New and Noteworthy Information—May 2017

The Biomarkers for Infant Brain Injury Score can identify infants with acute intracranial hemorrhage, according to a study published online ahead of print April 10 in JAMA Pediatrics. Binary logistic regression was used to develop a multivariable model incorporating three serum biomarkers and one clinical variable (total hemoglobin). The Biomarkers for Infant Brain Injury Score was applied to 599 infants (mean age, 4.7 months) at increased risk for abusive head trauma. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive and 48.0% specific for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.

The FDA has approved Ocrevus (ocrelizumab), an IV infusion, to treat adults with relapsing forms of multiple sclerosis (MS) and primary progressive MS. This drug is the first to be approved by the FDA for primary progressive MS. The efficacy of Ocrevus for the treatment of relapsing-remitting MS was shown in two clinical trials including 1,656 participants treated for 96 weeks. In both studies, patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability, compared with patients receiving interferon beta-1a. In a study of 732 participants with primary progressive MS treated for at least 120 weeks, participants receiving Ocrevus had a longer time to the worsening of disability, compared with participants receiving placebo. Common side effects include infusion-related reactions and upper respiratory tract infection. Genentech markets Ocrevus.

Unemployed men and women and reemployed men have an increased risk of hemorrhagic and ischemic stroke and mortality, according to a study published online ahead of print April 6 in Stroke. This prospective study included 21,902 men and 19,826 women, ages 40 to 59, from nine public health centers across Japan. Participants were followed up from 1990–1993 to the end of 2009–2014. During the follow-up period, 973 incident strokes and 275 deaths from stroke occurred in men, as well as 460 strokes and 131 deaths from stroke in women. Compared with continuously employed subjects, the multivariable hazard ratio (HR) for total stroke incidence was 1.58 in unemployed men and 1.51 in unemployed women. HR for total stroke mortality was 2.22 in men and 2.48 in women.

In people with uncomplicated childhood-onset epilepsy and five-year terminal remission, young adult social outcomes are comparable to those of sibling controls, according to a study published online ahead of print April 4 in Epilepsia. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, which included 361 individuals with epilepsy and 173 controls. Social outcomes for cases with uncomplicated epilepsy with five or more years’ terminal remission were comparable to those of controls. Cases with uncomplicated epilepsy and less than five years of seizure freedom were more likely to be less productive and not to have a driver’s license. Complicated cases with epilepsy and less than five years of seizure freedom had worse outcomes across multiple domains, including not graduating high school.

Deep brain stimulation of the ventralis oralis internus and centromedian-parafascicular thalamus is an effective and relatively safe treatment for severe, refractory Tourette syndrome, according to a study published online ahead of print April 7 in the Journal of Neurosurgery. Researchers retrospectively reviewed outcomes in 13 patients with refractory Tourette syndrome who underwent medial thalamic deep brain stimulation for seven years. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale. Patients showed an average decrease of 37% in total tic severity at their first postoperative visit. During their most recent visit, patient scores decreased from preoperative scores by an average of 50%, which was statistically significant. Device-related complications occurred in two patients, necessitating additional surgeries.

The FDA has approved Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia. Ingrezza is a selective vesicular monoamine transporter 2 inhibitor. The approval of Ingrezza was based on data from the Kinect 3 study, a phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study comparing once-daily Ingrezza (80 mg and 40 mg) to placebo over six weeks in patients with schizophrenia, schizoaffective disorder, or mood disorder. The mean change from baseline to week six in the AIMS dyskinesia total score was –3.2 for patients receiving 80 mg/day of Ingrezza, compared with –0.1 for controls. Ingrezza also was generally well tolerated, with somnolence as the only adverse event occurring at a rate of 5% or greater and twice the rate associated with placebo. Neurocrine Biosciences markets Ingrezza.

Benzodiazepine use is associated with an increased risk of pneumonia among patients with Alzheimer’s disease, according to a study published April 10 in CMAJ. Researchers obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland between 2005 and 2011 from the Medication use and Alzheimer’s disease cohort. Incident users of benzodiazepines and nonbenzodiazepines were identified using a one-year washout period and matched with nonusers through propensity scores. Among 49,484 eligible participants with Alzheimer’s disease, 5,232 taking benzodiazepines and 3,269 taking nonbenzodiazepines were matched 1:1 with people not taking these drugs. Benzodiazepine and nonbenzodiazepine use was associated with a 22% increased risk of pneumonia. When analyzed separately, benzodiazepine use was significantly associated with a 28% increased risk of pneumonia, but nonbenzodiazepine use was not.

Hospitalization rates for acute ischemic stroke in young adults are increasing, along with the prevalence of traditional stroke risk factors, according to a study published online ahead of print April 10 in JAMA Neurology. Hospitalization data from the National Inpatient Sample from 1995 through 2012 were used to analyze acute stroke hospitalization rates among people ages 18 to 64. The 2003–2004 set included 362,339 hospitalizations, and the 2011–2012 set included 421,815 hospitalizations. Acute ischemic stroke hospitalization rates increased significantly for men and women, and for certain racial and ethnic groups, among younger adults ages 18 to 54. The prevalence of stroke risk factors among people hospitalized for acute ischemic stroke continued to increase from 2003–2004 through 2011–2012 for men and women ages 18 to 64.

A polygenic hazard score may help quantify individual differences in age-specific genetic risk for Alzheimer’s disease, according to a study published March 21 in PLOS Medicine. The investigators reviewed single-nucleotide polymorphisms associated with Alzheimer’s disease risk. Using a Cox proportional hazard model, they calculated polygenic hazard scores for participants in the Alzheimer’s Disease Genetics Consortium and tested them in two independent cohorts. People in the top polygenic hazard score quartile developed Alzheimer’s disease at a considerably lower age and had the highest yearly Alzheimer’s disease incidence rate. Among people who did not have the APOE ε3 allele, polygenic hazard score modified the age of expected onset by more than 10 years between the lowest and highest deciles. In independent cohorts, the polygenic hazard score strongly predicted age of Alzheimer’s disease onset.

Generalized anxiety disorder (GAD) is associated with migraine, according to a study published in the March issue of Headache. Researchers performed a secondary data analysis of the 2012 Canadian Community Health Survey-Mental Health. The first subsample included people with and without migraine. The second subsample was restricted to people with migraine. Six percent of people with migraine had had GAD in the previous year, compared with 2.1% of people without migraine. The adjusted odds of previous year GAD were 2.5 times higher among people with migraine than among people without. In the sample containing only migraineurs, the factors associated with higher odds of 12-month GAD included having a university degree, having low income, being without a confidant, and being male.

The rates of childhood epilepsy increase with maternal overweight or obesity in a dose-response manner, according to a study published online ahead of print April 3 in JAMA Neurology. Researchers conducted a population-based cohort study of 1,441,623 live single births at 22 or more gestational weeks in Sweden from January 1, 1997, to December 31, 2011. The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women to 12.4 per 10,000 child-years among women with grade III obesity. Risk of epilepsy increased by 11% in children of overweight mothers, compared with children of normal-weight mothers. Grade I obesity was associated with a 20% increased risk, grade II obesity was associated with a 30% increased risk, and grade III obesity was associated with an 82% increased risk.

The FDA has approved a label expansion for Trokendi XR (topiramate) to include migraine prophylaxis in adults and adolescents age 12 and older. Trokendi XR is a once-daily extended release formulation. The drug previously was approved as initial monotherapy and adjunctive therapy in patients age 6 and older with partial onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients age 6 and older with seizures associated with Lennox-Gastaut syndrome. Trokendi XR is available in 25-mg, 50-mg, 100-mg, and 200-mg capsules. The drug may cause sudden decrease in vision, secondary angle closure glaucoma, or decreased sweating. Approximately one in 500 people who take Trokendi XR may have suicidal thoughts. Supernus Pharmaceuticals markets Trokendi XR.

The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Austedo was previously referred to by the name SD-809 and was granted Orphan Drug Designation by the FDA. Austedo is the second product approved for Huntington’s disease. The approval was based on phase III results in a randomized, double-blind, placebo-controlled, multicenter trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period, compared with approximately 1.9 units in the placebo group. At the week 13 follow-up visit (one week after discontinuation of the study drug), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline levels. Teva Pharmaceutical Industries markets Austedo.

—Kimberly Williams

The Biomarkers for Infant Brain Injury Score can identify infants with acute intracranial hemorrhage, according to a study published online ahead of print April 10 in JAMA Pediatrics. Binary logistic regression was used to develop a multivariable model incorporating three serum biomarkers and one clinical variable (total hemoglobin). The Biomarkers for Infant Brain Injury Score was applied to 599 infants (mean age, 4.7 months) at increased risk for abusive head trauma. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive and 48.0% specific for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.

The FDA has approved Ocrevus (ocrelizumab), an IV infusion, to treat adults with relapsing forms of multiple sclerosis (MS) and primary progressive MS. This drug is the first to be approved by the FDA for primary progressive MS. The efficacy of Ocrevus for the treatment of relapsing-remitting MS was shown in two clinical trials including 1,656 participants treated for 96 weeks. In both studies, patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability, compared with patients receiving interferon beta-1a. In a study of 732 participants with primary progressive MS treated for at least 120 weeks, participants receiving Ocrevus had a longer time to the worsening of disability, compared with participants receiving placebo. Common side effects include infusion-related reactions and upper respiratory tract infection. Genentech markets Ocrevus.

Unemployed men and women and reemployed men have an increased risk of hemorrhagic and ischemic stroke and mortality, according to a study published online ahead of print April 6 in Stroke. This prospective study included 21,902 men and 19,826 women, ages 40 to 59, from nine public health centers across Japan. Participants were followed up from 1990–1993 to the end of 2009–2014. During the follow-up period, 973 incident strokes and 275 deaths from stroke occurred in men, as well as 460 strokes and 131 deaths from stroke in women. Compared with continuously employed subjects, the multivariable hazard ratio (HR) for total stroke incidence was 1.58 in unemployed men and 1.51 in unemployed women. HR for total stroke mortality was 2.22 in men and 2.48 in women.

In people with uncomplicated childhood-onset epilepsy and five-year terminal remission, young adult social outcomes are comparable to those of sibling controls, according to a study published online ahead of print April 4 in Epilepsia. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, which included 361 individuals with epilepsy and 173 controls. Social outcomes for cases with uncomplicated epilepsy with five or more years’ terminal remission were comparable to those of controls. Cases with uncomplicated epilepsy and less than five years of seizure freedom were more likely to be less productive and not to have a driver’s license. Complicated cases with epilepsy and less than five years of seizure freedom had worse outcomes across multiple domains, including not graduating high school.

Deep brain stimulation of the ventralis oralis internus and centromedian-parafascicular thalamus is an effective and relatively safe treatment for severe, refractory Tourette syndrome, according to a study published online ahead of print April 7 in the Journal of Neurosurgery. Researchers retrospectively reviewed outcomes in 13 patients with refractory Tourette syndrome who underwent medial thalamic deep brain stimulation for seven years. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale. Patients showed an average decrease of 37% in total tic severity at their first postoperative visit. During their most recent visit, patient scores decreased from preoperative scores by an average of 50%, which was statistically significant. Device-related complications occurred in two patients, necessitating additional surgeries.

The FDA has approved Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia. Ingrezza is a selective vesicular monoamine transporter 2 inhibitor. The approval of Ingrezza was based on data from the Kinect 3 study, a phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study comparing once-daily Ingrezza (80 mg and 40 mg) to placebo over six weeks in patients with schizophrenia, schizoaffective disorder, or mood disorder. The mean change from baseline to week six in the AIMS dyskinesia total score was –3.2 for patients receiving 80 mg/day of Ingrezza, compared with –0.1 for controls. Ingrezza also was generally well tolerated, with somnolence as the only adverse event occurring at a rate of 5% or greater and twice the rate associated with placebo. Neurocrine Biosciences markets Ingrezza.

Benzodiazepine use is associated with an increased risk of pneumonia among patients with Alzheimer’s disease, according to a study published April 10 in CMAJ. Researchers obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland between 2005 and 2011 from the Medication use and Alzheimer’s disease cohort. Incident users of benzodiazepines and nonbenzodiazepines were identified using a one-year washout period and matched with nonusers through propensity scores. Among 49,484 eligible participants with Alzheimer’s disease, 5,232 taking benzodiazepines and 3,269 taking nonbenzodiazepines were matched 1:1 with people not taking these drugs. Benzodiazepine and nonbenzodiazepine use was associated with a 22% increased risk of pneumonia. When analyzed separately, benzodiazepine use was significantly associated with a 28% increased risk of pneumonia, but nonbenzodiazepine use was not.

Hospitalization rates for acute ischemic stroke in young adults are increasing, along with the prevalence of traditional stroke risk factors, according to a study published online ahead of print April 10 in JAMA Neurology. Hospitalization data from the National Inpatient Sample from 1995 through 2012 were used to analyze acute stroke hospitalization rates among people ages 18 to 64. The 2003–2004 set included 362,339 hospitalizations, and the 2011–2012 set included 421,815 hospitalizations. Acute ischemic stroke hospitalization rates increased significantly for men and women, and for certain racial and ethnic groups, among younger adults ages 18 to 54. The prevalence of stroke risk factors among people hospitalized for acute ischemic stroke continued to increase from 2003–2004 through 2011–2012 for men and women ages 18 to 64.

A polygenic hazard score may help quantify individual differences in age-specific genetic risk for Alzheimer’s disease, according to a study published March 21 in PLOS Medicine. The investigators reviewed single-nucleotide polymorphisms associated with Alzheimer’s disease risk. Using a Cox proportional hazard model, they calculated polygenic hazard scores for participants in the Alzheimer’s Disease Genetics Consortium and tested them in two independent cohorts. People in the top polygenic hazard score quartile developed Alzheimer’s disease at a considerably lower age and had the highest yearly Alzheimer’s disease incidence rate. Among people who did not have the APOE ε3 allele, polygenic hazard score modified the age of expected onset by more than 10 years between the lowest and highest deciles. In independent cohorts, the polygenic hazard score strongly predicted age of Alzheimer’s disease onset.

Generalized anxiety disorder (GAD) is associated with migraine, according to a study published in the March issue of Headache. Researchers performed a secondary data analysis of the 2012 Canadian Community Health Survey-Mental Health. The first subsample included people with and without migraine. The second subsample was restricted to people with migraine. Six percent of people with migraine had had GAD in the previous year, compared with 2.1% of people without migraine. The adjusted odds of previous year GAD were 2.5 times higher among people with migraine than among people without. In the sample containing only migraineurs, the factors associated with higher odds of 12-month GAD included having a university degree, having low income, being without a confidant, and being male.

The rates of childhood epilepsy increase with maternal overweight or obesity in a dose-response manner, according to a study published online ahead of print April 3 in JAMA Neurology. Researchers conducted a population-based cohort study of 1,441,623 live single births at 22 or more gestational weeks in Sweden from January 1, 1997, to December 31, 2011. The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women to 12.4 per 10,000 child-years among women with grade III obesity. Risk of epilepsy increased by 11% in children of overweight mothers, compared with children of normal-weight mothers. Grade I obesity was associated with a 20% increased risk, grade II obesity was associated with a 30% increased risk, and grade III obesity was associated with an 82% increased risk.

The FDA has approved a label expansion for Trokendi XR (topiramate) to include migraine prophylaxis in adults and adolescents age 12 and older. Trokendi XR is a once-daily extended release formulation. The drug previously was approved as initial monotherapy and adjunctive therapy in patients age 6 and older with partial onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients age 6 and older with seizures associated with Lennox-Gastaut syndrome. Trokendi XR is available in 25-mg, 50-mg, 100-mg, and 200-mg capsules. The drug may cause sudden decrease in vision, secondary angle closure glaucoma, or decreased sweating. Approximately one in 500 people who take Trokendi XR may have suicidal thoughts. Supernus Pharmaceuticals markets Trokendi XR.

The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Austedo was previously referred to by the name SD-809 and was granted Orphan Drug Designation by the FDA. Austedo is the second product approved for Huntington’s disease. The approval was based on phase III results in a randomized, double-blind, placebo-controlled, multicenter trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period, compared with approximately 1.9 units in the placebo group. At the week 13 follow-up visit (one week after discontinuation of the study drug), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline levels. Teva Pharmaceutical Industries markets Austedo.

—Kimberly Williams

The Biomarkers for Infant Brain Injury Score can identify infants with acute intracranial hemorrhage, according to a study published online ahead of print April 10 in JAMA Pediatrics. Binary logistic regression was used to develop a multivariable model incorporating three serum biomarkers and one clinical variable (total hemoglobin). The Biomarkers for Infant Brain Injury Score was applied to 599 infants (mean age, 4.7 months) at increased risk for abusive head trauma. Fifty-two percent were boys, 78% were white, and 8% were Hispanic. At a cutoff of 0.182, the model was 89.3% sensitive and 48.0% specific for acute intracranial hemorrhage. Positive and negative predictive values were 21.3% and 95.6%, respectively. The model was neither sensitive nor specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.

The FDA has approved Ocrevus (ocrelizumab), an IV infusion, to treat adults with relapsing forms of multiple sclerosis (MS) and primary progressive MS. This drug is the first to be approved by the FDA for primary progressive MS. The efficacy of Ocrevus for the treatment of relapsing-remitting MS was shown in two clinical trials including 1,656 participants treated for 96 weeks. In both studies, patients receiving Ocrevus had reduced relapse rates and reduced worsening of disability, compared with patients receiving interferon beta-1a. In a study of 732 participants with primary progressive MS treated for at least 120 weeks, participants receiving Ocrevus had a longer time to the worsening of disability, compared with participants receiving placebo. Common side effects include infusion-related reactions and upper respiratory tract infection. Genentech markets Ocrevus.

Unemployed men and women and reemployed men have an increased risk of hemorrhagic and ischemic stroke and mortality, according to a study published online ahead of print April 6 in Stroke. This prospective study included 21,902 men and 19,826 women, ages 40 to 59, from nine public health centers across Japan. Participants were followed up from 1990–1993 to the end of 2009–2014. During the follow-up period, 973 incident strokes and 275 deaths from stroke occurred in men, as well as 460 strokes and 131 deaths from stroke in women. Compared with continuously employed subjects, the multivariable hazard ratio (HR) for total stroke incidence was 1.58 in unemployed men and 1.51 in unemployed women. HR for total stroke mortality was 2.22 in men and 2.48 in women.

In people with uncomplicated childhood-onset epilepsy and five-year terminal remission, young adult social outcomes are comparable to those of sibling controls, according to a study published online ahead of print April 4 in Epilepsia. Long-term social outcomes were assessed at the 15-year follow-up of the Connecticut Study of Epilepsy, which included 361 individuals with epilepsy and 173 controls. Social outcomes for cases with uncomplicated epilepsy with five or more years’ terminal remission were comparable to those of controls. Cases with uncomplicated epilepsy and less than five years of seizure freedom were more likely to be less productive and not to have a driver’s license. Complicated cases with epilepsy and less than five years of seizure freedom had worse outcomes across multiple domains, including not graduating high school.

Deep brain stimulation of the ventralis oralis internus and centromedian-parafascicular thalamus is an effective and relatively safe treatment for severe, refractory Tourette syndrome, according to a study published online ahead of print April 7 in the Journal of Neurosurgery. Researchers retrospectively reviewed outcomes in 13 patients with refractory Tourette syndrome who underwent medial thalamic deep brain stimulation for seven years. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale and Yale-Brown Obsessive Compulsive Scale. Patients showed an average decrease of 37% in total tic severity at their first postoperative visit. During their most recent visit, patient scores decreased from preoperative scores by an average of 50%, which was statistically significant. Device-related complications occurred in two patients, necessitating additional surgeries.

The FDA has approved Ingrezza (valbenazine) capsules for the treatment of adults with tardive dyskinesia. Ingrezza is a selective vesicular monoamine transporter 2 inhibitor. The approval of Ingrezza was based on data from the Kinect 3 study, a phase III, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study comparing once-daily Ingrezza (80 mg and 40 mg) to placebo over six weeks in patients with schizophrenia, schizoaffective disorder, or mood disorder. The mean change from baseline to week six in the AIMS dyskinesia total score was –3.2 for patients receiving 80 mg/day of Ingrezza, compared with –0.1 for controls. Ingrezza also was generally well tolerated, with somnolence as the only adverse event occurring at a rate of 5% or greater and twice the rate associated with placebo. Neurocrine Biosciences markets Ingrezza.

Benzodiazepine use is associated with an increased risk of pneumonia among patients with Alzheimer’s disease, according to a study published April 10 in CMAJ. Researchers obtained data on all community-dwelling adults with a recent diagnosis of Alzheimer disease in Finland between 2005 and 2011 from the Medication use and Alzheimer’s disease cohort. Incident users of benzodiazepines and nonbenzodiazepines were identified using a one-year washout period and matched with nonusers through propensity scores. Among 49,484 eligible participants with Alzheimer’s disease, 5,232 taking benzodiazepines and 3,269 taking nonbenzodiazepines were matched 1:1 with people not taking these drugs. Benzodiazepine and nonbenzodiazepine use was associated with a 22% increased risk of pneumonia. When analyzed separately, benzodiazepine use was significantly associated with a 28% increased risk of pneumonia, but nonbenzodiazepine use was not.

Hospitalization rates for acute ischemic stroke in young adults are increasing, along with the prevalence of traditional stroke risk factors, according to a study published online ahead of print April 10 in JAMA Neurology. Hospitalization data from the National Inpatient Sample from 1995 through 2012 were used to analyze acute stroke hospitalization rates among people ages 18 to 64. The 2003–2004 set included 362,339 hospitalizations, and the 2011–2012 set included 421,815 hospitalizations. Acute ischemic stroke hospitalization rates increased significantly for men and women, and for certain racial and ethnic groups, among younger adults ages 18 to 54. The prevalence of stroke risk factors among people hospitalized for acute ischemic stroke continued to increase from 2003–2004 through 2011–2012 for men and women ages 18 to 64.

A polygenic hazard score may help quantify individual differences in age-specific genetic risk for Alzheimer’s disease, according to a study published March 21 in PLOS Medicine. The investigators reviewed single-nucleotide polymorphisms associated with Alzheimer’s disease risk. Using a Cox proportional hazard model, they calculated polygenic hazard scores for participants in the Alzheimer’s Disease Genetics Consortium and tested them in two independent cohorts. People in the top polygenic hazard score quartile developed Alzheimer’s disease at a considerably lower age and had the highest yearly Alzheimer’s disease incidence rate. Among people who did not have the APOE ε3 allele, polygenic hazard score modified the age of expected onset by more than 10 years between the lowest and highest deciles. In independent cohorts, the polygenic hazard score strongly predicted age of Alzheimer’s disease onset.

Generalized anxiety disorder (GAD) is associated with migraine, according to a study published in the March issue of Headache. Researchers performed a secondary data analysis of the 2012 Canadian Community Health Survey-Mental Health. The first subsample included people with and without migraine. The second subsample was restricted to people with migraine. Six percent of people with migraine had had GAD in the previous year, compared with 2.1% of people without migraine. The adjusted odds of previous year GAD were 2.5 times higher among people with migraine than among people without. In the sample containing only migraineurs, the factors associated with higher odds of 12-month GAD included having a university degree, having low income, being without a confidant, and being male.

The rates of childhood epilepsy increase with maternal overweight or obesity in a dose-response manner, according to a study published online ahead of print April 3 in JAMA Neurology. Researchers conducted a population-based cohort study of 1,441,623 live single births at 22 or more gestational weeks in Sweden from January 1, 1997, to December 31, 2011. The risk of childhood epilepsy increased by maternal BMI from 6.30 per 10,000 child-years among normal-weight women to 12.4 per 10,000 child-years among women with grade III obesity. Risk of epilepsy increased by 11% in children of overweight mothers, compared with children of normal-weight mothers. Grade I obesity was associated with a 20% increased risk, grade II obesity was associated with a 30% increased risk, and grade III obesity was associated with an 82% increased risk.

The FDA has approved a label expansion for Trokendi XR (topiramate) to include migraine prophylaxis in adults and adolescents age 12 and older. Trokendi XR is a once-daily extended release formulation. The drug previously was approved as initial monotherapy and adjunctive therapy in patients age 6 and older with partial onset or primary generalized tonic-clonic seizures and as adjunctive therapy in patients age 6 and older with seizures associated with Lennox-Gastaut syndrome. Trokendi XR is available in 25-mg, 50-mg, 100-mg, and 200-mg capsules. The drug may cause sudden decrease in vision, secondary angle closure glaucoma, or decreased sweating. Approximately one in 500 people who take Trokendi XR may have suicidal thoughts. Supernus Pharmaceuticals markets Trokendi XR.

The FDA has approved Austedo (deutetrabenazine) tablets for the treatment of chorea associated with Huntington’s disease. Austedo was previously referred to by the name SD-809 and was granted Orphan Drug Designation by the FDA. Austedo is the second product approved for Huntington’s disease. The approval was based on phase III results in a randomized, double-blind, placebo-controlled, multicenter trial conducted in 90 ambulatory patients with manifest chorea associated with Huntington’s disease. Total Maximal Chorea Scores for patients receiving Austedo improved by approximately 4.4 units from baseline to the maintenance period, compared with approximately 1.9 units in the placebo group. At the week 13 follow-up visit (one week after discontinuation of the study drug), the Total Maximal Chorea Scores of patients who had received Austedo returned to baseline levels. Teva Pharmaceutical Industries markets Austedo.

—Kimberly Williams