Multiple Sclerosis Hub

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.