Neurodevelopmental Disorders

The CDC estimates that about one in 68 US children has autism spectrum disorder, according to findings published in the March 28 issue of Morbidity and Mortality Weekly Report Surveillance Summaries. This prevalence is a 30% increase from the CDC’s estimate of one in 88 children using 2008 data.

The findings also show that autism spectrum disorder continues to be more prevalent in boys than in girls: one in 42 boys had autism spectrum disorder in the latest report, compared with one in 189 girls.

The increased prevalence could be attributed to improved clinician identification of autism, a growing number of autistic children with average to above-average intellectual ability, or a combination of both factors, said Coleen Boyle, PhD, Director of the CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD).

The CDC analyzed 2010 data collected by its Autism and Developmental Disabilities Monitoring (ADDM) Network, which provides population-based estimates of autism spectrum disorder prevalence in children age 8 at 11 sites in the United States based on records from community sources that diagnose and provide services to children with developmental disabilities.

Of the 11 sites studied, seven had information available on the intellectual ability of at least 70% of children with autism spectrum disorder. Of the 3,604 children for whom data were available, 31% were classified as having intellectual disability (IQ of 70 or lower), 23% were considered borderline (IQ = 71 to 85), and 46% had IQ scores of greater than 85, considered average or above average intellectual ability.

“We recognize now that autism is a spectrum, no longer limited to the severely affected,” said Marshalyn Yeargin-Allsopp, MD, Chief of the Developmental Disabilities branch of NCBDDD. “There are children with higher IQs being diagnosed who may not even be receiving special education services, and the numbers may reflect that.”

Non-Hispanic white children were 30% more likely to be diagnosed with autism spectrum disorder than were non-Hispanic black children and about 50% more likely to be diagnosed with autism spectrum disorder than were Hispanic children.

Dr. Boyle stressed the importance of early screening and identification of autism spectrum disorder in children (it can be diagnosed by the time a child reaches age 2) and urged parents to take action if a child shows any signs of developmental delays.

“Community leaders, health professionals, educators, and childcare providers should use these data to ensure that children with autism spectrum disorder are identified as early as possible and connected to the services they need,” said Dr. Boyle.

To help promote early intervention in autism spectrum disorder, the CDC will be launching an awareness initiative called “Birth to Five, Watch Me Thrive,” which aims to provide parents, teachers, and community members with information and resources about developmental milestones and screening for autism.

“Most children with autism are not diagnosed until after age 4,” said Dr. Boyle. “The CDC will continue to promote early identification and research. The earlier a child is identified and connected with services, the better.”

The CDC cited several limitations to the report. First, the surveillance sites were not selected to be representative of the entire United States. Second, population denominators used for this report were based on the 2010 decennial census. Comparisons with previous ADDM findings thus should be interpreted with caution because ADDM reports from nondecennial surveillance years are likely influenced by greater error in the population denominators used for those previous surveillance years, which were based on postcensus estimates. Third, three of the nine sites with access to review children’s education records did not receive permission to do so in all school districts within the site’s overall surveillance area. Fourth, findings that address intellectual ability might not be generalizable to all ADDM sites. Finally, race and ethnicity are presented in broad terms and should not be interpreted as generalizable to all persons within those categories.

—Madhu Rajaraman

The CDC estimates that about one in 68 US children has autism spectrum disorder, according to findings published in the March 28 issue of Morbidity and Mortality Weekly Report Surveillance Summaries. This prevalence is a 30% increase from the CDC’s estimate of one in 88 children using 2008 data.

The findings also show that autism spectrum disorder continues to be more prevalent in boys than in girls: one in 42 boys had autism spectrum disorder in the latest report, compared with one in 189 girls.

The increased prevalence could be attributed to improved clinician identification of autism, a growing number of autistic children with average to above-average intellectual ability, or a combination of both factors, said Coleen Boyle, PhD, Director of the CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD).

The CDC analyzed 2010 data collected by its Autism and Developmental Disabilities Monitoring (ADDM) Network, which provides population-based estimates of autism spectrum disorder prevalence in children age 8 at 11 sites in the United States based on records from community sources that diagnose and provide services to children with developmental disabilities.

Of the 11 sites studied, seven had information available on the intellectual ability of at least 70% of children with autism spectrum disorder. Of the 3,604 children for whom data were available, 31% were classified as having intellectual disability (IQ of 70 or lower), 23% were considered borderline (IQ = 71 to 85), and 46% had IQ scores of greater than 85, considered average or above average intellectual ability.

“We recognize now that autism is a spectrum, no longer limited to the severely affected,” said Marshalyn Yeargin-Allsopp, MD, Chief of the Developmental Disabilities branch of NCBDDD. “There are children with higher IQs being diagnosed who may not even be receiving special education services, and the numbers may reflect that.”

Non-Hispanic white children were 30% more likely to be diagnosed with autism spectrum disorder than were non-Hispanic black children and about 50% more likely to be diagnosed with autism spectrum disorder than were Hispanic children.

Dr. Boyle stressed the importance of early screening and identification of autism spectrum disorder in children (it can be diagnosed by the time a child reaches age 2) and urged parents to take action if a child shows any signs of developmental delays.

“Community leaders, health professionals, educators, and childcare providers should use these data to ensure that children with autism spectrum disorder are identified as early as possible and connected to the services they need,” said Dr. Boyle.

To help promote early intervention in autism spectrum disorder, the CDC will be launching an awareness initiative called “Birth to Five, Watch Me Thrive,” which aims to provide parents, teachers, and community members with information and resources about developmental milestones and screening for autism.

“Most children with autism are not diagnosed until after age 4,” said Dr. Boyle. “The CDC will continue to promote early identification and research. The earlier a child is identified and connected with services, the better.”

The CDC cited several limitations to the report. First, the surveillance sites were not selected to be representative of the entire United States. Second, population denominators used for this report were based on the 2010 decennial census. Comparisons with previous ADDM findings thus should be interpreted with caution because ADDM reports from nondecennial surveillance years are likely influenced by greater error in the population denominators used for those previous surveillance years, which were based on postcensus estimates. Third, three of the nine sites with access to review children’s education records did not receive permission to do so in all school districts within the site’s overall surveillance area. Fourth, findings that address intellectual ability might not be generalizable to all ADDM sites. Finally, race and ethnicity are presented in broad terms and should not be interpreted as generalizable to all persons within those categories.

—Madhu Rajaraman

The CDC estimates that about one in 68 US children has autism spectrum disorder, according to findings published in the March 28 issue of Morbidity and Mortality Weekly Report Surveillance Summaries. This prevalence is a 30% increase from the CDC’s estimate of one in 88 children using 2008 data.

The findings also show that autism spectrum disorder continues to be more prevalent in boys than in girls: one in 42 boys had autism spectrum disorder in the latest report, compared with one in 189 girls.

The increased prevalence could be attributed to improved clinician identification of autism, a growing number of autistic children with average to above-average intellectual ability, or a combination of both factors, said Coleen Boyle, PhD, Director of the CDC’s National Center on Birth Defects and Developmental Disabilities (NCBDDD).

The CDC analyzed 2010 data collected by its Autism and Developmental Disabilities Monitoring (ADDM) Network, which provides population-based estimates of autism spectrum disorder prevalence in children age 8 at 11 sites in the United States based on records from community sources that diagnose and provide services to children with developmental disabilities.

Of the 11 sites studied, seven had information available on the intellectual ability of at least 70% of children with autism spectrum disorder. Of the 3,604 children for whom data were available, 31% were classified as having intellectual disability (IQ of 70 or lower), 23% were considered borderline (IQ = 71 to 85), and 46% had IQ scores of greater than 85, considered average or above average intellectual ability.

“We recognize now that autism is a spectrum, no longer limited to the severely affected,” said Marshalyn Yeargin-Allsopp, MD, Chief of the Developmental Disabilities branch of NCBDDD. “There are children with higher IQs being diagnosed who may not even be receiving special education services, and the numbers may reflect that.”

Non-Hispanic white children were 30% more likely to be diagnosed with autism spectrum disorder than were non-Hispanic black children and about 50% more likely to be diagnosed with autism spectrum disorder than were Hispanic children.

Dr. Boyle stressed the importance of early screening and identification of autism spectrum disorder in children (it can be diagnosed by the time a child reaches age 2) and urged parents to take action if a child shows any signs of developmental delays.

“Community leaders, health professionals, educators, and childcare providers should use these data to ensure that children with autism spectrum disorder are identified as early as possible and connected to the services they need,” said Dr. Boyle.

To help promote early intervention in autism spectrum disorder, the CDC will be launching an awareness initiative called “Birth to Five, Watch Me Thrive,” which aims to provide parents, teachers, and community members with information and resources about developmental milestones and screening for autism.

“Most children with autism are not diagnosed until after age 4,” said Dr. Boyle. “The CDC will continue to promote early identification and research. The earlier a child is identified and connected with services, the better.”

The CDC cited several limitations to the report. First, the surveillance sites were not selected to be representative of the entire United States. Second, population denominators used for this report were based on the 2010 decennial census. Comparisons with previous ADDM findings thus should be interpreted with caution because ADDM reports from nondecennial surveillance years are likely influenced by greater error in the population denominators used for those previous surveillance years, which were based on postcensus estimates. Third, three of the nine sites with access to review children’s education records did not receive permission to do so in all school districts within the site’s overall surveillance area. Fourth, findings that address intellectual ability might not be generalizable to all ADDM sites. Finally, race and ethnicity are presented in broad terms and should not be interpreted as generalizable to all persons within those categories.

—Madhu Rajaraman

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

Researchers advise physicians to discuss the risks with women who have epilepsy and are of childbearing potential.

BALTIMORE—Fetal exposure to the antiepileptic drug (AED) valproate increases a child’s risk of autism and impairs his or her IQ until the age of 6, according to two studies presented at the 65th Annual Meeting of the American Epilepsy Society.

Children born to mothers on valproate monotherapy have a risk of childhood autism that is five times greater than that of children without prenatal exposure to the drug. In addition, children’s IQs are negatively associated with valproate dose, but not with carbamazepine, lamotrigine, or phenytoin.

Increased Risk of Autism
Previous research in animals and small studies involving humans have suggested that valproate treatment during pregnancy was associated with an increased risk of autism in the child.

To investigate this link, Jakob Christensen, PhD, a consultant neurologist at Aarhus University Hospital in Denmark, carried out a population-based cohort study. Using the Danish Civil Registration System, he identified 655,691 children born to 428,431 mothers between 1996 and 2006.
He looked to the Danish Prescription Register to identify women who had filled prescriptions for valproate from 30 days before the estimated date of conception to the day of birth.

Dr. Christensen also used the Danish Psychiatric Register to identify children diagnosed with an autism spectrum disorder and focused particularly on the subgroup that had been diagnosed with childhood autism. He and his colleagues then estimated the risk of autism in children born to mothers who used valproate during pregnancy and adjusted the risk estimates for parental psychiatric history, maternal age, and gender of the child.

Children born after prenatal exposure to valproate had more than twice the risk of an autism spectrum disorder than those without such exposure, according to the investigators. The risk of an autism spectrum disorder was 2.6 following valproate monotherapy and 2.5 following valproate polytherapy. The risk of childhood autism in children with prenatal exposure to valproate was 4.1 following valproate monotherapy and 6.8 following valproate polytherapy.

"Stopping any anticonvulsant medication poses a danger,” Dr. Christensen commented. “Women taking valproate who are contemplating pregnancy should consult with their doctors about the possibility of transitioning to another drug or reducing the dosage of their present medication when that isn’t possible.”

NeurodevelopmentalEffects of AEDs
Kimford Meador, MD, Director of the Emory Epilepsy Center and Professor of Neurology at Emory University in Atlanta, has directed the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. His preliminary analysis indicated that fetal exposure to valproate impaired children’s IQ at age 3. Dr. Meador and his colleagues conducted a new analysis to determine whether valproate’s effects on IQ continued until age 6.

The NEAD study enrolled pregnant women with epilepsy on AED monotherapy from 1999 to 2004. It aims to examine the long-term neurodevelopmental effects of four common AEDs: carbamazepine, lamotrigine, phenytoin, and valproate. The primary outcome for Dr. Meador’s new analysis was IQ at age 6, as measured by the Differential Ability Scale (DAS). The team also performed a secondary analysis of verbal and nonverbal cluster scores from the DAS. The sample size was 310 children.

Dr. Meador found that child IQ was lower with valproate exposure than it was with exposure to any of the other AEDs. The adjusted mean IQ for children born after valproate exposure was 97. By contrast, the adjusted mean IQ for carbamazepine was 105, the adjusted mean IQ for lamotrigine was 108, and the adjusted mean IQ for phenytoin was 108. The verbal cluster score was less than the nonverbal cluster score for lamotrigine and valproate.

In children born after fetal exposure to valproate, the risks of low IQ and decreased verbal and nonverbal abilities are dose-dependent. However, “the dose-dependent effect is not seen with other AEDs on any of these factors,” said Dr. Meador.

Women of childbearing potential need to understand the risks that valproate entails, said Dr. Meador. “In my mind, it’s a very poor first choice for women of childbearing potential.

“The quandary is that there’s a subgroup of women with primary generalized epilepsy who will only respond to valproate,” he added. “Because it is not possible to predict which women are in this category, neurologists should treat them with another AED before trying valproate,” said Dr. Meador.

To hear an audiocast related to this news article, please click here.

Researchers advise physicians to discuss the risks with women who have epilepsy and are of childbearing potential.

BALTIMORE—Fetal exposure to the antiepileptic drug (AED) valproate increases a child’s risk of autism and impairs his or her IQ until the age of 6, according to two studies presented at the 65th Annual Meeting of the American Epilepsy Society.

Children born to mothers on valproate monotherapy have a risk of childhood autism that is five times greater than that of children without prenatal exposure to the drug. In addition, children’s IQs are negatively associated with valproate dose, but not with carbamazepine, lamotrigine, or phenytoin.

Increased Risk of Autism
Previous research in animals and small studies involving humans have suggested that valproate treatment during pregnancy was associated with an increased risk of autism in the child.

To investigate this link, Jakob Christensen, PhD, a consultant neurologist at Aarhus University Hospital in Denmark, carried out a population-based cohort study. Using the Danish Civil Registration System, he identified 655,691 children born to 428,431 mothers between 1996 and 2006.
He looked to the Danish Prescription Register to identify women who had filled prescriptions for valproate from 30 days before the estimated date of conception to the day of birth.

Dr. Christensen also used the Danish Psychiatric Register to identify children diagnosed with an autism spectrum disorder and focused particularly on the subgroup that had been diagnosed with childhood autism. He and his colleagues then estimated the risk of autism in children born to mothers who used valproate during pregnancy and adjusted the risk estimates for parental psychiatric history, maternal age, and gender of the child.

Children born after prenatal exposure to valproate had more than twice the risk of an autism spectrum disorder than those without such exposure, according to the investigators. The risk of an autism spectrum disorder was 2.6 following valproate monotherapy and 2.5 following valproate polytherapy. The risk of childhood autism in children with prenatal exposure to valproate was 4.1 following valproate monotherapy and 6.8 following valproate polytherapy.

"Stopping any anticonvulsant medication poses a danger,” Dr. Christensen commented. “Women taking valproate who are contemplating pregnancy should consult with their doctors about the possibility of transitioning to another drug or reducing the dosage of their present medication when that isn’t possible.”

NeurodevelopmentalEffects of AEDs
Kimford Meador, MD, Director of the Emory Epilepsy Center and Professor of Neurology at Emory University in Atlanta, has directed the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. His preliminary analysis indicated that fetal exposure to valproate impaired children’s IQ at age 3. Dr. Meador and his colleagues conducted a new analysis to determine whether valproate’s effects on IQ continued until age 6.

The NEAD study enrolled pregnant women with epilepsy on AED monotherapy from 1999 to 2004. It aims to examine the long-term neurodevelopmental effects of four common AEDs: carbamazepine, lamotrigine, phenytoin, and valproate. The primary outcome for Dr. Meador’s new analysis was IQ at age 6, as measured by the Differential Ability Scale (DAS). The team also performed a secondary analysis of verbal and nonverbal cluster scores from the DAS. The sample size was 310 children.

Dr. Meador found that child IQ was lower with valproate exposure than it was with exposure to any of the other AEDs. The adjusted mean IQ for children born after valproate exposure was 97. By contrast, the adjusted mean IQ for carbamazepine was 105, the adjusted mean IQ for lamotrigine was 108, and the adjusted mean IQ for phenytoin was 108. The verbal cluster score was less than the nonverbal cluster score for lamotrigine and valproate.

In children born after fetal exposure to valproate, the risks of low IQ and decreased verbal and nonverbal abilities are dose-dependent. However, “the dose-dependent effect is not seen with other AEDs on any of these factors,” said Dr. Meador.

Women of childbearing potential need to understand the risks that valproate entails, said Dr. Meador. “In my mind, it’s a very poor first choice for women of childbearing potential.

“The quandary is that there’s a subgroup of women with primary generalized epilepsy who will only respond to valproate,” he added. “Because it is not possible to predict which women are in this category, neurologists should treat them with another AED before trying valproate,” said Dr. Meador.

To hear an audiocast related to this news article, please click here.

Researchers advise physicians to discuss the risks with women who have epilepsy and are of childbearing potential.

BALTIMORE—Fetal exposure to the antiepileptic drug (AED) valproate increases a child’s risk of autism and impairs his or her IQ until the age of 6, according to two studies presented at the 65th Annual Meeting of the American Epilepsy Society.

Children born to mothers on valproate monotherapy have a risk of childhood autism that is five times greater than that of children without prenatal exposure to the drug. In addition, children’s IQs are negatively associated with valproate dose, but not with carbamazepine, lamotrigine, or phenytoin.

Increased Risk of Autism
Previous research in animals and small studies involving humans have suggested that valproate treatment during pregnancy was associated with an increased risk of autism in the child.

To investigate this link, Jakob Christensen, PhD, a consultant neurologist at Aarhus University Hospital in Denmark, carried out a population-based cohort study. Using the Danish Civil Registration System, he identified 655,691 children born to 428,431 mothers between 1996 and 2006.
He looked to the Danish Prescription Register to identify women who had filled prescriptions for valproate from 30 days before the estimated date of conception to the day of birth.

Dr. Christensen also used the Danish Psychiatric Register to identify children diagnosed with an autism spectrum disorder and focused particularly on the subgroup that had been diagnosed with childhood autism. He and his colleagues then estimated the risk of autism in children born to mothers who used valproate during pregnancy and adjusted the risk estimates for parental psychiatric history, maternal age, and gender of the child.

Children born after prenatal exposure to valproate had more than twice the risk of an autism spectrum disorder than those without such exposure, according to the investigators. The risk of an autism spectrum disorder was 2.6 following valproate monotherapy and 2.5 following valproate polytherapy. The risk of childhood autism in children with prenatal exposure to valproate was 4.1 following valproate monotherapy and 6.8 following valproate polytherapy.

"Stopping any anticonvulsant medication poses a danger,” Dr. Christensen commented. “Women taking valproate who are contemplating pregnancy should consult with their doctors about the possibility of transitioning to another drug or reducing the dosage of their present medication when that isn’t possible.”

NeurodevelopmentalEffects of AEDs
Kimford Meador, MD, Director of the Emory Epilepsy Center and Professor of Neurology at Emory University in Atlanta, has directed the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study. His preliminary analysis indicated that fetal exposure to valproate impaired children’s IQ at age 3. Dr. Meador and his colleagues conducted a new analysis to determine whether valproate’s effects on IQ continued until age 6.

The NEAD study enrolled pregnant women with epilepsy on AED monotherapy from 1999 to 2004. It aims to examine the long-term neurodevelopmental effects of four common AEDs: carbamazepine, lamotrigine, phenytoin, and valproate. The primary outcome for Dr. Meador’s new analysis was IQ at age 6, as measured by the Differential Ability Scale (DAS). The team also performed a secondary analysis of verbal and nonverbal cluster scores from the DAS. The sample size was 310 children.

Dr. Meador found that child IQ was lower with valproate exposure than it was with exposure to any of the other AEDs. The adjusted mean IQ for children born after valproate exposure was 97. By contrast, the adjusted mean IQ for carbamazepine was 105, the adjusted mean IQ for lamotrigine was 108, and the adjusted mean IQ for phenytoin was 108. The verbal cluster score was less than the nonverbal cluster score for lamotrigine and valproate.

In children born after fetal exposure to valproate, the risks of low IQ and decreased verbal and nonverbal abilities are dose-dependent. However, “the dose-dependent effect is not seen with other AEDs on any of these factors,” said Dr. Meador.

Women of childbearing potential need to understand the risks that valproate entails, said Dr. Meador. “In my mind, it’s a very poor first choice for women of childbearing potential.

“The quandary is that there’s a subgroup of women with primary generalized epilepsy who will only respond to valproate,” he added. “Because it is not possible to predict which women are in this category, neurologists should treat them with another AED before trying valproate,” said Dr. Meador.

To hear an audiocast related to this news article, please click here.

When 150 children, 84 with epilepsy, were exposed to 15 minutes of three-dimensional TV, no seizures occurred—but some important EEG changes were observed.

BALTIMORE—Preliminary results from an ongoing study indicate that three-dimensional (3D) TV does not pose a significant safety hazard for children with epilepsy, researchers reported at the 65th Annual Meeting of the American Epilepsy Society.

The risk of suffering a seizure by watching 3D TV is very low, but not zero, and we think that it’s probably basically linked not to the 3D technique itself but to the content of the video,” said study coauthor Gerhard Kluger, MD, of Schön Klinik, Vogtareuth, Germany, and Paracelsus Medical University, Salzburg, Austria.

Although the electronics manufacturer Samsung has warned consumers that 3D TV may cause epileptic seizures, no previous research has investigated this possibility in children, especially in children with epilepsy, Dr. Kluger said. His study team, together with Herbert Plischke, MD, Managing Director of the Generation Research Program at the University of Munich, and other researchers, are doing so through a study that will eventually include at least 200 children with the condition.

The researchers are providing each study participant with two EEGs—a 20-minute, routine EEG that includes photo stimulation, and an EEG performed while the participant views 15 minutes of 3D video footage from the film Ice Age 3. Participants view this footage on a 50-inch 3D plasma TV while sitting about 2 meters away and wearing 3D shutter glasses.

The researchers have compiled data on 150 children and adolescents—84 with epilepsy and 66 with other neurologic conditions, such as headache, that suggested the risk of epilepsy. Participants had a mean age of 12, and 77 (51%) were male.

“We did not observe a single patient suffering a seizure during the 15 minutes” of 3D viewing, Dr. Kluger said. However, one participant with epilepsy, who typically experiences seizures four times per day, had a seizure two minutes following the viewing. “We cannot be sure it was linked to the 3D viewing, but we cannot exclude that a longer observation period might cause harm,” said Dr. Kluger.

In addition, three participants—all of whom were between the ages of 14 and 16 and had idiopathic generalized epilepsy—experienced a paroxysm increase of more than 100% during the 3D viewing. None of these adolescents made any complaints, showed any clinical signs, or experienced any subclinical seizures during the viewing.

“Interestingly, one boy with the diagnosis of ADHD (under treatment with methylphenidate) without a history of seizures showed a normal routine EEG with no epileptiform spikes but some spike during 3D viewing,” Dr. Kluger told Neurology Reviews.

It is likely that the observed paroxysm increases were triggered by non-3D content of the film, such as surprises and motion, according to Dr. Kluger. Laboratory time constraints necessitated the 15-minute period for 3D viewing and prevented researchers from comparing children’s reactions to 3D TV with their reactions to normal TV, he added.  The study team is planning to perform research with a longer 3D viewing period and different video material in the future.

Most participants experienced a significant increase in lambda waves during the viewing period. The researchers attributed this increase to normal augmentation of saccadic eye movements.

Although 15 children with no history of seizures were photosensitive, as indicated by photoparoxysmal reactions during the pre-viewing EEG, no child showed any paroxysmal increase while viewing 3D. “3D seems to be no special problem for this population—at least with the 3D technology and the method we have used so far,” Dr. Kluger said.

In 10 patients with epilepsy, there was a reduction in the frequency of epileptiform activity during the 3D viewing. “This is not unusual, and it may be easily explained by an increase in alertness” during the viewing, Dr. Kluger noted. “Typically, if a child with epilepsy is alert, then he or she doesn’t seize so often.”

Seventeen percent of the children complained of dizziness, headache, or nausea. “That’s quite a lot,” Dr. Kluger said. “And my impression is that the older the children, the more likely they didn’t like the 3D.

 “I think most of the children can go home and go to the video and watch it, but in some there’s doubt,” Dr. Kluger concluded. “Maybe when we study 200 children with epilepsy, we can answer these questions more precisely.”

Apart from the study, Dr. Kluger said, “I think we will continue offering this simulation for the parents, because they go home happy there was no reaction.” He also emphasized, “Children with epilepsy should do the same as children without epilepsy as much as possible.”          

When 150 children, 84 with epilepsy, were exposed to 15 minutes of three-dimensional TV, no seizures occurred—but some important EEG changes were observed.

BALTIMORE—Preliminary results from an ongoing study indicate that three-dimensional (3D) TV does not pose a significant safety hazard for children with epilepsy, researchers reported at the 65th Annual Meeting of the American Epilepsy Society.

The risk of suffering a seizure by watching 3D TV is very low, but not zero, and we think that it’s probably basically linked not to the 3D technique itself but to the content of the video,” said study coauthor Gerhard Kluger, MD, of Schön Klinik, Vogtareuth, Germany, and Paracelsus Medical University, Salzburg, Austria.

Although the electronics manufacturer Samsung has warned consumers that 3D TV may cause epileptic seizures, no previous research has investigated this possibility in children, especially in children with epilepsy, Dr. Kluger said. His study team, together with Herbert Plischke, MD, Managing Director of the Generation Research Program at the University of Munich, and other researchers, are doing so through a study that will eventually include at least 200 children with the condition.

The researchers are providing each study participant with two EEGs—a 20-minute, routine EEG that includes photo stimulation, and an EEG performed while the participant views 15 minutes of 3D video footage from the film Ice Age 3. Participants view this footage on a 50-inch 3D plasma TV while sitting about 2 meters away and wearing 3D shutter glasses.

The researchers have compiled data on 150 children and adolescents—84 with epilepsy and 66 with other neurologic conditions, such as headache, that suggested the risk of epilepsy. Participants had a mean age of 12, and 77 (51%) were male.

“We did not observe a single patient suffering a seizure during the 15 minutes” of 3D viewing, Dr. Kluger said. However, one participant with epilepsy, who typically experiences seizures four times per day, had a seizure two minutes following the viewing. “We cannot be sure it was linked to the 3D viewing, but we cannot exclude that a longer observation period might cause harm,” said Dr. Kluger.

In addition, three participants—all of whom were between the ages of 14 and 16 and had idiopathic generalized epilepsy—experienced a paroxysm increase of more than 100% during the 3D viewing. None of these adolescents made any complaints, showed any clinical signs, or experienced any subclinical seizures during the viewing.

“Interestingly, one boy with the diagnosis of ADHD (under treatment with methylphenidate) without a history of seizures showed a normal routine EEG with no epileptiform spikes but some spike during 3D viewing,” Dr. Kluger told Neurology Reviews.

It is likely that the observed paroxysm increases were triggered by non-3D content of the film, such as surprises and motion, according to Dr. Kluger. Laboratory time constraints necessitated the 15-minute period for 3D viewing and prevented researchers from comparing children’s reactions to 3D TV with their reactions to normal TV, he added.  The study team is planning to perform research with a longer 3D viewing period and different video material in the future.

Most participants experienced a significant increase in lambda waves during the viewing period. The researchers attributed this increase to normal augmentation of saccadic eye movements.

Although 15 children with no history of seizures were photosensitive, as indicated by photoparoxysmal reactions during the pre-viewing EEG, no child showed any paroxysmal increase while viewing 3D. “3D seems to be no special problem for this population—at least with the 3D technology and the method we have used so far,” Dr. Kluger said.

In 10 patients with epilepsy, there was a reduction in the frequency of epileptiform activity during the 3D viewing. “This is not unusual, and it may be easily explained by an increase in alertness” during the viewing, Dr. Kluger noted. “Typically, if a child with epilepsy is alert, then he or she doesn’t seize so often.”

Seventeen percent of the children complained of dizziness, headache, or nausea. “That’s quite a lot,” Dr. Kluger said. “And my impression is that the older the children, the more likely they didn’t like the 3D.

 “I think most of the children can go home and go to the video and watch it, but in some there’s doubt,” Dr. Kluger concluded. “Maybe when we study 200 children with epilepsy, we can answer these questions more precisely.”

Apart from the study, Dr. Kluger said, “I think we will continue offering this simulation for the parents, because they go home happy there was no reaction.” He also emphasized, “Children with epilepsy should do the same as children without epilepsy as much as possible.”          

When 150 children, 84 with epilepsy, were exposed to 15 minutes of three-dimensional TV, no seizures occurred—but some important EEG changes were observed.

BALTIMORE—Preliminary results from an ongoing study indicate that three-dimensional (3D) TV does not pose a significant safety hazard for children with epilepsy, researchers reported at the 65th Annual Meeting of the American Epilepsy Society.

The risk of suffering a seizure by watching 3D TV is very low, but not zero, and we think that it’s probably basically linked not to the 3D technique itself but to the content of the video,” said study coauthor Gerhard Kluger, MD, of Schön Klinik, Vogtareuth, Germany, and Paracelsus Medical University, Salzburg, Austria.

Although the electronics manufacturer Samsung has warned consumers that 3D TV may cause epileptic seizures, no previous research has investigated this possibility in children, especially in children with epilepsy, Dr. Kluger said. His study team, together with Herbert Plischke, MD, Managing Director of the Generation Research Program at the University of Munich, and other researchers, are doing so through a study that will eventually include at least 200 children with the condition.

The researchers are providing each study participant with two EEGs—a 20-minute, routine EEG that includes photo stimulation, and an EEG performed while the participant views 15 minutes of 3D video footage from the film Ice Age 3. Participants view this footage on a 50-inch 3D plasma TV while sitting about 2 meters away and wearing 3D shutter glasses.

The researchers have compiled data on 150 children and adolescents—84 with epilepsy and 66 with other neurologic conditions, such as headache, that suggested the risk of epilepsy. Participants had a mean age of 12, and 77 (51%) were male.

“We did not observe a single patient suffering a seizure during the 15 minutes” of 3D viewing, Dr. Kluger said. However, one participant with epilepsy, who typically experiences seizures four times per day, had a seizure two minutes following the viewing. “We cannot be sure it was linked to the 3D viewing, but we cannot exclude that a longer observation period might cause harm,” said Dr. Kluger.

In addition, three participants—all of whom were between the ages of 14 and 16 and had idiopathic generalized epilepsy—experienced a paroxysm increase of more than 100% during the 3D viewing. None of these adolescents made any complaints, showed any clinical signs, or experienced any subclinical seizures during the viewing.

“Interestingly, one boy with the diagnosis of ADHD (under treatment with methylphenidate) without a history of seizures showed a normal routine EEG with no epileptiform spikes but some spike during 3D viewing,” Dr. Kluger told Neurology Reviews.

It is likely that the observed paroxysm increases were triggered by non-3D content of the film, such as surprises and motion, according to Dr. Kluger. Laboratory time constraints necessitated the 15-minute period for 3D viewing and prevented researchers from comparing children’s reactions to 3D TV with their reactions to normal TV, he added.  The study team is planning to perform research with a longer 3D viewing period and different video material in the future.

Most participants experienced a significant increase in lambda waves during the viewing period. The researchers attributed this increase to normal augmentation of saccadic eye movements.

Although 15 children with no history of seizures were photosensitive, as indicated by photoparoxysmal reactions during the pre-viewing EEG, no child showed any paroxysmal increase while viewing 3D. “3D seems to be no special problem for this population—at least with the 3D technology and the method we have used so far,” Dr. Kluger said.

In 10 patients with epilepsy, there was a reduction in the frequency of epileptiform activity during the 3D viewing. “This is not unusual, and it may be easily explained by an increase in alertness” during the viewing, Dr. Kluger noted. “Typically, if a child with epilepsy is alert, then he or she doesn’t seize so often.”

Seventeen percent of the children complained of dizziness, headache, or nausea. “That’s quite a lot,” Dr. Kluger said. “And my impression is that the older the children, the more likely they didn’t like the 3D.

 “I think most of the children can go home and go to the video and watch it, but in some there’s doubt,” Dr. Kluger concluded. “Maybe when we study 200 children with epilepsy, we can answer these questions more precisely.”

Apart from the study, Dr. Kluger said, “I think we will continue offering this simulation for the parents, because they go home happy there was no reaction.” He also emphasized, “Children with epilepsy should do the same as children without epilepsy as much as possible.”          

Men show higher rates of amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI) than women, researchers reported in the January 31 Neurology. Starting in 2004, a cohort of Olmsted County, Minnesota, residents ages 70 to 89 underwent baseline and 15-month interval evaluations to assess their cognitive status. Of the 1,450 participants who were cognitively normal at baseline, 296 developed MCI, with an age- and sex-standardized incidence rate of 63.6 (per 1,000 person years) overall. Men (72.4) showed higher rates of MCI than women (57.3), and this trend continued for both aMCI and naMCI. Participants with fewer years of education had higher rates of MCI. “Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for aMCI and naMCI, and in men and women,” the study authors stated.

Infants who are eventually diagnosed with autism spectrum disorders (ASD) show abnormal development of white matter pathways starting as early as 6 months of age, according to a study published in the February 17 online American Journal of Psychiatry. Researchers analyzed imaging results from 92 high-risk infants who had siblings with autism. The participants underwent diffusion tensor imaging at 6 months, 12 months, and 24 months. After characterizing the white matter fiber tracts of the 28 infants who met criteria for ASD at 24 months and the 64 infants who did not meet the criteria, the investigators found notable differences in the infants’ development. Compared with the 64 infants who did not develop ASD, infants who had ASD had different white matter development for 12 of the 15 brain pathways studied. “These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life,” the researchers concluded.
Epilepsy surgery has long-term beneficial effects on patients’ seizure control and overall quality of life, according to research published in the February 7 online Epilepsia. Patients who underwent epilepsy surgery by Sidney Goldring, MD, from 1967 to 1990 were followed up for a mean duration of 26 years. Of the 361 patients who had epilepsy surgery, 117 completed follow-up interviews, and 80% reported a higher quality of life on the Quality of Life in Epilepsy (QOLIE-31) questionnaire after surgery. In addition, an association was observed between seizure freedom and better quality of life, and patients who underwent temporal lobe resection showed better seizure outcomes than those who had different procedures. Considering that the positive outcomes of epilepsy surgery from decades ago seem sustainable, the researchers said they are “optimistic that the outcomes from modern epilepsy surgery will be even better and that our present enthusiasm for this treatment modality is not misplaced.”

Elderly nursing home residents show an increased mortality risk with higher doses of antipsychotic drugs, according to a study in the February 23 online BMJ. All 75,445 study participants were age 65 or older, lived in nursing homes from 2001 to 2005, and were new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone). After comparing 180-day risks of all-cause and cause-specific mortality by individual drug, the researchers found that users of haloperidol had an increased rate of mortality and users of quetiapine had a decreased risk of mortality, compared with users of risperidone. These effects were seen for all causes of mortality examined, remained after adjustment for dose, and were strongest immediately following the start of treatment. “There was no evidence that the treatment effect differed for patients with a diagnosis of dementia or behavioral disturbances,” noted the researchers. They added that although their findings do not prove causality, “….they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need.”  

Men show higher rates of amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI) than women, researchers reported in the January 31 Neurology. Starting in 2004, a cohort of Olmsted County, Minnesota, residents ages 70 to 89 underwent baseline and 15-month interval evaluations to assess their cognitive status. Of the 1,450 participants who were cognitively normal at baseline, 296 developed MCI, with an age- and sex-standardized incidence rate of 63.6 (per 1,000 person years) overall. Men (72.4) showed higher rates of MCI than women (57.3), and this trend continued for both aMCI and naMCI. Participants with fewer years of education had higher rates of MCI. “Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for aMCI and naMCI, and in men and women,” the study authors stated.

Infants who are eventually diagnosed with autism spectrum disorders (ASD) show abnormal development of white matter pathways starting as early as 6 months of age, according to a study published in the February 17 online American Journal of Psychiatry. Researchers analyzed imaging results from 92 high-risk infants who had siblings with autism. The participants underwent diffusion tensor imaging at 6 months, 12 months, and 24 months. After characterizing the white matter fiber tracts of the 28 infants who met criteria for ASD at 24 months and the 64 infants who did not meet the criteria, the investigators found notable differences in the infants’ development. Compared with the 64 infants who did not develop ASD, infants who had ASD had different white matter development for 12 of the 15 brain pathways studied. “These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life,” the researchers concluded.
Epilepsy surgery has long-term beneficial effects on patients’ seizure control and overall quality of life, according to research published in the February 7 online Epilepsia. Patients who underwent epilepsy surgery by Sidney Goldring, MD, from 1967 to 1990 were followed up for a mean duration of 26 years. Of the 361 patients who had epilepsy surgery, 117 completed follow-up interviews, and 80% reported a higher quality of life on the Quality of Life in Epilepsy (QOLIE-31) questionnaire after surgery. In addition, an association was observed between seizure freedom and better quality of life, and patients who underwent temporal lobe resection showed better seizure outcomes than those who had different procedures. Considering that the positive outcomes of epilepsy surgery from decades ago seem sustainable, the researchers said they are “optimistic that the outcomes from modern epilepsy surgery will be even better and that our present enthusiasm for this treatment modality is not misplaced.”

Elderly nursing home residents show an increased mortality risk with higher doses of antipsychotic drugs, according to a study in the February 23 online BMJ. All 75,445 study participants were age 65 or older, lived in nursing homes from 2001 to 2005, and were new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone). After comparing 180-day risks of all-cause and cause-specific mortality by individual drug, the researchers found that users of haloperidol had an increased rate of mortality and users of quetiapine had a decreased risk of mortality, compared with users of risperidone. These effects were seen for all causes of mortality examined, remained after adjustment for dose, and were strongest immediately following the start of treatment. “There was no evidence that the treatment effect differed for patients with a diagnosis of dementia or behavioral disturbances,” noted the researchers. They added that although their findings do not prove causality, “….they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need.”  

Men show higher rates of amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI) than women, researchers reported in the January 31 Neurology. Starting in 2004, a cohort of Olmsted County, Minnesota, residents ages 70 to 89 underwent baseline and 15-month interval evaluations to assess their cognitive status. Of the 1,450 participants who were cognitively normal at baseline, 296 developed MCI, with an age- and sex-standardized incidence rate of 63.6 (per 1,000 person years) overall. Men (72.4) showed higher rates of MCI than women (57.3), and this trend continued for both aMCI and naMCI. Participants with fewer years of education had higher rates of MCI. “Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for aMCI and naMCI, and in men and women,” the study authors stated.

Infants who are eventually diagnosed with autism spectrum disorders (ASD) show abnormal development of white matter pathways starting as early as 6 months of age, according to a study published in the February 17 online American Journal of Psychiatry. Researchers analyzed imaging results from 92 high-risk infants who had siblings with autism. The participants underwent diffusion tensor imaging at 6 months, 12 months, and 24 months. After characterizing the white matter fiber tracts of the 28 infants who met criteria for ASD at 24 months and the 64 infants who did not meet the criteria, the investigators found notable differences in the infants’ development. Compared with the 64 infants who did not develop ASD, infants who had ASD had different white matter development for 12 of the 15 brain pathways studied. “These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life,” the researchers concluded.
Epilepsy surgery has long-term beneficial effects on patients’ seizure control and overall quality of life, according to research published in the February 7 online Epilepsia. Patients who underwent epilepsy surgery by Sidney Goldring, MD, from 1967 to 1990 were followed up for a mean duration of 26 years. Of the 361 patients who had epilepsy surgery, 117 completed follow-up interviews, and 80% reported a higher quality of life on the Quality of Life in Epilepsy (QOLIE-31) questionnaire after surgery. In addition, an association was observed between seizure freedom and better quality of life, and patients who underwent temporal lobe resection showed better seizure outcomes than those who had different procedures. Considering that the positive outcomes of epilepsy surgery from decades ago seem sustainable, the researchers said they are “optimistic that the outcomes from modern epilepsy surgery will be even better and that our present enthusiasm for this treatment modality is not misplaced.”

Elderly nursing home residents show an increased mortality risk with higher doses of antipsychotic drugs, according to a study in the February 23 online BMJ. All 75,445 study participants were age 65 or older, lived in nursing homes from 2001 to 2005, and were new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone). After comparing 180-day risks of all-cause and cause-specific mortality by individual drug, the researchers found that users of haloperidol had an increased rate of mortality and users of quetiapine had a decreased risk of mortality, compared with users of risperidone. These effects were seen for all causes of mortality examined, remained after adjustment for dose, and were strongest immediately following the start of treatment. “There was no evidence that the treatment effect differed for patients with a diagnosis of dementia or behavioral disturbances,” noted the researchers. They added that although their findings do not prove causality, “….they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need.”  

A recent finding may indicate brain irritability or hypersensitivity in children with autism spectrum disorders.

BALTIMORE—The incidence of a photoparoxysmal response among children older than 15 with autism spectrum disorders (ASD) is 25%, which is much higher than that for younger children with ASD, according to a study presented at the 65th Annual Meeting of the American Epilepsy Society. When children in the sample population without epilepsy are excluded, the incidence of a photoparoxysmal response among children older than 15 with ASD is 29.4%.

Epilepsy and frequent interictal discharges are common among children with ASD. Photoparoxysmal responses are interictal EEG discharges correlated with generalized, photosensitive epilepsy. A flashing strobe light, for example, can trigger a photoparoxysmal response in a predisposed individual. “The brain picks up that stimulus through the eye, and for some children, it can cause an abnormal brainwave pattern,” explained Jill Miller-Horn, MD, an epilepsy fellow at Children’s Hospital Boston.

“We already know that abnormal brainwave responses to flashing light can be associated with epilepsy. You might be familiar with what happened in Japan with the Pokemon cartoon, where there was bright, flashing colored light on the screen and hundreds of children then had seizures,” she added. Dr. Miller-Horn and her colleagues decided to study photoparoxysmal responses to photic stimulation in children with ASD, a topic that she said no researchers had previously investigated.

Identifying a Cohort of Children With ASD
The team conducted a retrospective pilot study of children with ASD to determine the rate of the photoparoxysmal response caused by intermittent photic stimulation during EEG studies at Children’s Hospital Boston. The investigators searched medical records that identified 333 children with ASD who were treated at the hospital between December 2010 and May 2011.

Of these children, 206 had had EEGs. In the group of 206 children, 118 had comorbid ASD and epilepsy, and 88 had ASD without seizures. Intermittent photic stimulation was part of 177 children’s EEG studies. The group of 177 included 138 boys and 39 girls, and the children’s average age was 9.

Photoparoxysmal Response Increases in Adolescence
A photoparoxysmal response was elicited in 13 of the 177 children who received photic stimulation during their EEGs. The 7.3% incidence of a photoparoxysmal response in children with ASD was within the range previously reported in the normal population, according to Dr. Miller-Horn. “Our study found that in the ASD population, there is an association between the photoparoxysmal response and epilepsy, as has been previously reported in children with epilepsy without ASD,” she said.

“When we subdivided these children with autism by age, we found that there’s an increase in the photoparoxysmal response as they entered adolescence,” commented Dr. Miller-Horn. The meaning of the result is unclear, “but it’s a difference from the normal population, and it’s a difference from other children who have epilepsy,” she added.

“This is a new finding that may be a clue to the pathophysiology for the high rate of ASD and epilepsy comorbidity,” Dr. Miller-Horn continued. “There may be irritability or hypersensitivity in the brain for children with autism that’s being revealed with the clue that they are more photosensitive.”

Large-scale and prospective studies are needed to confirm the trend, according to the investigators. Further studies could reveal the findings’ significance in the pathophysiology of epilepsy in children with ASD.

A recent finding may indicate brain irritability or hypersensitivity in children with autism spectrum disorders.

BALTIMORE—The incidence of a photoparoxysmal response among children older than 15 with autism spectrum disorders (ASD) is 25%, which is much higher than that for younger children with ASD, according to a study presented at the 65th Annual Meeting of the American Epilepsy Society. When children in the sample population without epilepsy are excluded, the incidence of a photoparoxysmal response among children older than 15 with ASD is 29.4%.

Epilepsy and frequent interictal discharges are common among children with ASD. Photoparoxysmal responses are interictal EEG discharges correlated with generalized, photosensitive epilepsy. A flashing strobe light, for example, can trigger a photoparoxysmal response in a predisposed individual. “The brain picks up that stimulus through the eye, and for some children, it can cause an abnormal brainwave pattern,” explained Jill Miller-Horn, MD, an epilepsy fellow at Children’s Hospital Boston.

“We already know that abnormal brainwave responses to flashing light can be associated with epilepsy. You might be familiar with what happened in Japan with the Pokemon cartoon, where there was bright, flashing colored light on the screen and hundreds of children then had seizures,” she added. Dr. Miller-Horn and her colleagues decided to study photoparoxysmal responses to photic stimulation in children with ASD, a topic that she said no researchers had previously investigated.

Identifying a Cohort of Children With ASD
The team conducted a retrospective pilot study of children with ASD to determine the rate of the photoparoxysmal response caused by intermittent photic stimulation during EEG studies at Children’s Hospital Boston. The investigators searched medical records that identified 333 children with ASD who were treated at the hospital between December 2010 and May 2011.

Of these children, 206 had had EEGs. In the group of 206 children, 118 had comorbid ASD and epilepsy, and 88 had ASD without seizures. Intermittent photic stimulation was part of 177 children’s EEG studies. The group of 177 included 138 boys and 39 girls, and the children’s average age was 9.

Photoparoxysmal Response Increases in Adolescence
A photoparoxysmal response was elicited in 13 of the 177 children who received photic stimulation during their EEGs. The 7.3% incidence of a photoparoxysmal response in children with ASD was within the range previously reported in the normal population, according to Dr. Miller-Horn. “Our study found that in the ASD population, there is an association between the photoparoxysmal response and epilepsy, as has been previously reported in children with epilepsy without ASD,” she said.

“When we subdivided these children with autism by age, we found that there’s an increase in the photoparoxysmal response as they entered adolescence,” commented Dr. Miller-Horn. The meaning of the result is unclear, “but it’s a difference from the normal population, and it’s a difference from other children who have epilepsy,” she added.

“This is a new finding that may be a clue to the pathophysiology for the high rate of ASD and epilepsy comorbidity,” Dr. Miller-Horn continued. “There may be irritability or hypersensitivity in the brain for children with autism that’s being revealed with the clue that they are more photosensitive.”

Large-scale and prospective studies are needed to confirm the trend, according to the investigators. Further studies could reveal the findings’ significance in the pathophysiology of epilepsy in children with ASD.

A recent finding may indicate brain irritability or hypersensitivity in children with autism spectrum disorders.

BALTIMORE—The incidence of a photoparoxysmal response among children older than 15 with autism spectrum disorders (ASD) is 25%, which is much higher than that for younger children with ASD, according to a study presented at the 65th Annual Meeting of the American Epilepsy Society. When children in the sample population without epilepsy are excluded, the incidence of a photoparoxysmal response among children older than 15 with ASD is 29.4%.

Epilepsy and frequent interictal discharges are common among children with ASD. Photoparoxysmal responses are interictal EEG discharges correlated with generalized, photosensitive epilepsy. A flashing strobe light, for example, can trigger a photoparoxysmal response in a predisposed individual. “The brain picks up that stimulus through the eye, and for some children, it can cause an abnormal brainwave pattern,” explained Jill Miller-Horn, MD, an epilepsy fellow at Children’s Hospital Boston.

“We already know that abnormal brainwave responses to flashing light can be associated with epilepsy. You might be familiar with what happened in Japan with the Pokemon cartoon, where there was bright, flashing colored light on the screen and hundreds of children then had seizures,” she added. Dr. Miller-Horn and her colleagues decided to study photoparoxysmal responses to photic stimulation in children with ASD, a topic that she said no researchers had previously investigated.

Identifying a Cohort of Children With ASD
The team conducted a retrospective pilot study of children with ASD to determine the rate of the photoparoxysmal response caused by intermittent photic stimulation during EEG studies at Children’s Hospital Boston. The investigators searched medical records that identified 333 children with ASD who were treated at the hospital between December 2010 and May 2011.

Of these children, 206 had had EEGs. In the group of 206 children, 118 had comorbid ASD and epilepsy, and 88 had ASD without seizures. Intermittent photic stimulation was part of 177 children’s EEG studies. The group of 177 included 138 boys and 39 girls, and the children’s average age was 9.

Photoparoxysmal Response Increases in Adolescence
A photoparoxysmal response was elicited in 13 of the 177 children who received photic stimulation during their EEGs. The 7.3% incidence of a photoparoxysmal response in children with ASD was within the range previously reported in the normal population, according to Dr. Miller-Horn. “Our study found that in the ASD population, there is an association between the photoparoxysmal response and epilepsy, as has been previously reported in children with epilepsy without ASD,” she said.

“When we subdivided these children with autism by age, we found that there’s an increase in the photoparoxysmal response as they entered adolescence,” commented Dr. Miller-Horn. The meaning of the result is unclear, “but it’s a difference from the normal population, and it’s a difference from other children who have epilepsy,” she added.

“This is a new finding that may be a clue to the pathophysiology for the high rate of ASD and epilepsy comorbidity,” Dr. Miller-Horn continued. “There may be irritability or hypersensitivity in the brain for children with autism that’s being revealed with the clue that they are more photosensitive.”

Large-scale and prospective studies are needed to confirm the trend, according to the investigators. Further studies could reveal the findings’ significance in the pathophysiology of epilepsy in children with ASD.

Researchers have found that having a transient ischemic attack (TIA) can reduce a person’s life expectancy up to 20%, according to a study published online November 10 in Stroke. “There is a lack of modern-day data quantifying the effect of TIA on survival, and recent data do not take into account expected survival,” the researchers commented. To investigate the impact of a TIA on survival, the investigators analyzed data from 22,157 patients hospitalized with a TIA, then estimated survival relative to the age- and sex-matched general population up to nine years after hospitalization. At one-year follow-up, 91.5% of TIA patients survived, compared with 95.0% expected survival in the general population; by nine-years follow-up, observed survival was 20% lower than expected. Older age, prior hospitalization for stroke (but not TIA), atrial fibrillation, and congestive heart failure significantly increased the risk of excess death in these patients.
Higher levels of urinary sodium excretion were associated with an increased risk of cardiovascular events, while lower levels were associated with cardiovascular death and hospitalization for congestive heart failure, according to a study published in the November 23 JAMA. “[Our objective was] to determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular events in patients with established cardiovascular disease or diabetes mellitus,” stated the researchers. The results of their observational analyses revealed that “compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all cardiovascular events.” In addition, a sodium excretion of less than 3 g per day was associated with increased risk of cardiovascular mortality and hospitalization for congestive heart failure, and a higher estimated potassium excretion was associated with a reduced risk of stroke.
Serum vitamin D levels are significantly lower in patients with recurrent inflammatory spinal cord disease, according to the results of a study published online November 14 in Archives of Neurology. The study authors performed a retrospective analysis evaluating vitamin D levels of 77 patients with monophasic and recurrent inflammatory spinal cord diseases. “Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race,” the investigators concluded. “This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.”
The FDA has approved AdaptiveStim with RestoreSensor neurostimulation system for the management of chronic pain. Unlike other implantable neurostimulation devices that require frequent manual adjustments with changes in body positions, the AdaptiveStim system (Medtronic, Inc; Minneapolis) automatically adapts stimulation levels to the needs of people with chronic back and/or leg pain by recognizing and remembering the correlation between a change in body position and the level of stimulation needed. The FDA’s approval was based on data from a clinical trial in which 86.5% of study participants with chronic pain experienced better pain relief and convenience when the system was turned on, compared with a control period when the participants manually adjusted neurostimulation settings; 80.3% of study participants also reported functional improvements, including improved comfort during position changes. The AdaptiveStim system was also approved for use in MRI head scans if recommended by a physician.
Brain overgrowth in boys with autism involves an abnormal excess number of neurons, according to the results of a small preliminary study published in the November 9 JAMA. “Autism often involves early brain overgrowth, including the prefrontal cortex,” the investigators stated. “Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.” To investigate whether this overgrowth in children with autism involves excess neuron numbers, the researchers compared postmortem tissue from the prefrontal cortex of seven boys (age range, 2 to 16) who had autism with postmortem tissue of six typically developing boys. They found that children with autism had 67% more neurons in the prefrontal cortex. “Brain weight in the autistic case differed from normative mean weight for age by a mean of 17.6%, while brains in controls differed by a mean of 0.2%,” the researchers reported.
A person’s stroke risk profile may also be helpful in predicting whether a person will develop memory problems and cognitive impairment later in life, according to a study published in the November 8 Neurology. “Participants included subjects without stroke at baseline … with at least two cognitive function assessments during the follow-up,” the researchers explained. “During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment.” The researchers determined that male sex, black race, less education, older age, and presence of left ventricular hypertrophy were related to the development of cognitive impairment. “Total Framingham Stroke Risk Profile score, elevated blood pressure, and left ventricular hypertrophy predict development of clinically significant cognitive dysfunction,” the investigators concluded. “Prevention and treatment of high blood pressure may be effective in preserving cognitive health.”
The FDA has approved Xarelto (rivaroxaban) to reduce the risk of stroke in people who have nonvalvular atrial fibrillation. Xarelto (Janssen Pharmaceuticals Inc; Titusville, New Jersey) is an oral anti-clotting drug that has also been approved to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery. The FDA’s approval was based on the results of a clinical trial with more than 14,000 patients that compared Xarelto with the anti-clotting drug warfarin; Xarelto proved similar to warfarin in its ability to prevent stroke. Bleeding was the most common adverse event reported by patients treated with Xarelto in this clinical trial, and the risk of bleeding was similar to the risk of bleeding associated with warfarin.
Patients with dementia who have a stroke have a higher likelihood of becoming disabled and being institutionalized, compared with patients who did not have dementia at the time of their stroke, according to a report in the November 1 Neurology. Investigators conducted a retrospective cohort study that included 9,304 patients with an acute ischemic stroke, 702 of whom had a history of dementia. “Patients with dementia were older (mean age, 81 vs 70), had more severe strokes, and were more likely to have atrial fibrillation than those without dementia,” the investigators determined. They also found that patients with dementia were slightly less likely to be admitted to a stroke unit, had a higher disability at discharge, and were less likely to be discharged to their prestroke place of residence. “In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system,” the researchers concluded.

Researchers have found that having a transient ischemic attack (TIA) can reduce a person’s life expectancy up to 20%, according to a study published online November 10 in Stroke. “There is a lack of modern-day data quantifying the effect of TIA on survival, and recent data do not take into account expected survival,” the researchers commented. To investigate the impact of a TIA on survival, the investigators analyzed data from 22,157 patients hospitalized with a TIA, then estimated survival relative to the age- and sex-matched general population up to nine years after hospitalization. At one-year follow-up, 91.5% of TIA patients survived, compared with 95.0% expected survival in the general population; by nine-years follow-up, observed survival was 20% lower than expected. Older age, prior hospitalization for stroke (but not TIA), atrial fibrillation, and congestive heart failure significantly increased the risk of excess death in these patients.
Higher levels of urinary sodium excretion were associated with an increased risk of cardiovascular events, while lower levels were associated with cardiovascular death and hospitalization for congestive heart failure, according to a study published in the November 23 JAMA. “[Our objective was] to determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular events in patients with established cardiovascular disease or diabetes mellitus,” stated the researchers. The results of their observational analyses revealed that “compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all cardiovascular events.” In addition, a sodium excretion of less than 3 g per day was associated with increased risk of cardiovascular mortality and hospitalization for congestive heart failure, and a higher estimated potassium excretion was associated with a reduced risk of stroke.
Serum vitamin D levels are significantly lower in patients with recurrent inflammatory spinal cord disease, according to the results of a study published online November 14 in Archives of Neurology. The study authors performed a retrospective analysis evaluating vitamin D levels of 77 patients with monophasic and recurrent inflammatory spinal cord diseases. “Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race,” the investigators concluded. “This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.”
The FDA has approved AdaptiveStim with RestoreSensor neurostimulation system for the management of chronic pain. Unlike other implantable neurostimulation devices that require frequent manual adjustments with changes in body positions, the AdaptiveStim system (Medtronic, Inc; Minneapolis) automatically adapts stimulation levels to the needs of people with chronic back and/or leg pain by recognizing and remembering the correlation between a change in body position and the level of stimulation needed. The FDA’s approval was based on data from a clinical trial in which 86.5% of study participants with chronic pain experienced better pain relief and convenience when the system was turned on, compared with a control period when the participants manually adjusted neurostimulation settings; 80.3% of study participants also reported functional improvements, including improved comfort during position changes. The AdaptiveStim system was also approved for use in MRI head scans if recommended by a physician.
Brain overgrowth in boys with autism involves an abnormal excess number of neurons, according to the results of a small preliminary study published in the November 9 JAMA. “Autism often involves early brain overgrowth, including the prefrontal cortex,” the investigators stated. “Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.” To investigate whether this overgrowth in children with autism involves excess neuron numbers, the researchers compared postmortem tissue from the prefrontal cortex of seven boys (age range, 2 to 16) who had autism with postmortem tissue of six typically developing boys. They found that children with autism had 67% more neurons in the prefrontal cortex. “Brain weight in the autistic case differed from normative mean weight for age by a mean of 17.6%, while brains in controls differed by a mean of 0.2%,” the researchers reported.
A person’s stroke risk profile may also be helpful in predicting whether a person will develop memory problems and cognitive impairment later in life, according to a study published in the November 8 Neurology. “Participants included subjects without stroke at baseline … with at least two cognitive function assessments during the follow-up,” the researchers explained. “During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment.” The researchers determined that male sex, black race, less education, older age, and presence of left ventricular hypertrophy were related to the development of cognitive impairment. “Total Framingham Stroke Risk Profile score, elevated blood pressure, and left ventricular hypertrophy predict development of clinically significant cognitive dysfunction,” the investigators concluded. “Prevention and treatment of high blood pressure may be effective in preserving cognitive health.”
The FDA has approved Xarelto (rivaroxaban) to reduce the risk of stroke in people who have nonvalvular atrial fibrillation. Xarelto (Janssen Pharmaceuticals Inc; Titusville, New Jersey) is an oral anti-clotting drug that has also been approved to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery. The FDA’s approval was based on the results of a clinical trial with more than 14,000 patients that compared Xarelto with the anti-clotting drug warfarin; Xarelto proved similar to warfarin in its ability to prevent stroke. Bleeding was the most common adverse event reported by patients treated with Xarelto in this clinical trial, and the risk of bleeding was similar to the risk of bleeding associated with warfarin.
Patients with dementia who have a stroke have a higher likelihood of becoming disabled and being institutionalized, compared with patients who did not have dementia at the time of their stroke, according to a report in the November 1 Neurology. Investigators conducted a retrospective cohort study that included 9,304 patients with an acute ischemic stroke, 702 of whom had a history of dementia. “Patients with dementia were older (mean age, 81 vs 70), had more severe strokes, and were more likely to have atrial fibrillation than those without dementia,” the investigators determined. They also found that patients with dementia were slightly less likely to be admitted to a stroke unit, had a higher disability at discharge, and were less likely to be discharged to their prestroke place of residence. “In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system,” the researchers concluded.

Researchers have found that having a transient ischemic attack (TIA) can reduce a person’s life expectancy up to 20%, according to a study published online November 10 in Stroke. “There is a lack of modern-day data quantifying the effect of TIA on survival, and recent data do not take into account expected survival,” the researchers commented. To investigate the impact of a TIA on survival, the investigators analyzed data from 22,157 patients hospitalized with a TIA, then estimated survival relative to the age- and sex-matched general population up to nine years after hospitalization. At one-year follow-up, 91.5% of TIA patients survived, compared with 95.0% expected survival in the general population; by nine-years follow-up, observed survival was 20% lower than expected. Older age, prior hospitalization for stroke (but not TIA), atrial fibrillation, and congestive heart failure significantly increased the risk of excess death in these patients.
Higher levels of urinary sodium excretion were associated with an increased risk of cardiovascular events, while lower levels were associated with cardiovascular death and hospitalization for congestive heart failure, according to a study published in the November 23 JAMA. “[Our objective was] to determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and cardiovascular events in patients with established cardiovascular disease or diabetes mellitus,” stated the researchers. The results of their observational analyses revealed that “compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all cardiovascular events.” In addition, a sodium excretion of less than 3 g per day was associated with increased risk of cardiovascular mortality and hospitalization for congestive heart failure, and a higher estimated potassium excretion was associated with a reduced risk of stroke.
Serum vitamin D levels are significantly lower in patients with recurrent inflammatory spinal cord disease, according to the results of a study published online November 14 in Archives of Neurology. The study authors performed a retrospective analysis evaluating vitamin D levels of 77 patients with monophasic and recurrent inflammatory spinal cord diseases. “Vitamin D levels are significantly lower in patients who developed recurrent spinal cord disease, adjusting for season, age, sex, and race,” the investigators concluded. “This study provides a basis for a prospective trial of measuring 25-hydroxyvitamin D levels in these patient populations and assessing the influence of vitamin D supplementation on the frequency of relapses in those with recurrent inflammatory spinal cord disease.”
The FDA has approved AdaptiveStim with RestoreSensor neurostimulation system for the management of chronic pain. Unlike other implantable neurostimulation devices that require frequent manual adjustments with changes in body positions, the AdaptiveStim system (Medtronic, Inc; Minneapolis) automatically adapts stimulation levels to the needs of people with chronic back and/or leg pain by recognizing and remembering the correlation between a change in body position and the level of stimulation needed. The FDA’s approval was based on data from a clinical trial in which 86.5% of study participants with chronic pain experienced better pain relief and convenience when the system was turned on, compared with a control period when the participants manually adjusted neurostimulation settings; 80.3% of study participants also reported functional improvements, including improved comfort during position changes. The AdaptiveStim system was also approved for use in MRI head scans if recommended by a physician.
Brain overgrowth in boys with autism involves an abnormal excess number of neurons, according to the results of a small preliminary study published in the November 9 JAMA. “Autism often involves early brain overgrowth, including the prefrontal cortex,” the investigators stated. “Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown.” To investigate whether this overgrowth in children with autism involves excess neuron numbers, the researchers compared postmortem tissue from the prefrontal cortex of seven boys (age range, 2 to 16) who had autism with postmortem tissue of six typically developing boys. They found that children with autism had 67% more neurons in the prefrontal cortex. “Brain weight in the autistic case differed from normative mean weight for age by a mean of 17.6%, while brains in controls differed by a mean of 0.2%,” the researchers reported.
A person’s stroke risk profile may also be helpful in predicting whether a person will develop memory problems and cognitive impairment later in life, according to a study published in the November 8 Neurology. “Participants included subjects without stroke at baseline … with at least two cognitive function assessments during the follow-up,” the researchers explained. “During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment.” The researchers determined that male sex, black race, less education, older age, and presence of left ventricular hypertrophy were related to the development of cognitive impairment. “Total Framingham Stroke Risk Profile score, elevated blood pressure, and left ventricular hypertrophy predict development of clinically significant cognitive dysfunction,” the investigators concluded. “Prevention and treatment of high blood pressure may be effective in preserving cognitive health.”
The FDA has approved Xarelto (rivaroxaban) to reduce the risk of stroke in people who have nonvalvular atrial fibrillation. Xarelto (Janssen Pharmaceuticals Inc; Titusville, New Jersey) is an oral anti-clotting drug that has also been approved to reduce the risk of blood clots, deep vein thrombosis, and pulmonary embolism following knee or hip replacement surgery. The FDA’s approval was based on the results of a clinical trial with more than 14,000 patients that compared Xarelto with the anti-clotting drug warfarin; Xarelto proved similar to warfarin in its ability to prevent stroke. Bleeding was the most common adverse event reported by patients treated with Xarelto in this clinical trial, and the risk of bleeding was similar to the risk of bleeding associated with warfarin.
Patients with dementia who have a stroke have a higher likelihood of becoming disabled and being institutionalized, compared with patients who did not have dementia at the time of their stroke, according to a report in the November 1 Neurology. Investigators conducted a retrospective cohort study that included 9,304 patients with an acute ischemic stroke, 702 of whom had a history of dementia. “Patients with dementia were older (mean age, 81 vs 70), had more severe strokes, and were more likely to have atrial fibrillation than those without dementia,” the investigators determined. They also found that patients with dementia were slightly less likely to be admitted to a stroke unit, had a higher disability at discharge, and were less likely to be discharged to their prestroke place of residence. “In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system,” the researchers concluded.

A study of twins finds that shared environmental factors influence the risk of autism more than previously thought and challenges previous findings about the significance of genetics.

Among identical and fraternal twins in whom at least one child has autism or autism spectrum disorder (ASD), shared environmental factors have a more substantial impact regarding development of the condition than do genetics, according to a study in the July 4 online Archives of General Psychiatry.
“A large proportion of the variance in liability can be explained by shared environmental factors (55% for autism and 58% for ASD) in addition to moderate genetic heritability (37% for autism and 38% for ASD),” reported Joachim Hallmayer, MD, Associate Professor of Psychiatry and Behavioral Sciences, Stanford University School of Medicine in Palo Alto, California, and colleagues. “Our study provides evidence that the rate of concordance in dizygotic twins may have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism, overestimated.”
A Shift in the Environment Versus Genetics Debate?
The study included data from monozygotic twin pairs (45 male, nine female) and dizygotic twin pairs (45 male, 13 female, and 80 sex-discordant) who were born between 1987 and 2004. The monozygotic twins were slightly older and had shorter gestation periods. The mothers of the dizygotic twins were also older than the mothers of the monozygotic twins, “consistent with the known increase in dizygotic twinning with maternal age, and more likely to be white and non-Hispanic,” noted the investigators.
For twins with strict autism, the researchers found that the probandwise concordance for male twins was 0.58 for 40 monozygotic pairs and 0.21 for 31 dizygotic pairs; for female twins, concordance was 0.60 for seven monozygotic twin pairs and 0.27 for 10 dizygotic pairs. For children with ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs and 0.31 for 45 dizygotic pairs; for female twins, concordance was 0.50 for nine monozygotic pairs and 0.36 for 13 dizygotic pairs.
“Because of the reported high heritability of autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes,” Dr. Hallmayer and colleagues wrote. “The finding of significant influence of the shared environment, experiences that are common to both twin individuals, may be important for future research paradigms.”
Increasing evidence has shown that overt symptoms of autism emerge toward the end of the first year of life, the authors noted. “Because the prenatal environment and early postnatal environment are shared between twin individuals, we hypothesize that at least some of the environmental factors impacting susceptibility to autism exert their effect during this critical period of life,” Dr. Hallmayer’s group commented. “Nongenetic risk factors that may index environmental influences included parental age, low birth weight, multiple births, and maternal infections during pregnancy. Future studies that seek to elucidate such factors and their role in enhancing or suppressing genetic susceptibility are likely to enhance our understanding of autism.”
A Disorder of Fetal Programming?
In an accompanying editorial, Peter Szatmari, MD, of the Offord Centre for Child Studies, McMaster University in Hamilton, Ontario, Canada, stated, “Perhaps ASD can be considered, at least in part, a disorder of fetal programming. There is in fact evidence that certain risk factors that affect the maternal fetal environment may place the fetus at increased risk for ASD. Clearly a renewed effort needs to be undertaken through the use of well-designed community-based epidemiologic studies.
“Whatever happens in the future, the finding by Hallmayer and colleagues is an extraordinarily important one and has the potential to shift autism research into a new field of study in much the same way that the original twin study by Folstein and Rutter accomplished back in 1977,” Dr. Szatmari concluded.

A Link Between Maternal Antidepressant Use and Autism Risk in Offspring?
Exposure to selective serotonin reuptake inhibitors (SSRIs) among pregnant women, especially during the first trimester, may modestly increase the risk of autism spectrum disorder (ASD) in their children, according to a study in the July 4 online Archives of General Psychiatry.
The findings were based on 298 children with ASD and 1,507 randomly selected control children and their mothers enrolled in the Kaiser Permanente Medical Care Program in Northern California. Data regarding prenatal exposure to antidepressants were available for 20 children and 50 controls. After adjusted logistic regression, the researchers found a twofold increased risk of ASD associated with SSRI treatment in mothers in the year before delivery (adjusted odds ratio, 2.2). The strongest effect was linked with treatment during the first trimester (adjusted odds ratio, 3.8). No increased risk was observed among mothers with a history of mental health treatment in the absence of prenatal exposure to SSRIs.
“The fraction of cases of ASD that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” stated Lisa A. Croen, PhD, of the Division of Research, Kaiser Permanente Northern California in Oakland, and colleagues. “Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or fetus of untreated mental health disorders.”
“Perhaps it is a coincidence that the odds ratio for ASD risk in the study by Croen and colleagues increases when first-trimester exposure to SSRIs is the sole factor,” stated Pat Levitt, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, in a related commentary. “However, it is exactly that time of human brain development during which cortical and subcortical neuronal populations are being produced, migrating to their final destinations and beginning the long process of wiring. While much occurs later, the establishment of a strong foundation developmentally may be an essential component of healthy brain development.”

A study of twins finds that shared environmental factors influence the risk of autism more than previously thought and challenges previous findings about the significance of genetics.

Among identical and fraternal twins in whom at least one child has autism or autism spectrum disorder (ASD), shared environmental factors have a more substantial impact regarding development of the condition than do genetics, according to a study in the July 4 online Archives of General Psychiatry.
“A large proportion of the variance in liability can be explained by shared environmental factors (55% for autism and 58% for ASD) in addition to moderate genetic heritability (37% for autism and 38% for ASD),” reported Joachim Hallmayer, MD, Associate Professor of Psychiatry and Behavioral Sciences, Stanford University School of Medicine in Palo Alto, California, and colleagues. “Our study provides evidence that the rate of concordance in dizygotic twins may have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism, overestimated.”
A Shift in the Environment Versus Genetics Debate?
The study included data from monozygotic twin pairs (45 male, nine female) and dizygotic twin pairs (45 male, 13 female, and 80 sex-discordant) who were born between 1987 and 2004. The monozygotic twins were slightly older and had shorter gestation periods. The mothers of the dizygotic twins were also older than the mothers of the monozygotic twins, “consistent with the known increase in dizygotic twinning with maternal age, and more likely to be white and non-Hispanic,” noted the investigators.
For twins with strict autism, the researchers found that the probandwise concordance for male twins was 0.58 for 40 monozygotic pairs and 0.21 for 31 dizygotic pairs; for female twins, concordance was 0.60 for seven monozygotic twin pairs and 0.27 for 10 dizygotic pairs. For children with ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs and 0.31 for 45 dizygotic pairs; for female twins, concordance was 0.50 for nine monozygotic pairs and 0.36 for 13 dizygotic pairs.
“Because of the reported high heritability of autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes,” Dr. Hallmayer and colleagues wrote. “The finding of significant influence of the shared environment, experiences that are common to both twin individuals, may be important for future research paradigms.”
Increasing evidence has shown that overt symptoms of autism emerge toward the end of the first year of life, the authors noted. “Because the prenatal environment and early postnatal environment are shared between twin individuals, we hypothesize that at least some of the environmental factors impacting susceptibility to autism exert their effect during this critical period of life,” Dr. Hallmayer’s group commented. “Nongenetic risk factors that may index environmental influences included parental age, low birth weight, multiple births, and maternal infections during pregnancy. Future studies that seek to elucidate such factors and their role in enhancing or suppressing genetic susceptibility are likely to enhance our understanding of autism.”
A Disorder of Fetal Programming?
In an accompanying editorial, Peter Szatmari, MD, of the Offord Centre for Child Studies, McMaster University in Hamilton, Ontario, Canada, stated, “Perhaps ASD can be considered, at least in part, a disorder of fetal programming. There is in fact evidence that certain risk factors that affect the maternal fetal environment may place the fetus at increased risk for ASD. Clearly a renewed effort needs to be undertaken through the use of well-designed community-based epidemiologic studies.
“Whatever happens in the future, the finding by Hallmayer and colleagues is an extraordinarily important one and has the potential to shift autism research into a new field of study in much the same way that the original twin study by Folstein and Rutter accomplished back in 1977,” Dr. Szatmari concluded.

A Link Between Maternal Antidepressant Use and Autism Risk in Offspring?
Exposure to selective serotonin reuptake inhibitors (SSRIs) among pregnant women, especially during the first trimester, may modestly increase the risk of autism spectrum disorder (ASD) in their children, according to a study in the July 4 online Archives of General Psychiatry.
The findings were based on 298 children with ASD and 1,507 randomly selected control children and their mothers enrolled in the Kaiser Permanente Medical Care Program in Northern California. Data regarding prenatal exposure to antidepressants were available for 20 children and 50 controls. After adjusted logistic regression, the researchers found a twofold increased risk of ASD associated with SSRI treatment in mothers in the year before delivery (adjusted odds ratio, 2.2). The strongest effect was linked with treatment during the first trimester (adjusted odds ratio, 3.8). No increased risk was observed among mothers with a history of mental health treatment in the absence of prenatal exposure to SSRIs.
“The fraction of cases of ASD that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” stated Lisa A. Croen, PhD, of the Division of Research, Kaiser Permanente Northern California in Oakland, and colleagues. “Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or fetus of untreated mental health disorders.”
“Perhaps it is a coincidence that the odds ratio for ASD risk in the study by Croen and colleagues increases when first-trimester exposure to SSRIs is the sole factor,” stated Pat Levitt, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, in a related commentary. “However, it is exactly that time of human brain development during which cortical and subcortical neuronal populations are being produced, migrating to their final destinations and beginning the long process of wiring. While much occurs later, the establishment of a strong foundation developmentally may be an essential component of healthy brain development.”

A study of twins finds that shared environmental factors influence the risk of autism more than previously thought and challenges previous findings about the significance of genetics.

Among identical and fraternal twins in whom at least one child has autism or autism spectrum disorder (ASD), shared environmental factors have a more substantial impact regarding development of the condition than do genetics, according to a study in the July 4 online Archives of General Psychiatry.
“A large proportion of the variance in liability can be explained by shared environmental factors (55% for autism and 58% for ASD) in addition to moderate genetic heritability (37% for autism and 38% for ASD),” reported Joachim Hallmayer, MD, Associate Professor of Psychiatry and Behavioral Sciences, Stanford University School of Medicine in Palo Alto, California, and colleagues. “Our study provides evidence that the rate of concordance in dizygotic twins may have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism, overestimated.”
A Shift in the Environment Versus Genetics Debate?
The study included data from monozygotic twin pairs (45 male, nine female) and dizygotic twin pairs (45 male, 13 female, and 80 sex-discordant) who were born between 1987 and 2004. The monozygotic twins were slightly older and had shorter gestation periods. The mothers of the dizygotic twins were also older than the mothers of the monozygotic twins, “consistent with the known increase in dizygotic twinning with maternal age, and more likely to be white and non-Hispanic,” noted the investigators.
For twins with strict autism, the researchers found that the probandwise concordance for male twins was 0.58 for 40 monozygotic pairs and 0.21 for 31 dizygotic pairs; for female twins, concordance was 0.60 for seven monozygotic twin pairs and 0.27 for 10 dizygotic pairs. For children with ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs and 0.31 for 45 dizygotic pairs; for female twins, concordance was 0.50 for nine monozygotic pairs and 0.36 for 13 dizygotic pairs.
“Because of the reported high heritability of autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes,” Dr. Hallmayer and colleagues wrote. “The finding of significant influence of the shared environment, experiences that are common to both twin individuals, may be important for future research paradigms.”
Increasing evidence has shown that overt symptoms of autism emerge toward the end of the first year of life, the authors noted. “Because the prenatal environment and early postnatal environment are shared between twin individuals, we hypothesize that at least some of the environmental factors impacting susceptibility to autism exert their effect during this critical period of life,” Dr. Hallmayer’s group commented. “Nongenetic risk factors that may index environmental influences included parental age, low birth weight, multiple births, and maternal infections during pregnancy. Future studies that seek to elucidate such factors and their role in enhancing or suppressing genetic susceptibility are likely to enhance our understanding of autism.”
A Disorder of Fetal Programming?
In an accompanying editorial, Peter Szatmari, MD, of the Offord Centre for Child Studies, McMaster University in Hamilton, Ontario, Canada, stated, “Perhaps ASD can be considered, at least in part, a disorder of fetal programming. There is in fact evidence that certain risk factors that affect the maternal fetal environment may place the fetus at increased risk for ASD. Clearly a renewed effort needs to be undertaken through the use of well-designed community-based epidemiologic studies.
“Whatever happens in the future, the finding by Hallmayer and colleagues is an extraordinarily important one and has the potential to shift autism research into a new field of study in much the same way that the original twin study by Folstein and Rutter accomplished back in 1977,” Dr. Szatmari concluded.

A Link Between Maternal Antidepressant Use and Autism Risk in Offspring?
Exposure to selective serotonin reuptake inhibitors (SSRIs) among pregnant women, especially during the first trimester, may modestly increase the risk of autism spectrum disorder (ASD) in their children, according to a study in the July 4 online Archives of General Psychiatry.
The findings were based on 298 children with ASD and 1,507 randomly selected control children and their mothers enrolled in the Kaiser Permanente Medical Care Program in Northern California. Data regarding prenatal exposure to antidepressants were available for 20 children and 50 controls. After adjusted logistic regression, the researchers found a twofold increased risk of ASD associated with SSRI treatment in mothers in the year before delivery (adjusted odds ratio, 2.2). The strongest effect was linked with treatment during the first trimester (adjusted odds ratio, 3.8). No increased risk was observed among mothers with a history of mental health treatment in the absence of prenatal exposure to SSRIs.
“The fraction of cases of ASD that may be attributed to use of antidepressants by the mother during pregnancy is less than 3% in our population, and it is reasonable to conclude that prenatal SSRI exposure is very unlikely to be a major risk factor for ASD,” stated Lisa A. Croen, PhD, of the Division of Research, Kaiser Permanente Northern California in Oakland, and colleagues. “Although these findings indicate that maternal treatment with SSRIs during pregnancy may confer some risk to the fetus with regard to neurodevelopment, this potential risk must be balanced with the risk to the mother or fetus of untreated mental health disorders.”
“Perhaps it is a coincidence that the odds ratio for ASD risk in the study by Croen and colleagues increases when first-trimester exposure to SSRIs is the sole factor,” stated Pat Levitt, PhD, of the Keck School of Medicine, University of Southern California, Los Angeles, in a related commentary. “However, it is exactly that time of human brain development during which cortical and subcortical neuronal populations are being produced, migrating to their final destinations and beginning the long process of wiring. While much occurs later, the establishment of a strong foundation developmentally may be an essential component of healthy brain development.”

The release of stress hormones can lead to the production of abnormally phosphorylated tau protein, and eventually to memory loss, researchers reported. “Severity of cognitive deficits in Alzheimer’s disease correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein tau,” the authors stated in the May 25 Journal of Neuroscience. “We thus examined whether stress, through the mediation of glucocorticoids, influences tau hyperphosphorylation, a critical and early event in the cascade of processes leading to Alzheimer’s disease pathology.” Results showed that chronic stress and hypersecretion of glucocorticoids induces abnormal hyperphosphorylation of tau in the hippocampus and prefrontal cortex, suggesting that they have a cumulative impact on the onset and progress of Alzheimer’s disease pathology.
Soluble amyloid proteins in the CSF of patients with mild cognitive impairment may be a potential biomarker for Alzheimer’s disease, according to research in the June 22 online Neurology. The investigators measured the concentrations of amyloid precursor protein, tau protein, and amyloid-beta 1-42 concentrations in the CSF of 58 patients with slight memory problems—21 of whom progressed to Alzheimer’s disease. Analysis of the samples revealed that the group that had progressed to Alzheimer’s disease had significantly higher concentrations of the soluble amyloid precursor proteins than those who reverted to normal and those who developed frontotemporal dementia. “These findings suggest that soluble amyloid precursor protein beta may be clinically useful, and superior to [amyloid-beta 1-42], in the early and differential diagnosis of Alzheimer’s disease,” the authors concluded.
Weak synchronization between brain hemispheres may be an early biomarker for autism, according to the results of a study published in the June 23 issue of Neuron. “Autism is often described as a disorder of neuronal synchronization,” the authors wrote. “However, it is unknown how early in development synchronization abnormalities emerge and whether they are related to the development of early autistic behavioral symptoms.” The researchers conducted an imaging study and found that toddlers with autism exhibited significantly weaker interhemispheric synchronization in putative language areas than did toddlers without the condition. In addition, toddlers with a greater strength of synchronization had higher verbal ability and lower autism severity. “Disrupted cortical synchronization, therefore, appears to be a notable characteristic of autism neurophysiology that is evident at very early stages of autism development,” they concluded.

The FDA has approved Potiga (ezogabine) tablets as an adjunctive treatment of partial-onset seizures in adults with epilepsy. It is the first neuronal potassium channel opener developed for the treatment of epilepsy. Although its mechanism of action is not firmly established, it is believed that ezogabine may act as an anticonvulsant by reducing excitability through the stabilization of neuronal potassium channels in an ‘open’ position. The FDA’s approval was based on the results of three controlled clinical studies involving 1,239 patients with epilepsy that investigated the ability of ezogabine to reduce seizure frequency during the double-blind treatment phase. The most common adverse events were dizziness, somnolence, and fatigue; approximately 2% of patients in clinical trials also experienced urinary retention. Researchers at GlaxoSmithKline and Valeant Pharmaceuticals International Inc believe that ezogabine tablets will benefit patients whose epilepsy is uncontrolled with their current medications.

Prenatal exposure to certain antiepileptic drugs has a higher risk for major congenital malformations, according to results of a study published in the July issue of Lancet Neurology. The researchers monitored pregnant women with epilepsy who were exposed to monotherapy with different doses of carbamazepine, lamotrigine, valproic acid, or phenobarbital. A total of 230 pregnancies associated with major birth defects were observed during the first year after birth; there was also an increase in malformation rates as the dose increased for each drug. The lowest rates of malformation occurred in women who took less than 300 mg per day of lamotrigine or less than 400 mg per day of carbamazepine. All doses of valproic acid and phenobarbital monotherapies had significantly higher risks for birth defects. “The risk of major congenital malformations is influenced not only by type of antiepileptic drug, but also by dose and other variables, which should be taken into account in the management of epilepsy in women of childbearing potential,” the authors concluded.

Peripheral nerve stimulation delivered via an implanted medical device significantly reduces the number of days per month that patients have chronic migraine headache and pain, according to data presented at the 15th Annual International Headache Congress in Berlin. Investigators enrolled 157 patients with migraine to evaluate the safety and efficacy of the device; after 12 weeks, patients who received stimulation reported a 28% decrease in headache days per month. Sixty-seven percent also reported an improvement in their quality of life. “Many migraine patients have exhausted all current treatment options and often are disabled by the pain and frequency of migraine attacks,” the principal investigator stated. “Achieving a reduction in the number of days they suffer from headache and a significant improvement in their quality of life may be even more important than pain reduction alone.”

Researchers have identified three susceptibility loci for common migraine in the general population, according to a study published in the June 12 online Nature Genetics. In a population-based genome-wide analysis that included 5,122 patients with migraine and 18,108 patients without migraine, investigators found seven single nucleotide polymorphisms (SNPs) associated with migraine. Subsequent testing and meta-analysis confirmed that three replicating SNPs (re2651899, rs10166942, and rs11172113) were significantly associated with migraine. “The associations at r2651899 and rs10166942 were specific for migraine compared with nonmigraine headache,” the researchers reported. In addition, none of the three SNP associations was preferential for migraine with aura or without aura; there were also no associations specific for migraine features, suggesting that there is a shared pathophysiology among common types of migraine. “The three new loci identified in the present work provide hypotheses for immediate further exploration,” the authors concluded.

People who have had a herpes zoster attack may be at a higher risk for developing multiple sclerosis (MS) than people who have not had an occurrence of the virus, researchers reported in the June 7 online Journal of Infectious Diseases. “Varicella zoster virus has been proposed to be involved in the pathogenesis of MS,” the investigators wrote. In the study, they followed 315,550 patients with herpes zoster and 946,650 subjects without the virus for one year; they then calculated the one-year MS–free survival rate. “Of 1,262,200 sampled patients, 29 from the study group (.009%) and 24 from the control group (.003%) had MS during the one-year follow-up period,” the authors reported. The odds ratio of developing MS was 3.96 times greater for the study group than for the control group, supporting the notion that occurrence of the disease could be associated with herpes zoster attack.

A study published in the June 7 issue of Neurology found that patients with Parkinson’s disease have a significantly higher risk of having melanoma than do healthy controls. The researchers conducted a meta-analysis of 12 publications on melanoma and Parkinson’s disease; eight of the publications had fewer than 10 cases with both Parkinson’s disease and melanoma. The pooled odds ratio was 2.11 overall, 2.04 for men, and 1.52 for women. Melanoma occurrence was significantly higher after the diagnosis of Parkinson’s disease, but not before Parkinson’s disease was diagnosed. After analyzing the data for nonmelanoma skin cancers, the researchers found no significant relationship. “Collective epidemiologic evidence supports an association of Parkinson’s disease with melanoma,” the authors concluded. “Further research is needed to examine the nature and mechanisms of this relationship.”

At-home physical training may be just as effective as locomotor training for improving the ability to walk in patients who have had a stroke, researchers reported in the May 26 New England Journal of Medicine. The investigators randomly assigned 408 participants with stroke to one of three training groups; one group received early locomotor training on a body weight–supported treadmill two months after stroke occurred, one group received the same training six months after stroke, and the third group completed an at-home exercise program guided by a physical therapist two months after stroke. At one year of training, 52% of all participants had increased functional walking ability. The researchers observed no significant differences in improvement between early or late locomotor training and home exercise. “All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life,” the authors noted.

High consumption of olive oil and high plasma oleic acid are associated with lower risk for stroke in older adults, according to the results of a study published in the June 15 online Neurology. To examine this relationship, the researchers looked at 7,625 older adults; in this sample, 148 incident strokes occurred. After adjusting for demographic and dietary variables and stroke risk factors, the investigators found that “compared to those who never used olive oil, those with intensive use had a 41% lower risk of stroke.” In a secondary sample, the researchers investigated the plasma oleic acid levels of 1,245 individuals (27 had incident stroke) and found that participants in the third tertile had a 73% reduction of stroke risk. “These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects,” the authors concluded.

The release of stress hormones can lead to the production of abnormally phosphorylated tau protein, and eventually to memory loss, researchers reported. “Severity of cognitive deficits in Alzheimer’s disease correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein tau,” the authors stated in the May 25 Journal of Neuroscience. “We thus examined whether stress, through the mediation of glucocorticoids, influences tau hyperphosphorylation, a critical and early event in the cascade of processes leading to Alzheimer’s disease pathology.” Results showed that chronic stress and hypersecretion of glucocorticoids induces abnormal hyperphosphorylation of tau in the hippocampus and prefrontal cortex, suggesting that they have a cumulative impact on the onset and progress of Alzheimer’s disease pathology.
Soluble amyloid proteins in the CSF of patients with mild cognitive impairment may be a potential biomarker for Alzheimer’s disease, according to research in the June 22 online Neurology. The investigators measured the concentrations of amyloid precursor protein, tau protein, and amyloid-beta 1-42 concentrations in the CSF of 58 patients with slight memory problems—21 of whom progressed to Alzheimer’s disease. Analysis of the samples revealed that the group that had progressed to Alzheimer’s disease had significantly higher concentrations of the soluble amyloid precursor proteins than those who reverted to normal and those who developed frontotemporal dementia. “These findings suggest that soluble amyloid precursor protein beta may be clinically useful, and superior to [amyloid-beta 1-42], in the early and differential diagnosis of Alzheimer’s disease,” the authors concluded.
Weak synchronization between brain hemispheres may be an early biomarker for autism, according to the results of a study published in the June 23 issue of Neuron. “Autism is often described as a disorder of neuronal synchronization,” the authors wrote. “However, it is unknown how early in development synchronization abnormalities emerge and whether they are related to the development of early autistic behavioral symptoms.” The researchers conducted an imaging study and found that toddlers with autism exhibited significantly weaker interhemispheric synchronization in putative language areas than did toddlers without the condition. In addition, toddlers with a greater strength of synchronization had higher verbal ability and lower autism severity. “Disrupted cortical synchronization, therefore, appears to be a notable characteristic of autism neurophysiology that is evident at very early stages of autism development,” they concluded.

The FDA has approved Potiga (ezogabine) tablets as an adjunctive treatment of partial-onset seizures in adults with epilepsy. It is the first neuronal potassium channel opener developed for the treatment of epilepsy. Although its mechanism of action is not firmly established, it is believed that ezogabine may act as an anticonvulsant by reducing excitability through the stabilization of neuronal potassium channels in an ‘open’ position. The FDA’s approval was based on the results of three controlled clinical studies involving 1,239 patients with epilepsy that investigated the ability of ezogabine to reduce seizure frequency during the double-blind treatment phase. The most common adverse events were dizziness, somnolence, and fatigue; approximately 2% of patients in clinical trials also experienced urinary retention. Researchers at GlaxoSmithKline and Valeant Pharmaceuticals International Inc believe that ezogabine tablets will benefit patients whose epilepsy is uncontrolled with their current medications.

Prenatal exposure to certain antiepileptic drugs has a higher risk for major congenital malformations, according to results of a study published in the July issue of Lancet Neurology. The researchers monitored pregnant women with epilepsy who were exposed to monotherapy with different doses of carbamazepine, lamotrigine, valproic acid, or phenobarbital. A total of 230 pregnancies associated with major birth defects were observed during the first year after birth; there was also an increase in malformation rates as the dose increased for each drug. The lowest rates of malformation occurred in women who took less than 300 mg per day of lamotrigine or less than 400 mg per day of carbamazepine. All doses of valproic acid and phenobarbital monotherapies had significantly higher risks for birth defects. “The risk of major congenital malformations is influenced not only by type of antiepileptic drug, but also by dose and other variables, which should be taken into account in the management of epilepsy in women of childbearing potential,” the authors concluded.

Peripheral nerve stimulation delivered via an implanted medical device significantly reduces the number of days per month that patients have chronic migraine headache and pain, according to data presented at the 15th Annual International Headache Congress in Berlin. Investigators enrolled 157 patients with migraine to evaluate the safety and efficacy of the device; after 12 weeks, patients who received stimulation reported a 28% decrease in headache days per month. Sixty-seven percent also reported an improvement in their quality of life. “Many migraine patients have exhausted all current treatment options and often are disabled by the pain and frequency of migraine attacks,” the principal investigator stated. “Achieving a reduction in the number of days they suffer from headache and a significant improvement in their quality of life may be even more important than pain reduction alone.”

Researchers have identified three susceptibility loci for common migraine in the general population, according to a study published in the June 12 online Nature Genetics. In a population-based genome-wide analysis that included 5,122 patients with migraine and 18,108 patients without migraine, investigators found seven single nucleotide polymorphisms (SNPs) associated with migraine. Subsequent testing and meta-analysis confirmed that three replicating SNPs (re2651899, rs10166942, and rs11172113) were significantly associated with migraine. “The associations at r2651899 and rs10166942 were specific for migraine compared with nonmigraine headache,” the researchers reported. In addition, none of the three SNP associations was preferential for migraine with aura or without aura; there were also no associations specific for migraine features, suggesting that there is a shared pathophysiology among common types of migraine. “The three new loci identified in the present work provide hypotheses for immediate further exploration,” the authors concluded.

People who have had a herpes zoster attack may be at a higher risk for developing multiple sclerosis (MS) than people who have not had an occurrence of the virus, researchers reported in the June 7 online Journal of Infectious Diseases. “Varicella zoster virus has been proposed to be involved in the pathogenesis of MS,” the investigators wrote. In the study, they followed 315,550 patients with herpes zoster and 946,650 subjects without the virus for one year; they then calculated the one-year MS–free survival rate. “Of 1,262,200 sampled patients, 29 from the study group (.009%) and 24 from the control group (.003%) had MS during the one-year follow-up period,” the authors reported. The odds ratio of developing MS was 3.96 times greater for the study group than for the control group, supporting the notion that occurrence of the disease could be associated with herpes zoster attack.

A study published in the June 7 issue of Neurology found that patients with Parkinson’s disease have a significantly higher risk of having melanoma than do healthy controls. The researchers conducted a meta-analysis of 12 publications on melanoma and Parkinson’s disease; eight of the publications had fewer than 10 cases with both Parkinson’s disease and melanoma. The pooled odds ratio was 2.11 overall, 2.04 for men, and 1.52 for women. Melanoma occurrence was significantly higher after the diagnosis of Parkinson’s disease, but not before Parkinson’s disease was diagnosed. After analyzing the data for nonmelanoma skin cancers, the researchers found no significant relationship. “Collective epidemiologic evidence supports an association of Parkinson’s disease with melanoma,” the authors concluded. “Further research is needed to examine the nature and mechanisms of this relationship.”

At-home physical training may be just as effective as locomotor training for improving the ability to walk in patients who have had a stroke, researchers reported in the May 26 New England Journal of Medicine. The investigators randomly assigned 408 participants with stroke to one of three training groups; one group received early locomotor training on a body weight–supported treadmill two months after stroke occurred, one group received the same training six months after stroke, and the third group completed an at-home exercise program guided by a physical therapist two months after stroke. At one year of training, 52% of all participants had increased functional walking ability. The researchers observed no significant differences in improvement between early or late locomotor training and home exercise. “All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life,” the authors noted.

High consumption of olive oil and high plasma oleic acid are associated with lower risk for stroke in older adults, according to the results of a study published in the June 15 online Neurology. To examine this relationship, the researchers looked at 7,625 older adults; in this sample, 148 incident strokes occurred. After adjusting for demographic and dietary variables and stroke risk factors, the investigators found that “compared to those who never used olive oil, those with intensive use had a 41% lower risk of stroke.” In a secondary sample, the researchers investigated the plasma oleic acid levels of 1,245 individuals (27 had incident stroke) and found that participants in the third tertile had a 73% reduction of stroke risk. “These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects,” the authors concluded.

The release of stress hormones can lead to the production of abnormally phosphorylated tau protein, and eventually to memory loss, researchers reported. “Severity of cognitive deficits in Alzheimer’s disease correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein tau,” the authors stated in the May 25 Journal of Neuroscience. “We thus examined whether stress, through the mediation of glucocorticoids, influences tau hyperphosphorylation, a critical and early event in the cascade of processes leading to Alzheimer’s disease pathology.” Results showed that chronic stress and hypersecretion of glucocorticoids induces abnormal hyperphosphorylation of tau in the hippocampus and prefrontal cortex, suggesting that they have a cumulative impact on the onset and progress of Alzheimer’s disease pathology.
Soluble amyloid proteins in the CSF of patients with mild cognitive impairment may be a potential biomarker for Alzheimer’s disease, according to research in the June 22 online Neurology. The investigators measured the concentrations of amyloid precursor protein, tau protein, and amyloid-beta 1-42 concentrations in the CSF of 58 patients with slight memory problems—21 of whom progressed to Alzheimer’s disease. Analysis of the samples revealed that the group that had progressed to Alzheimer’s disease had significantly higher concentrations of the soluble amyloid precursor proteins than those who reverted to normal and those who developed frontotemporal dementia. “These findings suggest that soluble amyloid precursor protein beta may be clinically useful, and superior to [amyloid-beta 1-42], in the early and differential diagnosis of Alzheimer’s disease,” the authors concluded.
Weak synchronization between brain hemispheres may be an early biomarker for autism, according to the results of a study published in the June 23 issue of Neuron. “Autism is often described as a disorder of neuronal synchronization,” the authors wrote. “However, it is unknown how early in development synchronization abnormalities emerge and whether they are related to the development of early autistic behavioral symptoms.” The researchers conducted an imaging study and found that toddlers with autism exhibited significantly weaker interhemispheric synchronization in putative language areas than did toddlers without the condition. In addition, toddlers with a greater strength of synchronization had higher verbal ability and lower autism severity. “Disrupted cortical synchronization, therefore, appears to be a notable characteristic of autism neurophysiology that is evident at very early stages of autism development,” they concluded.

The FDA has approved Potiga (ezogabine) tablets as an adjunctive treatment of partial-onset seizures in adults with epilepsy. It is the first neuronal potassium channel opener developed for the treatment of epilepsy. Although its mechanism of action is not firmly established, it is believed that ezogabine may act as an anticonvulsant by reducing excitability through the stabilization of neuronal potassium channels in an ‘open’ position. The FDA’s approval was based on the results of three controlled clinical studies involving 1,239 patients with epilepsy that investigated the ability of ezogabine to reduce seizure frequency during the double-blind treatment phase. The most common adverse events were dizziness, somnolence, and fatigue; approximately 2% of patients in clinical trials also experienced urinary retention. Researchers at GlaxoSmithKline and Valeant Pharmaceuticals International Inc believe that ezogabine tablets will benefit patients whose epilepsy is uncontrolled with their current medications.

Prenatal exposure to certain antiepileptic drugs has a higher risk for major congenital malformations, according to results of a study published in the July issue of Lancet Neurology. The researchers monitored pregnant women with epilepsy who were exposed to monotherapy with different doses of carbamazepine, lamotrigine, valproic acid, or phenobarbital. A total of 230 pregnancies associated with major birth defects were observed during the first year after birth; there was also an increase in malformation rates as the dose increased for each drug. The lowest rates of malformation occurred in women who took less than 300 mg per day of lamotrigine or less than 400 mg per day of carbamazepine. All doses of valproic acid and phenobarbital monotherapies had significantly higher risks for birth defects. “The risk of major congenital malformations is influenced not only by type of antiepileptic drug, but also by dose and other variables, which should be taken into account in the management of epilepsy in women of childbearing potential,” the authors concluded.

Peripheral nerve stimulation delivered via an implanted medical device significantly reduces the number of days per month that patients have chronic migraine headache and pain, according to data presented at the 15th Annual International Headache Congress in Berlin. Investigators enrolled 157 patients with migraine to evaluate the safety and efficacy of the device; after 12 weeks, patients who received stimulation reported a 28% decrease in headache days per month. Sixty-seven percent also reported an improvement in their quality of life. “Many migraine patients have exhausted all current treatment options and often are disabled by the pain and frequency of migraine attacks,” the principal investigator stated. “Achieving a reduction in the number of days they suffer from headache and a significant improvement in their quality of life may be even more important than pain reduction alone.”

Researchers have identified three susceptibility loci for common migraine in the general population, according to a study published in the June 12 online Nature Genetics. In a population-based genome-wide analysis that included 5,122 patients with migraine and 18,108 patients without migraine, investigators found seven single nucleotide polymorphisms (SNPs) associated with migraine. Subsequent testing and meta-analysis confirmed that three replicating SNPs (re2651899, rs10166942, and rs11172113) were significantly associated with migraine. “The associations at r2651899 and rs10166942 were specific for migraine compared with nonmigraine headache,” the researchers reported. In addition, none of the three SNP associations was preferential for migraine with aura or without aura; there were also no associations specific for migraine features, suggesting that there is a shared pathophysiology among common types of migraine. “The three new loci identified in the present work provide hypotheses for immediate further exploration,” the authors concluded.

People who have had a herpes zoster attack may be at a higher risk for developing multiple sclerosis (MS) than people who have not had an occurrence of the virus, researchers reported in the June 7 online Journal of Infectious Diseases. “Varicella zoster virus has been proposed to be involved in the pathogenesis of MS,” the investigators wrote. In the study, they followed 315,550 patients with herpes zoster and 946,650 subjects without the virus for one year; they then calculated the one-year MS–free survival rate. “Of 1,262,200 sampled patients, 29 from the study group (.009%) and 24 from the control group (.003%) had MS during the one-year follow-up period,” the authors reported. The odds ratio of developing MS was 3.96 times greater for the study group than for the control group, supporting the notion that occurrence of the disease could be associated with herpes zoster attack.

A study published in the June 7 issue of Neurology found that patients with Parkinson’s disease have a significantly higher risk of having melanoma than do healthy controls. The researchers conducted a meta-analysis of 12 publications on melanoma and Parkinson’s disease; eight of the publications had fewer than 10 cases with both Parkinson’s disease and melanoma. The pooled odds ratio was 2.11 overall, 2.04 for men, and 1.52 for women. Melanoma occurrence was significantly higher after the diagnosis of Parkinson’s disease, but not before Parkinson’s disease was diagnosed. After analyzing the data for nonmelanoma skin cancers, the researchers found no significant relationship. “Collective epidemiologic evidence supports an association of Parkinson’s disease with melanoma,” the authors concluded. “Further research is needed to examine the nature and mechanisms of this relationship.”

At-home physical training may be just as effective as locomotor training for improving the ability to walk in patients who have had a stroke, researchers reported in the May 26 New England Journal of Medicine. The investigators randomly assigned 408 participants with stroke to one of three training groups; one group received early locomotor training on a body weight–supported treadmill two months after stroke occurred, one group received the same training six months after stroke, and the third group completed an at-home exercise program guided by a physical therapist two months after stroke. At one year of training, 52% of all participants had increased functional walking ability. The researchers observed no significant differences in improvement between early or late locomotor training and home exercise. “All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life,” the authors noted.

High consumption of olive oil and high plasma oleic acid are associated with lower risk for stroke in older adults, according to the results of a study published in the June 15 online Neurology. To examine this relationship, the researchers looked at 7,625 older adults; in this sample, 148 incident strokes occurred. After adjusting for demographic and dietary variables and stroke risk factors, the investigators found that “compared to those who never used olive oil, those with intensive use had a 41% lower risk of stroke.” In a secondary sample, the researchers investigated the plasma oleic acid levels of 1,245 individuals (27 had incident stroke) and found that participants in the third tertile had a 73% reduction of stroke risk. “These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects,” the authors concluded.

Researchers determined that MRI imaging may predict which persons with cognitive impairment will progress to Alzheimer’s disease in a report published in the April 6 online Radiology. Baseline MRI was obtained for 164 individuals with late-onset Alzheimer’s disease, 317 with mild cognitive impairment, and 203 healthy controls. The investigators then used MRI to measure the thickness and amount of atrophy in the cerebral cortex. “Individualized risk estimates from baseline MRI examinations indicated that the one-year risk of conversion to Alzheimer’s disease ranged from 3% to 40%,” the researchers reported. “Relative to the risk of conversion to Alzheimer’s disease conferred by the clinical diagnosis of mild cognitive impairment alone, MRI measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available.”

Cotinine, a compound derived from tobacco, reduced brain plaques associated with dementia and memory loss, according to a study published in the online February 14 Journal of Alzheimer’s Disease. A group of investigators studied the effects of cotinine on b-amyloid plaque aggregation in the brains of mice with Alzheimer’s disease. Mice treated with the compound performed better than untreated mice on tasks measuring working memory and thinking skills; long-term treatment also appeared to prevent spatial memory impairment. Overall, the treated mice showed a 26% reduction in amyloid plaque deposits. “Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans,” the authors wrote. “The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of Alzheimer’s disease.”

A study published in the April 13 online Neurology provides evidence that treating certain vascular risk factors helps lower the risk for conversion from mild cognitive impairment to Alzheimer’s disease. Investigators assessed memory and thinking skills of 837 patients with mild cognitive impairment and then reassessed them five years later; 414 participants had at least one vascular risk factor at baseline. “At the end of follow-up 298 subjects converted to Alzheimer’s disease dementia, while 352 remained with mild cognitive impairment,” the investigators reported. “Treatment of individual vascular risk factors including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of Alzheimer’s disease conversion.” The findings of the study are observational, the authors concluded, but they suggest that active intervention and treatment of certain risk factors might reduce progression to Alzheimer’s disease.

Researchers have identified mutations of the synapsin 1 gene as a possible common genetic cause for both epilepsy and autism. Their study, published online in the April 12 Human Molecular Genetics, involved members of a large French-Canadian family who had autism spectrum disorders or epilepsy. The severe Q555X mutation appeared in all family members with epilepsy, and in all those who had an autism spectrum disorder. In addition, other mutations in synapsin 1 (A51G, A550T, and T567A) were found in 1% and 3.5% of a separate cohort of French-Canadian individuals with autism and epilepsy, respectively. “These results demonstrate that [synapsin 1] is a novel predisposing gene to [autism spectrum disorders], in addition to epilepsy,” the authors concluded. “[The results also] strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.”

Men who reported chronic ecstasy (MDMA) use were more likely to develop structural brain damage than those who did not use ecstasy, according to a study that was published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry. Using MRI, researchers measured the hippocampal volume of 10 male ecstasy users (average age, 21.3), compared with seven age- and gender-matched subjects who did not use ecstasy. The hippocampal volume of ecstasy users was 10.5% smaller than those of nonusing peers; the overall proportion of gray matter was 4.6% smaller, suggesting that the drug’s effects are not limited to the hippocampus. “These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage,” the authors wrote, adding: “Hippocampal atrophy is a hallmark for disease of progressive cognitive impairment in older patients, such as Alzheimer’s disease.”

In a study published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry, researchers reported that epileptic seizures carry a subsequent risk for brain tumor. “Our study suggests that tumor as an underlying cause for epilepsy may not become apparent for several years after onset, and indicates a need for ongoing vigilance,” the authors stated. In the retrospective cohort study, the investigators examined data regarding individuals with first-time epilepsy admissions and determined that, compared with patients admitted for other common and minor disorders, patients with epilepsy were almost 20 times more likely to develop cerebral tumor. The risk for developing malignant tumors was more than twice the risk for developing benign tumors. “The risk was highest for those aged 15 to 44 years at initial admission for epilepsy,” the authors reported. “The risk of cerebral tumor was still raised several years after initial admission for epilepsy.”

A novel gene transfer vector, NP2, is safe and well tolerated for the treatment of intractable pain, researchers reported in the April 11 online Annals of Neurology. Investigators conducted a multicenter, dose-escalation, phase I clinical trial of intradermal NP2 injection in 10 subjects with persistent pain caused by cancer, despite treatment with morphine or other analgesic. Participants who received the low dose of NP2 reported no substantive change in pain; patients in the middle and high dose cohorts reported pain relief. “There were no placebo controls in this relatively small study,” the authors concluded. “But the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.”

The FDA has approved DaTscan (ioflupane I 123 injection) for detecting dopamine transporters in the brains of adults with suspected Parkinsonian syndromes. The radiopharmaceutical agent is intended for use with single photon emission CT imaging to evaluate neurodegenerative movement disorders. The injection may be used as an adjunct to other diagnostic evaluation tools to distinguish between essential tremor and tremor due to Parkinson’s disease, as ioflupane I 123 injection alone cannot differentiate between different types of parkinsonian syndromes. The FDA’s approval was based on two phase III clinical trials in which the drug was used to evaluate dopamine transporter distribution in the brains of adult patients. As a new diagnostic adjunct to clinical assessments, ioflupane  I 123 can potentially help physicians select the appropriate treatments for patients with movement disorders.

Persons who are regularly exposed to welding fumes may be at an increased risk for brain damage, specifically in the same areas affected by Parkinson’s disease, researchers reported in the April 12 Neurology. “Welding exposes workers to manganese fumes, but it is unclear if this exposure damages dopaminergic neurons,” the authors stated. “The purpose of this study [was] to determine whether welding exposure is associated with damage to nigrostriatal neurons.” Using PET imaging on 20 welders with no parkinsonian symptoms, 20 individuals with symptoms, and 20 healthy controls, the investigators determined that asymptomatic welders had higher manganese levels in the blood and an average 11.7% reduction in dopamine in certain brain regions. The pattern of reduction seen in welders, however, was distinct from the dysfunction pattern found in symptomatic Parkinson’s disease.

The FDA has approved Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) for the treatment of pseudobulbar affect. The new therapy will help patients manage pseudobulbar affect that occurs secondary to multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, Parkinson’s disease, and other neurologic diseases. Nuedexta combines dextromethorphan hydrobromide and quinidine sulfate, a metabolic inhibitor that enables therapeutic dextromethorphan concentrations. These components act on NMDA receptors and sigma-1 in the brain, but the mechanism by which it exerts therapeutic effects in patients with pseudobulbar affect is unknown. The drug was tested in patients with ALS and MS and reduced involuntary laughing and crying episodes compared with placebo. 

Virtual reality may be an effective adjunctive therapy for patients experiencing upper arm motor deficits following stroke, according to a study published in the May Stroke. Researchers analyzed seven observational studies and five randomized trials that investigated the effects of virtual reality and video game technology on stroke patients’ upper arm strength and function. Among the observational studies, there was a 14.7% improvement in motor impairment and a 20.1% improvement in motor function; in the randomized trials, patients had an almost five times higher chance of improvement in motor function, compared with those who received traditional therapy. The researchers concluded, “Virtual reality and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.”

Investigators found that surgical revascularization can restore lost brain tissue in patients with cerebrovascular disease that impairs blood flow to the brain, as reported in the online April 14 Stroke. Twenty-nine patients who had undergone vascularization were included in the study. All patients had pre- and postsurgery studies of cerebrovascular reactivity using MRI, and cortical thickness in regions corresponding to steal physiology were measured. “At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere,” the authors stated. “Mean cortical thickness in the revascularized regions increased by 5.1%.” The investigators’ goal was to halt further loss of brain tissue due to strokes, “so it was remarkable to see the loss was actually reversed,” they commented.

Researchers determined that MRI imaging may predict which persons with cognitive impairment will progress to Alzheimer’s disease in a report published in the April 6 online Radiology. Baseline MRI was obtained for 164 individuals with late-onset Alzheimer’s disease, 317 with mild cognitive impairment, and 203 healthy controls. The investigators then used MRI to measure the thickness and amount of atrophy in the cerebral cortex. “Individualized risk estimates from baseline MRI examinations indicated that the one-year risk of conversion to Alzheimer’s disease ranged from 3% to 40%,” the researchers reported. “Relative to the risk of conversion to Alzheimer’s disease conferred by the clinical diagnosis of mild cognitive impairment alone, MRI measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available.”

Cotinine, a compound derived from tobacco, reduced brain plaques associated with dementia and memory loss, according to a study published in the online February 14 Journal of Alzheimer’s Disease. A group of investigators studied the effects of cotinine on b-amyloid plaque aggregation in the brains of mice with Alzheimer’s disease. Mice treated with the compound performed better than untreated mice on tasks measuring working memory and thinking skills; long-term treatment also appeared to prevent spatial memory impairment. Overall, the treated mice showed a 26% reduction in amyloid plaque deposits. “Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans,” the authors wrote. “The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of Alzheimer’s disease.”

A study published in the April 13 online Neurology provides evidence that treating certain vascular risk factors helps lower the risk for conversion from mild cognitive impairment to Alzheimer’s disease. Investigators assessed memory and thinking skills of 837 patients with mild cognitive impairment and then reassessed them five years later; 414 participants had at least one vascular risk factor at baseline. “At the end of follow-up 298 subjects converted to Alzheimer’s disease dementia, while 352 remained with mild cognitive impairment,” the investigators reported. “Treatment of individual vascular risk factors including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of Alzheimer’s disease conversion.” The findings of the study are observational, the authors concluded, but they suggest that active intervention and treatment of certain risk factors might reduce progression to Alzheimer’s disease.

Researchers have identified mutations of the synapsin 1 gene as a possible common genetic cause for both epilepsy and autism. Their study, published online in the April 12 Human Molecular Genetics, involved members of a large French-Canadian family who had autism spectrum disorders or epilepsy. The severe Q555X mutation appeared in all family members with epilepsy, and in all those who had an autism spectrum disorder. In addition, other mutations in synapsin 1 (A51G, A550T, and T567A) were found in 1% and 3.5% of a separate cohort of French-Canadian individuals with autism and epilepsy, respectively. “These results demonstrate that [synapsin 1] is a novel predisposing gene to [autism spectrum disorders], in addition to epilepsy,” the authors concluded. “[The results also] strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.”

Men who reported chronic ecstasy (MDMA) use were more likely to develop structural brain damage than those who did not use ecstasy, according to a study that was published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry. Using MRI, researchers measured the hippocampal volume of 10 male ecstasy users (average age, 21.3), compared with seven age- and gender-matched subjects who did not use ecstasy. The hippocampal volume of ecstasy users was 10.5% smaller than those of nonusing peers; the overall proportion of gray matter was 4.6% smaller, suggesting that the drug’s effects are not limited to the hippocampus. “These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage,” the authors wrote, adding: “Hippocampal atrophy is a hallmark for disease of progressive cognitive impairment in older patients, such as Alzheimer’s disease.”

In a study published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry, researchers reported that epileptic seizures carry a subsequent risk for brain tumor. “Our study suggests that tumor as an underlying cause for epilepsy may not become apparent for several years after onset, and indicates a need for ongoing vigilance,” the authors stated. In the retrospective cohort study, the investigators examined data regarding individuals with first-time epilepsy admissions and determined that, compared with patients admitted for other common and minor disorders, patients with epilepsy were almost 20 times more likely to develop cerebral tumor. The risk for developing malignant tumors was more than twice the risk for developing benign tumors. “The risk was highest for those aged 15 to 44 years at initial admission for epilepsy,” the authors reported. “The risk of cerebral tumor was still raised several years after initial admission for epilepsy.”

A novel gene transfer vector, NP2, is safe and well tolerated for the treatment of intractable pain, researchers reported in the April 11 online Annals of Neurology. Investigators conducted a multicenter, dose-escalation, phase I clinical trial of intradermal NP2 injection in 10 subjects with persistent pain caused by cancer, despite treatment with morphine or other analgesic. Participants who received the low dose of NP2 reported no substantive change in pain; patients in the middle and high dose cohorts reported pain relief. “There were no placebo controls in this relatively small study,” the authors concluded. “But the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.”

The FDA has approved DaTscan (ioflupane I 123 injection) for detecting dopamine transporters in the brains of adults with suspected Parkinsonian syndromes. The radiopharmaceutical agent is intended for use with single photon emission CT imaging to evaluate neurodegenerative movement disorders. The injection may be used as an adjunct to other diagnostic evaluation tools to distinguish between essential tremor and tremor due to Parkinson’s disease, as ioflupane I 123 injection alone cannot differentiate between different types of parkinsonian syndromes. The FDA’s approval was based on two phase III clinical trials in which the drug was used to evaluate dopamine transporter distribution in the brains of adult patients. As a new diagnostic adjunct to clinical assessments, ioflupane  I 123 can potentially help physicians select the appropriate treatments for patients with movement disorders.

Persons who are regularly exposed to welding fumes may be at an increased risk for brain damage, specifically in the same areas affected by Parkinson’s disease, researchers reported in the April 12 Neurology. “Welding exposes workers to manganese fumes, but it is unclear if this exposure damages dopaminergic neurons,” the authors stated. “The purpose of this study [was] to determine whether welding exposure is associated with damage to nigrostriatal neurons.” Using PET imaging on 20 welders with no parkinsonian symptoms, 20 individuals with symptoms, and 20 healthy controls, the investigators determined that asymptomatic welders had higher manganese levels in the blood and an average 11.7% reduction in dopamine in certain brain regions. The pattern of reduction seen in welders, however, was distinct from the dysfunction pattern found in symptomatic Parkinson’s disease.

The FDA has approved Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) for the treatment of pseudobulbar affect. The new therapy will help patients manage pseudobulbar affect that occurs secondary to multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, Parkinson’s disease, and other neurologic diseases. Nuedexta combines dextromethorphan hydrobromide and quinidine sulfate, a metabolic inhibitor that enables therapeutic dextromethorphan concentrations. These components act on NMDA receptors and sigma-1 in the brain, but the mechanism by which it exerts therapeutic effects in patients with pseudobulbar affect is unknown. The drug was tested in patients with ALS and MS and reduced involuntary laughing and crying episodes compared with placebo. 

Virtual reality may be an effective adjunctive therapy for patients experiencing upper arm motor deficits following stroke, according to a study published in the May Stroke. Researchers analyzed seven observational studies and five randomized trials that investigated the effects of virtual reality and video game technology on stroke patients’ upper arm strength and function. Among the observational studies, there was a 14.7% improvement in motor impairment and a 20.1% improvement in motor function; in the randomized trials, patients had an almost five times higher chance of improvement in motor function, compared with those who received traditional therapy. The researchers concluded, “Virtual reality and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.”

Investigators found that surgical revascularization can restore lost brain tissue in patients with cerebrovascular disease that impairs blood flow to the brain, as reported in the online April 14 Stroke. Twenty-nine patients who had undergone vascularization were included in the study. All patients had pre- and postsurgery studies of cerebrovascular reactivity using MRI, and cortical thickness in regions corresponding to steal physiology were measured. “At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere,” the authors stated. “Mean cortical thickness in the revascularized regions increased by 5.1%.” The investigators’ goal was to halt further loss of brain tissue due to strokes, “so it was remarkable to see the loss was actually reversed,” they commented.

Researchers determined that MRI imaging may predict which persons with cognitive impairment will progress to Alzheimer’s disease in a report published in the April 6 online Radiology. Baseline MRI was obtained for 164 individuals with late-onset Alzheimer’s disease, 317 with mild cognitive impairment, and 203 healthy controls. The investigators then used MRI to measure the thickness and amount of atrophy in the cerebral cortex. “Individualized risk estimates from baseline MRI examinations indicated that the one-year risk of conversion to Alzheimer’s disease ranged from 3% to 40%,” the researchers reported. “Relative to the risk of conversion to Alzheimer’s disease conferred by the clinical diagnosis of mild cognitive impairment alone, MRI measures yield substantially more informative patient-specific risk estimates. Such predictive prognostic information will be critical if disease-modifying therapies become available.”

Cotinine, a compound derived from tobacco, reduced brain plaques associated with dementia and memory loss, according to a study published in the online February 14 Journal of Alzheimer’s Disease. A group of investigators studied the effects of cotinine on b-amyloid plaque aggregation in the brains of mice with Alzheimer’s disease. Mice treated with the compound performed better than untreated mice on tasks measuring working memory and thinking skills; long-term treatment also appeared to prevent spatial memory impairment. Overall, the treated mice showed a 26% reduction in amyloid plaque deposits. “Cotinine, the main metabolite of nicotine, has a long half-life and does not have cardiovascular or addictive side effects in humans,” the authors wrote. “The good safety profile in humans and its beneficial effects suggest that cotinine may be an excellent therapeutic candidate for the treatment of Alzheimer’s disease.”

A study published in the April 13 online Neurology provides evidence that treating certain vascular risk factors helps lower the risk for conversion from mild cognitive impairment to Alzheimer’s disease. Investigators assessed memory and thinking skills of 837 patients with mild cognitive impairment and then reassessed them five years later; 414 participants had at least one vascular risk factor at baseline. “At the end of follow-up 298 subjects converted to Alzheimer’s disease dementia, while 352 remained with mild cognitive impairment,” the investigators reported. “Treatment of individual vascular risk factors including hypertension, diabetes, and hypercholesterolemia was associated with the reduced risk of Alzheimer’s disease conversion.” The findings of the study are observational, the authors concluded, but they suggest that active intervention and treatment of certain risk factors might reduce progression to Alzheimer’s disease.

Researchers have identified mutations of the synapsin 1 gene as a possible common genetic cause for both epilepsy and autism. Their study, published online in the April 12 Human Molecular Genetics, involved members of a large French-Canadian family who had autism spectrum disorders or epilepsy. The severe Q555X mutation appeared in all family members with epilepsy, and in all those who had an autism spectrum disorder. In addition, other mutations in synapsin 1 (A51G, A550T, and T567A) were found in 1% and 3.5% of a separate cohort of French-Canadian individuals with autism and epilepsy, respectively. “These results demonstrate that [synapsin 1] is a novel predisposing gene to [autism spectrum disorders], in addition to epilepsy,” the authors concluded. “[The results also] strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.”

Men who reported chronic ecstasy (MDMA) use were more likely to develop structural brain damage than those who did not use ecstasy, according to a study that was published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry. Using MRI, researchers measured the hippocampal volume of 10 male ecstasy users (average age, 21.3), compared with seven age- and gender-matched subjects who did not use ecstasy. The hippocampal volume of ecstasy users was 10.5% smaller than those of nonusing peers; the overall proportion of gray matter was 4.6% smaller, suggesting that the drug’s effects are not limited to the hippocampus. “These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage,” the authors wrote, adding: “Hippocampal atrophy is a hallmark for disease of progressive cognitive impairment in older patients, such as Alzheimer’s disease.”

In a study published in the March 28 online Journal of Neurology, Neurosurgery and Psychiatry, researchers reported that epileptic seizures carry a subsequent risk for brain tumor. “Our study suggests that tumor as an underlying cause for epilepsy may not become apparent for several years after onset, and indicates a need for ongoing vigilance,” the authors stated. In the retrospective cohort study, the investigators examined data regarding individuals with first-time epilepsy admissions and determined that, compared with patients admitted for other common and minor disorders, patients with epilepsy were almost 20 times more likely to develop cerebral tumor. The risk for developing malignant tumors was more than twice the risk for developing benign tumors. “The risk was highest for those aged 15 to 44 years at initial admission for epilepsy,” the authors reported. “The risk of cerebral tumor was still raised several years after initial admission for epilepsy.”

A novel gene transfer vector, NP2, is safe and well tolerated for the treatment of intractable pain, researchers reported in the April 11 online Annals of Neurology. Investigators conducted a multicenter, dose-escalation, phase I clinical trial of intradermal NP2 injection in 10 subjects with persistent pain caused by cancer, despite treatment with morphine or other analgesic. Participants who received the low dose of NP2 reported no substantive change in pain; patients in the middle and high dose cohorts reported pain relief. “There were no placebo controls in this relatively small study,” the authors concluded. “But the dose-responsive analgesic effects suggest that NP2 may be effective in reducing pain and warrants further clinical investigation.”

The FDA has approved DaTscan (ioflupane I 123 injection) for detecting dopamine transporters in the brains of adults with suspected Parkinsonian syndromes. The radiopharmaceutical agent is intended for use with single photon emission CT imaging to evaluate neurodegenerative movement disorders. The injection may be used as an adjunct to other diagnostic evaluation tools to distinguish between essential tremor and tremor due to Parkinson’s disease, as ioflupane I 123 injection alone cannot differentiate between different types of parkinsonian syndromes. The FDA’s approval was based on two phase III clinical trials in which the drug was used to evaluate dopamine transporter distribution in the brains of adult patients. As a new diagnostic adjunct to clinical assessments, ioflupane  I 123 can potentially help physicians select the appropriate treatments for patients with movement disorders.

Persons who are regularly exposed to welding fumes may be at an increased risk for brain damage, specifically in the same areas affected by Parkinson’s disease, researchers reported in the April 12 Neurology. “Welding exposes workers to manganese fumes, but it is unclear if this exposure damages dopaminergic neurons,” the authors stated. “The purpose of this study [was] to determine whether welding exposure is associated with damage to nigrostriatal neurons.” Using PET imaging on 20 welders with no parkinsonian symptoms, 20 individuals with symptoms, and 20 healthy controls, the investigators determined that asymptomatic welders had higher manganese levels in the blood and an average 11.7% reduction in dopamine in certain brain regions. The pattern of reduction seen in welders, however, was distinct from the dysfunction pattern found in symptomatic Parkinson’s disease.

The FDA has approved Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) for the treatment of pseudobulbar affect. The new therapy will help patients manage pseudobulbar affect that occurs secondary to multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), traumatic brain injury, stroke, Parkinson’s disease, and other neurologic diseases. Nuedexta combines dextromethorphan hydrobromide and quinidine sulfate, a metabolic inhibitor that enables therapeutic dextromethorphan concentrations. These components act on NMDA receptors and sigma-1 in the brain, but the mechanism by which it exerts therapeutic effects in patients with pseudobulbar affect is unknown. The drug was tested in patients with ALS and MS and reduced involuntary laughing and crying episodes compared with placebo. 

Virtual reality may be an effective adjunctive therapy for patients experiencing upper arm motor deficits following stroke, according to a study published in the May Stroke. Researchers analyzed seven observational studies and five randomized trials that investigated the effects of virtual reality and video game technology on stroke patients’ upper arm strength and function. Among the observational studies, there was a 14.7% improvement in motor impairment and a 20.1% improvement in motor function; in the randomized trials, patients had an almost five times higher chance of improvement in motor function, compared with those who received traditional therapy. The researchers concluded, “Virtual reality and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.”

Investigators found that surgical revascularization can restore lost brain tissue in patients with cerebrovascular disease that impairs blood flow to the brain, as reported in the online April 14 Stroke. Twenty-nine patients who had undergone vascularization were included in the study. All patients had pre- and postsurgery studies of cerebrovascular reactivity using MRI, and cortical thickness in regions corresponding to steal physiology were measured. “At an average of 11 months after surgery, cortical thickness increased in every successfully revascularized hemisphere,” the authors stated. “Mean cortical thickness in the revascularized regions increased by 5.1%.” The investigators’ goal was to halt further loss of brain tissue due to strokes, “so it was remarkable to see the loss was actually reversed,” they commented.