News Roundup

Fish oil may reduce seizure frequency in patients with epilepsy, according to a study published online ahead of print September 8 in the Journal of Neurology, Neurosurgery, and Psychiatry. Twenty-four patients with drug-resistant epilepsy were given three separate treatments for 10 weeks and separated by a six-week period. Participants were given three capsules of fish oil daily, plus three capsules of corn oil (placebo); six capsules of fish oil daily; and three capsules of corn oil twice daily. The average number of seizures among those taking low-dose fish oil was around 12 per month, compared with slightly more than 17 for the high dose, and slightly more than 18 for the placebo. Two people who had the low dose were seizure free during the 10-week trial. No one taking the high-dose fish oil or the placebo was seizure free.

Blood type AB and higher factor VIII (FVIII) are associated with increased incidence of cognitive impairment, according to a study published online ahead of print September 10 in Neurology. Findings are based on a cohort from the REGARDS Study, in which more than 30,000 people were followed for an average of 3.4 years. After adjusting for age, race, region, and sex, the researchers found that people with blood group AB (odds ratio [OR], 1.82) and those with higher FVIII (OR, 1.24) had an increased risk of cognitive impairment. The mean FVIII was higher in people with blood type AB (142 IU/dL), compared with O (104 IU/dL), and FVIII mediated 18% of the association between AB group and incident cognitive impairment, according to the researchers.

Magnesium sulfate administered IV to pregnant women at risk of giving birth before 30 weeks gestation was not associated with neurologic, cognitive, behavioral, growth, or functional outcomes in their children at school age, investigators reported in the September 17 issue of JAMA. Researchers randomly assigned magnesium sulfate or placebo to pregnant women (n = 535 magnesium; n = 527 placebo) for whom birth was planned or expected before 30 weeks gestation; 1,255 fetuses were known to be alive at randomization. Of the 867 survivors available for follow-up, outcomes at school age (6 to 11) were determined for 669 children (77%). The investigators found that receiving antenatal magnesium sulfate was not associated with any long-term benefits or harms, compared with placebo. The study authors also observed a nonsignificant reduction in the risk of death in the magnesium sulfate group.

Older patients with Parkinson’s disease who underwent deep brain stimulation (DBS) had a similar 90-day complication risk, compared with that in younger patients, according to a study published online ahead of print August 25 in JAMA Neurology. Researchers analyzed data from more than 1,750 patients who had DBS from 2000 to 2009. Of those, 7.5% of subjects experienced at least one complication within 90 days of having the device implanted. The investigators determined that increasing age did not significantly affect the overall complication rates. The findings suggest that age alone should not be a primary exclusion factor for determining candidacy for DBS. “Instead, a clear focus on patients with medication-refractory and difficult to control on-off fluctuations with preserved cognition, regardless of age, may allow for an expansion of the traditional therapeutic window,” the researchers concluded.

Confusional arousals are highly prevalent in the general population, according to a study published in the August 26 issue of Neurology. A total of 19,136 people age 18 and older were interviewed about their sleep habits and whether they had experienced symptoms of the disorder. Participants also were asked about any medications they took and about mental illness diagnoses. Results showed that 15% had experienced an episode in the last year, with more than half reporting more than one episode per week. In the majority of cases, 84% of those with confusional arousals (also known as sleep drunkenness) also had a sleep disorder, mental health disorder, or were taking psychotropic drugs. Fewer than 1% of the people with confusional arousals had no known cause or related condition. “These episodes of waking up confused have received considerably less attention than sleepwalking even though the consequences can be just as serious,” stated researchers.

High potassium intake is associated with a lower risk of all stroke and ischemic stroke and all-cause mortality in older women, investigators reported online ahead of print September 4 in Stroke. Researchers studied 90,137 postmenopausal women ages 50 to 79 for an average of 11 years. Women who consumed the most potassium were 10% less likely to die than were those who had consumed the least amount. The women also were 12% less likely to have a stroke and 16% less likely to have an ischemic stroke than were women who consumed the least amount. Those without hypertension who had consumed the most potassium had a 27% lower ischemic stroke risk and 21% reduced risk for all stroke types, compared with women who had the least potassium in their diets. Among women with hypertension, those who consumed the most potassium had a lower risk of mortality.

Regular blood transfusion therapy significantly reduced the recurrence of cerebral infarct in children with sickle cell anemia, according to a study published in the August 21 issue of the New England Journal of Medicine. During the three-year study, 196 children ages 5 through 15 with sickle cell anemia who had previously had a silent stroke were followed. Children who underwent regular transfusions were 58% less likely to have another silent stroke or an overt stroke, while those who had no transfusions were more than twice as likely to experience repeat strokes. In addition, children who had monthly transfusions were less likely to have a range of other sickle cell anemia–related problems, such as episodes of extreme pain. Overall, 295 pain episodes occurred among children who did not receive transfusions, compared with 126 episodes among those receiving treatment.

Stroke incidence and mortality rates decreased from 1987 to 2011, according to a study published in the July 16 issue of JAMA. The findings were based on data from the Atherosclerosis Risk in Communities cohort of 15,792 US residents between the ages of 45 and 64 who were monitored during the 1980s. The new study followed the progress of 14,357 participants who were free of stroke in 1987 and monitored hospitalizations from stroke and deaths from 1987 to 2011. Stroke incidence decreased over time in Caucasians and African Americans, with an age-adjusted incidence rate ratio of 0.76. The absolute decrease was 0.93 per 1,000 person-years overall. The overall mortality rate after stroke decreased over time (hazard ratio, 0.80), with an absolute decrease of 8.09 per 100 strokes after 10 years.

The FDA has approved Vimpat (lacosamide) C-V as monotherapy in the treatment of partial-onset seizures in patients with epilepsy ages 17 and older. The monotherapy approval for Vimpat is based on a phase III historical-control conversion to lacosamide monotherapy study in adult patients with epilepsy with partial-onset seizures. This study met its primary end point, demonstrating that the exit percentage for patients converting to lacosamide (400 mg/day) was lower than the historical control exit percentage used as a comparator. Lacosamide (300 mg/day) also met the prespecified criteria for efficacy. Based on individual patients’ needs, physicians can choose between Vimpat formulations—tablets, oral solution, or injection. Vimpat (UCB; Brussels) is already approved in the US as adjunctive treatment for partial-onset seizures in patients in this age group.

Disruption of intestinal homeostasis is an early and immune-mediated event in experimental autoimmune encephalomyelitis, according to a study published September 3 in PLoS ONE. Investigators observed structural changes in the mucous membrane of the small intestine and an increase in inflammatory T cells, as well as a reduction in immunosuppressive cells. “Our findings provide support for the idea that a damaged intestinal barrier can prevent the body ending an autoimmune reaction in the normal manner, leading to a chronic disease such as multiple sclerosis,” stated the study authors. “In particular, an increased understanding of the regulation of tight junctions at the blood–brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.”

Children and adolescents with autism have a surplus of synapses in the brain due to reduced developmental spine pruning, investigators reported in the September 3 issue of Neuron. Researchers examined brains from children with autism who had died from other causes. Thirteen brains were from children ages 2 to 9, 13 brains were from children ages 13 to 20, and 22 brains were from children without autism. The investigators measured synapse density in a small section of tissue in each brain by counting the number of tiny spines that branch from the cortical neurons. During late childhood, spine density had decreased by about half in the control brains, compared with 16% in the brains from patients with autism. “Hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning,” stated study authors.

Macromolecular proton fraction (MPF) mapping enables quantitative assessment of demyelination in normal-appearing brain tissues and shows primary clinical relevance of gray matter damage in multiple sclerosis (MS), according to a study published online ahead of print September 10 in Radiology. Researchers examined 30 patients with MS, 18 with relapsing-remitting MS (RRMS) and 12 with secondary progressive MS. Fourteen healthy controls also were included. Each participant underwent MRI on a 3-T imager, and the investigators reconstructed 3-D whole-brain MPF maps to examine normal-appearing white matter, gray matter, and MS lesions. MPF was significantly lower in both white and gray matter in patients with RRMS, compared with healthy controls, and it was significantly reduced in normal-appearing brain tissues and lesions of patients with secondary progressive MS, compared with patients with RRMS with the largest relative decrease in gray matter.

Type 2 diabetes mellitus is associated with mild cognitive impairment (MCI) and MCI subtypes in middle-aged, but not in elderly participants, according to a study published online ahead of print July 7 in the Journal of Alzheimer’s Disease. A total of 560 participants diagnosed with MCI were compared with 1,376 cognitively normal participants from the Heinz Nixdorf Recall study. Of participants with MCI, 289 had amnestic MCI and 271 had nonamnestic MCI. Type 2 diabetes mellitus was strongly associated with MCI and MCI subtypes in those ages 50 to 65. Examination of differences by gender revealed a stronger association of diabetes with amnestic MCI in middle-aged women and an even stronger association with nonamnestic MCI in middle-aged men.

—Kimberly D. Williams

Fish oil may reduce seizure frequency in patients with epilepsy, according to a study published online ahead of print September 8 in the Journal of Neurology, Neurosurgery, and Psychiatry. Twenty-four patients with drug-resistant epilepsy were given three separate treatments for 10 weeks and separated by a six-week period. Participants were given three capsules of fish oil daily, plus three capsules of corn oil (placebo); six capsules of fish oil daily; and three capsules of corn oil twice daily. The average number of seizures among those taking low-dose fish oil was around 12 per month, compared with slightly more than 17 for the high dose, and slightly more than 18 for the placebo. Two people who had the low dose were seizure free during the 10-week trial. No one taking the high-dose fish oil or the placebo was seizure free.

Blood type AB and higher factor VIII (FVIII) are associated with increased incidence of cognitive impairment, according to a study published online ahead of print September 10 in Neurology. Findings are based on a cohort from the REGARDS Study, in which more than 30,000 people were followed for an average of 3.4 years. After adjusting for age, race, region, and sex, the researchers found that people with blood group AB (odds ratio [OR], 1.82) and those with higher FVIII (OR, 1.24) had an increased risk of cognitive impairment. The mean FVIII was higher in people with blood type AB (142 IU/dL), compared with O (104 IU/dL), and FVIII mediated 18% of the association between AB group and incident cognitive impairment, according to the researchers.

Magnesium sulfate administered IV to pregnant women at risk of giving birth before 30 weeks gestation was not associated with neurologic, cognitive, behavioral, growth, or functional outcomes in their children at school age, investigators reported in the September 17 issue of JAMA. Researchers randomly assigned magnesium sulfate or placebo to pregnant women (n = 535 magnesium; n = 527 placebo) for whom birth was planned or expected before 30 weeks gestation; 1,255 fetuses were known to be alive at randomization. Of the 867 survivors available for follow-up, outcomes at school age (6 to 11) were determined for 669 children (77%). The investigators found that receiving antenatal magnesium sulfate was not associated with any long-term benefits or harms, compared with placebo. The study authors also observed a nonsignificant reduction in the risk of death in the magnesium sulfate group.

Older patients with Parkinson’s disease who underwent deep brain stimulation (DBS) had a similar 90-day complication risk, compared with that in younger patients, according to a study published online ahead of print August 25 in JAMA Neurology. Researchers analyzed data from more than 1,750 patients who had DBS from 2000 to 2009. Of those, 7.5% of subjects experienced at least one complication within 90 days of having the device implanted. The investigators determined that increasing age did not significantly affect the overall complication rates. The findings suggest that age alone should not be a primary exclusion factor for determining candidacy for DBS. “Instead, a clear focus on patients with medication-refractory and difficult to control on-off fluctuations with preserved cognition, regardless of age, may allow for an expansion of the traditional therapeutic window,” the researchers concluded.

Confusional arousals are highly prevalent in the general population, according to a study published in the August 26 issue of Neurology. A total of 19,136 people age 18 and older were interviewed about their sleep habits and whether they had experienced symptoms of the disorder. Participants also were asked about any medications they took and about mental illness diagnoses. Results showed that 15% had experienced an episode in the last year, with more than half reporting more than one episode per week. In the majority of cases, 84% of those with confusional arousals (also known as sleep drunkenness) also had a sleep disorder, mental health disorder, or were taking psychotropic drugs. Fewer than 1% of the people with confusional arousals had no known cause or related condition. “These episodes of waking up confused have received considerably less attention than sleepwalking even though the consequences can be just as serious,” stated researchers.

High potassium intake is associated with a lower risk of all stroke and ischemic stroke and all-cause mortality in older women, investigators reported online ahead of print September 4 in Stroke. Researchers studied 90,137 postmenopausal women ages 50 to 79 for an average of 11 years. Women who consumed the most potassium were 10% less likely to die than were those who had consumed the least amount. The women also were 12% less likely to have a stroke and 16% less likely to have an ischemic stroke than were women who consumed the least amount. Those without hypertension who had consumed the most potassium had a 27% lower ischemic stroke risk and 21% reduced risk for all stroke types, compared with women who had the least potassium in their diets. Among women with hypertension, those who consumed the most potassium had a lower risk of mortality.

Regular blood transfusion therapy significantly reduced the recurrence of cerebral infarct in children with sickle cell anemia, according to a study published in the August 21 issue of the New England Journal of Medicine. During the three-year study, 196 children ages 5 through 15 with sickle cell anemia who had previously had a silent stroke were followed. Children who underwent regular transfusions were 58% less likely to have another silent stroke or an overt stroke, while those who had no transfusions were more than twice as likely to experience repeat strokes. In addition, children who had monthly transfusions were less likely to have a range of other sickle cell anemia–related problems, such as episodes of extreme pain. Overall, 295 pain episodes occurred among children who did not receive transfusions, compared with 126 episodes among those receiving treatment.

Stroke incidence and mortality rates decreased from 1987 to 2011, according to a study published in the July 16 issue of JAMA. The findings were based on data from the Atherosclerosis Risk in Communities cohort of 15,792 US residents between the ages of 45 and 64 who were monitored during the 1980s. The new study followed the progress of 14,357 participants who were free of stroke in 1987 and monitored hospitalizations from stroke and deaths from 1987 to 2011. Stroke incidence decreased over time in Caucasians and African Americans, with an age-adjusted incidence rate ratio of 0.76. The absolute decrease was 0.93 per 1,000 person-years overall. The overall mortality rate after stroke decreased over time (hazard ratio, 0.80), with an absolute decrease of 8.09 per 100 strokes after 10 years.

The FDA has approved Vimpat (lacosamide) C-V as monotherapy in the treatment of partial-onset seizures in patients with epilepsy ages 17 and older. The monotherapy approval for Vimpat is based on a phase III historical-control conversion to lacosamide monotherapy study in adult patients with epilepsy with partial-onset seizures. This study met its primary end point, demonstrating that the exit percentage for patients converting to lacosamide (400 mg/day) was lower than the historical control exit percentage used as a comparator. Lacosamide (300 mg/day) also met the prespecified criteria for efficacy. Based on individual patients’ needs, physicians can choose between Vimpat formulations—tablets, oral solution, or injection. Vimpat (UCB; Brussels) is already approved in the US as adjunctive treatment for partial-onset seizures in patients in this age group.

Disruption of intestinal homeostasis is an early and immune-mediated event in experimental autoimmune encephalomyelitis, according to a study published September 3 in PLoS ONE. Investigators observed structural changes in the mucous membrane of the small intestine and an increase in inflammatory T cells, as well as a reduction in immunosuppressive cells. “Our findings provide support for the idea that a damaged intestinal barrier can prevent the body ending an autoimmune reaction in the normal manner, leading to a chronic disease such as multiple sclerosis,” stated the study authors. “In particular, an increased understanding of the regulation of tight junctions at the blood–brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.”

Children and adolescents with autism have a surplus of synapses in the brain due to reduced developmental spine pruning, investigators reported in the September 3 issue of Neuron. Researchers examined brains from children with autism who had died from other causes. Thirteen brains were from children ages 2 to 9, 13 brains were from children ages 13 to 20, and 22 brains were from children without autism. The investigators measured synapse density in a small section of tissue in each brain by counting the number of tiny spines that branch from the cortical neurons. During late childhood, spine density had decreased by about half in the control brains, compared with 16% in the brains from patients with autism. “Hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning,” stated study authors.

Macromolecular proton fraction (MPF) mapping enables quantitative assessment of demyelination in normal-appearing brain tissues and shows primary clinical relevance of gray matter damage in multiple sclerosis (MS), according to a study published online ahead of print September 10 in Radiology. Researchers examined 30 patients with MS, 18 with relapsing-remitting MS (RRMS) and 12 with secondary progressive MS. Fourteen healthy controls also were included. Each participant underwent MRI on a 3-T imager, and the investigators reconstructed 3-D whole-brain MPF maps to examine normal-appearing white matter, gray matter, and MS lesions. MPF was significantly lower in both white and gray matter in patients with RRMS, compared with healthy controls, and it was significantly reduced in normal-appearing brain tissues and lesions of patients with secondary progressive MS, compared with patients with RRMS with the largest relative decrease in gray matter.

Type 2 diabetes mellitus is associated with mild cognitive impairment (MCI) and MCI subtypes in middle-aged, but not in elderly participants, according to a study published online ahead of print July 7 in the Journal of Alzheimer’s Disease. A total of 560 participants diagnosed with MCI were compared with 1,376 cognitively normal participants from the Heinz Nixdorf Recall study. Of participants with MCI, 289 had amnestic MCI and 271 had nonamnestic MCI. Type 2 diabetes mellitus was strongly associated with MCI and MCI subtypes in those ages 50 to 65. Examination of differences by gender revealed a stronger association of diabetes with amnestic MCI in middle-aged women and an even stronger association with nonamnestic MCI in middle-aged men.

—Kimberly D. Williams

Fish oil may reduce seizure frequency in patients with epilepsy, according to a study published online ahead of print September 8 in the Journal of Neurology, Neurosurgery, and Psychiatry. Twenty-four patients with drug-resistant epilepsy were given three separate treatments for 10 weeks and separated by a six-week period. Participants were given three capsules of fish oil daily, plus three capsules of corn oil (placebo); six capsules of fish oil daily; and three capsules of corn oil twice daily. The average number of seizures among those taking low-dose fish oil was around 12 per month, compared with slightly more than 17 for the high dose, and slightly more than 18 for the placebo. Two people who had the low dose were seizure free during the 10-week trial. No one taking the high-dose fish oil or the placebo was seizure free.

Blood type AB and higher factor VIII (FVIII) are associated with increased incidence of cognitive impairment, according to a study published online ahead of print September 10 in Neurology. Findings are based on a cohort from the REGARDS Study, in which more than 30,000 people were followed for an average of 3.4 years. After adjusting for age, race, region, and sex, the researchers found that people with blood group AB (odds ratio [OR], 1.82) and those with higher FVIII (OR, 1.24) had an increased risk of cognitive impairment. The mean FVIII was higher in people with blood type AB (142 IU/dL), compared with O (104 IU/dL), and FVIII mediated 18% of the association between AB group and incident cognitive impairment, according to the researchers.

Magnesium sulfate administered IV to pregnant women at risk of giving birth before 30 weeks gestation was not associated with neurologic, cognitive, behavioral, growth, or functional outcomes in their children at school age, investigators reported in the September 17 issue of JAMA. Researchers randomly assigned magnesium sulfate or placebo to pregnant women (n = 535 magnesium; n = 527 placebo) for whom birth was planned or expected before 30 weeks gestation; 1,255 fetuses were known to be alive at randomization. Of the 867 survivors available for follow-up, outcomes at school age (6 to 11) were determined for 669 children (77%). The investigators found that receiving antenatal magnesium sulfate was not associated with any long-term benefits or harms, compared with placebo. The study authors also observed a nonsignificant reduction in the risk of death in the magnesium sulfate group.

Older patients with Parkinson’s disease who underwent deep brain stimulation (DBS) had a similar 90-day complication risk, compared with that in younger patients, according to a study published online ahead of print August 25 in JAMA Neurology. Researchers analyzed data from more than 1,750 patients who had DBS from 2000 to 2009. Of those, 7.5% of subjects experienced at least one complication within 90 days of having the device implanted. The investigators determined that increasing age did not significantly affect the overall complication rates. The findings suggest that age alone should not be a primary exclusion factor for determining candidacy for DBS. “Instead, a clear focus on patients with medication-refractory and difficult to control on-off fluctuations with preserved cognition, regardless of age, may allow for an expansion of the traditional therapeutic window,” the researchers concluded.

Confusional arousals are highly prevalent in the general population, according to a study published in the August 26 issue of Neurology. A total of 19,136 people age 18 and older were interviewed about their sleep habits and whether they had experienced symptoms of the disorder. Participants also were asked about any medications they took and about mental illness diagnoses. Results showed that 15% had experienced an episode in the last year, with more than half reporting more than one episode per week. In the majority of cases, 84% of those with confusional arousals (also known as sleep drunkenness) also had a sleep disorder, mental health disorder, or were taking psychotropic drugs. Fewer than 1% of the people with confusional arousals had no known cause or related condition. “These episodes of waking up confused have received considerably less attention than sleepwalking even though the consequences can be just as serious,” stated researchers.

High potassium intake is associated with a lower risk of all stroke and ischemic stroke and all-cause mortality in older women, investigators reported online ahead of print September 4 in Stroke. Researchers studied 90,137 postmenopausal women ages 50 to 79 for an average of 11 years. Women who consumed the most potassium were 10% less likely to die than were those who had consumed the least amount. The women also were 12% less likely to have a stroke and 16% less likely to have an ischemic stroke than were women who consumed the least amount. Those without hypertension who had consumed the most potassium had a 27% lower ischemic stroke risk and 21% reduced risk for all stroke types, compared with women who had the least potassium in their diets. Among women with hypertension, those who consumed the most potassium had a lower risk of mortality.

Regular blood transfusion therapy significantly reduced the recurrence of cerebral infarct in children with sickle cell anemia, according to a study published in the August 21 issue of the New England Journal of Medicine. During the three-year study, 196 children ages 5 through 15 with sickle cell anemia who had previously had a silent stroke were followed. Children who underwent regular transfusions were 58% less likely to have another silent stroke or an overt stroke, while those who had no transfusions were more than twice as likely to experience repeat strokes. In addition, children who had monthly transfusions were less likely to have a range of other sickle cell anemia–related problems, such as episodes of extreme pain. Overall, 295 pain episodes occurred among children who did not receive transfusions, compared with 126 episodes among those receiving treatment.

Stroke incidence and mortality rates decreased from 1987 to 2011, according to a study published in the July 16 issue of JAMA. The findings were based on data from the Atherosclerosis Risk in Communities cohort of 15,792 US residents between the ages of 45 and 64 who were monitored during the 1980s. The new study followed the progress of 14,357 participants who were free of stroke in 1987 and monitored hospitalizations from stroke and deaths from 1987 to 2011. Stroke incidence decreased over time in Caucasians and African Americans, with an age-adjusted incidence rate ratio of 0.76. The absolute decrease was 0.93 per 1,000 person-years overall. The overall mortality rate after stroke decreased over time (hazard ratio, 0.80), with an absolute decrease of 8.09 per 100 strokes after 10 years.

The FDA has approved Vimpat (lacosamide) C-V as monotherapy in the treatment of partial-onset seizures in patients with epilepsy ages 17 and older. The monotherapy approval for Vimpat is based on a phase III historical-control conversion to lacosamide monotherapy study in adult patients with epilepsy with partial-onset seizures. This study met its primary end point, demonstrating that the exit percentage for patients converting to lacosamide (400 mg/day) was lower than the historical control exit percentage used as a comparator. Lacosamide (300 mg/day) also met the prespecified criteria for efficacy. Based on individual patients’ needs, physicians can choose between Vimpat formulations—tablets, oral solution, or injection. Vimpat (UCB; Brussels) is already approved in the US as adjunctive treatment for partial-onset seizures in patients in this age group.

Disruption of intestinal homeostasis is an early and immune-mediated event in experimental autoimmune encephalomyelitis, according to a study published September 3 in PLoS ONE. Investigators observed structural changes in the mucous membrane of the small intestine and an increase in inflammatory T cells, as well as a reduction in immunosuppressive cells. “Our findings provide support for the idea that a damaged intestinal barrier can prevent the body ending an autoimmune reaction in the normal manner, leading to a chronic disease such as multiple sclerosis,” stated the study authors. “In particular, an increased understanding of the regulation of tight junctions at the blood–brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.”

Children and adolescents with autism have a surplus of synapses in the brain due to reduced developmental spine pruning, investigators reported in the September 3 issue of Neuron. Researchers examined brains from children with autism who had died from other causes. Thirteen brains were from children ages 2 to 9, 13 brains were from children ages 13 to 20, and 22 brains were from children without autism. The investigators measured synapse density in a small section of tissue in each brain by counting the number of tiny spines that branch from the cortical neurons. During late childhood, spine density had decreased by about half in the control brains, compared with 16% in the brains from patients with autism. “Hundreds of genes have been linked to autism, but almost all of our human subjects had overactive mTOR and decreased autophagy, and all appear to have a lack of normal synaptic pruning,” stated study authors.

Macromolecular proton fraction (MPF) mapping enables quantitative assessment of demyelination in normal-appearing brain tissues and shows primary clinical relevance of gray matter damage in multiple sclerosis (MS), according to a study published online ahead of print September 10 in Radiology. Researchers examined 30 patients with MS, 18 with relapsing-remitting MS (RRMS) and 12 with secondary progressive MS. Fourteen healthy controls also were included. Each participant underwent MRI on a 3-T imager, and the investigators reconstructed 3-D whole-brain MPF maps to examine normal-appearing white matter, gray matter, and MS lesions. MPF was significantly lower in both white and gray matter in patients with RRMS, compared with healthy controls, and it was significantly reduced in normal-appearing brain tissues and lesions of patients with secondary progressive MS, compared with patients with RRMS with the largest relative decrease in gray matter.

Type 2 diabetes mellitus is associated with mild cognitive impairment (MCI) and MCI subtypes in middle-aged, but not in elderly participants, according to a study published online ahead of print July 7 in the Journal of Alzheimer’s Disease. A total of 560 participants diagnosed with MCI were compared with 1,376 cognitively normal participants from the Heinz Nixdorf Recall study. Of participants with MCI, 289 had amnestic MCI and 271 had nonamnestic MCI. Type 2 diabetes mellitus was strongly associated with MCI and MCI subtypes in those ages 50 to 65. Examination of differences by gender revealed a stronger association of diabetes with amnestic MCI in middle-aged women and an even stronger association with nonamnestic MCI in middle-aged men.

—Kimberly D. Williams

HIV infection is associated with a significantly lower risk of developing multiple sclerosis (MS), according to a study published online ahead of print August 4 in the Journal of Neurology, Neurosurgery, & Psychiatry. Researchers investigated episodes of hospital care between 1999 and 2011 for patients with HIV. Compared with people who did not have HIV, patients with HIV were 62% less likely to develop MS. After more than a year between the two diagnoses, HIV-positive patients were 75% less likely to develop MS. “If subsequent studies demonstrate [that] there is a causal protective effect of HIV or its treatment, and if the magnitude of it proves to be similar … this would be the largest protective effect of any factor yet observed in relation to the development of MS,” the investigators concluded.

Colds and other minor infections may temporarily increase stroke risk in children, according to a study published online ahead of print August 20 in Neurology. Using the Kaiser Permanente database of 2.5 million children, researchers identified 102 children who had had an acute ischemic stroke and compared them with 306 children without stroke. Medical records for the children who had had a stroke were reviewed for minor infections for two years before their strokes. Ten (9.8%) of the 102 children with stroke had visited a physician for an infection within three days of the stroke. In comparison, two controls (0.7%) had an infection during the same time period. “Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury,” the investigators theorized.

Peripheral pulse monitoring in patients with stroke accurately distinguishes atrial fibrillation from normal heart rhythm, investigators reported in the August 12 issue of Neurology. The prospective study included 256 patients with acute ischemic stroke, as well as the patients’ relatives. Subjects were taught to measure the patient’s pulse to detect atrial fibrillation; measurements from the participants and health care professionals were compared with recordings of electrical activity in the heart. Fifty-seven patients had irregular heartbeats. Measurement of the peripheral pulse by health care professionals had a diagnostic sensitivity of 96.5%, compared with 76.5% for the patients’ relatives, regarding the detection of atrial fibrillation. The specificity was 94.0% for health care professionals and 92.9% for patients’ relatives. Self-measurements were performed by 89.1% of patients with a diagnostic sensitivity of 54.1% and 96.2% specificity.

Reducing smoking among people in a low socioeconomic position and among those with hypertension may reduce social inequality stroke incidence, researchers reported online ahead of print August 14 in Stroke. The findings are based on data from 68,643 adults between ages 30 and 70 who were grouped into low, medium, and high education levels and assessed for smoking status and blood pressure level. About 16% of men and 11% of women had a high risk of stroke because of low education level, high blood pressure, and smoking. Smokers with low education had a greater risk of stroke than smokers with high education, regardless of their blood pressure. About 10% of men and 9% of women at high risk had an ischemic stroke during follow-up. Overall, men had a higher risk of stroke than women, and their risk increased with age.

Motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, is common in older adults and is a strong and early risk factor for cognitive decline, according to a study published online ahead of print July 16 in Neurology. Among 26,802 participants from 22 cohorts, 2,808 subjects met MCR criteria. MCR prevalence was higher among older individuals, but there were no sex differences. MCR predicted the risk of developing incident cognitive impairment (adjusted hazard ratio, 2.0); in individual cohorts the adjusted hazard ratios ranged from 1.5 to 2.7. MCR also predicted dementia in the pooled sample (adjusted hazard ratio, 1.9). “MCR criteria can be easily applied in clinical settings with simple questions about cognitive complaints and timing gait; 90% of participants had walking timed over fixed distances without requiring major resource commitments,” the investigators stated.

The FDA has approved Plegridy (peginterferon beta-1a) for patients with relapsing forms of multiple sclerosis (MS). Approval of the drug is based on results from the ADVANCE study of more than 1,500 patients with MS. The drug can be administered subcutaneously with an autoinjector or a prefilled syringe. Dosed once every two weeks, the drug significantly reduced annualized relapse rate at one year by 36%, compared with placebo. Plegridy reduced the risk of 12-week confirmed disability progression by 38%, compared with placebo. The drug also significantly reduced the number of new gadolinium-enhancing lesions by 86% and decreased the number of new or newly enlarging T2-hyperintense lesions by 67%, compared with placebo. Common adverse reactions include injection-site reaction and flu-like illness. The drug is manufactured by Biogen Idec, which is headquartered in Cambridge, Massachusetts.

In patients who are hospitalized for surgery, perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, according to a study published in the August 13 issue of JAMA. Researchers studied 1,729,360 patients hospitalized for surgery between 2007 and 2011. Perioperative atrial fibrillation was documented in 24,711 patients (1.43%) during the index hospitalization. After discharge, 13,952 patients (0.81%) had an ischemic stroke. One year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47% in patients with perioperative atrial fibrillation and 0.36% in people without atrial fibrillation. One year after cardiac surgery, cumulative rates of stroke were 0.99% in patients with perioperative atrial fibrillation and 0.83% in patients without atrial fibrillation. The association with stroke was stronger for perioperative atrial fibrillation and noncardiac surgery, compared with cardiac surgery.

Approximately one-third of cases of Alzheimer’s disease worldwide might be attributed to potentially modifiable risk factors, investigators reported in the August issue of Lancet Neurology. An international team of researchers used relative risks from existing meta-analyses to estimate the population-attributable risk (PAR) of Alzheimer’s disease worldwide and in the United States, Europe, and the United Kingdom for seven potentially modifiable risk factors. Worldwide, the highest estimated PAR was for low educational attainment. In the US, Europe, and UK the highest estimated PAR was for physical inactivity. Assuming the risk factors’ independence, the combined worldwide PAR for the seven risk factors was 49.4%, which accounts for 16.8 million of the 33.9 million cases. Adjustment for the association between the risk factors decreased the estimate to 28.2%, which equates to 9.6 million cases.

The FDA has approved Belsomra (suvorexant) for adults with insomnia who have difficulty falling and staying asleep. The drug is the first approved orexin receptor antagonist. Orexins are involved in regulating the sleep–wake cycle and play a role in promoting arousal. In clinical trials, Belsomra (Merck; Whitehouse Station, New Jersey) was superior to placebo for reducing sleep latency and improving sleep maintenance, as assessed objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra should be taken no more than once per night, within 30 minutes of going to bed, with at least seven hours remaining before the planned time of waking. The total dose should not exceed 20 mg once daily. The most commonly reported adverse reaction among clinical trial participants taking Belsomra was drowsiness.

A clinical diagnosis of Parkinson’s disease identifies patients who will have pathologically confirmed Parkinson’s disease with a sensitivity of 88% and specificity of 68%, researchers reported in the July 29 issue of Neurology. Investigators analyzed data from an aging study to determine the predictive value of clinical diagnosis of Parkinson’s disease using two diagnostic confidence levels: possible and probable Parkinson’s disease. Approximately 26% of patients diagnosed with possible Parkinson’s disease were neuropathologically confirmed as having Parkinson’s disease; 82% of patients diagnosed with probable Parkinson’s disease were confirmed as having Parkinson’s disease. Researchers calculated a 26% accuracy rate for clinical diagnosis of Parkinson’s disease in untreated or not clearly responsive subjects, a 53% accuracy rate in early Parkinson’s disease responsive to medication (less than five year’s duration), and a greater than 85% diagnostic accuracy rate for longer duration, medication-responsive Parkinson’s disease.

Depressive symptoms in old age are associated with cognitive decline that is independent of dementia, according to a study published in the August 19 issue of Neurology. Investigators monitored 1,764 participants with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression and were evaluated for their memory and thinking skills for a mean of 7.8 years. A total of 922 (52%) participants developed mild cognitive impairment, and 315 (18%) developed dementia. Overall, having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, which accounted for 4.4% of the difference in decline that could not be attributed to the level of damage in the brain.

Researchers may have found a potential genetic link between epilepsy and neurodegenerative disorders, according to a study published in the July 29 Proceedings of the National Academy of Sciences. The investigators observed that seizure-prone prickle mutant flies have behavioral defects and electrophysiologic defects similar to those of other fly mutants used to study seizures. Altering the balance of two forms of the prickle gene disrupted neural information flow and caused epilepsy. The researchers also observed that reducing either of two motor proteins responsible for directional movement of vesicles along the tracks of structural proteins in axons could suppress seizures. “This is, to our knowledge, the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” stated the authors.

—Kimberly Williams

HIV infection is associated with a significantly lower risk of developing multiple sclerosis (MS), according to a study published online ahead of print August 4 in the Journal of Neurology, Neurosurgery, & Psychiatry. Researchers investigated episodes of hospital care between 1999 and 2011 for patients with HIV. Compared with people who did not have HIV, patients with HIV were 62% less likely to develop MS. After more than a year between the two diagnoses, HIV-positive patients were 75% less likely to develop MS. “If subsequent studies demonstrate [that] there is a causal protective effect of HIV or its treatment, and if the magnitude of it proves to be similar … this would be the largest protective effect of any factor yet observed in relation to the development of MS,” the investigators concluded.

Colds and other minor infections may temporarily increase stroke risk in children, according to a study published online ahead of print August 20 in Neurology. Using the Kaiser Permanente database of 2.5 million children, researchers identified 102 children who had had an acute ischemic stroke and compared them with 306 children without stroke. Medical records for the children who had had a stroke were reviewed for minor infections for two years before their strokes. Ten (9.8%) of the 102 children with stroke had visited a physician for an infection within three days of the stroke. In comparison, two controls (0.7%) had an infection during the same time period. “Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury,” the investigators theorized.

Peripheral pulse monitoring in patients with stroke accurately distinguishes atrial fibrillation from normal heart rhythm, investigators reported in the August 12 issue of Neurology. The prospective study included 256 patients with acute ischemic stroke, as well as the patients’ relatives. Subjects were taught to measure the patient’s pulse to detect atrial fibrillation; measurements from the participants and health care professionals were compared with recordings of electrical activity in the heart. Fifty-seven patients had irregular heartbeats. Measurement of the peripheral pulse by health care professionals had a diagnostic sensitivity of 96.5%, compared with 76.5% for the patients’ relatives, regarding the detection of atrial fibrillation. The specificity was 94.0% for health care professionals and 92.9% for patients’ relatives. Self-measurements were performed by 89.1% of patients with a diagnostic sensitivity of 54.1% and 96.2% specificity.

Reducing smoking among people in a low socioeconomic position and among those with hypertension may reduce social inequality stroke incidence, researchers reported online ahead of print August 14 in Stroke. The findings are based on data from 68,643 adults between ages 30 and 70 who were grouped into low, medium, and high education levels and assessed for smoking status and blood pressure level. About 16% of men and 11% of women had a high risk of stroke because of low education level, high blood pressure, and smoking. Smokers with low education had a greater risk of stroke than smokers with high education, regardless of their blood pressure. About 10% of men and 9% of women at high risk had an ischemic stroke during follow-up. Overall, men had a higher risk of stroke than women, and their risk increased with age.

Motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, is common in older adults and is a strong and early risk factor for cognitive decline, according to a study published online ahead of print July 16 in Neurology. Among 26,802 participants from 22 cohorts, 2,808 subjects met MCR criteria. MCR prevalence was higher among older individuals, but there were no sex differences. MCR predicted the risk of developing incident cognitive impairment (adjusted hazard ratio, 2.0); in individual cohorts the adjusted hazard ratios ranged from 1.5 to 2.7. MCR also predicted dementia in the pooled sample (adjusted hazard ratio, 1.9). “MCR criteria can be easily applied in clinical settings with simple questions about cognitive complaints and timing gait; 90% of participants had walking timed over fixed distances without requiring major resource commitments,” the investigators stated.

The FDA has approved Plegridy (peginterferon beta-1a) for patients with relapsing forms of multiple sclerosis (MS). Approval of the drug is based on results from the ADVANCE study of more than 1,500 patients with MS. The drug can be administered subcutaneously with an autoinjector or a prefilled syringe. Dosed once every two weeks, the drug significantly reduced annualized relapse rate at one year by 36%, compared with placebo. Plegridy reduced the risk of 12-week confirmed disability progression by 38%, compared with placebo. The drug also significantly reduced the number of new gadolinium-enhancing lesions by 86% and decreased the number of new or newly enlarging T2-hyperintense lesions by 67%, compared with placebo. Common adverse reactions include injection-site reaction and flu-like illness. The drug is manufactured by Biogen Idec, which is headquartered in Cambridge, Massachusetts.

In patients who are hospitalized for surgery, perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, according to a study published in the August 13 issue of JAMA. Researchers studied 1,729,360 patients hospitalized for surgery between 2007 and 2011. Perioperative atrial fibrillation was documented in 24,711 patients (1.43%) during the index hospitalization. After discharge, 13,952 patients (0.81%) had an ischemic stroke. One year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47% in patients with perioperative atrial fibrillation and 0.36% in people without atrial fibrillation. One year after cardiac surgery, cumulative rates of stroke were 0.99% in patients with perioperative atrial fibrillation and 0.83% in patients without atrial fibrillation. The association with stroke was stronger for perioperative atrial fibrillation and noncardiac surgery, compared with cardiac surgery.

Approximately one-third of cases of Alzheimer’s disease worldwide might be attributed to potentially modifiable risk factors, investigators reported in the August issue of Lancet Neurology. An international team of researchers used relative risks from existing meta-analyses to estimate the population-attributable risk (PAR) of Alzheimer’s disease worldwide and in the United States, Europe, and the United Kingdom for seven potentially modifiable risk factors. Worldwide, the highest estimated PAR was for low educational attainment. In the US, Europe, and UK the highest estimated PAR was for physical inactivity. Assuming the risk factors’ independence, the combined worldwide PAR for the seven risk factors was 49.4%, which accounts for 16.8 million of the 33.9 million cases. Adjustment for the association between the risk factors decreased the estimate to 28.2%, which equates to 9.6 million cases.

The FDA has approved Belsomra (suvorexant) for adults with insomnia who have difficulty falling and staying asleep. The drug is the first approved orexin receptor antagonist. Orexins are involved in regulating the sleep–wake cycle and play a role in promoting arousal. In clinical trials, Belsomra (Merck; Whitehouse Station, New Jersey) was superior to placebo for reducing sleep latency and improving sleep maintenance, as assessed objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra should be taken no more than once per night, within 30 minutes of going to bed, with at least seven hours remaining before the planned time of waking. The total dose should not exceed 20 mg once daily. The most commonly reported adverse reaction among clinical trial participants taking Belsomra was drowsiness.

A clinical diagnosis of Parkinson’s disease identifies patients who will have pathologically confirmed Parkinson’s disease with a sensitivity of 88% and specificity of 68%, researchers reported in the July 29 issue of Neurology. Investigators analyzed data from an aging study to determine the predictive value of clinical diagnosis of Parkinson’s disease using two diagnostic confidence levels: possible and probable Parkinson’s disease. Approximately 26% of patients diagnosed with possible Parkinson’s disease were neuropathologically confirmed as having Parkinson’s disease; 82% of patients diagnosed with probable Parkinson’s disease were confirmed as having Parkinson’s disease. Researchers calculated a 26% accuracy rate for clinical diagnosis of Parkinson’s disease in untreated or not clearly responsive subjects, a 53% accuracy rate in early Parkinson’s disease responsive to medication (less than five year’s duration), and a greater than 85% diagnostic accuracy rate for longer duration, medication-responsive Parkinson’s disease.

Depressive symptoms in old age are associated with cognitive decline that is independent of dementia, according to a study published in the August 19 issue of Neurology. Investigators monitored 1,764 participants with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression and were evaluated for their memory and thinking skills for a mean of 7.8 years. A total of 922 (52%) participants developed mild cognitive impairment, and 315 (18%) developed dementia. Overall, having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, which accounted for 4.4% of the difference in decline that could not be attributed to the level of damage in the brain.

Researchers may have found a potential genetic link between epilepsy and neurodegenerative disorders, according to a study published in the July 29 Proceedings of the National Academy of Sciences. The investigators observed that seizure-prone prickle mutant flies have behavioral defects and electrophysiologic defects similar to those of other fly mutants used to study seizures. Altering the balance of two forms of the prickle gene disrupted neural information flow and caused epilepsy. The researchers also observed that reducing either of two motor proteins responsible for directional movement of vesicles along the tracks of structural proteins in axons could suppress seizures. “This is, to our knowledge, the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” stated the authors.

—Kimberly Williams

HIV infection is associated with a significantly lower risk of developing multiple sclerosis (MS), according to a study published online ahead of print August 4 in the Journal of Neurology, Neurosurgery, & Psychiatry. Researchers investigated episodes of hospital care between 1999 and 2011 for patients with HIV. Compared with people who did not have HIV, patients with HIV were 62% less likely to develop MS. After more than a year between the two diagnoses, HIV-positive patients were 75% less likely to develop MS. “If subsequent studies demonstrate [that] there is a causal protective effect of HIV or its treatment, and if the magnitude of it proves to be similar … this would be the largest protective effect of any factor yet observed in relation to the development of MS,” the investigators concluded.

Colds and other minor infections may temporarily increase stroke risk in children, according to a study published online ahead of print August 20 in Neurology. Using the Kaiser Permanente database of 2.5 million children, researchers identified 102 children who had had an acute ischemic stroke and compared them with 306 children without stroke. Medical records for the children who had had a stroke were reviewed for minor infections for two years before their strokes. Ten (9.8%) of the 102 children with stroke had visited a physician for an infection within three days of the stroke. In comparison, two controls (0.7%) had an infection during the same time period. “Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury,” the investigators theorized.

Peripheral pulse monitoring in patients with stroke accurately distinguishes atrial fibrillation from normal heart rhythm, investigators reported in the August 12 issue of Neurology. The prospective study included 256 patients with acute ischemic stroke, as well as the patients’ relatives. Subjects were taught to measure the patient’s pulse to detect atrial fibrillation; measurements from the participants and health care professionals were compared with recordings of electrical activity in the heart. Fifty-seven patients had irregular heartbeats. Measurement of the peripheral pulse by health care professionals had a diagnostic sensitivity of 96.5%, compared with 76.5% for the patients’ relatives, regarding the detection of atrial fibrillation. The specificity was 94.0% for health care professionals and 92.9% for patients’ relatives. Self-measurements were performed by 89.1% of patients with a diagnostic sensitivity of 54.1% and 96.2% specificity.

Reducing smoking among people in a low socioeconomic position and among those with hypertension may reduce social inequality stroke incidence, researchers reported online ahead of print August 14 in Stroke. The findings are based on data from 68,643 adults between ages 30 and 70 who were grouped into low, medium, and high education levels and assessed for smoking status and blood pressure level. About 16% of men and 11% of women had a high risk of stroke because of low education level, high blood pressure, and smoking. Smokers with low education had a greater risk of stroke than smokers with high education, regardless of their blood pressure. About 10% of men and 9% of women at high risk had an ischemic stroke during follow-up. Overall, men had a higher risk of stroke than women, and their risk increased with age.

Motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, is common in older adults and is a strong and early risk factor for cognitive decline, according to a study published online ahead of print July 16 in Neurology. Among 26,802 participants from 22 cohorts, 2,808 subjects met MCR criteria. MCR prevalence was higher among older individuals, but there were no sex differences. MCR predicted the risk of developing incident cognitive impairment (adjusted hazard ratio, 2.0); in individual cohorts the adjusted hazard ratios ranged from 1.5 to 2.7. MCR also predicted dementia in the pooled sample (adjusted hazard ratio, 1.9). “MCR criteria can be easily applied in clinical settings with simple questions about cognitive complaints and timing gait; 90% of participants had walking timed over fixed distances without requiring major resource commitments,” the investigators stated.

The FDA has approved Plegridy (peginterferon beta-1a) for patients with relapsing forms of multiple sclerosis (MS). Approval of the drug is based on results from the ADVANCE study of more than 1,500 patients with MS. The drug can be administered subcutaneously with an autoinjector or a prefilled syringe. Dosed once every two weeks, the drug significantly reduced annualized relapse rate at one year by 36%, compared with placebo. Plegridy reduced the risk of 12-week confirmed disability progression by 38%, compared with placebo. The drug also significantly reduced the number of new gadolinium-enhancing lesions by 86% and decreased the number of new or newly enlarging T2-hyperintense lesions by 67%, compared with placebo. Common adverse reactions include injection-site reaction and flu-like illness. The drug is manufactured by Biogen Idec, which is headquartered in Cambridge, Massachusetts.

In patients who are hospitalized for surgery, perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, according to a study published in the August 13 issue of JAMA. Researchers studied 1,729,360 patients hospitalized for surgery between 2007 and 2011. Perioperative atrial fibrillation was documented in 24,711 patients (1.43%) during the index hospitalization. After discharge, 13,952 patients (0.81%) had an ischemic stroke. One year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47% in patients with perioperative atrial fibrillation and 0.36% in people without atrial fibrillation. One year after cardiac surgery, cumulative rates of stroke were 0.99% in patients with perioperative atrial fibrillation and 0.83% in patients without atrial fibrillation. The association with stroke was stronger for perioperative atrial fibrillation and noncardiac surgery, compared with cardiac surgery.

Approximately one-third of cases of Alzheimer’s disease worldwide might be attributed to potentially modifiable risk factors, investigators reported in the August issue of Lancet Neurology. An international team of researchers used relative risks from existing meta-analyses to estimate the population-attributable risk (PAR) of Alzheimer’s disease worldwide and in the United States, Europe, and the United Kingdom for seven potentially modifiable risk factors. Worldwide, the highest estimated PAR was for low educational attainment. In the US, Europe, and UK the highest estimated PAR was for physical inactivity. Assuming the risk factors’ independence, the combined worldwide PAR for the seven risk factors was 49.4%, which accounts for 16.8 million of the 33.9 million cases. Adjustment for the association between the risk factors decreased the estimate to 28.2%, which equates to 9.6 million cases.

The FDA has approved Belsomra (suvorexant) for adults with insomnia who have difficulty falling and staying asleep. The drug is the first approved orexin receptor antagonist. Orexins are involved in regulating the sleep–wake cycle and play a role in promoting arousal. In clinical trials, Belsomra (Merck; Whitehouse Station, New Jersey) was superior to placebo for reducing sleep latency and improving sleep maintenance, as assessed objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra should be taken no more than once per night, within 30 minutes of going to bed, with at least seven hours remaining before the planned time of waking. The total dose should not exceed 20 mg once daily. The most commonly reported adverse reaction among clinical trial participants taking Belsomra was drowsiness.

A clinical diagnosis of Parkinson’s disease identifies patients who will have pathologically confirmed Parkinson’s disease with a sensitivity of 88% and specificity of 68%, researchers reported in the July 29 issue of Neurology. Investigators analyzed data from an aging study to determine the predictive value of clinical diagnosis of Parkinson’s disease using two diagnostic confidence levels: possible and probable Parkinson’s disease. Approximately 26% of patients diagnosed with possible Parkinson’s disease were neuropathologically confirmed as having Parkinson’s disease; 82% of patients diagnosed with probable Parkinson’s disease were confirmed as having Parkinson’s disease. Researchers calculated a 26% accuracy rate for clinical diagnosis of Parkinson’s disease in untreated or not clearly responsive subjects, a 53% accuracy rate in early Parkinson’s disease responsive to medication (less than five year’s duration), and a greater than 85% diagnostic accuracy rate for longer duration, medication-responsive Parkinson’s disease.

Depressive symptoms in old age are associated with cognitive decline that is independent of dementia, according to a study published in the August 19 issue of Neurology. Investigators monitored 1,764 participants with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression and were evaluated for their memory and thinking skills for a mean of 7.8 years. A total of 922 (52%) participants developed mild cognitive impairment, and 315 (18%) developed dementia. Overall, having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, which accounted for 4.4% of the difference in decline that could not be attributed to the level of damage in the brain.

Researchers may have found a potential genetic link between epilepsy and neurodegenerative disorders, according to a study published in the July 29 Proceedings of the National Academy of Sciences. The investigators observed that seizure-prone prickle mutant flies have behavioral defects and electrophysiologic defects similar to those of other fly mutants used to study seizures. Altering the balance of two forms of the prickle gene disrupted neural information flow and caused epilepsy. The researchers also observed that reducing either of two motor proteins responsible for directional movement of vesicles along the tracks of structural proteins in axons could suppress seizures. “This is, to our knowledge, the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” stated the authors.

—Kimberly Williams

Older veterans with traumatic brain injury (TBI) are 60% more likely to develop dementia later in life, compared with veterans without TBI, according to a study published online ahead of print June 25 in Neurology. The study involved 188,764 veterans ages 55 and older. At the study’s outset, each participant was free of dementia and had at least one inpatient or outpatient visit to a health care facility at baseline (2000 to 2003) and during the follow-up (2003 to 2012). A total of 1,229 veterans had a TBI diagnosis; 196 veterans with TBI (16%) developed dementia, and 18,255 (10%) of those without TBI developed dementia. On average, veterans with TBI developed dementia two years earlier than those without TBI. “If we assume that this relationship is causal, it seems likely that the same increased risk probably occurs with TBI in the civilian population as well,” said the researchers.

Higher levels of depressive symptoms, stress, and hostility are associated with a significantly increased risk of stroke or transient ischemic attack (TIA) in middle-aged and older adults, according to a study published online ahead of print July 10 in Stroke. Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine how psychologic factors might influence the risk for chronic disease. The investigators examined data for 6,749 adults (ages 45 to 84; 53% women) as they completed questionnaires assessing chronic stress, depressive symptoms, anger, and hostility during a two-year period. Hazard ratios indicated a significantly elevated risk of stroke or TIA for the highest scoring group, compared with the lowest scoring group, for depressive symptoms (HR, 1.86), chronic stress (HR, 1.59), and hostility (HR, 2.22). No significant increased risk was associated with anger.

Patients with mild to moderate Parkinson’s disease can improve their symptoms with regular walking, according to a study published online ahead of print July 2 in Neurology. Investigators included 60 individuals who participated in a randomized trial of various exercise regimens for six months. Eighty-one percent of participants completed the study with a mean attendance of 83.3%. Subjects took additional tests to gauge their aerobic fitness, tiredness, and other factors. Brisk walking reduced tiredness by 11%, improved motor function and mood by 15%, improved attention and response control scores by 14%, and increased aerobic fitness and gait speed by 7%. With regard to motor function, participants improved by an average of 2.8 points. “The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” stated the researchers.

Mild traumatic brain injury (TBI) may result in brain damage and memory and thinking problems, according to a study published online ahead of print July 16 in Neurology. Fifty-three patients (44 with mild TBI and nine with moderate TBI) were compared with 33 participants without brain injury. Each subject underwent testing to assess his or her memory and thinking skills. Participants also had diffusion tensor imaging scans. Those with injuries had brain damage in white matter that consisted of disruption to nerve axons. Researchers also determined that scores on the verbal letter fluency task were 25% lower in individuals with injury than in individuals without injury. “We studied patients who had suffered clinically mild injuries, often from common accidents such as falling from a bicycle, or slow-speed car accidents. This finding is especially important, as 90% of all TBIs are mild to moderate,” said the researchers.

Patients with a traumatic brain injury (TBI) who received erythropoietin (EPO) or maintained a higher hemoglobin concentration through blood transfusion did not have an improved neurologic outcome at six months, according to a study published in the July 2 issue of JAMA. The randomized study included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two US level I trauma centers between May 2006 and August 2012. Patients were enrolled within six hours of injury and had to be unable to follow commands after initial stabilization. Overall, transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events. Researchers also observed a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) versus the threshold of 7 g/dL (8.1%)

Frontline Medical Communications and the National Organization for Rare Disorders (NORD) have signed a partnership agreement to develop educational programs about rare diseases for health care providers. Frontline and NORD also seek to improve awareness, recognition, and understanding of rare diseases among health care providers to accelerate diagnosis and promote optimal care for patients, facilitate the sharing of information among health care providers and rare disease medical experts, and update health care providers on new treatment options and clinical care standards. “Innovative multichannel educational programs, developed by both organizations and funded by commercial sponsors, will be distributed to more than 1.2 million health care providers using Frontline’s portfolio of 30 journal brands, corresponding websites, eNewsletters, and live events,” according to Frontline.

Upsher-Smith Laboratories (Maple Grove, Minnesota) announced that Qudexy XR (topiramate) extended-release capsules are now available in the United States. Qudexy XR, a broad-spectrum, once-daily antiepileptic drug is engineered to deliver a smooth pharmacokinetic profile. The FDA approved Qudexy XR in March 2014 as an initial monotherapy in patients 10 and older with primary generalized tonic-clonic seizures and partial-onset seizures. The drug also was approved as adjunctive therapy in patients 2 and older with primary generalized tonic-clonic seizures, partial-onset seizures, and seizures associated with Lennox-Gastaut syndrome. Overall, results from Upsher-Smith’s phase III trial showed that Qudexy XR is generally well tolerated and effective.

Transplanted brain cells producing dopamine remain viable in patients with Parkinson’s disease for several years, according to a study published June 26 in Cell Reports. The study included five patients with Parkinson’s disease who received transplants of fetal tissue-derived, dopamine-producing neurons four to 14 years earlier. Their transplanted dopamine neurons showed no signs of Parkinson’s disease–associated deterioration and appeared healthy. Researchers believe the findings provide further support for stem cells as a source for transplant-ready dopamine neurons. The investigators noted that the neuronal transplant has proven to be a durable treatment for many patients with Parkinson’s disease, with some improving for years without a need for standard medications. The study authors called the new finding “extremely encouraging,” adding that the long life of the transplanted neurons bodes well “for advancing [the technique] as a restoration therapy for Parkinson’s disease.”

Women may recover more quickly than men after a concussion, according to a study published online ahead of print May 6 in Radiology. Researchers examined the medical records and imaging results of 69 patients diagnosed with mild traumatic brain injury (TBI) between 2006 and 2013. The cohort included 47 men, 22 women, and 21 controls (10 men; median age of men, 17; median age of women, 16). Of the 47 men with TBI, 32 (68%) were injured while playing a sport, as were 10 of the 22 women (45%). Although all participants underwent the same evaluation, diffusion tensor imaging scans revealed that compared with the female patients with mild TBI, the male patients with mild TBI had significantly decreased uncinate fasciculus fractional anisotropy values. The average recovery time for all patients with concussion was 54 days. However, compared with women, who recovered in an average of 26.3 days, recovery was significantly longer for men (66.9 days).

Patients with mesial temporal lobe epilepsy who cannot be controlled with medication can now opt for a minimally invasive laser procedure performed under MRI guidance, according to a study published in the June issue of Neurosurgery. Researchers used an MRI-guided stereotactic laser amygdalohippocampotomy in 13 adult patients with epilepsy (median age, 24). During this procedure, a saline-cooled fiber-optic laser probe was targeted at the amygdalohippocampal complex. Using real-time MRI guidance, a neurosurgeon pinpointed the area of the brain responsible for seizure activity and destroyed this tissue without harming nearby brain tissue. Sixty percent of the amygdalohippocampal complex was destroyed, and the average length of the ablated area was 2.5 cm. “Such minimally invasive techniques may be more desirable to patients and result in increased use of epilepsy surgery among the large number of medically intractable epilepsy patients,” according to the investigators.

Researchers identified 10 proteins in the blood that can predict the onset of Alzheimer’s disease, according to a study published online ahead of print July 3 in Alzheimer’s & Dementia. In the international study of 1,148 individuals (220 with mild cognitive impairment [MCI], 452 elderly controls without dementia, and 476 with Alzheimer’s disease), blood samples were analyzed for 26 proteins previously associated with Alzheimer’s disease. Investigators found 16 of the 26 proteins to be strongly associated with brain shrinkage in Alzheimer’s disease or MCI. The researchers conducted a second series of tests to establish which of these proteins could predict the progression from MCI to Alzheimer’s disease. The study authors identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year with 87% accuracy. “Memory problems are common, but the challenge is identifying who is likely to develop dementia,” according to the researchers.

An international team of researchers has reviewed the diagnostic criteria for Alzheimer’s disease developed by the International Working Group (IWG) and US National Institute on Aging–Alzheimer’s Association, according to a study published in the June issue of Lancet Neurology. The team considered the strengths and weakness of the IWG criteria and proposed advances to improve the diagnostic framework. The investigators asserted that the diagnosis of Alzheimer’s disease can be simplified by requiring the presence of an appropriate clinical Alzheimer’s disease phenotype (typical or atypical) and a pathophysiologic biomarker consistent with the presence of Alzheimer’s pathology. “We propose that downstream topographic biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease,” the team stated

—Kimberly D. Williams

Older veterans with traumatic brain injury (TBI) are 60% more likely to develop dementia later in life, compared with veterans without TBI, according to a study published online ahead of print June 25 in Neurology. The study involved 188,764 veterans ages 55 and older. At the study’s outset, each participant was free of dementia and had at least one inpatient or outpatient visit to a health care facility at baseline (2000 to 2003) and during the follow-up (2003 to 2012). A total of 1,229 veterans had a TBI diagnosis; 196 veterans with TBI (16%) developed dementia, and 18,255 (10%) of those without TBI developed dementia. On average, veterans with TBI developed dementia two years earlier than those without TBI. “If we assume that this relationship is causal, it seems likely that the same increased risk probably occurs with TBI in the civilian population as well,” said the researchers.

Higher levels of depressive symptoms, stress, and hostility are associated with a significantly increased risk of stroke or transient ischemic attack (TIA) in middle-aged and older adults, according to a study published online ahead of print July 10 in Stroke. Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine how psychologic factors might influence the risk for chronic disease. The investigators examined data for 6,749 adults (ages 45 to 84; 53% women) as they completed questionnaires assessing chronic stress, depressive symptoms, anger, and hostility during a two-year period. Hazard ratios indicated a significantly elevated risk of stroke or TIA for the highest scoring group, compared with the lowest scoring group, for depressive symptoms (HR, 1.86), chronic stress (HR, 1.59), and hostility (HR, 2.22). No significant increased risk was associated with anger.

Patients with mild to moderate Parkinson’s disease can improve their symptoms with regular walking, according to a study published online ahead of print July 2 in Neurology. Investigators included 60 individuals who participated in a randomized trial of various exercise regimens for six months. Eighty-one percent of participants completed the study with a mean attendance of 83.3%. Subjects took additional tests to gauge their aerobic fitness, tiredness, and other factors. Brisk walking reduced tiredness by 11%, improved motor function and mood by 15%, improved attention and response control scores by 14%, and increased aerobic fitness and gait speed by 7%. With regard to motor function, participants improved by an average of 2.8 points. “The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” stated the researchers.

Mild traumatic brain injury (TBI) may result in brain damage and memory and thinking problems, according to a study published online ahead of print July 16 in Neurology. Fifty-three patients (44 with mild TBI and nine with moderate TBI) were compared with 33 participants without brain injury. Each subject underwent testing to assess his or her memory and thinking skills. Participants also had diffusion tensor imaging scans. Those with injuries had brain damage in white matter that consisted of disruption to nerve axons. Researchers also determined that scores on the verbal letter fluency task were 25% lower in individuals with injury than in individuals without injury. “We studied patients who had suffered clinically mild injuries, often from common accidents such as falling from a bicycle, or slow-speed car accidents. This finding is especially important, as 90% of all TBIs are mild to moderate,” said the researchers.

Patients with a traumatic brain injury (TBI) who received erythropoietin (EPO) or maintained a higher hemoglobin concentration through blood transfusion did not have an improved neurologic outcome at six months, according to a study published in the July 2 issue of JAMA. The randomized study included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two US level I trauma centers between May 2006 and August 2012. Patients were enrolled within six hours of injury and had to be unable to follow commands after initial stabilization. Overall, transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events. Researchers also observed a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) versus the threshold of 7 g/dL (8.1%)

Frontline Medical Communications and the National Organization for Rare Disorders (NORD) have signed a partnership agreement to develop educational programs about rare diseases for health care providers. Frontline and NORD also seek to improve awareness, recognition, and understanding of rare diseases among health care providers to accelerate diagnosis and promote optimal care for patients, facilitate the sharing of information among health care providers and rare disease medical experts, and update health care providers on new treatment options and clinical care standards. “Innovative multichannel educational programs, developed by both organizations and funded by commercial sponsors, will be distributed to more than 1.2 million health care providers using Frontline’s portfolio of 30 journal brands, corresponding websites, eNewsletters, and live events,” according to Frontline.

Upsher-Smith Laboratories (Maple Grove, Minnesota) announced that Qudexy XR (topiramate) extended-release capsules are now available in the United States. Qudexy XR, a broad-spectrum, once-daily antiepileptic drug is engineered to deliver a smooth pharmacokinetic profile. The FDA approved Qudexy XR in March 2014 as an initial monotherapy in patients 10 and older with primary generalized tonic-clonic seizures and partial-onset seizures. The drug also was approved as adjunctive therapy in patients 2 and older with primary generalized tonic-clonic seizures, partial-onset seizures, and seizures associated with Lennox-Gastaut syndrome. Overall, results from Upsher-Smith’s phase III trial showed that Qudexy XR is generally well tolerated and effective.

Transplanted brain cells producing dopamine remain viable in patients with Parkinson’s disease for several years, according to a study published June 26 in Cell Reports. The study included five patients with Parkinson’s disease who received transplants of fetal tissue-derived, dopamine-producing neurons four to 14 years earlier. Their transplanted dopamine neurons showed no signs of Parkinson’s disease–associated deterioration and appeared healthy. Researchers believe the findings provide further support for stem cells as a source for transplant-ready dopamine neurons. The investigators noted that the neuronal transplant has proven to be a durable treatment for many patients with Parkinson’s disease, with some improving for years without a need for standard medications. The study authors called the new finding “extremely encouraging,” adding that the long life of the transplanted neurons bodes well “for advancing [the technique] as a restoration therapy for Parkinson’s disease.”

Women may recover more quickly than men after a concussion, according to a study published online ahead of print May 6 in Radiology. Researchers examined the medical records and imaging results of 69 patients diagnosed with mild traumatic brain injury (TBI) between 2006 and 2013. The cohort included 47 men, 22 women, and 21 controls (10 men; median age of men, 17; median age of women, 16). Of the 47 men with TBI, 32 (68%) were injured while playing a sport, as were 10 of the 22 women (45%). Although all participants underwent the same evaluation, diffusion tensor imaging scans revealed that compared with the female patients with mild TBI, the male patients with mild TBI had significantly decreased uncinate fasciculus fractional anisotropy values. The average recovery time for all patients with concussion was 54 days. However, compared with women, who recovered in an average of 26.3 days, recovery was significantly longer for men (66.9 days).

Patients with mesial temporal lobe epilepsy who cannot be controlled with medication can now opt for a minimally invasive laser procedure performed under MRI guidance, according to a study published in the June issue of Neurosurgery. Researchers used an MRI-guided stereotactic laser amygdalohippocampotomy in 13 adult patients with epilepsy (median age, 24). During this procedure, a saline-cooled fiber-optic laser probe was targeted at the amygdalohippocampal complex. Using real-time MRI guidance, a neurosurgeon pinpointed the area of the brain responsible for seizure activity and destroyed this tissue without harming nearby brain tissue. Sixty percent of the amygdalohippocampal complex was destroyed, and the average length of the ablated area was 2.5 cm. “Such minimally invasive techniques may be more desirable to patients and result in increased use of epilepsy surgery among the large number of medically intractable epilepsy patients,” according to the investigators.

Researchers identified 10 proteins in the blood that can predict the onset of Alzheimer’s disease, according to a study published online ahead of print July 3 in Alzheimer’s & Dementia. In the international study of 1,148 individuals (220 with mild cognitive impairment [MCI], 452 elderly controls without dementia, and 476 with Alzheimer’s disease), blood samples were analyzed for 26 proteins previously associated with Alzheimer’s disease. Investigators found 16 of the 26 proteins to be strongly associated with brain shrinkage in Alzheimer’s disease or MCI. The researchers conducted a second series of tests to establish which of these proteins could predict the progression from MCI to Alzheimer’s disease. The study authors identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year with 87% accuracy. “Memory problems are common, but the challenge is identifying who is likely to develop dementia,” according to the researchers.

An international team of researchers has reviewed the diagnostic criteria for Alzheimer’s disease developed by the International Working Group (IWG) and US National Institute on Aging–Alzheimer’s Association, according to a study published in the June issue of Lancet Neurology. The team considered the strengths and weakness of the IWG criteria and proposed advances to improve the diagnostic framework. The investigators asserted that the diagnosis of Alzheimer’s disease can be simplified by requiring the presence of an appropriate clinical Alzheimer’s disease phenotype (typical or atypical) and a pathophysiologic biomarker consistent with the presence of Alzheimer’s pathology. “We propose that downstream topographic biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease,” the team stated

—Kimberly D. Williams

Older veterans with traumatic brain injury (TBI) are 60% more likely to develop dementia later in life, compared with veterans without TBI, according to a study published online ahead of print June 25 in Neurology. The study involved 188,764 veterans ages 55 and older. At the study’s outset, each participant was free of dementia and had at least one inpatient or outpatient visit to a health care facility at baseline (2000 to 2003) and during the follow-up (2003 to 2012). A total of 1,229 veterans had a TBI diagnosis; 196 veterans with TBI (16%) developed dementia, and 18,255 (10%) of those without TBI developed dementia. On average, veterans with TBI developed dementia two years earlier than those without TBI. “If we assume that this relationship is causal, it seems likely that the same increased risk probably occurs with TBI in the civilian population as well,” said the researchers.

Higher levels of depressive symptoms, stress, and hostility are associated with a significantly increased risk of stroke or transient ischemic attack (TIA) in middle-aged and older adults, according to a study published online ahead of print July 10 in Stroke. Researchers used data from the Multi-Ethnic Study of Atherosclerosis (MESA) to determine how psychologic factors might influence the risk for chronic disease. The investigators examined data for 6,749 adults (ages 45 to 84; 53% women) as they completed questionnaires assessing chronic stress, depressive symptoms, anger, and hostility during a two-year period. Hazard ratios indicated a significantly elevated risk of stroke or TIA for the highest scoring group, compared with the lowest scoring group, for depressive symptoms (HR, 1.86), chronic stress (HR, 1.59), and hostility (HR, 2.22). No significant increased risk was associated with anger.

Patients with mild to moderate Parkinson’s disease can improve their symptoms with regular walking, according to a study published online ahead of print July 2 in Neurology. Investigators included 60 individuals who participated in a randomized trial of various exercise regimens for six months. Eighty-one percent of participants completed the study with a mean attendance of 83.3%. Subjects took additional tests to gauge their aerobic fitness, tiredness, and other factors. Brisk walking reduced tiredness by 11%, improved motor function and mood by 15%, improved attention and response control scores by 14%, and increased aerobic fitness and gait speed by 7%. With regard to motor function, participants improved by an average of 2.8 points. “The results of our study suggest that walking may provide a safe and easily accessible way of improving the symptoms of Parkinson’s disease and improve quality of life,” stated the researchers.

Mild traumatic brain injury (TBI) may result in brain damage and memory and thinking problems, according to a study published online ahead of print July 16 in Neurology. Fifty-three patients (44 with mild TBI and nine with moderate TBI) were compared with 33 participants without brain injury. Each subject underwent testing to assess his or her memory and thinking skills. Participants also had diffusion tensor imaging scans. Those with injuries had brain damage in white matter that consisted of disruption to nerve axons. Researchers also determined that scores on the verbal letter fluency task were 25% lower in individuals with injury than in individuals without injury. “We studied patients who had suffered clinically mild injuries, often from common accidents such as falling from a bicycle, or slow-speed car accidents. This finding is especially important, as 90% of all TBIs are mild to moderate,” said the researchers.

Patients with a traumatic brain injury (TBI) who received erythropoietin (EPO) or maintained a higher hemoglobin concentration through blood transfusion did not have an improved neurologic outcome at six months, according to a study published in the July 2 issue of JAMA. The randomized study included 200 patients (erythropoietin, n = 102; placebo, n = 98) with a closed head injury at neurosurgical intensive care units in two US level I trauma centers between May 2006 and August 2012. Patients were enrolled within six hours of injury and had to be unable to follow commands after initial stabilization. Overall, transfusing at higher hemoglobin concentrations was associated with a higher risk of adverse events. Researchers also observed a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (21.8%) versus the threshold of 7 g/dL (8.1%)

Frontline Medical Communications and the National Organization for Rare Disorders (NORD) have signed a partnership agreement to develop educational programs about rare diseases for health care providers. Frontline and NORD also seek to improve awareness, recognition, and understanding of rare diseases among health care providers to accelerate diagnosis and promote optimal care for patients, facilitate the sharing of information among health care providers and rare disease medical experts, and update health care providers on new treatment options and clinical care standards. “Innovative multichannel educational programs, developed by both organizations and funded by commercial sponsors, will be distributed to more than 1.2 million health care providers using Frontline’s portfolio of 30 journal brands, corresponding websites, eNewsletters, and live events,” according to Frontline.

Upsher-Smith Laboratories (Maple Grove, Minnesota) announced that Qudexy XR (topiramate) extended-release capsules are now available in the United States. Qudexy XR, a broad-spectrum, once-daily antiepileptic drug is engineered to deliver a smooth pharmacokinetic profile. The FDA approved Qudexy XR in March 2014 as an initial monotherapy in patients 10 and older with primary generalized tonic-clonic seizures and partial-onset seizures. The drug also was approved as adjunctive therapy in patients 2 and older with primary generalized tonic-clonic seizures, partial-onset seizures, and seizures associated with Lennox-Gastaut syndrome. Overall, results from Upsher-Smith’s phase III trial showed that Qudexy XR is generally well tolerated and effective.

Transplanted brain cells producing dopamine remain viable in patients with Parkinson’s disease for several years, according to a study published June 26 in Cell Reports. The study included five patients with Parkinson’s disease who received transplants of fetal tissue-derived, dopamine-producing neurons four to 14 years earlier. Their transplanted dopamine neurons showed no signs of Parkinson’s disease–associated deterioration and appeared healthy. Researchers believe the findings provide further support for stem cells as a source for transplant-ready dopamine neurons. The investigators noted that the neuronal transplant has proven to be a durable treatment for many patients with Parkinson’s disease, with some improving for years without a need for standard medications. The study authors called the new finding “extremely encouraging,” adding that the long life of the transplanted neurons bodes well “for advancing [the technique] as a restoration therapy for Parkinson’s disease.”

Women may recover more quickly than men after a concussion, according to a study published online ahead of print May 6 in Radiology. Researchers examined the medical records and imaging results of 69 patients diagnosed with mild traumatic brain injury (TBI) between 2006 and 2013. The cohort included 47 men, 22 women, and 21 controls (10 men; median age of men, 17; median age of women, 16). Of the 47 men with TBI, 32 (68%) were injured while playing a sport, as were 10 of the 22 women (45%). Although all participants underwent the same evaluation, diffusion tensor imaging scans revealed that compared with the female patients with mild TBI, the male patients with mild TBI had significantly decreased uncinate fasciculus fractional anisotropy values. The average recovery time for all patients with concussion was 54 days. However, compared with women, who recovered in an average of 26.3 days, recovery was significantly longer for men (66.9 days).

Patients with mesial temporal lobe epilepsy who cannot be controlled with medication can now opt for a minimally invasive laser procedure performed under MRI guidance, according to a study published in the June issue of Neurosurgery. Researchers used an MRI-guided stereotactic laser amygdalohippocampotomy in 13 adult patients with epilepsy (median age, 24). During this procedure, a saline-cooled fiber-optic laser probe was targeted at the amygdalohippocampal complex. Using real-time MRI guidance, a neurosurgeon pinpointed the area of the brain responsible for seizure activity and destroyed this tissue without harming nearby brain tissue. Sixty percent of the amygdalohippocampal complex was destroyed, and the average length of the ablated area was 2.5 cm. “Such minimally invasive techniques may be more desirable to patients and result in increased use of epilepsy surgery among the large number of medically intractable epilepsy patients,” according to the investigators.

Researchers identified 10 proteins in the blood that can predict the onset of Alzheimer’s disease, according to a study published online ahead of print July 3 in Alzheimer’s & Dementia. In the international study of 1,148 individuals (220 with mild cognitive impairment [MCI], 452 elderly controls without dementia, and 476 with Alzheimer’s disease), blood samples were analyzed for 26 proteins previously associated with Alzheimer’s disease. Investigators found 16 of the 26 proteins to be strongly associated with brain shrinkage in Alzheimer’s disease or MCI. The researchers conducted a second series of tests to establish which of these proteins could predict the progression from MCI to Alzheimer’s disease. The study authors identified a combination of 10 proteins capable of predicting whether individuals with MCI would develop Alzheimer’s disease within a year with 87% accuracy. “Memory problems are common, but the challenge is identifying who is likely to develop dementia,” according to the researchers.

An international team of researchers has reviewed the diagnostic criteria for Alzheimer’s disease developed by the International Working Group (IWG) and US National Institute on Aging–Alzheimer’s Association, according to a study published in the June issue of Lancet Neurology. The team considered the strengths and weakness of the IWG criteria and proposed advances to improve the diagnostic framework. The investigators asserted that the diagnosis of Alzheimer’s disease can be simplified by requiring the presence of an appropriate clinical Alzheimer’s disease phenotype (typical or atypical) and a pathophysiologic biomarker consistent with the presence of Alzheimer’s pathology. “We propose that downstream topographic biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease,” the team stated

—Kimberly D. Williams

People with a higher education recover better from a moderate to severe traumatic brain injury (TBI), according to a study published May 6 in Neurology. Researchers found that patients with the equivalent of at least a college education were seven times more likely than those who did not finish high school to be disability-free one year after a TBI. The investigators examined 769 patients, 219 of whom were free of any detectable disability. The study authors theorized that TBI patients with increased cognitive reserve capabilities may heal in a different way that allows them to return to their pre-injury function. These patients also may be able to adapt and form new pathways in their brains to compensate for the injury.

The risk of stroke may be reduced by eating more fruits and vegetables, according to a study published online ahead of print May 8 in Stroke. Researchers conducted a meta-analysis of 20 studies published within the past 19 years to assess the effects of fruit and vegetable consumption on the risk of stroke; the combined studies included 760,629 men and 16,981 women who previously had strokes. The findings suggest that stroke risk decreased by 32% with every 200 grams of fruit consumed daily and 11% with every 200 grams of vegetables consumed daily. The investigators combined the results of six studies from the United States, six from Asia, and eight from Europe. “Improving diet and lifestyle is critical for heart and stroke risk reduction in the general population,” the researchers stated.

One-third of all unruptured intracranial aneurysms in people of working age ruptured during a lifelong follow-up, according to a study published online ahead of print May 22 in Stroke. Researchers monitored 118 patients (median age at diagnosis, 43.5) with aneurysms from 1956 until death or subarachnoid hemorrhage occurred. The risk of rupture was particularly high for female smokers with brain aneurysms 7 mm or more in diameter, and the size of an aneurysm had little impact on its risk for rupture, particularly for men. The risk of rupture among nonsmoking men was also exceptionally low. “Because even small unruptured intracranial aneurysms ruptured, treatment decisions of unruptured intracranial aneurysms should perhaps be based on the risk factor status,” the investigators concluded.

An international group of researchers in multiple sclerosis (MS) has proposed updated clinical course descriptions of the disease, according to a report published online ahead of print May 28 in Neurology. The International Advisory Committee on Clinical Trials of MS, which is jointly supported by the National MS Society and the European Committee for Treatment and Research in MS (ECTRIMS), suggested that clinicians not only determine a person’s course of MS, but also further subcategorize that course as active or not active and progressing or not progressing, based on clinical evidence of changes in disability. Another recommended area for further research by the committee includes long-term studies to track people with MS over time. “These revisions should make communication with patients and among physicians clearer and should also enhance the design, recruitment, and conduct of future clinical trials,” the investigators stated.

A moderate level of dietary protein intake may lower the risk of stroke, according to a meta-analysis that was published online ahead of print June 11 in Neurology. The analysis consisted of seven studies with a total of 254,489 participants who were followed for an average of 14 years. Overall, participants with the highest amount of protein in their diets were 20% less likely to develop a stroke, compared with those who had the lowest amount of protein in their diets. For every extra 20 grams per day of protein eaten, the risk of stroke decreased by 26%. The results accounted for other factors that could affect the risk of stroke, such as high cholesterol and smoking. “These results indicate that stroke risk may be reduced by replacing red meat with other protein sources, such as fish,” stated the researchers.

The FDA will review Genzyme’s resubmission of its supplemental Biologics License Application seeking approval of Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The resubmission is based on data from the same clinical trials included in the original application. It also provides additional information and supplemental analyses to address issues previously outlined by the FDA in its December 27, 2013, Complete Response Letter. A six-month review period has been assigned, and Genzyme (Cambridge, Massachusetts) expects the FDA to begin that review in the fourth quarter.

The risk of developing cognitive impairment is significantly higher for individuals with poor cardiovascular health than for those with intermediate or ideal cardiovascular health, investigators reported June 11 in the Journal of the American Heart Association. The study included 17,761 people ages 45 and older who had normal cognitive function and no history of stroke (mental function was evaluated four years later). The researchers used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study to determine cardiovascular health status based on the American Heart Association Life’s Simple 7 score. Study findings showed that people with the lowest cardiovascular health scores were more likely to have impairment on learning, memory, and verbal fluency tests than were their counterparts with intermediate or better risk profiles.

Researchers have developed an MRI technique that aids in the early diagnosis of Parkinson’s disease with 85% accuracy, according to a study published online ahead of print June 11 in Neurology. The investigators compared 19 people with early-stage Parkinson’s disease while not on medication with 19 healthy people, matched for gender and age. Data suggest that patients with Parkinson’s disease had much lower connectivity in the basal ganglia. The researchers defined a threshold level of connectivity within the basal ganglia network. Connectivity below this level helped to predict who had Parkinson’s disease with 100% sensitivity and 89.5% specificity. The study authors also conducted their MRI test in a second group of 13 early-stage Parkinson’s patients as a validation of the approach; they correctly identified 11 of the 13 patients.

Blood pressure in later life may affect brain pathology and cognitive performance, depending on blood pressure at midlife, according to a study that was published online ahead of print June 4 in Neurology. Researchers examined data regarding 4,057 older participants (average age, 76) without dementia whose blood pressure had been measured during middle age. The patients’ blood pressure was measured again, and participants underwent MRI and tests of memory and cognition. Higher blood pressure in late life was associated with an increased risk of brain lesions, especially among patients without high blood pressure in middle age. Among participants with high blood pressure in middle age, lower diastolic blood pressure in late life was associated with smaller brain volumes and decreased memory and cognitive performance.

A copper compound could provide a therapy for patients with amyotrophic lateral sclerosis (ALS), according to a study that was published June 4 in the Journal of Neuroscience. Mutations in copper–zinc-superoxide dismutase (SOD1) are believed to cause ALS in humans and transgenic mice. Investigators found that most SOD1 in the spinal cord of mouse models of ALS was copper deficient. Treatment with copper (ATSM) decreased the pool of copper-deficient SOD1 and increased the pool of fully metallated SOD1 in the mice’s spinal cords. In addition, the compound significantly extended the mice’s survival and improved their locomotor function. When the researchers tracked isotopically enriched copper, they found that the increase in fully metallated SOD1 depended on the transfer of copper from copper (ATSM) to SOD1, suggesting that increased copper content of mutant SOD1 improved survival and locomotor function.

Quantitative susceptibility (QS) MRI may reflect disease progression accurately in patients with multiple sclerosis (MS), according to a study published online ahead of print May 4 in Radiology. Twenty-five patients with relapsing-remitting MS or clinically isolated syndrome and 15 age- and sex-matched controls underwent 7-T MRI. Researchers computed quantitative maps of MRI susceptibility parameters. The QS maps identified voxel-level increases in iron deposition in the subcortical gray matter of patients with MS, compared with controls. QS was strongly correlated with patients’ Expanded Disability Status Scale (EDSS) scores. The volume of total white matter damage on QS maps correlated significantly with EDSS. Voxelwise QS indicated that age contributed to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide robust measures of disease severity.

—Kimberly Williams

People with a higher education recover better from a moderate to severe traumatic brain injury (TBI), according to a study published May 6 in Neurology. Researchers found that patients with the equivalent of at least a college education were seven times more likely than those who did not finish high school to be disability-free one year after a TBI. The investigators examined 769 patients, 219 of whom were free of any detectable disability. The study authors theorized that TBI patients with increased cognitive reserve capabilities may heal in a different way that allows them to return to their pre-injury function. These patients also may be able to adapt and form new pathways in their brains to compensate for the injury.

The risk of stroke may be reduced by eating more fruits and vegetables, according to a study published online ahead of print May 8 in Stroke. Researchers conducted a meta-analysis of 20 studies published within the past 19 years to assess the effects of fruit and vegetable consumption on the risk of stroke; the combined studies included 760,629 men and 16,981 women who previously had strokes. The findings suggest that stroke risk decreased by 32% with every 200 grams of fruit consumed daily and 11% with every 200 grams of vegetables consumed daily. The investigators combined the results of six studies from the United States, six from Asia, and eight from Europe. “Improving diet and lifestyle is critical for heart and stroke risk reduction in the general population,” the researchers stated.

One-third of all unruptured intracranial aneurysms in people of working age ruptured during a lifelong follow-up, according to a study published online ahead of print May 22 in Stroke. Researchers monitored 118 patients (median age at diagnosis, 43.5) with aneurysms from 1956 until death or subarachnoid hemorrhage occurred. The risk of rupture was particularly high for female smokers with brain aneurysms 7 mm or more in diameter, and the size of an aneurysm had little impact on its risk for rupture, particularly for men. The risk of rupture among nonsmoking men was also exceptionally low. “Because even small unruptured intracranial aneurysms ruptured, treatment decisions of unruptured intracranial aneurysms should perhaps be based on the risk factor status,” the investigators concluded.

An international group of researchers in multiple sclerosis (MS) has proposed updated clinical course descriptions of the disease, according to a report published online ahead of print May 28 in Neurology. The International Advisory Committee on Clinical Trials of MS, which is jointly supported by the National MS Society and the European Committee for Treatment and Research in MS (ECTRIMS), suggested that clinicians not only determine a person’s course of MS, but also further subcategorize that course as active or not active and progressing or not progressing, based on clinical evidence of changes in disability. Another recommended area for further research by the committee includes long-term studies to track people with MS over time. “These revisions should make communication with patients and among physicians clearer and should also enhance the design, recruitment, and conduct of future clinical trials,” the investigators stated.

A moderate level of dietary protein intake may lower the risk of stroke, according to a meta-analysis that was published online ahead of print June 11 in Neurology. The analysis consisted of seven studies with a total of 254,489 participants who were followed for an average of 14 years. Overall, participants with the highest amount of protein in their diets were 20% less likely to develop a stroke, compared with those who had the lowest amount of protein in their diets. For every extra 20 grams per day of protein eaten, the risk of stroke decreased by 26%. The results accounted for other factors that could affect the risk of stroke, such as high cholesterol and smoking. “These results indicate that stroke risk may be reduced by replacing red meat with other protein sources, such as fish,” stated the researchers.

The FDA will review Genzyme’s resubmission of its supplemental Biologics License Application seeking approval of Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The resubmission is based on data from the same clinical trials included in the original application. It also provides additional information and supplemental analyses to address issues previously outlined by the FDA in its December 27, 2013, Complete Response Letter. A six-month review period has been assigned, and Genzyme (Cambridge, Massachusetts) expects the FDA to begin that review in the fourth quarter.

The risk of developing cognitive impairment is significantly higher for individuals with poor cardiovascular health than for those with intermediate or ideal cardiovascular health, investigators reported June 11 in the Journal of the American Heart Association. The study included 17,761 people ages 45 and older who had normal cognitive function and no history of stroke (mental function was evaluated four years later). The researchers used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study to determine cardiovascular health status based on the American Heart Association Life’s Simple 7 score. Study findings showed that people with the lowest cardiovascular health scores were more likely to have impairment on learning, memory, and verbal fluency tests than were their counterparts with intermediate or better risk profiles.

Researchers have developed an MRI technique that aids in the early diagnosis of Parkinson’s disease with 85% accuracy, according to a study published online ahead of print June 11 in Neurology. The investigators compared 19 people with early-stage Parkinson’s disease while not on medication with 19 healthy people, matched for gender and age. Data suggest that patients with Parkinson’s disease had much lower connectivity in the basal ganglia. The researchers defined a threshold level of connectivity within the basal ganglia network. Connectivity below this level helped to predict who had Parkinson’s disease with 100% sensitivity and 89.5% specificity. The study authors also conducted their MRI test in a second group of 13 early-stage Parkinson’s patients as a validation of the approach; they correctly identified 11 of the 13 patients.

Blood pressure in later life may affect brain pathology and cognitive performance, depending on blood pressure at midlife, according to a study that was published online ahead of print June 4 in Neurology. Researchers examined data regarding 4,057 older participants (average age, 76) without dementia whose blood pressure had been measured during middle age. The patients’ blood pressure was measured again, and participants underwent MRI and tests of memory and cognition. Higher blood pressure in late life was associated with an increased risk of brain lesions, especially among patients without high blood pressure in middle age. Among participants with high blood pressure in middle age, lower diastolic blood pressure in late life was associated with smaller brain volumes and decreased memory and cognitive performance.

A copper compound could provide a therapy for patients with amyotrophic lateral sclerosis (ALS), according to a study that was published June 4 in the Journal of Neuroscience. Mutations in copper–zinc-superoxide dismutase (SOD1) are believed to cause ALS in humans and transgenic mice. Investigators found that most SOD1 in the spinal cord of mouse models of ALS was copper deficient. Treatment with copper (ATSM) decreased the pool of copper-deficient SOD1 and increased the pool of fully metallated SOD1 in the mice’s spinal cords. In addition, the compound significantly extended the mice’s survival and improved their locomotor function. When the researchers tracked isotopically enriched copper, they found that the increase in fully metallated SOD1 depended on the transfer of copper from copper (ATSM) to SOD1, suggesting that increased copper content of mutant SOD1 improved survival and locomotor function.

Quantitative susceptibility (QS) MRI may reflect disease progression accurately in patients with multiple sclerosis (MS), according to a study published online ahead of print May 4 in Radiology. Twenty-five patients with relapsing-remitting MS or clinically isolated syndrome and 15 age- and sex-matched controls underwent 7-T MRI. Researchers computed quantitative maps of MRI susceptibility parameters. The QS maps identified voxel-level increases in iron deposition in the subcortical gray matter of patients with MS, compared with controls. QS was strongly correlated with patients’ Expanded Disability Status Scale (EDSS) scores. The volume of total white matter damage on QS maps correlated significantly with EDSS. Voxelwise QS indicated that age contributed to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide robust measures of disease severity.

—Kimberly Williams

People with a higher education recover better from a moderate to severe traumatic brain injury (TBI), according to a study published May 6 in Neurology. Researchers found that patients with the equivalent of at least a college education were seven times more likely than those who did not finish high school to be disability-free one year after a TBI. The investigators examined 769 patients, 219 of whom were free of any detectable disability. The study authors theorized that TBI patients with increased cognitive reserve capabilities may heal in a different way that allows them to return to their pre-injury function. These patients also may be able to adapt and form new pathways in their brains to compensate for the injury.

The risk of stroke may be reduced by eating more fruits and vegetables, according to a study published online ahead of print May 8 in Stroke. Researchers conducted a meta-analysis of 20 studies published within the past 19 years to assess the effects of fruit and vegetable consumption on the risk of stroke; the combined studies included 760,629 men and 16,981 women who previously had strokes. The findings suggest that stroke risk decreased by 32% with every 200 grams of fruit consumed daily and 11% with every 200 grams of vegetables consumed daily. The investigators combined the results of six studies from the United States, six from Asia, and eight from Europe. “Improving diet and lifestyle is critical for heart and stroke risk reduction in the general population,” the researchers stated.

One-third of all unruptured intracranial aneurysms in people of working age ruptured during a lifelong follow-up, according to a study published online ahead of print May 22 in Stroke. Researchers monitored 118 patients (median age at diagnosis, 43.5) with aneurysms from 1956 until death or subarachnoid hemorrhage occurred. The risk of rupture was particularly high for female smokers with brain aneurysms 7 mm or more in diameter, and the size of an aneurysm had little impact on its risk for rupture, particularly for men. The risk of rupture among nonsmoking men was also exceptionally low. “Because even small unruptured intracranial aneurysms ruptured, treatment decisions of unruptured intracranial aneurysms should perhaps be based on the risk factor status,” the investigators concluded.

An international group of researchers in multiple sclerosis (MS) has proposed updated clinical course descriptions of the disease, according to a report published online ahead of print May 28 in Neurology. The International Advisory Committee on Clinical Trials of MS, which is jointly supported by the National MS Society and the European Committee for Treatment and Research in MS (ECTRIMS), suggested that clinicians not only determine a person’s course of MS, but also further subcategorize that course as active or not active and progressing or not progressing, based on clinical evidence of changes in disability. Another recommended area for further research by the committee includes long-term studies to track people with MS over time. “These revisions should make communication with patients and among physicians clearer and should also enhance the design, recruitment, and conduct of future clinical trials,” the investigators stated.

A moderate level of dietary protein intake may lower the risk of stroke, according to a meta-analysis that was published online ahead of print June 11 in Neurology. The analysis consisted of seven studies with a total of 254,489 participants who were followed for an average of 14 years. Overall, participants with the highest amount of protein in their diets were 20% less likely to develop a stroke, compared with those who had the lowest amount of protein in their diets. For every extra 20 grams per day of protein eaten, the risk of stroke decreased by 26%. The results accounted for other factors that could affect the risk of stroke, such as high cholesterol and smoking. “These results indicate that stroke risk may be reduced by replacing red meat with other protein sources, such as fish,” stated the researchers.

The FDA will review Genzyme’s resubmission of its supplemental Biologics License Application seeking approval of Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The resubmission is based on data from the same clinical trials included in the original application. It also provides additional information and supplemental analyses to address issues previously outlined by the FDA in its December 27, 2013, Complete Response Letter. A six-month review period has been assigned, and Genzyme (Cambridge, Massachusetts) expects the FDA to begin that review in the fourth quarter.

The risk of developing cognitive impairment is significantly higher for individuals with poor cardiovascular health than for those with intermediate or ideal cardiovascular health, investigators reported June 11 in the Journal of the American Heart Association. The study included 17,761 people ages 45 and older who had normal cognitive function and no history of stroke (mental function was evaluated four years later). The researchers used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study to determine cardiovascular health status based on the American Heart Association Life’s Simple 7 score. Study findings showed that people with the lowest cardiovascular health scores were more likely to have impairment on learning, memory, and verbal fluency tests than were their counterparts with intermediate or better risk profiles.

Researchers have developed an MRI technique that aids in the early diagnosis of Parkinson’s disease with 85% accuracy, according to a study published online ahead of print June 11 in Neurology. The investigators compared 19 people with early-stage Parkinson’s disease while not on medication with 19 healthy people, matched for gender and age. Data suggest that patients with Parkinson’s disease had much lower connectivity in the basal ganglia. The researchers defined a threshold level of connectivity within the basal ganglia network. Connectivity below this level helped to predict who had Parkinson’s disease with 100% sensitivity and 89.5% specificity. The study authors also conducted their MRI test in a second group of 13 early-stage Parkinson’s patients as a validation of the approach; they correctly identified 11 of the 13 patients.

Blood pressure in later life may affect brain pathology and cognitive performance, depending on blood pressure at midlife, according to a study that was published online ahead of print June 4 in Neurology. Researchers examined data regarding 4,057 older participants (average age, 76) without dementia whose blood pressure had been measured during middle age. The patients’ blood pressure was measured again, and participants underwent MRI and tests of memory and cognition. Higher blood pressure in late life was associated with an increased risk of brain lesions, especially among patients without high blood pressure in middle age. Among participants with high blood pressure in middle age, lower diastolic blood pressure in late life was associated with smaller brain volumes and decreased memory and cognitive performance.

A copper compound could provide a therapy for patients with amyotrophic lateral sclerosis (ALS), according to a study that was published June 4 in the Journal of Neuroscience. Mutations in copper–zinc-superoxide dismutase (SOD1) are believed to cause ALS in humans and transgenic mice. Investigators found that most SOD1 in the spinal cord of mouse models of ALS was copper deficient. Treatment with copper (ATSM) decreased the pool of copper-deficient SOD1 and increased the pool of fully metallated SOD1 in the mice’s spinal cords. In addition, the compound significantly extended the mice’s survival and improved their locomotor function. When the researchers tracked isotopically enriched copper, they found that the increase in fully metallated SOD1 depended on the transfer of copper from copper (ATSM) to SOD1, suggesting that increased copper content of mutant SOD1 improved survival and locomotor function.

Quantitative susceptibility (QS) MRI may reflect disease progression accurately in patients with multiple sclerosis (MS), according to a study published online ahead of print May 4 in Radiology. Twenty-five patients with relapsing-remitting MS or clinically isolated syndrome and 15 age- and sex-matched controls underwent 7-T MRI. Researchers computed quantitative maps of MRI susceptibility parameters. The QS maps identified voxel-level increases in iron deposition in the subcortical gray matter of patients with MS, compared with controls. QS was strongly correlated with patients’ Expanded Disability Status Scale (EDSS) scores. The volume of total white matter damage on QS maps correlated significantly with EDSS. Voxelwise QS indicated that age contributed to demyelination in patients with MS, suggesting that age-adjusted clinical scores may provide robust measures of disease severity.

—Kimberly Williams

Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.

People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.

Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.

The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.

The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.

The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.

Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.

The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]

Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.

A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.

Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.

Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.

Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.

—Erik Greb

Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.

People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.

Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.

The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.

The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.

The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.

Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.

The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]

Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.

A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.

Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.

Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.

Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.

—Erik Greb

Older patients with migraine may be more likely to have silent brain injury than older patients without migraine, according to research published online ahead of print May 15 in Stroke. Researchers analyzed data from the Northern Manhattan Study, which quantified subclinical brain infarctions and white matter hyperintensity volumes among participants with migraine. Of the 546 participants analyzed, 41% were men, 65% were Hispanic, and mean age at MRI was 71. Patients with migraine had double the odds of subclinical brain infarction, compared with those reporting no migraine, after the investigators adjusted for sociodemographics and vascular risk factors. No association was observed between migraine with or without aura and white matter hyperintensity volume. Patients with migraine should not worry, because their risk of ischemic stroke is small, said the authors.

People who are exposed to paint, glue, or degreaser fumes at work may experience memory and thinking problems in retirement, according to a study published May 13 in Neurology. Researchers examined data for 2,143 retired utility workers who underwent cognitive testing in 2010. The authors assessed workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene using a job exposure matrix. Approximately 33% of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. Workers highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination, the Digit Symbol Substitution Test, semantic fluency test, and the Trail Making Test B. Retirees at greatest risk for deficits had high lifetime exposure to solvents and were last exposed 12 to 30 years before testing.

Females susceptible to multiple sclerosis (MS) produce higher levels of the blood vessel receptor protein S1PR2 than males, according to data published online ahead of print May 8 in the Journal of Clinical Investigation. S1PR2 is present at high levels in the brain areas that MS typically damages. Investigators studied a mouse model of MS and found increased activity of S1PR2, which opens up the blood–brain barrier. When the researchers tested brain tissue samples obtained from 20 human patients after death, they found more S1PR2 in patients with MS than in those without the disorder. Brain tissue from females also had higher levels of S1PR2, compared with male brain tissue. These findings may help explain why more women than men get the disease, said the authors.

The FDA has required the manufacturer of the sleep drug Lunesta (eszopiclone) to lower the recommended starting dose from 2 mg to 1 mg for men and women. Data show that eszopiclone levels in some patients may be high enough on the morning after treatment to impair activities that require alertness, including driving. The 1-mg dose, taken at bedtime, can be increased to 2 mg or 3 mg if needed, but the higher doses are more likely to result in next-day impairment. Using lower doses ensures that less drug will remain in the body during the morning hours. Patients currently taking the 2-mg and 3-mg doses of Lunesta should contact their health care professional to ask for instructions, according to the FDA.

The rate of visits to an emergency department (ED) for traumatic brain injury (TBI) increased by approximately 30% between 2006 and 2010, according to research published in the May 14 issue of JAMA. The increase may be attributable to various factors, including increased awareness and diagnoses, said the authors. The investigators examined data from the Nationwide Emergency Department Sample database to determine national trends in ED visits for TBI from 2006 through 2010. An estimated 2.5 million ED visits for TBI occurred in 2010, representing a 29% increase in the rate of visits for TBI during the study period. By comparison, total ED visits increased by 3.6%. Children younger than 3 and adults older than 60 had the largest increase in TBI rates.

The pathophysiologic biomarkers and the topographic markers of Alzheimer’s disease should be revised, according to a position paper by the International Working Group published in the June issue of Lancet Neurology. The group proposed that biomarkers of Alzheimer’s pathology be restricted to those indicating the presence of tau pathology (ie, CSF or PET tau) and amyloid pathology (ie, CSF or PET amyloid). These biomarkers are specific enough to diagnose Alzheimer’s disease at any point on the disease continuum, said the authors. Downstream topographic markers of brain regional structural and metabolic changes have insufficient pathologic specificity and should not be used in diagnosis, according to the researchers. Instead, these markers can be used to measure disease progression. The group also provided diagnostic criteria for atypical, mixed, and preclinical Alzheimer’s disease.

Prenatal supplementation with docosahexaenoic acid (DHA) does not result in improved cognitive, problem-solving, or language abilities for children at age 4, according to the results of a trial published in the May 7 issue of JAMA. Investigators conducted longer-term follow-up from a previous study in which pregnant women received 800 mg/day of DHA or placebo. In the initial study, the researchers found that average cognitive, language, and motor scores did not differ between children at 18 months of age. Approximately 92% of eligible families participated in the follow-up study. The DHA group included 313 participants, and the control group included 333 participants. The investigators found that measures of cognition, the ability to perform complex mental processing, language, and executive functioning (eg, memory, reasoning, and problem solving) did not differ significantly between groups at age 4.

The FDA has informed Acorda Therapeutics that it has completed its review of the company’s new drug application for Plumiaz (diazepam) nasal spray and that the application cannot be approved in its present form. The drug was developed for the treatment of people with epilepsy who experience cluster seizures. Acorda Therapeutics is developing a response to address the items outlined in the letter. Based on the requirements for approval outlined in the letter, the company does not expect Plumiaz to receive FDA approval in 2014. Plumiaz previously received orphan drug designation for the treatment of cluster seizures. [For related news, see page 9.]

Older people with memory and thinking problems who do not have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published April 22 in Neurology. Researchers studied 2,627 people age 65 and older who did not have dementia at baseline. Participants underwent tests of memory and thinking skills at baseline and at three years. Follow-up lasted for an average of approximately 13 years. During the study, 1,003 participants died. About 34% of deaths occurred among patients with the fastest decline in thinking skills. Approximately 21% of participants in the group with the fastest decline in thinking skills died of cancer, compared with 29% of participants in the other two groups.

A new technique may predict with 95% accuracy which patients with stroke will benefit from IV t-PA and which will have potentially lethal bleeding in the brain, according to a study published online ahead of print May 15 in Stroke. Researchers used a computer program that shows physicians the amount of gadolinium, injected during an MRI scan, that has leaked into the brain tissue from surrounding blood vessels. By quantifying this damage in 75 patients with stroke, the researchers identified a threshold for determining how much leakage was dangerous. They applied this threshold to the records for the 75 patients to determine how well it would predict who had had a brain hemorrhage and who had not. The new test correctly predicted the outcome with 95% accuracy.

Freezing of gait in patients with Parkinson’s disease may correlate with poor quality of life, disease severity, apathy, and exposure to antimuscarinics, according to a study published online ahead of print May 19 in JAMA Neurology. Investigators performed a cross-sectional survey of 672 patients with idiopathic Parkinson’s disease. Patients with freezing of gait were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson’s Disease Rating Scale (UPDRS) in the on condition. Approximately 38% of patients reported freezing of gait during the on state, which was significantly related to lower quality of life scores. Freezing of gait was also correlated with longer disease duration, higher UPDRS parts II and III scores, apathy, and a higher levodopa equivalent daily dose.

Among college football players, concussion and years of football played may have a significant inverse relationship with hippocampal volume, according to research published May 14 in JAMA. Years of football experience also may correlate with slower reaction time. Investigators conducted a cross-sectional study of 25 college football players with a history of clinician-diagnosed concussion, 25 college football players without a history of concussion, and 25 nonfootball-playing, age-, sex-, and education-matched healthy controls. Players with and without a history of concussion had smaller hippocampal volumes, compared with healthy controls. Players with a history of concussion had smaller hippocampal volumes than players without concussion. In both athlete groups, investigators found a statistically significant inverse relationship between left hippocampal volume and number of years of football played.

Deficiencies in hyaluronan can lead to spontaneous epileptic seizures, according to research published April 30 in the Journal of Neuroscience. In a multicenter study, investigators examined the role of hyaluronan using mutant mice deficient in each of the three hyaluronan synthase genes (ie, Has1, Has2, Has3). The mutant mice were prone to epileptic seizures. In Has3(-/-) mice, this phenotype likely results from a reduction in the size of the brain extracellular space (ECS), said the researchers. Among the three Has knockout models, seizures were most prevalent in Has3(-/-) mice, which also had the greatest hyaluronan reduction in the hippocampus. The results provide the first direct evidence for the physiologic role of hyaluronan in the regulation of ECS volume, according to the investigators.

—Erik Greb

PET is a promising tool for determining which severely brain damaged individuals in vegetative states have the potential to recover consciousness, according to research published online ahead of print April 16 in Lancet. Investigators examined 81 patients in a minimally conscious state, 41 patients with unresponsive wakefulness syndrome, and four patients with locked-in syndrome. The researchers performed repeated standardized clinical assessments with the Coma Recovery Scale–Revised (CRS-R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI while the patients performed mental activation tasks. Mental imagery fMRI was less sensitive at diagnosing a minimally conscious state than FDG-PET (45% vs 93%) and had less agreement with behavioral CRS-R scores than FDG-PET (63% vs 85%). 18F-FDG PET correctly predicted outcome in 75 of 102 patients, and fMRI in 36 of 65 patients.

The risk of epilepsy may be heightened significantly among patients with autoimmune diseases, especially children, according to data published online ahead of print March 31 in JAMA Neurology. Researchers conducted a retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. All 2,518,034 participants included in the study were beneficiaries enrolled between 1999 and 2006. The investigators examined the relationship between epilepsy and type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease. The odds ratio of epilepsy was 3.8 among patients with autoimmune diseases and 5.2 among children. Based on their findings, the authors recommended that patients with epilepsy undergo surveillance for autoimmune disease, and vice versa.

Migraineurs whose stress decreases from one day to the next have a significantly increased risk of migraine onset on the subsequent day, according to a study published online ahead of print March 26 in Neurology. Twenty-two patients with migraine participated in a three-month electronic diary study. Participants entered data daily regarding migraine attack experience, as well as subjective stress ratings. Stress was assessed using the Perceived Stress Scale and the Self-Reported Stress Scale. Level of stress was generally not associated with migraine occurrence. Decline in stress from one evening diary to the next was associated with increased migraine onset during the subsequent six, 12, and 18 hours for the Perceived Stress Scale. Decline in stress was associated with migraine onset after controlling for level of stress for all time points.

Patients older than 60 with stroke resulting from blockage of the middle cerebral artery (MCA) benefit from hemicraniectomy, researchers reported March 20 in the New England Journal of Medicine. Investigators randomly assigned 112 patients age 61 or older with malignant MCA infarction to conservative treatment in the ICU or hemicraniectomy. The primary end point was survival without severe disability (defined as a score of 0 to 4 on the modified Rankin scale). The proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, compared with 18% in the control group. This difference resulted from lower mortality in the surgery group (33% vs 70%). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group.

The FDA has approved Topamax (topiramate) for the prevention of migraine headaches in adolescents ages 12 to 17. Topamax is the first drug with FDA approval for migraine prevention in this age group. The medication is taken daily to reduce the frequency of migraine headaches. A clinical trial that enrolled 103 participants established the safety and effectiveness of Topamax in preventing migraine headaches in adolescents ages 12 to 17. Participants treated with Topamax had a decrease in migraine frequency of approximately 72%, compared with 44% in participants who took placebo. The most common adverse reactions with the approved dose of Topamax (100 mg) were paresthesia, upper respiratory infection, anorexia, and abdominal pain. Topamax is manufactured by Janssen Pharmaceuticals of Titusville, New Jersey.

The FDA has approved Evzio (naloxone hydrochloride injection), a prescription treatment that family members or caregivers can use to treat a person suspected to have had an opioid overdose. Evzio rapidly delivers a single dose of naloxone through a handheld autoinjector that can be carried in a pocket or stored in a medicine cabinet. Evzio provides intramuscular or subcutaneous administration. Once turned on, the device provides verbal instruction about how to deliver the medication. In one pharmacokinetic study of 30 patients, a single Evzio injection provided equivalent naloxone, compared with a single dose of naloxone injection using a standard syringe. Administering Evzio to patients who are opioid dependent may result in severe opioid withdrawal. Evzio is manufactured by kaléo, which is based in Richmond, Virginia.

The International League Against Epilepsy has altered its practical definition of epilepsy per the recommendation of a task force, according to an article published online ahead of print April 14 in Epilepsia. Recognizing the limitations of the practical definition of epilepsy as two unprovoked seizures more than 24 hours apart, the task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring more than 24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (ie, at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome.

Older people who have apathy but not depression may have smaller brain volumes than those without apathy, according to data published online ahead of print April 16 in Neurology. Investigators performed cross-sectional analyses of data from 4,354 persons without dementia (average age, 76) participating in a population-based study. Apathy symptoms were assessed with the Geriatric Depression Scale. Brain volumes and total white matter lesion (WML) volume were estimated on 1.5-T MRI using an automated segmentation program. Regional WML load was calculated using a semiquantitative scale. Compared with individuals with fewer than two apathy symptoms, participants with two or more apathy symptoms had significantly smaller gray matter volumes, smaller white matter volumes, and smaller thalamus volumes. The latter individuals also were more likely to have WMLs in the frontal lobe.

The APOE4 gene variant confers a substantially greater risk for Alzheimer’s disease to women than it does to men, researchers reported online ahead of print April 14 in Annals of Neurology. The group performed Cox proportional hazards analysis to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in 5,496 healthy individuals and 2,588 patients with mild cognitive impairment (MCI). The investigators also tested the interaction in CSF biomarker levels of 980 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI or Alzheimer’s disease, but the effect was stronger in women (HR, 1.81 for women; HR, 1.27 for men). The interaction remained significant in a predefined subanalysis that was restricted to APOE3/3 and APOE3/4 genotypes.

The size and shape of the nucleus accumbens and the amygdala may differ in young adults who smoke marijuana at least once a week, according to a study published April 16 in the Journal of Neuroscience. Investigators collected high-resolution MRI scans on young adults who used recreational marijuana and on controls. The researchers conducted three independent analyses of morphometry in gray matter density, volume (total brain and regional volumes), and surface morphometry. The study authors found greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to the subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only.

Neuronal death in Parkinson’s disease may occur when the immune system mistakes neurons for foreign invaders and kills them, according to a study published April 16 in Nature Communications. An examination of postmortem brain tissue revealed major histocompatibility complex class I (MHC-1) proteins in catecholaminergic substantia nigra and locus coeruleus neurons. When researchers conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells, they found that under certain circumstances, including conditions that occur in Parkinson’s disease, the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson’s disease were far more responsive than other neurons to signals that triggered antigen display. The researchers also confirmed that T cells recognized and attacked neurons displaying specific antigens.

People who have had a stroke who consistently control their blood pressure may reduce the likelihood of a second stroke by more than half, according to research published online ahead of print March 27 in Stroke. In a post hoc analysis, 3,680 individuals with recent stroke who were followed up for two years were grouped according to the proportion of visits during which their blood pressure was controlled (ie, <140/90 mm Hg). Consistency of blood pressure control affected outcomes in individuals with baseline systolic blood pressure greater than 132 mm Hg. Among individuals with baseline systolic blood pressure higher than 153 mm Hg, risks of stroke, myocardial infarction, or vascular death were lower in those with blood pressure controlled during 75% or more visits, versus less than 25% of visits.

Individuals between ages 18 and 24 who occasionally use stimulant drugs may have impaired neuronal activity in the parts of the brain associated with anticipatory functioning, according to research published March 26 in the Journal of Neuroscience. Investigators recruited 158 nondependent occasional stimulant users and 47 stimulant-naive controls. Participants completed a stop signal task while undergoing functional MRI. Compared with controls, occasional stimulant users showed attenuated neural activation related to the magnitude of probabilistic expectations of inhibitory demand in several areas, including the left prefrontal cortex and left caudate. The results indicate that clinicians may be able to use brain activity patterns as a means of identifying at-risk youth long before they have any obvious outward signs of addictive behaviors, according to the investigators.

—Erik Greb

PET is a promising tool for determining which severely brain damaged individuals in vegetative states have the potential to recover consciousness, according to research published online ahead of print April 16 in Lancet. Investigators examined 81 patients in a minimally conscious state, 41 patients with unresponsive wakefulness syndrome, and four patients with locked-in syndrome. The researchers performed repeated standardized clinical assessments with the Coma Recovery Scale–Revised (CRS-R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI while the patients performed mental activation tasks. Mental imagery fMRI was less sensitive at diagnosing a minimally conscious state than FDG-PET (45% vs 93%) and had less agreement with behavioral CRS-R scores than FDG-PET (63% vs 85%). 18F-FDG PET correctly predicted outcome in 75 of 102 patients, and fMRI in 36 of 65 patients.

The risk of epilepsy may be heightened significantly among patients with autoimmune diseases, especially children, according to data published online ahead of print March 31 in JAMA Neurology. Researchers conducted a retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. All 2,518,034 participants included in the study were beneficiaries enrolled between 1999 and 2006. The investigators examined the relationship between epilepsy and type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease. The odds ratio of epilepsy was 3.8 among patients with autoimmune diseases and 5.2 among children. Based on their findings, the authors recommended that patients with epilepsy undergo surveillance for autoimmune disease, and vice versa.

Migraineurs whose stress decreases from one day to the next have a significantly increased risk of migraine onset on the subsequent day, according to a study published online ahead of print March 26 in Neurology. Twenty-two patients with migraine participated in a three-month electronic diary study. Participants entered data daily regarding migraine attack experience, as well as subjective stress ratings. Stress was assessed using the Perceived Stress Scale and the Self-Reported Stress Scale. Level of stress was generally not associated with migraine occurrence. Decline in stress from one evening diary to the next was associated with increased migraine onset during the subsequent six, 12, and 18 hours for the Perceived Stress Scale. Decline in stress was associated with migraine onset after controlling for level of stress for all time points.

Patients older than 60 with stroke resulting from blockage of the middle cerebral artery (MCA) benefit from hemicraniectomy, researchers reported March 20 in the New England Journal of Medicine. Investigators randomly assigned 112 patients age 61 or older with malignant MCA infarction to conservative treatment in the ICU or hemicraniectomy. The primary end point was survival without severe disability (defined as a score of 0 to 4 on the modified Rankin scale). The proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, compared with 18% in the control group. This difference resulted from lower mortality in the surgery group (33% vs 70%). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group.

The FDA has approved Topamax (topiramate) for the prevention of migraine headaches in adolescents ages 12 to 17. Topamax is the first drug with FDA approval for migraine prevention in this age group. The medication is taken daily to reduce the frequency of migraine headaches. A clinical trial that enrolled 103 participants established the safety and effectiveness of Topamax in preventing migraine headaches in adolescents ages 12 to 17. Participants treated with Topamax had a decrease in migraine frequency of approximately 72%, compared with 44% in participants who took placebo. The most common adverse reactions with the approved dose of Topamax (100 mg) were paresthesia, upper respiratory infection, anorexia, and abdominal pain. Topamax is manufactured by Janssen Pharmaceuticals of Titusville, New Jersey.

The FDA has approved Evzio (naloxone hydrochloride injection), a prescription treatment that family members or caregivers can use to treat a person suspected to have had an opioid overdose. Evzio rapidly delivers a single dose of naloxone through a handheld autoinjector that can be carried in a pocket or stored in a medicine cabinet. Evzio provides intramuscular or subcutaneous administration. Once turned on, the device provides verbal instruction about how to deliver the medication. In one pharmacokinetic study of 30 patients, a single Evzio injection provided equivalent naloxone, compared with a single dose of naloxone injection using a standard syringe. Administering Evzio to patients who are opioid dependent may result in severe opioid withdrawal. Evzio is manufactured by kaléo, which is based in Richmond, Virginia.

The International League Against Epilepsy has altered its practical definition of epilepsy per the recommendation of a task force, according to an article published online ahead of print April 14 in Epilepsia. Recognizing the limitations of the practical definition of epilepsy as two unprovoked seizures more than 24 hours apart, the task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring more than 24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (ie, at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome.

Older people who have apathy but not depression may have smaller brain volumes than those without apathy, according to data published online ahead of print April 16 in Neurology. Investigators performed cross-sectional analyses of data from 4,354 persons without dementia (average age, 76) participating in a population-based study. Apathy symptoms were assessed with the Geriatric Depression Scale. Brain volumes and total white matter lesion (WML) volume were estimated on 1.5-T MRI using an automated segmentation program. Regional WML load was calculated using a semiquantitative scale. Compared with individuals with fewer than two apathy symptoms, participants with two or more apathy symptoms had significantly smaller gray matter volumes, smaller white matter volumes, and smaller thalamus volumes. The latter individuals also were more likely to have WMLs in the frontal lobe.

The APOE4 gene variant confers a substantially greater risk for Alzheimer’s disease to women than it does to men, researchers reported online ahead of print April 14 in Annals of Neurology. The group performed Cox proportional hazards analysis to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in 5,496 healthy individuals and 2,588 patients with mild cognitive impairment (MCI). The investigators also tested the interaction in CSF biomarker levels of 980 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI or Alzheimer’s disease, but the effect was stronger in women (HR, 1.81 for women; HR, 1.27 for men). The interaction remained significant in a predefined subanalysis that was restricted to APOE3/3 and APOE3/4 genotypes.

The size and shape of the nucleus accumbens and the amygdala may differ in young adults who smoke marijuana at least once a week, according to a study published April 16 in the Journal of Neuroscience. Investigators collected high-resolution MRI scans on young adults who used recreational marijuana and on controls. The researchers conducted three independent analyses of morphometry in gray matter density, volume (total brain and regional volumes), and surface morphometry. The study authors found greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to the subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only.

Neuronal death in Parkinson’s disease may occur when the immune system mistakes neurons for foreign invaders and kills them, according to a study published April 16 in Nature Communications. An examination of postmortem brain tissue revealed major histocompatibility complex class I (MHC-1) proteins in catecholaminergic substantia nigra and locus coeruleus neurons. When researchers conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells, they found that under certain circumstances, including conditions that occur in Parkinson’s disease, the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson’s disease were far more responsive than other neurons to signals that triggered antigen display. The researchers also confirmed that T cells recognized and attacked neurons displaying specific antigens.

People who have had a stroke who consistently control their blood pressure may reduce the likelihood of a second stroke by more than half, according to research published online ahead of print March 27 in Stroke. In a post hoc analysis, 3,680 individuals with recent stroke who were followed up for two years were grouped according to the proportion of visits during which their blood pressure was controlled (ie, <140/90 mm Hg). Consistency of blood pressure control affected outcomes in individuals with baseline systolic blood pressure greater than 132 mm Hg. Among individuals with baseline systolic blood pressure higher than 153 mm Hg, risks of stroke, myocardial infarction, or vascular death were lower in those with blood pressure controlled during 75% or more visits, versus less than 25% of visits.

Individuals between ages 18 and 24 who occasionally use stimulant drugs may have impaired neuronal activity in the parts of the brain associated with anticipatory functioning, according to research published March 26 in the Journal of Neuroscience. Investigators recruited 158 nondependent occasional stimulant users and 47 stimulant-naive controls. Participants completed a stop signal task while undergoing functional MRI. Compared with controls, occasional stimulant users showed attenuated neural activation related to the magnitude of probabilistic expectations of inhibitory demand in several areas, including the left prefrontal cortex and left caudate. The results indicate that clinicians may be able to use brain activity patterns as a means of identifying at-risk youth long before they have any obvious outward signs of addictive behaviors, according to the investigators.

—Erik Greb

PET is a promising tool for determining which severely brain damaged individuals in vegetative states have the potential to recover consciousness, according to research published online ahead of print April 16 in Lancet. Investigators examined 81 patients in a minimally conscious state, 41 patients with unresponsive wakefulness syndrome, and four patients with locked-in syndrome. The researchers performed repeated standardized clinical assessments with the Coma Recovery Scale–Revised (CRS-R), cerebral 18F-fluorodeoxyglucose (FDG) PET, and fMRI while the patients performed mental activation tasks. Mental imagery fMRI was less sensitive at diagnosing a minimally conscious state than FDG-PET (45% vs 93%) and had less agreement with behavioral CRS-R scores than FDG-PET (63% vs 85%). 18F-FDG PET correctly predicted outcome in 75 of 102 patients, and fMRI in 36 of 65 patients.

The risk of epilepsy may be heightened significantly among patients with autoimmune diseases, especially children, according to data published online ahead of print March 31 in JAMA Neurology. Researchers conducted a retrospective population-based study using claims from a nationwide employer-provided health insurance plan in the United States. All 2,518,034 participants included in the study were beneficiaries enrolled between 1999 and 2006. The investigators examined the relationship between epilepsy and type 1 diabetes mellitus, psoriasis, rheumatoid arthritis, Graves disease, Hashimoto thyroiditis, Crohn disease, ulcerative colitis, systemic lupus erythematosus, antiphospholipid syndrome, Sjögren syndrome, myasthenia gravis, and celiac disease. The odds ratio of epilepsy was 3.8 among patients with autoimmune diseases and 5.2 among children. Based on their findings, the authors recommended that patients with epilepsy undergo surveillance for autoimmune disease, and vice versa.

Migraineurs whose stress decreases from one day to the next have a significantly increased risk of migraine onset on the subsequent day, according to a study published online ahead of print March 26 in Neurology. Twenty-two patients with migraine participated in a three-month electronic diary study. Participants entered data daily regarding migraine attack experience, as well as subjective stress ratings. Stress was assessed using the Perceived Stress Scale and the Self-Reported Stress Scale. Level of stress was generally not associated with migraine occurrence. Decline in stress from one evening diary to the next was associated with increased migraine onset during the subsequent six, 12, and 18 hours for the Perceived Stress Scale. Decline in stress was associated with migraine onset after controlling for level of stress for all time points.

Patients older than 60 with stroke resulting from blockage of the middle cerebral artery (MCA) benefit from hemicraniectomy, researchers reported March 20 in the New England Journal of Medicine. Investigators randomly assigned 112 patients age 61 or older with malignant MCA infarction to conservative treatment in the ICU or hemicraniectomy. The primary end point was survival without severe disability (defined as a score of 0 to 4 on the modified Rankin scale). The proportion of patients who survived without severe disability was 38% in the hemicraniectomy group, compared with 18% in the control group. This difference resulted from lower mortality in the surgery group (33% vs 70%). Infections were more frequent in the hemicraniectomy group, and herniation was more frequent in the control group.

The FDA has approved Topamax (topiramate) for the prevention of migraine headaches in adolescents ages 12 to 17. Topamax is the first drug with FDA approval for migraine prevention in this age group. The medication is taken daily to reduce the frequency of migraine headaches. A clinical trial that enrolled 103 participants established the safety and effectiveness of Topamax in preventing migraine headaches in adolescents ages 12 to 17. Participants treated with Topamax had a decrease in migraine frequency of approximately 72%, compared with 44% in participants who took placebo. The most common adverse reactions with the approved dose of Topamax (100 mg) were paresthesia, upper respiratory infection, anorexia, and abdominal pain. Topamax is manufactured by Janssen Pharmaceuticals of Titusville, New Jersey.

The FDA has approved Evzio (naloxone hydrochloride injection), a prescription treatment that family members or caregivers can use to treat a person suspected to have had an opioid overdose. Evzio rapidly delivers a single dose of naloxone through a handheld autoinjector that can be carried in a pocket or stored in a medicine cabinet. Evzio provides intramuscular or subcutaneous administration. Once turned on, the device provides verbal instruction about how to deliver the medication. In one pharmacokinetic study of 30 patients, a single Evzio injection provided equivalent naloxone, compared with a single dose of naloxone injection using a standard syringe. Administering Evzio to patients who are opioid dependent may result in severe opioid withdrawal. Evzio is manufactured by kaléo, which is based in Richmond, Virginia.

The International League Against Epilepsy has altered its practical definition of epilepsy per the recommendation of a task force, according to an article published online ahead of print April 14 in Epilepsia. Recognizing the limitations of the practical definition of epilepsy as two unprovoked seizures more than 24 hours apart, the task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring more than 24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (ie, at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome.

Older people who have apathy but not depression may have smaller brain volumes than those without apathy, according to data published online ahead of print April 16 in Neurology. Investigators performed cross-sectional analyses of data from 4,354 persons without dementia (average age, 76) participating in a population-based study. Apathy symptoms were assessed with the Geriatric Depression Scale. Brain volumes and total white matter lesion (WML) volume were estimated on 1.5-T MRI using an automated segmentation program. Regional WML load was calculated using a semiquantitative scale. Compared with individuals with fewer than two apathy symptoms, participants with two or more apathy symptoms had significantly smaller gray matter volumes, smaller white matter volumes, and smaller thalamus volumes. The latter individuals also were more likely to have WMLs in the frontal lobe.

The APOE4 gene variant confers a substantially greater risk for Alzheimer’s disease to women than it does to men, researchers reported online ahead of print April 14 in Annals of Neurology. The group performed Cox proportional hazards analysis to compute hazard ratios (HRs) for an APOE-by-sex interaction on conversion in 5,496 healthy individuals and 2,588 patients with mild cognitive impairment (MCI). The investigators also tested the interaction in CSF biomarker levels of 980 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Among controls, male and female carriers were more likely to convert to MCI or Alzheimer’s disease, but the effect was stronger in women (HR, 1.81 for women; HR, 1.27 for men). The interaction remained significant in a predefined subanalysis that was restricted to APOE3/3 and APOE3/4 genotypes.

The size and shape of the nucleus accumbens and the amygdala may differ in young adults who smoke marijuana at least once a week, according to a study published April 16 in the Journal of Neuroscience. Investigators collected high-resolution MRI scans on young adults who used recreational marijuana and on controls. The researchers conducted three independent analyses of morphometry in gray matter density, volume (total brain and regional volumes), and surface morphometry. The study authors found greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to the subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only.

Neuronal death in Parkinson’s disease may occur when the immune system mistakes neurons for foreign invaders and kills them, according to a study published April 16 in Nature Communications. An examination of postmortem brain tissue revealed major histocompatibility complex class I (MHC-1) proteins in catecholaminergic substantia nigra and locus coeruleus neurons. When researchers conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells, they found that under certain circumstances, including conditions that occur in Parkinson’s disease, the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson’s disease were far more responsive than other neurons to signals that triggered antigen display. The researchers also confirmed that T cells recognized and attacked neurons displaying specific antigens.

People who have had a stroke who consistently control their blood pressure may reduce the likelihood of a second stroke by more than half, according to research published online ahead of print March 27 in Stroke. In a post hoc analysis, 3,680 individuals with recent stroke who were followed up for two years were grouped according to the proportion of visits during which their blood pressure was controlled (ie, <140/90 mm Hg). Consistency of blood pressure control affected outcomes in individuals with baseline systolic blood pressure greater than 132 mm Hg. Among individuals with baseline systolic blood pressure higher than 153 mm Hg, risks of stroke, myocardial infarction, or vascular death were lower in those with blood pressure controlled during 75% or more visits, versus less than 25% of visits.

Individuals between ages 18 and 24 who occasionally use stimulant drugs may have impaired neuronal activity in the parts of the brain associated with anticipatory functioning, according to research published March 26 in the Journal of Neuroscience. Investigators recruited 158 nondependent occasional stimulant users and 47 stimulant-naive controls. Participants completed a stop signal task while undergoing functional MRI. Compared with controls, occasional stimulant users showed attenuated neural activation related to the magnitude of probabilistic expectations of inhibitory demand in several areas, including the left prefrontal cortex and left caudate. The results indicate that clinicians may be able to use brain activity patterns as a means of identifying at-risk youth long before they have any obvious outward signs of addictive behaviors, according to the investigators.

—Erik Greb

Little evidence suggests that most complementary or alternative medicine therapies treat the symptoms of multiple sclerosis (MS), according to an American Academy of Neurology guideline published March 25 in Neurology. Oral cannabis and oral medical marijuana spray, however, may ease patients’ reported symptoms of spasticity, pain related to spasticity, and frequent urination in MS. Not enough evidence is available to show whether smoking marijuana helps treat MS symptoms, according to the guideline. The authors concluded that magnetic therapy is probably effective for fatigue and probably ineffective for depression. Fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life, according to the guideline. In addition, evidence indicates that ginkgo biloba is ineffective for cognition and possibly effective for fatigue, said the authors.

People who develop diabetes and high blood pressure in middle age are more likely to have brain cell loss and problems with memory and thinking skills than people who never have diabetes or high blood pressure or who develop them in old age, according to a study published online ahead of print March 19 in Neurology. Investigators evaluated the thinking and memory skills of 1,437 people (average age, 80), conducted brain scans, and reviewed participants’ medical records to determine whether the latter had been diagnosed with diabetes or high blood pressure in middle age or later. Midlife diabetes was associated with subcortical infarctions, reduced hippocampal volume, reduced whole brain volume, and prevalent mild cognitive impairment. Midlife hypertension was associated with infarctions and white matter hyperintensity volume.

Each 15-minute decrease in treatment delay may provide a patient an average equivalent of one month of additional disability-free life, according to a study published online ahead of print March 13 in Stroke. Researchers examined observational prospective data for 2,258 consecutive stroke patients treated with IV thrombolysis to determine distributions of age, sex, stroke severity, onset-to-treatment times, and three-month modified Rankin Scale score in daily clinical practice. The investigators found that for every one-minute reduction in onset-to-treatment time, patients gained an average 1.8 days of healthy life. Although all patients benefited from faster treatment, younger patients with longer life expectancies gained a little more than older patients. Women gained slightly more than men throughout their longer lifetimes. The awareness of the importance of speed could promote practice change, said the authors.

The FDA has approved extended-release Qudexy XR (topiramate) capsules as initial monotherapy in patients 10 or older with partial-onset seizures or primary generalized tonic-clonic seizures. The drug also received approval as adjunctive therapy in patients age 2 or older with partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox–Gastaut syndrome. In a randomized, double-blind, placebo-controlled study, the drug demonstrated favorable safety and tolerability in patients with refractory partial-onset seizures. The extended-release formulation was associated with a significantly greater median percent reduction from baseline in seizure frequency, compared with placebo (39.5% vs 21.7%) after 11 weeks of treatment. Upsher-Smith Laboratories, headquartered in Maple Grove, Minnesota, manufactures the drug and expects it to be available during the second quarter of 2014.

The FDA has approved the Cefaly medical device as a preventive treatment for migraine headaches. The product is the first transcutaneous electrical nerve stimulation device specifically authorized for use before the onset of pain. The product is a small, portable, battery-powered unit resembling a plastic headband worn across the forehead once per day for 20 minutes. The device applies an electric current to the skin and underlying tissues to stimulate branches of the trigeminal nerve. In a study including 67 participants, patients who used Cefaly had significantly fewer days with migraines per month and used less migraine attack medication, compared with patients who used a placebo device. STX-Med, which is headquartered in Herstal, Liege, Belgium, manufactures the device, which is indicated for patients 18 and older.

Children with autism who are fed infant formula containing soy protein rather than milk protein may have a higher rate of seizures, according to research published March 12 in PLOS One. Researchers analyzed medical record data for 1,949 children with autism, including information on infant formula use, seizure incidence, the specific type of seizure exhibited, and IQ. Soy-based formula was given in 17.5% of the study population. About 13% of the subjects were female. The researchers found a 2.6-fold higher rate of febrile seizures (4.2% vs 1.6%), a 2.1-fold higher rate of epilepsy comorbidity (3.6% vs 1.7%), and a fourfold higher rate of simple partial seizures (1.2% vs 0.3%) in the children with autism who were fed soy-based formula. No statistically significant associations were found with other outcomes.

For patients with Alzheimer’s disease, levels of markers of neuronal injury in the spinal fluid may decrease as symptoms of memory loss and mental decline appear, according to research published March 5 in Science Translational Medicine. Investigators studied data from the Dominantly Inherited Alzheimer’s Network, which includes participants from families with genetic mutations that cause rare inherited forms of Alzheimer’s disease. The group examined levels of tau, p-tau, and visinin-like protein-1 (VILIP-1). Asymptomatic mutation carriers had elevated concentrations of CSF tau, p-tau181, and VILIP-1 10 to 20 years before their estimated age at symptom onset and before cognitive deficits were detected. The concentrations of CSF biomarkers of neuronal injury or death decreased after their estimated age at symptom onset, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression.

Men with poor cardiovascular fitness or a low IQ at age 18 are more likely to develop dementia before age 60, investigators reported online ahead of print March 6 in Brain. The researchers conducted a population-based cohort study of more than 1.1 million Swedish male conscripts (age 18) who underwent conscription exams between 1968 and 2005. Participants were followed for as long as 42 years. In fully adjusted models, low cardiovascular fitness and cognitive performance at age 18 were associated with increased risk for future early-onset dementia and mild cognitive impairment, compared with high cardiovascular fitness and cognitive performance. Poor performance on cardiovascular fitness and cognitive tests was associated with a greater-than-sevenfold and a greater than eightfold increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively.

A test that detects low levels of prion protein in the blood may accurately screen for infection with the agent responsible for variant Creutzfeldt-Jakob disease (vCJD), according to a study published online ahead of print March 3 in JAMA Neurology. Researchers performed the test on samples from national blood collection and prion disease centers in the US and the UK. The samples were taken from healthy donors, patients with nonprion neurodegenerative disease, patients in whom a prion disease diagnosis was likely, and patients with confirmed vCJD. The assay’s specificity was confirmed as 100% in a healthy UK cohort. No potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases tested positive. Two patients with sporadic CJD tested positive. The authors’ previous sensitivity estimate was reconfirmed but not refined.

The FDA has approved Neuraceq (florbetaben F18 injection) for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The approval is based on safety data from 872 patients who participated in global clinical trials, and on three studies that examined images from adults with a range of cognitive function. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta-amyloid neuritic plaques. Correlation of the visual PET interpretation with histopathology in these 82 brains demonstrated that Neuraceq (Piramal Imaging; Boston) accurately detects moderate to frequent beta-amyloid neuritic plaques in the brain.

A combination of human umbilical cord blood cells (hUCBs) and granulocyte colony stimulating factor (G-CSF) may provide more benefit for patients with traumatic brain injury (TBI) than either therapy alone, according to research published March 12 in PLOS One. Adult rats underwent moderate TBI and, seven days later, were treated with saline alone, G-CSF and saline, hUCB and saline, or hUCB and G-CSF. The rats treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized neurogenesis, and reduced hippocampal cell loss, compared with saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation, modest neurogenesis, and moderate reduction of hippocampal cell loss. Combined therapy robustly dampened neuroinflammation, enhanced endogenous neurogenesis, and reduced hippocampal cell loss.

The ability to learn new information may be significantly poorer among patients with Parkinson’s disease than among healthy individuals, according to research published online ahead of print February 24 in Movement Disorders. Investigators examined 27 patients with Parkinson’s disease without dementia and 27 age-, gender-, and education-matched healthy controls with a neuropsychologic test battery designed to assess new learning and memory. The researchers found a significant difference in the groups’ ability to learn a list of 10 semantically related words. Once the groups were equated on learning abilities, the investigators found no significant difference between patients with Parkinson’s disease and controls in recall or recognition of the newly learned material. The memory deficit in nondemented patients with Parkinson’s disease largely results from a deficit in learning new information, said the authors.

Chronic sleep loss may lead to irreversible physical damage to and loss of brain cells, according to research published March 19 in the Journal of Neuroscience. Investigators examined mice following periods of normal rest, short wakefulness, or extended wakefulness to model shift workers’ typical sleep patterns. In response to short-term sleep loss, locus coeruleus neurons upregulated the sirtuin type 3 (SirT3) protein, which protects neurons from metabolic injury. After several days of shift worker sleep patterns, locus coeruleus neurons in the mice had reduced SirT3 and increased cell death. In addition, oxidative stress and acetylation of mitochondrial proteins increased. The mice lost 25% of their locus coeruleus neurons. “This is the first report that sleep loss can actually result in a loss of neurons,” said the authors.

—Erik Greb

Little evidence suggests that most complementary or alternative medicine therapies treat the symptoms of multiple sclerosis (MS), according to an American Academy of Neurology guideline published March 25 in Neurology. Oral cannabis and oral medical marijuana spray, however, may ease patients’ reported symptoms of spasticity, pain related to spasticity, and frequent urination in MS. Not enough evidence is available to show whether smoking marijuana helps treat MS symptoms, according to the guideline. The authors concluded that magnetic therapy is probably effective for fatigue and probably ineffective for depression. Fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life, according to the guideline. In addition, evidence indicates that ginkgo biloba is ineffective for cognition and possibly effective for fatigue, said the authors.

People who develop diabetes and high blood pressure in middle age are more likely to have brain cell loss and problems with memory and thinking skills than people who never have diabetes or high blood pressure or who develop them in old age, according to a study published online ahead of print March 19 in Neurology. Investigators evaluated the thinking and memory skills of 1,437 people (average age, 80), conducted brain scans, and reviewed participants’ medical records to determine whether the latter had been diagnosed with diabetes or high blood pressure in middle age or later. Midlife diabetes was associated with subcortical infarctions, reduced hippocampal volume, reduced whole brain volume, and prevalent mild cognitive impairment. Midlife hypertension was associated with infarctions and white matter hyperintensity volume.

Each 15-minute decrease in treatment delay may provide a patient an average equivalent of one month of additional disability-free life, according to a study published online ahead of print March 13 in Stroke. Researchers examined observational prospective data for 2,258 consecutive stroke patients treated with IV thrombolysis to determine distributions of age, sex, stroke severity, onset-to-treatment times, and three-month modified Rankin Scale score in daily clinical practice. The investigators found that for every one-minute reduction in onset-to-treatment time, patients gained an average 1.8 days of healthy life. Although all patients benefited from faster treatment, younger patients with longer life expectancies gained a little more than older patients. Women gained slightly more than men throughout their longer lifetimes. The awareness of the importance of speed could promote practice change, said the authors.

The FDA has approved extended-release Qudexy XR (topiramate) capsules as initial monotherapy in patients 10 or older with partial-onset seizures or primary generalized tonic-clonic seizures. The drug also received approval as adjunctive therapy in patients age 2 or older with partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox–Gastaut syndrome. In a randomized, double-blind, placebo-controlled study, the drug demonstrated favorable safety and tolerability in patients with refractory partial-onset seizures. The extended-release formulation was associated with a significantly greater median percent reduction from baseline in seizure frequency, compared with placebo (39.5% vs 21.7%) after 11 weeks of treatment. Upsher-Smith Laboratories, headquartered in Maple Grove, Minnesota, manufactures the drug and expects it to be available during the second quarter of 2014.

The FDA has approved the Cefaly medical device as a preventive treatment for migraine headaches. The product is the first transcutaneous electrical nerve stimulation device specifically authorized for use before the onset of pain. The product is a small, portable, battery-powered unit resembling a plastic headband worn across the forehead once per day for 20 minutes. The device applies an electric current to the skin and underlying tissues to stimulate branches of the trigeminal nerve. In a study including 67 participants, patients who used Cefaly had significantly fewer days with migraines per month and used less migraine attack medication, compared with patients who used a placebo device. STX-Med, which is headquartered in Herstal, Liege, Belgium, manufactures the device, which is indicated for patients 18 and older.

Children with autism who are fed infant formula containing soy protein rather than milk protein may have a higher rate of seizures, according to research published March 12 in PLOS One. Researchers analyzed medical record data for 1,949 children with autism, including information on infant formula use, seizure incidence, the specific type of seizure exhibited, and IQ. Soy-based formula was given in 17.5% of the study population. About 13% of the subjects were female. The researchers found a 2.6-fold higher rate of febrile seizures (4.2% vs 1.6%), a 2.1-fold higher rate of epilepsy comorbidity (3.6% vs 1.7%), and a fourfold higher rate of simple partial seizures (1.2% vs 0.3%) in the children with autism who were fed soy-based formula. No statistically significant associations were found with other outcomes.

For patients with Alzheimer’s disease, levels of markers of neuronal injury in the spinal fluid may decrease as symptoms of memory loss and mental decline appear, according to research published March 5 in Science Translational Medicine. Investigators studied data from the Dominantly Inherited Alzheimer’s Network, which includes participants from families with genetic mutations that cause rare inherited forms of Alzheimer’s disease. The group examined levels of tau, p-tau, and visinin-like protein-1 (VILIP-1). Asymptomatic mutation carriers had elevated concentrations of CSF tau, p-tau181, and VILIP-1 10 to 20 years before their estimated age at symptom onset and before cognitive deficits were detected. The concentrations of CSF biomarkers of neuronal injury or death decreased after their estimated age at symptom onset, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression.

Men with poor cardiovascular fitness or a low IQ at age 18 are more likely to develop dementia before age 60, investigators reported online ahead of print March 6 in Brain. The researchers conducted a population-based cohort study of more than 1.1 million Swedish male conscripts (age 18) who underwent conscription exams between 1968 and 2005. Participants were followed for as long as 42 years. In fully adjusted models, low cardiovascular fitness and cognitive performance at age 18 were associated with increased risk for future early-onset dementia and mild cognitive impairment, compared with high cardiovascular fitness and cognitive performance. Poor performance on cardiovascular fitness and cognitive tests was associated with a greater-than-sevenfold and a greater than eightfold increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively.

A test that detects low levels of prion protein in the blood may accurately screen for infection with the agent responsible for variant Creutzfeldt-Jakob disease (vCJD), according to a study published online ahead of print March 3 in JAMA Neurology. Researchers performed the test on samples from national blood collection and prion disease centers in the US and the UK. The samples were taken from healthy donors, patients with nonprion neurodegenerative disease, patients in whom a prion disease diagnosis was likely, and patients with confirmed vCJD. The assay’s specificity was confirmed as 100% in a healthy UK cohort. No potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases tested positive. Two patients with sporadic CJD tested positive. The authors’ previous sensitivity estimate was reconfirmed but not refined.

The FDA has approved Neuraceq (florbetaben F18 injection) for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The approval is based on safety data from 872 patients who participated in global clinical trials, and on three studies that examined images from adults with a range of cognitive function. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta-amyloid neuritic plaques. Correlation of the visual PET interpretation with histopathology in these 82 brains demonstrated that Neuraceq (Piramal Imaging; Boston) accurately detects moderate to frequent beta-amyloid neuritic plaques in the brain.

A combination of human umbilical cord blood cells (hUCBs) and granulocyte colony stimulating factor (G-CSF) may provide more benefit for patients with traumatic brain injury (TBI) than either therapy alone, according to research published March 12 in PLOS One. Adult rats underwent moderate TBI and, seven days later, were treated with saline alone, G-CSF and saline, hUCB and saline, or hUCB and G-CSF. The rats treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized neurogenesis, and reduced hippocampal cell loss, compared with saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation, modest neurogenesis, and moderate reduction of hippocampal cell loss. Combined therapy robustly dampened neuroinflammation, enhanced endogenous neurogenesis, and reduced hippocampal cell loss.

The ability to learn new information may be significantly poorer among patients with Parkinson’s disease than among healthy individuals, according to research published online ahead of print February 24 in Movement Disorders. Investigators examined 27 patients with Parkinson’s disease without dementia and 27 age-, gender-, and education-matched healthy controls with a neuropsychologic test battery designed to assess new learning and memory. The researchers found a significant difference in the groups’ ability to learn a list of 10 semantically related words. Once the groups were equated on learning abilities, the investigators found no significant difference between patients with Parkinson’s disease and controls in recall or recognition of the newly learned material. The memory deficit in nondemented patients with Parkinson’s disease largely results from a deficit in learning new information, said the authors.

Chronic sleep loss may lead to irreversible physical damage to and loss of brain cells, according to research published March 19 in the Journal of Neuroscience. Investigators examined mice following periods of normal rest, short wakefulness, or extended wakefulness to model shift workers’ typical sleep patterns. In response to short-term sleep loss, locus coeruleus neurons upregulated the sirtuin type 3 (SirT3) protein, which protects neurons from metabolic injury. After several days of shift worker sleep patterns, locus coeruleus neurons in the mice had reduced SirT3 and increased cell death. In addition, oxidative stress and acetylation of mitochondrial proteins increased. The mice lost 25% of their locus coeruleus neurons. “This is the first report that sleep loss can actually result in a loss of neurons,” said the authors.

—Erik Greb

Little evidence suggests that most complementary or alternative medicine therapies treat the symptoms of multiple sclerosis (MS), according to an American Academy of Neurology guideline published March 25 in Neurology. Oral cannabis and oral medical marijuana spray, however, may ease patients’ reported symptoms of spasticity, pain related to spasticity, and frequent urination in MS. Not enough evidence is available to show whether smoking marijuana helps treat MS symptoms, according to the guideline. The authors concluded that magnetic therapy is probably effective for fatigue and probably ineffective for depression. Fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life, according to the guideline. In addition, evidence indicates that ginkgo biloba is ineffective for cognition and possibly effective for fatigue, said the authors.

People who develop diabetes and high blood pressure in middle age are more likely to have brain cell loss and problems with memory and thinking skills than people who never have diabetes or high blood pressure or who develop them in old age, according to a study published online ahead of print March 19 in Neurology. Investigators evaluated the thinking and memory skills of 1,437 people (average age, 80), conducted brain scans, and reviewed participants’ medical records to determine whether the latter had been diagnosed with diabetes or high blood pressure in middle age or later. Midlife diabetes was associated with subcortical infarctions, reduced hippocampal volume, reduced whole brain volume, and prevalent mild cognitive impairment. Midlife hypertension was associated with infarctions and white matter hyperintensity volume.

Each 15-minute decrease in treatment delay may provide a patient an average equivalent of one month of additional disability-free life, according to a study published online ahead of print March 13 in Stroke. Researchers examined observational prospective data for 2,258 consecutive stroke patients treated with IV thrombolysis to determine distributions of age, sex, stroke severity, onset-to-treatment times, and three-month modified Rankin Scale score in daily clinical practice. The investigators found that for every one-minute reduction in onset-to-treatment time, patients gained an average 1.8 days of healthy life. Although all patients benefited from faster treatment, younger patients with longer life expectancies gained a little more than older patients. Women gained slightly more than men throughout their longer lifetimes. The awareness of the importance of speed could promote practice change, said the authors.

The FDA has approved extended-release Qudexy XR (topiramate) capsules as initial monotherapy in patients 10 or older with partial-onset seizures or primary generalized tonic-clonic seizures. The drug also received approval as adjunctive therapy in patients age 2 or older with partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox–Gastaut syndrome. In a randomized, double-blind, placebo-controlled study, the drug demonstrated favorable safety and tolerability in patients with refractory partial-onset seizures. The extended-release formulation was associated with a significantly greater median percent reduction from baseline in seizure frequency, compared with placebo (39.5% vs 21.7%) after 11 weeks of treatment. Upsher-Smith Laboratories, headquartered in Maple Grove, Minnesota, manufactures the drug and expects it to be available during the second quarter of 2014.

The FDA has approved the Cefaly medical device as a preventive treatment for migraine headaches. The product is the first transcutaneous electrical nerve stimulation device specifically authorized for use before the onset of pain. The product is a small, portable, battery-powered unit resembling a plastic headband worn across the forehead once per day for 20 minutes. The device applies an electric current to the skin and underlying tissues to stimulate branches of the trigeminal nerve. In a study including 67 participants, patients who used Cefaly had significantly fewer days with migraines per month and used less migraine attack medication, compared with patients who used a placebo device. STX-Med, which is headquartered in Herstal, Liege, Belgium, manufactures the device, which is indicated for patients 18 and older.

Children with autism who are fed infant formula containing soy protein rather than milk protein may have a higher rate of seizures, according to research published March 12 in PLOS One. Researchers analyzed medical record data for 1,949 children with autism, including information on infant formula use, seizure incidence, the specific type of seizure exhibited, and IQ. Soy-based formula was given in 17.5% of the study population. About 13% of the subjects were female. The researchers found a 2.6-fold higher rate of febrile seizures (4.2% vs 1.6%), a 2.1-fold higher rate of epilepsy comorbidity (3.6% vs 1.7%), and a fourfold higher rate of simple partial seizures (1.2% vs 0.3%) in the children with autism who were fed soy-based formula. No statistically significant associations were found with other outcomes.

For patients with Alzheimer’s disease, levels of markers of neuronal injury in the spinal fluid may decrease as symptoms of memory loss and mental decline appear, according to research published March 5 in Science Translational Medicine. Investigators studied data from the Dominantly Inherited Alzheimer’s Network, which includes participants from families with genetic mutations that cause rare inherited forms of Alzheimer’s disease. The group examined levels of tau, p-tau, and visinin-like protein-1 (VILIP-1). Asymptomatic mutation carriers had elevated concentrations of CSF tau, p-tau181, and VILIP-1 10 to 20 years before their estimated age at symptom onset and before cognitive deficits were detected. The concentrations of CSF biomarkers of neuronal injury or death decreased after their estimated age at symptom onset, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression.

Men with poor cardiovascular fitness or a low IQ at age 18 are more likely to develop dementia before age 60, investigators reported online ahead of print March 6 in Brain. The researchers conducted a population-based cohort study of more than 1.1 million Swedish male conscripts (age 18) who underwent conscription exams between 1968 and 2005. Participants were followed for as long as 42 years. In fully adjusted models, low cardiovascular fitness and cognitive performance at age 18 were associated with increased risk for future early-onset dementia and mild cognitive impairment, compared with high cardiovascular fitness and cognitive performance. Poor performance on cardiovascular fitness and cognitive tests was associated with a greater-than-sevenfold and a greater than eightfold increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively.

A test that detects low levels of prion protein in the blood may accurately screen for infection with the agent responsible for variant Creutzfeldt-Jakob disease (vCJD), according to a study published online ahead of print March 3 in JAMA Neurology. Researchers performed the test on samples from national blood collection and prion disease centers in the US and the UK. The samples were taken from healthy donors, patients with nonprion neurodegenerative disease, patients in whom a prion disease diagnosis was likely, and patients with confirmed vCJD. The assay’s specificity was confirmed as 100% in a healthy UK cohort. No potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases tested positive. Two patients with sporadic CJD tested positive. The authors’ previous sensitivity estimate was reconfirmed but not refined.

The FDA has approved Neuraceq (florbetaben F18 injection) for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The approval is based on safety data from 872 patients who participated in global clinical trials, and on three studies that examined images from adults with a range of cognitive function. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta-amyloid neuritic plaques. Correlation of the visual PET interpretation with histopathology in these 82 brains demonstrated that Neuraceq (Piramal Imaging; Boston) accurately detects moderate to frequent beta-amyloid neuritic plaques in the brain.

A combination of human umbilical cord blood cells (hUCBs) and granulocyte colony stimulating factor (G-CSF) may provide more benefit for patients with traumatic brain injury (TBI) than either therapy alone, according to research published March 12 in PLOS One. Adult rats underwent moderate TBI and, seven days later, were treated with saline alone, G-CSF and saline, hUCB and saline, or hUCB and G-CSF. The rats treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized neurogenesis, and reduced hippocampal cell loss, compared with saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation, modest neurogenesis, and moderate reduction of hippocampal cell loss. Combined therapy robustly dampened neuroinflammation, enhanced endogenous neurogenesis, and reduced hippocampal cell loss.

The ability to learn new information may be significantly poorer among patients with Parkinson’s disease than among healthy individuals, according to research published online ahead of print February 24 in Movement Disorders. Investigators examined 27 patients with Parkinson’s disease without dementia and 27 age-, gender-, and education-matched healthy controls with a neuropsychologic test battery designed to assess new learning and memory. The researchers found a significant difference in the groups’ ability to learn a list of 10 semantically related words. Once the groups were equated on learning abilities, the investigators found no significant difference between patients with Parkinson’s disease and controls in recall or recognition of the newly learned material. The memory deficit in nondemented patients with Parkinson’s disease largely results from a deficit in learning new information, said the authors.

Chronic sleep loss may lead to irreversible physical damage to and loss of brain cells, according to research published March 19 in the Journal of Neuroscience. Investigators examined mice following periods of normal rest, short wakefulness, or extended wakefulness to model shift workers’ typical sleep patterns. In response to short-term sleep loss, locus coeruleus neurons upregulated the sirtuin type 3 (SirT3) protein, which protects neurons from metabolic injury. After several days of shift worker sleep patterns, locus coeruleus neurons in the mice had reduced SirT3 and increased cell death. In addition, oxidative stress and acetylation of mitochondrial proteins increased. The mice lost 25% of their locus coeruleus neurons. “This is the first report that sleep loss can actually result in a loss of neurons,” said the authors.

—Erik Greb

Patients who are dementia-free but have two parents with late-onset Alzheimer’s disease may show signs of the disease during brain imaging decades before symptoms appear, researchers reported online ahead of print February 12 in Neurology. A total of 52 persons with normal cognition—including four demographically balanced groups with maternal, paternal, and maternal and paternal family history of late-onset Alzheimer’s disease, as well as those with a negative family history—underwent MRI, ¹¹C-Pittsburgh compound B (PiB) PET, and ¹⁸F-fluoro-2-deoxyglucose PET. Subjects with both parents with a history of Alzheimer’s disease had more severe abnormalities in all three biomarkers, compared with the other groups, regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in participants with a maternal and paternal history of Alzheimer’s disease, according to the investigators.

Patients with nonvalvular atrial fibrillation are encouraged to take oral anticoagulants to prevent stroke, according to an updated guideline published in the February 25, 2014, issue of Neurology. Treatment with anticoagulants is especially important for people who have already had a stroke or a transient ischemic attack, according to the authors. The current guideline concludes that new anticoagulants such as dabigatran, rivaroxaban, and apixaban are at least as effective as, if not more effective than, warfarin and entail a lower risk of bleeding in the brain. An advantage of the new drugs is that they do not require frequent blood testing as warfarin does. The guideline also recommends new anticoagulants for the elderly, people with mild dementia, and people at moderate risk of falls.

Giving patients medications to lower blood pressure during the first 48 hours after a stroke may not reduce the likelihood of death or major disability, according to research published February 5 in JAMA. Within 48 hours of onset, 4,071 patients with nonthrombolysed ischemic stroke and elevated systolic blood pressure were randomized to receive antihypertensive treatment or to discontinuation of antihypertensive medications. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. At 14 days or hospital discharge, researchers recorded 683 incidences of death or major disability in the antihypertensive treatment group and 681 incidences in the control group.

The FDA has granted accelerated approval for Northera (droxidopa) capsules for the treatment of neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (eg, Parkinson’s disease or multiple system atrophy). Accelerated approval is granted to medicines that fill a serious unmet medical need. The capsules have a boxed warning to alert health care professionals and patients about the risk of supine hypertension, which can cause stroke. Two clinical trials involving people with NOH demonstrated droxidopa’s effectiveness over a period of two weeks. The drug, which is manufactured by Chelsea Therapeutics in Charlotte, North Carolina, has not been demonstrated to provide improvement in patient symptoms beyond two weeks. The most common adverse events reported by clinical trial participants taking droxidopa were headache, dizziness, nausea, high blood pressure, and fatigue.

Earlier treatment with an antiepileptic drug (AED) results in a shorter total seizure duration among children with febrile status epilepticus, according to a study published online ahead of print February 6 in Epilepsia. A total of 199 children (ages 1 month to 6 years), were included in the prospective, multicenter study. The median time from seizure onset to first administration of an AED by EMS or emergency department personnel was 30 minutes. The mean seizure duration for children who were given medication before admission to the emergency department was 81 minutes, compared with 95 minutes for those who were not treated beforehand. The median time from first dose of an AED to the end of a seizure was 38 minutes. “Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration,” the investigators concluded.

The FDA has granted 510(k) clearance to the Reveal LINQ Insertable Cardiac Monitor (ICM) System. The device is indicated for patients who have symptoms such as dizziness, palpitation, syncope, and chest pain that may suggest a cardiac arrhythmia, and for patients at increased risk for cardiac arrhythmias. The Reveal LINQ ICM is part of a system that allows physicians to monitor a patient’s heart continuously and wirelessly for as long as three years. The system also provides remote monitoring through the Carelink Network, which allows physicians to request notifications to alert them if their patients have had cardiac events. The Reveal LINQ ICM is approximately one-third the size of an AAA battery. The device is manufactured by Medtronic, which is headquartered in Minneapolis.

The final stage of the normal inflammatory process may be disrupted in patients with Alzheimer’s disease, according to research published online ahead of print February 14 in Alzheimer’s and Dementia. Researchers analyzed specialized proresolving mediators (SPMs), receptors, a biosynthetic enzyme, and downstream effectors involved in inflammation resolution in postmortem hippocampal tissue from patients with and without Alzheimer’s disease. SPMs were analyzed in CSF. Levels of the SPM lipoxin A₄ (LXA₄) were reduced in patients with Alzheimer’s disease in the CSF and the hippocampus. An enzyme involved in LXA4 synthesis and two SPM receptors were elevated in brains of patients with Alzheimer’s disease. LXA₄ and RvD1 levels in CSF correlated with Mini-Mental State Examination scores. Stimulation of inflammation resolution may reduce neuronal death in the brain, said the investigators.

Toxic chemicals may be triggering the recent increases in neurodevelopmental disabilities among children, according to a study published in the March issue of Lancet Neurology. In 2006, researchers identified five industrial chemicals as developmental neurotoxicants. The current study offers updated findings about those chemicals and adds information on six newly recognized ones, including manganese, fluoride, chlorpyrifos and DDT (ie, pesticides), tetrachloroethylene (a solvent), and the polybrominated diphenyl ethers (flame retardants). The study found that manganese is associated with diminished intellectual function and impaired motor skills, solvents are linked to hyperactivity and aggressive behavior, and certain pesticides may cause cognitive delays. More neurotoxicants may remain undiscovered, according to the investigators, who propose a global prevention strategy to control what they call a pandemic of developmental neurotoxicity.

For relatives of patients with multiple sclerosis (MS), the risk of developing the disease may be lower than previously assumed, according to a study published in the March issue of Brain. Researchers from Karolinska Institutet assessed the familial risks for MS using population registers and health care registries. They identified 28,396 patients with MS, along with first- and second-degree relatives and cousins. The investigators used matched population-based controls to calculate relative risks and found lower estimates of familial MS risks than previously reported. Despite a well-established lower prevalence of MS among males, the relative risks were equal among maternal and paternal relations. Using 74,757 twin pairs, the researchers estimated the disease’s heritability to be 0.64 and its shared environmental component to be 0.01.

Football helmets differ in their ability to reduce the risk of concussion, researchers reported online ahead of print January 31 in the Journal of Neurosurgery. The investigators conducted a retrospective analysis of head impact data from 1,833 collegiate football players from 2005 to 2010 who wore helmet-mounted accelerometer arrays for games and practices. The researchers compared concussion rates between players who wore the Riddell VSR4 and Riddell Revolution helmets. A total of 1,281,444 head impacts were recorded, and 64 concussions were diagnosed. The investigators found that the relative risk of sustaining a concussion in a Revolution helmet versus a VSR4 helmet was 46.1%. “Although helmet design may never prevent all concussions from occurring in football, evidence illustrates that it can reduce the incidence of this injury,” the researchers concluded.

Women have a worse quality of life, compared with men, for as long as 12 months after a stroke, even after adjustment for key sociodemographic variables, stroke severity, and disability, according to a study published online ahead of print February 7 in Neurology. Researchers assessed the quality of life in 1,370 patients (53.7% male; median age, 65) with ischemic stroke or transient ischemic attack (TIA) at three and 12 months postdischarge. Women had a significantly lower quality of life at three and 12 months poststroke. After multivariable adjustment for sociodemographic, clinical, and stroke-related factors, the investigators found that women continued to have a lower quality of life at three and 12 months. Women also had a poorer outcome in the dimensions of mobility, pain or discomfort, and anxiety or depression at three and 12 months.

High levels of high-density lipoprotein (HDL) cholesterol and low levels of low-density lipoprotein (LDL) cholesterol may be correlated with lower levels of amyloid plaque deposition in the brain, according to a study published in the February issue of JAMA Neurology. Investigators examined 74 individuals age 70 or older, including three participants with mild dementia, 33 cognitively normal participants, and 38 people with mild cognitive impairment. Cerebral amyloid-beta was measured with carbon C11–labeled Pittsburgh Compound B (PiB) PET. Statistical models that controlled for age and APOE ɛ4 revealed independent associations among the levels of LDL cholesterol, HDL cholesterol, and PiB index. Higher LDL cholesterol and lower HDL cholesterol levels were associated with a higher PiB index. The finding suggests an important role for cholesterol in amyloid-beta processing, said the researchers.

Patients with acute ischemic stroke who receive prompt treatment with t-PA may avoid a lengthy stay in an ICU, according to a study published February 12 in PLOS One. In a retrospective chart review of 153 patients who received IV t-PA for stroke, those with an NIH Stroke Scale (NIHSS) score of 10 or higher had a 7.7-times higher risk of requiring ICU resources, compared with patients who presented with an NIHSS score lower than 10. Eighty-one percent of patients with ICU needs developed them before the end of t-PA infusion, while 7% of those without ICU needs at the end of the t-PA infusion required ICU care later on. “We propose that patients without ICU needs by the end of the t-PA infusion might be safely monitored in a non-ICU setting if NIHSS at presentation is low,” the researchers advised.

—Erik Greb and Colby Stong

Patients who are dementia-free but have two parents with late-onset Alzheimer’s disease may show signs of the disease during brain imaging decades before symptoms appear, researchers reported online ahead of print February 12 in Neurology. A total of 52 persons with normal cognition—including four demographically balanced groups with maternal, paternal, and maternal and paternal family history of late-onset Alzheimer’s disease, as well as those with a negative family history—underwent MRI, ¹¹C-Pittsburgh compound B (PiB) PET, and ¹⁸F-fluoro-2-deoxyglucose PET. Subjects with both parents with a history of Alzheimer’s disease had more severe abnormalities in all three biomarkers, compared with the other groups, regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in participants with a maternal and paternal history of Alzheimer’s disease, according to the investigators.

Patients with nonvalvular atrial fibrillation are encouraged to take oral anticoagulants to prevent stroke, according to an updated guideline published in the February 25, 2014, issue of Neurology. Treatment with anticoagulants is especially important for people who have already had a stroke or a transient ischemic attack, according to the authors. The current guideline concludes that new anticoagulants such as dabigatran, rivaroxaban, and apixaban are at least as effective as, if not more effective than, warfarin and entail a lower risk of bleeding in the brain. An advantage of the new drugs is that they do not require frequent blood testing as warfarin does. The guideline also recommends new anticoagulants for the elderly, people with mild dementia, and people at moderate risk of falls.

Giving patients medications to lower blood pressure during the first 48 hours after a stroke may not reduce the likelihood of death or major disability, according to research published February 5 in JAMA. Within 48 hours of onset, 4,071 patients with nonthrombolysed ischemic stroke and elevated systolic blood pressure were randomized to receive antihypertensive treatment or to discontinuation of antihypertensive medications. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. At 14 days or hospital discharge, researchers recorded 683 incidences of death or major disability in the antihypertensive treatment group and 681 incidences in the control group.

The FDA has granted accelerated approval for Northera (droxidopa) capsules for the treatment of neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (eg, Parkinson’s disease or multiple system atrophy). Accelerated approval is granted to medicines that fill a serious unmet medical need. The capsules have a boxed warning to alert health care professionals and patients about the risk of supine hypertension, which can cause stroke. Two clinical trials involving people with NOH demonstrated droxidopa’s effectiveness over a period of two weeks. The drug, which is manufactured by Chelsea Therapeutics in Charlotte, North Carolina, has not been demonstrated to provide improvement in patient symptoms beyond two weeks. The most common adverse events reported by clinical trial participants taking droxidopa were headache, dizziness, nausea, high blood pressure, and fatigue.

Earlier treatment with an antiepileptic drug (AED) results in a shorter total seizure duration among children with febrile status epilepticus, according to a study published online ahead of print February 6 in Epilepsia. A total of 199 children (ages 1 month to 6 years), were included in the prospective, multicenter study. The median time from seizure onset to first administration of an AED by EMS or emergency department personnel was 30 minutes. The mean seizure duration for children who were given medication before admission to the emergency department was 81 minutes, compared with 95 minutes for those who were not treated beforehand. The median time from first dose of an AED to the end of a seizure was 38 minutes. “Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration,” the investigators concluded.

The FDA has granted 510(k) clearance to the Reveal LINQ Insertable Cardiac Monitor (ICM) System. The device is indicated for patients who have symptoms such as dizziness, palpitation, syncope, and chest pain that may suggest a cardiac arrhythmia, and for patients at increased risk for cardiac arrhythmias. The Reveal LINQ ICM is part of a system that allows physicians to monitor a patient’s heart continuously and wirelessly for as long as three years. The system also provides remote monitoring through the Carelink Network, which allows physicians to request notifications to alert them if their patients have had cardiac events. The Reveal LINQ ICM is approximately one-third the size of an AAA battery. The device is manufactured by Medtronic, which is headquartered in Minneapolis.

The final stage of the normal inflammatory process may be disrupted in patients with Alzheimer’s disease, according to research published online ahead of print February 14 in Alzheimer’s and Dementia. Researchers analyzed specialized proresolving mediators (SPMs), receptors, a biosynthetic enzyme, and downstream effectors involved in inflammation resolution in postmortem hippocampal tissue from patients with and without Alzheimer’s disease. SPMs were analyzed in CSF. Levels of the SPM lipoxin A₄ (LXA₄) were reduced in patients with Alzheimer’s disease in the CSF and the hippocampus. An enzyme involved in LXA4 synthesis and two SPM receptors were elevated in brains of patients with Alzheimer’s disease. LXA₄ and RvD1 levels in CSF correlated with Mini-Mental State Examination scores. Stimulation of inflammation resolution may reduce neuronal death in the brain, said the investigators.

Toxic chemicals may be triggering the recent increases in neurodevelopmental disabilities among children, according to a study published in the March issue of Lancet Neurology. In 2006, researchers identified five industrial chemicals as developmental neurotoxicants. The current study offers updated findings about those chemicals and adds information on six newly recognized ones, including manganese, fluoride, chlorpyrifos and DDT (ie, pesticides), tetrachloroethylene (a solvent), and the polybrominated diphenyl ethers (flame retardants). The study found that manganese is associated with diminished intellectual function and impaired motor skills, solvents are linked to hyperactivity and aggressive behavior, and certain pesticides may cause cognitive delays. More neurotoxicants may remain undiscovered, according to the investigators, who propose a global prevention strategy to control what they call a pandemic of developmental neurotoxicity.

For relatives of patients with multiple sclerosis (MS), the risk of developing the disease may be lower than previously assumed, according to a study published in the March issue of Brain. Researchers from Karolinska Institutet assessed the familial risks for MS using population registers and health care registries. They identified 28,396 patients with MS, along with first- and second-degree relatives and cousins. The investigators used matched population-based controls to calculate relative risks and found lower estimates of familial MS risks than previously reported. Despite a well-established lower prevalence of MS among males, the relative risks were equal among maternal and paternal relations. Using 74,757 twin pairs, the researchers estimated the disease’s heritability to be 0.64 and its shared environmental component to be 0.01.

Football helmets differ in their ability to reduce the risk of concussion, researchers reported online ahead of print January 31 in the Journal of Neurosurgery. The investigators conducted a retrospective analysis of head impact data from 1,833 collegiate football players from 2005 to 2010 who wore helmet-mounted accelerometer arrays for games and practices. The researchers compared concussion rates between players who wore the Riddell VSR4 and Riddell Revolution helmets. A total of 1,281,444 head impacts were recorded, and 64 concussions were diagnosed. The investigators found that the relative risk of sustaining a concussion in a Revolution helmet versus a VSR4 helmet was 46.1%. “Although helmet design may never prevent all concussions from occurring in football, evidence illustrates that it can reduce the incidence of this injury,” the researchers concluded.

Women have a worse quality of life, compared with men, for as long as 12 months after a stroke, even after adjustment for key sociodemographic variables, stroke severity, and disability, according to a study published online ahead of print February 7 in Neurology. Researchers assessed the quality of life in 1,370 patients (53.7% male; median age, 65) with ischemic stroke or transient ischemic attack (TIA) at three and 12 months postdischarge. Women had a significantly lower quality of life at three and 12 months poststroke. After multivariable adjustment for sociodemographic, clinical, and stroke-related factors, the investigators found that women continued to have a lower quality of life at three and 12 months. Women also had a poorer outcome in the dimensions of mobility, pain or discomfort, and anxiety or depression at three and 12 months.

High levels of high-density lipoprotein (HDL) cholesterol and low levels of low-density lipoprotein (LDL) cholesterol may be correlated with lower levels of amyloid plaque deposition in the brain, according to a study published in the February issue of JAMA Neurology. Investigators examined 74 individuals age 70 or older, including three participants with mild dementia, 33 cognitively normal participants, and 38 people with mild cognitive impairment. Cerebral amyloid-beta was measured with carbon C11–labeled Pittsburgh Compound B (PiB) PET. Statistical models that controlled for age and APOE ɛ4 revealed independent associations among the levels of LDL cholesterol, HDL cholesterol, and PiB index. Higher LDL cholesterol and lower HDL cholesterol levels were associated with a higher PiB index. The finding suggests an important role for cholesterol in amyloid-beta processing, said the researchers.

Patients with acute ischemic stroke who receive prompt treatment with t-PA may avoid a lengthy stay in an ICU, according to a study published February 12 in PLOS One. In a retrospective chart review of 153 patients who received IV t-PA for stroke, those with an NIH Stroke Scale (NIHSS) score of 10 or higher had a 7.7-times higher risk of requiring ICU resources, compared with patients who presented with an NIHSS score lower than 10. Eighty-one percent of patients with ICU needs developed them before the end of t-PA infusion, while 7% of those without ICU needs at the end of the t-PA infusion required ICU care later on. “We propose that patients without ICU needs by the end of the t-PA infusion might be safely monitored in a non-ICU setting if NIHSS at presentation is low,” the researchers advised.

—Erik Greb and Colby Stong

Patients who are dementia-free but have two parents with late-onset Alzheimer’s disease may show signs of the disease during brain imaging decades before symptoms appear, researchers reported online ahead of print February 12 in Neurology. A total of 52 persons with normal cognition—including four demographically balanced groups with maternal, paternal, and maternal and paternal family history of late-onset Alzheimer’s disease, as well as those with a negative family history—underwent MRI, ¹¹C-Pittsburgh compound B (PiB) PET, and ¹⁸F-fluoro-2-deoxyglucose PET. Subjects with both parents with a history of Alzheimer’s disease had more severe abnormalities in all three biomarkers, compared with the other groups, regarding the number of regions affected and magnitude of impairment. PiB retention and hypometabolism were most pronounced in participants with a maternal and paternal history of Alzheimer’s disease, according to the investigators.

Patients with nonvalvular atrial fibrillation are encouraged to take oral anticoagulants to prevent stroke, according to an updated guideline published in the February 25, 2014, issue of Neurology. Treatment with anticoagulants is especially important for people who have already had a stroke or a transient ischemic attack, according to the authors. The current guideline concludes that new anticoagulants such as dabigatran, rivaroxaban, and apixaban are at least as effective as, if not more effective than, warfarin and entail a lower risk of bleeding in the brain. An advantage of the new drugs is that they do not require frequent blood testing as warfarin does. The guideline also recommends new anticoagulants for the elderly, people with mild dementia, and people at moderate risk of falls.

Giving patients medications to lower blood pressure during the first 48 hours after a stroke may not reduce the likelihood of death or major disability, according to research published February 5 in JAMA. Within 48 hours of onset, 4,071 patients with nonthrombolysed ischemic stroke and elevated systolic blood pressure were randomized to receive antihypertensive treatment or to discontinuation of antihypertensive medications. Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg in the control group within 24 hours after randomization. At 14 days or hospital discharge, researchers recorded 683 incidences of death or major disability in the antihypertensive treatment group and 681 incidences in the control group.

The FDA has granted accelerated approval for Northera (droxidopa) capsules for the treatment of neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (eg, Parkinson’s disease or multiple system atrophy). Accelerated approval is granted to medicines that fill a serious unmet medical need. The capsules have a boxed warning to alert health care professionals and patients about the risk of supine hypertension, which can cause stroke. Two clinical trials involving people with NOH demonstrated droxidopa’s effectiveness over a period of two weeks. The drug, which is manufactured by Chelsea Therapeutics in Charlotte, North Carolina, has not been demonstrated to provide improvement in patient symptoms beyond two weeks. The most common adverse events reported by clinical trial participants taking droxidopa were headache, dizziness, nausea, high blood pressure, and fatigue.

Earlier treatment with an antiepileptic drug (AED) results in a shorter total seizure duration among children with febrile status epilepticus, according to a study published online ahead of print February 6 in Epilepsia. A total of 199 children (ages 1 month to 6 years), were included in the prospective, multicenter study. The median time from seizure onset to first administration of an AED by EMS or emergency department personnel was 30 minutes. The mean seizure duration for children who were given medication before admission to the emergency department was 81 minutes, compared with 95 minutes for those who were not treated beforehand. The median time from first dose of an AED to the end of a seizure was 38 minutes. “Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration,” the investigators concluded.

The FDA has granted 510(k) clearance to the Reveal LINQ Insertable Cardiac Monitor (ICM) System. The device is indicated for patients who have symptoms such as dizziness, palpitation, syncope, and chest pain that may suggest a cardiac arrhythmia, and for patients at increased risk for cardiac arrhythmias. The Reveal LINQ ICM is part of a system that allows physicians to monitor a patient’s heart continuously and wirelessly for as long as three years. The system also provides remote monitoring through the Carelink Network, which allows physicians to request notifications to alert them if their patients have had cardiac events. The Reveal LINQ ICM is approximately one-third the size of an AAA battery. The device is manufactured by Medtronic, which is headquartered in Minneapolis.

The final stage of the normal inflammatory process may be disrupted in patients with Alzheimer’s disease, according to research published online ahead of print February 14 in Alzheimer’s and Dementia. Researchers analyzed specialized proresolving mediators (SPMs), receptors, a biosynthetic enzyme, and downstream effectors involved in inflammation resolution in postmortem hippocampal tissue from patients with and without Alzheimer’s disease. SPMs were analyzed in CSF. Levels of the SPM lipoxin A₄ (LXA₄) were reduced in patients with Alzheimer’s disease in the CSF and the hippocampus. An enzyme involved in LXA4 synthesis and two SPM receptors were elevated in brains of patients with Alzheimer’s disease. LXA₄ and RvD1 levels in CSF correlated with Mini-Mental State Examination scores. Stimulation of inflammation resolution may reduce neuronal death in the brain, said the investigators.

Toxic chemicals may be triggering the recent increases in neurodevelopmental disabilities among children, according to a study published in the March issue of Lancet Neurology. In 2006, researchers identified five industrial chemicals as developmental neurotoxicants. The current study offers updated findings about those chemicals and adds information on six newly recognized ones, including manganese, fluoride, chlorpyrifos and DDT (ie, pesticides), tetrachloroethylene (a solvent), and the polybrominated diphenyl ethers (flame retardants). The study found that manganese is associated with diminished intellectual function and impaired motor skills, solvents are linked to hyperactivity and aggressive behavior, and certain pesticides may cause cognitive delays. More neurotoxicants may remain undiscovered, according to the investigators, who propose a global prevention strategy to control what they call a pandemic of developmental neurotoxicity.

For relatives of patients with multiple sclerosis (MS), the risk of developing the disease may be lower than previously assumed, according to a study published in the March issue of Brain. Researchers from Karolinska Institutet assessed the familial risks for MS using population registers and health care registries. They identified 28,396 patients with MS, along with first- and second-degree relatives and cousins. The investigators used matched population-based controls to calculate relative risks and found lower estimates of familial MS risks than previously reported. Despite a well-established lower prevalence of MS among males, the relative risks were equal among maternal and paternal relations. Using 74,757 twin pairs, the researchers estimated the disease’s heritability to be 0.64 and its shared environmental component to be 0.01.

Football helmets differ in their ability to reduce the risk of concussion, researchers reported online ahead of print January 31 in the Journal of Neurosurgery. The investigators conducted a retrospective analysis of head impact data from 1,833 collegiate football players from 2005 to 2010 who wore helmet-mounted accelerometer arrays for games and practices. The researchers compared concussion rates between players who wore the Riddell VSR4 and Riddell Revolution helmets. A total of 1,281,444 head impacts were recorded, and 64 concussions were diagnosed. The investigators found that the relative risk of sustaining a concussion in a Revolution helmet versus a VSR4 helmet was 46.1%. “Although helmet design may never prevent all concussions from occurring in football, evidence illustrates that it can reduce the incidence of this injury,” the researchers concluded.

Women have a worse quality of life, compared with men, for as long as 12 months after a stroke, even after adjustment for key sociodemographic variables, stroke severity, and disability, according to a study published online ahead of print February 7 in Neurology. Researchers assessed the quality of life in 1,370 patients (53.7% male; median age, 65) with ischemic stroke or transient ischemic attack (TIA) at three and 12 months postdischarge. Women had a significantly lower quality of life at three and 12 months poststroke. After multivariable adjustment for sociodemographic, clinical, and stroke-related factors, the investigators found that women continued to have a lower quality of life at three and 12 months. Women also had a poorer outcome in the dimensions of mobility, pain or discomfort, and anxiety or depression at three and 12 months.

High levels of high-density lipoprotein (HDL) cholesterol and low levels of low-density lipoprotein (LDL) cholesterol may be correlated with lower levels of amyloid plaque deposition in the brain, according to a study published in the February issue of JAMA Neurology. Investigators examined 74 individuals age 70 or older, including three participants with mild dementia, 33 cognitively normal participants, and 38 people with mild cognitive impairment. Cerebral amyloid-beta was measured with carbon C11–labeled Pittsburgh Compound B (PiB) PET. Statistical models that controlled for age and APOE ɛ4 revealed independent associations among the levels of LDL cholesterol, HDL cholesterol, and PiB index. Higher LDL cholesterol and lower HDL cholesterol levels were associated with a higher PiB index. The finding suggests an important role for cholesterol in amyloid-beta processing, said the researchers.

Patients with acute ischemic stroke who receive prompt treatment with t-PA may avoid a lengthy stay in an ICU, according to a study published February 12 in PLOS One. In a retrospective chart review of 153 patients who received IV t-PA for stroke, those with an NIH Stroke Scale (NIHSS) score of 10 or higher had a 7.7-times higher risk of requiring ICU resources, compared with patients who presented with an NIHSS score lower than 10. Eighty-one percent of patients with ICU needs developed them before the end of t-PA infusion, while 7% of those without ICU needs at the end of the t-PA infusion required ICU care later on. “We propose that patients without ICU needs by the end of the t-PA infusion might be safely monitored in a non-ICU setting if NIHSS at presentation is low,” the researchers advised.

—Erik Greb and Colby Stong

Alcohol consumption may reduce the risk of developing multiple sclerosis (MS) and attenuate the effect of smoking, according to research published online ahead of print January 6 in JAMA Neurology. Scientists examined data from the Epidemiological Investigation of MS (EIMS), which included 745 cases and 1,761 controls, and from the Genes and Environment in MS (GEMS) study, which recruited 5,874 cases and 5,246 controls. In EIMS, women who reported high alcohol consumption (>112 g/week) had an odds ratio (OR) of 0.6 of developing MS, compared with nondrinking women. Men with high alcohol consumption (>168 g/week) in EIMS had an OR of 0.5, compared with nondrinking men. The OR for the comparison in GEMS was 0.7 for women and 0.7 for men. In both studies, the detrimental effect of smoking was more pronounced among nondrinkers.

A lentiviral vector-based gene therapy may be safe and improve motor behavior in patients with Parkinson’s disease, according to a study published online ahead of print January 10 in Lancet. In a phase I–II open-label trial, 15 patients received bilateral injections of gene therapy into the putamen and were followed up for 12 months. Participants received a low dose (1.9 × 107 transducing units [TU]), medium dose (4.0 × 107 TU), or a high dose (1 × 108 TU) of gene therapy. Patients reported 51 mild adverse events, three moderate adverse events, and no serious adverse events. The investigators noted a significant improvement in mean Unified Parkinson’s Disease Rating Scale part III motor scores off medication in all patients at six months, compared with baseline.

The FDA has approved a three-times-per-week formulation of Copaxone 40 mg/mL. The new formulation will enable a less-frequent dosing regimen to be administered subcutaneously to patients with relapsing forms of multiple sclerosis (MS). The approval is based on data from the Phase III Glatiramer Acetate Low-Frequency Administration study of more than 1,400 patients. In the trial, investigators found that a 40-mg/mL dose of Copaxone administered subcutaneously three times per week significantly reduced relapse rates at 12 months and demonstrated a favorable safety and tolerability profile in patients with relapsing-remitting MS. In addition to the newly approved dose, daily Copaxone 20 mg/mL will continue to be available. The daily subcutaneous injection was approved in 1996. Both formulations are manufactured by Teva Pharmaceutical Industries, which is headquartered in Jerusalem.

When administered with amitriptyline, cognitive behavioral therapy (CBT) may result in greater reductions in days with headache and in migraine-related disability among young persons with chronic migraine, compared with headache education, according to research published December 25, 2013, in JAMA. In a randomized clinical trial, 135 children (ages 10 to 17) with chronic migraine and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to CBT plus amitriptyline or headache education plus amitriptyline. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group, compared with 6.8 for the headache education plus amitriptyline group. The PedMIDAS decreased by 52.7 points for the CBT group and by 38.6 points for the headache education group.

Low levels of vitamin D early in the course of multiple sclerosis (MS) are a strong risk factor for long-term disease activity and progression in patients who were primarily treated with interferon beta-1b, according to a study published online January 20 in JAMA Neurology. Researchers compared early and delayed interferon beta-1b treatment in 468 patients with clinically isolated syndrome, measuring serum levels of 25-hydroxyvitamin D (25[OH]D) at baseline and at six, 12, and 24 months. “A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions, 57% lower relapse rate, 25% lower yearly increase in T2 lesion volume, and 0.41% lower yearly loss in brain volume from months 12 to 60,” stated the study authors.

Excessive alcohol consumption in men was associated with faster cognitive decline, compared with light to moderate alcohol consumption, researchers reported online ahead of print January 15 in Neurology. The findings are based on data from 5,054 men and 2,099 women (mean age, 56) who had their alcohol consumption analyzed three times in the 10 years preceding the first cognitive assessment. In men, the investigators observed no differences in cognitive decline among alcohol abstainers, those who quit using alcohol, and light or moderate alcohol drinkers (<20 g/day). Alcohol consumption ≥36 g/day was associated with faster decline in all cognitive domains, compared with consumption between 0.1 and 19.9 g/day. In women, 10-year abstainers had a faster decline in the global cognitive score and executive function, compared with those drinking between 0.1 and 9.9 g/day of alcohol.

Vitamin D supplements may reduce pain in patients with fibromyalgia syndrome, according to a study in the February issue of Pain. The randomized controlled trial enrolled 30 women with fibromyalgia syndrome with serum calcifediol levels <32 ng/mL (80 nmol/L), in whom the goal was to achieve serum calcifediol levels between 32 and 48 ng/mL for 20 weeks with an oral cholecalciferol supplement. Re-evaluation was performed in both groups after an additional 24 weeks without cholecalciferol supplementation. The researchers observed a marked reduction in pain during the treatment period in those who received the supplement, and optimization of calcifediol levels had a positive effect on the perception of pain. “This economical therapy with a low side effect profile may well be considered in patients with fibromyalgia syndrome,” the researchers concluded.

A simple on-field blood test may help diagnose sports concussion. Relative and absolute increases in the astroglial protein, serum S100B, can accurately distinguish sports-related concussion from sports-related exertion, according to a study published online January 8 in PLOS One. Serum S100B was measured in 46 collegiate and semiprofessional contact sport athletes at preseason baseline, within three hours of injury, and at days 2, 3, and 7 post–sports-related concussion. Twenty-two athletes had a sports-related concussion, and 17 had S100B testing within three hours postinjury. The mean three-hour post–sports-related concussion S100B level was significantly higher than at preseason baseline, while the mean postexertion S100B level was not significantly different than that from the preseason baseline. S100B levels at postinjury days 2, 3, and 7 were significantly lower than at the three-hour level and were not different than at baseline.

Herpes zoster is an independent risk factor for vascular disease, particularly for stroke, transient ischemic attack, and myocardial infarction, in patients affected before age 40, researchers reported online ahead of print January 2 in Neurology. The findings are based on a retrospective cohort of 106,601 cases of herpes zoster and 213,202 controls from a general practice database in the United Kingdom. The investigators found that risk factors for vascular disease were significantly increased in patients with herpes zoster compared with controls. In addition, adjusted hazard ratios for TIA and myocardial infarction, but not stroke, were increased in all patients with herpes zoster. Stroke, TIA, and myocardial infarction were increased in cases in which herpes zoster occurred when the participants were younger than 40.

A study appearing January 22 online in Neurology found that a higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured eight years later. Researchers assessed RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes in 1,111 postmenopausal women from the Women’s Health Initiative Memory Study. In fully adjusted models, a 1-SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm3 larger brain volume. “DHA was marginally correlated with total brain volume while EPA was less so,” reported the investigators. In fully adjusted models, a 1-SD greater omega-3 index was correlated with greater hippocampal volume. “While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy,” wrote the investigators.

Exposure to DDT may increase the risk of developing Alzheimer’s disease, particularly in people older than 60, according to a study published online ahead of print January 27 in JAMA Neurology. Researchers examined the level of DDE, the chemical compound produced when DDT breaks down in the body, in the blood of 86 patients with Alzheimer’s disease and 79 controls. Blood levels of DDE were almost four times higher in 74 of the patients with Alzheimer’s disease than in the controls. Patients with APOE4, which greatly increases the risk of developing Alzheimer’s disease, and high blood levels of DDE exhibited more severe cognitive impairment than patients without the gene. In addition, DDT and DDE apparently increased the amount of a protein associated with plaques believed to be a hallmark of Alzheimer’s disease.

Mortality is higher among patients with multiple sclerosis (MS) than among Americans without the disease, according to research published online ahead of print December 26, 2013, in Multiple Sclerosis and Related Disorders. Investigators extracted records from a US commercial health insurance database—the OptumInsight Research database—for 30,402 patients with MS and 89,818 healthy comparators. Patient data were recorded from 1996 to 2009. Annual mortality rates were 899/100,000 among patients with MS and 446/100,000 among comparators. Standardized mortality ratio was 1.70 for patients with MS and 0.80 for the general US population. Kaplan–Meier analysis yielded a median survival from birth that was six years lower among patients with MS than among comparators. The six-year decrement in lifespan is consistent with a decrement found in recent research conducted in Canada, said the investigators.

Chronic obstructive pulmonary disease (COPD) may increase the risk of mild cognitive impairment (MCI), researchers reported in the November 2013 issue of Mayo Clinic Proceedings. The investigators evaluated 1,927 patients (ages 70 to 89) enrolled in the population-based Mayo Clinic Study of Aging. Participants received a nurse assessment, neurologic evaluation, and neuropsychologic testing. A consensus panel diagnosed MCI according to standardized criteria. COPD was identified by the review of medical records. A total of 288 patients had COPD. Prevalence of MCI was 27% among patients with COPD and 15% among patients without COPD. The odds ratio for MCI was 1.60 in patients who had had COPD for five years or fewer and 2.10 in patients who had had COPD for more than five years.

—Erik Greb and Colby Stong

Alcohol consumption may reduce the risk of developing multiple sclerosis (MS) and attenuate the effect of smoking, according to research published online ahead of print January 6 in JAMA Neurology. Scientists examined data from the Epidemiological Investigation of MS (EIMS), which included 745 cases and 1,761 controls, and from the Genes and Environment in MS (GEMS) study, which recruited 5,874 cases and 5,246 controls. In EIMS, women who reported high alcohol consumption (>112 g/week) had an odds ratio (OR) of 0.6 of developing MS, compared with nondrinking women. Men with high alcohol consumption (>168 g/week) in EIMS had an OR of 0.5, compared with nondrinking men. The OR for the comparison in GEMS was 0.7 for women and 0.7 for men. In both studies, the detrimental effect of smoking was more pronounced among nondrinkers.

A lentiviral vector-based gene therapy may be safe and improve motor behavior in patients with Parkinson’s disease, according to a study published online ahead of print January 10 in Lancet. In a phase I–II open-label trial, 15 patients received bilateral injections of gene therapy into the putamen and were followed up for 12 months. Participants received a low dose (1.9 × 107 transducing units [TU]), medium dose (4.0 × 107 TU), or a high dose (1 × 108 TU) of gene therapy. Patients reported 51 mild adverse events, three moderate adverse events, and no serious adverse events. The investigators noted a significant improvement in mean Unified Parkinson’s Disease Rating Scale part III motor scores off medication in all patients at six months, compared with baseline.

The FDA has approved a three-times-per-week formulation of Copaxone 40 mg/mL. The new formulation will enable a less-frequent dosing regimen to be administered subcutaneously to patients with relapsing forms of multiple sclerosis (MS). The approval is based on data from the Phase III Glatiramer Acetate Low-Frequency Administration study of more than 1,400 patients. In the trial, investigators found that a 40-mg/mL dose of Copaxone administered subcutaneously three times per week significantly reduced relapse rates at 12 months and demonstrated a favorable safety and tolerability profile in patients with relapsing-remitting MS. In addition to the newly approved dose, daily Copaxone 20 mg/mL will continue to be available. The daily subcutaneous injection was approved in 1996. Both formulations are manufactured by Teva Pharmaceutical Industries, which is headquartered in Jerusalem.

When administered with amitriptyline, cognitive behavioral therapy (CBT) may result in greater reductions in days with headache and in migraine-related disability among young persons with chronic migraine, compared with headache education, according to research published December 25, 2013, in JAMA. In a randomized clinical trial, 135 children (ages 10 to 17) with chronic migraine and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to CBT plus amitriptyline or headache education plus amitriptyline. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group, compared with 6.8 for the headache education plus amitriptyline group. The PedMIDAS decreased by 52.7 points for the CBT group and by 38.6 points for the headache education group.

Low levels of vitamin D early in the course of multiple sclerosis (MS) are a strong risk factor for long-term disease activity and progression in patients who were primarily treated with interferon beta-1b, according to a study published online January 20 in JAMA Neurology. Researchers compared early and delayed interferon beta-1b treatment in 468 patients with clinically isolated syndrome, measuring serum levels of 25-hydroxyvitamin D (25[OH]D) at baseline and at six, 12, and 24 months. “A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions, 57% lower relapse rate, 25% lower yearly increase in T2 lesion volume, and 0.41% lower yearly loss in brain volume from months 12 to 60,” stated the study authors.

Excessive alcohol consumption in men was associated with faster cognitive decline, compared with light to moderate alcohol consumption, researchers reported online ahead of print January 15 in Neurology. The findings are based on data from 5,054 men and 2,099 women (mean age, 56) who had their alcohol consumption analyzed three times in the 10 years preceding the first cognitive assessment. In men, the investigators observed no differences in cognitive decline among alcohol abstainers, those who quit using alcohol, and light or moderate alcohol drinkers (<20 g/day). Alcohol consumption ≥36 g/day was associated with faster decline in all cognitive domains, compared with consumption between 0.1 and 19.9 g/day. In women, 10-year abstainers had a faster decline in the global cognitive score and executive function, compared with those drinking between 0.1 and 9.9 g/day of alcohol.

Vitamin D supplements may reduce pain in patients with fibromyalgia syndrome, according to a study in the February issue of Pain. The randomized controlled trial enrolled 30 women with fibromyalgia syndrome with serum calcifediol levels <32 ng/mL (80 nmol/L), in whom the goal was to achieve serum calcifediol levels between 32 and 48 ng/mL for 20 weeks with an oral cholecalciferol supplement. Re-evaluation was performed in both groups after an additional 24 weeks without cholecalciferol supplementation. The researchers observed a marked reduction in pain during the treatment period in those who received the supplement, and optimization of calcifediol levels had a positive effect on the perception of pain. “This economical therapy with a low side effect profile may well be considered in patients with fibromyalgia syndrome,” the researchers concluded.

A simple on-field blood test may help diagnose sports concussion. Relative and absolute increases in the astroglial protein, serum S100B, can accurately distinguish sports-related concussion from sports-related exertion, according to a study published online January 8 in PLOS One. Serum S100B was measured in 46 collegiate and semiprofessional contact sport athletes at preseason baseline, within three hours of injury, and at days 2, 3, and 7 post–sports-related concussion. Twenty-two athletes had a sports-related concussion, and 17 had S100B testing within three hours postinjury. The mean three-hour post–sports-related concussion S100B level was significantly higher than at preseason baseline, while the mean postexertion S100B level was not significantly different than that from the preseason baseline. S100B levels at postinjury days 2, 3, and 7 were significantly lower than at the three-hour level and were not different than at baseline.

Herpes zoster is an independent risk factor for vascular disease, particularly for stroke, transient ischemic attack, and myocardial infarction, in patients affected before age 40, researchers reported online ahead of print January 2 in Neurology. The findings are based on a retrospective cohort of 106,601 cases of herpes zoster and 213,202 controls from a general practice database in the United Kingdom. The investigators found that risk factors for vascular disease were significantly increased in patients with herpes zoster compared with controls. In addition, adjusted hazard ratios for TIA and myocardial infarction, but not stroke, were increased in all patients with herpes zoster. Stroke, TIA, and myocardial infarction were increased in cases in which herpes zoster occurred when the participants were younger than 40.

A study appearing January 22 online in Neurology found that a higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured eight years later. Researchers assessed RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes in 1,111 postmenopausal women from the Women’s Health Initiative Memory Study. In fully adjusted models, a 1-SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm3 larger brain volume. “DHA was marginally correlated with total brain volume while EPA was less so,” reported the investigators. In fully adjusted models, a 1-SD greater omega-3 index was correlated with greater hippocampal volume. “While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy,” wrote the investigators.

Exposure to DDT may increase the risk of developing Alzheimer’s disease, particularly in people older than 60, according to a study published online ahead of print January 27 in JAMA Neurology. Researchers examined the level of DDE, the chemical compound produced when DDT breaks down in the body, in the blood of 86 patients with Alzheimer’s disease and 79 controls. Blood levels of DDE were almost four times higher in 74 of the patients with Alzheimer’s disease than in the controls. Patients with APOE4, which greatly increases the risk of developing Alzheimer’s disease, and high blood levels of DDE exhibited more severe cognitive impairment than patients without the gene. In addition, DDT and DDE apparently increased the amount of a protein associated with plaques believed to be a hallmark of Alzheimer’s disease.

Mortality is higher among patients with multiple sclerosis (MS) than among Americans without the disease, according to research published online ahead of print December 26, 2013, in Multiple Sclerosis and Related Disorders. Investigators extracted records from a US commercial health insurance database—the OptumInsight Research database—for 30,402 patients with MS and 89,818 healthy comparators. Patient data were recorded from 1996 to 2009. Annual mortality rates were 899/100,000 among patients with MS and 446/100,000 among comparators. Standardized mortality ratio was 1.70 for patients with MS and 0.80 for the general US population. Kaplan–Meier analysis yielded a median survival from birth that was six years lower among patients with MS than among comparators. The six-year decrement in lifespan is consistent with a decrement found in recent research conducted in Canada, said the investigators.

Chronic obstructive pulmonary disease (COPD) may increase the risk of mild cognitive impairment (MCI), researchers reported in the November 2013 issue of Mayo Clinic Proceedings. The investigators evaluated 1,927 patients (ages 70 to 89) enrolled in the population-based Mayo Clinic Study of Aging. Participants received a nurse assessment, neurologic evaluation, and neuropsychologic testing. A consensus panel diagnosed MCI according to standardized criteria. COPD was identified by the review of medical records. A total of 288 patients had COPD. Prevalence of MCI was 27% among patients with COPD and 15% among patients without COPD. The odds ratio for MCI was 1.60 in patients who had had COPD for five years or fewer and 2.10 in patients who had had COPD for more than five years.

—Erik Greb and Colby Stong

Alcohol consumption may reduce the risk of developing multiple sclerosis (MS) and attenuate the effect of smoking, according to research published online ahead of print January 6 in JAMA Neurology. Scientists examined data from the Epidemiological Investigation of MS (EIMS), which included 745 cases and 1,761 controls, and from the Genes and Environment in MS (GEMS) study, which recruited 5,874 cases and 5,246 controls. In EIMS, women who reported high alcohol consumption (>112 g/week) had an odds ratio (OR) of 0.6 of developing MS, compared with nondrinking women. Men with high alcohol consumption (>168 g/week) in EIMS had an OR of 0.5, compared with nondrinking men. The OR for the comparison in GEMS was 0.7 for women and 0.7 for men. In both studies, the detrimental effect of smoking was more pronounced among nondrinkers.

A lentiviral vector-based gene therapy may be safe and improve motor behavior in patients with Parkinson’s disease, according to a study published online ahead of print January 10 in Lancet. In a phase I–II open-label trial, 15 patients received bilateral injections of gene therapy into the putamen and were followed up for 12 months. Participants received a low dose (1.9 × 107 transducing units [TU]), medium dose (4.0 × 107 TU), or a high dose (1 × 108 TU) of gene therapy. Patients reported 51 mild adverse events, three moderate adverse events, and no serious adverse events. The investigators noted a significant improvement in mean Unified Parkinson’s Disease Rating Scale part III motor scores off medication in all patients at six months, compared with baseline.

The FDA has approved a three-times-per-week formulation of Copaxone 40 mg/mL. The new formulation will enable a less-frequent dosing regimen to be administered subcutaneously to patients with relapsing forms of multiple sclerosis (MS). The approval is based on data from the Phase III Glatiramer Acetate Low-Frequency Administration study of more than 1,400 patients. In the trial, investigators found that a 40-mg/mL dose of Copaxone administered subcutaneously three times per week significantly reduced relapse rates at 12 months and demonstrated a favorable safety and tolerability profile in patients with relapsing-remitting MS. In addition to the newly approved dose, daily Copaxone 20 mg/mL will continue to be available. The daily subcutaneous injection was approved in 1996. Both formulations are manufactured by Teva Pharmaceutical Industries, which is headquartered in Jerusalem.

When administered with amitriptyline, cognitive behavioral therapy (CBT) may result in greater reductions in days with headache and in migraine-related disability among young persons with chronic migraine, compared with headache education, according to research published December 25, 2013, in JAMA. In a randomized clinical trial, 135 children (ages 10 to 17) with chronic migraine and a Pediatric Migraine Disability Assessment Score (PedMIDAS) greater than 20 points were assigned to CBT plus amitriptyline or headache education plus amitriptyline. At the 20-week end point, days with headache were reduced by 11.5 for the CBT plus amitriptyline group, compared with 6.8 for the headache education plus amitriptyline group. The PedMIDAS decreased by 52.7 points for the CBT group and by 38.6 points for the headache education group.

Low levels of vitamin D early in the course of multiple sclerosis (MS) are a strong risk factor for long-term disease activity and progression in patients who were primarily treated with interferon beta-1b, according to a study published online January 20 in JAMA Neurology. Researchers compared early and delayed interferon beta-1b treatment in 468 patients with clinically isolated syndrome, measuring serum levels of 25-hydroxyvitamin D (25[OH]D) at baseline and at six, 12, and 24 months. “A 50-nmol/L (20-ng/mL) increment in average serum 25(OH)D levels within the first 12 months predicted a 57% lower rate of new active lesions, 57% lower relapse rate, 25% lower yearly increase in T2 lesion volume, and 0.41% lower yearly loss in brain volume from months 12 to 60,” stated the study authors.

Excessive alcohol consumption in men was associated with faster cognitive decline, compared with light to moderate alcohol consumption, researchers reported online ahead of print January 15 in Neurology. The findings are based on data from 5,054 men and 2,099 women (mean age, 56) who had their alcohol consumption analyzed three times in the 10 years preceding the first cognitive assessment. In men, the investigators observed no differences in cognitive decline among alcohol abstainers, those who quit using alcohol, and light or moderate alcohol drinkers (<20 g/day). Alcohol consumption ≥36 g/day was associated with faster decline in all cognitive domains, compared with consumption between 0.1 and 19.9 g/day. In women, 10-year abstainers had a faster decline in the global cognitive score and executive function, compared with those drinking between 0.1 and 9.9 g/day of alcohol.

Vitamin D supplements may reduce pain in patients with fibromyalgia syndrome, according to a study in the February issue of Pain. The randomized controlled trial enrolled 30 women with fibromyalgia syndrome with serum calcifediol levels <32 ng/mL (80 nmol/L), in whom the goal was to achieve serum calcifediol levels between 32 and 48 ng/mL for 20 weeks with an oral cholecalciferol supplement. Re-evaluation was performed in both groups after an additional 24 weeks without cholecalciferol supplementation. The researchers observed a marked reduction in pain during the treatment period in those who received the supplement, and optimization of calcifediol levels had a positive effect on the perception of pain. “This economical therapy with a low side effect profile may well be considered in patients with fibromyalgia syndrome,” the researchers concluded.

A simple on-field blood test may help diagnose sports concussion. Relative and absolute increases in the astroglial protein, serum S100B, can accurately distinguish sports-related concussion from sports-related exertion, according to a study published online January 8 in PLOS One. Serum S100B was measured in 46 collegiate and semiprofessional contact sport athletes at preseason baseline, within three hours of injury, and at days 2, 3, and 7 post–sports-related concussion. Twenty-two athletes had a sports-related concussion, and 17 had S100B testing within three hours postinjury. The mean three-hour post–sports-related concussion S100B level was significantly higher than at preseason baseline, while the mean postexertion S100B level was not significantly different than that from the preseason baseline. S100B levels at postinjury days 2, 3, and 7 were significantly lower than at the three-hour level and were not different than at baseline.

Herpes zoster is an independent risk factor for vascular disease, particularly for stroke, transient ischemic attack, and myocardial infarction, in patients affected before age 40, researchers reported online ahead of print January 2 in Neurology. The findings are based on a retrospective cohort of 106,601 cases of herpes zoster and 213,202 controls from a general practice database in the United Kingdom. The investigators found that risk factors for vascular disease were significantly increased in patients with herpes zoster compared with controls. In addition, adjusted hazard ratios for TIA and myocardial infarction, but not stroke, were increased in all patients with herpes zoster. Stroke, TIA, and myocardial infarction were increased in cases in which herpes zoster occurred when the participants were younger than 40.

A study appearing January 22 online in Neurology found that a higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured eight years later. Researchers assessed RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes in 1,111 postmenopausal women from the Women’s Health Initiative Memory Study. In fully adjusted models, a 1-SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm3 larger brain volume. “DHA was marginally correlated with total brain volume while EPA was less so,” reported the investigators. In fully adjusted models, a 1-SD greater omega-3 index was correlated with greater hippocampal volume. “While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy,” wrote the investigators.

Exposure to DDT may increase the risk of developing Alzheimer’s disease, particularly in people older than 60, according to a study published online ahead of print January 27 in JAMA Neurology. Researchers examined the level of DDE, the chemical compound produced when DDT breaks down in the body, in the blood of 86 patients with Alzheimer’s disease and 79 controls. Blood levels of DDE were almost four times higher in 74 of the patients with Alzheimer’s disease than in the controls. Patients with APOE4, which greatly increases the risk of developing Alzheimer’s disease, and high blood levels of DDE exhibited more severe cognitive impairment than patients without the gene. In addition, DDT and DDE apparently increased the amount of a protein associated with plaques believed to be a hallmark of Alzheimer’s disease.

Mortality is higher among patients with multiple sclerosis (MS) than among Americans without the disease, according to research published online ahead of print December 26, 2013, in Multiple Sclerosis and Related Disorders. Investigators extracted records from a US commercial health insurance database—the OptumInsight Research database—for 30,402 patients with MS and 89,818 healthy comparators. Patient data were recorded from 1996 to 2009. Annual mortality rates were 899/100,000 among patients with MS and 446/100,000 among comparators. Standardized mortality ratio was 1.70 for patients with MS and 0.80 for the general US population. Kaplan–Meier analysis yielded a median survival from birth that was six years lower among patients with MS than among comparators. The six-year decrement in lifespan is consistent with a decrement found in recent research conducted in Canada, said the investigators.

Chronic obstructive pulmonary disease (COPD) may increase the risk of mild cognitive impairment (MCI), researchers reported in the November 2013 issue of Mayo Clinic Proceedings. The investigators evaluated 1,927 patients (ages 70 to 89) enrolled in the population-based Mayo Clinic Study of Aging. Participants received a nurse assessment, neurologic evaluation, and neuropsychologic testing. A consensus panel diagnosed MCI according to standardized criteria. COPD was identified by the review of medical records. A total of 288 patients had COPD. Prevalence of MCI was 27% among patients with COPD and 15% among patients without COPD. The odds ratio for MCI was 1.60 in patients who had had COPD for five years or fewer and 2.10 in patients who had had COPD for more than five years.

—Erik Greb and Colby Stong

The Bacille Calmette-Guérin (BCG) vaccine may benefit patients with clinically isolated syndrome (CIS), according to research published online ahead of print December 4, 2013, in Neurology. A total of 82 participants with CIS were randomized to BCG or placebo and monitored monthly with brain MRI for six months. All patients subsequently received IM interferon β-1a for 12 months. In an open-label extension phase, patients received disease-modifying therapies (DMTs) recommended by their neurologists. During the initial six months, the number of cumulative lesions was significantly lower among vaccinated subjects. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18. After 60 months, the probability of clinically definite multiple sclerosis was lower in the BCG plus DMT arm, and more vaccinated people remained DMT-free.

Exercise programs may significantly improve the ability of people with dementia to perform activities of daily living, according to a study published online ahead of print December 4, 2013, in the Cochrane Library. Exercise also may improve cognition in these patients, but may not affect depression. Investigators reviewed randomized controlled trials in which older people diagnosed with dementia were allocated to exercise programs or to control groups, which received standard care or social contact. Sixteen trials with 937 participants met the inclusion criteria. The trials were highly heterogeneous in terms of subtype and severity of participants’ dementia, and type, duration, and frequency of exercise. The researchers found that informal caregivers’ burden may be reduced when the family member with dementia participates in an exercise program.

Thrombin activity may enable neurologists to detect multiple sclerosis (MS) before clinical signs of the disease are present, according to research published online ahead of print November 29, 2013, in Annals of Neurology. Using a novel molecular probe, investigators characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded the onset of neurologic signs; increased at disease peak; and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Scientists may be able to use thrombin activity to develop sensitive probes for the preclinical detection and monitoring of neuroinflammation and MS progression, according to the investigators.

An athlete with concussion symptoms should not be allowed to return to play on the same day, according to the latest consensus statement on sports-related concussion, which was summarized in the December 2013 issue of Neurosurgery. The Concussion in Sport Group (CISG 4) based its recommendations on the advice of an expert panel that was sponsored by five international sports governing bodies. Between 80% and 90% of concussions resolve within seven to 10 days, but recovery may take longer in children and adolescents, according to the consensus statement. The updated statement emphasizes the distinction between concussion and mild traumatic brain injury. The CISG 4 suggests that patients with concussion have normal findings on brain neuroimaging studies (eg, CT scan), but those with traumatic brain injury have abnormal imaging findings.

Vitamin D may prevent multiple sclerosis (MS) by blocking T helper (T_H) cells from migrating into the CNS, according to research published online ahead of print December 9, 2013, in Proceedings of the National Academy of Sciences. Investigators administered 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃], the bioactive form of vitamin D, to animals with experimental autoimmune encephalomyelitis, a mouse model of MS. Myelin-reactive T_H cells were generated in the presence of 1,25(OH)₂D₃, secreted proinflammatory cytokines, and did not preferentially differentiate into suppressor T cells. The cells left the lymph node, entered the peripheral circulation, and migrated to the immunization sites. T_H cells from 1,25(OH)₂D₃-treated mice were unable to enter the CNS parenchyma, however. Instead, the cells were maintained in the periphery. The mice developed experimental autoimmune encephalomyelitis when treatment ceased.

Among people with type 2 diabetes, dementia incidence may be highest among Native Americans and African Americans and lowest among Asians, according to a study published online ahead of print November 22, 2013, in Diabetes Care. Scientists identified 22,171 patients age 60 or older with diabetes and without preexisting dementia in the Kaiser Permanente Northern California Diabetes Registry. The investigators abstracted prevalent medical history and dementia incidence from medical records and calculated age-adjusted incidence densities. Dementia was diagnosed in 17.1% of patients. Age-adjusted dementia incidence densities were 34/1,000 person-years among Native Americans, 27/1,000 person-years among African Americans, and 19/1,000 person-years among Asians. Hazard ratios (relative to Asians) were 1.64 for Native Americans, 1.44 for African Americans, 1.30 for non-Hispanic whites, and 1.19 for Latinos.

Veterans with blast injuries have changes in brain tissue that may be apparent on imaging years later, according to data presented at the 99th Annual Meeting of the Radiological Society of North America. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with mild traumatic brain injury with those of 10 healthy controls. The average time elapsed between the blast-induced injury and DTI scan among the patients was 51.3 months. FA values were significantly different between the two groups, and the researchers found significant correlations between FA values and attention, delayed memory, and psychomotor test scores. The results suggest that blast injury may have a long-term impact on the brain.

Among college athletes, head impact exposure may be related to white matter diffusion measures and cognition during the course of one playing season, even in the absence of diagnosed concussion, according to data published online ahead of print December 11, 2013, in Neurology. Researchers prospectively studied 79 noncontact sport athletes and 80 nonconcussed varsity football and ice hockey players who wore helmets that recorded the acceleration-time history of the head following impact. Mean diffusivity (MD) in the corpus callosum was significantly different between groups. Measures of head impact exposure correlated with white matter diffusivity measures in the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.

Among veterans, traumatic brain injury (TBI) during the most recent deployment is the strongest predictor of postdeployment symptoms of post-traumatic stress disorder (PTSD), even when accounting for predeployment symptoms, prior TBI, and combat intensity, according to research published online ahead of print December 11, 2013, in JAMA Psychiatry. A total of 1,648 active-duty Marine and Navy servicemen underwent clinical interviews and completed self-assessments approximately one month before a seven-month deployment and three to six months after deployment. At the predeployment assessment, 56.8% of participants reported prior TBI. At postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments. Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. TBI doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.

Fidgetin inhibition could promote tissue regeneration and repair the broken cell connections that occur in spinal cord injury and other conditions, according to research presented at the 2013 Annual Meeting of the American Society for Cell Biology. Fidgetin prunes unstable microtubule scaffolding in cells, as well as unneeded connections in the neuronal network as the latter grows. Researchers used a novel nanoparticle technology to block fidgetin in the injured nerves of adult rats. The nanoparticles were infused with small interfering RNA that bound the messenger RNA (mRNA) transcribed from the fidgetin gene. The mRNA for fidgetin was not translated, and the cell did not produce fidgetin. Blocking fidgetin restarted tissue growth in the animals. The technique could benefit patients with myocardial infarction or chronic cutaneous wounds.

Deep brain stimulation may improve driving ability for people with Parkinson’s disease, according to a study published online ahead of print December 18, 2013, in Neurology. Investigators studied 23 people who had deep brain stimulators, 21 people with Parkinson’s disease without stimulators, and 21 healthy individuals. Participants were tested with a driving simulator. Individuals with stimulators completed the test once with the stimulator on, once with it off, and once with the stimulator off after receiving levodopa. People with Parkinson’s disease without stimulators performed worse than controls in almost every category. People with stimulators did not perform significantly worse than the controls. Participants with stimulators had an average of 3.8 slight driving errors on the test, compared with 7.5 for the controls and 11.4 for people with Parkinson’s disease without stimulators.

Gadolinium-based contrast medium (Gd-CM) may be associated with abnormalities on brain MRI, according to research published online ahead of print December 17, 2013, in Radiology. Researchers compared unenhanced T1-weighted MR images of 19 patients who had undergone six or more contrast-enhanced brain scans with images of 16 people who had received six or fewer unenhanced scans. The hyperintensity of the dentate nucleus and globus pallidus correlated with the number of Gd-CM administrations. Hyperintensity in the dentate nucleus and globus pallidus on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations, according to the researchers. Because gadolinium has a high signal intensity in the body, the data suggest that the toxic gadolinium component remains in the body in patients with normal renal function.

—Erik Greb

The Bacille Calmette-Guérin (BCG) vaccine may benefit patients with clinically isolated syndrome (CIS), according to research published online ahead of print December 4, 2013, in Neurology. A total of 82 participants with CIS were randomized to BCG or placebo and monitored monthly with brain MRI for six months. All patients subsequently received IM interferon β-1a for 12 months. In an open-label extension phase, patients received disease-modifying therapies (DMTs) recommended by their neurologists. During the initial six months, the number of cumulative lesions was significantly lower among vaccinated subjects. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18. After 60 months, the probability of clinically definite multiple sclerosis was lower in the BCG plus DMT arm, and more vaccinated people remained DMT-free.

Exercise programs may significantly improve the ability of people with dementia to perform activities of daily living, according to a study published online ahead of print December 4, 2013, in the Cochrane Library. Exercise also may improve cognition in these patients, but may not affect depression. Investigators reviewed randomized controlled trials in which older people diagnosed with dementia were allocated to exercise programs or to control groups, which received standard care or social contact. Sixteen trials with 937 participants met the inclusion criteria. The trials were highly heterogeneous in terms of subtype and severity of participants’ dementia, and type, duration, and frequency of exercise. The researchers found that informal caregivers’ burden may be reduced when the family member with dementia participates in an exercise program.

Thrombin activity may enable neurologists to detect multiple sclerosis (MS) before clinical signs of the disease are present, according to research published online ahead of print November 29, 2013, in Annals of Neurology. Using a novel molecular probe, investigators characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded the onset of neurologic signs; increased at disease peak; and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Scientists may be able to use thrombin activity to develop sensitive probes for the preclinical detection and monitoring of neuroinflammation and MS progression, according to the investigators.

An athlete with concussion symptoms should not be allowed to return to play on the same day, according to the latest consensus statement on sports-related concussion, which was summarized in the December 2013 issue of Neurosurgery. The Concussion in Sport Group (CISG 4) based its recommendations on the advice of an expert panel that was sponsored by five international sports governing bodies. Between 80% and 90% of concussions resolve within seven to 10 days, but recovery may take longer in children and adolescents, according to the consensus statement. The updated statement emphasizes the distinction between concussion and mild traumatic brain injury. The CISG 4 suggests that patients with concussion have normal findings on brain neuroimaging studies (eg, CT scan), but those with traumatic brain injury have abnormal imaging findings.

Vitamin D may prevent multiple sclerosis (MS) by blocking T helper (T_H) cells from migrating into the CNS, according to research published online ahead of print December 9, 2013, in Proceedings of the National Academy of Sciences. Investigators administered 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃], the bioactive form of vitamin D, to animals with experimental autoimmune encephalomyelitis, a mouse model of MS. Myelin-reactive T_H cells were generated in the presence of 1,25(OH)₂D₃, secreted proinflammatory cytokines, and did not preferentially differentiate into suppressor T cells. The cells left the lymph node, entered the peripheral circulation, and migrated to the immunization sites. T_H cells from 1,25(OH)₂D₃-treated mice were unable to enter the CNS parenchyma, however. Instead, the cells were maintained in the periphery. The mice developed experimental autoimmune encephalomyelitis when treatment ceased.

Among people with type 2 diabetes, dementia incidence may be highest among Native Americans and African Americans and lowest among Asians, according to a study published online ahead of print November 22, 2013, in Diabetes Care. Scientists identified 22,171 patients age 60 or older with diabetes and without preexisting dementia in the Kaiser Permanente Northern California Diabetes Registry. The investigators abstracted prevalent medical history and dementia incidence from medical records and calculated age-adjusted incidence densities. Dementia was diagnosed in 17.1% of patients. Age-adjusted dementia incidence densities were 34/1,000 person-years among Native Americans, 27/1,000 person-years among African Americans, and 19/1,000 person-years among Asians. Hazard ratios (relative to Asians) were 1.64 for Native Americans, 1.44 for African Americans, 1.30 for non-Hispanic whites, and 1.19 for Latinos.

Veterans with blast injuries have changes in brain tissue that may be apparent on imaging years later, according to data presented at the 99th Annual Meeting of the Radiological Society of North America. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with mild traumatic brain injury with those of 10 healthy controls. The average time elapsed between the blast-induced injury and DTI scan among the patients was 51.3 months. FA values were significantly different between the two groups, and the researchers found significant correlations between FA values and attention, delayed memory, and psychomotor test scores. The results suggest that blast injury may have a long-term impact on the brain.

Among college athletes, head impact exposure may be related to white matter diffusion measures and cognition during the course of one playing season, even in the absence of diagnosed concussion, according to data published online ahead of print December 11, 2013, in Neurology. Researchers prospectively studied 79 noncontact sport athletes and 80 nonconcussed varsity football and ice hockey players who wore helmets that recorded the acceleration-time history of the head following impact. Mean diffusivity (MD) in the corpus callosum was significantly different between groups. Measures of head impact exposure correlated with white matter diffusivity measures in the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.

Among veterans, traumatic brain injury (TBI) during the most recent deployment is the strongest predictor of postdeployment symptoms of post-traumatic stress disorder (PTSD), even when accounting for predeployment symptoms, prior TBI, and combat intensity, according to research published online ahead of print December 11, 2013, in JAMA Psychiatry. A total of 1,648 active-duty Marine and Navy servicemen underwent clinical interviews and completed self-assessments approximately one month before a seven-month deployment and three to six months after deployment. At the predeployment assessment, 56.8% of participants reported prior TBI. At postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments. Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. TBI doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.

Fidgetin inhibition could promote tissue regeneration and repair the broken cell connections that occur in spinal cord injury and other conditions, according to research presented at the 2013 Annual Meeting of the American Society for Cell Biology. Fidgetin prunes unstable microtubule scaffolding in cells, as well as unneeded connections in the neuronal network as the latter grows. Researchers used a novel nanoparticle technology to block fidgetin in the injured nerves of adult rats. The nanoparticles were infused with small interfering RNA that bound the messenger RNA (mRNA) transcribed from the fidgetin gene. The mRNA for fidgetin was not translated, and the cell did not produce fidgetin. Blocking fidgetin restarted tissue growth in the animals. The technique could benefit patients with myocardial infarction or chronic cutaneous wounds.

Deep brain stimulation may improve driving ability for people with Parkinson’s disease, according to a study published online ahead of print December 18, 2013, in Neurology. Investigators studied 23 people who had deep brain stimulators, 21 people with Parkinson’s disease without stimulators, and 21 healthy individuals. Participants were tested with a driving simulator. Individuals with stimulators completed the test once with the stimulator on, once with it off, and once with the stimulator off after receiving levodopa. People with Parkinson’s disease without stimulators performed worse than controls in almost every category. People with stimulators did not perform significantly worse than the controls. Participants with stimulators had an average of 3.8 slight driving errors on the test, compared with 7.5 for the controls and 11.4 for people with Parkinson’s disease without stimulators.

Gadolinium-based contrast medium (Gd-CM) may be associated with abnormalities on brain MRI, according to research published online ahead of print December 17, 2013, in Radiology. Researchers compared unenhanced T1-weighted MR images of 19 patients who had undergone six or more contrast-enhanced brain scans with images of 16 people who had received six or fewer unenhanced scans. The hyperintensity of the dentate nucleus and globus pallidus correlated with the number of Gd-CM administrations. Hyperintensity in the dentate nucleus and globus pallidus on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations, according to the researchers. Because gadolinium has a high signal intensity in the body, the data suggest that the toxic gadolinium component remains in the body in patients with normal renal function.

—Erik Greb

The Bacille Calmette-Guérin (BCG) vaccine may benefit patients with clinically isolated syndrome (CIS), according to research published online ahead of print December 4, 2013, in Neurology. A total of 82 participants with CIS were randomized to BCG or placebo and monitored monthly with brain MRI for six months. All patients subsequently received IM interferon β-1a for 12 months. In an open-label extension phase, patients received disease-modifying therapies (DMTs) recommended by their neurologists. During the initial six months, the number of cumulative lesions was significantly lower among vaccinated subjects. The number of total T1-hypointense lesions was lower in the BCG group at months 6, 12, and 18. After 60 months, the probability of clinically definite multiple sclerosis was lower in the BCG plus DMT arm, and more vaccinated people remained DMT-free.

Exercise programs may significantly improve the ability of people with dementia to perform activities of daily living, according to a study published online ahead of print December 4, 2013, in the Cochrane Library. Exercise also may improve cognition in these patients, but may not affect depression. Investigators reviewed randomized controlled trials in which older people diagnosed with dementia were allocated to exercise programs or to control groups, which received standard care or social contact. Sixteen trials with 937 participants met the inclusion criteria. The trials were highly heterogeneous in terms of subtype and severity of participants’ dementia, and type, duration, and frequency of exercise. The researchers found that informal caregivers’ burden may be reduced when the family member with dementia participates in an exercise program.

Thrombin activity may enable neurologists to detect multiple sclerosis (MS) before clinical signs of the disease are present, according to research published online ahead of print November 29, 2013, in Annals of Neurology. Using a novel molecular probe, investigators characterized the activity pattern of thrombin, the central protease of the coagulation cascade, in experimental autoimmune encephalomyelitis. Thrombin activity preceded the onset of neurologic signs; increased at disease peak; and correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin confirmed the specificity of the thrombin probe. Scientists may be able to use thrombin activity to develop sensitive probes for the preclinical detection and monitoring of neuroinflammation and MS progression, according to the investigators.

An athlete with concussion symptoms should not be allowed to return to play on the same day, according to the latest consensus statement on sports-related concussion, which was summarized in the December 2013 issue of Neurosurgery. The Concussion in Sport Group (CISG 4) based its recommendations on the advice of an expert panel that was sponsored by five international sports governing bodies. Between 80% and 90% of concussions resolve within seven to 10 days, but recovery may take longer in children and adolescents, according to the consensus statement. The updated statement emphasizes the distinction between concussion and mild traumatic brain injury. The CISG 4 suggests that patients with concussion have normal findings on brain neuroimaging studies (eg, CT scan), but those with traumatic brain injury have abnormal imaging findings.

Vitamin D may prevent multiple sclerosis (MS) by blocking T helper (T_H) cells from migrating into the CNS, according to research published online ahead of print December 9, 2013, in Proceedings of the National Academy of Sciences. Investigators administered 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃], the bioactive form of vitamin D, to animals with experimental autoimmune encephalomyelitis, a mouse model of MS. Myelin-reactive T_H cells were generated in the presence of 1,25(OH)₂D₃, secreted proinflammatory cytokines, and did not preferentially differentiate into suppressor T cells. The cells left the lymph node, entered the peripheral circulation, and migrated to the immunization sites. T_H cells from 1,25(OH)₂D₃-treated mice were unable to enter the CNS parenchyma, however. Instead, the cells were maintained in the periphery. The mice developed experimental autoimmune encephalomyelitis when treatment ceased.

Among people with type 2 diabetes, dementia incidence may be highest among Native Americans and African Americans and lowest among Asians, according to a study published online ahead of print November 22, 2013, in Diabetes Care. Scientists identified 22,171 patients age 60 or older with diabetes and without preexisting dementia in the Kaiser Permanente Northern California Diabetes Registry. The investigators abstracted prevalent medical history and dementia incidence from medical records and calculated age-adjusted incidence densities. Dementia was diagnosed in 17.1% of patients. Age-adjusted dementia incidence densities were 34/1,000 person-years among Native Americans, 27/1,000 person-years among African Americans, and 19/1,000 person-years among Asians. Hazard ratios (relative to Asians) were 1.64 for Native Americans, 1.44 for African Americans, 1.30 for non-Hispanic whites, and 1.19 for Latinos.

Veterans with blast injuries have changes in brain tissue that may be apparent on imaging years later, according to data presented at the 99th Annual Meeting of the Radiological Society of North America. Researchers compared diffusion tensor imaging (DTI)-derived fractional anisotropy (FA) values in 10 veterans of Operations Iraqi Freedom and Enduring Freedom who had been diagnosed with mild traumatic brain injury with those of 10 healthy controls. The average time elapsed between the blast-induced injury and DTI scan among the patients was 51.3 months. FA values were significantly different between the two groups, and the researchers found significant correlations between FA values and attention, delayed memory, and psychomotor test scores. The results suggest that blast injury may have a long-term impact on the brain.

Among college athletes, head impact exposure may be related to white matter diffusion measures and cognition during the course of one playing season, even in the absence of diagnosed concussion, according to data published online ahead of print December 11, 2013, in Neurology. Researchers prospectively studied 79 noncontact sport athletes and 80 nonconcussed varsity football and ice hockey players who wore helmets that recorded the acceleration-time history of the head following impact. Mean diffusivity (MD) in the corpus callosum was significantly different between groups. Measures of head impact exposure correlated with white matter diffusivity measures in the corpus callosum, amygdala, cerebellar white matter, hippocampus, and thalamus. The magnitude of change in corpus callosum MD postseason was associated with poorer performance on a measure of verbal learning and memory.

Among veterans, traumatic brain injury (TBI) during the most recent deployment is the strongest predictor of postdeployment symptoms of post-traumatic stress disorder (PTSD), even when accounting for predeployment symptoms, prior TBI, and combat intensity, according to research published online ahead of print December 11, 2013, in JAMA Psychiatry. A total of 1,648 active-duty Marine and Navy servicemen underwent clinical interviews and completed self-assessments approximately one month before a seven-month deployment and three to six months after deployment. At the predeployment assessment, 56.8% of participants reported prior TBI. At postdeployment assessment, 19.8% reported sustaining TBI between predeployment and postdeployment assessments. Probability of PTSD was highest for participants with severe predeployment symptoms, high combat intensity, and deployment-related TBI. TBI doubled the PTSD rates for participants with less severe predeployment PTSD symptoms.

Fidgetin inhibition could promote tissue regeneration and repair the broken cell connections that occur in spinal cord injury and other conditions, according to research presented at the 2013 Annual Meeting of the American Society for Cell Biology. Fidgetin prunes unstable microtubule scaffolding in cells, as well as unneeded connections in the neuronal network as the latter grows. Researchers used a novel nanoparticle technology to block fidgetin in the injured nerves of adult rats. The nanoparticles were infused with small interfering RNA that bound the messenger RNA (mRNA) transcribed from the fidgetin gene. The mRNA for fidgetin was not translated, and the cell did not produce fidgetin. Blocking fidgetin restarted tissue growth in the animals. The technique could benefit patients with myocardial infarction or chronic cutaneous wounds.

Deep brain stimulation may improve driving ability for people with Parkinson’s disease, according to a study published online ahead of print December 18, 2013, in Neurology. Investigators studied 23 people who had deep brain stimulators, 21 people with Parkinson’s disease without stimulators, and 21 healthy individuals. Participants were tested with a driving simulator. Individuals with stimulators completed the test once with the stimulator on, once with it off, and once with the stimulator off after receiving levodopa. People with Parkinson’s disease without stimulators performed worse than controls in almost every category. People with stimulators did not perform significantly worse than the controls. Participants with stimulators had an average of 3.8 slight driving errors on the test, compared with 7.5 for the controls and 11.4 for people with Parkinson’s disease without stimulators.

Gadolinium-based contrast medium (Gd-CM) may be associated with abnormalities on brain MRI, according to research published online ahead of print December 17, 2013, in Radiology. Researchers compared unenhanced T1-weighted MR images of 19 patients who had undergone six or more contrast-enhanced brain scans with images of 16 people who had received six or fewer unenhanced scans. The hyperintensity of the dentate nucleus and globus pallidus correlated with the number of Gd-CM administrations. Hyperintensity in the dentate nucleus and globus pallidus on unenhanced MRI may be a consequence of the number of previous Gd-CM administrations, according to the researchers. Because gadolinium has a high signal intensity in the body, the data suggest that the toxic gadolinium component remains in the body in patients with normal renal function.

—Erik Greb