New and Noteworthy Information—October 2013

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

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

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

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

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

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

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

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

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

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

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

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

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

—Erik Greb
Senior Associate Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

—Erik Greb
Senior Associate Editor

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

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

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

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

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

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

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

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

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

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

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

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

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

—Erik Greb
Senior Associate Editor