News Roundup: New and Noteworthy Information

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.