News Roundup

Using a nicotine patch may induce cognitive improvement in patients with amnestic mild cognitive impairment (MCI) who do not smoke, researchers reported in the January 10 Neurology. All 74 subjects enrolled in the study had amnestic MCI and did not smoke; the investigators randomized 39 participants to receive 15 mg of transdermal nicotine daily for six months and 35 to receive placebo daily for the same time period. Results showed that participants safely tolerated the transdermal nicotine and that they improved on measures of attention, memory, and mental processing, but not in clinical overall impression of change. “We conclude that this initial study provides evidence for nicotine–induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies,” the researchers wrote.

Physicians may need to be cautious of potential drug interactions when selecting seizure medications for people with HIV/AIDs, according to a new guideline issued by the American Academy of Neurology and published in the online January 4 Neurology. A systematic review of the literature showed that antiepileptic drug (AED) and antiretroviral drug administration may be indicated in up to 55% of patients taking  antiretrovirals. Investigators found that clinicians might need to adjust the dosage of seizure drugs such as phenytoin and valproic acid to avoid adversely affecting patients’  antiretroviral levels. “It may be important to avoid enzyme-inducing AEDs in people on antiretroviral regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure,” the study authors said. The researchers recommend that physicians use pharmacokinetic assessment to monitor patients who must be on certain AED regimens for seizure control.

Subclinical atrial tachyarrhythmias were frequently observed in patients with pacemakers and were linked with a heightened risk of ischemic stroke or systemic embolism, according to a study published in the January 12 New England Journal of Medicine. For three months, researchers monitored 2,580 patients 65 and older for subclinical atrial tachyarrhythmias, defined as episodes of atrial rate of greater than 190 beats per minute for more than six minutes. The patients, who had hypertension and no history of atrial fibrillation, had recently been implanted with a pacemaker or defibrillator and were followed for a mean of 2.5 years for ischemic stroke or systemic embolism. Of the 2,580 patients, 261 experienced subclinical atrial tachyarrhythmias, which were associated with an increased risk of clinical atrial fibrillation and of ischemic stroke or systemic embolism. “The data from the present study support the concept that there is a link between subclinical atrial fibrillation and cryptogenic stroke,” the investigators stated.

The FDA has permitted marketing of the Stratify JCV (John Cunningham Virus) Antibody ELISA test to help determine the risk of progressive multifocal leukoencephalopathy (PML) in patients taking natalizumab to treat multiple sclerosis (MS) or Crohn’s disease. The test, which cannot diagnose PML, is intended to be used in conjunction with other clinical data from patients, such as the presence of anti-JCV antibodies, treatment with natalizumab for longer than two years, and treatment with certain immunosuppressants before receiving natalizumab. By considering these patient risk factors as well as the results of the Stratify JCV Antibody ELISA test, physicians may better assess the risks of continuing natalizumab treatment in patients on immunomodulatory therapy. The test will be available only to professionals, administered by prescription, and performed at Focus Diagnostics’ Reference Laboratory in Cypress, California.

Patients who experience stroke and later develop delirium are likely to have a higher mortality, longer hospitalizations, and a greater degree of dependence after discharge, researchers reported in the January 19 online Stroke. Investigators determined that 10 of 78 eligible studies met approval criteria for eligibility, validity, and quality, and a review of those studies showed that patients with stroke and delirium had higher in-patient mortality as well as mortality at 12 months, compared to patients without delirium. Furthermore, patients with stroke and delirium remained in the hospital for more time than those without delirium. Patients with stroke and delirium were also more likely to be discharged to an institution, such as a nursing home. “Early recognition and prevention of delirium may improve outcomes in stroke patients,” the researchers concluded.   

Using a nicotine patch may induce cognitive improvement in patients with amnestic mild cognitive impairment (MCI) who do not smoke, researchers reported in the January 10 Neurology. All 74 subjects enrolled in the study had amnestic MCI and did not smoke; the investigators randomized 39 participants to receive 15 mg of transdermal nicotine daily for six months and 35 to receive placebo daily for the same time period. Results showed that participants safely tolerated the transdermal nicotine and that they improved on measures of attention, memory, and mental processing, but not in clinical overall impression of change. “We conclude that this initial study provides evidence for nicotine–induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies,” the researchers wrote.

Physicians may need to be cautious of potential drug interactions when selecting seizure medications for people with HIV/AIDs, according to a new guideline issued by the American Academy of Neurology and published in the online January 4 Neurology. A systematic review of the literature showed that antiepileptic drug (AED) and antiretroviral drug administration may be indicated in up to 55% of patients taking  antiretrovirals. Investigators found that clinicians might need to adjust the dosage of seizure drugs such as phenytoin and valproic acid to avoid adversely affecting patients’  antiretroviral levels. “It may be important to avoid enzyme-inducing AEDs in people on antiretroviral regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure,” the study authors said. The researchers recommend that physicians use pharmacokinetic assessment to monitor patients who must be on certain AED regimens for seizure control.

Subclinical atrial tachyarrhythmias were frequently observed in patients with pacemakers and were linked with a heightened risk of ischemic stroke or systemic embolism, according to a study published in the January 12 New England Journal of Medicine. For three months, researchers monitored 2,580 patients 65 and older for subclinical atrial tachyarrhythmias, defined as episodes of atrial rate of greater than 190 beats per minute for more than six minutes. The patients, who had hypertension and no history of atrial fibrillation, had recently been implanted with a pacemaker or defibrillator and were followed for a mean of 2.5 years for ischemic stroke or systemic embolism. Of the 2,580 patients, 261 experienced subclinical atrial tachyarrhythmias, which were associated with an increased risk of clinical atrial fibrillation and of ischemic stroke or systemic embolism. “The data from the present study support the concept that there is a link between subclinical atrial fibrillation and cryptogenic stroke,” the investigators stated.

The FDA has permitted marketing of the Stratify JCV (John Cunningham Virus) Antibody ELISA test to help determine the risk of progressive multifocal leukoencephalopathy (PML) in patients taking natalizumab to treat multiple sclerosis (MS) or Crohn’s disease. The test, which cannot diagnose PML, is intended to be used in conjunction with other clinical data from patients, such as the presence of anti-JCV antibodies, treatment with natalizumab for longer than two years, and treatment with certain immunosuppressants before receiving natalizumab. By considering these patient risk factors as well as the results of the Stratify JCV Antibody ELISA test, physicians may better assess the risks of continuing natalizumab treatment in patients on immunomodulatory therapy. The test will be available only to professionals, administered by prescription, and performed at Focus Diagnostics’ Reference Laboratory in Cypress, California.

Patients who experience stroke and later develop delirium are likely to have a higher mortality, longer hospitalizations, and a greater degree of dependence after discharge, researchers reported in the January 19 online Stroke. Investigators determined that 10 of 78 eligible studies met approval criteria for eligibility, validity, and quality, and a review of those studies showed that patients with stroke and delirium had higher in-patient mortality as well as mortality at 12 months, compared to patients without delirium. Furthermore, patients with stroke and delirium remained in the hospital for more time than those without delirium. Patients with stroke and delirium were also more likely to be discharged to an institution, such as a nursing home. “Early recognition and prevention of delirium may improve outcomes in stroke patients,” the researchers concluded.   

Using a nicotine patch may induce cognitive improvement in patients with amnestic mild cognitive impairment (MCI) who do not smoke, researchers reported in the January 10 Neurology. All 74 subjects enrolled in the study had amnestic MCI and did not smoke; the investigators randomized 39 participants to receive 15 mg of transdermal nicotine daily for six months and 35 to receive placebo daily for the same time period. Results showed that participants safely tolerated the transdermal nicotine and that they improved on measures of attention, memory, and mental processing, but not in clinical overall impression of change. “We conclude that this initial study provides evidence for nicotine–induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies,” the researchers wrote.

Physicians may need to be cautious of potential drug interactions when selecting seizure medications for people with HIV/AIDs, according to a new guideline issued by the American Academy of Neurology and published in the online January 4 Neurology. A systematic review of the literature showed that antiepileptic drug (AED) and antiretroviral drug administration may be indicated in up to 55% of patients taking  antiretrovirals. Investigators found that clinicians might need to adjust the dosage of seizure drugs such as phenytoin and valproic acid to avoid adversely affecting patients’  antiretroviral levels. “It may be important to avoid enzyme-inducing AEDs in people on antiretroviral regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure,” the study authors said. The researchers recommend that physicians use pharmacokinetic assessment to monitor patients who must be on certain AED regimens for seizure control.

Subclinical atrial tachyarrhythmias were frequently observed in patients with pacemakers and were linked with a heightened risk of ischemic stroke or systemic embolism, according to a study published in the January 12 New England Journal of Medicine. For three months, researchers monitored 2,580 patients 65 and older for subclinical atrial tachyarrhythmias, defined as episodes of atrial rate of greater than 190 beats per minute for more than six minutes. The patients, who had hypertension and no history of atrial fibrillation, had recently been implanted with a pacemaker or defibrillator and were followed for a mean of 2.5 years for ischemic stroke or systemic embolism. Of the 2,580 patients, 261 experienced subclinical atrial tachyarrhythmias, which were associated with an increased risk of clinical atrial fibrillation and of ischemic stroke or systemic embolism. “The data from the present study support the concept that there is a link between subclinical atrial fibrillation and cryptogenic stroke,” the investigators stated.

The FDA has permitted marketing of the Stratify JCV (John Cunningham Virus) Antibody ELISA test to help determine the risk of progressive multifocal leukoencephalopathy (PML) in patients taking natalizumab to treat multiple sclerosis (MS) or Crohn’s disease. The test, which cannot diagnose PML, is intended to be used in conjunction with other clinical data from patients, such as the presence of anti-JCV antibodies, treatment with natalizumab for longer than two years, and treatment with certain immunosuppressants before receiving natalizumab. By considering these patient risk factors as well as the results of the Stratify JCV Antibody ELISA test, physicians may better assess the risks of continuing natalizumab treatment in patients on immunomodulatory therapy. The test will be available only to professionals, administered by prescription, and performed at Focus Diagnostics’ Reference Laboratory in Cypress, California.

Patients who experience stroke and later develop delirium are likely to have a higher mortality, longer hospitalizations, and a greater degree of dependence after discharge, researchers reported in the January 19 online Stroke. Investigators determined that 10 of 78 eligible studies met approval criteria for eligibility, validity, and quality, and a review of those studies showed that patients with stroke and delirium had higher in-patient mortality as well as mortality at 12 months, compared to patients without delirium. Furthermore, patients with stroke and delirium remained in the hospital for more time than those without delirium. Patients with stroke and delirium were also more likely to be discharged to an institution, such as a nursing home. “Early recognition and prevention of delirium may improve outcomes in stroke patients,” the researchers concluded.   

Premature birth may increase the risk of epilepsy as an adult, according to a study published in the October 4 Neurology. Investigators observed rates of hospitalization for epilepsy and prescription of antiepileptic drugs during a four-year period in 630,090 adults (including 27,953 who were born preterm). “We found a strong association between preterm birth and epilepsy that increased by earlier gestational age,” the researchers stated. After adjusting for fetal growth and potential confounders, the investigators found that individuals who were born at 23 to 31 weeks were almost five times more likely to be hospitalized for epilepsy than those who were born full-term. The odds ratios for those born at 32 to 34 weeks and 35 to 36 weeks were 1.98 and 1.76, respectively. “These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors,” the investigators noted.

The use of attention-deficit/hyperactivity disorder (ADHD) medications is not associated with an increased risk of serious cardiovascular events, as some adverse-event reports have suggested, according to a report published online November 1 in the New England Journal of Medicine. A group of researchers estimated the risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) among more than 1 million children and young adults (age range, 2 to 24). There were 81 cardiovascular events among the cohort members and seven serious cardiovascular events in current users. “Current users of ADHD drugs were not at increased risk for serious cardiovascular events (hazard ratio, 0.75),” the investigators reported. “Risk was not increased for any of the individual end points, or for current users as compared with former users (hazard ratio, 0.70).”

Researchers have identified several genetic variants that contribute to early stent thrombosis, as reported in the October 26 JAMA. Twenty-three genetic variants were examined in 15 different genes in a population of patients undergoing percutaneous coronary intervention. “Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (odds ratio, 1.99), ABCB1 3435 TT genotype (odds ratio, 2.16), and ITGB3 PLA2 carriage (odds ratio, 0.52),” the investigators reported. The researchers also found that certain nongenetic factors (including use of proton pump inhibitors and higher clopidogrel loading doses) were associated with early stent thrombosis. “Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts,” the investigators concluded.

Changes in the blurring of the cortical gray and white matter border were associated with lower verbal expression abilities, according to a study that was published in the October 26 issue of the Journal of Neuroscience. Healthy participants underwent MRI to determine their gray and white matter contrast (GWC), and they also completed measures of verbal expression and verbal working memory. The investigators found that blurring in the participants’ left hemisphere inferior frontal cortex and temporal pole was associated with reduced verbal expression abilities, and that reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. “Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomic substrates of cognition in healthy and diseased populations,” the researchers concluded.

The FDA has approved ONFI (clobazam) for use as an adjunctive therapy for seizures that are associated with Lennox-Gastaut syndrome in patients who are two years and older. ONFI (Lundbeck, Inc; Deerfield, Illinois) is an oral antiepileptic drug and is a derivative of benzodiazepine. The drug will be available in 5-, 10-, and 20-mg tablets. The exact mechanism of action of clobazam is not fully understood, but it is thought to involve potentiation of GABA-ergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor. The FDA’s approval was based on the results of two multicenter controlled studies, including a phase 3 trial involving 238 patients with Lennox-Gastaut syndrome who experienced a significant reduction in the weekly frequency of drop seizures. The most common side effects of clobazam include sleepiness, fever, drooling, aggressive behavior, irritability, and lack of coordination.

People who rate their health as poor or fair may be significantly more likely to develop Alzheimer’s disease or vascular dementia, compared with those who rate their health as good, according to a study that was published in the October 11 issue of Neurology. Study participants rated their health status at baseline (as “good,” “fair,” or “poor”) and were followed for a median of 6.7 years for the incidence of dementia. During the follow-up period, 618 participants developed dementia, and risk of dementia was increased among participants with poor (hazard ratio, 1.70) or fair (hazard ratio, 1.34) self-rated health, compared with participants with good self-rated health. “Self-rated health could help raise awareness of medical doctors about a patient’s risk of dementia, especially in those without conditions indicative of potential cognitive impairment,” the investigators concluded.

Diffusion-weighted imaging (DWI) had a higher predictive value than fluid-attenuated inversion recovery (FLAIR) MRI for detecting patients within the recommended time window for thrombolysis, according to a study that was published in the November issue of Lancet Neurology. Researchers analyzed the clinical and MRI data from patients with acute stroke who had undergone DWI and FLAIR imaging within 12 hours of symptom onset, and they determined that patients with an acute ischemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. “DWI-FLAIR mismatch identified patients within four to five hours of symptom onset with 62% sensitivity, 78% specificity, 83% positive predictive value, and 54% negative predictive value,” the investigators stated. “These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomized trial of thrombolysis in patients with unknown time of symptom onset.”

Older adults who were taking statins before sustaining moderate or severe head injury had improved survival and functional outcomes, according to the results of a study that was published in the October issue of the Journal of Trauma. “Of 523 eligible individuals, 117 (22%) used statins at the time of injury,” the investigators wrote. “Statin use was associated with a 76% lower adjusted risk of in-hospital death.” Patients who took the cholesterol-lowering drugs were also 13% more likely to have a good recovery at 12 months postinjury, compared with patients who did not use statins. However, individuals with cardiovascular comorbidities lose this benefit, the investigators noted. “Statins, as possible protective agents in head trauma, warrant further study,” the study authors concluded.

A neuron’s inability to secrete beta-amyloid (Aß) plays a major role in the pathogenesis of Alzheimer’s disease, a finding that contradicts the dominant theory in Alzheimer’s disease pathology, according to a study in the October 26 Journal of Neuroscience. By studying neurons in Alzheimer’s disease–transgenic and wild-type mice, the investigators found that an increase in intracellular Aß occurred early in the beginning stages of the disease, and that this accumulation of Aß inside the neuron was caused by the neuron’s inability to properly secrete Aß. “We demonstrate that synaptic activity promotes an increase in the Aß-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aß42,” the investigators stated. “Remarkably, Alzheimer’s disease–transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Ab and reduce intraneuronal Aß has important implications for the pathogenesis and treatment of Alzheimer’s disease.”

Long-term estrogen deprivation in aging rats is associated with a decrease in estrogen receptors in the brain, and with a loss of the hormone’s neuroprotective effects, according to a study that was published in the August 30 issue of the Proceedings of the National Academy of Sciences. Researchers studied estrogen levels in middle-aged rats that had undergone long periods of estrogen deprivation and observed an enhanced interaction between estrogen receptors and the CHIP enzyme (a carboxyl terminus of Hsc70-interacting protein), which contributed to the decrease of estrogen receptors in the hippocampus. They also found that administration of 17b-estradiol (E2) replacement therapy shortly before, but not after, the drop in hormone levels prevented degradation of estrogen receptors in the brain, and preserved estrogen’s neuroprotective effects. “As a whole, the study provides support for a ‘critical period’ for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period,” the researchers concluded.

Premature birth may increase the risk of epilepsy as an adult, according to a study published in the October 4 Neurology. Investigators observed rates of hospitalization for epilepsy and prescription of antiepileptic drugs during a four-year period in 630,090 adults (including 27,953 who were born preterm). “We found a strong association between preterm birth and epilepsy that increased by earlier gestational age,” the researchers stated. After adjusting for fetal growth and potential confounders, the investigators found that individuals who were born at 23 to 31 weeks were almost five times more likely to be hospitalized for epilepsy than those who were born full-term. The odds ratios for those born at 32 to 34 weeks and 35 to 36 weeks were 1.98 and 1.76, respectively. “These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors,” the investigators noted.

The use of attention-deficit/hyperactivity disorder (ADHD) medications is not associated with an increased risk of serious cardiovascular events, as some adverse-event reports have suggested, according to a report published online November 1 in the New England Journal of Medicine. A group of researchers estimated the risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) among more than 1 million children and young adults (age range, 2 to 24). There were 81 cardiovascular events among the cohort members and seven serious cardiovascular events in current users. “Current users of ADHD drugs were not at increased risk for serious cardiovascular events (hazard ratio, 0.75),” the investigators reported. “Risk was not increased for any of the individual end points, or for current users as compared with former users (hazard ratio, 0.70).”

Researchers have identified several genetic variants that contribute to early stent thrombosis, as reported in the October 26 JAMA. Twenty-three genetic variants were examined in 15 different genes in a population of patients undergoing percutaneous coronary intervention. “Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (odds ratio, 1.99), ABCB1 3435 TT genotype (odds ratio, 2.16), and ITGB3 PLA2 carriage (odds ratio, 0.52),” the investigators reported. The researchers also found that certain nongenetic factors (including use of proton pump inhibitors and higher clopidogrel loading doses) were associated with early stent thrombosis. “Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts,” the investigators concluded.

Changes in the blurring of the cortical gray and white matter border were associated with lower verbal expression abilities, according to a study that was published in the October 26 issue of the Journal of Neuroscience. Healthy participants underwent MRI to determine their gray and white matter contrast (GWC), and they also completed measures of verbal expression and verbal working memory. The investigators found that blurring in the participants’ left hemisphere inferior frontal cortex and temporal pole was associated with reduced verbal expression abilities, and that reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. “Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomic substrates of cognition in healthy and diseased populations,” the researchers concluded.

The FDA has approved ONFI (clobazam) for use as an adjunctive therapy for seizures that are associated with Lennox-Gastaut syndrome in patients who are two years and older. ONFI (Lundbeck, Inc; Deerfield, Illinois) is an oral antiepileptic drug and is a derivative of benzodiazepine. The drug will be available in 5-, 10-, and 20-mg tablets. The exact mechanism of action of clobazam is not fully understood, but it is thought to involve potentiation of GABA-ergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor. The FDA’s approval was based on the results of two multicenter controlled studies, including a phase 3 trial involving 238 patients with Lennox-Gastaut syndrome who experienced a significant reduction in the weekly frequency of drop seizures. The most common side effects of clobazam include sleepiness, fever, drooling, aggressive behavior, irritability, and lack of coordination.

People who rate their health as poor or fair may be significantly more likely to develop Alzheimer’s disease or vascular dementia, compared with those who rate their health as good, according to a study that was published in the October 11 issue of Neurology. Study participants rated their health status at baseline (as “good,” “fair,” or “poor”) and were followed for a median of 6.7 years for the incidence of dementia. During the follow-up period, 618 participants developed dementia, and risk of dementia was increased among participants with poor (hazard ratio, 1.70) or fair (hazard ratio, 1.34) self-rated health, compared with participants with good self-rated health. “Self-rated health could help raise awareness of medical doctors about a patient’s risk of dementia, especially in those without conditions indicative of potential cognitive impairment,” the investigators concluded.

Diffusion-weighted imaging (DWI) had a higher predictive value than fluid-attenuated inversion recovery (FLAIR) MRI for detecting patients within the recommended time window for thrombolysis, according to a study that was published in the November issue of Lancet Neurology. Researchers analyzed the clinical and MRI data from patients with acute stroke who had undergone DWI and FLAIR imaging within 12 hours of symptom onset, and they determined that patients with an acute ischemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. “DWI-FLAIR mismatch identified patients within four to five hours of symptom onset with 62% sensitivity, 78% specificity, 83% positive predictive value, and 54% negative predictive value,” the investigators stated. “These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomized trial of thrombolysis in patients with unknown time of symptom onset.”

Older adults who were taking statins before sustaining moderate or severe head injury had improved survival and functional outcomes, according to the results of a study that was published in the October issue of the Journal of Trauma. “Of 523 eligible individuals, 117 (22%) used statins at the time of injury,” the investigators wrote. “Statin use was associated with a 76% lower adjusted risk of in-hospital death.” Patients who took the cholesterol-lowering drugs were also 13% more likely to have a good recovery at 12 months postinjury, compared with patients who did not use statins. However, individuals with cardiovascular comorbidities lose this benefit, the investigators noted. “Statins, as possible protective agents in head trauma, warrant further study,” the study authors concluded.

A neuron’s inability to secrete beta-amyloid (Aß) plays a major role in the pathogenesis of Alzheimer’s disease, a finding that contradicts the dominant theory in Alzheimer’s disease pathology, according to a study in the October 26 Journal of Neuroscience. By studying neurons in Alzheimer’s disease–transgenic and wild-type mice, the investigators found that an increase in intracellular Aß occurred early in the beginning stages of the disease, and that this accumulation of Aß inside the neuron was caused by the neuron’s inability to properly secrete Aß. “We demonstrate that synaptic activity promotes an increase in the Aß-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aß42,” the investigators stated. “Remarkably, Alzheimer’s disease–transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Ab and reduce intraneuronal Aß has important implications for the pathogenesis and treatment of Alzheimer’s disease.”

Long-term estrogen deprivation in aging rats is associated with a decrease in estrogen receptors in the brain, and with a loss of the hormone’s neuroprotective effects, according to a study that was published in the August 30 issue of the Proceedings of the National Academy of Sciences. Researchers studied estrogen levels in middle-aged rats that had undergone long periods of estrogen deprivation and observed an enhanced interaction between estrogen receptors and the CHIP enzyme (a carboxyl terminus of Hsc70-interacting protein), which contributed to the decrease of estrogen receptors in the hippocampus. They also found that administration of 17b-estradiol (E2) replacement therapy shortly before, but not after, the drop in hormone levels prevented degradation of estrogen receptors in the brain, and preserved estrogen’s neuroprotective effects. “As a whole, the study provides support for a ‘critical period’ for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period,” the researchers concluded.

Premature birth may increase the risk of epilepsy as an adult, according to a study published in the October 4 Neurology. Investigators observed rates of hospitalization for epilepsy and prescription of antiepileptic drugs during a four-year period in 630,090 adults (including 27,953 who were born preterm). “We found a strong association between preterm birth and epilepsy that increased by earlier gestational age,” the researchers stated. After adjusting for fetal growth and potential confounders, the investigators found that individuals who were born at 23 to 31 weeks were almost five times more likely to be hospitalized for epilepsy than those who were born full-term. The odds ratios for those born at 32 to 34 weeks and 35 to 36 weeks were 1.98 and 1.76, respectively. “These associations persisted after excluding individuals with cerebral palsy, inflammatory diseases of the CNS, cerebrovascular disease, and brain tumors,” the investigators noted.

The use of attention-deficit/hyperactivity disorder (ADHD) medications is not associated with an increased risk of serious cardiovascular events, as some adverse-event reports have suggested, according to a report published online November 1 in the New England Journal of Medicine. A group of researchers estimated the risk of serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) among more than 1 million children and young adults (age range, 2 to 24). There were 81 cardiovascular events among the cohort members and seven serious cardiovascular events in current users. “Current users of ADHD drugs were not at increased risk for serious cardiovascular events (hazard ratio, 0.75),” the investigators reported. “Risk was not increased for any of the individual end points, or for current users as compared with former users (hazard ratio, 0.70).”

Researchers have identified several genetic variants that contribute to early stent thrombosis, as reported in the October 26 JAMA. Twenty-three genetic variants were examined in 15 different genes in a population of patients undergoing percutaneous coronary intervention. “Among the 23 genetic variants investigated in 15 different genes, the significant determinants of early stent thrombosis were CYP2C19 metabolic status (odds ratio, 1.99), ABCB1 3435 TT genotype (odds ratio, 2.16), and ITGB3 PLA2 carriage (odds ratio, 0.52),” the investigators reported. The researchers also found that certain nongenetic factors (including use of proton pump inhibitors and higher clopidogrel loading doses) were associated with early stent thrombosis. “Future studies are needed to validate the prognostic accuracy of these risk factors in prospective cohorts,” the investigators concluded.

Changes in the blurring of the cortical gray and white matter border were associated with lower verbal expression abilities, according to a study that was published in the October 26 issue of the Journal of Neuroscience. Healthy participants underwent MRI to determine their gray and white matter contrast (GWC), and they also completed measures of verbal expression and verbal working memory. The investigators found that blurring in the participants’ left hemisphere inferior frontal cortex and temporal pole was associated with reduced verbal expression abilities, and that reduced verbal working memory was associated with blurring in widespread left frontal and temporal cortices. “Such lateralized and focal results provide support for GWC as a measure of regional functional integrity and highlight its potential role in probing the neuroanatomic substrates of cognition in healthy and diseased populations,” the researchers concluded.

The FDA has approved ONFI (clobazam) for use as an adjunctive therapy for seizures that are associated with Lennox-Gastaut syndrome in patients who are two years and older. ONFI (Lundbeck, Inc; Deerfield, Illinois) is an oral antiepileptic drug and is a derivative of benzodiazepine. The drug will be available in 5-, 10-, and 20-mg tablets. The exact mechanism of action of clobazam is not fully understood, but it is thought to involve potentiation of GABA-ergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor. The FDA’s approval was based on the results of two multicenter controlled studies, including a phase 3 trial involving 238 patients with Lennox-Gastaut syndrome who experienced a significant reduction in the weekly frequency of drop seizures. The most common side effects of clobazam include sleepiness, fever, drooling, aggressive behavior, irritability, and lack of coordination.

People who rate their health as poor or fair may be significantly more likely to develop Alzheimer’s disease or vascular dementia, compared with those who rate their health as good, according to a study that was published in the October 11 issue of Neurology. Study participants rated their health status at baseline (as “good,” “fair,” or “poor”) and were followed for a median of 6.7 years for the incidence of dementia. During the follow-up period, 618 participants developed dementia, and risk of dementia was increased among participants with poor (hazard ratio, 1.70) or fair (hazard ratio, 1.34) self-rated health, compared with participants with good self-rated health. “Self-rated health could help raise awareness of medical doctors about a patient’s risk of dementia, especially in those without conditions indicative of potential cognitive impairment,” the investigators concluded.

Diffusion-weighted imaging (DWI) had a higher predictive value than fluid-attenuated inversion recovery (FLAIR) MRI for detecting patients within the recommended time window for thrombolysis, according to a study that was published in the November issue of Lancet Neurology. Researchers analyzed the clinical and MRI data from patients with acute stroke who had undergone DWI and FLAIR imaging within 12 hours of symptom onset, and they determined that patients with an acute ischemic lesion detected with DWI but not with FLAIR imaging are likely to be within a time window for which thrombolysis is safe and effective. “DWI-FLAIR mismatch identified patients within four to five hours of symptom onset with 62% sensitivity, 78% specificity, 83% positive predictive value, and 54% negative predictive value,” the investigators stated. “These findings lend support to the use of DWI-FLAIR mismatch for selection of patients in a future randomized trial of thrombolysis in patients with unknown time of symptom onset.”

Older adults who were taking statins before sustaining moderate or severe head injury had improved survival and functional outcomes, according to the results of a study that was published in the October issue of the Journal of Trauma. “Of 523 eligible individuals, 117 (22%) used statins at the time of injury,” the investigators wrote. “Statin use was associated with a 76% lower adjusted risk of in-hospital death.” Patients who took the cholesterol-lowering drugs were also 13% more likely to have a good recovery at 12 months postinjury, compared with patients who did not use statins. However, individuals with cardiovascular comorbidities lose this benefit, the investigators noted. “Statins, as possible protective agents in head trauma, warrant further study,” the study authors concluded.

A neuron’s inability to secrete beta-amyloid (Aß) plays a major role in the pathogenesis of Alzheimer’s disease, a finding that contradicts the dominant theory in Alzheimer’s disease pathology, according to a study in the October 26 Journal of Neuroscience. By studying neurons in Alzheimer’s disease–transgenic and wild-type mice, the investigators found that an increase in intracellular Aß occurred early in the beginning stages of the disease, and that this accumulation of Aß inside the neuron was caused by the neuron’s inability to properly secrete Aß. “We demonstrate that synaptic activity promotes an increase in the Aß-degrading protease neprilysin at the cell surface and a concomitant increase in colocalization with Aß42,” the investigators stated. “Remarkably, Alzheimer’s disease–transgenic but not wild-type neurons show reduced levels of neprilysin with time in culture. This impaired ability to secrete Ab and reduce intraneuronal Aß has important implications for the pathogenesis and treatment of Alzheimer’s disease.”

Long-term estrogen deprivation in aging rats is associated with a decrease in estrogen receptors in the brain, and with a loss of the hormone’s neuroprotective effects, according to a study that was published in the August 30 issue of the Proceedings of the National Academy of Sciences. Researchers studied estrogen levels in middle-aged rats that had undergone long periods of estrogen deprivation and observed an enhanced interaction between estrogen receptors and the CHIP enzyme (a carboxyl terminus of Hsc70-interacting protein), which contributed to the decrease of estrogen receptors in the hippocampus. They also found that administration of 17b-estradiol (E2) replacement therapy shortly before, but not after, the drop in hormone levels prevented degradation of estrogen receptors in the brain, and preserved estrogen’s neuroprotective effects. “As a whole, the study provides support for a ‘critical period’ for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period,” the researchers concluded.

Comprehensive cardiac rehabilitation may be effective for prevention of future stroke in patients who have had a transient ischemic stroke (TIA) or a mild, nondisabling stroke, according to a study published in the online September 22 Stroke. Researchers tested the effectiveness of the rehabilitation program, which integrates structured lifestyle interventions and medications, in 80 participants who had at least one vascular risk factor. After six months of intervention, the investigators reported favorable and significant changes in aerobic capacity, cholesterol levels, triglycerides, waist circumference, body mass index, and body weight. “Comprehensive cardiac rehabilitation is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities,” the authors concluded.

Two separate teams of investigators have identified a new human genetic mutation that may be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both studies appear in the online September 21 Neuron. Previous research has linked the 9p21 region of chromosome 9 with both ALS and FTD; using this theory, each research group performed a genetic analysis in patients with 9p21-associated ALS or FTD. Both groups discovered a large hexanucleotide repeat expansion in the C9ORF72 gene, which may accumulate as abnormal RNA foci inside neurons and promote disease pathogenesis and neurodegeneration. The investigators reported that this mutation may explain at least one-third of all familial cases of ALS and FTD, as well as some noninherited cases.

Depression is associated with a significant increase in fatal and ischemic stroke, but not hemorrhagic stroke, according to a study published in the September 21 JAMA. Investigators conducted a systematic review and meta-analysis of 28 prospective studies (8,478 cases of stroke) that reported risk estimates of stroke morbidity or mortality. Individuals with depression had a 45% higher risk for total stroke, 55% higher risk for fatal stroke, and 25% higher risk for ischemic stroke. The corresponding absolute risk differences were 106 cases for total stroke, 53 cases for ischemic stroke, and 22 cases for fatal stroke per 100,000 individuals per year. “Depression is associated with a significantly increased risk of stroke morbidity and mortality,” the investigators wrote. “More studies are needed to explore the underlying mechanisms and elucidate the causal pathways that link depression and stroke.”

Patients with refractory epilepsy who receive adjunctive treatment with antiepileptic drugs have nearly a seven times lower risk of sudden unexpected death in epilepsy (SUDEP) compared to those that receive placebo treatments, according to a meta-analysis published September 19 online in Lancet Neurology.  The researchers analyzed 33 deaths reported in a collection of randomized placebo-controlled trials involving patients with refractory epilepsy to determine if adjunctive antiepileptic drugs in efficacious doses lowered the incidence of sudden unexpected death. “Definite or probable SUDEP, all SUDEP, and all causes of death were significantly less frequent in the efficacious antiepileptic drug group than in the placebo group,” the researchers concluded. “This result provides evidence in favor of active treatment revision for patients with refractory epilepsy.”

Investigators have identified a strong bidirectional relationship between epilepsy and schizophrenia, according to a study appearing in the September 19 Epilepsia. The investigators analyzed the incidence and risk of developing epilepsy in a group of 5,195 patients with schizophrenia, as well as the incidence and risk of developing schizophrenia in a group of 11,527 patients with epilepsy; they then compared these results to healthy controls. “The incidence of epilepsy was higher in the schizophrenia cohort than in the nonschizophrenia cohort with an adjusted hazard ratio of 5.88,” the investigators reported. “The incidence of schizophrenia was higher in the epilepsy cohort than in the nonepilepsy comparison cohort with an adjusted hazard ratio of 7.65.” The researchers concluded that the two conditions may share a mutual susceptibility, but noted that further studies on the mechanisms for this relationship are necessary.

The Genesis implanted neurostimulation device (St. Jude Medical, Inc; St. Paul, Minnesota) has received European regulatory approval for the treatment of intractable chronic migraine. The peripheral nerve stimulation system delivers mild electrical pulses to the occipital nerves to help manage the pain and disability associated with this condition. Approval was achieved based on the results of a randomized, double-blind, controlled study of 157 patients with chronic migraine. After one year of peripheral nerve stimulation therapy, 65% of participants reported excellent or good pain relief, 68% expressed an improvement in their quality of life, and 67% were satisfied with the results of their procedure. The system developers hope that this approval will expand treatment options for patients who have exhausted all other treatment options for chronic migraine

Compared to civilians, veterans experience a greater delay in diagnosis of psychogenic nonepileptic seizures (PNES), according to a study published in the September 6 Neurology. “PNES are frequently encountered in epilepsy monitoring units and can result in significant long-term disability,” the investigators wrote. “We reviewed our experience with veterans undergoing seizure evaluation in the epilepsy monitoring units to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug treatment.” They found that PNES were identified in 25% of veterans and 26% of civilians admitted to epilepsy monitoring units, and that the average delay from onset to diagnosis was about five years for veterans and one year for civilians. In addition, treatment with antiepileptic drugs was four times greater for veterans with PNES compared with civilians.

Rates of hospitalizations for ischemic stroke in adolescents and young adults increased up to 37% between 1995 and 2008, according to a study published in the September 2 online Annals of Neurology. Investigators analyzed discharge data for patients between the ages of 5 and 44 hospitalized for ischemic stroke, as well as information about comorbidites and stroke risk factors. The prevalence of hospitalizations increased among all age and gender groups, except females ages 5 to 14 years, the researchers reported. The most common coexisting conditions among the study population were hypertension, diabetes, obesity, lipid disorders, and tobacco use; these were increased among patients hospitalized with acute ischemic stroke. “Our results … accentuate the need for public health initiatives to reduce risk factors for stroke among adolescents and young adults,” the investigators concluded.

Researchers have identified a mutation in the sigma-1 receptor that is responsible for the development of juvenile amyotrophic lateral sclerosis (ALS). The results of the study, appearing in the August 12 online Annals of Neurology, could lead to the development of potential therapeutic targets for the disease. “We performed homozygosity and direct sequencing to detect the genetic variant and tested the effect of this variant on a motor neuron-like cell line model expressing the wild-type or mutant gene,” the investigators explained. They identified a shared homozygosity region in persons with the disease; they also observed that cells expressing the mutant protein were less resistant to apoptosis induced by endoplasmic reticulum stress. “Sigma-1 receptors are known to have neuroprotective properties,” the authors concluded. “Our findings emphasize the role of sigma-1 receptors in motor neuron function and disease.”

Comprehensive cardiac rehabilitation may be effective for prevention of future stroke in patients who have had a transient ischemic stroke (TIA) or a mild, nondisabling stroke, according to a study published in the online September 22 Stroke. Researchers tested the effectiveness of the rehabilitation program, which integrates structured lifestyle interventions and medications, in 80 participants who had at least one vascular risk factor. After six months of intervention, the investigators reported favorable and significant changes in aerobic capacity, cholesterol levels, triglycerides, waist circumference, body mass index, and body weight. “Comprehensive cardiac rehabilitation is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities,” the authors concluded.

Two separate teams of investigators have identified a new human genetic mutation that may be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both studies appear in the online September 21 Neuron. Previous research has linked the 9p21 region of chromosome 9 with both ALS and FTD; using this theory, each research group performed a genetic analysis in patients with 9p21-associated ALS or FTD. Both groups discovered a large hexanucleotide repeat expansion in the C9ORF72 gene, which may accumulate as abnormal RNA foci inside neurons and promote disease pathogenesis and neurodegeneration. The investigators reported that this mutation may explain at least one-third of all familial cases of ALS and FTD, as well as some noninherited cases.

Depression is associated with a significant increase in fatal and ischemic stroke, but not hemorrhagic stroke, according to a study published in the September 21 JAMA. Investigators conducted a systematic review and meta-analysis of 28 prospective studies (8,478 cases of stroke) that reported risk estimates of stroke morbidity or mortality. Individuals with depression had a 45% higher risk for total stroke, 55% higher risk for fatal stroke, and 25% higher risk for ischemic stroke. The corresponding absolute risk differences were 106 cases for total stroke, 53 cases for ischemic stroke, and 22 cases for fatal stroke per 100,000 individuals per year. “Depression is associated with a significantly increased risk of stroke morbidity and mortality,” the investigators wrote. “More studies are needed to explore the underlying mechanisms and elucidate the causal pathways that link depression and stroke.”

Patients with refractory epilepsy who receive adjunctive treatment with antiepileptic drugs have nearly a seven times lower risk of sudden unexpected death in epilepsy (SUDEP) compared to those that receive placebo treatments, according to a meta-analysis published September 19 online in Lancet Neurology.  The researchers analyzed 33 deaths reported in a collection of randomized placebo-controlled trials involving patients with refractory epilepsy to determine if adjunctive antiepileptic drugs in efficacious doses lowered the incidence of sudden unexpected death. “Definite or probable SUDEP, all SUDEP, and all causes of death were significantly less frequent in the efficacious antiepileptic drug group than in the placebo group,” the researchers concluded. “This result provides evidence in favor of active treatment revision for patients with refractory epilepsy.”

Investigators have identified a strong bidirectional relationship between epilepsy and schizophrenia, according to a study appearing in the September 19 Epilepsia. The investigators analyzed the incidence and risk of developing epilepsy in a group of 5,195 patients with schizophrenia, as well as the incidence and risk of developing schizophrenia in a group of 11,527 patients with epilepsy; they then compared these results to healthy controls. “The incidence of epilepsy was higher in the schizophrenia cohort than in the nonschizophrenia cohort with an adjusted hazard ratio of 5.88,” the investigators reported. “The incidence of schizophrenia was higher in the epilepsy cohort than in the nonepilepsy comparison cohort with an adjusted hazard ratio of 7.65.” The researchers concluded that the two conditions may share a mutual susceptibility, but noted that further studies on the mechanisms for this relationship are necessary.

The Genesis implanted neurostimulation device (St. Jude Medical, Inc; St. Paul, Minnesota) has received European regulatory approval for the treatment of intractable chronic migraine. The peripheral nerve stimulation system delivers mild electrical pulses to the occipital nerves to help manage the pain and disability associated with this condition. Approval was achieved based on the results of a randomized, double-blind, controlled study of 157 patients with chronic migraine. After one year of peripheral nerve stimulation therapy, 65% of participants reported excellent or good pain relief, 68% expressed an improvement in their quality of life, and 67% were satisfied with the results of their procedure. The system developers hope that this approval will expand treatment options for patients who have exhausted all other treatment options for chronic migraine

Compared to civilians, veterans experience a greater delay in diagnosis of psychogenic nonepileptic seizures (PNES), according to a study published in the September 6 Neurology. “PNES are frequently encountered in epilepsy monitoring units and can result in significant long-term disability,” the investigators wrote. “We reviewed our experience with veterans undergoing seizure evaluation in the epilepsy monitoring units to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug treatment.” They found that PNES were identified in 25% of veterans and 26% of civilians admitted to epilepsy monitoring units, and that the average delay from onset to diagnosis was about five years for veterans and one year for civilians. In addition, treatment with antiepileptic drugs was four times greater for veterans with PNES compared with civilians.

Rates of hospitalizations for ischemic stroke in adolescents and young adults increased up to 37% between 1995 and 2008, according to a study published in the September 2 online Annals of Neurology. Investigators analyzed discharge data for patients between the ages of 5 and 44 hospitalized for ischemic stroke, as well as information about comorbidites and stroke risk factors. The prevalence of hospitalizations increased among all age and gender groups, except females ages 5 to 14 years, the researchers reported. The most common coexisting conditions among the study population were hypertension, diabetes, obesity, lipid disorders, and tobacco use; these were increased among patients hospitalized with acute ischemic stroke. “Our results … accentuate the need for public health initiatives to reduce risk factors for stroke among adolescents and young adults,” the investigators concluded.

Researchers have identified a mutation in the sigma-1 receptor that is responsible for the development of juvenile amyotrophic lateral sclerosis (ALS). The results of the study, appearing in the August 12 online Annals of Neurology, could lead to the development of potential therapeutic targets for the disease. “We performed homozygosity and direct sequencing to detect the genetic variant and tested the effect of this variant on a motor neuron-like cell line model expressing the wild-type or mutant gene,” the investigators explained. They identified a shared homozygosity region in persons with the disease; they also observed that cells expressing the mutant protein were less resistant to apoptosis induced by endoplasmic reticulum stress. “Sigma-1 receptors are known to have neuroprotective properties,” the authors concluded. “Our findings emphasize the role of sigma-1 receptors in motor neuron function and disease.”

Comprehensive cardiac rehabilitation may be effective for prevention of future stroke in patients who have had a transient ischemic stroke (TIA) or a mild, nondisabling stroke, according to a study published in the online September 22 Stroke. Researchers tested the effectiveness of the rehabilitation program, which integrates structured lifestyle interventions and medications, in 80 participants who had at least one vascular risk factor. After six months of intervention, the investigators reported favorable and significant changes in aerobic capacity, cholesterol levels, triglycerides, waist circumference, body mass index, and body weight. “Comprehensive cardiac rehabilitation is feasible and effective for secondary prevention after transient ischemic attack or mild, nondisabling stroke, offering a promising model for vascular protection across chronic disease entities,” the authors concluded.

Two separate teams of investigators have identified a new human genetic mutation that may be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both studies appear in the online September 21 Neuron. Previous research has linked the 9p21 region of chromosome 9 with both ALS and FTD; using this theory, each research group performed a genetic analysis in patients with 9p21-associated ALS or FTD. Both groups discovered a large hexanucleotide repeat expansion in the C9ORF72 gene, which may accumulate as abnormal RNA foci inside neurons and promote disease pathogenesis and neurodegeneration. The investigators reported that this mutation may explain at least one-third of all familial cases of ALS and FTD, as well as some noninherited cases.

Depression is associated with a significant increase in fatal and ischemic stroke, but not hemorrhagic stroke, according to a study published in the September 21 JAMA. Investigators conducted a systematic review and meta-analysis of 28 prospective studies (8,478 cases of stroke) that reported risk estimates of stroke morbidity or mortality. Individuals with depression had a 45% higher risk for total stroke, 55% higher risk for fatal stroke, and 25% higher risk for ischemic stroke. The corresponding absolute risk differences were 106 cases for total stroke, 53 cases for ischemic stroke, and 22 cases for fatal stroke per 100,000 individuals per year. “Depression is associated with a significantly increased risk of stroke morbidity and mortality,” the investigators wrote. “More studies are needed to explore the underlying mechanisms and elucidate the causal pathways that link depression and stroke.”

Patients with refractory epilepsy who receive adjunctive treatment with antiepileptic drugs have nearly a seven times lower risk of sudden unexpected death in epilepsy (SUDEP) compared to those that receive placebo treatments, according to a meta-analysis published September 19 online in Lancet Neurology.  The researchers analyzed 33 deaths reported in a collection of randomized placebo-controlled trials involving patients with refractory epilepsy to determine if adjunctive antiepileptic drugs in efficacious doses lowered the incidence of sudden unexpected death. “Definite or probable SUDEP, all SUDEP, and all causes of death were significantly less frequent in the efficacious antiepileptic drug group than in the placebo group,” the researchers concluded. “This result provides evidence in favor of active treatment revision for patients with refractory epilepsy.”

Investigators have identified a strong bidirectional relationship between epilepsy and schizophrenia, according to a study appearing in the September 19 Epilepsia. The investigators analyzed the incidence and risk of developing epilepsy in a group of 5,195 patients with schizophrenia, as well as the incidence and risk of developing schizophrenia in a group of 11,527 patients with epilepsy; they then compared these results to healthy controls. “The incidence of epilepsy was higher in the schizophrenia cohort than in the nonschizophrenia cohort with an adjusted hazard ratio of 5.88,” the investigators reported. “The incidence of schizophrenia was higher in the epilepsy cohort than in the nonepilepsy comparison cohort with an adjusted hazard ratio of 7.65.” The researchers concluded that the two conditions may share a mutual susceptibility, but noted that further studies on the mechanisms for this relationship are necessary.

The Genesis implanted neurostimulation device (St. Jude Medical, Inc; St. Paul, Minnesota) has received European regulatory approval for the treatment of intractable chronic migraine. The peripheral nerve stimulation system delivers mild electrical pulses to the occipital nerves to help manage the pain and disability associated with this condition. Approval was achieved based on the results of a randomized, double-blind, controlled study of 157 patients with chronic migraine. After one year of peripheral nerve stimulation therapy, 65% of participants reported excellent or good pain relief, 68% expressed an improvement in their quality of life, and 67% were satisfied with the results of their procedure. The system developers hope that this approval will expand treatment options for patients who have exhausted all other treatment options for chronic migraine

Compared to civilians, veterans experience a greater delay in diagnosis of psychogenic nonepileptic seizures (PNES), according to a study published in the September 6 Neurology. “PNES are frequently encountered in epilepsy monitoring units and can result in significant long-term disability,” the investigators wrote. “We reviewed our experience with veterans undergoing seizure evaluation in the epilepsy monitoring units to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug treatment.” They found that PNES were identified in 25% of veterans and 26% of civilians admitted to epilepsy monitoring units, and that the average delay from onset to diagnosis was about five years for veterans and one year for civilians. In addition, treatment with antiepileptic drugs was four times greater for veterans with PNES compared with civilians.

Rates of hospitalizations for ischemic stroke in adolescents and young adults increased up to 37% between 1995 and 2008, according to a study published in the September 2 online Annals of Neurology. Investigators analyzed discharge data for patients between the ages of 5 and 44 hospitalized for ischemic stroke, as well as information about comorbidites and stroke risk factors. The prevalence of hospitalizations increased among all age and gender groups, except females ages 5 to 14 years, the researchers reported. The most common coexisting conditions among the study population were hypertension, diabetes, obesity, lipid disorders, and tobacco use; these were increased among patients hospitalized with acute ischemic stroke. “Our results … accentuate the need for public health initiatives to reduce risk factors for stroke among adolescents and young adults,” the investigators concluded.

Researchers have identified a mutation in the sigma-1 receptor that is responsible for the development of juvenile amyotrophic lateral sclerosis (ALS). The results of the study, appearing in the August 12 online Annals of Neurology, could lead to the development of potential therapeutic targets for the disease. “We performed homozygosity and direct sequencing to detect the genetic variant and tested the effect of this variant on a motor neuron-like cell line model expressing the wild-type or mutant gene,” the investigators explained. They identified a shared homozygosity region in persons with the disease; they also observed that cells expressing the mutant protein were less resistant to apoptosis induced by endoplasmic reticulum stress. “Sigma-1 receptors are known to have neuroprotective properties,” the authors concluded. “Our findings emphasize the role of sigma-1 receptors in motor neuron function and disease.”

Investigators have developed a simple test to identify people with asymptomatic carotid stenosis who have an increased risk of stroke, as reported in the August 17 online Neurology. “Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD),” the authors wrote. To explore the predictive value of a composite score based on these two measures, the investigators recruited 435 participants with  asymptomatic carotid stenosis and collected baseline ultrasound images and TCD data. “Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in  asymptomatic carotid stenosis,” the authors wrote. They also noted that the combination of both markers allows a greater prediction than either measure alone.

Researchers have identified a possible common cause of several forms of amyotrophic lateral sclerosis (ALS), according to a study published in the August 21 online Nature. Although some genetic mutations have been shown to cause certain forms of the disease, the causes of certain types of familial ALS and of the vast majority of sporadic ALS had been unknown. “Here, we show that mutations in the UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS, and ALS/dementia,” the investigators reported. They also performed functional analysis that showed that these mutations lead to impairment in protein degradation. “Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation, and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention,” the authors concluded.

Using computational approaches and drug and genomic information, scientists can predict new uses for existing medicines, according to two studies published online in the August 17 Science Translational Medicine. The practice, known as drug repositioning, was investigated in a study supported by the NIH. The researchers used a computer program that searched through possible drug-disease combinations (from a set of 164 established drug compounds and 100 diseases) to identify drug and disease combinations whose gene expression patterns essentially canceled each other out. In one specific case, topiramate, an anticonvulsant for the treatment of epilepsy, was found to be a potential therapeutic option for inflammatory bowel disease. “The application of established drug compounds to new therapeutic indications … offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval,” the authors wrote. “This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.”

Women with depression may have an increased risk of subsequent stroke, according to the results of a study published in the August 11 Stroke. A group of researchers followed-up more than 80,000 women (age range, 54 to 79) without a history of stroke from the Nurses’ Health Study to determine if depression was associated with stroke. Depressive symptoms were assessed at multiple time points, and antidepressant medication use and physician-diagnosed depression were recorded biennially. “During six years of follow-up, 1,033 incident strokes were documented,” the authors reported. “For each cycle, participants who reported current depression had an increased risk of stroke (hazard ratio, 1.41), whereas individuals who only had a history of depression were at nonsignificantly elevated risk (hazard ratio, 1.23), compared with women who never reported a diagnosis of depression or antidepressant medication use.”

According to a study published in the August 11 online JAMA, women with sleep-disordered breathing were more likely to develop dementia or cognitive impairment, compared with women without the disorder. “Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults,” the authors wrote. “However, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.” To investigate this association and its potential mechanisms, the researchers conducted a prospective sleep and cognition study of 298 women without dementia who underwent polysomnography. “Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% versus 44.8%),” they reported. “Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.”

Older patients (ages 80 to 91) with Alzheimer’s disease experience less severe cognitive or brain changes than younger patients (ages 60 to 75) with the disease, according to a study published in the August 10 online Neurology. Researchers compared hippocampal volume and cortical gray matter thickness of 105 patients with Alzheimer’s disease and 125 healthy controls to determine if brain morphometric and cognitive profiles differed according to age. “Several cognitive domains (executive function, immediate memory, and attention/processing speed) were less abnormal in the very old with Alzheimer’s disease than in the young old with Alzheimer’s disease,” the investigators wrote. “Similarly, the very old with Alzheimer’s disease showed less severe cortical thinning than the young old with Alzheimer’s disease.” The authors noted that mild cases of Alzheimer’s disease in older people might go undetected due to these age-related differences in cognitive and morphometric changes.

Researchers have found new genetic variants associated with multiple sclerosis (MS), as reported in the August 10 Nature. “In a collaborative genome-wide association study involving 9,772 cases of European descent … we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci,” the authors wrote. One-third of the genes they identified have previously been implicated in other autoimmune diseases, suggesting that the same general processes occur in more than one type of autoimmune disease; two of the genes were also involved in the metabolism of vitamin D, supporting the existence of a link between genetic and environmental risk factors. “Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of MS,” the investigators concluded.

The US Food and Drug Administration (FDA) has approved Botox (onabotulinumtoxinA) for injection for the treatment of urinary incontinence caused by detrusor overactivity in adults with neurologic conditions, including multiple sclerosis (MS) and spinal cord injury. The FDA’s approval was based on two phase III clinical trials in which onabotulinumtoxinA was administered to 691 patients with MS or spinal cord injury and urinary incontinence; when the drug was injected directly into the bladder muscle, episodes of urinary incontinence were significantly reduced. Researchers at Allergan, Inc (Irvine, California) believe the drug will benefit people who cannot tolerate an oral anticholinergic medication.

Patients with Parkinson’s disease who visit a neurologist are less likely to be placed in a nursing home, have a lower risk of hip fracture, and have a lower likelihood of death than those who do not receive care from a neurologist, according to a study published online in the August 10 online Neurology. Only 58% of patients visited a neurologist, and race and sex were significant demographic predictors for receiving treatment. “Women and minorities with Parkinson’s disease obtain specialist care less often than white men,” the researchers stated. “Neurologist care of patients with Parkinson’s disease may be associated with improved selected clinical outcomes and greater survival.”

A survey of graduating neurology residents reveals that 94% feel comfortable using t-PA, compared with 73% in a survey from 2000. The results of the survey were published online in the August 4 Stroke. The researchers sent a 12-item survey to neurology residents about their experience and confidence with assessment of patients with acute stroke and treatment with t-PA. Of 491 residents, 281 (58%) responded, with 95% reporting that they had personally administered t-PA and 98% reporting that they had been involved in post–t-PA care. “Neurology residents’ experience and comfort treating acute ischemic stroke with t-PA increased significantly between 2000 and 2010,” the authors concluded, “as did resident exposure to stroke teams and formal training in the NIH Stroke Scale.”

Hypertension, diabetes, smoking, and obesity during midlife are associated with an increased rate of progression of vascular brain injury, hippocampal atrophy, and decline in executive function later in life, researchers reported in the August 2 Neurology. “Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline,” the investigators wrote. More than 1,300 people without dementia (mean age, 54) were enrolled in the study. After ten years, the researchers recorded changes in participants’ regional and total brain volume, memory recall, and performance on executive functioning tests. Hypertension and obesity in midlife were most greatly associated with diminished executive function; diabetes and smoking were associated with a more rapid increase in atrophy and decrease in brain volume. “Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function,” the authors concluded.

Statins may lower the risk for future stroke in young adults who have already had an ischemic stroke, according to research published in the August 2 Neurology. Researchers investigated the effects of these cholesterol-lowering drugs in 215 patients (mean age, 39.1) who had an ischemic stroke of unknown etiology and categorized them into three groups based on statin use (never used, continuous use, or discontinuous use). “Seventy-two patients (33%) used a statin at some time during follow-up,” the researchers reported. “Twenty-nine (20%) events occurred among the 143 patients never on a statin, none among the 36 with continuous statin, and 4 (1%) among the 36 with discontinuous statin.” The risk of a second event was 77% lower for patients who had used a statin after first stroke.

Researchers believe they have found a better approach to diagnosing temporal lobe epilepsy (TLE) using 7-Tesla MRI, according to a study in the July 11 online Radiology. The investigators performed 7-Tesla MRI on eight patients with TLE and 11 healthy controls. “All eight patients with TLE had hippocampal abnormalities on the epileptogenic side,” the researchers stated. “Hippocampal malrotation was observed in three patients with TLE and four control subjects.” Subsequent subregional analysis revealed that six patients with TLE had selective lateral Ammon horn atrophy, and one patient had diffuse Ammon horn and dentate gyrus atrophy. The authors concluded: “Ultrahigh-field-strength MRI permitted detection of selectively greater Ammon horn atrophy in patients with TLE and hippocampal sclerosis.”

Investigators have developed a simple test to identify people with asymptomatic carotid stenosis who have an increased risk of stroke, as reported in the August 17 online Neurology. “Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD),” the authors wrote. To explore the predictive value of a composite score based on these two measures, the investigators recruited 435 participants with  asymptomatic carotid stenosis and collected baseline ultrasound images and TCD data. “Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in  asymptomatic carotid stenosis,” the authors wrote. They also noted that the combination of both markers allows a greater prediction than either measure alone.

Researchers have identified a possible common cause of several forms of amyotrophic lateral sclerosis (ALS), according to a study published in the August 21 online Nature. Although some genetic mutations have been shown to cause certain forms of the disease, the causes of certain types of familial ALS and of the vast majority of sporadic ALS had been unknown. “Here, we show that mutations in the UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS, and ALS/dementia,” the investigators reported. They also performed functional analysis that showed that these mutations lead to impairment in protein degradation. “Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation, and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention,” the authors concluded.

Using computational approaches and drug and genomic information, scientists can predict new uses for existing medicines, according to two studies published online in the August 17 Science Translational Medicine. The practice, known as drug repositioning, was investigated in a study supported by the NIH. The researchers used a computer program that searched through possible drug-disease combinations (from a set of 164 established drug compounds and 100 diseases) to identify drug and disease combinations whose gene expression patterns essentially canceled each other out. In one specific case, topiramate, an anticonvulsant for the treatment of epilepsy, was found to be a potential therapeutic option for inflammatory bowel disease. “The application of established drug compounds to new therapeutic indications … offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval,” the authors wrote. “This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.”

Women with depression may have an increased risk of subsequent stroke, according to the results of a study published in the August 11 Stroke. A group of researchers followed-up more than 80,000 women (age range, 54 to 79) without a history of stroke from the Nurses’ Health Study to determine if depression was associated with stroke. Depressive symptoms were assessed at multiple time points, and antidepressant medication use and physician-diagnosed depression were recorded biennially. “During six years of follow-up, 1,033 incident strokes were documented,” the authors reported. “For each cycle, participants who reported current depression had an increased risk of stroke (hazard ratio, 1.41), whereas individuals who only had a history of depression were at nonsignificantly elevated risk (hazard ratio, 1.23), compared with women who never reported a diagnosis of depression or antidepressant medication use.”

According to a study published in the August 11 online JAMA, women with sleep-disordered breathing were more likely to develop dementia or cognitive impairment, compared with women without the disorder. “Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults,” the authors wrote. “However, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.” To investigate this association and its potential mechanisms, the researchers conducted a prospective sleep and cognition study of 298 women without dementia who underwent polysomnography. “Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% versus 44.8%),” they reported. “Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.”

Older patients (ages 80 to 91) with Alzheimer’s disease experience less severe cognitive or brain changes than younger patients (ages 60 to 75) with the disease, according to a study published in the August 10 online Neurology. Researchers compared hippocampal volume and cortical gray matter thickness of 105 patients with Alzheimer’s disease and 125 healthy controls to determine if brain morphometric and cognitive profiles differed according to age. “Several cognitive domains (executive function, immediate memory, and attention/processing speed) were less abnormal in the very old with Alzheimer’s disease than in the young old with Alzheimer’s disease,” the investigators wrote. “Similarly, the very old with Alzheimer’s disease showed less severe cortical thinning than the young old with Alzheimer’s disease.” The authors noted that mild cases of Alzheimer’s disease in older people might go undetected due to these age-related differences in cognitive and morphometric changes.

Researchers have found new genetic variants associated with multiple sclerosis (MS), as reported in the August 10 Nature. “In a collaborative genome-wide association study involving 9,772 cases of European descent … we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci,” the authors wrote. One-third of the genes they identified have previously been implicated in other autoimmune diseases, suggesting that the same general processes occur in more than one type of autoimmune disease; two of the genes were also involved in the metabolism of vitamin D, supporting the existence of a link between genetic and environmental risk factors. “Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of MS,” the investigators concluded.

The US Food and Drug Administration (FDA) has approved Botox (onabotulinumtoxinA) for injection for the treatment of urinary incontinence caused by detrusor overactivity in adults with neurologic conditions, including multiple sclerosis (MS) and spinal cord injury. The FDA’s approval was based on two phase III clinical trials in which onabotulinumtoxinA was administered to 691 patients with MS or spinal cord injury and urinary incontinence; when the drug was injected directly into the bladder muscle, episodes of urinary incontinence were significantly reduced. Researchers at Allergan, Inc (Irvine, California) believe the drug will benefit people who cannot tolerate an oral anticholinergic medication.

Patients with Parkinson’s disease who visit a neurologist are less likely to be placed in a nursing home, have a lower risk of hip fracture, and have a lower likelihood of death than those who do not receive care from a neurologist, according to a study published online in the August 10 online Neurology. Only 58% of patients visited a neurologist, and race and sex were significant demographic predictors for receiving treatment. “Women and minorities with Parkinson’s disease obtain specialist care less often than white men,” the researchers stated. “Neurologist care of patients with Parkinson’s disease may be associated with improved selected clinical outcomes and greater survival.”

A survey of graduating neurology residents reveals that 94% feel comfortable using t-PA, compared with 73% in a survey from 2000. The results of the survey were published online in the August 4 Stroke. The researchers sent a 12-item survey to neurology residents about their experience and confidence with assessment of patients with acute stroke and treatment with t-PA. Of 491 residents, 281 (58%) responded, with 95% reporting that they had personally administered t-PA and 98% reporting that they had been involved in post–t-PA care. “Neurology residents’ experience and comfort treating acute ischemic stroke with t-PA increased significantly between 2000 and 2010,” the authors concluded, “as did resident exposure to stroke teams and formal training in the NIH Stroke Scale.”

Hypertension, diabetes, smoking, and obesity during midlife are associated with an increased rate of progression of vascular brain injury, hippocampal atrophy, and decline in executive function later in life, researchers reported in the August 2 Neurology. “Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline,” the investigators wrote. More than 1,300 people without dementia (mean age, 54) were enrolled in the study. After ten years, the researchers recorded changes in participants’ regional and total brain volume, memory recall, and performance on executive functioning tests. Hypertension and obesity in midlife were most greatly associated with diminished executive function; diabetes and smoking were associated with a more rapid increase in atrophy and decrease in brain volume. “Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function,” the authors concluded.

Statins may lower the risk for future stroke in young adults who have already had an ischemic stroke, according to research published in the August 2 Neurology. Researchers investigated the effects of these cholesterol-lowering drugs in 215 patients (mean age, 39.1) who had an ischemic stroke of unknown etiology and categorized them into three groups based on statin use (never used, continuous use, or discontinuous use). “Seventy-two patients (33%) used a statin at some time during follow-up,” the researchers reported. “Twenty-nine (20%) events occurred among the 143 patients never on a statin, none among the 36 with continuous statin, and 4 (1%) among the 36 with discontinuous statin.” The risk of a second event was 77% lower for patients who had used a statin after first stroke.

Researchers believe they have found a better approach to diagnosing temporal lobe epilepsy (TLE) using 7-Tesla MRI, according to a study in the July 11 online Radiology. The investigators performed 7-Tesla MRI on eight patients with TLE and 11 healthy controls. “All eight patients with TLE had hippocampal abnormalities on the epileptogenic side,” the researchers stated. “Hippocampal malrotation was observed in three patients with TLE and four control subjects.” Subsequent subregional analysis revealed that six patients with TLE had selective lateral Ammon horn atrophy, and one patient had diffuse Ammon horn and dentate gyrus atrophy. The authors concluded: “Ultrahigh-field-strength MRI permitted detection of selectively greater Ammon horn atrophy in patients with TLE and hippocampal sclerosis.”

Investigators have developed a simple test to identify people with asymptomatic carotid stenosis who have an increased risk of stroke, as reported in the August 17 online Neurology. “Two potential markers of high risk are echolucent plaque morphology on carotid ultrasound and embolic signals in the ipsilateral middle cerebral artery on transcranial Doppler ultrasound (TCD),” the authors wrote. To explore the predictive value of a composite score based on these two measures, the investigators recruited 435 participants with  asymptomatic carotid stenosis and collected baseline ultrasound images and TCD data. “Plaque morphology assessed using a simple, and clinically applicable, visual rating scale predicts ipsilateral stroke risk in  asymptomatic carotid stenosis,” the authors wrote. They also noted that the combination of both markers allows a greater prediction than either measure alone.

Researchers have identified a possible common cause of several forms of amyotrophic lateral sclerosis (ALS), according to a study published in the August 21 online Nature. Although some genetic mutations have been shown to cause certain forms of the disease, the causes of certain types of familial ALS and of the vast majority of sporadic ALS had been unknown. “Here, we show that mutations in the UBQLN2, which encodes the ubiquitin-like protein ubiquilin 2, cause dominantly inherited, chromosome-X-linked ALS, and ALS/dementia,” the investigators reported. They also performed functional analysis that showed that these mutations lead to impairment in protein degradation. “Therefore, our findings link abnormalities in ubiquilin 2 to defects in the protein degradation pathway, abnormal protein aggregation, and neurodegeneration, indicating a common pathogenic mechanism that can be exploited for therapeutic intervention,” the authors concluded.

Using computational approaches and drug and genomic information, scientists can predict new uses for existing medicines, according to two studies published online in the August 17 Science Translational Medicine. The practice, known as drug repositioning, was investigated in a study supported by the NIH. The researchers used a computer program that searched through possible drug-disease combinations (from a set of 164 established drug compounds and 100 diseases) to identify drug and disease combinations whose gene expression patterns essentially canceled each other out. In one specific case, topiramate, an anticonvulsant for the treatment of epilepsy, was found to be a potential therapeutic option for inflammatory bowel disease. “The application of established drug compounds to new therapeutic indications … offers several advantages over traditional drug development, including reduced development costs and shorter paths to approval,” the authors wrote. “This computational method provides a systematic approach for repositioning established drugs to treat a wide range of human diseases.”

Women with depression may have an increased risk of subsequent stroke, according to the results of a study published in the August 11 Stroke. A group of researchers followed-up more than 80,000 women (age range, 54 to 79) without a history of stroke from the Nurses’ Health Study to determine if depression was associated with stroke. Depressive symptoms were assessed at multiple time points, and antidepressant medication use and physician-diagnosed depression were recorded biennially. “During six years of follow-up, 1,033 incident strokes were documented,” the authors reported. “For each cycle, participants who reported current depression had an increased risk of stroke (hazard ratio, 1.41), whereas individuals who only had a history of depression were at nonsignificantly elevated risk (hazard ratio, 1.23), compared with women who never reported a diagnosis of depression or antidepressant medication use.”

According to a study published in the August 11 online JAMA, women with sleep-disordered breathing were more likely to develop dementia or cognitive impairment, compared with women without the disorder. “Sleep-disordered breathing (characterized by recurrent arousals from sleep and intermittent hypoxemia) is common among older adults,” the authors wrote. “However, it remains unclear whether sleep-disordered breathing precedes cognitive impairment in older adults.” To investigate this association and its potential mechanisms, the researchers conducted a prospective sleep and cognition study of 298 women without dementia who underwent polysomnography. “Compared with the 193 women without sleep-disordered breathing, the 105 women (35.2%) with sleep-disordered breathing were more likely to develop mild cognitive impairment or dementia (31.1% versus 44.8%),” they reported. “Measures of sleep fragmentation (arousal index and wake after sleep onset) or sleep duration (total sleep time) were not associated with risk of cognitive impairment.”

Older patients (ages 80 to 91) with Alzheimer’s disease experience less severe cognitive or brain changes than younger patients (ages 60 to 75) with the disease, according to a study published in the August 10 online Neurology. Researchers compared hippocampal volume and cortical gray matter thickness of 105 patients with Alzheimer’s disease and 125 healthy controls to determine if brain morphometric and cognitive profiles differed according to age. “Several cognitive domains (executive function, immediate memory, and attention/processing speed) were less abnormal in the very old with Alzheimer’s disease than in the young old with Alzheimer’s disease,” the investigators wrote. “Similarly, the very old with Alzheimer’s disease showed less severe cortical thinning than the young old with Alzheimer’s disease.” The authors noted that mild cases of Alzheimer’s disease in older people might go undetected due to these age-related differences in cognitive and morphometric changes.

Researchers have found new genetic variants associated with multiple sclerosis (MS), as reported in the August 10 Nature. “In a collaborative genome-wide association study involving 9,772 cases of European descent … we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci,” the authors wrote. One-third of the genes they identified have previously been implicated in other autoimmune diseases, suggesting that the same general processes occur in more than one type of autoimmune disease; two of the genes were also involved in the metabolism of vitamin D, supporting the existence of a link between genetic and environmental risk factors. “Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of MS,” the investigators concluded.

The US Food and Drug Administration (FDA) has approved Botox (onabotulinumtoxinA) for injection for the treatment of urinary incontinence caused by detrusor overactivity in adults with neurologic conditions, including multiple sclerosis (MS) and spinal cord injury. The FDA’s approval was based on two phase III clinical trials in which onabotulinumtoxinA was administered to 691 patients with MS or spinal cord injury and urinary incontinence; when the drug was injected directly into the bladder muscle, episodes of urinary incontinence were significantly reduced. Researchers at Allergan, Inc (Irvine, California) believe the drug will benefit people who cannot tolerate an oral anticholinergic medication.

Patients with Parkinson’s disease who visit a neurologist are less likely to be placed in a nursing home, have a lower risk of hip fracture, and have a lower likelihood of death than those who do not receive care from a neurologist, according to a study published online in the August 10 online Neurology. Only 58% of patients visited a neurologist, and race and sex were significant demographic predictors for receiving treatment. “Women and minorities with Parkinson’s disease obtain specialist care less often than white men,” the researchers stated. “Neurologist care of patients with Parkinson’s disease may be associated with improved selected clinical outcomes and greater survival.”

A survey of graduating neurology residents reveals that 94% feel comfortable using t-PA, compared with 73% in a survey from 2000. The results of the survey were published online in the August 4 Stroke. The researchers sent a 12-item survey to neurology residents about their experience and confidence with assessment of patients with acute stroke and treatment with t-PA. Of 491 residents, 281 (58%) responded, with 95% reporting that they had personally administered t-PA and 98% reporting that they had been involved in post–t-PA care. “Neurology residents’ experience and comfort treating acute ischemic stroke with t-PA increased significantly between 2000 and 2010,” the authors concluded, “as did resident exposure to stroke teams and formal training in the NIH Stroke Scale.”

Hypertension, diabetes, smoking, and obesity during midlife are associated with an increased rate of progression of vascular brain injury, hippocampal atrophy, and decline in executive function later in life, researchers reported in the August 2 Neurology. “Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline,” the investigators wrote. More than 1,300 people without dementia (mean age, 54) were enrolled in the study. After ten years, the researchers recorded changes in participants’ regional and total brain volume, memory recall, and performance on executive functioning tests. Hypertension and obesity in midlife were most greatly associated with diminished executive function; diabetes and smoking were associated with a more rapid increase in atrophy and decrease in brain volume. “Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function,” the authors concluded.

Statins may lower the risk for future stroke in young adults who have already had an ischemic stroke, according to research published in the August 2 Neurology. Researchers investigated the effects of these cholesterol-lowering drugs in 215 patients (mean age, 39.1) who had an ischemic stroke of unknown etiology and categorized them into three groups based on statin use (never used, continuous use, or discontinuous use). “Seventy-two patients (33%) used a statin at some time during follow-up,” the researchers reported. “Twenty-nine (20%) events occurred among the 143 patients never on a statin, none among the 36 with continuous statin, and 4 (1%) among the 36 with discontinuous statin.” The risk of a second event was 77% lower for patients who had used a statin after first stroke.

Researchers believe they have found a better approach to diagnosing temporal lobe epilepsy (TLE) using 7-Tesla MRI, according to a study in the July 11 online Radiology. The investigators performed 7-Tesla MRI on eight patients with TLE and 11 healthy controls. “All eight patients with TLE had hippocampal abnormalities on the epileptogenic side,” the researchers stated. “Hippocampal malrotation was observed in three patients with TLE and four control subjects.” Subsequent subregional analysis revealed that six patients with TLE had selective lateral Ammon horn atrophy, and one patient had diffuse Ammon horn and dentate gyrus atrophy. The authors concluded: “Ultrahigh-field-strength MRI permitted detection of selectively greater Ammon horn atrophy in patients with TLE and hippocampal sclerosis.”

Vascular conditions, including atherosclerosis, may play an important role in the development of cognitive impairment and dementia, according to a report published online in the July 21 Stroke. The authors used previously published guidelines and literature, as well as personal experience, to summarize existing evidence, indicate gaps in current knowledge, and formulate recommendations regarding vascular contributions to cognitive decline late in life. Observed vascular risk factors included atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia, all of which, the researchers noted, were also risk factors for stroke and Alzheimer’s disease. “The neuropathology of cognitive impairment later in life is often a mixture of Alzheimer’s disease and microvascular brain damage,” the authors wrote. “Detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of vascular cognitive impairment, even in older people.”
Women with epilepsy experience greater seizure frequency during anovulatory cycles than during cycles when ovulation occurs, according to results of a study published July 14 online ahead of print in Epilepsia. Almost 300 women with epilepsy were enrolled in the study; 92 had completed both cycles during the study period. Their average daily seizure frequency, seizure type, and progesterone/estradiol serum level ratios were recorded. “Average daily seizure frequency was 29.5% greater for secondary generalized tonic-clonic seizures during anovulatory than during ovulatory cycles,” the researchers wrote. Frequency did not differ significantly for complex or simple partial seizures, or for all seizure types combined. “Because the proportional increases in secondary generalized tonic-clonic seizure frequency during anovulatory cycles correlate with the proportional increases in estradiol/progesterone serum level ratios, these findings support a possible role for reproductive steroids in [seizure] occurrence.”
Researchers have identified a new genetic risk factor for restless legs syndrome (RLS), as reported in the July 14 PLoS Genetics. The authors conducted a genome-wide association study of 922 patients with RLS, and compared the results with 1,526 controls. The researchers included 301,406 single nucleotide polymorphisms (SNPs) in the study, followed by a replication of 76 candidate SNPs in 3,935 patients and 5,754 controls. “We identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972) and a locus on 16q12.1 (rs3104767) in a linkage disequilibrium block of 40 kb containing the 5´-end of TOX3 and the adjacent noncoding RNA BC034767,” the investigators reported. They concluded, “The physiologic role of TOX3 and BC034767 in the CNS and a possible involvement of these two genes in RLS pathogenesis remain to be established.”
Breastfeeding does not significantly provide protection against postpartum relapses in women with multiple sclerosis (MS), a finding that contradicts results from previous studies, researchers reported in the July 12 Neurology. The investigators prospectively followed up pregnancies in 298 women with MS and gathered data on breastfeeding; they monitored relapse rates for up to one year after delivery. “The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not,” the authors reported. The only significant predictors of postpartum relapses were relapses before and during pregnancy. “Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity,” the investigators concluded.
Low bone density and osteoporosis commonly appear in the early stages of multiple sclerosis (MS), according to a study published in the July 12 Neurology. “If vitamin D exerts a major effect on MS risk,” the investigators hypothesized, “skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS.” To test their hypothesis, the researchers measured the bone mineral density of 99 patients in the early stages of the disease with no or minor disability; these results were compared with the densities of 159 healthy controls. Half of the patients had either osteopenia or osteoporosis, compared with 37.1% of the controls. “[This finding is] compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS,” the authors concluded.
According to a study published in the July 12 online BMJ, there is no significant link between adjuvanted vaccines used during the 2009 swine flu pandemic and Guillain-Barré syndrome. The investigators performed a case-control study in five European countries of 104 patients with the syndrome and age-, sex-, and location-matched controls. The initial, unadjusted pooled risk estimate for all countries was 2.8, and case recruitment and vaccine coverage varied considerably between countries. “After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome,” the investigators reported. They did note, however, “the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people.”
A team of researchers has found a genetic determinant of late-onset Parkinson’s disease, according to a study published in the July 9 issue of American Journal of Human Genetics. “To identify rare causal variants in late-onset Parkinson’s disease, we investigated an Austrian family with 16 affected individuals by exome sequencing,” the investigators explained. “We found a missense mutation, c.1858G>A, in the VPS35 gene in all seven affected family members who are alive.” Screening the entire VPS35 coding sequence in additional Parkinson’s disease cases and controls revealed six other missense variants; three were only present in patients, two were only present in controls, and one was present in both groups. The investigators also noted, “VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer’s disease.”
Researchers have found that African-American patients with ischemic stroke are significantly less likely to be treated with IV t-PA, due to delayed presentation and stroke severity, according to a study published in the June 30 online Stroke. The investigators performed a systematic chart review on patients admitted to seven Washington, DC–area hospitals; of 1,044 patients with ischemic stroke, 74% were black and 5% received t-PA. African-American patients were one-third less likely than white patients to receive IV t-PA, were less likely to present at the hospital within three hours of symptom onset, and were less likely to be eligible for t-PA treatment. African-American patients also had a greater rate of contraindications to t-PA treatment, including hypertension, recent stroke, or use of blood thinners.
People with a history of traumatic brain injury (TBI) are more likely to develop long-term neurodegeneration than those who have never experienced a brain injury, according to research appearing in the June 29 online Brain Pathology. Investigators examined postmortem brains from 39 survivors of a single TBI and 47 brains of uninjured, age-matched controls using immunochemistry and thioflavin-S staining. “Neurofibrillary tangles were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases,” the researchers reported. In addition, patients with TBI had a greater density of amyloid-beta plaques than controls. “These data demonstrate widespread neurofibrillary tangles and amyloid-beta plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease,” the authors concluded.
A group of researchers presented a new set of practice guidelines regarding genetic counseling, as reported in the June Genetics in Medicine. The guidelines, developed through a joint effort by the American College of Medical Genetics and the National Society of Genetic Counselors, seek to provide medical professionals with guidance in the complex area of genetic testing. “Despite its limited utility, patients express concern over their risk and, in some instances, request testing,” the authors wrote. “This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer’s disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for Alzheimer’s disease,” they concluded.
Regions important for cognitive and motor control are smaller in the brains of children with attention-deficit hyperactivity disorder (ADHD) than in typically developing children, researchers reported in the June 9 online Clinical Neuropsychologist. To understand the neurobiologic development of ADHD, the investigators examined high-resolution anatomic images of 13 children with ADHD and 13 controls (ages 4 to 5). “Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this range,” the authors observed. Left caudate volume was a significant predictor of hyperactive and impulsive symptom severity, but not inattention. “Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD,” the researchers concluded.
A diet low in saturated fat and simple carbohydrates may modulate the risk of developing dementia that precedes Alzheimer’s disease, researchers reported in the June Archives of Neurology. To compare the effects of different diets on insulin and lipid metabolism, CSF markers of Alzheimer’s disease, and cognition, the investigators randomized 20 healthy adults and 29 adults with amnestic mild cognitive impairment to either a high- or low-fat and glycemic index diet. In the cognitively impaired group, the “low” diet increased CSF amyloid-beta 42 concentrations; the opposite was true for healthy patients on this diet. For both groups, the “low” diet improved visual memory. “Diet may be a powerful environmental factor that modulates Alzheimer’s disease risk through its effects on CNS concentrations of amyloid-beta 42, lipoproteins, oxidative stress, and insulin,” the investigators concluded.
A study in the June Headache found that prophylactic medications and behavioral interventions for migraine are cost-competitive and cost-efficient options during the early phases of treatment. Researchers distributed surveys to physicians and behavioral specialists to gather data about costs of prototypical regimens for preventive pharmacologic treatment, clinic-based behavioral treatment, minimal contact behavioral treatment, and group behavioral treatment. During the initial months of treatment, pharmacologic treatment with inexpensive medications was the least costly option (

Vascular conditions, including atherosclerosis, may play an important role in the development of cognitive impairment and dementia, according to a report published online in the July 21 Stroke. The authors used previously published guidelines and literature, as well as personal experience, to summarize existing evidence, indicate gaps in current knowledge, and formulate recommendations regarding vascular contributions to cognitive decline late in life. Observed vascular risk factors included atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia, all of which, the researchers noted, were also risk factors for stroke and Alzheimer’s disease. “The neuropathology of cognitive impairment later in life is often a mixture of Alzheimer’s disease and microvascular brain damage,” the authors wrote. “Detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of vascular cognitive impairment, even in older people.”
Women with epilepsy experience greater seizure frequency during anovulatory cycles than during cycles when ovulation occurs, according to results of a study published July 14 online ahead of print in Epilepsia. Almost 300 women with epilepsy were enrolled in the study; 92 had completed both cycles during the study period. Their average daily seizure frequency, seizure type, and progesterone/estradiol serum level ratios were recorded. “Average daily seizure frequency was 29.5% greater for secondary generalized tonic-clonic seizures during anovulatory than during ovulatory cycles,” the researchers wrote. Frequency did not differ significantly for complex or simple partial seizures, or for all seizure types combined. “Because the proportional increases in secondary generalized tonic-clonic seizure frequency during anovulatory cycles correlate with the proportional increases in estradiol/progesterone serum level ratios, these findings support a possible role for reproductive steroids in [seizure] occurrence.”
Researchers have identified a new genetic risk factor for restless legs syndrome (RLS), as reported in the July 14 PLoS Genetics. The authors conducted a genome-wide association study of 922 patients with RLS, and compared the results with 1,526 controls. The researchers included 301,406 single nucleotide polymorphisms (SNPs) in the study, followed by a replication of 76 candidate SNPs in 3,935 patients and 5,754 controls. “We identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972) and a locus on 16q12.1 (rs3104767) in a linkage disequilibrium block of 40 kb containing the 5´-end of TOX3 and the adjacent noncoding RNA BC034767,” the investigators reported. They concluded, “The physiologic role of TOX3 and BC034767 in the CNS and a possible involvement of these two genes in RLS pathogenesis remain to be established.”
Breastfeeding does not significantly provide protection against postpartum relapses in women with multiple sclerosis (MS), a finding that contradicts results from previous studies, researchers reported in the July 12 Neurology. The investigators prospectively followed up pregnancies in 298 women with MS and gathered data on breastfeeding; they monitored relapse rates for up to one year after delivery. “The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not,” the authors reported. The only significant predictors of postpartum relapses were relapses before and during pregnancy. “Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity,” the investigators concluded.
Low bone density and osteoporosis commonly appear in the early stages of multiple sclerosis (MS), according to a study published in the July 12 Neurology. “If vitamin D exerts a major effect on MS risk,” the investigators hypothesized, “skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS.” To test their hypothesis, the researchers measured the bone mineral density of 99 patients in the early stages of the disease with no or minor disability; these results were compared with the densities of 159 healthy controls. Half of the patients had either osteopenia or osteoporosis, compared with 37.1% of the controls. “[This finding is] compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS,” the authors concluded.
According to a study published in the July 12 online BMJ, there is no significant link between adjuvanted vaccines used during the 2009 swine flu pandemic and Guillain-Barré syndrome. The investigators performed a case-control study in five European countries of 104 patients with the syndrome and age-, sex-, and location-matched controls. The initial, unadjusted pooled risk estimate for all countries was 2.8, and case recruitment and vaccine coverage varied considerably between countries. “After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome,” the investigators reported. They did note, however, “the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people.”
A team of researchers has found a genetic determinant of late-onset Parkinson’s disease, according to a study published in the July 9 issue of American Journal of Human Genetics. “To identify rare causal variants in late-onset Parkinson’s disease, we investigated an Austrian family with 16 affected individuals by exome sequencing,” the investigators explained. “We found a missense mutation, c.1858G>A, in the VPS35 gene in all seven affected family members who are alive.” Screening the entire VPS35 coding sequence in additional Parkinson’s disease cases and controls revealed six other missense variants; three were only present in patients, two were only present in controls, and one was present in both groups. The investigators also noted, “VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer’s disease.”
Researchers have found that African-American patients with ischemic stroke are significantly less likely to be treated with IV t-PA, due to delayed presentation and stroke severity, according to a study published in the June 30 online Stroke. The investigators performed a systematic chart review on patients admitted to seven Washington, DC–area hospitals; of 1,044 patients with ischemic stroke, 74% were black and 5% received t-PA. African-American patients were one-third less likely than white patients to receive IV t-PA, were less likely to present at the hospital within three hours of symptom onset, and were less likely to be eligible for t-PA treatment. African-American patients also had a greater rate of contraindications to t-PA treatment, including hypertension, recent stroke, or use of blood thinners.
People with a history of traumatic brain injury (TBI) are more likely to develop long-term neurodegeneration than those who have never experienced a brain injury, according to research appearing in the June 29 online Brain Pathology. Investigators examined postmortem brains from 39 survivors of a single TBI and 47 brains of uninjured, age-matched controls using immunochemistry and thioflavin-S staining. “Neurofibrillary tangles were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases,” the researchers reported. In addition, patients with TBI had a greater density of amyloid-beta plaques than controls. “These data demonstrate widespread neurofibrillary tangles and amyloid-beta plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease,” the authors concluded.
A group of researchers presented a new set of practice guidelines regarding genetic counseling, as reported in the June Genetics in Medicine. The guidelines, developed through a joint effort by the American College of Medical Genetics and the National Society of Genetic Counselors, seek to provide medical professionals with guidance in the complex area of genetic testing. “Despite its limited utility, patients express concern over their risk and, in some instances, request testing,” the authors wrote. “This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer’s disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for Alzheimer’s disease,” they concluded.
Regions important for cognitive and motor control are smaller in the brains of children with attention-deficit hyperactivity disorder (ADHD) than in typically developing children, researchers reported in the June 9 online Clinical Neuropsychologist. To understand the neurobiologic development of ADHD, the investigators examined high-resolution anatomic images of 13 children with ADHD and 13 controls (ages 4 to 5). “Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this range,” the authors observed. Left caudate volume was a significant predictor of hyperactive and impulsive symptom severity, but not inattention. “Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD,” the researchers concluded.
A diet low in saturated fat and simple carbohydrates may modulate the risk of developing dementia that precedes Alzheimer’s disease, researchers reported in the June Archives of Neurology. To compare the effects of different diets on insulin and lipid metabolism, CSF markers of Alzheimer’s disease, and cognition, the investigators randomized 20 healthy adults and 29 adults with amnestic mild cognitive impairment to either a high- or low-fat and glycemic index diet. In the cognitively impaired group, the “low” diet increased CSF amyloid-beta 42 concentrations; the opposite was true for healthy patients on this diet. For both groups, the “low” diet improved visual memory. “Diet may be a powerful environmental factor that modulates Alzheimer’s disease risk through its effects on CNS concentrations of amyloid-beta 42, lipoproteins, oxidative stress, and insulin,” the investigators concluded.
A study in the June Headache found that prophylactic medications and behavioral interventions for migraine are cost-competitive and cost-efficient options during the early phases of treatment. Researchers distributed surveys to physicians and behavioral specialists to gather data about costs of prototypical regimens for preventive pharmacologic treatment, clinic-based behavioral treatment, minimal contact behavioral treatment, and group behavioral treatment. During the initial months of treatment, pharmacologic treatment with inexpensive medications was the least costly option (

Vascular conditions, including atherosclerosis, may play an important role in the development of cognitive impairment and dementia, according to a report published online in the July 21 Stroke. The authors used previously published guidelines and literature, as well as personal experience, to summarize existing evidence, indicate gaps in current knowledge, and formulate recommendations regarding vascular contributions to cognitive decline late in life. Observed vascular risk factors included atrial fibrillation, hypertension, diabetes mellitus, and hypercholesterolemia, all of which, the researchers noted, were also risk factors for stroke and Alzheimer’s disease. “The neuropathology of cognitive impairment later in life is often a mixture of Alzheimer’s disease and microvascular brain damage,” the authors wrote. “Detection and control of the traditional risk factors for stroke and cardiovascular disease may be effective in the prevention of vascular cognitive impairment, even in older people.”
Women with epilepsy experience greater seizure frequency during anovulatory cycles than during cycles when ovulation occurs, according to results of a study published July 14 online ahead of print in Epilepsia. Almost 300 women with epilepsy were enrolled in the study; 92 had completed both cycles during the study period. Their average daily seizure frequency, seizure type, and progesterone/estradiol serum level ratios were recorded. “Average daily seizure frequency was 29.5% greater for secondary generalized tonic-clonic seizures during anovulatory than during ovulatory cycles,” the researchers wrote. Frequency did not differ significantly for complex or simple partial seizures, or for all seizure types combined. “Because the proportional increases in secondary generalized tonic-clonic seizure frequency during anovulatory cycles correlate with the proportional increases in estradiol/progesterone serum level ratios, these findings support a possible role for reproductive steroids in [seizure] occurrence.”
Researchers have identified a new genetic risk factor for restless legs syndrome (RLS), as reported in the July 14 PLoS Genetics. The authors conducted a genome-wide association study of 922 patients with RLS, and compared the results with 1,526 controls. The researchers included 301,406 single nucleotide polymorphisms (SNPs) in the study, followed by a replication of 76 candidate SNPs in 3,935 patients and 5,754 controls. “We identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972) and a locus on 16q12.1 (rs3104767) in a linkage disequilibrium block of 40 kb containing the 5´-end of TOX3 and the adjacent noncoding RNA BC034767,” the investigators reported. They concluded, “The physiologic role of TOX3 and BC034767 in the CNS and a possible involvement of these two genes in RLS pathogenesis remain to be established.”
Breastfeeding does not significantly provide protection against postpartum relapses in women with multiple sclerosis (MS), a finding that contradicts results from previous studies, researchers reported in the July 12 Neurology. The investigators prospectively followed up pregnancies in 298 women with MS and gathered data on breastfeeding; they monitored relapse rates for up to one year after delivery. “The time-dependent profile of the relapse rate before, during, and after pregnancy did not differ between patients who breastfed and patients who did not,” the authors reported. The only significant predictors of postpartum relapses were relapses before and during pregnancy. “Therefore, the reported association between breastfeeding and a lower risk of postpartum relapses may simply reflect different patient behavior, biased by the disease activity,” the investigators concluded.
Low bone density and osteoporosis commonly appear in the early stages of multiple sclerosis (MS), according to a study published in the July 12 Neurology. “If vitamin D exerts a major effect on MS risk,” the investigators hypothesized, “skeletal consequences of hypovitaminosis D could be apparent shortly after the onset of MS.” To test their hypothesis, the researchers measured the bone mineral density of 99 patients in the early stages of the disease with no or minor disability; these results were compared with the densities of 159 healthy controls. Half of the patients had either osteopenia or osteoporosis, compared with 37.1% of the controls. “[This finding is] compatible with shared etiologic or pathogenic factors in MS and osteoporosis, and calls for an active approach to optimize bone health in early stages of MS,” the authors concluded.
According to a study published in the July 12 online BMJ, there is no significant link between adjuvanted vaccines used during the 2009 swine flu pandemic and Guillain-Barré syndrome. The investigators performed a case-control study in five European countries of 104 patients with the syndrome and age-, sex-, and location-matched controls. The initial, unadjusted pooled risk estimate for all countries was 2.8, and case recruitment and vaccine coverage varied considerably between countries. “After adjustment for influenza-like illness/upper respiratory tract infection and seasonal influenza vaccination, receipt of pandemic influenza vaccine was not associated with an increased risk of Guillain-Barré syndrome,” the investigators reported. They did note, however, “the upper limit does not exclude a potential increase in risk up to 2.7-fold or three excess cases per one million vaccinated people.”
A team of researchers has found a genetic determinant of late-onset Parkinson’s disease, according to a study published in the July 9 issue of American Journal of Human Genetics. “To identify rare causal variants in late-onset Parkinson’s disease, we investigated an Austrian family with 16 affected individuals by exome sequencing,” the investigators explained. “We found a missense mutation, c.1858G>A, in the VPS35 gene in all seven affected family members who are alive.” Screening the entire VPS35 coding sequence in additional Parkinson’s disease cases and controls revealed six other missense variants; three were only present in patients, two were only present in controls, and one was present in both groups. The investigators also noted, “VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer’s disease.”
Researchers have found that African-American patients with ischemic stroke are significantly less likely to be treated with IV t-PA, due to delayed presentation and stroke severity, according to a study published in the June 30 online Stroke. The investigators performed a systematic chart review on patients admitted to seven Washington, DC–area hospitals; of 1,044 patients with ischemic stroke, 74% were black and 5% received t-PA. African-American patients were one-third less likely than white patients to receive IV t-PA, were less likely to present at the hospital within three hours of symptom onset, and were less likely to be eligible for t-PA treatment. African-American patients also had a greater rate of contraindications to t-PA treatment, including hypertension, recent stroke, or use of blood thinners.
People with a history of traumatic brain injury (TBI) are more likely to develop long-term neurodegeneration than those who have never experienced a brain injury, according to research appearing in the June 29 online Brain Pathology. Investigators examined postmortem brains from 39 survivors of a single TBI and 47 brains of uninjured, age-matched controls using immunochemistry and thioflavin-S staining. “Neurofibrillary tangles were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases,” the researchers reported. In addition, patients with TBI had a greater density of amyloid-beta plaques than controls. “These data demonstrate widespread neurofibrillary tangles and amyloid-beta plaque pathologies are present in a proportion of patients following a single TBI, suggesting that some individuals who experience a single TBI may develop long-term neuropathological changes akin to those found in neurodegenerative disease,” the authors concluded.
A group of researchers presented a new set of practice guidelines regarding genetic counseling, as reported in the June Genetics in Medicine. The guidelines, developed through a joint effort by the American College of Medical Genetics and the National Society of Genetic Counselors, seek to provide medical professionals with guidance in the complex area of genetic testing. “Despite its limited utility, patients express concern over their risk and, in some instances, request testing,” the authors wrote. “This practice guideline provides clinicians with a framework for assessing their patients’ genetic risk for Alzheimer’s disease, identifying which individuals may benefit from genetic testing, and providing the key elements of genetic counseling for Alzheimer’s disease,” they concluded.
Regions important for cognitive and motor control are smaller in the brains of children with attention-deficit hyperactivity disorder (ADHD) than in typically developing children, researchers reported in the June 9 online Clinical Neuropsychologist. To understand the neurobiologic development of ADHD, the investigators examined high-resolution anatomic images of 13 children with ADHD and 13 controls (ages 4 to 5). “Children with ADHD showed significantly reduced caudate volumes bilaterally; in contrast there were no significant group differences in cortical volume or thickness in this range,” the authors observed. Left caudate volume was a significant predictor of hyperactive and impulsive symptom severity, but not inattention. “Anomalous basal ganglia, particularly caudate, development appears to play an important role among children presenting with early onset symptoms of ADHD,” the researchers concluded.
A diet low in saturated fat and simple carbohydrates may modulate the risk of developing dementia that precedes Alzheimer’s disease, researchers reported in the June Archives of Neurology. To compare the effects of different diets on insulin and lipid metabolism, CSF markers of Alzheimer’s disease, and cognition, the investigators randomized 20 healthy adults and 29 adults with amnestic mild cognitive impairment to either a high- or low-fat and glycemic index diet. In the cognitively impaired group, the “low” diet increased CSF amyloid-beta 42 concentrations; the opposite was true for healthy patients on this diet. For both groups, the “low” diet improved visual memory. “Diet may be a powerful environmental factor that modulates Alzheimer’s disease risk through its effects on CNS concentrations of amyloid-beta 42, lipoproteins, oxidative stress, and insulin,” the investigators concluded.
A study in the June Headache found that prophylactic medications and behavioral interventions for migraine are cost-competitive and cost-efficient options during the early phases of treatment. Researchers distributed surveys to physicians and behavioral specialists to gather data about costs of prototypical regimens for preventive pharmacologic treatment, clinic-based behavioral treatment, minimal contact behavioral treatment, and group behavioral treatment. During the initial months of treatment, pharmacologic treatment with inexpensive medications was the least costly option (

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.

One third of patients with pathologically confirmed early-onset Alzheimer’s disease presented with atypical symptoms, and 53% of patients with nonamnestic presentations were initially misdiagnosed, according to a study in the May 17 Neurology. Researchers conducted a retrospective review of clinical data from patients with confirmed early-onset Alzheimer’s disease to determine the frequency and types of incorrect diagnoses. The majority of these cases were diagnosed with other types of dementia, including pseudodementia with depression, semantic dementia, and primary progressive aphasia. “Early-onset Alzheimer’s disease diagnosis often represents a challenge because of the high frequency of atypical presentations,” the study authors wrote. More than one-third (37.5%) of patients presented with atypical symptoms other than memory problems; the most prevalent of these was behavioral/executive dysfunction.

Neuronal activity may be a potential mechanism for vulnerability to amyloid-β deposition in certain areas of the brain, researchers reported in the May 1 online Nature Neuroscience. The investigators examined endogenous neuronal activity in mice with Alzheimer’s disease and determined that this activity regulates the regional concentration of interstitial fluid amyloid-β, which drives local aggregation of amyloid-β. Using unilateral vibrissal stimulation in the contralateral barrel cortex, they found that activity increased interstitial fluid amyloid-β. Unilateral vibrissal deprivation decreased interstitial fluid amyloid-β deposition; long-term deprivation also decreased amyloid plaque formation and growth. “Our results suggest a mechanism to account for the vulnerability of specific brain regions to amyloid-β deposition in Alzheimer’s disease,” the authors concluded.

A newly confirmed genetic risk allele of the clusterin gene contributes to white matter degeneration in young adults and may increase the risk for Alzheimer’s disease later in life, according to results published in the May 4 Journal of Neuroscience. Investigators used diffusion-tensor MRI to scan the brains of 398 healthy young adults (mean age, 23.6) and to evaluate whether the C-allele clusterin risk variant was associated with lower white matter integrity. “Each C-allele copy of the clusterin variant was associated with lower fractional anisotropy—a widely accepted measure of white matter integrity—in multiple brain regions,” the authors wrote. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. “Young healthy carriers of the clusterin gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing Alzheimer’s disease later in life,” the researchers concluded.

A higher BMI may improve survival in patients with amyotrophic lateral sclerosis (ALS). As published in the May 23 online Muscle & Nerve, investigators aimed to determine whether cholesterol levels are an independent predictor of ALS survival. They measured cholesterol levels in 427 people with ALS from three clinical trial databases and found that the low-density and high-density lipoprotein level ratio did not decrease over time, even though BMI significantly declined. “After adjusting for BMI, forced vital capacity, and age, the lipid ratio was not associated with survival,” the investigators wrote. The highest survival rate, though, was found among patients with a BMI between 30 and 35, or mild obesity. “We found that dyslipidemia is not an independent predictor of survival in ALS,” the researchers concluded, whereas, “BMI is an independent prognostic factor for survival after adjusting for markers of disease severity.”

Patients with a history of intracerebral hemorrhage (ICH) should avoid using statins for prevention of ischemic cardiac and cerebrovascular disease, according to a study in the May Archives of Neurology. Statins are widely prescribed for disease prevention, the authors noted, and “although serious adverse effects are uncommon, results from a recent clinical trial suggested increased risk of ICH associated with statin use.” To determine if statin therapy should be avoided in patients with a baseline elevated risk of ICH, investigators evaluated the risks and benefits of the therapy in patients with prior ICH using clinical parameters such as hemorrhage location (deep or lobar). For survivors of ICH both with and without prior cardiovascular events, the benefits of statin therapy were not strong enough to offset the increased risk for hemorrhage recurrence.

Adverse changes in sleep duration are associated with poorer cognitive function in middle-aged adults, per a study in the May 1 Sleep. Researchers conducted cross-sectional studies of women and men (age range, 45 to 69) to examine the effect of changes in sleep duration on cognitive function. Participants’ cognitive function was assessed at baseline, and their sleep duration on an average weeknight was measured once at baseline and again an average of 5.4 years later. After adjustment for age, gender, education, and occupation, the authors reported that “firm evidence remained for an association between an increase from seven or eight hours sleep and lower cognitive function for all tests, except memory, and between a decrease from six or eight hours sleep and poorer reasoning, vocabulary, and Mini-Mental State Examination score.” These adverse changes in duration were equivalent to a four- to seven-year increase in age.

African Americans with multiple sclerosis (MS) have lower vitamin D levels than their healthy counterparts, according to a study published in the May 24 Neurology. Researchers conducted a cross-sectional study of 339 African-American patients with MS and 342 without MS to determine if vitamin D levels were associated with MS disease severity. Between 71% and 77% of all participants were vitamin D–deficient and 93% to 94% were vitamin D–insufficient, the authors reported. Overall, vitamin D levels were lower in patients with MS, but this was due to differences in climate and geography and did not have an impact on disease severity. “These results are consistent with observations in other populations that lower [vitamin D level] is associated with having MS,” the investigators concluded, “but also highlight the importance of climate and ancestry in determining vitamin D status.”

Protein-based human-induced pluripotent stem cells (hiPSCs) and those derived from human embryonic stem cells (hESCs) may be effective in the treatment of Parkinson’s disease, according to a study in the May 16 Journal of Clinical Investigation. Results showed that neuronal precursors cells derived from hESCs and protein-based hiPSCs reversed disease when transplanted into the brains of rats modeling Parkinson’s disease. The researchers attempted to use neuronal cells derived from virus-based hiPSCs but were unable to do so because these virus-based cells exhibited apoptotic cell death. “[hiPSCs] are a potentially unlimited source of patient-specific cells for transplantation…. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of Parkinson’s disease,” the investigators concluded.

Women may have a greater risk than men for adverse events following certain stroke prevention procedures, as reported in the May 6 online Lancet Neurology. A total of 2,502 patients with symptomatic and asymptomatic stenosis were randomized to undergo carotid endarterectomy or carotid artery stenting. The rates of periprocedural stroke, myocardial infarction, and death were similar in men who underwent endarterectomy (4.9%) and stenting (4.3%). In women, however, a significant difference in rates of adverse events was observed—3.8% for endarterectomy versus 6.8% for stenting. “Periprocedural risk of events seems to be higher in women who have carotid artery stenting than those who have carotid endarterectomy, whereas there is little difference in men,” the authors concluded. “Additional data are needed to confirm whether this differential risk should be taken into account in decisions for treatment of carotid disease in women.”

About 14% of ischemic strokes presented at emergency departments are wake-up strokes, researchers reported in the May 10 Neurology. Wake-up strokes, according to the authors, cannot be distinguished from other types of stroke based on clinical features or outcome, making them difficult to treat with effective clot-busting therapies. The researchers analyzed data from patients presenting at emergency departments with ischemic stroke; they identified 1,854 ischemic stroke cases, 273 of which were wake-up strokes. “There were no differences between wake-up strokes and all other strokes with regard to clinical features or outcomes except for minor differences in age and baseline retrospective NIH Stroke Scale score,” the authors reported. “Of the wake-up strokes, at least 98 (35.9%) would have been eligible for thrombolysis if arrival time were not a factor.”

The annual rate of coronary artery bypass graft surgeries decreased 30% between 2001 and 2008, while rates of other percutaneous coronary interventions remained stable, according to an examination of national trends published in the May 4 JAMA. Investigators conducted a serial cross-sectional study to examine time trends of patients undergoing revascularization procedures, and determined that the annual surgery rate decreased from 1,742 to 1,081 per million adults in 2008. “Between 2001 and 2008, the number of hospitals … providing [coronary artery bypass graft surgery] increased by 12%, and the number of [percutaneous coronary interventions] hospitals increased by 26%,” the authors reported. They noted that new revascularization technologies, new clinical evidence from trials, and updated clinical guidelines may have affected the volume and distribution of coronary revascularizations.

Patients with traumatic brain injury (TBI) and refractory intracranial hypertension may benefit from decompressive craniectomy, but they may also experience unfavorable outcomes, according to a study in the April 21 New England Journal of Medicine. Researchers randomly assigned 155 adults with TBI and intracranial hypertension to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The results revealed that the standard-care group had higher levels of intracranial pressure and longer stays in the intensive care unit. “However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care,” the authors noted. Patients with craniectomy were also more than twice as likely to experience an unfavorable outcome, including death, vegetative state, or severe disability.