New and Noteworthy Information—January 2016

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams