophy or mean diffusivity at either time point.

Researchers detailed the early clinical course, morbidity, and mortality of the 2012 outbreak of fungal infections associated with methylprednisolone injections in two articles published October 24, 2013, in the New England Journal of Medicine. As of July 1, 2013, a total of 749 cases of infection had been reported in 20 states, including 61 deaths. Of 728 patients for whom data were available, 31% had meningitis and no other documented infection. Of 328 patients without peripheral joint infection who were included in one investigation, 81% had CNS infection, and 19% had non-CNS infections only. The investigators found evidence of Exserohilum rostratum in 36% of patients for whom samples were available. Patients’ median age was 64, and the median incubation period was 47 days. Forty patients had a stroke.

An algorithm may accurately predict time to death, institutionalization, and need for full-time care in patients with Alzheimer’s disease, according to an article published online ahead of print September 24 in the Journal of Alzheimer’s Disease. Investigators followed two study cohorts with mild Alzheimer’s disease for 10 years. The first cohort included 252 patients, and the second included 254 patients. Participants underwent semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. For each of the three outcome measures, the predicted survival curves were well within the 95% confidence intervals of the observed survival curves. The actual and predicted survival curves were statistically equivalent. The algorithm can be adapted to predict other important disease end points, according to the researchers.

High pulse pressure may be associated with increased CSF phosphorylated tau and decreased β-amyloid 1–42 (Aβ_1–42) in cognitively normal older adults, according to research published online ahead of print November 13 in Neurology. A total of 177 cognitively normal, stroke-free older adults underwent blood pressure assessment for determination of pulse pressure, as well as lumbar puncture for measurement of CSF Aβ_1–42 and phosphorylated tau. High pulse pressure was associated with increased phosphorylated tau, reduced Aβ_1–42, and increased phosphorylated tau to Aβ_1–42 ratio. After controlling for covariates, the investigators found that pulse pressure remained associated with phosphorylated tau and phosphorylated tau to Aβ_1–42 ratio, but was no longer associated with Aβ_1–42. The relationship between pulse pressure and CSF biomarkers is age-dependent, said the researchers.

Acute stroke care in hospitals with neurology residency programs may be associated with an increased use of thrombolytics, investigators reported online ahead of print November 1 in Neurology. The disparities between the thrombolysis rates in hospitals with neurology residency programs and those in other teaching hospitals and nonteaching hospitals may be greater among elderly patients. Researchers retrospectively studied a nationally representative sample of patients with ischemic stroke. A total of 712,433 individuals from 6,839 hospital samples were included. Of these patients, 10.1%, 29.1%, and 60.8% were treated in hospitals with neurology residency programs, other teaching hospitals, and nonteaching hospitals, respectively. Patients in hospitals with neurology residency programs received thrombolysis more frequently (3.74%) than those in other teaching hospitals (2.28%) and those in nonteaching hospitals (1.44%).

The FDA has approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat partial-onset seizures associated with epilepsy. In three large, phase III safety and efficacy trials that included more than 1,400 patients with inadequately controlled partial-onset seizures, eslicarbazepine acetate was associated with statistically significant reductions in standardized seizure frequency, compared with placebo. Significantly more patients who received eslicarbazepine acetate had a reduction in seizure frequency of 50% or more, compared with controls. The most common side effects include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, and blurred vision. Eslicarbazepine acetate will not be classified as a controlled substance. Sunovion (Marlborough, Massachusetts) markets the drug and expects it to be available in the US during the second quarter of 2014.

The FDA has approved the NeuroPace RNS System, a device intended to reduce the frequency of seizures in patients with epilepsy who have not responded well to medications. The device consists of a small neurostimulator implanted within the skull. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. When it detects abnormal electrical activity, the neurostimulator delivers electrical stimulation to normalize brain activity and prevent seizures. In a randomized study of 191 patients, the average number of seizures per month was reduced by approximately 38% at three months in patients in whom the device was turned on. The RNS System is manufactured by NeuroPace (Mountainview, California).

Reducing blood pressure with antihypertensive medications may not decrease the likelihood of death and major disability among patients with acute ischemic stroke, according to a study published online ahead of print November 17 in JAMA. Researchers studied 4,071 patients with nonthrombolyzed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were randomized to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. The researchers found no difference in the rates of death and major disability between the treatment groups.

Persons with high urinary concentrations of tungsten may have an increased risk of stroke, according to a study published November 11 in PLOS One. Investigators analyzed associations between tungsten, commonly used in mobile phones and computers, and cardiovascular disease or stroke using crude and adjusted logistic regression models in a cohort of 8,614 adults (ages 18 to 74) with 193 reported stroke diagnoses and 428 reported diagnoses of cardiovascular disease. The researchers also stratified the data to characterize associations in a subset of individuals between ages 18 and 50. Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (odds ratio: 1.66). The association between tungsten and stroke in the young age category was still evident (odds ratio: 2.17).

Traumatic brain injury (TBI) may be associated with increased amyloid deposition, according to research published online ahead of print November 11 in JAMA Neurology. Investigators used carbon 11-labeled Pittsburgh Compound B ([¹¹C]PiB) PET to image amyloid deposition in 11 controls and 15 patients between one and 361 days after TBI. Compared with the controls, the patients with TBI had significantly increased [¹¹C]PiB distribution volume ratios in cortical gray matter and the striatum, but not in the thalamus or white matter. The investigators observed increases in [¹¹C]PiB distribution volume ratios in patients with TBI across most cortical subregions. The increases were replicated using comparisons of standardized uptake value ratios and could not be accounted for by methodologic confounders.

Compared with persons who speak only one language, bilingual individuals may have a delayed onset of dementia, according to a study published online ahead of print November 6 in Neurology. Investigators reviewed case records of 648 patients with dementia (391 bilinguals) diagnosed in a specialist clinic. They compared age at onset of first symptoms between monolingual and bilingual groups and examined the influence of the number of languages spoken, education, occupation, and other potentially interacting variables. Bilingual patients developed dementia 4.5 years later than the monolingual patients. The researchers found a significant difference in age at onset of Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. The age difference was also observed in illiterate patients. The investigators found no additional benefit to speaking more than two languages.

Temporal lobe epilepsy (TLE) may entail altered structural connectivity in the brain, according to a study published online ahead of print November 8 in Radiology. Investigators analyzed 60-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MRI volumes for 24 patients with left TLE and 24 healthy control subjects. MP-RAGE volumes were segmented into 1,015 regions of interest that spanned the entire brain. Patients with TLE had 22% to 45% reduced distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with healthy subjects. Local connectivity, as measured by means of network efficiency, was increased by 85% to 270% in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE, compared with healthy subjects.

Gray matter damage may be a key factor associated with long-term accumulation of disability and cognitive impairment in multiple sclerosis (MS), according to research published November 12 in Neurology. Investigators obtained conventional and magnetization transfer (MT) MRI brain scans at baseline and at 12 months for 73 patients with MS, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score and the MS severity score for a median of 13.3 years. At 13-year follow-up, 66% of patients had significant worsening of disability, and 37% had worse cognition. The multivariable model identified baseline gray matter fraction as the only predictor of disability worsening. Baseline disease duration and average gray matter lesion MT ratio were independent variables associated with cognitive deterioration.

—Erik Greb
Senior Associate Editor

Mild traumatic brain injury (TBI) may be associated with increased cortical fractional anisotropy, but not with cortical or subcortical atrophy, according to research published online ahead of print November 20 in Neurology. Investigators evaluated 50 patients and 50 sex-, age-, and education-matched controls with a clinical and neuroimaging battery approximately 14 days after TBI. A total of 26 patients returned for follow-up four months after injury. Patients had increased fractional anisotropy in the bilateral superior frontal cortex during the semiacute phase of injury. Fractional anisotropy in the left superior frontal cortex remained elevated at four months after injury. The researchers found no significant differences between patients and matched controls on neuropsychologic testing or measures of gray matter atrophy or mean diffusivity at either time point.

Researchers detailed the early clinical course, morbidity, and mortality of the 2012 outbreak of fungal infections associated with methylprednisolone injections in two articles published October 24, 2013, in the New England Journal of Medicine. As of July 1, 2013, a total of 749 cases of infection had been reported in 20 states, including 61 deaths. Of 728 patients for whom data were available, 31% had meningitis and no other documented infection. Of 328 patients without peripheral joint infection who were included in one investigation, 81% had CNS infection, and 19% had non-CNS infections only. The investigators found evidence of Exserohilum rostratum in 36% of patients for whom samples were available. Patients’ median age was 64, and the median incubation period was 47 days. Forty patients had a stroke.

An algorithm may accurately predict time to death, institutionalization, and need for full-time care in patients with Alzheimer’s disease, according to an article published online ahead of print September 24 in the Journal of Alzheimer’s Disease. Investigators followed two study cohorts with mild Alzheimer’s disease for 10 years. The first cohort included 252 patients, and the second included 254 patients. Participants underwent semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. For each of the three outcome measures, the predicted survival curves were well within the 95% confidence intervals of the observed survival curves. The actual and predicted survival curves were statistically equivalent. The algorithm can be adapted to predict other important disease end points, according to the researchers.

High pulse pressure may be associated with increased CSF phosphorylated tau and decreased β-amyloid 1–42 (Aβ_1–42) in cognitively normal older adults, according to research published online ahead of print November 13 in Neurology. A total of 177 cognitively normal, stroke-free older adults underwent blood pressure assessment for determination of pulse pressure, as well as lumbar puncture for measurement of CSF Aβ_1–42 and phosphorylated tau. High pulse pressure was associated with increased phosphorylated tau, reduced Aβ_1–42, and increased phosphorylated tau to Aβ_1–42 ratio. After controlling for covariates, the investigators found that pulse pressure remained associated with phosphorylated tau and phosphorylated tau to Aβ_1–42 ratio, but was no longer associated with Aβ_1–42. The relationship between pulse pressure and CSF biomarkers is age-dependent, said the researchers.

Acute stroke care in hospitals with neurology residency programs may be associated with an increased use of thrombolytics, investigators reported online ahead of print November 1 in Neurology. The disparities between the thrombolysis rates in hospitals with neurology residency programs and those in other teaching hospitals and nonteaching hospitals may be greater among elderly patients. Researchers retrospectively studied a nationally representative sample of patients with ischemic stroke. A total of 712,433 individuals from 6,839 hospital samples were included. Of these patients, 10.1%, 29.1%, and 60.8% were treated in hospitals with neurology residency programs, other teaching hospitals, and nonteaching hospitals, respectively. Patients in hospitals with neurology residency programs received thrombolysis more frequently (3.74%) than those in other teaching hospitals (2.28%) and those in nonteaching hospitals (1.44%).

The FDA has approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat partial-onset seizures associated with epilepsy. In three large, phase III safety and efficacy trials that included more than 1,400 patients with inadequately controlled partial-onset seizures, eslicarbazepine acetate was associated with statistically significant reductions in standardized seizure frequency, compared with placebo. Significantly more patients who received eslicarbazepine acetate had a reduction in seizure frequency of 50% or more, compared with controls. The most common side effects include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, and blurred vision. Eslicarbazepine acetate will not be classified as a controlled substance. Sunovion (Marlborough, Massachusetts) markets the drug and expects it to be available in the US during the second quarter of 2014.

The FDA has approved the NeuroPace RNS System, a device intended to reduce the frequency of seizures in patients with epilepsy who have not responded well to medications. The device consists of a small neurostimulator implanted within the skull. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. When it detects abnormal electrical activity, the neurostimulator delivers electrical stimulation to normalize brain activity and prevent seizures. In a randomized study of 191 patients, the average number of seizures per month was reduced by approximately 38% at three months in patients in whom the device was turned on. The RNS System is manufactured by NeuroPace (Mountainview, California).

Reducing blood pressure with antihypertensive medications may not decrease the likelihood of death and major disability among patients with acute ischemic stroke, according to a study published online ahead of print November 17 in JAMA. Researchers studied 4,071 patients with nonthrombolyzed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were randomized to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. The researchers found no difference in the rates of death and major disability between the treatment groups.

Persons with high urinary concentrations of tungsten may have an increased risk of stroke, according to a study published November 11 in PLOS One. Investigators analyzed associations between tungsten, commonly used in mobile phones and computers, and cardiovascular disease or stroke using crude and adjusted logistic regression models in a cohort of 8,614 adults (ages 18 to 74) with 193 reported stroke diagnoses and 428 reported diagnoses of cardiovascular disease. The researchers also stratified the data to characterize associations in a subset of individuals between ages 18 and 50. Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (odds ratio: 1.66). The association between tungsten and stroke in the young age category was still evident (odds ratio: 2.17).

Traumatic brain injury (TBI) may be associated with increased amyloid deposition, according to research published online ahead of print November 11 in JAMA Neurology. Investigators used carbon 11-labeled Pittsburgh Compound B ([¹¹C]PiB) PET to image amyloid deposition in 11 controls and 15 patients between one and 361 days after TBI. Compared with the controls, the patients with TBI had significantly increased [¹¹C]PiB distribution volume ratios in cortical gray matter and the striatum, but not in the thalamus or white matter. The investigators observed increases in [¹¹C]PiB distribution volume ratios in patients with TBI across most cortical subregions. The increases were replicated using comparisons of standardized uptake value ratios and could not be accounted for by methodologic confounders.

Compared with persons who speak only one language, bilingual individuals may have a delayed onset of dementia, according to a study published online ahead of print November 6 in Neurology. Investigators reviewed case records of 648 patients with dementia (391 bilinguals) diagnosed in a specialist clinic. They compared age at onset of first symptoms between monolingual and bilingual groups and examined the influence of the number of languages spoken, education, occupation, and other potentially interacting variables. Bilingual patients developed dementia 4.5 years later than the monolingual patients. The researchers found a significant difference in age at onset of Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. The age difference was also observed in illiterate patients. The investigators found no additional benefit to speaking more than two languages.

Temporal lobe epilepsy (TLE) may entail altered structural connectivity in the brain, according to a study published online ahead of print November 8 in Radiology. Investigators analyzed 60-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MRI volumes for 24 patients with left TLE and 24 healthy control subjects. MP-RAGE volumes were segmented into 1,015 regions of interest that spanned the entire brain. Patients with TLE had 22% to 45% reduced distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with healthy subjects. Local connectivity, as measured by means of network efficiency, was increased by 85% to 270% in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE, compared with healthy subjects.

Gray matter damage may be a key factor associated with long-term accumulation of disability and cognitive impairment in multiple sclerosis (MS), according to research published November 12 in Neurology. Investigators obtained conventional and magnetization transfer (MT) MRI brain scans at baseline and at 12 months for 73 patients with MS, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score and the MS severity score for a median of 13.3 years. At 13-year follow-up, 66% of patients had significant worsening of disability, and 37% had worse cognition. The multivariable model identified baseline gray matter fraction as the only predictor of disability worsening. Baseline disease duration and average gray matter lesion MT ratio were independent variables associated with cognitive deterioration.

—Erik Greb
Senior Associate Editor

Mild traumatic brain injury (TBI) may be associated with increased cortical fractional anisotropy, but not with cortical or subcortical atrophy, according to research published online ahead of print November 20 in Neurology. Investigators evaluated 50 patients and 50 sex-, age-, and education-matched controls with a clinical and neuroimaging battery approximately 14 days after TBI. A total of 26 patients returned for follow-up four months after injury. Patients had increased fractional anisotropy in the bilateral superior frontal cortex during the semiacute phase of injury. Fractional anisotropy in the left superior frontal cortex remained elevated at four months after injury. The researchers found no significant differences between patients and matched controls on neuropsychologic testing or measures of gray matter atrophy or mean diffusivity at either time point.

Researchers detailed the early clinical course, morbidity, and mortality of the 2012 outbreak of fungal infections associated with methylprednisolone injections in two articles published October 24, 2013, in the New England Journal of Medicine. As of July 1, 2013, a total of 749 cases of infection had been reported in 20 states, including 61 deaths. Of 728 patients for whom data were available, 31% had meningitis and no other documented infection. Of 328 patients without peripheral joint infection who were included in one investigation, 81% had CNS infection, and 19% had non-CNS infections only. The investigators found evidence of Exserohilum rostratum in 36% of patients for whom samples were available. Patients’ median age was 64, and the median incubation period was 47 days. Forty patients had a stroke.

An algorithm may accurately predict time to death, institutionalization, and need for full-time care in patients with Alzheimer’s disease, according to an article published online ahead of print September 24 in the Journal of Alzheimer’s Disease. Investigators followed two study cohorts with mild Alzheimer’s disease for 10 years. The first cohort included 252 patients, and the second included 254 patients. Participants underwent semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. For each of the three outcome measures, the predicted survival curves were well within the 95% confidence intervals of the observed survival curves. The actual and predicted survival curves were statistically equivalent. The algorithm can be adapted to predict other important disease end points, according to the researchers.

High pulse pressure may be associated with increased CSF phosphorylated tau and decreased β-amyloid 1–42 (Aβ_1–42) in cognitively normal older adults, according to research published online ahead of print November 13 in Neurology. A total of 177 cognitively normal, stroke-free older adults underwent blood pressure assessment for determination of pulse pressure, as well as lumbar puncture for measurement of CSF Aβ_1–42 and phosphorylated tau. High pulse pressure was associated with increased phosphorylated tau, reduced Aβ_1–42, and increased phosphorylated tau to Aβ_1–42 ratio. After controlling for covariates, the investigators found that pulse pressure remained associated with phosphorylated tau and phosphorylated tau to Aβ_1–42 ratio, but was no longer associated with Aβ_1–42. The relationship between pulse pressure and CSF biomarkers is age-dependent, said the researchers.

Acute stroke care in hospitals with neurology residency programs may be associated with an increased use of thrombolytics, investigators reported online ahead of print November 1 in Neurology. The disparities between the thrombolysis rates in hospitals with neurology residency programs and those in other teaching hospitals and nonteaching hospitals may be greater among elderly patients. Researchers retrospectively studied a nationally representative sample of patients with ischemic stroke. A total of 712,433 individuals from 6,839 hospital samples were included. Of these patients, 10.1%, 29.1%, and 60.8% were treated in hospitals with neurology residency programs, other teaching hospitals, and nonteaching hospitals, respectively. Patients in hospitals with neurology residency programs received thrombolysis more frequently (3.74%) than those in other teaching hospitals (2.28%) and those in nonteaching hospitals (1.44%).

The FDA has approved Aptiom (eslicarbazepine acetate) as an add-on medication to treat partial-onset seizures associated with epilepsy. In three large, phase III safety and efficacy trials that included more than 1,400 patients with inadequately controlled partial-onset seizures, eslicarbazepine acetate was associated with statistically significant reductions in standardized seizure frequency, compared with placebo. Significantly more patients who received eslicarbazepine acetate had a reduction in seizure frequency of 50% or more, compared with controls. The most common side effects include dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, and blurred vision. Eslicarbazepine acetate will not be classified as a controlled substance. Sunovion (Marlborough, Massachusetts) markets the drug and expects it to be available in the US during the second quarter of 2014.

The FDA has approved the NeuroPace RNS System, a device intended to reduce the frequency of seizures in patients with epilepsy who have not responded well to medications. The device consists of a small neurostimulator implanted within the skull. The neurostimulator is connected to one or two electrodes that are placed where the seizures are suspected to originate within the brain or on the surface of the brain. When it detects abnormal electrical activity, the neurostimulator delivers electrical stimulation to normalize brain activity and prevent seizures. In a randomized study of 191 patients, the average number of seizures per month was reduced by approximately 38% at three months in patients in whom the device was turned on. The RNS System is manufactured by NeuroPace (Mountainview, California).

Reducing blood pressure with antihypertensive medications may not decrease the likelihood of death and major disability among patients with acute ischemic stroke, according to a study published online ahead of print November 17 in JAMA. Researchers studied 4,071 patients with nonthrombolyzed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were randomized to receive antihypertensive treatment or to discontinue all antihypertensive medications during hospitalization. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. The researchers found no difference in the rates of death and major disability between the treatment groups.

Persons with high urinary concentrations of tungsten may have an increased risk of stroke, according to a study published November 11 in PLOS One. Investigators analyzed associations between tungsten, commonly used in mobile phones and computers, and cardiovascular disease or stroke using crude and adjusted logistic regression models in a cohort of 8,614 adults (ages 18 to 74) with 193 reported stroke diagnoses and 428 reported diagnoses of cardiovascular disease. The researchers also stratified the data to characterize associations in a subset of individuals between ages 18 and 50. Elevated tungsten concentrations were strongly associated with an increase in the prevalence of stroke, independent of typical risk factors (odds ratio: 1.66). The association between tungsten and stroke in the young age category was still evident (odds ratio: 2.17).

Traumatic brain injury (TBI) may be associated with increased amyloid deposition, according to research published online ahead of print November 11 in JAMA Neurology. Investigators used carbon 11-labeled Pittsburgh Compound B ([¹¹C]PiB) PET to image amyloid deposition in 11 controls and 15 patients between one and 361 days after TBI. Compared with the controls, the patients with TBI had significantly increased [¹¹C]PiB distribution volume ratios in cortical gray matter and the striatum, but not in the thalamus or white matter. The investigators observed increases in [¹¹C]PiB distribution volume ratios in patients with TBI across most cortical subregions. The increases were replicated using comparisons of standardized uptake value ratios and could not be accounted for by methodologic confounders.

Compared with persons who speak only one language, bilingual individuals may have a delayed onset of dementia, according to a study published online ahead of print November 6 in Neurology. Investigators reviewed case records of 648 patients with dementia (391 bilinguals) diagnosed in a specialist clinic. They compared age at onset of first symptoms between monolingual and bilingual groups and examined the influence of the number of languages spoken, education, occupation, and other potentially interacting variables. Bilingual patients developed dementia 4.5 years later than the monolingual patients. The researchers found a significant difference in age at onset of Alzheimer’s disease dementia, frontotemporal dementia, and vascular dementia. The age difference was also observed in illiterate patients. The investigators found no additional benefit to speaking more than two languages.

Temporal lobe epilepsy (TLE) may entail altered structural connectivity in the brain, according to a study published online ahead of print November 8 in Radiology. Investigators analyzed 60-direction diffusion-tensor imaging and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MRI volumes for 24 patients with left TLE and 24 healthy control subjects. MP-RAGE volumes were segmented into 1,015 regions of interest that spanned the entire brain. Patients with TLE had 22% to 45% reduced distant connectivity in the medial orbitofrontal cortex, temporal cortex, posterior cingulate cortex, and precuneus, compared with healthy subjects. Local connectivity, as measured by means of network efficiency, was increased by 85% to 270% in the medial and lateral frontal cortices, insular cortex, posterior cingulate cortex, precuneus, and occipital cortex in patients with TLE, compared with healthy subjects.

Gray matter damage may be a key factor associated with long-term accumulation of disability and cognitive impairment in multiple sclerosis (MS), according to research published November 12 in Neurology. Investigators obtained conventional and magnetization transfer (MT) MRI brain scans at baseline and at 12 months for 73 patients with MS, who were followed prospectively with clinical visits and rating of the Expanded Disability Status Scale (EDSS) score and the MS severity score for a median of 13.3 years. At 13-year follow-up, 66% of patients had significant worsening of disability, and 37% had worse cognition. The multivariable model identified baseline gray matter fraction as the only predictor of disability worsening. Baseline disease duration and average gray matter lesion MT ratio were independent variables associated with cognitive deterioration.

—Erik Greb
Senior Associate Editor

In early December 2013, the FDA will formally recommend to the US Department of Health and Human Services (HHS) that hydrocodone combination products be reclassified as Schedule II drugs. The proposed change would tighten the controls on these products, which now are classified as Schedule III. The recommendation follows the US Drug Enforcement Administration’s (DEA) 2009 request for guidance from HHS regarding hydrocodone combination products such as Vicodin. The FDA’s determination is the result of an analysis of the scientific literature, a review of hundreds of public comments on the issue, and several public meetings, according to a statement by Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research. The recommendation will influence the DEA’s final decision on the appropriate scheduling of these products.

Influenza vaccination may reduce patients’ risk of major adverse cardiovascular events, including stroke, according to a meta-analysis published October 23 in JAMA. Researchers conducted a systematic review of randomized clinical trials listed in MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials that compared influenza vaccine with placebo or control in patients at high risk of cardiovascular disease. Six trials encompassing 6,735 patients were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome. The greatest treatment effect was observed among the highest-risk patients with more active coronary disease, and a larger trial is warranted to assess these findings, said the researchers.

Short sleep duration and poor sleep quality may be associated with greater β-amyloid burden among community-dwelling older adults, according to research published online ahead of print October 21 in JAMA Neurology. Investigators performed a cross-sectional study of 70 adult participants (mean age, 76) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. The study’s main outcome measure was β-amyloid burden, measured by carbon 11-labeled Pittsburgh compound B PET distribution volume ratios. After adjustment for potential confounders, the researchers found an association between reports of shorter sleep duration and greater β-amyloid burden, measured by mean cortical distribution volume ratio and precuneus distribution volume ratio. Reports of lower sleep quality were associated with greater β-amyloid burden, measured by precuneus distribution volume ratio.

High blood glucose levels may adversely affect cognition, even among patients without type 2 diabetes or impaired glucose tolerance, researchers reported online ahead of print October 23 in Neurology. The effect may be mediated by structural changes in learning-relevant brain areas, the authors noted. The group tested memory in 141 individuals using the Rey Auditory Verbal Learning Test and acquired peripheral levels of fasting HbA1c, glucose, and insulin. Clinicians performed 3-T MRI scans to assess hippocampal volume and microstructure. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Mediation analyses indicated that beneficial effects of lower HbA1c on memory are partly mediated by hippocampal volume and microstructure.

Among older adults, arterial stiffness may be associated with b-amyloid plaque deposition in the brain, independent of blood pressure and APOE ε4 allele, according to a study published online ahead of print October 16 in Neurology. Investigators studied 91 dementia-free participants between ages 83 and 96. Participants underwent brain MRI and PET imaging with Pittsburgh compound B. The researchers measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed vascular beds. A total of 44 subjects were β-amyloid positive on PET scan. The investigators found that β-amyloid deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in brachial ankle PWV resulted in a twofold increase in the odds of being β-amyloid positive.

The FDA has approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug, for use with PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia. Vizamyl attaches to β-amyloid and produces a PET image that is used to evaluate the presence of β-amyloid. The drug’s effectiveness was established in two clinical studies of 384 participants with a range of cognitive function. All participants were injected with Vizamyl and scanned. The images were interpreted by five independent readers masked to all clinical information. A portion of scan results was also confirmed by autopsy. Following the approval of Amyvid (Florbetapir F 18 injection) in 2012, Vizamyl, manufactured by Medi-Physics (Arlington Heights, Illinois), becomes the second diagnostic drug available for visualizing β-amyloid on a PET scan of the brain.

Clostridium perfringens type B, an epsilon toxin-secreting bacillus, may trigger multiple sclerosis (MS), according to research published October 16 in PLOS One. After detecting C. perfringens type B in a woman with MS, investigators tested blood and CSF from patients with MS and controls for antibody reactivity to the epsilon toxin. Levels of epsilon toxin antibodies were 10 times higher in patients with MS, compared with controls. After examining stool samples, the study authors found the human commensal C. perfringens type A in approximately 50% of healthy controls, compared with 23% of patients with MS. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation because these lesions are characterized by blood–brain barrier permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate, said the researchers.

Chronic cerebrospinal venous insufficiency (CCSVI), which has been proposed as a contributor to multiple sclerosis (MS), occurs rarely in patients with MS and in controls, according to a study published online ahead of print October 8 in Lancet. Researchers performed an assessor-blinded, case-control, multicenter study of 79 people with MS, 55 unaffected siblings, and 43 unrelated healthy volunteers. Catheter venography criteria for CCSVI were positive for 2% of people with MS, 2% of siblings, and 3% of unrelated controls. Greater than 50% narrowing of any major vein was present in 74% of people with MS, 66% of siblings, and 70% of unrelated controls. The Zamboni ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography, and the significance of venous narrowing to MS remains unknown, said the investigators.

Measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with Parkinson’s disease, according to research published online ahead of print October 2 in Neurology. Investigators examined 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The researchers performed autonomic testing and skin biopsies at the distal leg, distal thigh, and proximal thigh for all participants. Deposition of α-synuclein and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. The investigators normalized α-synuclein deposition to nerve fiber density. Patients with Parkinson’s disease had greater α-synuclein deposition and higher α-synuclein ratios than controls within pilomotor nerves and sudomotor nerves, but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores, sympathetic adrenergic function, and parasympathetic function.

Depression may be an independent risk factor for Parkinson’s disease, according to research published October 22 in Neurology. Investigators conducted a retrospective study of 4,634 patients with depression and 18,544 matched controls who were selected from a national health insurance database. Patients were observed for a maximum of 10 years to determine the rates of new-onset Parkinson’s disease. Cox regression was used to identify the predictors of the disease. During the follow-up period, 66 patients with depression and 97 controls were diagnosed with Parkinson’s disease. After adjusting for age and sex, the researchers found that patients with depression were 3.24 times more likely to develop Parkinson’s disease, compared with the control patients. The investigators observed that age and difficult-to-treat depression are independent risk factors for Parkinson’s disease in patients with depression.

The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in red blood cells may have no association with age-associated cognitive decline, researchers reported in the October 22 issue of Neurology. The investigators conducted a retrospective cohort study of 2,157 women with normal cognition who were followed with annual cognitive testing for a median of 5.9 years. End points were composite cognitive function and performance in seven cognitive domains. After adjustment for demographic, clinical, and behavioral characteristics, the investigators found no significant cross-sectional cognitive differences between women in the high and low DHA and EPA tertiles at the first annual cognitive battery. In addition, no significant differences were found between the high and low DHA and EPA tertiles in the rate of cognitive change over time.

Common psychosocial stressors (eg, divorce, widowhood, work problems, and illness in a relative) may have severe and long-standing physiologic and psychologic consequences such as dementia, according to research published September 30 in BMJ Open. In a prospective longitudinal population study, clinicians performed psychiatric examinations for 800 women born in 1914, 1918, 1922, and 1930. Baseline examinations took place in 1968, and follow-up occurred in 1974, 1980, 1992, 2000, and 2005. During follow-up, 153 women developed dementia. The number of psychosocial stressors in 1968 was associated with higher incidence of dementia and Alzheimer’s disease (AD) between 1968 and 2005 in multivariate Cox regressions. The number of psychosocial stressors in 1968 was also associated with distress in 1968, 1974, 1980, 2000, and 2005 in multivariate logistic regressions.

Aggressive medical management may provide more benefit than percutaneous transluminal angioplasty and stenting (PTAS) for high-risk patients with atherosclerotic intracranial arterial stenosis, according to a study published online ahead of print October 26 in Lancet. Investigators randomized 451 patients with recent transient ischemic attack or stroke to aggressive medical management or aggressive medical management plus stenting with the Wingspan stent. The cumulative probability of stroke or death was smaller in the medical group vs the PTAS group. Beyond 30 days, 10% of patients in the medical group and 10% of patients in the stenting group had a primary end point. The absolute differences in the primary end point rates between the two groups were 7.1% at year 1, 6.5% at year 2 and 9.0% at year 3.

—Erik Greb
Senior Associate Editor

In early December 2013, the FDA will formally recommend to the US Department of Health and Human Services (HHS) that hydrocodone combination products be reclassified as Schedule II drugs. The proposed change would tighten the controls on these products, which now are classified as Schedule III. The recommendation follows the US Drug Enforcement Administration’s (DEA) 2009 request for guidance from HHS regarding hydrocodone combination products such as Vicodin. The FDA’s determination is the result of an analysis of the scientific literature, a review of hundreds of public comments on the issue, and several public meetings, according to a statement by Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research. The recommendation will influence the DEA’s final decision on the appropriate scheduling of these products.

Influenza vaccination may reduce patients’ risk of major adverse cardiovascular events, including stroke, according to a meta-analysis published October 23 in JAMA. Researchers conducted a systematic review of randomized clinical trials listed in MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials that compared influenza vaccine with placebo or control in patients at high risk of cardiovascular disease. Six trials encompassing 6,735 patients were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome. The greatest treatment effect was observed among the highest-risk patients with more active coronary disease, and a larger trial is warranted to assess these findings, said the researchers.

Short sleep duration and poor sleep quality may be associated with greater β-amyloid burden among community-dwelling older adults, according to research published online ahead of print October 21 in JAMA Neurology. Investigators performed a cross-sectional study of 70 adult participants (mean age, 76) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. The study’s main outcome measure was β-amyloid burden, measured by carbon 11-labeled Pittsburgh compound B PET distribution volume ratios. After adjustment for potential confounders, the researchers found an association between reports of shorter sleep duration and greater β-amyloid burden, measured by mean cortical distribution volume ratio and precuneus distribution volume ratio. Reports of lower sleep quality were associated with greater β-amyloid burden, measured by precuneus distribution volume ratio.

High blood glucose levels may adversely affect cognition, even among patients without type 2 diabetes or impaired glucose tolerance, researchers reported online ahead of print October 23 in Neurology. The effect may be mediated by structural changes in learning-relevant brain areas, the authors noted. The group tested memory in 141 individuals using the Rey Auditory Verbal Learning Test and acquired peripheral levels of fasting HbA1c, glucose, and insulin. Clinicians performed 3-T MRI scans to assess hippocampal volume and microstructure. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Mediation analyses indicated that beneficial effects of lower HbA1c on memory are partly mediated by hippocampal volume and microstructure.

Among older adults, arterial stiffness may be associated with b-amyloid plaque deposition in the brain, independent of blood pressure and APOE ε4 allele, according to a study published online ahead of print October 16 in Neurology. Investigators studied 91 dementia-free participants between ages 83 and 96. Participants underwent brain MRI and PET imaging with Pittsburgh compound B. The researchers measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed vascular beds. A total of 44 subjects were β-amyloid positive on PET scan. The investigators found that β-amyloid deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in brachial ankle PWV resulted in a twofold increase in the odds of being β-amyloid positive.

The FDA has approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug, for use with PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia. Vizamyl attaches to β-amyloid and produces a PET image that is used to evaluate the presence of β-amyloid. The drug’s effectiveness was established in two clinical studies of 384 participants with a range of cognitive function. All participants were injected with Vizamyl and scanned. The images were interpreted by five independent readers masked to all clinical information. A portion of scan results was also confirmed by autopsy. Following the approval of Amyvid (Florbetapir F 18 injection) in 2012, Vizamyl, manufactured by Medi-Physics (Arlington Heights, Illinois), becomes the second diagnostic drug available for visualizing β-amyloid on a PET scan of the brain.

Clostridium perfringens type B, an epsilon toxin-secreting bacillus, may trigger multiple sclerosis (MS), according to research published October 16 in PLOS One. After detecting C. perfringens type B in a woman with MS, investigators tested blood and CSF from patients with MS and controls for antibody reactivity to the epsilon toxin. Levels of epsilon toxin antibodies were 10 times higher in patients with MS, compared with controls. After examining stool samples, the study authors found the human commensal C. perfringens type A in approximately 50% of healthy controls, compared with 23% of patients with MS. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation because these lesions are characterized by blood–brain barrier permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate, said the researchers.

Chronic cerebrospinal venous insufficiency (CCSVI), which has been proposed as a contributor to multiple sclerosis (MS), occurs rarely in patients with MS and in controls, according to a study published online ahead of print October 8 in Lancet. Researchers performed an assessor-blinded, case-control, multicenter study of 79 people with MS, 55 unaffected siblings, and 43 unrelated healthy volunteers. Catheter venography criteria for CCSVI were positive for 2% of people with MS, 2% of siblings, and 3% of unrelated controls. Greater than 50% narrowing of any major vein was present in 74% of people with MS, 66% of siblings, and 70% of unrelated controls. The Zamboni ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography, and the significance of venous narrowing to MS remains unknown, said the investigators.

Measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with Parkinson’s disease, according to research published online ahead of print October 2 in Neurology. Investigators examined 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The researchers performed autonomic testing and skin biopsies at the distal leg, distal thigh, and proximal thigh for all participants. Deposition of α-synuclein and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. The investigators normalized α-synuclein deposition to nerve fiber density. Patients with Parkinson’s disease had greater α-synuclein deposition and higher α-synuclein ratios than controls within pilomotor nerves and sudomotor nerves, but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores, sympathetic adrenergic function, and parasympathetic function.

Depression may be an independent risk factor for Parkinson’s disease, according to research published October 22 in Neurology. Investigators conducted a retrospective study of 4,634 patients with depression and 18,544 matched controls who were selected from a national health insurance database. Patients were observed for a maximum of 10 years to determine the rates of new-onset Parkinson’s disease. Cox regression was used to identify the predictors of the disease. During the follow-up period, 66 patients with depression and 97 controls were diagnosed with Parkinson’s disease. After adjusting for age and sex, the researchers found that patients with depression were 3.24 times more likely to develop Parkinson’s disease, compared with the control patients. The investigators observed that age and difficult-to-treat depression are independent risk factors for Parkinson’s disease in patients with depression.

The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in red blood cells may have no association with age-associated cognitive decline, researchers reported in the October 22 issue of Neurology. The investigators conducted a retrospective cohort study of 2,157 women with normal cognition who were followed with annual cognitive testing for a median of 5.9 years. End points were composite cognitive function and performance in seven cognitive domains. After adjustment for demographic, clinical, and behavioral characteristics, the investigators found no significant cross-sectional cognitive differences between women in the high and low DHA and EPA tertiles at the first annual cognitive battery. In addition, no significant differences were found between the high and low DHA and EPA tertiles in the rate of cognitive change over time.

Common psychosocial stressors (eg, divorce, widowhood, work problems, and illness in a relative) may have severe and long-standing physiologic and psychologic consequences such as dementia, according to research published September 30 in BMJ Open. In a prospective longitudinal population study, clinicians performed psychiatric examinations for 800 women born in 1914, 1918, 1922, and 1930. Baseline examinations took place in 1968, and follow-up occurred in 1974, 1980, 1992, 2000, and 2005. During follow-up, 153 women developed dementia. The number of psychosocial stressors in 1968 was associated with higher incidence of dementia and Alzheimer’s disease (AD) between 1968 and 2005 in multivariate Cox regressions. The number of psychosocial stressors in 1968 was also associated with distress in 1968, 1974, 1980, 2000, and 2005 in multivariate logistic regressions.

Aggressive medical management may provide more benefit than percutaneous transluminal angioplasty and stenting (PTAS) for high-risk patients with atherosclerotic intracranial arterial stenosis, according to a study published online ahead of print October 26 in Lancet. Investigators randomized 451 patients with recent transient ischemic attack or stroke to aggressive medical management or aggressive medical management plus stenting with the Wingspan stent. The cumulative probability of stroke or death was smaller in the medical group vs the PTAS group. Beyond 30 days, 10% of patients in the medical group and 10% of patients in the stenting group had a primary end point. The absolute differences in the primary end point rates between the two groups were 7.1% at year 1, 6.5% at year 2 and 9.0% at year 3.

—Erik Greb
Senior Associate Editor

In early December 2013, the FDA will formally recommend to the US Department of Health and Human Services (HHS) that hydrocodone combination products be reclassified as Schedule II drugs. The proposed change would tighten the controls on these products, which now are classified as Schedule III. The recommendation follows the US Drug Enforcement Administration’s (DEA) 2009 request for guidance from HHS regarding hydrocodone combination products such as Vicodin. The FDA’s determination is the result of an analysis of the scientific literature, a review of hundreds of public comments on the issue, and several public meetings, according to a statement by Janet Woodcock, MD, Director of the Center for Drug Evaluation and Research. The recommendation will influence the DEA’s final decision on the appropriate scheduling of these products.

Influenza vaccination may reduce patients’ risk of major adverse cardiovascular events, including stroke, according to a meta-analysis published October 23 in JAMA. Researchers conducted a systematic review of randomized clinical trials listed in MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials that compared influenza vaccine with placebo or control in patients at high risk of cardiovascular disease. Six trials encompassing 6,735 patients were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%) in published trials. A treatment interaction was detected between patients with and without recent acute coronary syndrome. The greatest treatment effect was observed among the highest-risk patients with more active coronary disease, and a larger trial is warranted to assess these findings, said the researchers.

Short sleep duration and poor sleep quality may be associated with greater β-amyloid burden among community-dwelling older adults, according to research published online ahead of print October 21 in JAMA Neurology. Investigators performed a cross-sectional study of 70 adult participants (mean age, 76) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. The study’s main outcome measure was β-amyloid burden, measured by carbon 11-labeled Pittsburgh compound B PET distribution volume ratios. After adjustment for potential confounders, the researchers found an association between reports of shorter sleep duration and greater β-amyloid burden, measured by mean cortical distribution volume ratio and precuneus distribution volume ratio. Reports of lower sleep quality were associated with greater β-amyloid burden, measured by precuneus distribution volume ratio.

High blood glucose levels may adversely affect cognition, even among patients without type 2 diabetes or impaired glucose tolerance, researchers reported online ahead of print October 23 in Neurology. The effect may be mediated by structural changes in learning-relevant brain areas, the authors noted. The group tested memory in 141 individuals using the Rey Auditory Verbal Learning Test and acquired peripheral levels of fasting HbA1c, glucose, and insulin. Clinicians performed 3-T MRI scans to assess hippocampal volume and microstructure. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Mediation analyses indicated that beneficial effects of lower HbA1c on memory are partly mediated by hippocampal volume and microstructure.

Among older adults, arterial stiffness may be associated with b-amyloid plaque deposition in the brain, independent of blood pressure and APOE ε4 allele, according to a study published online ahead of print October 16 in Neurology. Investigators studied 91 dementia-free participants between ages 83 and 96. Participants underwent brain MRI and PET imaging with Pittsburgh compound B. The researchers measured resting blood pressure (BP), mean arterial pressure (MAP), and arterial stiffness by pulse wave velocity (PWV) in the central, peripheral, and mixed vascular beds. A total of 44 subjects were β-amyloid positive on PET scan. The investigators found that β-amyloid deposition was associated with mixed PWV, systolic BP, and MAP. One SD increase in brachial ankle PWV resulted in a twofold increase in the odds of being β-amyloid positive.

The FDA has approved Vizamyl (flutemetamol F 18 injection), a radioactive diagnostic drug, for use with PET imaging of the brain in adults being evaluated for Alzheimer’s disease and dementia. Vizamyl attaches to β-amyloid and produces a PET image that is used to evaluate the presence of β-amyloid. The drug’s effectiveness was established in two clinical studies of 384 participants with a range of cognitive function. All participants were injected with Vizamyl and scanned. The images were interpreted by five independent readers masked to all clinical information. A portion of scan results was also confirmed by autopsy. Following the approval of Amyvid (Florbetapir F 18 injection) in 2012, Vizamyl, manufactured by Medi-Physics (Arlington Heights, Illinois), becomes the second diagnostic drug available for visualizing β-amyloid on a PET scan of the brain.

Clostridium perfringens type B, an epsilon toxin-secreting bacillus, may trigger multiple sclerosis (MS), according to research published October 16 in PLOS One. After detecting C. perfringens type B in a woman with MS, investigators tested blood and CSF from patients with MS and controls for antibody reactivity to the epsilon toxin. Levels of epsilon toxin antibodies were 10 times higher in patients with MS, compared with controls. After examining stool samples, the study authors found the human commensal C. perfringens type A in approximately 50% of healthy controls, compared with 23% of patients with MS. C. perfringens epsilon toxin fits mechanistically with nascent MS lesion formation because these lesions are characterized by blood–brain barrier permeability and oligodendrocyte cell death in the absence of an adaptive immune infiltrate, said the researchers.

Chronic cerebrospinal venous insufficiency (CCSVI), which has been proposed as a contributor to multiple sclerosis (MS), occurs rarely in patients with MS and in controls, according to a study published online ahead of print October 8 in Lancet. Researchers performed an assessor-blinded, case-control, multicenter study of 79 people with MS, 55 unaffected siblings, and 43 unrelated healthy volunteers. Catheter venography criteria for CCSVI were positive for 2% of people with MS, 2% of siblings, and 3% of unrelated controls. Greater than 50% narrowing of any major vein was present in 74% of people with MS, 66% of siblings, and 70% of unrelated controls. The Zamboni ultrasound criteria are neither sensitive nor specific for narrowing on catheter venography, and the significance of venous narrowing to MS remains unknown, said the investigators.

Measures of α-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with Parkinson’s disease, according to research published online ahead of print October 2 in Neurology. Investigators examined 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The researchers performed autonomic testing and skin biopsies at the distal leg, distal thigh, and proximal thigh for all participants. Deposition of α-synuclein and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. The investigators normalized α-synuclein deposition to nerve fiber density. Patients with Parkinson’s disease had greater α-synuclein deposition and higher α-synuclein ratios than controls within pilomotor nerves and sudomotor nerves, but not sensory nerves. Higher α-synuclein ratios correlated with Hoehn and Yahr scores, sympathetic adrenergic function, and parasympathetic function.

Depression may be an independent risk factor for Parkinson’s disease, according to research published October 22 in Neurology. Investigators conducted a retrospective study of 4,634 patients with depression and 18,544 matched controls who were selected from a national health insurance database. Patients were observed for a maximum of 10 years to determine the rates of new-onset Parkinson’s disease. Cox regression was used to identify the predictors of the disease. During the follow-up period, 66 patients with depression and 97 controls were diagnosed with Parkinson’s disease. After adjusting for age and sex, the researchers found that patients with depression were 3.24 times more likely to develop Parkinson’s disease, compared with the control patients. The investigators observed that age and difficult-to-treat depression are independent risk factors for Parkinson’s disease in patients with depression.

The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in red blood cells may have no association with age-associated cognitive decline, researchers reported in the October 22 issue of Neurology. The investigators conducted a retrospective cohort study of 2,157 women with normal cognition who were followed with annual cognitive testing for a median of 5.9 years. End points were composite cognitive function and performance in seven cognitive domains. After adjustment for demographic, clinical, and behavioral characteristics, the investigators found no significant cross-sectional cognitive differences between women in the high and low DHA and EPA tertiles at the first annual cognitive battery. In addition, no significant differences were found between the high and low DHA and EPA tertiles in the rate of cognitive change over time.

Common psychosocial stressors (eg, divorce, widowhood, work problems, and illness in a relative) may have severe and long-standing physiologic and psychologic consequences such as dementia, according to research published September 30 in BMJ Open. In a prospective longitudinal population study, clinicians performed psychiatric examinations for 800 women born in 1914, 1918, 1922, and 1930. Baseline examinations took place in 1968, and follow-up occurred in 1974, 1980, 1992, 2000, and 2005. During follow-up, 153 women developed dementia. The number of psychosocial stressors in 1968 was associated with higher incidence of dementia and Alzheimer’s disease (AD) between 1968 and 2005 in multivariate Cox regressions. The number of psychosocial stressors in 1968 was also associated with distress in 1968, 1974, 1980, 2000, and 2005 in multivariate logistic regressions.

Aggressive medical management may provide more benefit than percutaneous transluminal angioplasty and stenting (PTAS) for high-risk patients with atherosclerotic intracranial arterial stenosis, according to a study published online ahead of print October 26 in Lancet. Investigators randomized 451 patients with recent transient ischemic attack or stroke to aggressive medical management or aggressive medical management plus stenting with the Wingspan stent. The cumulative probability of stroke or death was smaller in the medical group vs the PTAS group. Beyond 30 days, 10% of patients in the medical group and 10% of patients in the stenting group had a primary end point. The absolute differences in the primary end point rates between the two groups were 7.1% at year 1, 6.5% at year 2 and 9.0% at year 3.

—Erik Greb
Senior Associate Editor

By lowering homocysteine levels, vitamin B supplementation may reduce the risk of stroke significantly for some individuals, according to research published online ahead of print September 18 in Neurology. Investigators analyzed data from 14 randomized controlled trials published before August 2012. The trials included 54,913 participants, and the investigators measured the association between B vitamin supplementation and end point events using a fixed-effects model and χ2 tests. The group observed a reduction in overall stroke events resulting from reduction in homocysteine levels following B vitamin supplementation, but not in subgroups divided according to primary or secondary prevention measures, ischemic versus hemorrhagic stroke, or occurrence of fatal stroke. Vitamin B reduced stroke events in subgroups with three or more years of follow-up and without cereal folate fortification or chronic kidney disease.

The deletion of information from chromosome 22 may be a genetic risk factor for early-onset Parkinson’s disease, researchers reported online ahead of print September 9 in JAMA Neurology. The investigators conducted an observational study of the occurrence of Parkinson’s disease in a cohort of 159 adults with a molecularly confirmed diagnosis of 22q11.2 deletion syndrome. The group examined postmortem brain tissue from patients with 22q11.2 deletion syndrome and a clinical history of Parkinson’s disease for neurodegenerative changes and compared it with tissue from persons with no history of a movement disorder. Adults with 22q11.2 deletion syndrome had a significantly elevated occurrence of Parkinson’s disease, compared with standard population estimates. Individuals with early-onset Parkinson’s disease and classic features of 22q11.2 deletion syndrome should be considered for genetic testing, said the authors.

High levels of lipid-depleted (LD) apolipoproteins are associated with cognitive difficulties but may be mitigated by diet, according to research published in the August issue of JAMA Neurology. Investigators randomized 20 adults with normal cognition (mean age, 69) and 27 adults with amnestic mild cognitive impairment (mean age, 67) to a diet high in saturated fat content and with a high glycemic index or to a diet low in saturated fat content and with a low glycemic index. Baseline levels of LD b-amyloid were greater for adults with mild cognitive impairment, compared with adults with normal cognition. The diet low in saturated fat tended to decrease LD b-amyloid levels, and the diet high in saturated fat increased these fractions.

The parkin protein may trigger the destruction of the bacterium that causes tuberculosis, according to research published online ahead of print September 4 in Nature. Genetic polymorphisms in the PARK2 regulatory region are associated with increased susceptibility to intracellular bacterial pathogens in humans. In mouse and human macrophages infected with Mycobacterium tuberculosis, parkin played a role in fighting the bacteria. Mice genetically engineered to lack parkin died after being infected by M. tuberculosis, while control mice survived the infection. In addition, parkin-deficient mice and flies were more sensitive to intracellular bacterial infections. The study results reveal an unexpected functional link between mitophagy and infectious disease, said the researchers. Strategies under investigation for combating Parkinson’s disease also might help fight tuberculosis, the authors added.

Low cardiovascular fitness early in life may be associated with an increased risk of epilepsy in adulthood, according to research published September 17 in Neurology. Investigators examined a population-based cohort study of approximately 1.2 million Swedish male conscripts born from 1950 to 1987 who were followed for as many as 40 years. Data on cardiovascular fitness were collected during conscription exams, and researchers linked the data with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models. Low and medium cardiovascular fitness (compared with high cardiovascular fitness) at age 18 was associated with increased risk of future epilepsy (hazard ratios 1.79 and 1.36, respectively). The associations changed marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes.

Whole-body MRI may predict cardiac and cerebrovascular events in patients with diabetes, according to a study published online ahead of print September 10 in Radiology. Researchers followed up 65 patients with types 1 and 2 diabetes who underwent a comprehensive, contrast-enhanced whole-body MRI protocol at baseline. Follow-up was performed by phone interview. The primary end point was a major adverse cardiac and cerebrovascular event (MACCE), which was defined as composite cardiac-cerebrovascular death, myocardial infarction, cerebrovascular event, or revascularization. Follow-up was completed in 61 patients. Normal whole-body MRI excluded MACCE during the follow-up period, but detectable ischemic or atherosclerotic changes at whole-body MRI were associated with a cumulative event rate of 20% at three years and 35% at six years. Whole-body MRI summary estimate of disease was strongly predictive for MACCE.

Obese individuals may have an elevated risk of episodic migraine, compared with healthy persons, according to research published online ahead of print September 11 in Neurology. Investigators analyzed data for 3,862 adult participants (including African Americans and Caucasians) in the National Comorbidity Survey Replication. Diagnostic criteria for episodic migraine were based on the International Classification of Headache Disorders. BMI was classified as underweight (<18.5 kg/m²), normal (18.5 to 24.9 kg/m²), overweight (25 to 29.9 kg/m²), or obese (≥30 kg/m²). The adjusted odds of episodic migraine were 81% greater in individuals who were obese, compared with those of normal weight. Stratified analyses demonstrated that the odds of episodic migraine were greater in obese, compared with normal-weight individuals, who were younger than 50, Caucasian, or female.

Approximately 15% of all ischemic strokes occur in young adults and adolescents, according to a consensus document developed by an expert panel of the American Academy of Neurology and published September 17 in Neurology. Few public-health and research initiatives have focused on stroke in the young, said the authors. Early diagnosis of ischemic stroke is challenging because of the lack of awareness and the relative infrequency of stroke, compared with stroke mimics. The heterogeneity and relative rarity of the causes of ischemic stroke in the young result in uncertainties about diagnostic evaluation and cause-specific management. For these reasons, it is important to formulate and enact strategies to increase awareness and access to resources for young patients with stroke, their caregivers and families, and health care professionals, said the authors.

Retired National Football League (NFL) players may have an increased prevalence of late-life cognitive impairment indicative of diminished cerebral reserve, according to research published in the September issue of the Journal of the International Neuropsychological Society. After examining informant AD8 inventory data for a sample of 513 retired NFL players, the researchers found that 35.1% of the sample had possible cognitive impairment. When the researchers compared neurocognitive profiles in a subsample of this group to those in a clinical sample of patients with a diagnosis of mild cognitive impairment due to Alzheimer’s disease, they found a highly similar profile of impairments. However, said lead author Christopher Randolph, PhD, “there is essentially no evidence to support the existence of any unique clinical disorder such as CTE.” The findings emphasize the need for larger, controlled studies on this issue, he added.

Treatment with 4 g/day of ascorbic acid may not improve neuropathy in subjects with Charcot-Marie-Tooth disease type 1A, according to research published in the August issue of JAMA Neurology. Researchers randomized 110 patients with Charcot-Marie-Tooth disease type 1A to oral ascorbic acid (87 subjects) or matching placebo (23 individuals). Patients’ mean two-year change in Charcot-Marie-Tooth Neuropathy Score (CMTNS) was −0.21 for the ascorbic acid group and −0.92 for the placebo group. The mean two-year change according to natural history is +1.33. Because the results were well below 50% reduction of CMTNS worsening from natural history, the investigators could not declare the study futile. It is unlikely that the results support undertaking a larger trial of 4 g/day of ascorbic acid, said the researchers.

Pilots with occupational exposure to hypobaria may have significantly greater volume and number of white-matter hyperintensity (WMH) lesions, compared with controls, according to data published August 20 in Neurology. Researchers used a 3-T MRI scanner to collect three-dimensional, T2-weighted, high-resolution imaging data for 102 U-2 pilots and 91 controls matched for age, health, and education levels. The investigators compared whole-brain and regional WMH volume and number between groups using a two-tailed Wilcoxon rank sum test. U-2 pilots had an increase in volume (394%) and number (295%) of WMH. Also, WMH were more uniformly distributed throughout the brain in U-2 pilots, compared with a predominantly frontal distribution in controls. Further studies will be necessary to clarify the pathologic mechanisms responsible for the damage, said the researchers.

Nine independent risk factors that can be traced to adolescence, most of which are modifiable, may account for most cases of young-onset dementia in men, according to a study published online ahead of print August 12 in JAMA Internal Medicine. Investigators analyzed data for 488,484 Swedish men from the Swedish Military Service Conscription Register. Multivariate Cox regression analysis indicated that alcohol intoxication, stroke, antipsychotic use, depression, father’s dementia, intoxication with drugs other than alcohol, low cognitive function at conscription, low height at conscription, and high systolic blood pressure at conscription were significant risk factors for young-onset dementia. The population-attributable risk associated with all nine risk factors was 68%. The study results suggest excellent opportunities for early prevention, according to the researchers.

Researchers observed a novel brain phenomenon in humans and animals in a coma and with an isoelectric (ie, “flat”) EEG, according to research published September 18 in PLOS One. The researchers first detected the state in a human in postanoxic coma who had received medication. They replicated the state by applying high doses of isoflurane in cats. All subjects had an EEG activity of quasi-rhythmic sharp waves that the investigators propose to call Nu-complexes. Simultaneous intracellular recordings in vivo in the cortex and hippocampus, especially in the CA3 region, demonstrated that Nu-complexes arise in the hippocampus and are transmitted to the cortex. The creation of a hippocampal Nu-complex depends on another hippocampal activity (ie, ripple activity), which is not overtly detectable at the cortical level.

—Erik Greb
Senior Associate Editor

By lowering homocysteine levels, vitamin B supplementation may reduce the risk of stroke significantly for some individuals, according to research published online ahead of print September 18 in Neurology. Investigators analyzed data from 14 randomized controlled trials published before August 2012. The trials included 54,913 participants, and the investigators measured the association between B vitamin supplementation and end point events using a fixed-effects model and χ2 tests. The group observed a reduction in overall stroke events resulting from reduction in homocysteine levels following B vitamin supplementation, but not in subgroups divided according to primary or secondary prevention measures, ischemic versus hemorrhagic stroke, or occurrence of fatal stroke. Vitamin B reduced stroke events in subgroups with three or more years of follow-up and without cereal folate fortification or chronic kidney disease.

The deletion of information from chromosome 22 may be a genetic risk factor for early-onset Parkinson’s disease, researchers reported online ahead of print September 9 in JAMA Neurology. The investigators conducted an observational study of the occurrence of Parkinson’s disease in a cohort of 159 adults with a molecularly confirmed diagnosis of 22q11.2 deletion syndrome. The group examined postmortem brain tissue from patients with 22q11.2 deletion syndrome and a clinical history of Parkinson’s disease for neurodegenerative changes and compared it with tissue from persons with no history of a movement disorder. Adults with 22q11.2 deletion syndrome had a significantly elevated occurrence of Parkinson’s disease, compared with standard population estimates. Individuals with early-onset Parkinson’s disease and classic features of 22q11.2 deletion syndrome should be considered for genetic testing, said the authors.

High levels of lipid-depleted (LD) apolipoproteins are associated with cognitive difficulties but may be mitigated by diet, according to research published in the August issue of JAMA Neurology. Investigators randomized 20 adults with normal cognition (mean age, 69) and 27 adults with amnestic mild cognitive impairment (mean age, 67) to a diet high in saturated fat content and with a high glycemic index or to a diet low in saturated fat content and with a low glycemic index. Baseline levels of LD b-amyloid were greater for adults with mild cognitive impairment, compared with adults with normal cognition. The diet low in saturated fat tended to decrease LD b-amyloid levels, and the diet high in saturated fat increased these fractions.

The parkin protein may trigger the destruction of the bacterium that causes tuberculosis, according to research published online ahead of print September 4 in Nature. Genetic polymorphisms in the PARK2 regulatory region are associated with increased susceptibility to intracellular bacterial pathogens in humans. In mouse and human macrophages infected with Mycobacterium tuberculosis, parkin played a role in fighting the bacteria. Mice genetically engineered to lack parkin died after being infected by M. tuberculosis, while control mice survived the infection. In addition, parkin-deficient mice and flies were more sensitive to intracellular bacterial infections. The study results reveal an unexpected functional link between mitophagy and infectious disease, said the researchers. Strategies under investigation for combating Parkinson’s disease also might help fight tuberculosis, the authors added.

Low cardiovascular fitness early in life may be associated with an increased risk of epilepsy in adulthood, according to research published September 17 in Neurology. Investigators examined a population-based cohort study of approximately 1.2 million Swedish male conscripts born from 1950 to 1987 who were followed for as many as 40 years. Data on cardiovascular fitness were collected during conscription exams, and researchers linked the data with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models. Low and medium cardiovascular fitness (compared with high cardiovascular fitness) at age 18 was associated with increased risk of future epilepsy (hazard ratios 1.79 and 1.36, respectively). The associations changed marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes.

Whole-body MRI may predict cardiac and cerebrovascular events in patients with diabetes, according to a study published online ahead of print September 10 in Radiology. Researchers followed up 65 patients with types 1 and 2 diabetes who underwent a comprehensive, contrast-enhanced whole-body MRI protocol at baseline. Follow-up was performed by phone interview. The primary end point was a major adverse cardiac and cerebrovascular event (MACCE), which was defined as composite cardiac-cerebrovascular death, myocardial infarction, cerebrovascular event, or revascularization. Follow-up was completed in 61 patients. Normal whole-body MRI excluded MACCE during the follow-up period, but detectable ischemic or atherosclerotic changes at whole-body MRI were associated with a cumulative event rate of 20% at three years and 35% at six years. Whole-body MRI summary estimate of disease was strongly predictive for MACCE.

Obese individuals may have an elevated risk of episodic migraine, compared with healthy persons, according to research published online ahead of print September 11 in Neurology. Investigators analyzed data for 3,862 adult participants (including African Americans and Caucasians) in the National Comorbidity Survey Replication. Diagnostic criteria for episodic migraine were based on the International Classification of Headache Disorders. BMI was classified as underweight (<18.5 kg/m²), normal (18.5 to 24.9 kg/m²), overweight (25 to 29.9 kg/m²), or obese (≥30 kg/m²). The adjusted odds of episodic migraine were 81% greater in individuals who were obese, compared with those of normal weight. Stratified analyses demonstrated that the odds of episodic migraine were greater in obese, compared with normal-weight individuals, who were younger than 50, Caucasian, or female.

Approximately 15% of all ischemic strokes occur in young adults and adolescents, according to a consensus document developed by an expert panel of the American Academy of Neurology and published September 17 in Neurology. Few public-health and research initiatives have focused on stroke in the young, said the authors. Early diagnosis of ischemic stroke is challenging because of the lack of awareness and the relative infrequency of stroke, compared with stroke mimics. The heterogeneity and relative rarity of the causes of ischemic stroke in the young result in uncertainties about diagnostic evaluation and cause-specific management. For these reasons, it is important to formulate and enact strategies to increase awareness and access to resources for young patients with stroke, their caregivers and families, and health care professionals, said the authors.

Retired National Football League (NFL) players may have an increased prevalence of late-life cognitive impairment indicative of diminished cerebral reserve, according to research published in the September issue of the Journal of the International Neuropsychological Society. After examining informant AD8 inventory data for a sample of 513 retired NFL players, the researchers found that 35.1% of the sample had possible cognitive impairment. When the researchers compared neurocognitive profiles in a subsample of this group to those in a clinical sample of patients with a diagnosis of mild cognitive impairment due to Alzheimer’s disease, they found a highly similar profile of impairments. However, said lead author Christopher Randolph, PhD, “there is essentially no evidence to support the existence of any unique clinical disorder such as CTE.” The findings emphasize the need for larger, controlled studies on this issue, he added.

Treatment with 4 g/day of ascorbic acid may not improve neuropathy in subjects with Charcot-Marie-Tooth disease type 1A, according to research published in the August issue of JAMA Neurology. Researchers randomized 110 patients with Charcot-Marie-Tooth disease type 1A to oral ascorbic acid (87 subjects) or matching placebo (23 individuals). Patients’ mean two-year change in Charcot-Marie-Tooth Neuropathy Score (CMTNS) was −0.21 for the ascorbic acid group and −0.92 for the placebo group. The mean two-year change according to natural history is +1.33. Because the results were well below 50% reduction of CMTNS worsening from natural history, the investigators could not declare the study futile. It is unlikely that the results support undertaking a larger trial of 4 g/day of ascorbic acid, said the researchers.

Pilots with occupational exposure to hypobaria may have significantly greater volume and number of white-matter hyperintensity (WMH) lesions, compared with controls, according to data published August 20 in Neurology. Researchers used a 3-T MRI scanner to collect three-dimensional, T2-weighted, high-resolution imaging data for 102 U-2 pilots and 91 controls matched for age, health, and education levels. The investigators compared whole-brain and regional WMH volume and number between groups using a two-tailed Wilcoxon rank sum test. U-2 pilots had an increase in volume (394%) and number (295%) of WMH. Also, WMH were more uniformly distributed throughout the brain in U-2 pilots, compared with a predominantly frontal distribution in controls. Further studies will be necessary to clarify the pathologic mechanisms responsible for the damage, said the researchers.

Nine independent risk factors that can be traced to adolescence, most of which are modifiable, may account for most cases of young-onset dementia in men, according to a study published online ahead of print August 12 in JAMA Internal Medicine. Investigators analyzed data for 488,484 Swedish men from the Swedish Military Service Conscription Register. Multivariate Cox regression analysis indicated that alcohol intoxication, stroke, antipsychotic use, depression, father’s dementia, intoxication with drugs other than alcohol, low cognitive function at conscription, low height at conscription, and high systolic blood pressure at conscription were significant risk factors for young-onset dementia. The population-attributable risk associated with all nine risk factors was 68%. The study results suggest excellent opportunities for early prevention, according to the researchers.

Researchers observed a novel brain phenomenon in humans and animals in a coma and with an isoelectric (ie, “flat”) EEG, according to research published September 18 in PLOS One. The researchers first detected the state in a human in postanoxic coma who had received medication. They replicated the state by applying high doses of isoflurane in cats. All subjects had an EEG activity of quasi-rhythmic sharp waves that the investigators propose to call Nu-complexes. Simultaneous intracellular recordings in vivo in the cortex and hippocampus, especially in the CA3 region, demonstrated that Nu-complexes arise in the hippocampus and are transmitted to the cortex. The creation of a hippocampal Nu-complex depends on another hippocampal activity (ie, ripple activity), which is not overtly detectable at the cortical level.

—Erik Greb
Senior Associate Editor

By lowering homocysteine levels, vitamin B supplementation may reduce the risk of stroke significantly for some individuals, according to research published online ahead of print September 18 in Neurology. Investigators analyzed data from 14 randomized controlled trials published before August 2012. The trials included 54,913 participants, and the investigators measured the association between B vitamin supplementation and end point events using a fixed-effects model and χ2 tests. The group observed a reduction in overall stroke events resulting from reduction in homocysteine levels following B vitamin supplementation, but not in subgroups divided according to primary or secondary prevention measures, ischemic versus hemorrhagic stroke, or occurrence of fatal stroke. Vitamin B reduced stroke events in subgroups with three or more years of follow-up and without cereal folate fortification or chronic kidney disease.

The deletion of information from chromosome 22 may be a genetic risk factor for early-onset Parkinson’s disease, researchers reported online ahead of print September 9 in JAMA Neurology. The investigators conducted an observational study of the occurrence of Parkinson’s disease in a cohort of 159 adults with a molecularly confirmed diagnosis of 22q11.2 deletion syndrome. The group examined postmortem brain tissue from patients with 22q11.2 deletion syndrome and a clinical history of Parkinson’s disease for neurodegenerative changes and compared it with tissue from persons with no history of a movement disorder. Adults with 22q11.2 deletion syndrome had a significantly elevated occurrence of Parkinson’s disease, compared with standard population estimates. Individuals with early-onset Parkinson’s disease and classic features of 22q11.2 deletion syndrome should be considered for genetic testing, said the authors.

High levels of lipid-depleted (LD) apolipoproteins are associated with cognitive difficulties but may be mitigated by diet, according to research published in the August issue of JAMA Neurology. Investigators randomized 20 adults with normal cognition (mean age, 69) and 27 adults with amnestic mild cognitive impairment (mean age, 67) to a diet high in saturated fat content and with a high glycemic index or to a diet low in saturated fat content and with a low glycemic index. Baseline levels of LD b-amyloid were greater for adults with mild cognitive impairment, compared with adults with normal cognition. The diet low in saturated fat tended to decrease LD b-amyloid levels, and the diet high in saturated fat increased these fractions.

The parkin protein may trigger the destruction of the bacterium that causes tuberculosis, according to research published online ahead of print September 4 in Nature. Genetic polymorphisms in the PARK2 regulatory region are associated with increased susceptibility to intracellular bacterial pathogens in humans. In mouse and human macrophages infected with Mycobacterium tuberculosis, parkin played a role in fighting the bacteria. Mice genetically engineered to lack parkin died after being infected by M. tuberculosis, while control mice survived the infection. In addition, parkin-deficient mice and flies were more sensitive to intracellular bacterial infections. The study results reveal an unexpected functional link between mitophagy and infectious disease, said the researchers. Strategies under investigation for combating Parkinson’s disease also might help fight tuberculosis, the authors added.

Low cardiovascular fitness early in life may be associated with an increased risk of epilepsy in adulthood, according to research published September 17 in Neurology. Investigators examined a population-based cohort study of approximately 1.2 million Swedish male conscripts born from 1950 to 1987 who were followed for as many as 40 years. Data on cardiovascular fitness were collected during conscription exams, and researchers linked the data with hospital registers to calculate later risk of epilepsy using Cox proportional hazard models. Low and medium cardiovascular fitness (compared with high cardiovascular fitness) at age 18 was associated with increased risk of future epilepsy (hazard ratios 1.79 and 1.36, respectively). The associations changed marginally after adjustment for familial influences and prior severe traumatic brain injury, cerebrovascular disease, or diabetes.

Whole-body MRI may predict cardiac and cerebrovascular events in patients with diabetes, according to a study published online ahead of print September 10 in Radiology. Researchers followed up 65 patients with types 1 and 2 diabetes who underwent a comprehensive, contrast-enhanced whole-body MRI protocol at baseline. Follow-up was performed by phone interview. The primary end point was a major adverse cardiac and cerebrovascular event (MACCE), which was defined as composite cardiac-cerebrovascular death, myocardial infarction, cerebrovascular event, or revascularization. Follow-up was completed in 61 patients. Normal whole-body MRI excluded MACCE during the follow-up period, but detectable ischemic or atherosclerotic changes at whole-body MRI were associated with a cumulative event rate of 20% at three years and 35% at six years. Whole-body MRI summary estimate of disease was strongly predictive for MACCE.

Obese individuals may have an elevated risk of episodic migraine, compared with healthy persons, according to research published online ahead of print September 11 in Neurology. Investigators analyzed data for 3,862 adult participants (including African Americans and Caucasians) in the National Comorbidity Survey Replication. Diagnostic criteria for episodic migraine were based on the International Classification of Headache Disorders. BMI was classified as underweight (<18.5 kg/m²), normal (18.5 to 24.9 kg/m²), overweight (25 to 29.9 kg/m²), or obese (≥30 kg/m²). The adjusted odds of episodic migraine were 81% greater in individuals who were obese, compared with those of normal weight. Stratified analyses demonstrated that the odds of episodic migraine were greater in obese, compared with normal-weight individuals, who were younger than 50, Caucasian, or female.

Approximately 15% of all ischemic strokes occur in young adults and adolescents, according to a consensus document developed by an expert panel of the American Academy of Neurology and published September 17 in Neurology. Few public-health and research initiatives have focused on stroke in the young, said the authors. Early diagnosis of ischemic stroke is challenging because of the lack of awareness and the relative infrequency of stroke, compared with stroke mimics. The heterogeneity and relative rarity of the causes of ischemic stroke in the young result in uncertainties about diagnostic evaluation and cause-specific management. For these reasons, it is important to formulate and enact strategies to increase awareness and access to resources for young patients with stroke, their caregivers and families, and health care professionals, said the authors.

Retired National Football League (NFL) players may have an increased prevalence of late-life cognitive impairment indicative of diminished cerebral reserve, according to research published in the September issue of the Journal of the International Neuropsychological Society. After examining informant AD8 inventory data for a sample of 513 retired NFL players, the researchers found that 35.1% of the sample had possible cognitive impairment. When the researchers compared neurocognitive profiles in a subsample of this group to those in a clinical sample of patients with a diagnosis of mild cognitive impairment due to Alzheimer’s disease, they found a highly similar profile of impairments. However, said lead author Christopher Randolph, PhD, “there is essentially no evidence to support the existence of any unique clinical disorder such as CTE.” The findings emphasize the need for larger, controlled studies on this issue, he added.

Treatment with 4 g/day of ascorbic acid may not improve neuropathy in subjects with Charcot-Marie-Tooth disease type 1A, according to research published in the August issue of JAMA Neurology. Researchers randomized 110 patients with Charcot-Marie-Tooth disease type 1A to oral ascorbic acid (87 subjects) or matching placebo (23 individuals). Patients’ mean two-year change in Charcot-Marie-Tooth Neuropathy Score (CMTNS) was −0.21 for the ascorbic acid group and −0.92 for the placebo group. The mean two-year change according to natural history is +1.33. Because the results were well below 50% reduction of CMTNS worsening from natural history, the investigators could not declare the study futile. It is unlikely that the results support undertaking a larger trial of 4 g/day of ascorbic acid, said the researchers.

Pilots with occupational exposure to hypobaria may have significantly greater volume and number of white-matter hyperintensity (WMH) lesions, compared with controls, according to data published August 20 in Neurology. Researchers used a 3-T MRI scanner to collect three-dimensional, T2-weighted, high-resolution imaging data for 102 U-2 pilots and 91 controls matched for age, health, and education levels. The investigators compared whole-brain and regional WMH volume and number between groups using a two-tailed Wilcoxon rank sum test. U-2 pilots had an increase in volume (394%) and number (295%) of WMH. Also, WMH were more uniformly distributed throughout the brain in U-2 pilots, compared with a predominantly frontal distribution in controls. Further studies will be necessary to clarify the pathologic mechanisms responsible for the damage, said the researchers.

Nine independent risk factors that can be traced to adolescence, most of which are modifiable, may account for most cases of young-onset dementia in men, according to a study published online ahead of print August 12 in JAMA Internal Medicine. Investigators analyzed data for 488,484 Swedish men from the Swedish Military Service Conscription Register. Multivariate Cox regression analysis indicated that alcohol intoxication, stroke, antipsychotic use, depression, father’s dementia, intoxication with drugs other than alcohol, low cognitive function at conscription, low height at conscription, and high systolic blood pressure at conscription were significant risk factors for young-onset dementia. The population-attributable risk associated with all nine risk factors was 68%. The study results suggest excellent opportunities for early prevention, according to the researchers.

Researchers observed a novel brain phenomenon in humans and animals in a coma and with an isoelectric (ie, “flat”) EEG, according to research published September 18 in PLOS One. The researchers first detected the state in a human in postanoxic coma who had received medication. They replicated the state by applying high doses of isoflurane in cats. All subjects had an EEG activity of quasi-rhythmic sharp waves that the investigators propose to call Nu-complexes. Simultaneous intracellular recordings in vivo in the cortex and hippocampus, especially in the CA3 region, demonstrated that Nu-complexes arise in the hippocampus and are transmitted to the cortex. The creation of a hippocampal Nu-complex depends on another hippocampal activity (ie, ripple activity), which is not overtly detectable at the cortical level.

—Erik Greb
Senior Associate Editor

A recent case–control study provides further evidence against the Zamboni hypothesis that chronic cerebrospinal venous insufficiency is involved with multiple sclerosis (MS), researchers reported August 14 in PLOS One. The researchers randomly selected 100 patients with MS between ages 18 and 65 and 100 controls with no known history of MS or other neurologic condition. All participants underwent ultrasound imaging of the veins of the neck and the deep cerebral veins, as well as MRI of the neck veins and brain. The investigators found no evidence of reflux, stenosis, or blockage in the internal jugular veins or vertebral veins in any study participant and no evidence of reflux or cessation of flow in the deep cerebral veins in any subject.

Breastfeeding may reduce a woman’s risk of Alzheimer’s disease, according to research published online ahead of print July 23 in the Journal of Alzheimer’s Disease. Investigators collected reproductive history data from and conducted Alzheimer’s disease diagnostic interviews with a cohort of elderly British women. Analysis using Cox proportional-hazard models indicated that longer breastfeeding duration corresponded to reduced risk of Alzheimer’s disease. Women who breastfed had lower risk of Alzheimer’s disease than women who did not breastfeed. Breastfeeding practices are an important modifier of cumulative endogenous hormone exposure for mothers, according to the researchers. Future studies should consider how reproductive history leads to variation in endogenous hormone exposure and how this variation may influence the relationship between hormones and Alzheimer’s disease, the investigators concluded.

Among older adults, anemia may be associated with an increased risk of dementia, according to a study published August 6 in Neurology. Researchers studied 2,552 older adults (mean age, 76) participating in the Health, Aging, and Body Composition study and who were free of dementia at baseline. Of the total population, 392 participants had anemia at baseline. Over 11 years of follow-up, 455 participants developed dementia. An unadjusted analysis indicated that subjects with baseline anemia had an increased risk of dementia (23% vs 17%) compared with subjects without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline Modified Mini-Mental State score, comorbidities, and renal function. Additional adjustment for other anemia measures, erythropoietin, and C-reactive protein did not affect the results significantly.

The FDA has approved Trokendi XR, a once-daily extended release formulation of topiramate for the treatment of epilepsy. The agency granted a waiver for certain pediatric study requirements and a deferral for the submission of postmarketing pediatric pharmacokinetic assessments. Trokendi XR is indicated for initial monotherapy in patients ages 10 and older with partial onset or primary generalized tonic–clonic seizures. The drug also is approved as adjunctive therapy in patients ages 6 and older with partial onset or primary generalized tonic–clonic seizures, and as adjunctive therapy in patients ages 6 and older with seizures associated with Lennox–Gastaut syndrome. The product will be available in 25-, 50-, 100- and 200-mg extended-release capsules. Supernus Pharmaceuticals (Rockville, Maryland) expects to launch the product in September 2013.

The FDA has approved scored tablet and oral suspension formulations of ONFI (clobazam) CIV. ONFI is an oral antiepileptic drug of the benzodiazepine class (ie, a 1,5 benzodiazepine). The agency originally approved ONFI in 2011 as a prescription medication to treat seizures associated with Lennox–Gastaut syndrome in adults and children age 2 or older. The new oval-shaped ONFI scored tablets (10 mg and 20 mg) will replace the round, nonscored tablets and are similar in size. The new tablets contain the same ingredients as the round tablet, and the score allows patients or their caregivers to split the tablets in half. ONFI oral suspension (2.5 mg/mL) has a berry flavor. ONFI, manufactured by Lundbeck (Deerfield, Illinois), will no longer be available in a 5-mg tablet.

An incomplete circle of Willis may be more common in patients with migraine with aura than in the general population, according to research published July 26 in PLOS One. Investigators enrolled 56 migraineurs with aura, 61 migraineurs without aura, and 53 controls in an observational study. The researchers performed magnetic resonance angiography to examine subjects’ circle of Willis anatomy and measured cerebral blood flow with arterial spin–labeled perfusion MRI. An incomplete circle of Willis was significantly more common in migraineurs with aura, compared with controls (73% vs 51%). A similar trend was observed among migraineurs without aura (67% vs 51%). Compared with subjects with a complete circle of Willis, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow.

Some patients with chronic pain diagnosed as fibromyalgia may have unrecognized small-fiber polyneuropathy (SFPN), according to research published online ahead of print June 7 in Pain. Investigators analyzed symptoms associated with SFPN, neurologic examinations, and pathologic and physiologic markers in 27 patients with fibromyalgia and 30 matched normal controls. Study instruments included the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, and autonomic-function testing (AFT). Approximately 41% of skin biopsies from subjects with fibromyalgia supported a diagnosis of SFPN, compared with 3% of biopsies from control subjects. MNSI and UENS scores were higher in patients with fibromyalgia than in control subjects. Abnormal AFTs were prevalent among patients with fibromyalgia, suggesting that fibromyalgia-associated SFPN is primarily somatic, said the researchers.

High glucose levels may be a risk factor for dementia, even among persons without diabetes, according to a study published August 8 in the New England Journal of Medicine. Researchers examined 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2,067 participants (1,228 women) without dementia. Participants’ mean age at baseline was 76. Of the total population, 232 participants had diabetes. During a median follow-up of 6.8 years, 524 participants developed dementia (74 with diabetes). Among participants without diabetes, higher average glucose levels within the preceding five years were related to an increased risk of dementia. A glucose level of 115 mg/dL, compared with 100 mg/dL, was associated with an adjusted hazard ratio for dementia of 1.18.

A majority of Alzheimer’s disease investigators favor disclosing amyloid imaging results to participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), according to a survey published online ahead of print August 21 in Neurology. Shortly before the FDA approved the amyloid-binding radiotracer florbetapir, all ADNI investigators and personnel were asked to complete an anonymous online survey that contained fixed-choice and free-text questions. Although ADNI participants often requested amyloid imaging results, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to the participants. Most investigators reported that if the FDA approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, however. ADNI investigators emphasized the need for guidance on how to provide these results to participants.

A sudden decrease of testosterone may induce nigrostriatal pathologies in mice through a decrease in glial-derived neurotrophic factor (GDNF) mediated by inducible nitric-oxide synthase (iNOS), investigators reported in the July 19 Journal of Biological Chemistry. Levels of iNOS, glial markers, and α-synuclein were higher in the nigra of castrated male mice than in normal male mice. After castration, the level of GDNF markedly decreased in the nigra of male mice, however. Subcutaneous implantation of 5 α-dihydrotestosterone pellets reversed nigrostriatal pathologies in castrated male mice, suggesting that the male sex hormone plays a role in castration-induced nigrostriatal pathology. Castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study Parkinson’s disease-related nigrostriatal pathologies, thus facilitating the screening of drugs against Parkinson’s disease, said the researchers.

IV thrombolysis within 90 minutes may be associated with excellent outcomes in patients with moderate and mild stroke, according to research published online ahead of print August 22 in Stroke. Investigators prospectively collected data for consecutive ischemic stroke patients who received IV thrombolysis at 10 European stroke centers. Logistic regression analysis suggested that shorter onset-to-treatment time was significantly associated with excellent outcome. Patients with onset-to-treatment time of 90 minutes or less had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, the researchers found that onset-to-treatment time of 90 minutes or less was associated with excellent outcome in patients with NIH Stroke Scale (NIHSS) score from 7 to 12, but not in patients with baseline NIHSS score greater than 12 and baseline NIHSS 0 to 6.

A neo-substrate approach involving the adenosine triphosphate (ATP) analog kinetin triphosphate (KTP) can increase the activity of Parkinson’s disease–related mutant PINK1^G309D and PINK1^WT, according to research published on August 15 in Cell. Investigators found that the normal and mutated versions of PINK1 bind to KTP. The application of KTP precursor kinetin to cells resulted in biologically significant increases in PINK1 activity, which were manifest as higher levels of Parkin recruitment to depolarized mitochondria, reduced mitochondrial motility in axons, and lower levels of apoptosis. Kinetin could treat patients with a known PINK1 mutation and also slow disease progression in patients without a family history of the disease, said the researchers. The search for neo-substrates for kinases could provide a novel way of regulating kinase activity, they concluded.

The effect of copper on brain amyloid-β homeostasis depends on whether it is accumulated in the capillaries or in the parenchyma, researchers reported online ahead of print August 19 in Proceedings of the National Academy of Sciences. In aging mice, the accumulation of copper in brain capillaries was associated with its reduction in low-density lipoprotein receptor–related protein 1 (LRP1) and higher brain amyloid-β levels. In human brain endothelial cells, normal labile levels of copper caused the downregulation of LRP1 by inducing nitrotyrosination and subsequent proteosomal-dependent degradation, partly because of interactions between copper, cellular prion protein, and LRP1. In APP^sw/0 mice, copper downregulated LRP1 in brain capillaries and increased amyloid-b production and neuroinflammation. The effect resulted from the accumulation of copper in brain capillaries and in the parenchyma.

—Erik Greb
Senior Associate Editor

A recent case–control study provides further evidence against the Zamboni hypothesis that chronic cerebrospinal venous insufficiency is involved with multiple sclerosis (MS), researchers reported August 14 in PLOS One. The researchers randomly selected 100 patients with MS between ages 18 and 65 and 100 controls with no known history of MS or other neurologic condition. All participants underwent ultrasound imaging of the veins of the neck and the deep cerebral veins, as well as MRI of the neck veins and brain. The investigators found no evidence of reflux, stenosis, or blockage in the internal jugular veins or vertebral veins in any study participant and no evidence of reflux or cessation of flow in the deep cerebral veins in any subject.

Breastfeeding may reduce a woman’s risk of Alzheimer’s disease, according to research published online ahead of print July 23 in the Journal of Alzheimer’s Disease. Investigators collected reproductive history data from and conducted Alzheimer’s disease diagnostic interviews with a cohort of elderly British women. Analysis using Cox proportional-hazard models indicated that longer breastfeeding duration corresponded to reduced risk of Alzheimer’s disease. Women who breastfed had lower risk of Alzheimer’s disease than women who did not breastfeed. Breastfeeding practices are an important modifier of cumulative endogenous hormone exposure for mothers, according to the researchers. Future studies should consider how reproductive history leads to variation in endogenous hormone exposure and how this variation may influence the relationship between hormones and Alzheimer’s disease, the investigators concluded.

Among older adults, anemia may be associated with an increased risk of dementia, according to a study published August 6 in Neurology. Researchers studied 2,552 older adults (mean age, 76) participating in the Health, Aging, and Body Composition study and who were free of dementia at baseline. Of the total population, 392 participants had anemia at baseline. Over 11 years of follow-up, 455 participants developed dementia. An unadjusted analysis indicated that subjects with baseline anemia had an increased risk of dementia (23% vs 17%) compared with subjects without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline Modified Mini-Mental State score, comorbidities, and renal function. Additional adjustment for other anemia measures, erythropoietin, and C-reactive protein did not affect the results significantly.

The FDA has approved Trokendi XR, a once-daily extended release formulation of topiramate for the treatment of epilepsy. The agency granted a waiver for certain pediatric study requirements and a deferral for the submission of postmarketing pediatric pharmacokinetic assessments. Trokendi XR is indicated for initial monotherapy in patients ages 10 and older with partial onset or primary generalized tonic–clonic seizures. The drug also is approved as adjunctive therapy in patients ages 6 and older with partial onset or primary generalized tonic–clonic seizures, and as adjunctive therapy in patients ages 6 and older with seizures associated with Lennox–Gastaut syndrome. The product will be available in 25-, 50-, 100- and 200-mg extended-release capsules. Supernus Pharmaceuticals (Rockville, Maryland) expects to launch the product in September 2013.

The FDA has approved scored tablet and oral suspension formulations of ONFI (clobazam) CIV. ONFI is an oral antiepileptic drug of the benzodiazepine class (ie, a 1,5 benzodiazepine). The agency originally approved ONFI in 2011 as a prescription medication to treat seizures associated with Lennox–Gastaut syndrome in adults and children age 2 or older. The new oval-shaped ONFI scored tablets (10 mg and 20 mg) will replace the round, nonscored tablets and are similar in size. The new tablets contain the same ingredients as the round tablet, and the score allows patients or their caregivers to split the tablets in half. ONFI oral suspension (2.5 mg/mL) has a berry flavor. ONFI, manufactured by Lundbeck (Deerfield, Illinois), will no longer be available in a 5-mg tablet.

An incomplete circle of Willis may be more common in patients with migraine with aura than in the general population, according to research published July 26 in PLOS One. Investigators enrolled 56 migraineurs with aura, 61 migraineurs without aura, and 53 controls in an observational study. The researchers performed magnetic resonance angiography to examine subjects’ circle of Willis anatomy and measured cerebral blood flow with arterial spin–labeled perfusion MRI. An incomplete circle of Willis was significantly more common in migraineurs with aura, compared with controls (73% vs 51%). A similar trend was observed among migraineurs without aura (67% vs 51%). Compared with subjects with a complete circle of Willis, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow.

Some patients with chronic pain diagnosed as fibromyalgia may have unrecognized small-fiber polyneuropathy (SFPN), according to research published online ahead of print June 7 in Pain. Investigators analyzed symptoms associated with SFPN, neurologic examinations, and pathologic and physiologic markers in 27 patients with fibromyalgia and 30 matched normal controls. Study instruments included the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, and autonomic-function testing (AFT). Approximately 41% of skin biopsies from subjects with fibromyalgia supported a diagnosis of SFPN, compared with 3% of biopsies from control subjects. MNSI and UENS scores were higher in patients with fibromyalgia than in control subjects. Abnormal AFTs were prevalent among patients with fibromyalgia, suggesting that fibromyalgia-associated SFPN is primarily somatic, said the researchers.

High glucose levels may be a risk factor for dementia, even among persons without diabetes, according to a study published August 8 in the New England Journal of Medicine. Researchers examined 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2,067 participants (1,228 women) without dementia. Participants’ mean age at baseline was 76. Of the total population, 232 participants had diabetes. During a median follow-up of 6.8 years, 524 participants developed dementia (74 with diabetes). Among participants without diabetes, higher average glucose levels within the preceding five years were related to an increased risk of dementia. A glucose level of 115 mg/dL, compared with 100 mg/dL, was associated with an adjusted hazard ratio for dementia of 1.18.

A majority of Alzheimer’s disease investigators favor disclosing amyloid imaging results to participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), according to a survey published online ahead of print August 21 in Neurology. Shortly before the FDA approved the amyloid-binding radiotracer florbetapir, all ADNI investigators and personnel were asked to complete an anonymous online survey that contained fixed-choice and free-text questions. Although ADNI participants often requested amyloid imaging results, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to the participants. Most investigators reported that if the FDA approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, however. ADNI investigators emphasized the need for guidance on how to provide these results to participants.

A sudden decrease of testosterone may induce nigrostriatal pathologies in mice through a decrease in glial-derived neurotrophic factor (GDNF) mediated by inducible nitric-oxide synthase (iNOS), investigators reported in the July 19 Journal of Biological Chemistry. Levels of iNOS, glial markers, and α-synuclein were higher in the nigra of castrated male mice than in normal male mice. After castration, the level of GDNF markedly decreased in the nigra of male mice, however. Subcutaneous implantation of 5 α-dihydrotestosterone pellets reversed nigrostriatal pathologies in castrated male mice, suggesting that the male sex hormone plays a role in castration-induced nigrostriatal pathology. Castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study Parkinson’s disease-related nigrostriatal pathologies, thus facilitating the screening of drugs against Parkinson’s disease, said the researchers.

IV thrombolysis within 90 minutes may be associated with excellent outcomes in patients with moderate and mild stroke, according to research published online ahead of print August 22 in Stroke. Investigators prospectively collected data for consecutive ischemic stroke patients who received IV thrombolysis at 10 European stroke centers. Logistic regression analysis suggested that shorter onset-to-treatment time was significantly associated with excellent outcome. Patients with onset-to-treatment time of 90 minutes or less had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, the researchers found that onset-to-treatment time of 90 minutes or less was associated with excellent outcome in patients with NIH Stroke Scale (NIHSS) score from 7 to 12, but not in patients with baseline NIHSS score greater than 12 and baseline NIHSS 0 to 6.

A neo-substrate approach involving the adenosine triphosphate (ATP) analog kinetin triphosphate (KTP) can increase the activity of Parkinson’s disease–related mutant PINK1^G309D and PINK1^WT, according to research published on August 15 in Cell. Investigators found that the normal and mutated versions of PINK1 bind to KTP. The application of KTP precursor kinetin to cells resulted in biologically significant increases in PINK1 activity, which were manifest as higher levels of Parkin recruitment to depolarized mitochondria, reduced mitochondrial motility in axons, and lower levels of apoptosis. Kinetin could treat patients with a known PINK1 mutation and also slow disease progression in patients without a family history of the disease, said the researchers. The search for neo-substrates for kinases could provide a novel way of regulating kinase activity, they concluded.

The effect of copper on brain amyloid-β homeostasis depends on whether it is accumulated in the capillaries or in the parenchyma, researchers reported online ahead of print August 19 in Proceedings of the National Academy of Sciences. In aging mice, the accumulation of copper in brain capillaries was associated with its reduction in low-density lipoprotein receptor–related protein 1 (LRP1) and higher brain amyloid-β levels. In human brain endothelial cells, normal labile levels of copper caused the downregulation of LRP1 by inducing nitrotyrosination and subsequent proteosomal-dependent degradation, partly because of interactions between copper, cellular prion protein, and LRP1. In APP^sw/0 mice, copper downregulated LRP1 in brain capillaries and increased amyloid-b production and neuroinflammation. The effect resulted from the accumulation of copper in brain capillaries and in the parenchyma.

—Erik Greb
Senior Associate Editor

A recent case–control study provides further evidence against the Zamboni hypothesis that chronic cerebrospinal venous insufficiency is involved with multiple sclerosis (MS), researchers reported August 14 in PLOS One. The researchers randomly selected 100 patients with MS between ages 18 and 65 and 100 controls with no known history of MS or other neurologic condition. All participants underwent ultrasound imaging of the veins of the neck and the deep cerebral veins, as well as MRI of the neck veins and brain. The investigators found no evidence of reflux, stenosis, or blockage in the internal jugular veins or vertebral veins in any study participant and no evidence of reflux or cessation of flow in the deep cerebral veins in any subject.

Breastfeeding may reduce a woman’s risk of Alzheimer’s disease, according to research published online ahead of print July 23 in the Journal of Alzheimer’s Disease. Investigators collected reproductive history data from and conducted Alzheimer’s disease diagnostic interviews with a cohort of elderly British women. Analysis using Cox proportional-hazard models indicated that longer breastfeeding duration corresponded to reduced risk of Alzheimer’s disease. Women who breastfed had lower risk of Alzheimer’s disease than women who did not breastfeed. Breastfeeding practices are an important modifier of cumulative endogenous hormone exposure for mothers, according to the researchers. Future studies should consider how reproductive history leads to variation in endogenous hormone exposure and how this variation may influence the relationship between hormones and Alzheimer’s disease, the investigators concluded.

Among older adults, anemia may be associated with an increased risk of dementia, according to a study published August 6 in Neurology. Researchers studied 2,552 older adults (mean age, 76) participating in the Health, Aging, and Body Composition study and who were free of dementia at baseline. Of the total population, 392 participants had anemia at baseline. Over 11 years of follow-up, 455 participants developed dementia. An unadjusted analysis indicated that subjects with baseline anemia had an increased risk of dementia (23% vs 17%) compared with subjects without anemia. The association remained significant after adjusting for demographics, APOE ε4, baseline Modified Mini-Mental State score, comorbidities, and renal function. Additional adjustment for other anemia measures, erythropoietin, and C-reactive protein did not affect the results significantly.

The FDA has approved Trokendi XR, a once-daily extended release formulation of topiramate for the treatment of epilepsy. The agency granted a waiver for certain pediatric study requirements and a deferral for the submission of postmarketing pediatric pharmacokinetic assessments. Trokendi XR is indicated for initial monotherapy in patients ages 10 and older with partial onset or primary generalized tonic–clonic seizures. The drug also is approved as adjunctive therapy in patients ages 6 and older with partial onset or primary generalized tonic–clonic seizures, and as adjunctive therapy in patients ages 6 and older with seizures associated with Lennox–Gastaut syndrome. The product will be available in 25-, 50-, 100- and 200-mg extended-release capsules. Supernus Pharmaceuticals (Rockville, Maryland) expects to launch the product in September 2013.

The FDA has approved scored tablet and oral suspension formulations of ONFI (clobazam) CIV. ONFI is an oral antiepileptic drug of the benzodiazepine class (ie, a 1,5 benzodiazepine). The agency originally approved ONFI in 2011 as a prescription medication to treat seizures associated with Lennox–Gastaut syndrome in adults and children age 2 or older. The new oval-shaped ONFI scored tablets (10 mg and 20 mg) will replace the round, nonscored tablets and are similar in size. The new tablets contain the same ingredients as the round tablet, and the score allows patients or their caregivers to split the tablets in half. ONFI oral suspension (2.5 mg/mL) has a berry flavor. ONFI, manufactured by Lundbeck (Deerfield, Illinois), will no longer be available in a 5-mg tablet.

An incomplete circle of Willis may be more common in patients with migraine with aura than in the general population, according to research published July 26 in PLOS One. Investigators enrolled 56 migraineurs with aura, 61 migraineurs without aura, and 53 controls in an observational study. The researchers performed magnetic resonance angiography to examine subjects’ circle of Willis anatomy and measured cerebral blood flow with arterial spin–labeled perfusion MRI. An incomplete circle of Willis was significantly more common in migraineurs with aura, compared with controls (73% vs 51%). A similar trend was observed among migraineurs without aura (67% vs 51%). Compared with subjects with a complete circle of Willis, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow.

Some patients with chronic pain diagnosed as fibromyalgia may have unrecognized small-fiber polyneuropathy (SFPN), according to research published online ahead of print June 7 in Pain. Investigators analyzed symptoms associated with SFPN, neurologic examinations, and pathologic and physiologic markers in 27 patients with fibromyalgia and 30 matched normal controls. Study instruments included the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, and autonomic-function testing (AFT). Approximately 41% of skin biopsies from subjects with fibromyalgia supported a diagnosis of SFPN, compared with 3% of biopsies from control subjects. MNSI and UENS scores were higher in patients with fibromyalgia than in control subjects. Abnormal AFTs were prevalent among patients with fibromyalgia, suggesting that fibromyalgia-associated SFPN is primarily somatic, said the researchers.

High glucose levels may be a risk factor for dementia, even among persons without diabetes, according to a study published August 8 in the New England Journal of Medicine. Researchers examined 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2,067 participants (1,228 women) without dementia. Participants’ mean age at baseline was 76. Of the total population, 232 participants had diabetes. During a median follow-up of 6.8 years, 524 participants developed dementia (74 with diabetes). Among participants without diabetes, higher average glucose levels within the preceding five years were related to an increased risk of dementia. A glucose level of 115 mg/dL, compared with 100 mg/dL, was associated with an adjusted hazard ratio for dementia of 1.18.

A majority of Alzheimer’s disease investigators favor disclosing amyloid imaging results to participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), according to a survey published online ahead of print August 21 in Neurology. Shortly before the FDA approved the amyloid-binding radiotracer florbetapir, all ADNI investigators and personnel were asked to complete an anonymous online survey that contained fixed-choice and free-text questions. Although ADNI participants often requested amyloid imaging results, the majority of ADNI investigators (approximately 90%) did not return amyloid imaging results to the participants. Most investigators reported that if the FDA approved florbetapir, they would support the return of amyloid imaging results to participants with mild cognitive impairment and normal cognition, however. ADNI investigators emphasized the need for guidance on how to provide these results to participants.

A sudden decrease of testosterone may induce nigrostriatal pathologies in mice through a decrease in glial-derived neurotrophic factor (GDNF) mediated by inducible nitric-oxide synthase (iNOS), investigators reported in the July 19 Journal of Biological Chemistry. Levels of iNOS, glial markers, and α-synuclein were higher in the nigra of castrated male mice than in normal male mice. After castration, the level of GDNF markedly decreased in the nigra of male mice, however. Subcutaneous implantation of 5 α-dihydrotestosterone pellets reversed nigrostriatal pathologies in castrated male mice, suggesting that the male sex hormone plays a role in castration-induced nigrostriatal pathology. Castrated young male mice may be used as a simple, toxin-free, and nontransgenic animal model to study Parkinson’s disease-related nigrostriatal pathologies, thus facilitating the screening of drugs against Parkinson’s disease, said the researchers.

IV thrombolysis within 90 minutes may be associated with excellent outcomes in patients with moderate and mild stroke, according to research published online ahead of print August 22 in Stroke. Investigators prospectively collected data for consecutive ischemic stroke patients who received IV thrombolysis at 10 European stroke centers. Logistic regression analysis suggested that shorter onset-to-treatment time was significantly associated with excellent outcome. Patients with onset-to-treatment time of 90 minutes or less had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, the researchers found that onset-to-treatment time of 90 minutes or less was associated with excellent outcome in patients with NIH Stroke Scale (NIHSS) score from 7 to 12, but not in patients with baseline NIHSS score greater than 12 and baseline NIHSS 0 to 6.

A neo-substrate approach involving the adenosine triphosphate (ATP) analog kinetin triphosphate (KTP) can increase the activity of Parkinson’s disease–related mutant PINK1^G309D and PINK1^WT, according to research published on August 15 in Cell. Investigators found that the normal and mutated versions of PINK1 bind to KTP. The application of KTP precursor kinetin to cells resulted in biologically significant increases in PINK1 activity, which were manifest as higher levels of Parkin recruitment to depolarized mitochondria, reduced mitochondrial motility in axons, and lower levels of apoptosis. Kinetin could treat patients with a known PINK1 mutation and also slow disease progression in patients without a family history of the disease, said the researchers. The search for neo-substrates for kinases could provide a novel way of regulating kinase activity, they concluded.

The effect of copper on brain amyloid-β homeostasis depends on whether it is accumulated in the capillaries or in the parenchyma, researchers reported online ahead of print August 19 in Proceedings of the National Academy of Sciences. In aging mice, the accumulation of copper in brain capillaries was associated with its reduction in low-density lipoprotein receptor–related protein 1 (LRP1) and higher brain amyloid-β levels. In human brain endothelial cells, normal labile levels of copper caused the downregulation of LRP1 by inducing nitrotyrosination and subsequent proteosomal-dependent degradation, partly because of interactions between copper, cellular prion protein, and LRP1. In APP^sw/0 mice, copper downregulated LRP1 in brain capillaries and increased amyloid-b production and neuroinflammation. The effect resulted from the accumulation of copper in brain capillaries and in the parenchyma.

—Erik Greb
Senior Associate Editor

Patients with Alzheimer’s disease are less likely to have cancer, and patients with cancer are less likely to have Alzheimer’s disease, according to data published online ahead of print July 10 in Neurology. Researchers conducted a cohort study of more than one million people in northern Italy. They derived cancer incidence using the local health authority’s tumor registry and calculated the incidence of Alzheimer’s dementia from registries of drug prescriptions, hospitalizations, and payment exemptions. The risk of cancer in patients with Alzheimer’s dementia was reduced by 50%, and the risk of Alzheimer’s dementia in patients with cancer was reduced by 35%. The investigators observed this relationship in almost all subgroup analyses, suggesting that anticipated potential confounding factors did not significantly influence the results.

Children exposed to antiepileptic drugs in utero may have an increased risk of adverse development within their first three years of life, according to research published online ahead of print July 19 in Epilepsia. From mid-1999 through December 2008, researchers followed children born to mothers who had been recruited at 13 to 17 weeks of pregnancy. Mothers reported their children’s motor development, language, social skills, and autistic traits at 18 months and 36 months. A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, exposed children had an increased risk of abnormal scores for gross motor skills and autistic traits, compared with nonexposed children. At 36 months, exposed children had an increased risk of abnormal scores for gross motor skills, sentence skills, and autistic traits.

The spatial pattern of amyloid deposition may be related to cognitive performance, according to a study published online ahead of print July 15 in Neurobiology of Aging. Researchers examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue PET data from the Baltimore Longitudinal Study of Aging. The group approximated spatial patterns of the temporal progression of amyloid plaque deposition from cross-sectional data. Results were consistent with patterns of progression known from autopsy studies. When the investigators categorized participants into subgroups based on longitudinal change in memory performance, they found significantly different spatial patterns of the estimated progression of amyloid deposition between these subgroups. This finding may affect the use of amyloid imaging as a biomarker in research and clinical applications, said the researchers.

A low frequency of physical activity may be associated with an increased risk of stroke, according to data published online ahead of print July 18 in Stroke. Researchers analyzed data for 27,348 participants in the Reasons for Geographic And Racial Differences in Stroke study who had no prior diagnosis of stroke. Participants reported their frequency of moderate-to-vigorous physical activity at baseline according to three categories. Physical inactivity was reported by 33% of participants and was associated with a 20% higher risk of stroke. Adjustment for demographics and socioeconomic factors did not affect the risk, but further adjustment for traditional stroke risk factors completely attenuated the risk. Effects of physical activity are likely to be mediated through the reduction of traditional risk factors, said the researchers.

FTY-720, an immunomodulator for treating multiple sclerosis, may alleviate existing cardiac hypertrophy, according to research published in the July 1 issue of Circulation: Heart Failure. Investigators subjected male C57/Bl6 mice to transverse aortic constriction (TAC) for one week. The researchers treated the mice with FTY-720 for two subsequent weeks while continuing to subject them to TAC. Mice treated with FTY-720 had significantly reduced ventricular mass, ameliorated fibrosis, and improved cardiac performance, compared with mice that received vehicle. Mechanistic studies suggested that FTY-720 appreciably inhibited nuclear factor of activated T-cells activity. In addition, pertussis toxin (Gi-coupled receptor inhibitor) substantially blocked the antihypertrophic effect of FTY-720 in primary rat and human cardiomyocytes. FTY-720 or its analogs could be a promising approach for treating hypertrophic heart disease, said the investigators.

For patients with cardiac arrest who require vasopressors, a combination of vasopressin, epinephrine, and methylprednisolone during cardiopulmonary resuscitation (CPR) and stress-dose hydrocortisone in postresuscitation shock may improve survival to hospital discharge and result in favorable neurologic status, according to data published in the July 17 JAMA. Researchers studied 268 consecutive patients with cardiac arrest requiring epinephrine. Patients received vasopressin plus epinephrine or saline placebo plus epinephrine for the first five CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the intervention group received methylprednisolone, and patients in the control group received saline placebo. Patients in the treatment arm had higher probability for return of spontaneous circulation of 20 minutes or longer and survival to hospital discharge with cerebral performance category score of 1 or 2.

Chinese people may have a higher risk of stroke than Caucasians, according to research published in the July 16 Neurology. Investigators analyzed studies conducted since 1990 in Chinese populations of first-ever stroke incidence and pathologic types and subtypes of stroke. The team examined hospital- and community-based studies. They also examined community-based stroke studies in Caucasian populations. Age-standardized, annual, first-ever stroke incidence in community-based studies was higher among Chinese than among Caucasian populations. Intracerebral hemorrhage accounted for a larger, more variable proportion of strokes in China than in Taiwan, in Chinese community-based than in hospital-based studies, and in community-based Chinese than in Caucasian studies. The overall proportion of lacunar ischemic stroke was higher in Chinese than in Caucasian populations, but variable study methodologies precluded reliable comparisons.

Narcolepsy in humans may be triggered partly by a proliferation of cells containing histamine, according to data published online ahead of print July 2 in Annals of Neurology. Investigators used immunohistochemistry for histidine decarboxylase (HDC) and quantitative microscopy to detect histamine cells in patients with narcolepsy, Hcrt receptor-2 mutant dogs, and three mouse narcolepsy models. The researchers found an average 64% increase in the number of histamine neurons in human narcolepsy with cataplexy, with no overlap between patients with narcolepsy and controls. The investigators did not observe altered numbers of HDC cells in any of the animal models of narcolepsy, however. The increased histamine cell numbers observed in human narcolepsy may be related to the process causing the human disorder, said the study authors.

Epilepsy may be associated with an early onset of cognitive decline, according to data published online ahead of print on July 8 in JAMA Neurology. Investigators conducted a retrospective observational study of patients at a memory and aging center from 2007 to 2012. Twelve participants had amnestic mild cognitive impairment (aMCI) plus epilepsy, 35 had Alzheimer’s disease plus epilepsy, and seven had Alzheimer’s disease plus subclinical epileptiform activity. Patients with aMCI and epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy. Patients with Alzheimer’s disease who had epilepsy presented with cognitive decline 5.5 years earlier than patients with Alzheimer’s disease who did not have epilepsy. Patients with Alzheimer’s disease and subclinical epileptiform activity also had an early onset of cognitive decline.

Globus pallidus interna (GPi) deep brain stimulation (DBS) may be an effective therapy for DYT1-associated torsion dystonia, according to a study published in the July issue of Neurosurgery. Researchers conducted a retrospective chart review of 47 consecutive patients with DYT1 who were treated by a single surgical team during a 10-year period and followed for up to 96 months. Symptom severity was quantified with the Burke–Fahn–Marsden Dystonia Rating Scale. Motor symptom severity was reduced to less than 20% of baseline after two years of DBS therapy. Disability scores were reduced to less than 30% of baseline. Symptomatic improvement was sustained throughout follow-up. Sixty-one percent of patients had discontinued all dystonia-related medications at their last follow-up. Ninety-one percent had discontinued at least one class of medication.

Concurrent cerebrovascular disease is a common neuropathologic finding in older individuals with dementia, according to an article published online ahead of print July 10 in Brain. Cerebrovascular disease, vascular pathology, and vascular risk factors were studied in 5,715 cases from the National Alzheimer’s Coordinating Centre database who had a single neurodegenerative disease diagnosis based on a neuropathologic examination with or without cerebrovascular disease. After controlling for age and gender, the researchers found a lower prevalence of coincident cerebrovascular disease among patients with α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease than among patients with Alzheimer’s disease. This result was more significant in younger patients. Data suggest that these disorders should be targeted by treatments for cerebrovascular disease, according to the researchers.

Athletes who do not get enough sleep the night before undergoing baseline concussion testing may not perform as well as they expect, according to research presented at the 2013 Annual Meeting of the American Orthopaedic Society for Sports Medicine in Chicago. Researchers reviewed 3,686 nonconcussed athletes (1,315 female) with baseline symptom and ImPACT neurocognitive scores. Individuals reported their previous night’s sleep duration as fewer than seven hours, seven to nine hours, or more than nine hours. The study authors observed significant differences in reaction time, verbal memory, and visual memory in the group that had slept less than seven hours. Visual-motor speed scores did not seem to be affected. Significant differences in the total number of reported symptoms were associated with sleeping fewer than seven hours.

Continuation of lipophilic statin therapy may be associated with a decreased risk of Parkinson’s disease, compared with discontinuation, according to research published online ahead of print July 24 in Neurology. Between 2001 and 2008, investigators recruited participants without Parkinson’s disease who had initiated statin therapy. Among 43,810 subjects, the incidence rate for Parkinson’s disease was 1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins, respectively. Continuation of lipophilic statins was associated with a decreased risk of Parkinson’s disease, compared with statin discontinuation. No association between hydrophilic statins and occurrence of Parkinson’s disease was observed. Among lipophilic statins, a significant association was observed for simvastatin and atorvastatin, especially in females. Long-term use of lipophilic or hydrophilic statins was not significantly associated with Parkinson’s disease.

—Erik Greb
Senior Associate Editor

Patients with Alzheimer’s disease are less likely to have cancer, and patients with cancer are less likely to have Alzheimer’s disease, according to data published online ahead of print July 10 in Neurology. Researchers conducted a cohort study of more than one million people in northern Italy. They derived cancer incidence using the local health authority’s tumor registry and calculated the incidence of Alzheimer’s dementia from registries of drug prescriptions, hospitalizations, and payment exemptions. The risk of cancer in patients with Alzheimer’s dementia was reduced by 50%, and the risk of Alzheimer’s dementia in patients with cancer was reduced by 35%. The investigators observed this relationship in almost all subgroup analyses, suggesting that anticipated potential confounding factors did not significantly influence the results.

Children exposed to antiepileptic drugs in utero may have an increased risk of adverse development within their first three years of life, according to research published online ahead of print July 19 in Epilepsia. From mid-1999 through December 2008, researchers followed children born to mothers who had been recruited at 13 to 17 weeks of pregnancy. Mothers reported their children’s motor development, language, social skills, and autistic traits at 18 months and 36 months. A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, exposed children had an increased risk of abnormal scores for gross motor skills and autistic traits, compared with nonexposed children. At 36 months, exposed children had an increased risk of abnormal scores for gross motor skills, sentence skills, and autistic traits.

The spatial pattern of amyloid deposition may be related to cognitive performance, according to a study published online ahead of print July 15 in Neurobiology of Aging. Researchers examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue PET data from the Baltimore Longitudinal Study of Aging. The group approximated spatial patterns of the temporal progression of amyloid plaque deposition from cross-sectional data. Results were consistent with patterns of progression known from autopsy studies. When the investigators categorized participants into subgroups based on longitudinal change in memory performance, they found significantly different spatial patterns of the estimated progression of amyloid deposition between these subgroups. This finding may affect the use of amyloid imaging as a biomarker in research and clinical applications, said the researchers.

A low frequency of physical activity may be associated with an increased risk of stroke, according to data published online ahead of print July 18 in Stroke. Researchers analyzed data for 27,348 participants in the Reasons for Geographic And Racial Differences in Stroke study who had no prior diagnosis of stroke. Participants reported their frequency of moderate-to-vigorous physical activity at baseline according to three categories. Physical inactivity was reported by 33% of participants and was associated with a 20% higher risk of stroke. Adjustment for demographics and socioeconomic factors did not affect the risk, but further adjustment for traditional stroke risk factors completely attenuated the risk. Effects of physical activity are likely to be mediated through the reduction of traditional risk factors, said the researchers.

FTY-720, an immunomodulator for treating multiple sclerosis, may alleviate existing cardiac hypertrophy, according to research published in the July 1 issue of Circulation: Heart Failure. Investigators subjected male C57/Bl6 mice to transverse aortic constriction (TAC) for one week. The researchers treated the mice with FTY-720 for two subsequent weeks while continuing to subject them to TAC. Mice treated with FTY-720 had significantly reduced ventricular mass, ameliorated fibrosis, and improved cardiac performance, compared with mice that received vehicle. Mechanistic studies suggested that FTY-720 appreciably inhibited nuclear factor of activated T-cells activity. In addition, pertussis toxin (Gi-coupled receptor inhibitor) substantially blocked the antihypertrophic effect of FTY-720 in primary rat and human cardiomyocytes. FTY-720 or its analogs could be a promising approach for treating hypertrophic heart disease, said the investigators.

For patients with cardiac arrest who require vasopressors, a combination of vasopressin, epinephrine, and methylprednisolone during cardiopulmonary resuscitation (CPR) and stress-dose hydrocortisone in postresuscitation shock may improve survival to hospital discharge and result in favorable neurologic status, according to data published in the July 17 JAMA. Researchers studied 268 consecutive patients with cardiac arrest requiring epinephrine. Patients received vasopressin plus epinephrine or saline placebo plus epinephrine for the first five CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the intervention group received methylprednisolone, and patients in the control group received saline placebo. Patients in the treatment arm had higher probability for return of spontaneous circulation of 20 minutes or longer and survival to hospital discharge with cerebral performance category score of 1 or 2.

Chinese people may have a higher risk of stroke than Caucasians, according to research published in the July 16 Neurology. Investigators analyzed studies conducted since 1990 in Chinese populations of first-ever stroke incidence and pathologic types and subtypes of stroke. The team examined hospital- and community-based studies. They also examined community-based stroke studies in Caucasian populations. Age-standardized, annual, first-ever stroke incidence in community-based studies was higher among Chinese than among Caucasian populations. Intracerebral hemorrhage accounted for a larger, more variable proportion of strokes in China than in Taiwan, in Chinese community-based than in hospital-based studies, and in community-based Chinese than in Caucasian studies. The overall proportion of lacunar ischemic stroke was higher in Chinese than in Caucasian populations, but variable study methodologies precluded reliable comparisons.

Narcolepsy in humans may be triggered partly by a proliferation of cells containing histamine, according to data published online ahead of print July 2 in Annals of Neurology. Investigators used immunohistochemistry for histidine decarboxylase (HDC) and quantitative microscopy to detect histamine cells in patients with narcolepsy, Hcrt receptor-2 mutant dogs, and three mouse narcolepsy models. The researchers found an average 64% increase in the number of histamine neurons in human narcolepsy with cataplexy, with no overlap between patients with narcolepsy and controls. The investigators did not observe altered numbers of HDC cells in any of the animal models of narcolepsy, however. The increased histamine cell numbers observed in human narcolepsy may be related to the process causing the human disorder, said the study authors.

Epilepsy may be associated with an early onset of cognitive decline, according to data published online ahead of print on July 8 in JAMA Neurology. Investigators conducted a retrospective observational study of patients at a memory and aging center from 2007 to 2012. Twelve participants had amnestic mild cognitive impairment (aMCI) plus epilepsy, 35 had Alzheimer’s disease plus epilepsy, and seven had Alzheimer’s disease plus subclinical epileptiform activity. Patients with aMCI and epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy. Patients with Alzheimer’s disease who had epilepsy presented with cognitive decline 5.5 years earlier than patients with Alzheimer’s disease who did not have epilepsy. Patients with Alzheimer’s disease and subclinical epileptiform activity also had an early onset of cognitive decline.

Globus pallidus interna (GPi) deep brain stimulation (DBS) may be an effective therapy for DYT1-associated torsion dystonia, according to a study published in the July issue of Neurosurgery. Researchers conducted a retrospective chart review of 47 consecutive patients with DYT1 who were treated by a single surgical team during a 10-year period and followed for up to 96 months. Symptom severity was quantified with the Burke–Fahn–Marsden Dystonia Rating Scale. Motor symptom severity was reduced to less than 20% of baseline after two years of DBS therapy. Disability scores were reduced to less than 30% of baseline. Symptomatic improvement was sustained throughout follow-up. Sixty-one percent of patients had discontinued all dystonia-related medications at their last follow-up. Ninety-one percent had discontinued at least one class of medication.

Concurrent cerebrovascular disease is a common neuropathologic finding in older individuals with dementia, according to an article published online ahead of print July 10 in Brain. Cerebrovascular disease, vascular pathology, and vascular risk factors were studied in 5,715 cases from the National Alzheimer’s Coordinating Centre database who had a single neurodegenerative disease diagnosis based on a neuropathologic examination with or without cerebrovascular disease. After controlling for age and gender, the researchers found a lower prevalence of coincident cerebrovascular disease among patients with α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease than among patients with Alzheimer’s disease. This result was more significant in younger patients. Data suggest that these disorders should be targeted by treatments for cerebrovascular disease, according to the researchers.

Athletes who do not get enough sleep the night before undergoing baseline concussion testing may not perform as well as they expect, according to research presented at the 2013 Annual Meeting of the American Orthopaedic Society for Sports Medicine in Chicago. Researchers reviewed 3,686 nonconcussed athletes (1,315 female) with baseline symptom and ImPACT neurocognitive scores. Individuals reported their previous night’s sleep duration as fewer than seven hours, seven to nine hours, or more than nine hours. The study authors observed significant differences in reaction time, verbal memory, and visual memory in the group that had slept less than seven hours. Visual-motor speed scores did not seem to be affected. Significant differences in the total number of reported symptoms were associated with sleeping fewer than seven hours.

Continuation of lipophilic statin therapy may be associated with a decreased risk of Parkinson’s disease, compared with discontinuation, according to research published online ahead of print July 24 in Neurology. Between 2001 and 2008, investigators recruited participants without Parkinson’s disease who had initiated statin therapy. Among 43,810 subjects, the incidence rate for Parkinson’s disease was 1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins, respectively. Continuation of lipophilic statins was associated with a decreased risk of Parkinson’s disease, compared with statin discontinuation. No association between hydrophilic statins and occurrence of Parkinson’s disease was observed. Among lipophilic statins, a significant association was observed for simvastatin and atorvastatin, especially in females. Long-term use of lipophilic or hydrophilic statins was not significantly associated with Parkinson’s disease.

—Erik Greb
Senior Associate Editor

Patients with Alzheimer’s disease are less likely to have cancer, and patients with cancer are less likely to have Alzheimer’s disease, according to data published online ahead of print July 10 in Neurology. Researchers conducted a cohort study of more than one million people in northern Italy. They derived cancer incidence using the local health authority’s tumor registry and calculated the incidence of Alzheimer’s dementia from registries of drug prescriptions, hospitalizations, and payment exemptions. The risk of cancer in patients with Alzheimer’s dementia was reduced by 50%, and the risk of Alzheimer’s dementia in patients with cancer was reduced by 35%. The investigators observed this relationship in almost all subgroup analyses, suggesting that anticipated potential confounding factors did not significantly influence the results.

Children exposed to antiepileptic drugs in utero may have an increased risk of adverse development within their first three years of life, according to research published online ahead of print July 19 in Epilepsia. From mid-1999 through December 2008, researchers followed children born to mothers who had been recruited at 13 to 17 weeks of pregnancy. Mothers reported their children’s motor development, language, social skills, and autistic traits at 18 months and 36 months. A total of 333 children were exposed to antiepileptic drugs in utero. At 18 months, exposed children had an increased risk of abnormal scores for gross motor skills and autistic traits, compared with nonexposed children. At 36 months, exposed children had an increased risk of abnormal scores for gross motor skills, sentence skills, and autistic traits.

The spatial pattern of amyloid deposition may be related to cognitive performance, according to a study published online ahead of print July 15 in Neurobiology of Aging. Researchers examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue PET data from the Baltimore Longitudinal Study of Aging. The group approximated spatial patterns of the temporal progression of amyloid plaque deposition from cross-sectional data. Results were consistent with patterns of progression known from autopsy studies. When the investigators categorized participants into subgroups based on longitudinal change in memory performance, they found significantly different spatial patterns of the estimated progression of amyloid deposition between these subgroups. This finding may affect the use of amyloid imaging as a biomarker in research and clinical applications, said the researchers.

A low frequency of physical activity may be associated with an increased risk of stroke, according to data published online ahead of print July 18 in Stroke. Researchers analyzed data for 27,348 participants in the Reasons for Geographic And Racial Differences in Stroke study who had no prior diagnosis of stroke. Participants reported their frequency of moderate-to-vigorous physical activity at baseline according to three categories. Physical inactivity was reported by 33% of participants and was associated with a 20% higher risk of stroke. Adjustment for demographics and socioeconomic factors did not affect the risk, but further adjustment for traditional stroke risk factors completely attenuated the risk. Effects of physical activity are likely to be mediated through the reduction of traditional risk factors, said the researchers.

FTY-720, an immunomodulator for treating multiple sclerosis, may alleviate existing cardiac hypertrophy, according to research published in the July 1 issue of Circulation: Heart Failure. Investigators subjected male C57/Bl6 mice to transverse aortic constriction (TAC) for one week. The researchers treated the mice with FTY-720 for two subsequent weeks while continuing to subject them to TAC. Mice treated with FTY-720 had significantly reduced ventricular mass, ameliorated fibrosis, and improved cardiac performance, compared with mice that received vehicle. Mechanistic studies suggested that FTY-720 appreciably inhibited nuclear factor of activated T-cells activity. In addition, pertussis toxin (Gi-coupled receptor inhibitor) substantially blocked the antihypertrophic effect of FTY-720 in primary rat and human cardiomyocytes. FTY-720 or its analogs could be a promising approach for treating hypertrophic heart disease, said the investigators.

For patients with cardiac arrest who require vasopressors, a combination of vasopressin, epinephrine, and methylprednisolone during cardiopulmonary resuscitation (CPR) and stress-dose hydrocortisone in postresuscitation shock may improve survival to hospital discharge and result in favorable neurologic status, according to data published in the July 17 JAMA. Researchers studied 268 consecutive patients with cardiac arrest requiring epinephrine. Patients received vasopressin plus epinephrine or saline placebo plus epinephrine for the first five CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the intervention group received methylprednisolone, and patients in the control group received saline placebo. Patients in the treatment arm had higher probability for return of spontaneous circulation of 20 minutes or longer and survival to hospital discharge with cerebral performance category score of 1 or 2.

Chinese people may have a higher risk of stroke than Caucasians, according to research published in the July 16 Neurology. Investigators analyzed studies conducted since 1990 in Chinese populations of first-ever stroke incidence and pathologic types and subtypes of stroke. The team examined hospital- and community-based studies. They also examined community-based stroke studies in Caucasian populations. Age-standardized, annual, first-ever stroke incidence in community-based studies was higher among Chinese than among Caucasian populations. Intracerebral hemorrhage accounted for a larger, more variable proportion of strokes in China than in Taiwan, in Chinese community-based than in hospital-based studies, and in community-based Chinese than in Caucasian studies. The overall proportion of lacunar ischemic stroke was higher in Chinese than in Caucasian populations, but variable study methodologies precluded reliable comparisons.

Narcolepsy in humans may be triggered partly by a proliferation of cells containing histamine, according to data published online ahead of print July 2 in Annals of Neurology. Investigators used immunohistochemistry for histidine decarboxylase (HDC) and quantitative microscopy to detect histamine cells in patients with narcolepsy, Hcrt receptor-2 mutant dogs, and three mouse narcolepsy models. The researchers found an average 64% increase in the number of histamine neurons in human narcolepsy with cataplexy, with no overlap between patients with narcolepsy and controls. The investigators did not observe altered numbers of HDC cells in any of the animal models of narcolepsy, however. The increased histamine cell numbers observed in human narcolepsy may be related to the process causing the human disorder, said the study authors.

Epilepsy may be associated with an early onset of cognitive decline, according to data published online ahead of print on July 8 in JAMA Neurology. Investigators conducted a retrospective observational study of patients at a memory and aging center from 2007 to 2012. Twelve participants had amnestic mild cognitive impairment (aMCI) plus epilepsy, 35 had Alzheimer’s disease plus epilepsy, and seven had Alzheimer’s disease plus subclinical epileptiform activity. Patients with aMCI and epilepsy presented with symptoms of cognitive decline 6.8 years earlier than patients with aMCI who did not have epilepsy. Patients with Alzheimer’s disease who had epilepsy presented with cognitive decline 5.5 years earlier than patients with Alzheimer’s disease who did not have epilepsy. Patients with Alzheimer’s disease and subclinical epileptiform activity also had an early onset of cognitive decline.

Globus pallidus interna (GPi) deep brain stimulation (DBS) may be an effective therapy for DYT1-associated torsion dystonia, according to a study published in the July issue of Neurosurgery. Researchers conducted a retrospective chart review of 47 consecutive patients with DYT1 who were treated by a single surgical team during a 10-year period and followed for up to 96 months. Symptom severity was quantified with the Burke–Fahn–Marsden Dystonia Rating Scale. Motor symptom severity was reduced to less than 20% of baseline after two years of DBS therapy. Disability scores were reduced to less than 30% of baseline. Symptomatic improvement was sustained throughout follow-up. Sixty-one percent of patients had discontinued all dystonia-related medications at their last follow-up. Ninety-one percent had discontinued at least one class of medication.

Concurrent cerebrovascular disease is a common neuropathologic finding in older individuals with dementia, according to an article published online ahead of print July 10 in Brain. Cerebrovascular disease, vascular pathology, and vascular risk factors were studied in 5,715 cases from the National Alzheimer’s Coordinating Centre database who had a single neurodegenerative disease diagnosis based on a neuropathologic examination with or without cerebrovascular disease. After controlling for age and gender, the researchers found a lower prevalence of coincident cerebrovascular disease among patients with α-synucleinopathies, frontotemporal lobar degeneration due to tau and TAR DNA-binding protein 43, and prion disease than among patients with Alzheimer’s disease. This result was more significant in younger patients. Data suggest that these disorders should be targeted by treatments for cerebrovascular disease, according to the researchers.

Athletes who do not get enough sleep the night before undergoing baseline concussion testing may not perform as well as they expect, according to research presented at the 2013 Annual Meeting of the American Orthopaedic Society for Sports Medicine in Chicago. Researchers reviewed 3,686 nonconcussed athletes (1,315 female) with baseline symptom and ImPACT neurocognitive scores. Individuals reported their previous night’s sleep duration as fewer than seven hours, seven to nine hours, or more than nine hours. The study authors observed significant differences in reaction time, verbal memory, and visual memory in the group that had slept less than seven hours. Visual-motor speed scores did not seem to be affected. Significant differences in the total number of reported symptoms were associated with sleeping fewer than seven hours.

Continuation of lipophilic statin therapy may be associated with a decreased risk of Parkinson’s disease, compared with discontinuation, according to research published online ahead of print July 24 in Neurology. Between 2001 and 2008, investigators recruited participants without Parkinson’s disease who had initiated statin therapy. Among 43,810 subjects, the incidence rate for Parkinson’s disease was 1.68 and 3.52 per 1,000,000 person-days for lipophilic and hydrophilic statins, respectively. Continuation of lipophilic statins was associated with a decreased risk of Parkinson’s disease, compared with statin discontinuation. No association between hydrophilic statins and occurrence of Parkinson’s disease was observed. Among lipophilic statins, a significant association was observed for simvastatin and atorvastatin, especially in females. Long-term use of lipophilic or hydrophilic statins was not significantly associated with Parkinson’s disease.

—Erik Greb
Senior Associate Editor

In patients with arterial disease, low baseline diastolic blood pressure may correspond with increased progression of subcortical atrophy, researchers reported online ahead of print June 10 in JAMA Neurology. The association may not depend on subsequent change in blood pressure. Researchers measured blood pressure for 663 participants at baseline and at a mean of 3.9 years later. Change in brain parenchymal fraction, cortical gray matter fraction, and ventricular fraction were quantified as indicators of progression of global, cortical, and subcortical brain atrophy. Patients with lower baseline diastolic blood pressure or mean arterial pressure had more progression of subcortical atrophy. Of patients with higher baseline blood pressure, those with declining blood pressure over time had less progression of subcortical atrophy, compared with those with increasing blood pressure.

Diffusion tensor imaging (DTI) of the basal ganglia and cerebellum may accurately diagnose Parkinson’s disease and other movement disorders, according to a study published online ahead of print May 14 in Movement Disorders. Investigators studied 72 subjects with DTI at 3 T. The technique distinguished between controls and patients with movement disorder with 92% sensitivity and 88% specificity. DTI also distinguished between controls and patients with parkinsonism (93% sensitivity, 91% specificity), Parkinson’s disease and atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson’s disease and multiple system atrophy (94% sensitivity, 100% specificity), Parkinson’s disease and progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy and progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson’s disease and essential tremor (92% sensitivity, 87% specificity).

Heading a soccer ball may be associated with abnormal white matter microstructure and poor neurocognitive performance, according to research published online ahead of print June 11 in Radiology. Thirty-seven amateur soccer players answered a questionnaire about heading in the previous 12 months and lifetime history of concussions. Investigators performed diffusion-tensor MRI on the players and evaluated their cognitive function. The players had headed a median of 432 times during the previous year. Heading was associated with lower fractional anisotropy (FA) at three locations in temporo-occipital white matter with a threshold that varied according to location. Heading more than 1,800 times per year was associated with lower levels of FA and poorer memory scores. Concussion history and demographic features were not significantly associated with FA or cognitive performance.

Restless legs syndrome (RLS) may entail an increased risk of mortality, independent of known risk factors, according to a study published online ahead of print June 12 in Neurology. Researchers conducted a prospective cohort study of 18,425 American men without diabetes, arthritis, or renal failure. RLS was assessed using standardized questions. During eight years of follow-up, 2,765 deaths occurred. In an age-adjusted model, RLS was associated with a 39% increased risk of mortality. The association between RLS and mortality was slightly attenuated after further adjustment for BMI, lifestyle factors, chronic conditions, sleep duration, and other sleep-related disorders. When patients with major chronic conditions (eg, cancer, high blood pressure, cardiovascular disease, and other comorbidities) were excluded, the adjusted hazard ratio for RLS was 1.92.

Patients with stroke who are about to undergo surgery can safely continue to take aspirin or warfarin in many instances, according to a guideline published in the May 28 Neurology. Researchers systematically reviewed the literature to assess evidence about the periprocedural management of antithrombotic drugs in patients with ischemic cerebrovascular disease. Stroke patients undergoing dental procedures should routinely continue aspirin, according to the guideline. Stroke patients undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound–guided prostate biopsy, spinal or epidural procedures, and carpal tunnel surgery should probably continue aspirin. Stroke patients requiring warfarin should routinely continue it when undergoing dental procedures and probably continue it for dermatologic procedures. Some patients undergoing EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein should possibly continue warfarin.

Exposure to pesticides or solvents could be a risk factor for Parkinson’s disease, investigators concluded in the May 28 Neurology. Researchers performed a meta-analysis of prospective cohort and case-control studies that estimated the risk of Parkinson’s disease associated with exposure to pesticides or solvents. Parkinson’s disease was associated with farming, and the association between the disease and pesticides was highly significant in the studies in which Parkinson’s disease diagnosis was self-reported. In high-quality case-control studies, exposure to any pesticides, herbicides, and solvents increased the risk of Parkinson’s disease. Exposure to paraquat or maneb/mancozeb was associated with about a twofold increase in risk. Study quality was not a source of heterogeneity among prospective studies. In case-control studies, study quality was a source of heterogeneity in risk estimates for some exposures.

Atrial fibrillation may be associated with faster cognitive decline, according to a study published online ahead of print June 5 in Neurology. Researchers studied 5,150 men and women 65 or older who did not have atrial fibrillation or a history of stroke at baseline. Atrial fibrillation was identified by examining hospital discharge records and annual ECGs. A total of 552 patients (10.7%) developed incident atrial fibrillation during a mean seven years of follow-up. Mean Modified Mini-Mental State Examination (MMMSE) scores declined faster in patients with incident atrial fibrillation than in patients without atrial fibrillation. The predicted five-year decline in mean MMMSE score from age 80 to age 85 was −6.4 points for participants without atrial fibrillation and −10.3 points for participants with incident atrial fibrillation at age 80.

The level of interleukin 17F (IL-17F) in a patient with relapsing-remitting multiple sclerosis (MS) may not predict his or her response to treatment with interferon beta, according to research published online ahead of print June 3 in JAMA Neurology. Researchers analyzed serum samples from 239 randomly selected patients treated with interferon beta-1b (250 μg) for at least two years. Using clinical and MRI criteria, the investigators found that levels of IL-17F measured at baseline and month six did not correlate with lack of response to treatment after two years. Relapses and new lesions on MRI were not associated with pretreatment serum IL-17F levels. The results did not change when patients with neutralizing antibodies were excluded. Patients with levels of IL-17F higher than 200 pg/mL had poor response and clinical or radiologic activity.

Earlier treatment with thrombolytics may be associated with reduced mortality for patients with stroke, according to data published in the June 19 JAMA. Researchers analyzed data from 58,353 patients with acute ischemic stroke who were treated with t-PA within 4.5 hours of symptom onset in 1,395 hospitals. Patients’ median age was 72, 50.3% of patients were women, and median time to treatment was 144 minutes. A total of 5,142 in-hospital deaths occurred. Faster time to treatment, in 15-minute increments, was associated with reduced in-hospital mortality, reduced symptomatic intracranial hemorrhage, increased achievement of independent ambulation at discharge, and increased discharge to home. Patient factors most strongly associated with shorter time to treatment included greater stroke severity, arrival by ambulance, and arrival during regular hours.

High serum iron levels may be associated with a decreased risk of developing Parkinson’s disease, according to a study published June 4 in PLOS Medicine. Researchers investigated three polymorphisms in the genes HFE and TMPRSS6. For each polymorphism, they performed a meta-analysis of studies investigating the genetic effect on iron levels and a meta-analysis of studies investigating the genetic effect on the risk of Parkinson’s disease. Using three Mendelian randomization analyses, the investigators estimated the effect of iron on Parkinson’s disease for the three polymorphisms. Every 10 µg/dl increase in blood iron corresponded to a 3% reduction in the risk of Parkinson’s disease. Thus, increased blood iron levels may have a protective effect against Parkinson’s disease, but the underlying mechanism remains unclear, said the researchers.

Diabetes and dementia may have a bidirectional association, according to research published online ahead of print June 10 in JAMA Internal Medicine. Investigators examined 783 older adults with diabetes who were participating in a prospective population-based study. Subjects’ mean age was 74, and their baseline Modified Mini-Mental State Examination scores were 80 or higher. Approximately 47% of subjects were African American, and 47% were female. During the 12-year follow-up, 61 participants had a reported hypoglycemic event, and 148 developed dementia. Subjects who had a hypoglycemic event had a twofold increased risk for developing dementia, compared with those who did not have a hypoglycemic event. Subjects with diabetes who developed dementia had a greater risk for having a subsequent hypoglycemic event, compared with participants who did not develop dementia.

Cardiovascular biomarkers may help identify patients with subclinical cerebral injury, according to research published online ahead of print May 9 in Stroke. A total of 1,920 subjects received a brain MRI and had their levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T (hs-cTnT) measured. Of the total group, 1,112 had a follow-up MRI between nine and 13 years later. Individuals with the highest NT-proBNP levels had significantly more silent brain infarcts and white matter lesions on the baseline MRI and more incident silent brain infarcts and white matter lesion progression on the follow-up MRI. Individuals with the highest hs-cTnT levels had more silent brain infarcts and white matter lesions on the initial MRI and more white matter lesion progression on the follow-up MRI.

Stroke symptoms or transient ischemic attack (TIA) may be strongly associated with incident cognitive impairment, researchers concluded in a study published online ahead of print June 19 in Neurology. The investigators studied 23,830 participants without cognitive impairment or history of stroke enrolled in the Reasons for Geographic and Racial Differences in Stroke Study. Subjects reported stroke symptoms and TIA every six months and were screened annually for cognitive impairment. Among Caucasians, the odds ratio for incident cognitive impairment was 2.08 for subjects reporting at least one stroke symptom or TIA, compared with those reporting no stroke symptom or TIA. Among African Americans, the odds ratio was 1.66 using the same modeling. The magnitude of impact was largest among participants with fewer traditional stroke risk factors.

—Erik Greb
Senior Associate Editor

In patients with arterial disease, low baseline diastolic blood pressure may correspond with increased progression of subcortical atrophy, researchers reported online ahead of print June 10 in JAMA Neurology. The association may not depend on subsequent change in blood pressure. Researchers measured blood pressure for 663 participants at baseline and at a mean of 3.9 years later. Change in brain parenchymal fraction, cortical gray matter fraction, and ventricular fraction were quantified as indicators of progression of global, cortical, and subcortical brain atrophy. Patients with lower baseline diastolic blood pressure or mean arterial pressure had more progression of subcortical atrophy. Of patients with higher baseline blood pressure, those with declining blood pressure over time had less progression of subcortical atrophy, compared with those with increasing blood pressure.

Diffusion tensor imaging (DTI) of the basal ganglia and cerebellum may accurately diagnose Parkinson’s disease and other movement disorders, according to a study published online ahead of print May 14 in Movement Disorders. Investigators studied 72 subjects with DTI at 3 T. The technique distinguished between controls and patients with movement disorder with 92% sensitivity and 88% specificity. DTI also distinguished between controls and patients with parkinsonism (93% sensitivity, 91% specificity), Parkinson’s disease and atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson’s disease and multiple system atrophy (94% sensitivity, 100% specificity), Parkinson’s disease and progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy and progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson’s disease and essential tremor (92% sensitivity, 87% specificity).

Heading a soccer ball may be associated with abnormal white matter microstructure and poor neurocognitive performance, according to research published online ahead of print June 11 in Radiology. Thirty-seven amateur soccer players answered a questionnaire about heading in the previous 12 months and lifetime history of concussions. Investigators performed diffusion-tensor MRI on the players and evaluated their cognitive function. The players had headed a median of 432 times during the previous year. Heading was associated with lower fractional anisotropy (FA) at three locations in temporo-occipital white matter with a threshold that varied according to location. Heading more than 1,800 times per year was associated with lower levels of FA and poorer memory scores. Concussion history and demographic features were not significantly associated with FA or cognitive performance.

Restless legs syndrome (RLS) may entail an increased risk of mortality, independent of known risk factors, according to a study published online ahead of print June 12 in Neurology. Researchers conducted a prospective cohort study of 18,425 American men without diabetes, arthritis, or renal failure. RLS was assessed using standardized questions. During eight years of follow-up, 2,765 deaths occurred. In an age-adjusted model, RLS was associated with a 39% increased risk of mortality. The association between RLS and mortality was slightly attenuated after further adjustment for BMI, lifestyle factors, chronic conditions, sleep duration, and other sleep-related disorders. When patients with major chronic conditions (eg, cancer, high blood pressure, cardiovascular disease, and other comorbidities) were excluded, the adjusted hazard ratio for RLS was 1.92.

Patients with stroke who are about to undergo surgery can safely continue to take aspirin or warfarin in many instances, according to a guideline published in the May 28 Neurology. Researchers systematically reviewed the literature to assess evidence about the periprocedural management of antithrombotic drugs in patients with ischemic cerebrovascular disease. Stroke patients undergoing dental procedures should routinely continue aspirin, according to the guideline. Stroke patients undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound–guided prostate biopsy, spinal or epidural procedures, and carpal tunnel surgery should probably continue aspirin. Stroke patients requiring warfarin should routinely continue it when undergoing dental procedures and probably continue it for dermatologic procedures. Some patients undergoing EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein should possibly continue warfarin.

Exposure to pesticides or solvents could be a risk factor for Parkinson’s disease, investigators concluded in the May 28 Neurology. Researchers performed a meta-analysis of prospective cohort and case-control studies that estimated the risk of Parkinson’s disease associated with exposure to pesticides or solvents. Parkinson’s disease was associated with farming, and the association between the disease and pesticides was highly significant in the studies in which Parkinson’s disease diagnosis was self-reported. In high-quality case-control studies, exposure to any pesticides, herbicides, and solvents increased the risk of Parkinson’s disease. Exposure to paraquat or maneb/mancozeb was associated with about a twofold increase in risk. Study quality was not a source of heterogeneity among prospective studies. In case-control studies, study quality was a source of heterogeneity in risk estimates for some exposures.

Atrial fibrillation may be associated with faster cognitive decline, according to a study published online ahead of print June 5 in Neurology. Researchers studied 5,150 men and women 65 or older who did not have atrial fibrillation or a history of stroke at baseline. Atrial fibrillation was identified by examining hospital discharge records and annual ECGs. A total of 552 patients (10.7%) developed incident atrial fibrillation during a mean seven years of follow-up. Mean Modified Mini-Mental State Examination (MMMSE) scores declined faster in patients with incident atrial fibrillation than in patients without atrial fibrillation. The predicted five-year decline in mean MMMSE score from age 80 to age 85 was −6.4 points for participants without atrial fibrillation and −10.3 points for participants with incident atrial fibrillation at age 80.

The level of interleukin 17F (IL-17F) in a patient with relapsing-remitting multiple sclerosis (MS) may not predict his or her response to treatment with interferon beta, according to research published online ahead of print June 3 in JAMA Neurology. Researchers analyzed serum samples from 239 randomly selected patients treated with interferon beta-1b (250 μg) for at least two years. Using clinical and MRI criteria, the investigators found that levels of IL-17F measured at baseline and month six did not correlate with lack of response to treatment after two years. Relapses and new lesions on MRI were not associated with pretreatment serum IL-17F levels. The results did not change when patients with neutralizing antibodies were excluded. Patients with levels of IL-17F higher than 200 pg/mL had poor response and clinical or radiologic activity.

Earlier treatment with thrombolytics may be associated with reduced mortality for patients with stroke, according to data published in the June 19 JAMA. Researchers analyzed data from 58,353 patients with acute ischemic stroke who were treated with t-PA within 4.5 hours of symptom onset in 1,395 hospitals. Patients’ median age was 72, 50.3% of patients were women, and median time to treatment was 144 minutes. A total of 5,142 in-hospital deaths occurred. Faster time to treatment, in 15-minute increments, was associated with reduced in-hospital mortality, reduced symptomatic intracranial hemorrhage, increased achievement of independent ambulation at discharge, and increased discharge to home. Patient factors most strongly associated with shorter time to treatment included greater stroke severity, arrival by ambulance, and arrival during regular hours.

High serum iron levels may be associated with a decreased risk of developing Parkinson’s disease, according to a study published June 4 in PLOS Medicine. Researchers investigated three polymorphisms in the genes HFE and TMPRSS6. For each polymorphism, they performed a meta-analysis of studies investigating the genetic effect on iron levels and a meta-analysis of studies investigating the genetic effect on the risk of Parkinson’s disease. Using three Mendelian randomization analyses, the investigators estimated the effect of iron on Parkinson’s disease for the three polymorphisms. Every 10 µg/dl increase in blood iron corresponded to a 3% reduction in the risk of Parkinson’s disease. Thus, increased blood iron levels may have a protective effect against Parkinson’s disease, but the underlying mechanism remains unclear, said the researchers.

Diabetes and dementia may have a bidirectional association, according to research published online ahead of print June 10 in JAMA Internal Medicine. Investigators examined 783 older adults with diabetes who were participating in a prospective population-based study. Subjects’ mean age was 74, and their baseline Modified Mini-Mental State Examination scores were 80 or higher. Approximately 47% of subjects were African American, and 47% were female. During the 12-year follow-up, 61 participants had a reported hypoglycemic event, and 148 developed dementia. Subjects who had a hypoglycemic event had a twofold increased risk for developing dementia, compared with those who did not have a hypoglycemic event. Subjects with diabetes who developed dementia had a greater risk for having a subsequent hypoglycemic event, compared with participants who did not develop dementia.

Cardiovascular biomarkers may help identify patients with subclinical cerebral injury, according to research published online ahead of print May 9 in Stroke. A total of 1,920 subjects received a brain MRI and had their levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T (hs-cTnT) measured. Of the total group, 1,112 had a follow-up MRI between nine and 13 years later. Individuals with the highest NT-proBNP levels had significantly more silent brain infarcts and white matter lesions on the baseline MRI and more incident silent brain infarcts and white matter lesion progression on the follow-up MRI. Individuals with the highest hs-cTnT levels had more silent brain infarcts and white matter lesions on the initial MRI and more white matter lesion progression on the follow-up MRI.

Stroke symptoms or transient ischemic attack (TIA) may be strongly associated with incident cognitive impairment, researchers concluded in a study published online ahead of print June 19 in Neurology. The investigators studied 23,830 participants without cognitive impairment or history of stroke enrolled in the Reasons for Geographic and Racial Differences in Stroke Study. Subjects reported stroke symptoms and TIA every six months and were screened annually for cognitive impairment. Among Caucasians, the odds ratio for incident cognitive impairment was 2.08 for subjects reporting at least one stroke symptom or TIA, compared with those reporting no stroke symptom or TIA. Among African Americans, the odds ratio was 1.66 using the same modeling. The magnitude of impact was largest among participants with fewer traditional stroke risk factors.

—Erik Greb
Senior Associate Editor

In patients with arterial disease, low baseline diastolic blood pressure may correspond with increased progression of subcortical atrophy, researchers reported online ahead of print June 10 in JAMA Neurology. The association may not depend on subsequent change in blood pressure. Researchers measured blood pressure for 663 participants at baseline and at a mean of 3.9 years later. Change in brain parenchymal fraction, cortical gray matter fraction, and ventricular fraction were quantified as indicators of progression of global, cortical, and subcortical brain atrophy. Patients with lower baseline diastolic blood pressure or mean arterial pressure had more progression of subcortical atrophy. Of patients with higher baseline blood pressure, those with declining blood pressure over time had less progression of subcortical atrophy, compared with those with increasing blood pressure.

Diffusion tensor imaging (DTI) of the basal ganglia and cerebellum may accurately diagnose Parkinson’s disease and other movement disorders, according to a study published online ahead of print May 14 in Movement Disorders. Investigators studied 72 subjects with DTI at 3 T. The technique distinguished between controls and patients with movement disorder with 92% sensitivity and 88% specificity. DTI also distinguished between controls and patients with parkinsonism (93% sensitivity, 91% specificity), Parkinson’s disease and atypical parkinsonism (90% sensitivity, 100% specificity), Parkinson’s disease and multiple system atrophy (94% sensitivity, 100% specificity), Parkinson’s disease and progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy and progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinson’s disease and essential tremor (92% sensitivity, 87% specificity).

Heading a soccer ball may be associated with abnormal white matter microstructure and poor neurocognitive performance, according to research published online ahead of print June 11 in Radiology. Thirty-seven amateur soccer players answered a questionnaire about heading in the previous 12 months and lifetime history of concussions. Investigators performed diffusion-tensor MRI on the players and evaluated their cognitive function. The players had headed a median of 432 times during the previous year. Heading was associated with lower fractional anisotropy (FA) at three locations in temporo-occipital white matter with a threshold that varied according to location. Heading more than 1,800 times per year was associated with lower levels of FA and poorer memory scores. Concussion history and demographic features were not significantly associated with FA or cognitive performance.

Restless legs syndrome (RLS) may entail an increased risk of mortality, independent of known risk factors, according to a study published online ahead of print June 12 in Neurology. Researchers conducted a prospective cohort study of 18,425 American men without diabetes, arthritis, or renal failure. RLS was assessed using standardized questions. During eight years of follow-up, 2,765 deaths occurred. In an age-adjusted model, RLS was associated with a 39% increased risk of mortality. The association between RLS and mortality was slightly attenuated after further adjustment for BMI, lifestyle factors, chronic conditions, sleep duration, and other sleep-related disorders. When patients with major chronic conditions (eg, cancer, high blood pressure, cardiovascular disease, and other comorbidities) were excluded, the adjusted hazard ratio for RLS was 1.92.

Patients with stroke who are about to undergo surgery can safely continue to take aspirin or warfarin in many instances, according to a guideline published in the May 28 Neurology. Researchers systematically reviewed the literature to assess evidence about the periprocedural management of antithrombotic drugs in patients with ischemic cerebrovascular disease. Stroke patients undergoing dental procedures should routinely continue aspirin, according to the guideline. Stroke patients undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound–guided prostate biopsy, spinal or epidural procedures, and carpal tunnel surgery should probably continue aspirin. Stroke patients requiring warfarin should routinely continue it when undergoing dental procedures and probably continue it for dermatologic procedures. Some patients undergoing EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein should possibly continue warfarin.

Exposure to pesticides or solvents could be a risk factor for Parkinson’s disease, investigators concluded in the May 28 Neurology. Researchers performed a meta-analysis of prospective cohort and case-control studies that estimated the risk of Parkinson’s disease associated with exposure to pesticides or solvents. Parkinson’s disease was associated with farming, and the association between the disease and pesticides was highly significant in the studies in which Parkinson’s disease diagnosis was self-reported. In high-quality case-control studies, exposure to any pesticides, herbicides, and solvents increased the risk of Parkinson’s disease. Exposure to paraquat or maneb/mancozeb was associated with about a twofold increase in risk. Study quality was not a source of heterogeneity among prospective studies. In case-control studies, study quality was a source of heterogeneity in risk estimates for some exposures.

Atrial fibrillation may be associated with faster cognitive decline, according to a study published online ahead of print June 5 in Neurology. Researchers studied 5,150 men and women 65 or older who did not have atrial fibrillation or a history of stroke at baseline. Atrial fibrillation was identified by examining hospital discharge records and annual ECGs. A total of 552 patients (10.7%) developed incident atrial fibrillation during a mean seven years of follow-up. Mean Modified Mini-Mental State Examination (MMMSE) scores declined faster in patients with incident atrial fibrillation than in patients without atrial fibrillation. The predicted five-year decline in mean MMMSE score from age 80 to age 85 was −6.4 points for participants without atrial fibrillation and −10.3 points for participants with incident atrial fibrillation at age 80.

The level of interleukin 17F (IL-17F) in a patient with relapsing-remitting multiple sclerosis (MS) may not predict his or her response to treatment with interferon beta, according to research published online ahead of print June 3 in JAMA Neurology. Researchers analyzed serum samples from 239 randomly selected patients treated with interferon beta-1b (250 μg) for at least two years. Using clinical and MRI criteria, the investigators found that levels of IL-17F measured at baseline and month six did not correlate with lack of response to treatment after two years. Relapses and new lesions on MRI were not associated with pretreatment serum IL-17F levels. The results did not change when patients with neutralizing antibodies were excluded. Patients with levels of IL-17F higher than 200 pg/mL had poor response and clinical or radiologic activity.

Earlier treatment with thrombolytics may be associated with reduced mortality for patients with stroke, according to data published in the June 19 JAMA. Researchers analyzed data from 58,353 patients with acute ischemic stroke who were treated with t-PA within 4.5 hours of symptom onset in 1,395 hospitals. Patients’ median age was 72, 50.3% of patients were women, and median time to treatment was 144 minutes. A total of 5,142 in-hospital deaths occurred. Faster time to treatment, in 15-minute increments, was associated with reduced in-hospital mortality, reduced symptomatic intracranial hemorrhage, increased achievement of independent ambulation at discharge, and increased discharge to home. Patient factors most strongly associated with shorter time to treatment included greater stroke severity, arrival by ambulance, and arrival during regular hours.

High serum iron levels may be associated with a decreased risk of developing Parkinson’s disease, according to a study published June 4 in PLOS Medicine. Researchers investigated three polymorphisms in the genes HFE and TMPRSS6. For each polymorphism, they performed a meta-analysis of studies investigating the genetic effect on iron levels and a meta-analysis of studies investigating the genetic effect on the risk of Parkinson’s disease. Using three Mendelian randomization analyses, the investigators estimated the effect of iron on Parkinson’s disease for the three polymorphisms. Every 10 µg/dl increase in blood iron corresponded to a 3% reduction in the risk of Parkinson’s disease. Thus, increased blood iron levels may have a protective effect against Parkinson’s disease, but the underlying mechanism remains unclear, said the researchers.

Diabetes and dementia may have a bidirectional association, according to research published online ahead of print June 10 in JAMA Internal Medicine. Investigators examined 783 older adults with diabetes who were participating in a prospective population-based study. Subjects’ mean age was 74, and their baseline Modified Mini-Mental State Examination scores were 80 or higher. Approximately 47% of subjects were African American, and 47% were female. During the 12-year follow-up, 61 participants had a reported hypoglycemic event, and 148 developed dementia. Subjects who had a hypoglycemic event had a twofold increased risk for developing dementia, compared with those who did not have a hypoglycemic event. Subjects with diabetes who developed dementia had a greater risk for having a subsequent hypoglycemic event, compared with participants who did not develop dementia.

Cardiovascular biomarkers may help identify patients with subclinical cerebral injury, according to research published online ahead of print May 9 in Stroke. A total of 1,920 subjects received a brain MRI and had their levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T (hs-cTnT) measured. Of the total group, 1,112 had a follow-up MRI between nine and 13 years later. Individuals with the highest NT-proBNP levels had significantly more silent brain infarcts and white matter lesions on the baseline MRI and more incident silent brain infarcts and white matter lesion progression on the follow-up MRI. Individuals with the highest hs-cTnT levels had more silent brain infarcts and white matter lesions on the initial MRI and more white matter lesion progression on the follow-up MRI.

Stroke symptoms or transient ischemic attack (TIA) may be strongly associated with incident cognitive impairment, researchers concluded in a study published online ahead of print June 19 in Neurology. The investigators studied 23,830 participants without cognitive impairment or history of stroke enrolled in the Reasons for Geographic and Racial Differences in Stroke Study. Subjects reported stroke symptoms and TIA every six months and were screened annually for cognitive impairment. Among Caucasians, the odds ratio for incident cognitive impairment was 2.08 for subjects reporting at least one stroke symptom or TIA, compared with those reporting no stroke symptom or TIA. Among African Americans, the odds ratio was 1.66 using the same modeling. The magnitude of impact was largest among participants with fewer traditional stroke risk factors.

—Erik Greb
Senior Associate Editor

Living in the stroke belt as an adolescent is significantly associated with a high risk of stroke, according to research published online ahead of print April 24 in Neurology. Researchers examined data for 24,544 stroke-free participants in the Reasons for Geographic and Racial Differences in Stroke study. Stroke belt exposure was calculated by combinations of stroke belt birthplace, current residence, and proportion of years in the stroke belt during discrete age categories. Risk of stroke was significantly associated with proportion of life in the stroke belt and with all other exposure periods except birth, ages 31 to 45, and current residence. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in the stroke belt during adolescence.

Increased levels of trimethylamine-N-oxide (TMAO), a proatherosclerotic metabolite, are associated with an increased risk of stroke, myocardial infarction, or death, according to research published in the April 25 New England Journal of Medicine. Investigators measured TMAO, choline, and betaine levels in patients who had eaten two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after suppressing intestinal microbiota with antibiotics. They also examined the relationship between fasting plasma levels of TMAO and major adverse cardiovascular events during three years of follow-up. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event. An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors, as well as in lower-risk subgroups.

A single-nucleotide polymorphism (SNP) in the ABCA7 gene was significantly linked with an increased risk of Alzheimer’s disease among African Americans, according to research published in the April 10 JAMA. African Americans with this mutation have nearly double the risk of Alzheimer’s disease, but the SNP is not associated with the disease among Europeans. The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358. Investigators examined data for 5,896 African Americans (1,968 with Alzheimer’s disease and 3,928 controls) who were 60 or older. Data were collected between 1989 and 2011 at multiple sites. The team assessed the association of Alzheimer’s disease with genotyped and imputed SNPs in case–control and in family-based data sets.

The FDA has approved the Precision Spectra Spinal Cord Stimulator (SCS) System, which is designed to provide improved pain relief to patients with chronic pain. The system, manufactured by Boston Scientific (Natick, Massachusetts), includes Illumina 3D software intended to improve physicians’ control of the stimulation field. It is based on a proprietary computer model that takes into account 3-D anatomical structures, including the conductivity of the spinal cord and surrounding tissue. The physician can select a desired location on the spinal cord and prompt the programming software to create a customized stimulation field to mask the patient’s pain. Previous SCS systems included 16 contacts, but the Precision Spectra system includes 32 contacts and is designed to offer more coverage of the spinal cord.

Framingham risk scores may be better than a dementia risk score for assessing individuals’ risk of cognitive decline and targeting modifiable risk factors, according to research published in the April 2 Neurology. Researchers examined data for participants in the Whitehall II longitudinal cohort study. Subjects’ mean age at baseline was 55.6. The investigators compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging, and Dementia risk score. Patients underwent cognitive tests of reasoning, memory, verbal fluency, vocabulary, and global cognition three times over 10 years. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline. The differences were statistically significant for semantic fluency and global cognitive scores.

Children born to women who used valproate during pregnancy may have a significantly increased risk of autism spectrum disorder and childhood autism, according to research published in the April 24 JAMA. Investigators used national registers to identify Danish children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders. The researchers analyzed the risks associated with all autism spectrum disorders, as well as childhood autism, and adjusted for potential confounders. The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. The 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder and an absolute risk of 2.50% for childhood autism. Results changed slightly after considering only the children born to women with epilepsy.

The antisense oligonucleotide ISIS 333611 is a safe treatment for amyotrophic lateral sclerosis (ALS), according to a trial published online ahead of print March 29 in Lancet Neurology. Investigators studied 32 patients with SOD1-positive ALS in a randomized, placebo-controlled, phase I trial. The researchers delivered the drug by intrathecal infusion using an external pump over 11.5 hours at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, and 3.00 mg). Approximately 88% of patients in the placebo group had adverse events, compared with 83% in the active group. The most common events were post-lumbar puncture syndrome, back pain, and nausea. The investigators found no dose-limiting toxic effects or safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611.

Thalamic atrophy in patients with clinically isolated syndrome (CIS) is associated with the development of clinically definite multiple sclerosis (MS), according to a study published online ahead of print April 23 in Radiology. Using MRI, researchers assessed 216 patients with CIS at baseline, six months, one year, and two years. MRI measures of progression included new and enlarged T2 lesions and changes in whole-brain, tissue-specific global, and regional gray matter volumes. In mixed-effect model analysis, the lateral ventricle volume, accumulation of new total T2 and new enlarging T2 lesions increase, and thalamic and whole-brain volume decrease were associated with development of clinically definite MS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes were associated with the development of clinically definite MS.

Functional MRI (fMRI) can identify pain caused by heat in healthy persons, according to research published in the April 11 New England Journal of Medicine. In four studies of 114 participants, investigators developed an fMRI-based measure that predicts pain intensity, tested its sensitivity and specificity to pain versus warmth, assessed its specificity relative to social pain, and assessed the responsiveness of the measure to the analgesic remifentanil. The neurologic signature distinguished painful heat from nonpainful warmth, pain anticipation, and pain recall with sensitivity and specificity of 94% or more. The signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity. It also distinguished between physical pain and social pain with 85% sensitivity and 73% specificity. The strength of the signature response was substantially reduced after remifentanil administration.

Family history of late-onset Alzheimer’s disease is associated with an increased prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in patients with mild cognitive impairment (MCI), according to a study published on April 17 in PLOS One. Investigators studied 257 participants (ages 55 to 89) in the Alzheimer’s Disease Neuroimaging Initiative. Subjects were categorized as cognitively normal, having MCI, or having Alzheimer’s disease. Among patients with MCI, CSF Ab42 was lower, t-tau was higher, and t-tau–Ab42 ratio was higher in patients with a family history of Alzheimer’s disease than in patients without. A significant residual effect of family history on pathologic markers in MCI remained after adjusting for APOE e4. The effect of family history was not significant in patients with Alzheimer’s disease.

Most potential migraine triggers are so variable that it may not be possible to identify them without formal experimentation, according to a study published in the April issue of Headache. Investigators examined the similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine patients with headache and regular menstrual cycles. A threshold of 90% similarity using Gower’s index identified similar days for comparison. The day-to-day variability in the three headache triggers was substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine) occurred infrequently. Fluctuations in weather patterns resulted in a median of 2.3 similar days each year.

Elevated low-density lipoprotein (LDL) cholesterol and altered cholesterol homeostasis may promote neurodegeneration, atherosclerosis, and Alzheimer’s disease by disrupting chromosome segregation, according to research published on April 12 in PLOS One. In a study of mice, investigators observed that high dietary cholesterol induced aneuploidy. In a separate study, the accumulation of intracellular cholesterol was associated with the accumulation of aneuploid fibroblasts, neurons, and glia in patients with Niemann-Pick C1. The researchers also observed that oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induced chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors. LDL-induced aneuploidy required the LDL receptor, but not Ab. Cholesterol treatment disrupted the structure of the mitotic spindle, providing a cell biologic mechanism for its aneugenic activity, and ethanol or calcium chelation attenuated lipoprotein-induced chromosome mis-segregation.

The incidence of dementia in central Stockholm may have decreased from the late 1980s to the early 2000s, according to research published online ahead of print April 17 in Neurology. Investigators analyzed data from two cross-sectional surveys of people ages 75 or older. One study was conducted from 1987 to 1989 and included 1,700 participants; the other was conducted from 2001 to 2004 and included 1,575 subjects. The team inferred the incidence of dementia according to its relationship with prevalence and survival. The adjusted odds ratio of dementia in the later study versus the earlier study was 1.17. The multiadjusted hazard ratio of death in the later study versus the earlier study was 0.71 in subjects with dementia, 0.68 in those without dementia, and 0.66 in all participants.

—Erik Greb
Senior Associate Editor

Living in the stroke belt as an adolescent is significantly associated with a high risk of stroke, according to research published online ahead of print April 24 in Neurology. Researchers examined data for 24,544 stroke-free participants in the Reasons for Geographic and Racial Differences in Stroke study. Stroke belt exposure was calculated by combinations of stroke belt birthplace, current residence, and proportion of years in the stroke belt during discrete age categories. Risk of stroke was significantly associated with proportion of life in the stroke belt and with all other exposure periods except birth, ages 31 to 45, and current residence. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in the stroke belt during adolescence.

Increased levels of trimethylamine-N-oxide (TMAO), a proatherosclerotic metabolite, are associated with an increased risk of stroke, myocardial infarction, or death, according to research published in the April 25 New England Journal of Medicine. Investigators measured TMAO, choline, and betaine levels in patients who had eaten two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after suppressing intestinal microbiota with antibiotics. They also examined the relationship between fasting plasma levels of TMAO and major adverse cardiovascular events during three years of follow-up. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event. An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors, as well as in lower-risk subgroups.

A single-nucleotide polymorphism (SNP) in the ABCA7 gene was significantly linked with an increased risk of Alzheimer’s disease among African Americans, according to research published in the April 10 JAMA. African Americans with this mutation have nearly double the risk of Alzheimer’s disease, but the SNP is not associated with the disease among Europeans. The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358. Investigators examined data for 5,896 African Americans (1,968 with Alzheimer’s disease and 3,928 controls) who were 60 or older. Data were collected between 1989 and 2011 at multiple sites. The team assessed the association of Alzheimer’s disease with genotyped and imputed SNPs in case–control and in family-based data sets.

The FDA has approved the Precision Spectra Spinal Cord Stimulator (SCS) System, which is designed to provide improved pain relief to patients with chronic pain. The system, manufactured by Boston Scientific (Natick, Massachusetts), includes Illumina 3D software intended to improve physicians’ control of the stimulation field. It is based on a proprietary computer model that takes into account 3-D anatomical structures, including the conductivity of the spinal cord and surrounding tissue. The physician can select a desired location on the spinal cord and prompt the programming software to create a customized stimulation field to mask the patient’s pain. Previous SCS systems included 16 contacts, but the Precision Spectra system includes 32 contacts and is designed to offer more coverage of the spinal cord.

Framingham risk scores may be better than a dementia risk score for assessing individuals’ risk of cognitive decline and targeting modifiable risk factors, according to research published in the April 2 Neurology. Researchers examined data for participants in the Whitehall II longitudinal cohort study. Subjects’ mean age at baseline was 55.6. The investigators compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging, and Dementia risk score. Patients underwent cognitive tests of reasoning, memory, verbal fluency, vocabulary, and global cognition three times over 10 years. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline. The differences were statistically significant for semantic fluency and global cognitive scores.

Children born to women who used valproate during pregnancy may have a significantly increased risk of autism spectrum disorder and childhood autism, according to research published in the April 24 JAMA. Investigators used national registers to identify Danish children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders. The researchers analyzed the risks associated with all autism spectrum disorders, as well as childhood autism, and adjusted for potential confounders. The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. The 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder and an absolute risk of 2.50% for childhood autism. Results changed slightly after considering only the children born to women with epilepsy.

The antisense oligonucleotide ISIS 333611 is a safe treatment for amyotrophic lateral sclerosis (ALS), according to a trial published online ahead of print March 29 in Lancet Neurology. Investigators studied 32 patients with SOD1-positive ALS in a randomized, placebo-controlled, phase I trial. The researchers delivered the drug by intrathecal infusion using an external pump over 11.5 hours at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, and 3.00 mg). Approximately 88% of patients in the placebo group had adverse events, compared with 83% in the active group. The most common events were post-lumbar puncture syndrome, back pain, and nausea. The investigators found no dose-limiting toxic effects or safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611.

Thalamic atrophy in patients with clinically isolated syndrome (CIS) is associated with the development of clinically definite multiple sclerosis (MS), according to a study published online ahead of print April 23 in Radiology. Using MRI, researchers assessed 216 patients with CIS at baseline, six months, one year, and two years. MRI measures of progression included new and enlarged T2 lesions and changes in whole-brain, tissue-specific global, and regional gray matter volumes. In mixed-effect model analysis, the lateral ventricle volume, accumulation of new total T2 and new enlarging T2 lesions increase, and thalamic and whole-brain volume decrease were associated with development of clinically definite MS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes were associated with the development of clinically definite MS.

Functional MRI (fMRI) can identify pain caused by heat in healthy persons, according to research published in the April 11 New England Journal of Medicine. In four studies of 114 participants, investigators developed an fMRI-based measure that predicts pain intensity, tested its sensitivity and specificity to pain versus warmth, assessed its specificity relative to social pain, and assessed the responsiveness of the measure to the analgesic remifentanil. The neurologic signature distinguished painful heat from nonpainful warmth, pain anticipation, and pain recall with sensitivity and specificity of 94% or more. The signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity. It also distinguished between physical pain and social pain with 85% sensitivity and 73% specificity. The strength of the signature response was substantially reduced after remifentanil administration.

Family history of late-onset Alzheimer’s disease is associated with an increased prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in patients with mild cognitive impairment (MCI), according to a study published on April 17 in PLOS One. Investigators studied 257 participants (ages 55 to 89) in the Alzheimer’s Disease Neuroimaging Initiative. Subjects were categorized as cognitively normal, having MCI, or having Alzheimer’s disease. Among patients with MCI, CSF Ab42 was lower, t-tau was higher, and t-tau–Ab42 ratio was higher in patients with a family history of Alzheimer’s disease than in patients without. A significant residual effect of family history on pathologic markers in MCI remained after adjusting for APOE e4. The effect of family history was not significant in patients with Alzheimer’s disease.

Most potential migraine triggers are so variable that it may not be possible to identify them without formal experimentation, according to a study published in the April issue of Headache. Investigators examined the similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine patients with headache and regular menstrual cycles. A threshold of 90% similarity using Gower’s index identified similar days for comparison. The day-to-day variability in the three headache triggers was substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine) occurred infrequently. Fluctuations in weather patterns resulted in a median of 2.3 similar days each year.

Elevated low-density lipoprotein (LDL) cholesterol and altered cholesterol homeostasis may promote neurodegeneration, atherosclerosis, and Alzheimer’s disease by disrupting chromosome segregation, according to research published on April 12 in PLOS One. In a study of mice, investigators observed that high dietary cholesterol induced aneuploidy. In a separate study, the accumulation of intracellular cholesterol was associated with the accumulation of aneuploid fibroblasts, neurons, and glia in patients with Niemann-Pick C1. The researchers also observed that oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induced chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors. LDL-induced aneuploidy required the LDL receptor, but not Ab. Cholesterol treatment disrupted the structure of the mitotic spindle, providing a cell biologic mechanism for its aneugenic activity, and ethanol or calcium chelation attenuated lipoprotein-induced chromosome mis-segregation.

The incidence of dementia in central Stockholm may have decreased from the late 1980s to the early 2000s, according to research published online ahead of print April 17 in Neurology. Investigators analyzed data from two cross-sectional surveys of people ages 75 or older. One study was conducted from 1987 to 1989 and included 1,700 participants; the other was conducted from 2001 to 2004 and included 1,575 subjects. The team inferred the incidence of dementia according to its relationship with prevalence and survival. The adjusted odds ratio of dementia in the later study versus the earlier study was 1.17. The multiadjusted hazard ratio of death in the later study versus the earlier study was 0.71 in subjects with dementia, 0.68 in those without dementia, and 0.66 in all participants.

—Erik Greb
Senior Associate Editor

Living in the stroke belt as an adolescent is significantly associated with a high risk of stroke, according to research published online ahead of print April 24 in Neurology. Researchers examined data for 24,544 stroke-free participants in the Reasons for Geographic and Racial Differences in Stroke study. Stroke belt exposure was calculated by combinations of stroke belt birthplace, current residence, and proportion of years in the stroke belt during discrete age categories. Risk of stroke was significantly associated with proportion of life in the stroke belt and with all other exposure periods except birth, ages 31 to 45, and current residence. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in the stroke belt during adolescence.

Increased levels of trimethylamine-N-oxide (TMAO), a proatherosclerotic metabolite, are associated with an increased risk of stroke, myocardial infarction, or death, according to research published in the April 25 New England Journal of Medicine. Investigators measured TMAO, choline, and betaine levels in patients who had eaten two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine before and after suppressing intestinal microbiota with antibiotics. They also examined the relationship between fasting plasma levels of TMAO and major adverse cardiovascular events during three years of follow-up. Increased plasma levels of TMAO were associated with an increased risk of a major adverse cardiovascular event. An elevated TMAO level predicted an increased risk of major adverse cardiovascular events after adjustment for traditional risk factors, as well as in lower-risk subgroups.

A single-nucleotide polymorphism (SNP) in the ABCA7 gene was significantly linked with an increased risk of Alzheimer’s disease among African Americans, according to research published in the April 10 JAMA. African Americans with this mutation have nearly double the risk of Alzheimer’s disease, but the SNP is not associated with the disease among Europeans. The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4–determining SNP rs429358. Investigators examined data for 5,896 African Americans (1,968 with Alzheimer’s disease and 3,928 controls) who were 60 or older. Data were collected between 1989 and 2011 at multiple sites. The team assessed the association of Alzheimer’s disease with genotyped and imputed SNPs in case–control and in family-based data sets.

The FDA has approved the Precision Spectra Spinal Cord Stimulator (SCS) System, which is designed to provide improved pain relief to patients with chronic pain. The system, manufactured by Boston Scientific (Natick, Massachusetts), includes Illumina 3D software intended to improve physicians’ control of the stimulation field. It is based on a proprietary computer model that takes into account 3-D anatomical structures, including the conductivity of the spinal cord and surrounding tissue. The physician can select a desired location on the spinal cord and prompt the programming software to create a customized stimulation field to mask the patient’s pain. Previous SCS systems included 16 contacts, but the Precision Spectra system includes 32 contacts and is designed to offer more coverage of the spinal cord.

Framingham risk scores may be better than a dementia risk score for assessing individuals’ risk of cognitive decline and targeting modifiable risk factors, according to research published in the April 2 Neurology. Researchers examined data for participants in the Whitehall II longitudinal cohort study. Subjects’ mean age at baseline was 55.6. The investigators compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging, and Dementia risk score. Patients underwent cognitive tests of reasoning, memory, verbal fluency, vocabulary, and global cognition three times over 10 years. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline. The differences were statistically significant for semantic fluency and global cognitive scores.

Children born to women who used valproate during pregnancy may have a significantly increased risk of autism spectrum disorder and childhood autism, according to research published in the April 24 JAMA. Investigators used national registers to identify Danish children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders. The researchers analyzed the risks associated with all autism spectrum disorders, as well as childhood autism, and adjusted for potential confounders. The estimated absolute risk after 14 years of follow-up was 1.53% for autism spectrum disorder and 0.48% for childhood autism. The 508 children exposed to valproate had an absolute risk of 4.42% for autism spectrum disorder and an absolute risk of 2.50% for childhood autism. Results changed slightly after considering only the children born to women with epilepsy.

The antisense oligonucleotide ISIS 333611 is a safe treatment for amyotrophic lateral sclerosis (ALS), according to a trial published online ahead of print March 29 in Lancet Neurology. Investigators studied 32 patients with SOD1-positive ALS in a randomized, placebo-controlled, phase I trial. The researchers delivered the drug by intrathecal infusion using an external pump over 11.5 hours at increasing doses (0.15 mg, 0.50 mg, 1.50 mg, and 3.00 mg). Approximately 88% of patients in the placebo group had adverse events, compared with 83% in the active group. The most common events were post-lumbar puncture syndrome, back pain, and nausea. The investigators found no dose-limiting toxic effects or safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611.

Thalamic atrophy in patients with clinically isolated syndrome (CIS) is associated with the development of clinically definite multiple sclerosis (MS), according to a study published online ahead of print April 23 in Radiology. Using MRI, researchers assessed 216 patients with CIS at baseline, six months, one year, and two years. MRI measures of progression included new and enlarged T2 lesions and changes in whole-brain, tissue-specific global, and regional gray matter volumes. In mixed-effect model analysis, the lateral ventricle volume, accumulation of new total T2 and new enlarging T2 lesions increase, and thalamic and whole-brain volume decrease were associated with development of clinically definite MS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes were associated with the development of clinically definite MS.

Functional MRI (fMRI) can identify pain caused by heat in healthy persons, according to research published in the April 11 New England Journal of Medicine. In four studies of 114 participants, investigators developed an fMRI-based measure that predicts pain intensity, tested its sensitivity and specificity to pain versus warmth, assessed its specificity relative to social pain, and assessed the responsiveness of the measure to the analgesic remifentanil. The neurologic signature distinguished painful heat from nonpainful warmth, pain anticipation, and pain recall with sensitivity and specificity of 94% or more. The signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity. It also distinguished between physical pain and social pain with 85% sensitivity and 73% specificity. The strength of the signature response was substantially reduced after remifentanil administration.

Family history of late-onset Alzheimer’s disease is associated with an increased prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in patients with mild cognitive impairment (MCI), according to a study published on April 17 in PLOS One. Investigators studied 257 participants (ages 55 to 89) in the Alzheimer’s Disease Neuroimaging Initiative. Subjects were categorized as cognitively normal, having MCI, or having Alzheimer’s disease. Among patients with MCI, CSF Ab42 was lower, t-tau was higher, and t-tau–Ab42 ratio was higher in patients with a family history of Alzheimer’s disease than in patients without. A significant residual effect of family history on pathologic markers in MCI remained after adjusting for APOE e4. The effect of family history was not significant in patients with Alzheimer’s disease.

Most potential migraine triggers are so variable that it may not be possible to identify them without formal experimentation, according to a study published in the April issue of Headache. Investigators examined the similarity of day-to-day weather conditions over four years, as well as the similarity of ovarian hormones and perceived stress over a median of 89 days in nine patients with headache and regular menstrual cycles. A threshold of 90% similarity using Gower’s index identified similar days for comparison. The day-to-day variability in the three headache triggers was substantial enough that finding two naturally similar days for which to contrast the effect of a fourth trigger (eg, drinking wine) occurred infrequently. Fluctuations in weather patterns resulted in a median of 2.3 similar days each year.

Elevated low-density lipoprotein (LDL) cholesterol and altered cholesterol homeostasis may promote neurodegeneration, atherosclerosis, and Alzheimer’s disease by disrupting chromosome segregation, according to research published on April 12 in PLOS One. In a study of mice, investigators observed that high dietary cholesterol induced aneuploidy. In a separate study, the accumulation of intracellular cholesterol was associated with the accumulation of aneuploid fibroblasts, neurons, and glia in patients with Niemann-Pick C1. The researchers also observed that oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL), induced chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors. LDL-induced aneuploidy required the LDL receptor, but not Ab. Cholesterol treatment disrupted the structure of the mitotic spindle, providing a cell biologic mechanism for its aneugenic activity, and ethanol or calcium chelation attenuated lipoprotein-induced chromosome mis-segregation.

The incidence of dementia in central Stockholm may have decreased from the late 1980s to the early 2000s, according to research published online ahead of print April 17 in Neurology. Investigators analyzed data from two cross-sectional surveys of people ages 75 or older. One study was conducted from 1987 to 1989 and included 1,700 participants; the other was conducted from 2001 to 2004 and included 1,575 subjects. The team inferred the incidence of dementia according to its relationship with prevalence and survival. The adjusted odds ratio of dementia in the later study versus the earlier study was 1.17. The multiadjusted hazard ratio of death in the later study versus the earlier study was 0.71 in subjects with dementia, 0.68 in those without dementia, and 0.66 in all participants.

—Erik Greb
Senior Associate Editor

Greater dietary fiber intake is significantly associated with a lower risk of first stroke, according to a study published online ahead of print March 28 in Stroke. Investigators searched several electronic databases for healthy participant studies published between January 1990 and May 2012 that reported fiber intake and incidence of first hemorrhagic or ischemic stroke. The group identified eight cohort studies from the United States, Europe, Australia, and Japan that met their inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke. The researchers found evidence of heterogeneity between the studies. Soluble fiber intake of 4 g/day was not associated with stroke risk reduction, and the investigators found evidence of low heterogeneity on this point between the studies.

In women who have episodic migraine, the ratio of high molecular weight to low molecular weight ictal adiponectin (ADP) may be associated with migraine severity and predict acute treatment response, according to a study published in the March Headache. Investigators collected peripheral blood specimens from women with episodic migraine before and after acute abortive treatment with sumatriptan and naproxen sodium or placebo. In all participants, increases in the ratio of high molecular weight to low molecular weight ADP were associated with increases in pain severity. For every 0.25-μg/mL increase in low molecular weight ADP, pain severity decreased by 0.20. In treatment responders, total ADP levels were reduced at 30, 60, and 120 minutes after treatment, compared with onset.

The FDA has approved Tecfidera (dimethyl fumarate) capsules to treat adults with relapsing forms of multiple sclerosis (MS). In two clinical trials, patients with MS who took dimethyl fumarate had fewer relapses compared with people who received placebo. In one of the trials, patients who took dimethyl fumarate experienced a worsening of disability less often than patients who took a placebo. Dimethyl fumarate may decrease a person's white blood cell count, but the drug was not associated with a significant increase in infections in clinical trials. Before starting treatment, and annually thereafter, the FDA recommends that a patient's white blood cell count be assessed by a health care provider. Flushing and stomach problems were the most common adverse reactions reported. Tecfidera is manufactured by Biogen Idec (Weston, Massachusetts).

Mild cognitive impairment (MCI) at the time of Parkinson's disease diagnosis may predict a highly increased risk for early dementia, according to a study published online ahead of print March 25 in JAMA Neurology. Researchers examined data for a population-based cohort of 182 patients with incident Parkinson's disease who were monitored for three years. Significantly more patients with MCI than without MCI at baseline (27.0% versus 0.7%) progressed to dementia during follow-up. Mild cognitive impairment at the one-year visit was associated with a similar progression rate to dementia (ie, 27.8%) and reversion rate to normal cognition (ie, 19.4%). Among the 22 patients with persistent MCI at baseline and the one-year visit, 10 developed dementia and two reverted to normal cognition by the end of the study.

Higher consumption of green tea and coffee may reduce the risk of cardiovascular disease and stroke, according to a study published online ahead of print March 14 in Stroke. Investigators studied 82,369 Japanese persons between ages 45 and 74 without cardiovascular disease or cancer. Green tea and coffee consumption was assessed by a self-administered questionnaire at baseline. Compared with seldom drinking green tea, the multivariable-adjusted hazard ratios of all strokes were 0.86 and 0.80 in individuals who drank two to three and four or more cups of green tea per day, respectively. Compared with seldom drinking coffee, the multivariable-adjusted hazard ratios of all strokes were 0.89, 0.80, and 0.81 for individuals who drank coffee three to six times per week, once daily, and twice or more daily, respectively.

Updated Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries recommend against the use of steroids, including methylprednisolone, in acute spinal cord injury in the first 24 to 48 hours after injury. The use of steroids previously was recommended for this indication with consideration of the risk–reward profile, as evaluated by the physician. In the first new treatment guidelines in a decade, which were issued by the Joint Section on Disorders of the Spine and Peripheral Nerves of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, the standard has been revised based on the lack of medical evidence supporting the benefits of these drugs in the clinical setting. The report cites strong evidence that "high-dose steroids are associated with harmful side effects, including death."

Abnormalities in cortical surface area may indicate an individual's predisposition to developing migraine, and abnormalities in cortical thickness may result from migraine-related processes, according to research published online ahead of print March 26 in Radiology. Investigators took T2-weighted and three-dimensional T1-weighted MRIs of the brain for 63 migraineurs and 18 controls. They estimated cortical thickness and cortical surface area. Compared with control subjects, patients with migraine had reduced cortical thickness and surface area in pain-processing regions. These reductions were greater in regions involved in executive functions and visual-motion processing. Cortical thickness and cortical surface area abnormalities had minimal areas of overlap. Cortical thickness and surface area abnormalities were related to aura and white matter hyperintensities, but not to disease duration and attack frequency.

Primary stroke centers are more likely to administer t-PA than noncertified hospitals, according to research published online ahead of print March 26 in the Journal of the American Heart Association. Investigators analyzed data obtained from the Nationwide Inpatient Sample between 2004 and 2009 for patients age 18 or older with a primary diagnosis of acute ischemic stroke. IV t-PA was administered to 3.1% of patients overall. The drug was given to 2.2% of patients at noncertified hospitals and to 6.7% of patients at primary stroke centers. Between 2004 and 2009, t-PA administration increased from 1.4% to 3.3% of patients at noncertified hospitals and from 6.0% to 7.6% of patients at primary stroke centers. In a multivariable model, evaluation at a primary stroke center was significantly associated with t-PA use.

Control and prevention of risk factors such as hypertension earlier in life may limit or delay neuropathologic brain changes such as Alzheimer's disease with aging, researchers reported in a study published online ahead of print March 18 in JAMA Neurology. The investigators studied 118 cognitively normal adults ages 47 to 89. Participants were classified as having hypertension if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic on seven occasions. Participants underwent Ab PET imaging with radiotracer fluorine 18–labeled florbetapir, were genotyped for apolipoprotein E, and were classified as ε4+ or ε4−. Subjects with hypertension and at least one ε4 allele had significantly more amyloid burden than those with one or no risk factors.

Physicians can discontinue chronic antipsychotic medication for many elderly adults with Alzheimer's dementia and neuropsychiatric symptoms without causing detrimental effects on their behavior, according to a review published online March 28 in the Cochrane Database of Systematic Reviews. Investigators examined data from nine randomized controlled trials that compared antipsychotic withdrawal strategies with continuation of antipsychotics in patients with dementia. Although neurologists have concerns about the potential adverse events of antipsychotics, it is not clear whether withdrawal is beneficial for patients' cognition or psychomotor status. In two studies of patients whose agitation or psychosis had previously responded well to antipsychotic treatment, discontinuation was associated with an increased risk of relapse or shorter time to relapse. Two studies suggested that patients with severe neuropsychiatric symptoms at baseline could benefit from continuing their antipsychotic medication.

Greater exposure to pathogens associated with stroke risk and atherosclerosis may correlate with poorer cognitive performance, according to research published in the March 26 Neurology. Investigators tested for various pathogens (eg, Chlamydia pneumonia and Helicobacter pylori) in 1,625 participants in the Northern Manhattan Study. The researchers assessed patients' cognitive performance at baseline and at annual follow-up visits. Higher infectious burden index was associated with worse cognition. Each standard deviation in infectious burden correlated with a 0.77-point decline in Mini-Mental State Examination (MMSE) score. Adjustment for risk factors weakened the effect, however. Infectious burden was associated with an MMSE score of 24 or lower. Infectious burden was not associated with cognitive decline over time. Past infections may contribute to cognitive impairment, said the researchers.

Smoking cessation was associated with a decreased risk of cardiovascular disease events, and subsequent weight gain did not modify this association, researchers reported in the March 13 JAMA. Investigators analyzed data collected from 1984 through 2011 in the Framingham Offspring Study. Participants' self-reported smoking status was recorded during four-year examinations. Median four-year weight gain was 2.7 kg for recent smoking quitters without diabetes, 3.6 kg for recent quitters with diabetes, and 0.9 kg for long-term quitters. After adjustment for cardiovascular risk factors, compared with smokers, recent smoking quitters had a hazard ratio for cardiovascular disease of 0.47, and long-term quitters had a hazard ratio of 0.46. The results changed minimally after further adjustment for weight change. Similar point estimates for participants with diabetes did not reach statistical significance.

Women who enter menopause prematurely after bilateral ovariectomy may have a significantly increased risk for cognitive decline and dementia, according to a study published online ahead of print March 9 in Brain. The investigators studied rats 10 weeks after they had undergone bilateral ovariectomy and found that long-term estrogen deprivation dramatically increased the hippocampal CA3 region's sensitivity to ischemic stress, which correlated with a worse cognitive outcome. Long-term ovariectomized rats had robust hyperinduction of Alzheimer's disease-related proteins in the CA3 region. Following ischemic stress, amyloid-precursor protein processing switched from nonamyloidogenic to amyloidogenic. Replacement of 17β-estradiol at the end of the estrogen-deprivation period could not prevent CA3 hypersensitivity and amyloidogenesis, but if 17β-estradiol was initiated at ovariectomy and maintained throughout the estrogen deprivation period, it completely prevented these events.

Greater dietary fiber intake is significantly associated with a lower risk of first stroke, according to a study published online ahead of print March 28 in Stroke. Investigators searched several electronic databases for healthy participant studies published between January 1990 and May 2012 that reported fiber intake and incidence of first hemorrhagic or ischemic stroke. The group identified eight cohort studies from the United States, Europe, Australia, and Japan that met their inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke. The researchers found evidence of heterogeneity between the studies. Soluble fiber intake of 4 g/day was not associated with stroke risk reduction, and the investigators found evidence of low heterogeneity on this point between the studies.

In women who have episodic migraine, the ratio of high molecular weight to low molecular weight ictal adiponectin (ADP) may be associated with migraine severity and predict acute treatment response, according to a study published in the March Headache. Investigators collected peripheral blood specimens from women with episodic migraine before and after acute abortive treatment with sumatriptan and naproxen sodium or placebo. In all participants, increases in the ratio of high molecular weight to low molecular weight ADP were associated with increases in pain severity. For every 0.25-μg/mL increase in low molecular weight ADP, pain severity decreased by 0.20. In treatment responders, total ADP levels were reduced at 30, 60, and 120 minutes after treatment, compared with onset.

The FDA has approved Tecfidera (dimethyl fumarate) capsules to treat adults with relapsing forms of multiple sclerosis (MS). In two clinical trials, patients with MS who took dimethyl fumarate had fewer relapses compared with people who received placebo. In one of the trials, patients who took dimethyl fumarate experienced a worsening of disability less often than patients who took a placebo. Dimethyl fumarate may decrease a person's white blood cell count, but the drug was not associated with a significant increase in infections in clinical trials. Before starting treatment, and annually thereafter, the FDA recommends that a patient's white blood cell count be assessed by a health care provider. Flushing and stomach problems were the most common adverse reactions reported. Tecfidera is manufactured by Biogen Idec (Weston, Massachusetts).

Mild cognitive impairment (MCI) at the time of Parkinson's disease diagnosis may predict a highly increased risk for early dementia, according to a study published online ahead of print March 25 in JAMA Neurology. Researchers examined data for a population-based cohort of 182 patients with incident Parkinson's disease who were monitored for three years. Significantly more patients with MCI than without MCI at baseline (27.0% versus 0.7%) progressed to dementia during follow-up. Mild cognitive impairment at the one-year visit was associated with a similar progression rate to dementia (ie, 27.8%) and reversion rate to normal cognition (ie, 19.4%). Among the 22 patients with persistent MCI at baseline and the one-year visit, 10 developed dementia and two reverted to normal cognition by the end of the study.

Higher consumption of green tea and coffee may reduce the risk of cardiovascular disease and stroke, according to a study published online ahead of print March 14 in Stroke. Investigators studied 82,369 Japanese persons between ages 45 and 74 without cardiovascular disease or cancer. Green tea and coffee consumption was assessed by a self-administered questionnaire at baseline. Compared with seldom drinking green tea, the multivariable-adjusted hazard ratios of all strokes were 0.86 and 0.80 in individuals who drank two to three and four or more cups of green tea per day, respectively. Compared with seldom drinking coffee, the multivariable-adjusted hazard ratios of all strokes were 0.89, 0.80, and 0.81 for individuals who drank coffee three to six times per week, once daily, and twice or more daily, respectively.

Updated Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries recommend against the use of steroids, including methylprednisolone, in acute spinal cord injury in the first 24 to 48 hours after injury. The use of steroids previously was recommended for this indication with consideration of the risk–reward profile, as evaluated by the physician. In the first new treatment guidelines in a decade, which were issued by the Joint Section on Disorders of the Spine and Peripheral Nerves of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, the standard has been revised based on the lack of medical evidence supporting the benefits of these drugs in the clinical setting. The report cites strong evidence that "high-dose steroids are associated with harmful side effects, including death."

Abnormalities in cortical surface area may indicate an individual's predisposition to developing migraine, and abnormalities in cortical thickness may result from migraine-related processes, according to research published online ahead of print March 26 in Radiology. Investigators took T2-weighted and three-dimensional T1-weighted MRIs of the brain for 63 migraineurs and 18 controls. They estimated cortical thickness and cortical surface area. Compared with control subjects, patients with migraine had reduced cortical thickness and surface area in pain-processing regions. These reductions were greater in regions involved in executive functions and visual-motion processing. Cortical thickness and cortical surface area abnormalities had minimal areas of overlap. Cortical thickness and surface area abnormalities were related to aura and white matter hyperintensities, but not to disease duration and attack frequency.

Primary stroke centers are more likely to administer t-PA than noncertified hospitals, according to research published online ahead of print March 26 in the Journal of the American Heart Association. Investigators analyzed data obtained from the Nationwide Inpatient Sample between 2004 and 2009 for patients age 18 or older with a primary diagnosis of acute ischemic stroke. IV t-PA was administered to 3.1% of patients overall. The drug was given to 2.2% of patients at noncertified hospitals and to 6.7% of patients at primary stroke centers. Between 2004 and 2009, t-PA administration increased from 1.4% to 3.3% of patients at noncertified hospitals and from 6.0% to 7.6% of patients at primary stroke centers. In a multivariable model, evaluation at a primary stroke center was significantly associated with t-PA use.

Control and prevention of risk factors such as hypertension earlier in life may limit or delay neuropathologic brain changes such as Alzheimer's disease with aging, researchers reported in a study published online ahead of print March 18 in JAMA Neurology. The investigators studied 118 cognitively normal adults ages 47 to 89. Participants were classified as having hypertension if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic on seven occasions. Participants underwent Ab PET imaging with radiotracer fluorine 18–labeled florbetapir, were genotyped for apolipoprotein E, and were classified as ε4+ or ε4−. Subjects with hypertension and at least one ε4 allele had significantly more amyloid burden than those with one or no risk factors.

Physicians can discontinue chronic antipsychotic medication for many elderly adults with Alzheimer's dementia and neuropsychiatric symptoms without causing detrimental effects on their behavior, according to a review published online March 28 in the Cochrane Database of Systematic Reviews. Investigators examined data from nine randomized controlled trials that compared antipsychotic withdrawal strategies with continuation of antipsychotics in patients with dementia. Although neurologists have concerns about the potential adverse events of antipsychotics, it is not clear whether withdrawal is beneficial for patients' cognition or psychomotor status. In two studies of patients whose agitation or psychosis had previously responded well to antipsychotic treatment, discontinuation was associated with an increased risk of relapse or shorter time to relapse. Two studies suggested that patients with severe neuropsychiatric symptoms at baseline could benefit from continuing their antipsychotic medication.

Greater exposure to pathogens associated with stroke risk and atherosclerosis may correlate with poorer cognitive performance, according to research published in the March 26 Neurology. Investigators tested for various pathogens (eg, Chlamydia pneumonia and Helicobacter pylori) in 1,625 participants in the Northern Manhattan Study. The researchers assessed patients' cognitive performance at baseline and at annual follow-up visits. Higher infectious burden index was associated with worse cognition. Each standard deviation in infectious burden correlated with a 0.77-point decline in Mini-Mental State Examination (MMSE) score. Adjustment for risk factors weakened the effect, however. Infectious burden was associated with an MMSE score of 24 or lower. Infectious burden was not associated with cognitive decline over time. Past infections may contribute to cognitive impairment, said the researchers.

Smoking cessation was associated with a decreased risk of cardiovascular disease events, and subsequent weight gain did not modify this association, researchers reported in the March 13 JAMA. Investigators analyzed data collected from 1984 through 2011 in the Framingham Offspring Study. Participants' self-reported smoking status was recorded during four-year examinations. Median four-year weight gain was 2.7 kg for recent smoking quitters without diabetes, 3.6 kg for recent quitters with diabetes, and 0.9 kg for long-term quitters. After adjustment for cardiovascular risk factors, compared with smokers, recent smoking quitters had a hazard ratio for cardiovascular disease of 0.47, and long-term quitters had a hazard ratio of 0.46. The results changed minimally after further adjustment for weight change. Similar point estimates for participants with diabetes did not reach statistical significance.

Women who enter menopause prematurely after bilateral ovariectomy may have a significantly increased risk for cognitive decline and dementia, according to a study published online ahead of print March 9 in Brain. The investigators studied rats 10 weeks after they had undergone bilateral ovariectomy and found that long-term estrogen deprivation dramatically increased the hippocampal CA3 region's sensitivity to ischemic stress, which correlated with a worse cognitive outcome. Long-term ovariectomized rats had robust hyperinduction of Alzheimer's disease-related proteins in the CA3 region. Following ischemic stress, amyloid-precursor protein processing switched from nonamyloidogenic to amyloidogenic. Replacement of 17β-estradiol at the end of the estrogen-deprivation period could not prevent CA3 hypersensitivity and amyloidogenesis, but if 17β-estradiol was initiated at ovariectomy and maintained throughout the estrogen deprivation period, it completely prevented these events.

Greater dietary fiber intake is significantly associated with a lower risk of first stroke, according to a study published online ahead of print March 28 in Stroke. Investigators searched several electronic databases for healthy participant studies published between January 1990 and May 2012 that reported fiber intake and incidence of first hemorrhagic or ischemic stroke. The group identified eight cohort studies from the United States, Europe, Australia, and Japan that met their inclusion criteria. Total dietary fiber intake was inversely associated with risk of hemorrhagic plus ischemic stroke. The researchers found evidence of heterogeneity between the studies. Soluble fiber intake of 4 g/day was not associated with stroke risk reduction, and the investigators found evidence of low heterogeneity on this point between the studies.

In women who have episodic migraine, the ratio of high molecular weight to low molecular weight ictal adiponectin (ADP) may be associated with migraine severity and predict acute treatment response, according to a study published in the March Headache. Investigators collected peripheral blood specimens from women with episodic migraine before and after acute abortive treatment with sumatriptan and naproxen sodium or placebo. In all participants, increases in the ratio of high molecular weight to low molecular weight ADP were associated with increases in pain severity. For every 0.25-μg/mL increase in low molecular weight ADP, pain severity decreased by 0.20. In treatment responders, total ADP levels were reduced at 30, 60, and 120 minutes after treatment, compared with onset.

The FDA has approved Tecfidera (dimethyl fumarate) capsules to treat adults with relapsing forms of multiple sclerosis (MS). In two clinical trials, patients with MS who took dimethyl fumarate had fewer relapses compared with people who received placebo. In one of the trials, patients who took dimethyl fumarate experienced a worsening of disability less often than patients who took a placebo. Dimethyl fumarate may decrease a person's white blood cell count, but the drug was not associated with a significant increase in infections in clinical trials. Before starting treatment, and annually thereafter, the FDA recommends that a patient's white blood cell count be assessed by a health care provider. Flushing and stomach problems were the most common adverse reactions reported. Tecfidera is manufactured by Biogen Idec (Weston, Massachusetts).

Mild cognitive impairment (MCI) at the time of Parkinson's disease diagnosis may predict a highly increased risk for early dementia, according to a study published online ahead of print March 25 in JAMA Neurology. Researchers examined data for a population-based cohort of 182 patients with incident Parkinson's disease who were monitored for three years. Significantly more patients with MCI than without MCI at baseline (27.0% versus 0.7%) progressed to dementia during follow-up. Mild cognitive impairment at the one-year visit was associated with a similar progression rate to dementia (ie, 27.8%) and reversion rate to normal cognition (ie, 19.4%). Among the 22 patients with persistent MCI at baseline and the one-year visit, 10 developed dementia and two reverted to normal cognition by the end of the study.

Higher consumption of green tea and coffee may reduce the risk of cardiovascular disease and stroke, according to a study published online ahead of print March 14 in Stroke. Investigators studied 82,369 Japanese persons between ages 45 and 74 without cardiovascular disease or cancer. Green tea and coffee consumption was assessed by a self-administered questionnaire at baseline. Compared with seldom drinking green tea, the multivariable-adjusted hazard ratios of all strokes were 0.86 and 0.80 in individuals who drank two to three and four or more cups of green tea per day, respectively. Compared with seldom drinking coffee, the multivariable-adjusted hazard ratios of all strokes were 0.89, 0.80, and 0.81 for individuals who drank coffee three to six times per week, once daily, and twice or more daily, respectively.

Updated Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries recommend against the use of steroids, including methylprednisolone, in acute spinal cord injury in the first 24 to 48 hours after injury. The use of steroids previously was recommended for this indication with consideration of the risk–reward profile, as evaluated by the physician. In the first new treatment guidelines in a decade, which were issued by the Joint Section on Disorders of the Spine and Peripheral Nerves of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, the standard has been revised based on the lack of medical evidence supporting the benefits of these drugs in the clinical setting. The report cites strong evidence that "high-dose steroids are associated with harmful side effects, including death."

Abnormalities in cortical surface area may indicate an individual's predisposition to developing migraine, and abnormalities in cortical thickness may result from migraine-related processes, according to research published online ahead of print March 26 in Radiology. Investigators took T2-weighted and three-dimensional T1-weighted MRIs of the brain for 63 migraineurs and 18 controls. They estimated cortical thickness and cortical surface area. Compared with control subjects, patients with migraine had reduced cortical thickness and surface area in pain-processing regions. These reductions were greater in regions involved in executive functions and visual-motion processing. Cortical thickness and cortical surface area abnormalities had minimal areas of overlap. Cortical thickness and surface area abnormalities were related to aura and white matter hyperintensities, but not to disease duration and attack frequency.

Primary stroke centers are more likely to administer t-PA than noncertified hospitals, according to research published online ahead of print March 26 in the Journal of the American Heart Association. Investigators analyzed data obtained from the Nationwide Inpatient Sample between 2004 and 2009 for patients age 18 or older with a primary diagnosis of acute ischemic stroke. IV t-PA was administered to 3.1% of patients overall. The drug was given to 2.2% of patients at noncertified hospitals and to 6.7% of patients at primary stroke centers. Between 2004 and 2009, t-PA administration increased from 1.4% to 3.3% of patients at noncertified hospitals and from 6.0% to 7.6% of patients at primary stroke centers. In a multivariable model, evaluation at a primary stroke center was significantly associated with t-PA use.

Control and prevention of risk factors such as hypertension earlier in life may limit or delay neuropathologic brain changes such as Alzheimer's disease with aging, researchers reported in a study published online ahead of print March 18 in JAMA Neurology. The investigators studied 118 cognitively normal adults ages 47 to 89. Participants were classified as having hypertension if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic on seven occasions. Participants underwent Ab PET imaging with radiotracer fluorine 18–labeled florbetapir, were genotyped for apolipoprotein E, and were classified as ε4+ or ε4−. Subjects with hypertension and at least one ε4 allele had significantly more amyloid burden than those with one or no risk factors.

Physicians can discontinue chronic antipsychotic medication for many elderly adults with Alzheimer's dementia and neuropsychiatric symptoms without causing detrimental effects on their behavior, according to a review published online March 28 in the Cochrane Database of Systematic Reviews. Investigators examined data from nine randomized controlled trials that compared antipsychotic withdrawal strategies with continuation of antipsychotics in patients with dementia. Although neurologists have concerns about the potential adverse events of antipsychotics, it is not clear whether withdrawal is beneficial for patients' cognition or psychomotor status. In two studies of patients whose agitation or psychosis had previously responded well to antipsychotic treatment, discontinuation was associated with an increased risk of relapse or shorter time to relapse. Two studies suggested that patients with severe neuropsychiatric symptoms at baseline could benefit from continuing their antipsychotic medication.

Greater exposure to pathogens associated with stroke risk and atherosclerosis may correlate with poorer cognitive performance, according to research published in the March 26 Neurology. Investigators tested for various pathogens (eg, Chlamydia pneumonia and Helicobacter pylori) in 1,625 participants in the Northern Manhattan Study. The researchers assessed patients' cognitive performance at baseline and at annual follow-up visits. Higher infectious burden index was associated with worse cognition. Each standard deviation in infectious burden correlated with a 0.77-point decline in Mini-Mental State Examination (MMSE) score. Adjustment for risk factors weakened the effect, however. Infectious burden was associated with an MMSE score of 24 or lower. Infectious burden was not associated with cognitive decline over time. Past infections may contribute to cognitive impairment, said the researchers.

Smoking cessation was associated with a decreased risk of cardiovascular disease events, and subsequent weight gain did not modify this association, researchers reported in the March 13 JAMA. Investigators analyzed data collected from 1984 through 2011 in the Framingham Offspring Study. Participants' self-reported smoking status was recorded during four-year examinations. Median four-year weight gain was 2.7 kg for recent smoking quitters without diabetes, 3.6 kg for recent quitters with diabetes, and 0.9 kg for long-term quitters. After adjustment for cardiovascular risk factors, compared with smokers, recent smoking quitters had a hazard ratio for cardiovascular disease of 0.47, and long-term quitters had a hazard ratio of 0.46. The results changed minimally after further adjustment for weight change. Similar point estimates for participants with diabetes did not reach statistical significance.

Women who enter menopause prematurely after bilateral ovariectomy may have a significantly increased risk for cognitive decline and dementia, according to a study published online ahead of print March 9 in Brain. The investigators studied rats 10 weeks after they had undergone bilateral ovariectomy and found that long-term estrogen deprivation dramatically increased the hippocampal CA3 region's sensitivity to ischemic stress, which correlated with a worse cognitive outcome. Long-term ovariectomized rats had robust hyperinduction of Alzheimer's disease-related proteins in the CA3 region. Following ischemic stress, amyloid-precursor protein processing switched from nonamyloidogenic to amyloidogenic. Replacement of 17β-estradiol at the end of the estrogen-deprivation period could not prevent CA3 hypersensitivity and amyloidogenesis, but if 17β-estradiol was initiated at ovariectomy and maintained throughout the estrogen deprivation period, it completely prevented these events.

Childhood obesity may increase the risk of developing multiple sclerosis (MS) or clinically isolated syndrome (CIS), particularly for adolescent girls, according to a study published in the February 5 issue of Neurology. Researchers identified 75 patients between ages 11 and 18 with newly diagnosed MS or CIS. BMI was obtained before symptom onset for patients with MS or CIS, and through the Kaiser Permanente Southern California children’s health study for the underlying cohort. Obesity was associated with a significantly increased risk of MS or CIS in girls, but not in boys. The risk of CIS or MS was 1.58 among overweight girls, 1.78 among moderately obese girls, and 3.76 among extremely obese girls, compared with girls of normal weight.

Among individuals at high cardiovascular risk, a Mediterranean diet may reduce the likelihood of major cardiovascular events, including stroke, according to research published online in the February 25 New England Journal of Medicine. Researchers randomly assigned 7,447 participants to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet. Participants’ age ranged from 55 to 80, and 57% were women. A total of 288 participants had myocardial infarction, stroke, or death from cardiovascular causes. The multivariable-adjusted hazard ratios were 0.70 and 0.72 for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events).

The total level of antioxidants in the diet does not appear to predict a patient’s risks of dementia and stroke, researchers reported in the February 20 online Neurology. The investigators prospectively studied 5,395 participants in the Rotterdam Study. The participants were age 55 and older and dementia-free. The researchers elicited dietary information at baseline using a semiquantitative food-frequency questionnaire and combined it with food-specific ferric-reducing antioxidant power (FRAP) measurements from published tables. During a median 13.8 years of follow-up, the authors identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, they observed no associations between dietary FRAP scores and risk of dementia or risk of stroke. Results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes.

Eating foods high in carotenoids may help prevent or delay the onset of amyotrophic lateral sclerosis (ALS), according to research published online ahead of print January 29 in the Annals of Neurology. Investigators examined data for 1,100,910 participants (562,942 men) in the NIH–Association of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study, and the Nurses Health Study. A total of 1,153 deaths related to ALS occurred. Greater consumption of major carotenoids was associated with a reduced risk of ALS. Higher dietary intakes of b-carotene and lutein were inversely associated with ALS risk. Lycopene, b-cryptoxanthin, and vitamin C were not associated with reduced risk of ALS.

A device that delivers supraorbital transcutaneous stimulation may be a safe and effective preventive therapy for migraine, according to research published in the February 19 issue of Neurology. After a one-month run-in, 67 patients with at least two migraine attacks per month were randomized to stimulation or sham stimulation. Participants applied the stimulator daily for 20 minutes over the course of three months. The mean number of migraine days decreased significantly in the stimulation group (ie, from 6.94 to 4.88), but not in the sham group (ie, from 6.54 to 6.22), between the run-in and third month of treatment. Monthly migraine attacks, monthly headache days, and monthly acute antimigraine drug intake were also significantly reduced in the stimulation group, but not in the sham group.

Small-vessel cerebrovascular disease, manifested as white matter hyperintensities (WMHs) on MRI, may contribute independently to the development of Alzheimer’s disease, reported investigators in the February 18 online ahead of print JAMA Neurology. Researchers retrospectively examined baseline amyloid deposits for 21 controls, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined Alzheimer’s disease. The team derived total WMH volume from patients’ MRI data. Amyloid positivity and increased total WMH volume independently predicted a diagnosis of Alzheimer’s disease. Among amyloid-positive patients, subjects with Alzheimer’s disease had greater WMH volume than controls. Among subjects with mild cognitive impairment, WMH and amyloid positivity at baseline conferred risk for a future diagnosis of Alzheimer’s disease. The findings suggest that prevention strategies for Alzheimer’s disease may be possible.

Motor benefits may continue for patients with dystonia after deep brain stimulation (DBS) is turned off, according to research published February 11 online ahead of print in Movement Disorders. Two patients with primary generalized dystonia were treated successfully with bilateral DBS: one for 18 months, and one for five years. By accident, DBS was interrupted unilaterally for three and seven months, respectively, and bilaterally for two days and two months, respectively. The patients retained their motor benefits for several months after the inadvertent interruption of stimulation. Symptoms of dystonia partially returned during the period of therapy interruption and rapidly and completely resolved after stimulation resumed. Young age, short duration of disease, and chronic DBS therapy with relatively low stimulation energy may influence whether motor benefits continue for an individual.

Unlike the adult human brain, the neonatal brain may respond to external stimulus with an increase in deoxyhemoglobin, corresponding to a negative blood oxygen level-dependent (BOLD) signal on functional MRI, according to research published February 20 online ahead of print in the Proceedings of the National Academy of Sciences. Researchers studied the evolution of the cortical blood flow response in neonatal rats during postnatal development using exposed-cortex multispectral optical imaging. Day-12–13 rats, which are equivalent to human newborns, exhibited an inverted hemodynamic response with early signs of oxygen consumption, followed by delayed, active constriction of pial arteries. The hemodynamic response matured through the development of an initial hyperemic (ie, positive BOLD) phase that eventually masked oxygen consumption and balanced vasoconstriction toward adulthood.

Neurologists may have an approximately 15-year interval during which to treat patients with amyloid buildup in an attempt to prevent Alzheimer’s disease, according to research published February 27 online ahead of print in Neurology. Investigators studied 260 participants ages 70 to 92, all of whom underwent two or more serial amyloid PET examinations. A total of 205 participants were cognitively normal, 47 had mild cognitive impairment, and eight had Alzheimer dementia. Rates of amyloid accumulation were low among patients who had low or high amyloid levels at baseline, and high among patients with moderate levels of amyloid at baseline. The researchers estimated that the average time required to travel from a low rate of accumulation to a high rate of accumulation is approximately 15 years.

Overexpression of α-synuclein may be associated with hypertrophy of membrane systems of the presynaptic terminal and the disruption of vesicle recycling, according to a study published in the February 6 issue of the Journal of Neuroscience. Progressive degeneration and cell death are the potential consequences of this disruption. Overexpressed α-synuclein was associated with a large and poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. The α-synuclein was found in several parts of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. The data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation, said the investigators.

Patients with multiple sclerosis (MS) and problems with cognition, memory, attention, or concentration have more damage to areas in the brain responsible for cognitive processes than patients with MS who do not have cognitive problems, according to research published in the March 6 Neurology. Investigators used MRI and diffusion tensor imaging to compare brain measurements in 20 patients with MS who had related cognitive problems, 35 patients with MS who did not have cognitive problems, and 30 healthy controls. About 49% of brain white matter examined had impaired integrity in individuals with MS and no cognitive problems, compared with 76% in patients with MS and cognitive problems. White matter dysfunction was particularly evident in the thalamus in individuals with MS-related cognitive problems.

Epidural steroid injections (ESIs) may be associated with significantly less improvement among patients with spinal stenosis, according to a study published in the February 15 Spine. Researchers performed a subgroup analysis of a prospective, randomized database from the Spine Patient Outcomes Research Trial. ESI patients who ultimately underwent surgery had an average 26-minute increase in operative time and an increased length of stay by 0.9 days. Over four years, surgically treated ESI patients had significantly less improvement in 36-Item Short Form Health Survey (SF-36) Physical Function, compared with patients who had not received ESI. Nonsurgically treated patients who received ESI also had significantly less improvement in SF-36 Body Pain and SF-36 Physical Function than patients who did not receive ESI.

C9RANT, an abnormal protein that forms as a result of genetic abnormalities, may play a role in the development of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD), researchers reported in the February 20 issue of Neuron. Investigators found insoluble accumulations of C9RANT in the brain tissue of patients with ALS or FTD, but not in patients with other neurodegenerative diseases. Repeat expansions in a noncoding region of the C9ORF72 gene are the major cause of C9RANT, and these expansions are the most common cause of ALS and FTD. The investigators found C9RANT in brain tissue after creating a novel antibody to detect it. C9RANT is a potential biomarker for FTD and ALS and a potential target to prevent neuronal loss, according to the researchers.

Childhood obesity may increase the risk of developing multiple sclerosis (MS) or clinically isolated syndrome (CIS), particularly for adolescent girls, according to a study published in the February 5 issue of Neurology. Researchers identified 75 patients between ages 11 and 18 with newly diagnosed MS or CIS. BMI was obtained before symptom onset for patients with MS or CIS, and through the Kaiser Permanente Southern California children’s health study for the underlying cohort. Obesity was associated with a significantly increased risk of MS or CIS in girls, but not in boys. The risk of CIS or MS was 1.58 among overweight girls, 1.78 among moderately obese girls, and 3.76 among extremely obese girls, compared with girls of normal weight.

Among individuals at high cardiovascular risk, a Mediterranean diet may reduce the likelihood of major cardiovascular events, including stroke, according to research published online in the February 25 New England Journal of Medicine. Researchers randomly assigned 7,447 participants to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet. Participants’ age ranged from 55 to 80, and 57% were women. A total of 288 participants had myocardial infarction, stroke, or death from cardiovascular causes. The multivariable-adjusted hazard ratios were 0.70 and 0.72 for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events).

The total level of antioxidants in the diet does not appear to predict a patient’s risks of dementia and stroke, researchers reported in the February 20 online Neurology. The investigators prospectively studied 5,395 participants in the Rotterdam Study. The participants were age 55 and older and dementia-free. The researchers elicited dietary information at baseline using a semiquantitative food-frequency questionnaire and combined it with food-specific ferric-reducing antioxidant power (FRAP) measurements from published tables. During a median 13.8 years of follow-up, the authors identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, they observed no associations between dietary FRAP scores and risk of dementia or risk of stroke. Results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes.

Eating foods high in carotenoids may help prevent or delay the onset of amyotrophic lateral sclerosis (ALS), according to research published online ahead of print January 29 in the Annals of Neurology. Investigators examined data for 1,100,910 participants (562,942 men) in the NIH–Association of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study, and the Nurses Health Study. A total of 1,153 deaths related to ALS occurred. Greater consumption of major carotenoids was associated with a reduced risk of ALS. Higher dietary intakes of b-carotene and lutein were inversely associated with ALS risk. Lycopene, b-cryptoxanthin, and vitamin C were not associated with reduced risk of ALS.

A device that delivers supraorbital transcutaneous stimulation may be a safe and effective preventive therapy for migraine, according to research published in the February 19 issue of Neurology. After a one-month run-in, 67 patients with at least two migraine attacks per month were randomized to stimulation or sham stimulation. Participants applied the stimulator daily for 20 minutes over the course of three months. The mean number of migraine days decreased significantly in the stimulation group (ie, from 6.94 to 4.88), but not in the sham group (ie, from 6.54 to 6.22), between the run-in and third month of treatment. Monthly migraine attacks, monthly headache days, and monthly acute antimigraine drug intake were also significantly reduced in the stimulation group, but not in the sham group.

Small-vessel cerebrovascular disease, manifested as white matter hyperintensities (WMHs) on MRI, may contribute independently to the development of Alzheimer’s disease, reported investigators in the February 18 online ahead of print JAMA Neurology. Researchers retrospectively examined baseline amyloid deposits for 21 controls, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined Alzheimer’s disease. The team derived total WMH volume from patients’ MRI data. Amyloid positivity and increased total WMH volume independently predicted a diagnosis of Alzheimer’s disease. Among amyloid-positive patients, subjects with Alzheimer’s disease had greater WMH volume than controls. Among subjects with mild cognitive impairment, WMH and amyloid positivity at baseline conferred risk for a future diagnosis of Alzheimer’s disease. The findings suggest that prevention strategies for Alzheimer’s disease may be possible.

Motor benefits may continue for patients with dystonia after deep brain stimulation (DBS) is turned off, according to research published February 11 online ahead of print in Movement Disorders. Two patients with primary generalized dystonia were treated successfully with bilateral DBS: one for 18 months, and one for five years. By accident, DBS was interrupted unilaterally for three and seven months, respectively, and bilaterally for two days and two months, respectively. The patients retained their motor benefits for several months after the inadvertent interruption of stimulation. Symptoms of dystonia partially returned during the period of therapy interruption and rapidly and completely resolved after stimulation resumed. Young age, short duration of disease, and chronic DBS therapy with relatively low stimulation energy may influence whether motor benefits continue for an individual.

Unlike the adult human brain, the neonatal brain may respond to external stimulus with an increase in deoxyhemoglobin, corresponding to a negative blood oxygen level-dependent (BOLD) signal on functional MRI, according to research published February 20 online ahead of print in the Proceedings of the National Academy of Sciences. Researchers studied the evolution of the cortical blood flow response in neonatal rats during postnatal development using exposed-cortex multispectral optical imaging. Day-12–13 rats, which are equivalent to human newborns, exhibited an inverted hemodynamic response with early signs of oxygen consumption, followed by delayed, active constriction of pial arteries. The hemodynamic response matured through the development of an initial hyperemic (ie, positive BOLD) phase that eventually masked oxygen consumption and balanced vasoconstriction toward adulthood.

Neurologists may have an approximately 15-year interval during which to treat patients with amyloid buildup in an attempt to prevent Alzheimer’s disease, according to research published February 27 online ahead of print in Neurology. Investigators studied 260 participants ages 70 to 92, all of whom underwent two or more serial amyloid PET examinations. A total of 205 participants were cognitively normal, 47 had mild cognitive impairment, and eight had Alzheimer dementia. Rates of amyloid accumulation were low among patients who had low or high amyloid levels at baseline, and high among patients with moderate levels of amyloid at baseline. The researchers estimated that the average time required to travel from a low rate of accumulation to a high rate of accumulation is approximately 15 years.

Overexpression of α-synuclein may be associated with hypertrophy of membrane systems of the presynaptic terminal and the disruption of vesicle recycling, according to a study published in the February 6 issue of the Journal of Neuroscience. Progressive degeneration and cell death are the potential consequences of this disruption. Overexpressed α-synuclein was associated with a large and poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. The α-synuclein was found in several parts of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. The data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation, said the investigators.

Patients with multiple sclerosis (MS) and problems with cognition, memory, attention, or concentration have more damage to areas in the brain responsible for cognitive processes than patients with MS who do not have cognitive problems, according to research published in the March 6 Neurology. Investigators used MRI and diffusion tensor imaging to compare brain measurements in 20 patients with MS who had related cognitive problems, 35 patients with MS who did not have cognitive problems, and 30 healthy controls. About 49% of brain white matter examined had impaired integrity in individuals with MS and no cognitive problems, compared with 76% in patients with MS and cognitive problems. White matter dysfunction was particularly evident in the thalamus in individuals with MS-related cognitive problems.

Epidural steroid injections (ESIs) may be associated with significantly less improvement among patients with spinal stenosis, according to a study published in the February 15 Spine. Researchers performed a subgroup analysis of a prospective, randomized database from the Spine Patient Outcomes Research Trial. ESI patients who ultimately underwent surgery had an average 26-minute increase in operative time and an increased length of stay by 0.9 days. Over four years, surgically treated ESI patients had significantly less improvement in 36-Item Short Form Health Survey (SF-36) Physical Function, compared with patients who had not received ESI. Nonsurgically treated patients who received ESI also had significantly less improvement in SF-36 Body Pain and SF-36 Physical Function than patients who did not receive ESI.

C9RANT, an abnormal protein that forms as a result of genetic abnormalities, may play a role in the development of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD), researchers reported in the February 20 issue of Neuron. Investigators found insoluble accumulations of C9RANT in the brain tissue of patients with ALS or FTD, but not in patients with other neurodegenerative diseases. Repeat expansions in a noncoding region of the C9ORF72 gene are the major cause of C9RANT, and these expansions are the most common cause of ALS and FTD. The investigators found C9RANT in brain tissue after creating a novel antibody to detect it. C9RANT is a potential biomarker for FTD and ALS and a potential target to prevent neuronal loss, according to the researchers.

Childhood obesity may increase the risk of developing multiple sclerosis (MS) or clinically isolated syndrome (CIS), particularly for adolescent girls, according to a study published in the February 5 issue of Neurology. Researchers identified 75 patients between ages 11 and 18 with newly diagnosed MS or CIS. BMI was obtained before symptom onset for patients with MS or CIS, and through the Kaiser Permanente Southern California children’s health study for the underlying cohort. Obesity was associated with a significantly increased risk of MS or CIS in girls, but not in boys. The risk of CIS or MS was 1.58 among overweight girls, 1.78 among moderately obese girls, and 3.76 among extremely obese girls, compared with girls of normal weight.

Among individuals at high cardiovascular risk, a Mediterranean diet may reduce the likelihood of major cardiovascular events, including stroke, according to research published online in the February 25 New England Journal of Medicine. Researchers randomly assigned 7,447 participants to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet. Participants’ age ranged from 55 to 80, and 57% were women. A total of 288 participants had myocardial infarction, stroke, or death from cardiovascular causes. The multivariable-adjusted hazard ratios were 0.70 and 0.72 for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events).

The total level of antioxidants in the diet does not appear to predict a patient’s risks of dementia and stroke, researchers reported in the February 20 online Neurology. The investigators prospectively studied 5,395 participants in the Rotterdam Study. The participants were age 55 and older and dementia-free. The researchers elicited dietary information at baseline using a semiquantitative food-frequency questionnaire and combined it with food-specific ferric-reducing antioxidant power (FRAP) measurements from published tables. During a median 13.8 years of follow-up, the authors identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, they observed no associations between dietary FRAP scores and risk of dementia or risk of stroke. Results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes.

Eating foods high in carotenoids may help prevent or delay the onset of amyotrophic lateral sclerosis (ALS), according to research published online ahead of print January 29 in the Annals of Neurology. Investigators examined data for 1,100,910 participants (562,942 men) in the NIH–Association of American Retired Persons Diet and Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort, the Health Professionals Follow-up Study, and the Nurses Health Study. A total of 1,153 deaths related to ALS occurred. Greater consumption of major carotenoids was associated with a reduced risk of ALS. Higher dietary intakes of b-carotene and lutein were inversely associated with ALS risk. Lycopene, b-cryptoxanthin, and vitamin C were not associated with reduced risk of ALS.

A device that delivers supraorbital transcutaneous stimulation may be a safe and effective preventive therapy for migraine, according to research published in the February 19 issue of Neurology. After a one-month run-in, 67 patients with at least two migraine attacks per month were randomized to stimulation or sham stimulation. Participants applied the stimulator daily for 20 minutes over the course of three months. The mean number of migraine days decreased significantly in the stimulation group (ie, from 6.94 to 4.88), but not in the sham group (ie, from 6.54 to 6.22), between the run-in and third month of treatment. Monthly migraine attacks, monthly headache days, and monthly acute antimigraine drug intake were also significantly reduced in the stimulation group, but not in the sham group.

Small-vessel cerebrovascular disease, manifested as white matter hyperintensities (WMHs) on MRI, may contribute independently to the development of Alzheimer’s disease, reported investigators in the February 18 online ahead of print JAMA Neurology. Researchers retrospectively examined baseline amyloid deposits for 21 controls, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined Alzheimer’s disease. The team derived total WMH volume from patients’ MRI data. Amyloid positivity and increased total WMH volume independently predicted a diagnosis of Alzheimer’s disease. Among amyloid-positive patients, subjects with Alzheimer’s disease had greater WMH volume than controls. Among subjects with mild cognitive impairment, WMH and amyloid positivity at baseline conferred risk for a future diagnosis of Alzheimer’s disease. The findings suggest that prevention strategies for Alzheimer’s disease may be possible.

Motor benefits may continue for patients with dystonia after deep brain stimulation (DBS) is turned off, according to research published February 11 online ahead of print in Movement Disorders. Two patients with primary generalized dystonia were treated successfully with bilateral DBS: one for 18 months, and one for five years. By accident, DBS was interrupted unilaterally for three and seven months, respectively, and bilaterally for two days and two months, respectively. The patients retained their motor benefits for several months after the inadvertent interruption of stimulation. Symptoms of dystonia partially returned during the period of therapy interruption and rapidly and completely resolved after stimulation resumed. Young age, short duration of disease, and chronic DBS therapy with relatively low stimulation energy may influence whether motor benefits continue for an individual.

Unlike the adult human brain, the neonatal brain may respond to external stimulus with an increase in deoxyhemoglobin, corresponding to a negative blood oxygen level-dependent (BOLD) signal on functional MRI, according to research published February 20 online ahead of print in the Proceedings of the National Academy of Sciences. Researchers studied the evolution of the cortical blood flow response in neonatal rats during postnatal development using exposed-cortex multispectral optical imaging. Day-12–13 rats, which are equivalent to human newborns, exhibited an inverted hemodynamic response with early signs of oxygen consumption, followed by delayed, active constriction of pial arteries. The hemodynamic response matured through the development of an initial hyperemic (ie, positive BOLD) phase that eventually masked oxygen consumption and balanced vasoconstriction toward adulthood.

Neurologists may have an approximately 15-year interval during which to treat patients with amyloid buildup in an attempt to prevent Alzheimer’s disease, according to research published February 27 online ahead of print in Neurology. Investigators studied 260 participants ages 70 to 92, all of whom underwent two or more serial amyloid PET examinations. A total of 205 participants were cognitively normal, 47 had mild cognitive impairment, and eight had Alzheimer dementia. Rates of amyloid accumulation were low among patients who had low or high amyloid levels at baseline, and high among patients with moderate levels of amyloid at baseline. The researchers estimated that the average time required to travel from a low rate of accumulation to a high rate of accumulation is approximately 15 years.

Overexpression of α-synuclein may be associated with hypertrophy of membrane systems of the presynaptic terminal and the disruption of vesicle recycling, according to a study published in the February 6 issue of the Journal of Neuroscience. Progressive degeneration and cell death are the potential consequences of this disruption. Overexpressed α-synuclein was associated with a large and poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. The α-synuclein was found in several parts of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. The data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation, said the investigators.

Patients with multiple sclerosis (MS) and problems with cognition, memory, attention, or concentration have more damage to areas in the brain responsible for cognitive processes than patients with MS who do not have cognitive problems, according to research published in the March 6 Neurology. Investigators used MRI and diffusion tensor imaging to compare brain measurements in 20 patients with MS who had related cognitive problems, 35 patients with MS who did not have cognitive problems, and 30 healthy controls. About 49% of brain white matter examined had impaired integrity in individuals with MS and no cognitive problems, compared with 76% in patients with MS and cognitive problems. White matter dysfunction was particularly evident in the thalamus in individuals with MS-related cognitive problems.

Epidural steroid injections (ESIs) may be associated with significantly less improvement among patients with spinal stenosis, according to a study published in the February 15 Spine. Researchers performed a subgroup analysis of a prospective, randomized database from the Spine Patient Outcomes Research Trial. ESI patients who ultimately underwent surgery had an average 26-minute increase in operative time and an increased length of stay by 0.9 days. Over four years, surgically treated ESI patients had significantly less improvement in 36-Item Short Form Health Survey (SF-36) Physical Function, compared with patients who had not received ESI. Nonsurgically treated patients who received ESI also had significantly less improvement in SF-36 Body Pain and SF-36 Physical Function than patients who did not receive ESI.

C9RANT, an abnormal protein that forms as a result of genetic abnormalities, may play a role in the development of amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD), researchers reported in the February 20 issue of Neuron. Investigators found insoluble accumulations of C9RANT in the brain tissue of patients with ALS or FTD, but not in patients with other neurodegenerative diseases. Repeat expansions in a noncoding region of the C9ORF72 gene are the major cause of C9RANT, and these expansions are the most common cause of ALS and FTD. The investigators found C9RANT in brain tissue after creating a novel antibody to detect it. C9RANT is a potential biomarker for FTD and ALS and a potential target to prevent neuronal loss, according to the researchers.

Patients with multiple sclerosis (MS) disease activity have a higher rate of thinning of the ganglion cell/inner plexiform (GCIP) layer of the eye, researchers reported in the January 1 Neurology. Annual rates of GCIP thinning may be highest among patients with new gadolinium-enhancing lesions, new T2 lesions, and disease duration of less than five years. The investigators performed spectral-domain optical coherence tomography scans every six months on 164 patients with MS and 59 healthy controls. The mean follow-up time was 21.1 months. Annual GCIP thinning occurred 42% faster in patients with relapses, 54% faster in patients with new gadolinium-enhanced lesions, and 36% faster in patients with new T2 lesions.

Vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine does not appear to be associated with an increased risk of epileptic seizures, according to research published in the December 28, 2012, BMJ. Researchers studied 373,398 people with and without epilepsy who had received the vaccine. The primary end point was admission to a hospital or outpatient hospital care with epileptic seizures. The investigators found no increased risk of seizures in patients with epilepsy and a nonsignificantly decreased risk of seizures in persons without epilepsy during the initial seven-day risk period. During the subsequent 23-day risk period, people without epilepsy had a nonsignificantly increased risk of seizures, but patients with epilepsy had no increase in risk of seizures.

Variations in some genes associated with risk for psychiatric disorders may be observed as differences in brain structure in neonates, according to a study published in the January 2 online Cerebral Cortex. Investigators performed automated region-of-interest volumetry and tensor-based morphometry on 272 newborns who had had high-resolution MRI scans. The group found that estrogen receptor alpha (rs9340799) predicted intracranial volume. Polymorphisms in estrogen receptor alpha (rs9340799), as well as in disrupted-in-schizophrenia 1 (DISC1, rs821616), catechol-O-methyltransferase (COMT), neuregulin 1, apolipoprotein E, and brain-derived neurotrophic factor, were significantly associated with local variation in gray matter volume. “The results highlight the importance of prenatal brain development in mediating psychiatric risk,” noted the authors.

Four months after mild traumatic brain injury (TBI), white matter abnormalities may persist in children, even if cognitive symptoms have resolved, according to research published in the December 12, 2012, Journal of Neuroscience. The magnitude and duration of these abnormalities also appear to be greater in children with mild TBI than in adults with mild TBI. Researchers performed fractional anisotropy, axial diffusivity, and radial diffusivity on 15 children with semiacute mild TBI and 15 matched controls. Post-TBI cognitive dysfunction was observed in the domains of attention and processing speed. Increased anisotropy identified patients with pediatric mild TBI with 90% accuracy but was not associated with neuropsychologic deficits. Anisotropic diffusion may provide an objective biomarker of pediatric mild TBI.

The FDA has approved Eliquis (apixaban) for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In a phase III clinical trial, Eliquis, an oral anticoagulant, reduced the risk of stroke or systemic embolism by 21%, compared with warfarin. The drug primarily reduced the risk of hemorrhagic stroke and ischemic stroke that converted to hemorrhagic stroke, and it also decreased the risks of major bleeding and all-cause mortality, compared with warfarin. Eliquis inhibits Factor Xa, a blood-clotting protein, thus decreasing thrombin generation and blood clots. The recommended dose is 5 mg twice daily. For patients age 80 or older and those who weigh 60 kg or less, the recommended dose is 2.5 mg twice daily. Eliquis is manufactured by Bristol-Myers Squibb (New York City) and comarketed with Pfizer (New York City).

Intermittent fasting, together with a ketogenic diet, may reduce seizures in children with epilepsy to a greater extent than the ketogenic diet alone, investigators reported in the November 30, 2012, online Epilepsy Research. The researchers placed six children with an incomplete response to a ketogenic diet on an intermittent fasting regimen. The children, ages 2 to 7, fasted on alternate days. Four children had transient improvement in seizure control, but they also had hunger-related adverse reactions. Three patients adhered to the combined intermittent fasting and ketogenic diet regimen for two months. The ketogenic diet and intermittent fasting may not share the same anticonvulsant mechanisms, noted the authors.

The available evidence does not support the use of cannabis extract to treat multiple sclerosis (MS), according to a review published in the December 2012 Drug and Therapeutics Bulletin. Researchers concluded that the trial data for nabiximols, a mouth spray for patients with MS containing dronabinol and cannabidiol, were limited. In the trials, which were the basis for the drug’s approval, symptoms decreased in a slightly higher number of patients taking nabiximols, compared with patients taking placebo. The drug was used for relatively short periods (ie, six weeks to four months) in many of these studies, however, and no study compared nabiximols with another active ingredient. One properly designed trial with a sufficient number of patients showed no difference in symptom relief between participants who took nabiximols and those who did not.

Baseline depression was associated with mild cognitive impairment (MCI) and dementia in individuals 65 or older, researchers reported in the December 31, 2012, Archives of Neurology. Depression may coincide with cognitive impairment, but may not precede it, the study authors noted. The investigators studied 2,160 community-dwelling Medicare recipients in New York City. The team defined depression as a score of 4 or more on the Center for Epidemiological Studies Depression scale. MCI, dementia, and progression from MCI to dementia were the study’s main outcome measures. Baseline depression was associated with an increased risk of incident dementia, but not with incident MCI. Participants with MCI and comorbid depression at baseline had a higher risk of progression to dementia, but not Alzheimer’s disease.

Consumption of fructose resulted in a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels than consumption of glucose, according to research published in the January 2 JAMA. Glucose ingestion was associated with a significantly greater reduction in hypothalamic cerebral blood flow than fructose ingestion. Researchers performed MRIs of 20 healthy adults at baseline and after ingestion of a glucose or fructose drink. The blinded study had a random-order crossover design. Compared with baseline, glucose ingestion increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus, but not the striatum. Fructose reduced regional cerebral blood flow in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex.

Research published in the January 7 online Epilepsia provides evidence for a shared genetic susceptibility to epilespsy and migraine with aura. Compared with migraine without aura, the prevalence of migraine with aura was significantly increased among patients with epilepsy who have two or more first-degree relatives with epilepsy. Investigators studied the prevalence of a history of migraine in 730 participants in the Epilepsy Phenome/Genome Project. Eligible participants were 12 or older, had nonacquired focal epilepsy or generalized epilepsy, and had one or more relative epilepsy of unknown cause. The researchers collected information on migraine with and without aura using an instrument validated for individuals 12 and older. The team also interviewed participants about the history of seizure disorders in nonenrolled family members.

Higher exposure to benomyl is associated with an increased risk for Parkinson’s disease, according to an epidemiologic study published in the December 24, 2012, online Proceedings of the National Academy of Sciences. In primary mesencephalic neurons, benomyl exposure inhibits aldehyde dehydrogenase (ALDH) and alters dopamine homeostasis. Investigators tested the effects of benomyl in cell cultures and confirmed that the chemical damaged or destroyed dopaminergic neurons. The researchers also found that benomyl caused the loss of dopaminergic neurons in zebrafish. The ALDH model for Parkinson’s disease etiology may help explain the selective vulnerability of dopaminergic neurons and describe the mechanism through which environmental toxicants contribute to Parkinson’s disease pathogenesis, the authors theorized.

Patients with a history of traumatic brain injury (TBI) and loss of consciousness may have an increased risk for future TBI and loss of consciousness, according to a study published in the November 21, 2012, online Journal of Neurology, Neurosurgery, and Psychiatry. Researchers are conducting an ongoing study of 4,225 nondemented adults age 65 and older. Participants are seen every two years, and 14% have reported a lifetime history of TBI and loss of consciousness. Individuals reporting a first injury before age 25 had an adjusted hazard ratio of 2.54 for TBI and loss of consciousness, compared with a hazard ratio of 3.79 for adults with first injury after age 55.

Patients with multiple sclerosis (MS) disease activity have a higher rate of thinning of the ganglion cell/inner plexiform (GCIP) layer of the eye, researchers reported in the January 1 Neurology. Annual rates of GCIP thinning may be highest among patients with new gadolinium-enhancing lesions, new T2 lesions, and disease duration of less than five years. The investigators performed spectral-domain optical coherence tomography scans every six months on 164 patients with MS and 59 healthy controls. The mean follow-up time was 21.1 months. Annual GCIP thinning occurred 42% faster in patients with relapses, 54% faster in patients with new gadolinium-enhanced lesions, and 36% faster in patients with new T2 lesions.

Vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine does not appear to be associated with an increased risk of epileptic seizures, according to research published in the December 28, 2012, BMJ. Researchers studied 373,398 people with and without epilepsy who had received the vaccine. The primary end point was admission to a hospital or outpatient hospital care with epileptic seizures. The investigators found no increased risk of seizures in patients with epilepsy and a nonsignificantly decreased risk of seizures in persons without epilepsy during the initial seven-day risk period. During the subsequent 23-day risk period, people without epilepsy had a nonsignificantly increased risk of seizures, but patients with epilepsy had no increase in risk of seizures.

Variations in some genes associated with risk for psychiatric disorders may be observed as differences in brain structure in neonates, according to a study published in the January 2 online Cerebral Cortex. Investigators performed automated region-of-interest volumetry and tensor-based morphometry on 272 newborns who had had high-resolution MRI scans. The group found that estrogen receptor alpha (rs9340799) predicted intracranial volume. Polymorphisms in estrogen receptor alpha (rs9340799), as well as in disrupted-in-schizophrenia 1 (DISC1, rs821616), catechol-O-methyltransferase (COMT), neuregulin 1, apolipoprotein E, and brain-derived neurotrophic factor, were significantly associated with local variation in gray matter volume. “The results highlight the importance of prenatal brain development in mediating psychiatric risk,” noted the authors.

Four months after mild traumatic brain injury (TBI), white matter abnormalities may persist in children, even if cognitive symptoms have resolved, according to research published in the December 12, 2012, Journal of Neuroscience. The magnitude and duration of these abnormalities also appear to be greater in children with mild TBI than in adults with mild TBI. Researchers performed fractional anisotropy, axial diffusivity, and radial diffusivity on 15 children with semiacute mild TBI and 15 matched controls. Post-TBI cognitive dysfunction was observed in the domains of attention and processing speed. Increased anisotropy identified patients with pediatric mild TBI with 90% accuracy but was not associated with neuropsychologic deficits. Anisotropic diffusion may provide an objective biomarker of pediatric mild TBI.

The FDA has approved Eliquis (apixaban) for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In a phase III clinical trial, Eliquis, an oral anticoagulant, reduced the risk of stroke or systemic embolism by 21%, compared with warfarin. The drug primarily reduced the risk of hemorrhagic stroke and ischemic stroke that converted to hemorrhagic stroke, and it also decreased the risks of major bleeding and all-cause mortality, compared with warfarin. Eliquis inhibits Factor Xa, a blood-clotting protein, thus decreasing thrombin generation and blood clots. The recommended dose is 5 mg twice daily. For patients age 80 or older and those who weigh 60 kg or less, the recommended dose is 2.5 mg twice daily. Eliquis is manufactured by Bristol-Myers Squibb (New York City) and comarketed with Pfizer (New York City).

Intermittent fasting, together with a ketogenic diet, may reduce seizures in children with epilepsy to a greater extent than the ketogenic diet alone, investigators reported in the November 30, 2012, online Epilepsy Research. The researchers placed six children with an incomplete response to a ketogenic diet on an intermittent fasting regimen. The children, ages 2 to 7, fasted on alternate days. Four children had transient improvement in seizure control, but they also had hunger-related adverse reactions. Three patients adhered to the combined intermittent fasting and ketogenic diet regimen for two months. The ketogenic diet and intermittent fasting may not share the same anticonvulsant mechanisms, noted the authors.

The available evidence does not support the use of cannabis extract to treat multiple sclerosis (MS), according to a review published in the December 2012 Drug and Therapeutics Bulletin. Researchers concluded that the trial data for nabiximols, a mouth spray for patients with MS containing dronabinol and cannabidiol, were limited. In the trials, which were the basis for the drug’s approval, symptoms decreased in a slightly higher number of patients taking nabiximols, compared with patients taking placebo. The drug was used for relatively short periods (ie, six weeks to four months) in many of these studies, however, and no study compared nabiximols with another active ingredient. One properly designed trial with a sufficient number of patients showed no difference in symptom relief between participants who took nabiximols and those who did not.

Baseline depression was associated with mild cognitive impairment (MCI) and dementia in individuals 65 or older, researchers reported in the December 31, 2012, Archives of Neurology. Depression may coincide with cognitive impairment, but may not precede it, the study authors noted. The investigators studied 2,160 community-dwelling Medicare recipients in New York City. The team defined depression as a score of 4 or more on the Center for Epidemiological Studies Depression scale. MCI, dementia, and progression from MCI to dementia were the study’s main outcome measures. Baseline depression was associated with an increased risk of incident dementia, but not with incident MCI. Participants with MCI and comorbid depression at baseline had a higher risk of progression to dementia, but not Alzheimer’s disease.

Consumption of fructose resulted in a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels than consumption of glucose, according to research published in the January 2 JAMA. Glucose ingestion was associated with a significantly greater reduction in hypothalamic cerebral blood flow than fructose ingestion. Researchers performed MRIs of 20 healthy adults at baseline and after ingestion of a glucose or fructose drink. The blinded study had a random-order crossover design. Compared with baseline, glucose ingestion increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus, but not the striatum. Fructose reduced regional cerebral blood flow in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex.

Research published in the January 7 online Epilepsia provides evidence for a shared genetic susceptibility to epilespsy and migraine with aura. Compared with migraine without aura, the prevalence of migraine with aura was significantly increased among patients with epilepsy who have two or more first-degree relatives with epilepsy. Investigators studied the prevalence of a history of migraine in 730 participants in the Epilepsy Phenome/Genome Project. Eligible participants were 12 or older, had nonacquired focal epilepsy or generalized epilepsy, and had one or more relative epilepsy of unknown cause. The researchers collected information on migraine with and without aura using an instrument validated for individuals 12 and older. The team also interviewed participants about the history of seizure disorders in nonenrolled family members.

Higher exposure to benomyl is associated with an increased risk for Parkinson’s disease, according to an epidemiologic study published in the December 24, 2012, online Proceedings of the National Academy of Sciences. In primary mesencephalic neurons, benomyl exposure inhibits aldehyde dehydrogenase (ALDH) and alters dopamine homeostasis. Investigators tested the effects of benomyl in cell cultures and confirmed that the chemical damaged or destroyed dopaminergic neurons. The researchers also found that benomyl caused the loss of dopaminergic neurons in zebrafish. The ALDH model for Parkinson’s disease etiology may help explain the selective vulnerability of dopaminergic neurons and describe the mechanism through which environmental toxicants contribute to Parkinson’s disease pathogenesis, the authors theorized.

Patients with a history of traumatic brain injury (TBI) and loss of consciousness may have an increased risk for future TBI and loss of consciousness, according to a study published in the November 21, 2012, online Journal of Neurology, Neurosurgery, and Psychiatry. Researchers are conducting an ongoing study of 4,225 nondemented adults age 65 and older. Participants are seen every two years, and 14% have reported a lifetime history of TBI and loss of consciousness. Individuals reporting a first injury before age 25 had an adjusted hazard ratio of 2.54 for TBI and loss of consciousness, compared with a hazard ratio of 3.79 for adults with first injury after age 55.

Patients with multiple sclerosis (MS) disease activity have a higher rate of thinning of the ganglion cell/inner plexiform (GCIP) layer of the eye, researchers reported in the January 1 Neurology. Annual rates of GCIP thinning may be highest among patients with new gadolinium-enhancing lesions, new T2 lesions, and disease duration of less than five years. The investigators performed spectral-domain optical coherence tomography scans every six months on 164 patients with MS and 59 healthy controls. The mean follow-up time was 21.1 months. Annual GCIP thinning occurred 42% faster in patients with relapses, 54% faster in patients with new gadolinium-enhanced lesions, and 36% faster in patients with new T2 lesions.

Vaccination with a monovalent AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine does not appear to be associated with an increased risk of epileptic seizures, according to research published in the December 28, 2012, BMJ. Researchers studied 373,398 people with and without epilepsy who had received the vaccine. The primary end point was admission to a hospital or outpatient hospital care with epileptic seizures. The investigators found no increased risk of seizures in patients with epilepsy and a nonsignificantly decreased risk of seizures in persons without epilepsy during the initial seven-day risk period. During the subsequent 23-day risk period, people without epilepsy had a nonsignificantly increased risk of seizures, but patients with epilepsy had no increase in risk of seizures.

Variations in some genes associated with risk for psychiatric disorders may be observed as differences in brain structure in neonates, according to a study published in the January 2 online Cerebral Cortex. Investigators performed automated region-of-interest volumetry and tensor-based morphometry on 272 newborns who had had high-resolution MRI scans. The group found that estrogen receptor alpha (rs9340799) predicted intracranial volume. Polymorphisms in estrogen receptor alpha (rs9340799), as well as in disrupted-in-schizophrenia 1 (DISC1, rs821616), catechol-O-methyltransferase (COMT), neuregulin 1, apolipoprotein E, and brain-derived neurotrophic factor, were significantly associated with local variation in gray matter volume. “The results highlight the importance of prenatal brain development in mediating psychiatric risk,” noted the authors.

Four months after mild traumatic brain injury (TBI), white matter abnormalities may persist in children, even if cognitive symptoms have resolved, according to research published in the December 12, 2012, Journal of Neuroscience. The magnitude and duration of these abnormalities also appear to be greater in children with mild TBI than in adults with mild TBI. Researchers performed fractional anisotropy, axial diffusivity, and radial diffusivity on 15 children with semiacute mild TBI and 15 matched controls. Post-TBI cognitive dysfunction was observed in the domains of attention and processing speed. Increased anisotropy identified patients with pediatric mild TBI with 90% accuracy but was not associated with neuropsychologic deficits. Anisotropic diffusion may provide an objective biomarker of pediatric mild TBI.

The FDA has approved Eliquis (apixaban) for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In a phase III clinical trial, Eliquis, an oral anticoagulant, reduced the risk of stroke or systemic embolism by 21%, compared with warfarin. The drug primarily reduced the risk of hemorrhagic stroke and ischemic stroke that converted to hemorrhagic stroke, and it also decreased the risks of major bleeding and all-cause mortality, compared with warfarin. Eliquis inhibits Factor Xa, a blood-clotting protein, thus decreasing thrombin generation and blood clots. The recommended dose is 5 mg twice daily. For patients age 80 or older and those who weigh 60 kg or less, the recommended dose is 2.5 mg twice daily. Eliquis is manufactured by Bristol-Myers Squibb (New York City) and comarketed with Pfizer (New York City).

Intermittent fasting, together with a ketogenic diet, may reduce seizures in children with epilepsy to a greater extent than the ketogenic diet alone, investigators reported in the November 30, 2012, online Epilepsy Research. The researchers placed six children with an incomplete response to a ketogenic diet on an intermittent fasting regimen. The children, ages 2 to 7, fasted on alternate days. Four children had transient improvement in seizure control, but they also had hunger-related adverse reactions. Three patients adhered to the combined intermittent fasting and ketogenic diet regimen for two months. The ketogenic diet and intermittent fasting may not share the same anticonvulsant mechanisms, noted the authors.

The available evidence does not support the use of cannabis extract to treat multiple sclerosis (MS), according to a review published in the December 2012 Drug and Therapeutics Bulletin. Researchers concluded that the trial data for nabiximols, a mouth spray for patients with MS containing dronabinol and cannabidiol, were limited. In the trials, which were the basis for the drug’s approval, symptoms decreased in a slightly higher number of patients taking nabiximols, compared with patients taking placebo. The drug was used for relatively short periods (ie, six weeks to four months) in many of these studies, however, and no study compared nabiximols with another active ingredient. One properly designed trial with a sufficient number of patients showed no difference in symptom relief between participants who took nabiximols and those who did not.

Baseline depression was associated with mild cognitive impairment (MCI) and dementia in individuals 65 or older, researchers reported in the December 31, 2012, Archives of Neurology. Depression may coincide with cognitive impairment, but may not precede it, the study authors noted. The investigators studied 2,160 community-dwelling Medicare recipients in New York City. The team defined depression as a score of 4 or more on the Center for Epidemiological Studies Depression scale. MCI, dementia, and progression from MCI to dementia were the study’s main outcome measures. Baseline depression was associated with an increased risk of incident dementia, but not with incident MCI. Participants with MCI and comorbid depression at baseline had a higher risk of progression to dementia, but not Alzheimer’s disease.

Consumption of fructose resulted in a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels than consumption of glucose, according to research published in the January 2 JAMA. Glucose ingestion was associated with a significantly greater reduction in hypothalamic cerebral blood flow than fructose ingestion. Researchers performed MRIs of 20 healthy adults at baseline and after ingestion of a glucose or fructose drink. The blinded study had a random-order crossover design. Compared with baseline, glucose ingestion increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus, but not the striatum. Fructose reduced regional cerebral blood flow in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex.

Research published in the January 7 online Epilepsia provides evidence for a shared genetic susceptibility to epilespsy and migraine with aura. Compared with migraine without aura, the prevalence of migraine with aura was significantly increased among patients with epilepsy who have two or more first-degree relatives with epilepsy. Investigators studied the prevalence of a history of migraine in 730 participants in the Epilepsy Phenome/Genome Project. Eligible participants were 12 or older, had nonacquired focal epilepsy or generalized epilepsy, and had one or more relative epilepsy of unknown cause. The researchers collected information on migraine with and without aura using an instrument validated for individuals 12 and older. The team also interviewed participants about the history of seizure disorders in nonenrolled family members.

Higher exposure to benomyl is associated with an increased risk for Parkinson’s disease, according to an epidemiologic study published in the December 24, 2012, online Proceedings of the National Academy of Sciences. In primary mesencephalic neurons, benomyl exposure inhibits aldehyde dehydrogenase (ALDH) and alters dopamine homeostasis. Investigators tested the effects of benomyl in cell cultures and confirmed that the chemical damaged or destroyed dopaminergic neurons. The researchers also found that benomyl caused the loss of dopaminergic neurons in zebrafish. The ALDH model for Parkinson’s disease etiology may help explain the selective vulnerability of dopaminergic neurons and describe the mechanism through which environmental toxicants contribute to Parkinson’s disease pathogenesis, the authors theorized.

Patients with a history of traumatic brain injury (TBI) and loss of consciousness may have an increased risk for future TBI and loss of consciousness, according to a study published in the November 21, 2012, online Journal of Neurology, Neurosurgery, and Psychiatry. Researchers are conducting an ongoing study of 4,225 nondemented adults age 65 and older. Participants are seen every two years, and 14% have reported a lifetime history of TBI and loss of consciousness. Individuals reporting a first injury before age 25 had an adjusted hazard ratio of 2.54 for TBI and loss of consciousness, compared with a hazard ratio of 3.79 for adults with first injury after age 55.