Literature Review

Benign epilepsy with centrotemporal spikes (BECTS) is associated with a low risk of sudden unexpected death in epilepsy (SUDEP), according to a study published in the June 1 JAMA Neurology. Clinicians should consider discussing this rare outcome with patients and their families and factoring this risk into treatment decisions, according to the authors.

“Our data suggest that even children with BECTS who have only focal motor or infrequent seizures are at risk for SUDEP,” said Kyra Doumlele, of New York University School of Medicine’s Department of Neurology, and colleagues.

BECTS is the most common focal epilepsy syndrome among children. This form of epilepsy typically has a good prognosis and tends to resolve before age 16. As a result, many neurologists do not prescribe antiseizure medications for patients with BECTS. However, patients with this disease have predominantly nocturnal seizures and some generalized tonic-clonic seizures, which could put them at risk for SUDEP.

SUDEP in well-characterized patients with BECTS has not been documented. Ms. Doumlele and colleagues sought to determine whether cases of BECTS were present in the North American SUDEP Registry (NASR), a clinical and biospecimen repository established to investigate the risk factors and mechanisms for SUDEP.

Researchers searched records of 189 decedents enrolled in the NASR from June 3, 2011, to June 3, 2016. Investigators identified cases based on a diagnosis of BECTS by parental report during the intake interview and confirmation from treating physicians. Diagnostic criteria for BECTS included the onset of epilepsy at age 3 to age 13, normal cognition and development before onset of seizures, no symptomatic cause of epilepsy, and EEG results reporting discharges consistent with BECTS.

Investigators identified three boys who had received a diagnosis of BECTS. The first patient and third patient met all clinical and EEG features for a diagnosis of BECTS. The second patient had limited EEG data, but had classic clinical features of BECTS.

The first patient (age 9) had seizure onset at age 5. He experienced an increase in focal motor and secondary generalized tonic-clonic seizures in the six months before his death.

The second patient (age 12) developed epilepsy at age 11. Four months prior to death, he experienced at least three nocturnal generalized tonic-clonic seizures. The autopsy report listed his cause of death as “cardiac dysrhythmia associated with lymphocytic myocarditis, left anterior descending coronary artery intramuscular tunneling, and possible hypertrophic cardiomyopathy.”

The third patient (age 13) developed epilepsy at age 3. His severe postictal state indicated that he might have had two generalized tonic-clonic seizures in the year before he died. His death was unwitnessed, and no autopsy was performed. None of these patients had received antiseizure medications or counseling with their families about the risk of SUDEP.

“These cases illustrate that SUDEP is a rare complication of BECTS, and this information should be shared with families at or soon after diagnosis,” said Ms. Doumlele and colleagues.

—Erica Tricarico

Suggested Reading

Doumlele K, Friedman D, Buchhalter J, et al. Sudden unexpected death in epilepsy among patients with benign childhood epilepsy with centrotemporal spikes. JAMA Neurol. 2017;74(6):645-649.

Benign epilepsy with centrotemporal spikes (BECTS) is associated with a low risk of sudden unexpected death in epilepsy (SUDEP), according to a study published in the June 1 JAMA Neurology. Clinicians should consider discussing this rare outcome with patients and their families and factoring this risk into treatment decisions, according to the authors.

“Our data suggest that even children with BECTS who have only focal motor or infrequent seizures are at risk for SUDEP,” said Kyra Doumlele, of New York University School of Medicine’s Department of Neurology, and colleagues.

BECTS is the most common focal epilepsy syndrome among children. This form of epilepsy typically has a good prognosis and tends to resolve before age 16. As a result, many neurologists do not prescribe antiseizure medications for patients with BECTS. However, patients with this disease have predominantly nocturnal seizures and some generalized tonic-clonic seizures, which could put them at risk for SUDEP.

SUDEP in well-characterized patients with BECTS has not been documented. Ms. Doumlele and colleagues sought to determine whether cases of BECTS were present in the North American SUDEP Registry (NASR), a clinical and biospecimen repository established to investigate the risk factors and mechanisms for SUDEP.

Researchers searched records of 189 decedents enrolled in the NASR from June 3, 2011, to June 3, 2016. Investigators identified cases based on a diagnosis of BECTS by parental report during the intake interview and confirmation from treating physicians. Diagnostic criteria for BECTS included the onset of epilepsy at age 3 to age 13, normal cognition and development before onset of seizures, no symptomatic cause of epilepsy, and EEG results reporting discharges consistent with BECTS.

Investigators identified three boys who had received a diagnosis of BECTS. The first patient and third patient met all clinical and EEG features for a diagnosis of BECTS. The second patient had limited EEG data, but had classic clinical features of BECTS.

The first patient (age 9) had seizure onset at age 5. He experienced an increase in focal motor and secondary generalized tonic-clonic seizures in the six months before his death.

The second patient (age 12) developed epilepsy at age 11. Four months prior to death, he experienced at least three nocturnal generalized tonic-clonic seizures. The autopsy report listed his cause of death as “cardiac dysrhythmia associated with lymphocytic myocarditis, left anterior descending coronary artery intramuscular tunneling, and possible hypertrophic cardiomyopathy.”

The third patient (age 13) developed epilepsy at age 3. His severe postictal state indicated that he might have had two generalized tonic-clonic seizures in the year before he died. His death was unwitnessed, and no autopsy was performed. None of these patients had received antiseizure medications or counseling with their families about the risk of SUDEP.

“These cases illustrate that SUDEP is a rare complication of BECTS, and this information should be shared with families at or soon after diagnosis,” said Ms. Doumlele and colleagues.

—Erica Tricarico

Suggested Reading

Doumlele K, Friedman D, Buchhalter J, et al. Sudden unexpected death in epilepsy among patients with benign childhood epilepsy with centrotemporal spikes. JAMA Neurol. 2017;74(6):645-649.

Benign epilepsy with centrotemporal spikes (BECTS) is associated with a low risk of sudden unexpected death in epilepsy (SUDEP), according to a study published in the June 1 JAMA Neurology. Clinicians should consider discussing this rare outcome with patients and their families and factoring this risk into treatment decisions, according to the authors.

“Our data suggest that even children with BECTS who have only focal motor or infrequent seizures are at risk for SUDEP,” said Kyra Doumlele, of New York University School of Medicine’s Department of Neurology, and colleagues.

BECTS is the most common focal epilepsy syndrome among children. This form of epilepsy typically has a good prognosis and tends to resolve before age 16. As a result, many neurologists do not prescribe antiseizure medications for patients with BECTS. However, patients with this disease have predominantly nocturnal seizures and some generalized tonic-clonic seizures, which could put them at risk for SUDEP.

SUDEP in well-characterized patients with BECTS has not been documented. Ms. Doumlele and colleagues sought to determine whether cases of BECTS were present in the North American SUDEP Registry (NASR), a clinical and biospecimen repository established to investigate the risk factors and mechanisms for SUDEP.

Researchers searched records of 189 decedents enrolled in the NASR from June 3, 2011, to June 3, 2016. Investigators identified cases based on a diagnosis of BECTS by parental report during the intake interview and confirmation from treating physicians. Diagnostic criteria for BECTS included the onset of epilepsy at age 3 to age 13, normal cognition and development before onset of seizures, no symptomatic cause of epilepsy, and EEG results reporting discharges consistent with BECTS.

Investigators identified three boys who had received a diagnosis of BECTS. The first patient and third patient met all clinical and EEG features for a diagnosis of BECTS. The second patient had limited EEG data, but had classic clinical features of BECTS.

The first patient (age 9) had seizure onset at age 5. He experienced an increase in focal motor and secondary generalized tonic-clonic seizures in the six months before his death.

The second patient (age 12) developed epilepsy at age 11. Four months prior to death, he experienced at least three nocturnal generalized tonic-clonic seizures. The autopsy report listed his cause of death as “cardiac dysrhythmia associated with lymphocytic myocarditis, left anterior descending coronary artery intramuscular tunneling, and possible hypertrophic cardiomyopathy.”

The third patient (age 13) developed epilepsy at age 3. His severe postictal state indicated that he might have had two generalized tonic-clonic seizures in the year before he died. His death was unwitnessed, and no autopsy was performed. None of these patients had received antiseizure medications or counseling with their families about the risk of SUDEP.

“These cases illustrate that SUDEP is a rare complication of BECTS, and this information should be shared with families at or soon after diagnosis,” said Ms. Doumlele and colleagues.

—Erica Tricarico

Suggested Reading

Doumlele K, Friedman D, Buchhalter J, et al. Sudden unexpected death in epilepsy among patients with benign childhood epilepsy with centrotemporal spikes. JAMA Neurol. 2017;74(6):645-649.

Mindfulness training is as effective as prophylactic medications for treating chronic migraine associated with medication overuse (CM-MO), according to research published online ahead of print February 4 in the Journal of Headache and Pain.

“Our results further suggest that a mindfulness-based treatment may be comparable to standard pharmacologic prophylaxis with regard to relevant primary outcomes such as headache frequency reduction and reduction in the consumption of acute medications,” said Licia Grazzi, MD, a neurologist at Istituto Neurologico Carlo Besta in Milan.

Research has suggested that mindfulness may be beneficial for headache. Previous studies, however, have been limited by inadequate consideration of several significant end points in chronic headache, such as frequency of headache and consumption of medications for acute headache management, said the authors.

To address these limitations, Dr. Grazzi and colleagues conducted an exploratory clinical trial that compared conventional prophylactic pharmacologic treatment with a mindfulness-based treatment for patients diagnosed with CM-MO. Researchers hypothesized that the mindfulness-based approach would be as effective as conventional prophylactic treatment.

Eligible participants were between ages 18 and 65 and had been diagnosed with CM-MO according to the International Classification of Headache Disorders, third edition (beta version), and had presented for treatment at the Headache Center of the Istituto Neurologico Carlo Besta  between February 2014 and June 2015. In addition, participants had a history of chronic migraine for at least 10 years that was associated with overuse of triptans and nonsteroidal anti-inflammatory drugs for a minimum of the past five years.

All patients completed a five-day medication withdrawal program and were encouraged to exercise at least 45 minutes twice a week, to stay properly hydrated, and to consume three meals every day.

Participants were separated into two groups. In one group, patients were treated with prophylactic medications. In the second group, patients participated in a mindfulness-based training that consisted of six weekly sessions of guided mindfulness. Patients were invited to practice mindfulness training for seven to 10 minutes per day. At each follow-up visit, the Headache Impact Test, the Migraine Disability Assessment, the State and Trait Anxiety Inventory, and the Beck Depression Inventory were administered. Patients also kept headache diaries.

A total of 44 patients participated in the study. The average age was 44.5, the average headache frequency per month was 20.5, and the average monthly medication intake was 18.4 pills. Overall, data indicated a similar improvement over time in the mindfulness group and pharmacologic prophylaxis group for headache frequency, use of medication, Migraine Disability Assessment, Headache Impact Test, and Beck Depression Inventory. No changes on State and Trait Anxiety Inventory were reported. Both groups had significant and equivalent proportions of participants who achieved at least 50% reduction of headaches, compared with baseline. The majority of patients in each group no longer satisfied criteria for chronic migraine.

“Our findings support the value of conducting further … well-controlled studies (incorporating random assignment, larger sample sizes, and checks on integrity of treatment),” said Dr. Grazzi. “[Such studies] are warranted to more fully explore the benefits, boundaries, and mechanisms of action for mindfulness in treating chronic migraine by itself and when it is complicated by medication overuse and medical or psychological comorbidities.”

—Erica Tricarico

Suggested Reading

Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

Mindfulness training is as effective as prophylactic medications for treating chronic migraine associated with medication overuse (CM-MO), according to research published online ahead of print February 4 in the Journal of Headache and Pain.

“Our results further suggest that a mindfulness-based treatment may be comparable to standard pharmacologic prophylaxis with regard to relevant primary outcomes such as headache frequency reduction and reduction in the consumption of acute medications,” said Licia Grazzi, MD, a neurologist at Istituto Neurologico Carlo Besta in Milan.

Research has suggested that mindfulness may be beneficial for headache. Previous studies, however, have been limited by inadequate consideration of several significant end points in chronic headache, such as frequency of headache and consumption of medications for acute headache management, said the authors.

To address these limitations, Dr. Grazzi and colleagues conducted an exploratory clinical trial that compared conventional prophylactic pharmacologic treatment with a mindfulness-based treatment for patients diagnosed with CM-MO. Researchers hypothesized that the mindfulness-based approach would be as effective as conventional prophylactic treatment.

Eligible participants were between ages 18 and 65 and had been diagnosed with CM-MO according to the International Classification of Headache Disorders, third edition (beta version), and had presented for treatment at the Headache Center of the Istituto Neurologico Carlo Besta  between February 2014 and June 2015. In addition, participants had a history of chronic migraine for at least 10 years that was associated with overuse of triptans and nonsteroidal anti-inflammatory drugs for a minimum of the past five years.

All patients completed a five-day medication withdrawal program and were encouraged to exercise at least 45 minutes twice a week, to stay properly hydrated, and to consume three meals every day.

Participants were separated into two groups. In one group, patients were treated with prophylactic medications. In the second group, patients participated in a mindfulness-based training that consisted of six weekly sessions of guided mindfulness. Patients were invited to practice mindfulness training for seven to 10 minutes per day. At each follow-up visit, the Headache Impact Test, the Migraine Disability Assessment, the State and Trait Anxiety Inventory, and the Beck Depression Inventory were administered. Patients also kept headache diaries.

A total of 44 patients participated in the study. The average age was 44.5, the average headache frequency per month was 20.5, and the average monthly medication intake was 18.4 pills. Overall, data indicated a similar improvement over time in the mindfulness group and pharmacologic prophylaxis group for headache frequency, use of medication, Migraine Disability Assessment, Headache Impact Test, and Beck Depression Inventory. No changes on State and Trait Anxiety Inventory were reported. Both groups had significant and equivalent proportions of participants who achieved at least 50% reduction of headaches, compared with baseline. The majority of patients in each group no longer satisfied criteria for chronic migraine.

“Our findings support the value of conducting further … well-controlled studies (incorporating random assignment, larger sample sizes, and checks on integrity of treatment),” said Dr. Grazzi. “[Such studies] are warranted to more fully explore the benefits, boundaries, and mechanisms of action for mindfulness in treating chronic migraine by itself and when it is complicated by medication overuse and medical or psychological comorbidities.”

—Erica Tricarico

Suggested Reading

Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

Mindfulness training is as effective as prophylactic medications for treating chronic migraine associated with medication overuse (CM-MO), according to research published online ahead of print February 4 in the Journal of Headache and Pain.

“Our results further suggest that a mindfulness-based treatment may be comparable to standard pharmacologic prophylaxis with regard to relevant primary outcomes such as headache frequency reduction and reduction in the consumption of acute medications,” said Licia Grazzi, MD, a neurologist at Istituto Neurologico Carlo Besta in Milan.

Research has suggested that mindfulness may be beneficial for headache. Previous studies, however, have been limited by inadequate consideration of several significant end points in chronic headache, such as frequency of headache and consumption of medications for acute headache management, said the authors.

To address these limitations, Dr. Grazzi and colleagues conducted an exploratory clinical trial that compared conventional prophylactic pharmacologic treatment with a mindfulness-based treatment for patients diagnosed with CM-MO. Researchers hypothesized that the mindfulness-based approach would be as effective as conventional prophylactic treatment.

Eligible participants were between ages 18 and 65 and had been diagnosed with CM-MO according to the International Classification of Headache Disorders, third edition (beta version), and had presented for treatment at the Headache Center of the Istituto Neurologico Carlo Besta  between February 2014 and June 2015. In addition, participants had a history of chronic migraine for at least 10 years that was associated with overuse of triptans and nonsteroidal anti-inflammatory drugs for a minimum of the past five years.

All patients completed a five-day medication withdrawal program and were encouraged to exercise at least 45 minutes twice a week, to stay properly hydrated, and to consume three meals every day.

Participants were separated into two groups. In one group, patients were treated with prophylactic medications. In the second group, patients participated in a mindfulness-based training that consisted of six weekly sessions of guided mindfulness. Patients were invited to practice mindfulness training for seven to 10 minutes per day. At each follow-up visit, the Headache Impact Test, the Migraine Disability Assessment, the State and Trait Anxiety Inventory, and the Beck Depression Inventory were administered. Patients also kept headache diaries.

A total of 44 patients participated in the study. The average age was 44.5, the average headache frequency per month was 20.5, and the average monthly medication intake was 18.4 pills. Overall, data indicated a similar improvement over time in the mindfulness group and pharmacologic prophylaxis group for headache frequency, use of medication, Migraine Disability Assessment, Headache Impact Test, and Beck Depression Inventory. No changes on State and Trait Anxiety Inventory were reported. Both groups had significant and equivalent proportions of participants who achieved at least 50% reduction of headaches, compared with baseline. The majority of patients in each group no longer satisfied criteria for chronic migraine.

“Our findings support the value of conducting further … well-controlled studies (incorporating random assignment, larger sample sizes, and checks on integrity of treatment),” said Dr. Grazzi. “[Such studies] are warranted to more fully explore the benefits, boundaries, and mechanisms of action for mindfulness in treating chronic migraine by itself and when it is complicated by medication overuse and medical or psychological comorbidities.”

—Erica Tricarico

Suggested Reading

Grazzi L, Sansone E, Raggi A, et al. Mindfulness and pharmacological prophylaxis after withdrawal from medication overuse in patients with chronic migraine: an effectiveness trial with a one-year follow-up. J Headache Pain. 2017;18(1):15.

Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin familial amyloid polyneuropathy (ATTR-FAP), according to research published online ahead of print April 10 in Amyloid.

ATTR-FAP is a progressive condition caused by mutations in the TTR gene that destabilize the TTR protein, thereby facilitating misfolding and aggregation. The neuropathy may be accompanied by cardiac, gastrointestinal, renal, or ocular symptoms, and death occurs at an average of 10 years after symptom onset.

A pivotal phase III trial compared tafamidis with placebo over 18 months in 128 patients with early-stage ATTR-FAP. Researchers observed a trend toward a smaller increase in Neuropathy Impairment Score for Lower Limbs (NIS-LL) with tafamidis, compared with placebo, but the result was not statistically significant. Baseline NIS-LL values were higher among controls than among actively treated patients, however, and many participants dropped out of the study for liver transplantation.

In a post hoc analysis, the investigators took these factors into account and reanalyzed change from baseline in NIS-LL in the trial. They also analyzed change in NIS-LL plus three small-fiber nerve tests (NIS-LL+Σ3) and NIS-LL plus seven nerve tests (NIS-LL+Σ7) without baseline measurements as covariates.

The analysis indicated a significant benefit of tafamidis, compared with placebo, at Months 12 and 18. The baseline-adjusted mean increase in NIS-LL from baseline to Month 12 was 1.5 points in the tafamidis group versus 4.5 points in the placebo group. By Month 18, the mean change from baseline was 2.9 points in the tafamidis group versus 5.6 points in the placebo group.

When the researchers applied sensitivity analysis based on multiple imputation for missing data by treatment group, the mean estimates of the increase in NIS-LL total score from baseline to Month 18 were significantly lower for tafamidis, compared with placebo. A more conservative model based on multiple imputation showed a benefit of tafamidis, but results did not reach statistical significance.

The researchers also found a statistically significant benefit of tafamidis, compared with placebo, on NIS-LL+Σ3 at Months 12 and 18. Significant differences favoring tafamidis also were observed on NIS-LL+Σ7 at Months 12 and 18. Four of the study’s five authors are employees of Pfizer, which owns tafamidis and sponsored the study.

—Erik Greb

Suggested Reading

Keohane D, Schwartz J, Gundapaneni B, et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Apr 10 [Epub ahead of print].

Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin familial amyloid polyneuropathy (ATTR-FAP), according to research published online ahead of print April 10 in Amyloid.

ATTR-FAP is a progressive condition caused by mutations in the TTR gene that destabilize the TTR protein, thereby facilitating misfolding and aggregation. The neuropathy may be accompanied by cardiac, gastrointestinal, renal, or ocular symptoms, and death occurs at an average of 10 years after symptom onset.

A pivotal phase III trial compared tafamidis with placebo over 18 months in 128 patients with early-stage ATTR-FAP. Researchers observed a trend toward a smaller increase in Neuropathy Impairment Score for Lower Limbs (NIS-LL) with tafamidis, compared with placebo, but the result was not statistically significant. Baseline NIS-LL values were higher among controls than among actively treated patients, however, and many participants dropped out of the study for liver transplantation.

In a post hoc analysis, the investigators took these factors into account and reanalyzed change from baseline in NIS-LL in the trial. They also analyzed change in NIS-LL plus three small-fiber nerve tests (NIS-LL+Σ3) and NIS-LL plus seven nerve tests (NIS-LL+Σ7) without baseline measurements as covariates.

The analysis indicated a significant benefit of tafamidis, compared with placebo, at Months 12 and 18. The baseline-adjusted mean increase in NIS-LL from baseline to Month 12 was 1.5 points in the tafamidis group versus 4.5 points in the placebo group. By Month 18, the mean change from baseline was 2.9 points in the tafamidis group versus 5.6 points in the placebo group.

When the researchers applied sensitivity analysis based on multiple imputation for missing data by treatment group, the mean estimates of the increase in NIS-LL total score from baseline to Month 18 were significantly lower for tafamidis, compared with placebo. A more conservative model based on multiple imputation showed a benefit of tafamidis, but results did not reach statistical significance.

The researchers also found a statistically significant benefit of tafamidis, compared with placebo, on NIS-LL+Σ3 at Months 12 and 18. Significant differences favoring tafamidis also were observed on NIS-LL+Σ7 at Months 12 and 18. Four of the study’s five authors are employees of Pfizer, which owns tafamidis and sponsored the study.

—Erik Greb

Suggested Reading

Keohane D, Schwartz J, Gundapaneni B, et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Apr 10 [Epub ahead of print].

Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin familial amyloid polyneuropathy (ATTR-FAP), according to research published online ahead of print April 10 in Amyloid.

ATTR-FAP is a progressive condition caused by mutations in the TTR gene that destabilize the TTR protein, thereby facilitating misfolding and aggregation. The neuropathy may be accompanied by cardiac, gastrointestinal, renal, or ocular symptoms, and death occurs at an average of 10 years after symptom onset.

A pivotal phase III trial compared tafamidis with placebo over 18 months in 128 patients with early-stage ATTR-FAP. Researchers observed a trend toward a smaller increase in Neuropathy Impairment Score for Lower Limbs (NIS-LL) with tafamidis, compared with placebo, but the result was not statistically significant. Baseline NIS-LL values were higher among controls than among actively treated patients, however, and many participants dropped out of the study for liver transplantation.

In a post hoc analysis, the investigators took these factors into account and reanalyzed change from baseline in NIS-LL in the trial. They also analyzed change in NIS-LL plus three small-fiber nerve tests (NIS-LL+Σ3) and NIS-LL plus seven nerve tests (NIS-LL+Σ7) without baseline measurements as covariates.

The analysis indicated a significant benefit of tafamidis, compared with placebo, at Months 12 and 18. The baseline-adjusted mean increase in NIS-LL from baseline to Month 12 was 1.5 points in the tafamidis group versus 4.5 points in the placebo group. By Month 18, the mean change from baseline was 2.9 points in the tafamidis group versus 5.6 points in the placebo group.

When the researchers applied sensitivity analysis based on multiple imputation for missing data by treatment group, the mean estimates of the increase in NIS-LL total score from baseline to Month 18 were significantly lower for tafamidis, compared with placebo. A more conservative model based on multiple imputation showed a benefit of tafamidis, but results did not reach statistical significance.

The researchers also found a statistically significant benefit of tafamidis, compared with placebo, on NIS-LL+Σ3 at Months 12 and 18. Significant differences favoring tafamidis also were observed on NIS-LL+Σ7 at Months 12 and 18. Four of the study’s five authors are employees of Pfizer, which owns tafamidis and sponsored the study.

—Erik Greb

Suggested Reading

Keohane D, Schwartz J, Gundapaneni B, et al. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Apr 10 [Epub ahead of print].

Researchers have shown that the negative prognostic characteristics of the C9orf72 repeat expansion in amyotrophic lateral sclerosis (ALS) apply primarily to males with spinal-onset disease, according to a report in the April issue of the Journal of Neurology, Neurosurgery and Psychiatry. This finding represents “a hitherto unrecognized gender-mediated effect of the genetic variant,” said lead author James Rooney, MD, a research fellow in the Academic Unit of Neurology at Trinity College Dublin.

The C9orf72 mutation represents the most common genetic cause of ALS. It affects up to 50% of familial cases and 20% of sporadic cases and is associated with a distinctive clinical phenotype that sometimes includes frontotemporal dementia. The C9orf72 repeat expansion previously has been reported as a negative prognostic factor in ALS, but studies have not been sufficiently powered to determine how the expanded variant affects subgroups of patients. To further explore the interaction of the genetic variant with demographic features, Dr. Rooney and colleagues examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset.

C9orf72 status in combination with demographic and clinical data was drawn from 4,925 patients with ALS in three prospective national ALS registries (Ireland, Italy, and the Netherlands) and clinical data sets in the United Kingdom and Belgium. Flexible parametric survival models were built including known prognostic factors (eg, age, diagnostic delay, and site of onset), gender, and the presence of an expanded repeat in C9orf72. These models were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data meta-analysis was used to estimate hazard ratios for results of particular importance.

A total of 457 (8.95%) of the 4,925 patients carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival hazard ratio of 1.36 (range, 1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion primarily occurred in males with spinal-onset disease (hazard ratio, 1.56).

“Within this cohort, the median age of onset was 59.3, and the median survival was 2.29 years,” Dr. Rooney reported. These results compared with a median age of onset of 62.3 and median survival of 2.77 years in all other spinal-onset disease, with a median age of onset of 65 and median survival of 2.38 years in all bulbar-onset disease. “Moreover, and contrary to the usual pattern in young-onset disease, male spinal-onset C9orf72 expanded cases were also more likely to have experienced a shorter diagnostic delay, suggesting rapidly progressing disease,” he said.

“Dissecting prognostic factors associated with C9orf72 remains essential and highly relevant for the design of future therapeutic strategies,” said José Manuel Matamala, MD, and colleagues in an accompanying editorial. Dr. Matamala is affiliated with the Brain and Mind Centre at the University of Sydney.

—Glenn S. Williams

Suggested Reading

Rooney J, Fogh I, Westeneng HJ, et al. C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(4):295-300.

Matamala JM, Dharmadasa T, Kiernan MC. Prognostic factors in C9orf72 amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(4):281.

Researchers have shown that the negative prognostic characteristics of the C9orf72 repeat expansion in amyotrophic lateral sclerosis (ALS) apply primarily to males with spinal-onset disease, according to a report in the April issue of the Journal of Neurology, Neurosurgery and Psychiatry. This finding represents “a hitherto unrecognized gender-mediated effect of the genetic variant,” said lead author James Rooney, MD, a research fellow in the Academic Unit of Neurology at Trinity College Dublin.

The C9orf72 mutation represents the most common genetic cause of ALS. It affects up to 50% of familial cases and 20% of sporadic cases and is associated with a distinctive clinical phenotype that sometimes includes frontotemporal dementia. The C9orf72 repeat expansion previously has been reported as a negative prognostic factor in ALS, but studies have not been sufficiently powered to determine how the expanded variant affects subgroups of patients. To further explore the interaction of the genetic variant with demographic features, Dr. Rooney and colleagues examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset.

C9orf72 status in combination with demographic and clinical data was drawn from 4,925 patients with ALS in three prospective national ALS registries (Ireland, Italy, and the Netherlands) and clinical data sets in the United Kingdom and Belgium. Flexible parametric survival models were built including known prognostic factors (eg, age, diagnostic delay, and site of onset), gender, and the presence of an expanded repeat in C9orf72. These models were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data meta-analysis was used to estimate hazard ratios for results of particular importance.

A total of 457 (8.95%) of the 4,925 patients carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival hazard ratio of 1.36 (range, 1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion primarily occurred in males with spinal-onset disease (hazard ratio, 1.56).

“Within this cohort, the median age of onset was 59.3, and the median survival was 2.29 years,” Dr. Rooney reported. These results compared with a median age of onset of 62.3 and median survival of 2.77 years in all other spinal-onset disease, with a median age of onset of 65 and median survival of 2.38 years in all bulbar-onset disease. “Moreover, and contrary to the usual pattern in young-onset disease, male spinal-onset C9orf72 expanded cases were also more likely to have experienced a shorter diagnostic delay, suggesting rapidly progressing disease,” he said.

“Dissecting prognostic factors associated with C9orf72 remains essential and highly relevant for the design of future therapeutic strategies,” said José Manuel Matamala, MD, and colleagues in an accompanying editorial. Dr. Matamala is affiliated with the Brain and Mind Centre at the University of Sydney.

—Glenn S. Williams

Suggested Reading

Rooney J, Fogh I, Westeneng HJ, et al. C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(4):295-300.

Matamala JM, Dharmadasa T, Kiernan MC. Prognostic factors in C9orf72 amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(4):281.

Researchers have shown that the negative prognostic characteristics of the C9orf72 repeat expansion in amyotrophic lateral sclerosis (ALS) apply primarily to males with spinal-onset disease, according to a report in the April issue of the Journal of Neurology, Neurosurgery and Psychiatry. This finding represents “a hitherto unrecognized gender-mediated effect of the genetic variant,” said lead author James Rooney, MD, a research fellow in the Academic Unit of Neurology at Trinity College Dublin.

The C9orf72 mutation represents the most common genetic cause of ALS. It affects up to 50% of familial cases and 20% of sporadic cases and is associated with a distinctive clinical phenotype that sometimes includes frontotemporal dementia. The C9orf72 repeat expansion previously has been reported as a negative prognostic factor in ALS, but studies have not been sufficiently powered to determine how the expanded variant affects subgroups of patients. To further explore the interaction of the genetic variant with demographic features, Dr. Rooney and colleagues examined the prognostic impact of the C9orf72 repeat expansion in European subgroups based on gender and site of onset.

C9orf72 status in combination with demographic and clinical data was drawn from 4,925 patients with ALS in three prospective national ALS registries (Ireland, Italy, and the Netherlands) and clinical data sets in the United Kingdom and Belgium. Flexible parametric survival models were built including known prognostic factors (eg, age, diagnostic delay, and site of onset), gender, and the presence of an expanded repeat in C9orf72. These models were used to explore the effects of C9orf72 on survival by gender and site of onset. Individual patient data meta-analysis was used to estimate hazard ratios for results of particular importance.

A total of 457 (8.95%) of the 4,925 patients carried the C9orf72 repeat expansion. A meta-analysis of C9orf72 estimated a survival hazard ratio of 1.36 (range, 1.18 to 1.57) for those carrying the expansion. Models evaluating interaction between gender and C9orf72 repeat expansions demonstrated that the reduced survival due to C9orf72 expansion primarily occurred in males with spinal-onset disease (hazard ratio, 1.56).

“Within this cohort, the median age of onset was 59.3, and the median survival was 2.29 years,” Dr. Rooney reported. These results compared with a median age of onset of 62.3 and median survival of 2.77 years in all other spinal-onset disease, with a median age of onset of 65 and median survival of 2.38 years in all bulbar-onset disease. “Moreover, and contrary to the usual pattern in young-onset disease, male spinal-onset C9orf72 expanded cases were also more likely to have experienced a shorter diagnostic delay, suggesting rapidly progressing disease,” he said.

“Dissecting prognostic factors associated with C9orf72 remains essential and highly relevant for the design of future therapeutic strategies,” said José Manuel Matamala, MD, and colleagues in an accompanying editorial. Dr. Matamala is affiliated with the Brain and Mind Centre at the University of Sydney.

—Glenn S. Williams

Suggested Reading

Rooney J, Fogh I, Westeneng HJ, et al. C9orf72 expansion differentially affects males with spinal onset amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(4):295-300.

Matamala JM, Dharmadasa T, Kiernan MC. Prognostic factors in C9orf72 amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(4):281.

A new guideline codeveloped by the American Academy of Neurology and the American Epilepsy Society is intended to aid clinicians as they counsel patients about SUDEP. The practice guideline, published in the April 25 issue of Neurology, provides information about SUDEP incidence in different epilepsy populations, data about risk factors, and recommendations for patient care.

“Our guideline brings clarity to the [SUDEP] discussion, giving health care providers practical information they can use to help people with epilepsy reduce their risk,” said Cynthia Harden, MD, Director of Epilepsy Services for the Mount Sinai Health System in New York City.

A panel of experts searched the MEDLINE and Embase databases from the earliest available article to November 2010. An identical search was performed in April 2015 for articles published since November 2010. The keywords for both searches were “SUDEP” and other traditional medical subheadings for epilepsy (eg, “epilepsy/abnormalities,” “epilepsy/drug effects,” or “epilepsy/therapy”).

After reviewing more than 1,000 abstracts, the panel selected 70 relevant articles. The team then conducted a systematic review and developed conclusions using the modified Grading Recommendations Assessment, Development, and Evaluation process. All recommendations were made by consensus.

Incidence rates were based on 12 Class I studies. The systematic review found that SUDEP affects one in 4,500 children with epilepsy per year. Based on these findings, the experts recommend that clinicians inform parents or guardians about this low risk of SUDEP in children (Level B). In addition, the panel recommends that clinicians inform adult patients about the small risk of SUDEP, which typically affects one in 1,000 adults with epilepsy annually (Level B).

The panel also found that generalized tonic-clonic seizures, which involve convulsions and loss of consciousness, are a major risk factor for SUDEP. In addition, they noted that patients who have three or more of these seizures per year have a 15-fold increased risk of SUDEP. To reduce this risk, clinicians are advised to manage epilepsy therapies actively in these patients to reduce seizures (Level B).

The guideline also recommends nocturnal supervision or other nocturnal precautions for patients who experience frequent generalized tonic-clonic seizures and nocturnal seizures (Level C). Furthermore, the presence of an additional person age 10 or older in the bedroom is associated with a decreased SUDEP risk. If individualized epilepsy and psychosocial circumstances permit, such a person should be present, said the panel. Providing nighttime observation might be overly burdensome or intrusive for some patients, the authors added.

Finally, clinicians are advised to inform patients that seizure freedom, especially freedom from generalized tonic-clonic seizures, is strongly associated with a decreased risk of SUDEP (Level B). The panel also analyzed other SUDEP risk factors (eg, lamotrigine use in women, heart rate variability, and male gender), but too little evidence was available to support recommendations.

“Research to identify preventable risk factors should be supported and encouraged so that future clinical trials will be conducted to reduce SUDEP occurrence,” said Dr. Harden.

—Erica Tricarico

Suggested Reading

Harden C, Tomson T, Gloss D, et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2017;88(17):1674-1680.

A new guideline codeveloped by the American Academy of Neurology and the American Epilepsy Society is intended to aid clinicians as they counsel patients about SUDEP. The practice guideline, published in the April 25 issue of Neurology, provides information about SUDEP incidence in different epilepsy populations, data about risk factors, and recommendations for patient care.

“Our guideline brings clarity to the [SUDEP] discussion, giving health care providers practical information they can use to help people with epilepsy reduce their risk,” said Cynthia Harden, MD, Director of Epilepsy Services for the Mount Sinai Health System in New York City.

A panel of experts searched the MEDLINE and Embase databases from the earliest available article to November 2010. An identical search was performed in April 2015 for articles published since November 2010. The keywords for both searches were “SUDEP” and other traditional medical subheadings for epilepsy (eg, “epilepsy/abnormalities,” “epilepsy/drug effects,” or “epilepsy/therapy”).

After reviewing more than 1,000 abstracts, the panel selected 70 relevant articles. The team then conducted a systematic review and developed conclusions using the modified Grading Recommendations Assessment, Development, and Evaluation process. All recommendations were made by consensus.

Incidence rates were based on 12 Class I studies. The systematic review found that SUDEP affects one in 4,500 children with epilepsy per year. Based on these findings, the experts recommend that clinicians inform parents or guardians about this low risk of SUDEP in children (Level B). In addition, the panel recommends that clinicians inform adult patients about the small risk of SUDEP, which typically affects one in 1,000 adults with epilepsy annually (Level B).

The panel also found that generalized tonic-clonic seizures, which involve convulsions and loss of consciousness, are a major risk factor for SUDEP. In addition, they noted that patients who have three or more of these seizures per year have a 15-fold increased risk of SUDEP. To reduce this risk, clinicians are advised to manage epilepsy therapies actively in these patients to reduce seizures (Level B).

The guideline also recommends nocturnal supervision or other nocturnal precautions for patients who experience frequent generalized tonic-clonic seizures and nocturnal seizures (Level C). Furthermore, the presence of an additional person age 10 or older in the bedroom is associated with a decreased SUDEP risk. If individualized epilepsy and psychosocial circumstances permit, such a person should be present, said the panel. Providing nighttime observation might be overly burdensome or intrusive for some patients, the authors added.

Finally, clinicians are advised to inform patients that seizure freedom, especially freedom from generalized tonic-clonic seizures, is strongly associated with a decreased risk of SUDEP (Level B). The panel also analyzed other SUDEP risk factors (eg, lamotrigine use in women, heart rate variability, and male gender), but too little evidence was available to support recommendations.

“Research to identify preventable risk factors should be supported and encouraged so that future clinical trials will be conducted to reduce SUDEP occurrence,” said Dr. Harden.

—Erica Tricarico

Suggested Reading

Harden C, Tomson T, Gloss D, et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2017;88(17):1674-1680.

A new guideline codeveloped by the American Academy of Neurology and the American Epilepsy Society is intended to aid clinicians as they counsel patients about SUDEP. The practice guideline, published in the April 25 issue of Neurology, provides information about SUDEP incidence in different epilepsy populations, data about risk factors, and recommendations for patient care.

“Our guideline brings clarity to the [SUDEP] discussion, giving health care providers practical information they can use to help people with epilepsy reduce their risk,” said Cynthia Harden, MD, Director of Epilepsy Services for the Mount Sinai Health System in New York City.

A panel of experts searched the MEDLINE and Embase databases from the earliest available article to November 2010. An identical search was performed in April 2015 for articles published since November 2010. The keywords for both searches were “SUDEP” and other traditional medical subheadings for epilepsy (eg, “epilepsy/abnormalities,” “epilepsy/drug effects,” or “epilepsy/therapy”).

After reviewing more than 1,000 abstracts, the panel selected 70 relevant articles. The team then conducted a systematic review and developed conclusions using the modified Grading Recommendations Assessment, Development, and Evaluation process. All recommendations were made by consensus.

Incidence rates were based on 12 Class I studies. The systematic review found that SUDEP affects one in 4,500 children with epilepsy per year. Based on these findings, the experts recommend that clinicians inform parents or guardians about this low risk of SUDEP in children (Level B). In addition, the panel recommends that clinicians inform adult patients about the small risk of SUDEP, which typically affects one in 1,000 adults with epilepsy annually (Level B).

The panel also found that generalized tonic-clonic seizures, which involve convulsions and loss of consciousness, are a major risk factor for SUDEP. In addition, they noted that patients who have three or more of these seizures per year have a 15-fold increased risk of SUDEP. To reduce this risk, clinicians are advised to manage epilepsy therapies actively in these patients to reduce seizures (Level B).

The guideline also recommends nocturnal supervision or other nocturnal precautions for patients who experience frequent generalized tonic-clonic seizures and nocturnal seizures (Level C). Furthermore, the presence of an additional person age 10 or older in the bedroom is associated with a decreased SUDEP risk. If individualized epilepsy and psychosocial circumstances permit, such a person should be present, said the panel. Providing nighttime observation might be overly burdensome or intrusive for some patients, the authors added.

Finally, clinicians are advised to inform patients that seizure freedom, especially freedom from generalized tonic-clonic seizures, is strongly associated with a decreased risk of SUDEP (Level B). The panel also analyzed other SUDEP risk factors (eg, lamotrigine use in women, heart rate variability, and male gender), but too little evidence was available to support recommendations.

“Research to identify preventable risk factors should be supported and encouraged so that future clinical trials will be conducted to reduce SUDEP occurrence,” said Dr. Harden.

—Erica Tricarico

Suggested Reading

Harden C, Tomson T, Gloss D, et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2017;88(17):1674-1680.

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

A Large Case–Control Analysis

Previous studies have provided evidence for an MS prodrome that occurs years before a demyelinating event or the onset of clinical symptoms. Many of these studies, however, have been limited by a retrospective design or by the absence of a control group.

To analyze the question further, Dr. Tremlett and colleagues examined data from linked health administrative and clinical databases in the Canadian provinces of British Columbia, Saskatchewan, Manitoba, and Nova Scotia, which were chosen for their geographic diversity and comprehensive data. The researchers created a health administrative cohort, which was based on administrative data, and an MS clinic-derived cohort, which used administrative and clinical data. The study’s primary outcome was all-cause use of health care during each of the five years before the health administrative index date (ie, the first demyelinating disease-related claim) or clinical index date (ie, the date of MS symptom onset).

Health Care Use Increased in Prodromal MS

The health administrative cohort included 14,428 people with MS and 72,059 matched controls. In all, 10,525 (73%) of the patients with MS were women, and their mean age at the health administrative index date was 43. Compared with controls, annual health care use increased steadily between five years and one year before the first demyelinating disease claim in these patients.

The mean number of hospital admissions was 26% higher in people with MS than in controls in the fifth year before the index date, and 78% higher in the year before the index date. The mean number of physician claims was 24% higher in people with MS than in controls in the fifth year before the index date, and 88% higher in people with MS than in controls in the year before the index date. Also, the mean number of prescribed drug classes was 23% higher in people with MS than in matched controls in the fifth year before the index date, and 49% higher in people with MS than in controls in the year before the index date.

The MS clinic cohort included 3,202 people with MS and 16,006 matched controls. In all, 2,368 (74%) of people with MS were women, and the mean age at the clinical index date was approximately 37. Compared with the health administrative cohort, this cohort had similar patterns for physician claims and prescriptions, although the differences in use in each of the five years mostly did not reach statistical significance.

“To gain a better insight into the MS prodrome, the complex reasons for increased health care use will need to be established, for example, through access of additional administrative data such as the specific diagnostic codes related to a hospital admission or physician visit, or the therapeutic drug class for a prescription,” Dr. Tremlett concluded.

—Erik Greb

Suggested Reading

Wijnands JMA, Kingwell E, Zhu F, et al. Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study. Lancet Neurol. 2017 Apr 20 [Epub ahead of print].

Contrary to the widespread belief that depressive disorders are more common than anxiety disorders among people with epilepsy, these psychiatric comorbidities appear to have equivalent prevalence, according to research published online ahead of print May 3 in Epilepsia. In addition, variability in the observed prevalence of anxiety disorders in previous studies partly results from the method of diagnosis.

“These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy,” said Amelia J. Scott, a PhD candidate at the University of Sydney.

Comorbid anxiety and depressive disorders are highly prevalent in patients with epilepsy, compared with the general population. The prevalence of anxiety disorders reported in previous studies of people with epilepsy has been highly variable, however. Ms. Scott and colleagues conducted a study to clarify the prevalence of anxiety and depressive disorders in patients with epilepsy and to determine which factors account for the variability in estimates of these disorders’ prevalence.

The investigators searched electronic databases to find studies that reported the prevalence of anxiety and depressive disorders in people with epilepsy until July 2016. Journal articles or dissertations that reported on current diagnoses of anxiety and depressive disorders based on a structured diagnostic interview or a clinician evaluation were included. Clinician evaluations followed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or the International Classification of Diseases, Tenth Revision or more recent.

The investigators excluded studies of participants younger than 16. In addition, studies that reported diagnoses of anxiety and depressive disorders using self-report measures and studies that only reported a depression diagnosis or only an anxiety diagnosis were also excluded. Finally, researchers excluded studies if recruitment was based on additional medical comorbidity or on results of prescreening measures of distress.

Extracted data included the prevalence of anxiety and depressive disorders and moderators of interest (eg, method of diagnosis and prevalence of drug-resistant epilepsy). Using these data, Ms. Scott and colleagues conducted a meta-analysis of the overall pooled prevalence of anxiety and depressive disorders.

In all, 27 studies met the inclusion criteria. The pooled prevalence of anxiety disorders was 20.2%, and the pooled prevalence of depressive disorders was 22.9%. Ms. Scott and colleagues also observed that the method of diagnosis significantly affected the observed prevalence of anxiety disorders. The prevalence of anxiety disorders based on unstructured clinician assessment was 8.1%, compared with a prevalence of 27.3% based on a structured clinical interview. No significant moderators of depressive disorder diagnosis were reported, however.

“Future research should aim to improve the detection and management of comorbidities in people with epilepsy, particularly anxiety disorders, which have remained relatively neglected,” said Ms. Scott. “An improvement in our understanding, detection, and management of both anxiety and depressive disorders in people with epilepsy is crucial to improve the quality of life of people with epilepsy.”

—Erica Tricarico

Suggested Reading

Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017 May 3 [Epub ahead of print].

Contrary to the widespread belief that depressive disorders are more common than anxiety disorders among people with epilepsy, these psychiatric comorbidities appear to have equivalent prevalence, according to research published online ahead of print May 3 in Epilepsia. In addition, variability in the observed prevalence of anxiety disorders in previous studies partly results from the method of diagnosis.

“These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy,” said Amelia J. Scott, a PhD candidate at the University of Sydney.

Comorbid anxiety and depressive disorders are highly prevalent in patients with epilepsy, compared with the general population. The prevalence of anxiety disorders reported in previous studies of people with epilepsy has been highly variable, however. Ms. Scott and colleagues conducted a study to clarify the prevalence of anxiety and depressive disorders in patients with epilepsy and to determine which factors account for the variability in estimates of these disorders’ prevalence.

The investigators searched electronic databases to find studies that reported the prevalence of anxiety and depressive disorders in people with epilepsy until July 2016. Journal articles or dissertations that reported on current diagnoses of anxiety and depressive disorders based on a structured diagnostic interview or a clinician evaluation were included. Clinician evaluations followed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or the International Classification of Diseases, Tenth Revision or more recent.

The investigators excluded studies of participants younger than 16. In addition, studies that reported diagnoses of anxiety and depressive disorders using self-report measures and studies that only reported a depression diagnosis or only an anxiety diagnosis were also excluded. Finally, researchers excluded studies if recruitment was based on additional medical comorbidity or on results of prescreening measures of distress.

Extracted data included the prevalence of anxiety and depressive disorders and moderators of interest (eg, method of diagnosis and prevalence of drug-resistant epilepsy). Using these data, Ms. Scott and colleagues conducted a meta-analysis of the overall pooled prevalence of anxiety and depressive disorders.

In all, 27 studies met the inclusion criteria. The pooled prevalence of anxiety disorders was 20.2%, and the pooled prevalence of depressive disorders was 22.9%. Ms. Scott and colleagues also observed that the method of diagnosis significantly affected the observed prevalence of anxiety disorders. The prevalence of anxiety disorders based on unstructured clinician assessment was 8.1%, compared with a prevalence of 27.3% based on a structured clinical interview. No significant moderators of depressive disorder diagnosis were reported, however.

“Future research should aim to improve the detection and management of comorbidities in people with epilepsy, particularly anxiety disorders, which have remained relatively neglected,” said Ms. Scott. “An improvement in our understanding, detection, and management of both anxiety and depressive disorders in people with epilepsy is crucial to improve the quality of life of people with epilepsy.”

—Erica Tricarico

Suggested Reading

Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017 May 3 [Epub ahead of print].

Contrary to the widespread belief that depressive disorders are more common than anxiety disorders among people with epilepsy, these psychiatric comorbidities appear to have equivalent prevalence, according to research published online ahead of print May 3 in Epilepsia. In addition, variability in the observed prevalence of anxiety disorders in previous studies partly results from the method of diagnosis.

“These findings also challenge widely held assumptions that psychiatric comorbidity is more common in people with drug-resistant epilepsy,” said Amelia J. Scott, a PhD candidate at the University of Sydney.

Comorbid anxiety and depressive disorders are highly prevalent in patients with epilepsy, compared with the general population. The prevalence of anxiety disorders reported in previous studies of people with epilepsy has been highly variable, however. Ms. Scott and colleagues conducted a study to clarify the prevalence of anxiety and depressive disorders in patients with epilepsy and to determine which factors account for the variability in estimates of these disorders’ prevalence.

The investigators searched electronic databases to find studies that reported the prevalence of anxiety and depressive disorders in people with epilepsy until July 2016. Journal articles or dissertations that reported on current diagnoses of anxiety and depressive disorders based on a structured diagnostic interview or a clinician evaluation were included. Clinician evaluations followed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition or the International Classification of Diseases, Tenth Revision or more recent.

The investigators excluded studies of participants younger than 16. In addition, studies that reported diagnoses of anxiety and depressive disorders using self-report measures and studies that only reported a depression diagnosis or only an anxiety diagnosis were also excluded. Finally, researchers excluded studies if recruitment was based on additional medical comorbidity or on results of prescreening measures of distress.

Extracted data included the prevalence of anxiety and depressive disorders and moderators of interest (eg, method of diagnosis and prevalence of drug-resistant epilepsy). Using these data, Ms. Scott and colleagues conducted a meta-analysis of the overall pooled prevalence of anxiety and depressive disorders.

In all, 27 studies met the inclusion criteria. The pooled prevalence of anxiety disorders was 20.2%, and the pooled prevalence of depressive disorders was 22.9%. Ms. Scott and colleagues also observed that the method of diagnosis significantly affected the observed prevalence of anxiety disorders. The prevalence of anxiety disorders based on unstructured clinician assessment was 8.1%, compared with a prevalence of 27.3% based on a structured clinical interview. No significant moderators of depressive disorder diagnosis were reported, however.

“Future research should aim to improve the detection and management of comorbidities in people with epilepsy, particularly anxiety disorders, which have remained relatively neglected,” said Ms. Scott. “An improvement in our understanding, detection, and management of both anxiety and depressive disorders in people with epilepsy is crucial to improve the quality of life of people with epilepsy.”

—Erica Tricarico

Suggested Reading

Scott AJ, Sharpe L, Hunt C, Gandy M. Anxiety and depressive disorders in people with epilepsy: A meta-analysis. Epilepsia. 2017 May 3 [Epub ahead of print].

Truncal vagotomy may be associated with a reduced risk of incident Parkinson’s disease, according to data published online ahead of print April 26 in Neurology. Selective vagotomy, however, is not associated with risk of Parkinson’s disease. These findings provide support for the theory that Parkinson’s disease begins in the gut and spreads to the brain via the vagus nerve, according to the authors.

Braak et al have hypothesized that Lewy pathology in Parkinson’s disease may start in peripheral nerves, such as the enteric nervous system, and spread to the CNS in a way similar to the propagation of prions. Researchers have found Lewy-type deposition in the gut of people with prodromal Parkinson’s disease. In addition, resection of the vagus nerve before administration of rotenone, which prompts alpha-synuclein accumulation, stopped the spread of parkinsonian pathology in mice.

To examine whether vagotomy decreases the risk of Parkinson’s disease, Bojing Liu, a doctoral student at the Karolinska Institutet in Stockholm, and colleagues conducted a matched-cohort study using data from nationwide Swedish registers. The investigators identified 9,430 patients who underwent vagotomy (3,445 truncal, 5,978 selective, and seven unknown) between 1970 and 2010. Eligible participants were born before 1970 and lived in Sweden without a diagnosis of Parkinson’s disease before vagotomy. To each of these patients, the researchers individually matched 377,200 reference individuals from the general population by sex and year of birth in a 40:1 ratio. Participants were followed up from the date of vagotomy until Parkinson’s disease diagnosis, death, emigration out of Sweden, or December 31, 2010, whichever occurred first.

Participants’ mean age at index date was 54. The investigators identified 4,930 cases of Parkinson’s disease during follow-up, and mean age at diagnosis was 76. Although the study groups were otherwise well balanced, proportionally more patients who underwent vagotomy were born outside Sweden, compared with controls. Participants who underwent truncal vagotomy were older than those who underwent selective vagotomy and older than controls.

Ms. Liu and colleagues did not find an association between vagotomy and Parkinson’s disease overall. They did, however, observe a lower risk of Parkinson’s disease more than five years after truncal vagotomy (hazard ratio [HR], 0.59) and more than 10 years after truncal vagotomy (HR, 0.62). Selective vagotomy was not associated with Parkinson’s disease risk in any of the analyses.

“Our observation of the temporal relationship is consistent with the possibility that Parkinson’s disease pathology may start at multiple sites of the peripheral nervous system. Therefore, even truncal vagotomy may delay rather than eliminate the risk for Parkinson’s disease,” said Ms. Liu and colleagues. She acknowledged that she and her colleagues were unable to control for potential individual confounders such as smoking, coffee consumption, or genetic factors.

“If the observed association is confirmed and proven to be biologic, we expect the results could be generalized to populations in other parts of the world,” Ms. Liu continued. “These data provide preliminary and indirect support for the Braak and prion-like hypotheses for Parkinson’s disease prodromal development.”

—Erik Greb

Suggested Reading

Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology. 2017 Apr 26 [Epub ahead of print].

Truncal vagotomy may be associated with a reduced risk of incident Parkinson’s disease, according to data published online ahead of print April 26 in Neurology. Selective vagotomy, however, is not associated with risk of Parkinson’s disease. These findings provide support for the theory that Parkinson’s disease begins in the gut and spreads to the brain via the vagus nerve, according to the authors.

Braak et al have hypothesized that Lewy pathology in Parkinson’s disease may start in peripheral nerves, such as the enteric nervous system, and spread to the CNS in a way similar to the propagation of prions. Researchers have found Lewy-type deposition in the gut of people with prodromal Parkinson’s disease. In addition, resection of the vagus nerve before administration of rotenone, which prompts alpha-synuclein accumulation, stopped the spread of parkinsonian pathology in mice.

To examine whether vagotomy decreases the risk of Parkinson’s disease, Bojing Liu, a doctoral student at the Karolinska Institutet in Stockholm, and colleagues conducted a matched-cohort study using data from nationwide Swedish registers. The investigators identified 9,430 patients who underwent vagotomy (3,445 truncal, 5,978 selective, and seven unknown) between 1970 and 2010. Eligible participants were born before 1970 and lived in Sweden without a diagnosis of Parkinson’s disease before vagotomy. To each of these patients, the researchers individually matched 377,200 reference individuals from the general population by sex and year of birth in a 40:1 ratio. Participants were followed up from the date of vagotomy until Parkinson’s disease diagnosis, death, emigration out of Sweden, or December 31, 2010, whichever occurred first.

Participants’ mean age at index date was 54. The investigators identified 4,930 cases of Parkinson’s disease during follow-up, and mean age at diagnosis was 76. Although the study groups were otherwise well balanced, proportionally more patients who underwent vagotomy were born outside Sweden, compared with controls. Participants who underwent truncal vagotomy were older than those who underwent selective vagotomy and older than controls.

Ms. Liu and colleagues did not find an association between vagotomy and Parkinson’s disease overall. They did, however, observe a lower risk of Parkinson’s disease more than five years after truncal vagotomy (hazard ratio [HR], 0.59) and more than 10 years after truncal vagotomy (HR, 0.62). Selective vagotomy was not associated with Parkinson’s disease risk in any of the analyses.

“Our observation of the temporal relationship is consistent with the possibility that Parkinson’s disease pathology may start at multiple sites of the peripheral nervous system. Therefore, even truncal vagotomy may delay rather than eliminate the risk for Parkinson’s disease,” said Ms. Liu and colleagues. She acknowledged that she and her colleagues were unable to control for potential individual confounders such as smoking, coffee consumption, or genetic factors.

“If the observed association is confirmed and proven to be biologic, we expect the results could be generalized to populations in other parts of the world,” Ms. Liu continued. “These data provide preliminary and indirect support for the Braak and prion-like hypotheses for Parkinson’s disease prodromal development.”

—Erik Greb

Suggested Reading

Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology. 2017 Apr 26 [Epub ahead of print].

Truncal vagotomy may be associated with a reduced risk of incident Parkinson’s disease, according to data published online ahead of print April 26 in Neurology. Selective vagotomy, however, is not associated with risk of Parkinson’s disease. These findings provide support for the theory that Parkinson’s disease begins in the gut and spreads to the brain via the vagus nerve, according to the authors.

Braak et al have hypothesized that Lewy pathology in Parkinson’s disease may start in peripheral nerves, such as the enteric nervous system, and spread to the CNS in a way similar to the propagation of prions. Researchers have found Lewy-type deposition in the gut of people with prodromal Parkinson’s disease. In addition, resection of the vagus nerve before administration of rotenone, which prompts alpha-synuclein accumulation, stopped the spread of parkinsonian pathology in mice.

To examine whether vagotomy decreases the risk of Parkinson’s disease, Bojing Liu, a doctoral student at the Karolinska Institutet in Stockholm, and colleagues conducted a matched-cohort study using data from nationwide Swedish registers. The investigators identified 9,430 patients who underwent vagotomy (3,445 truncal, 5,978 selective, and seven unknown) between 1970 and 2010. Eligible participants were born before 1970 and lived in Sweden without a diagnosis of Parkinson’s disease before vagotomy. To each of these patients, the researchers individually matched 377,200 reference individuals from the general population by sex and year of birth in a 40:1 ratio. Participants were followed up from the date of vagotomy until Parkinson’s disease diagnosis, death, emigration out of Sweden, or December 31, 2010, whichever occurred first.

Participants’ mean age at index date was 54. The investigators identified 4,930 cases of Parkinson’s disease during follow-up, and mean age at diagnosis was 76. Although the study groups were otherwise well balanced, proportionally more patients who underwent vagotomy were born outside Sweden, compared with controls. Participants who underwent truncal vagotomy were older than those who underwent selective vagotomy and older than controls.

Ms. Liu and colleagues did not find an association between vagotomy and Parkinson’s disease overall. They did, however, observe a lower risk of Parkinson’s disease more than five years after truncal vagotomy (hazard ratio [HR], 0.59) and more than 10 years after truncal vagotomy (HR, 0.62). Selective vagotomy was not associated with Parkinson’s disease risk in any of the analyses.

“Our observation of the temporal relationship is consistent with the possibility that Parkinson’s disease pathology may start at multiple sites of the peripheral nervous system. Therefore, even truncal vagotomy may delay rather than eliminate the risk for Parkinson’s disease,” said Ms. Liu and colleagues. She acknowledged that she and her colleagues were unable to control for potential individual confounders such as smoking, coffee consumption, or genetic factors.

“If the observed association is confirmed and proven to be biologic, we expect the results could be generalized to populations in other parts of the world,” Ms. Liu continued. “These data provide preliminary and indirect support for the Braak and prion-like hypotheses for Parkinson’s disease prodromal development.”

—Erik Greb

Suggested Reading

Liu B, Fang F, Pedersen NL, et al. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology. 2017 Apr 26 [Epub ahead of print].

Brain-responsive neurostimulation may be an effective treatment option for patients with mesial temporal lobe epilepsy, according to a recent study of 111 subjects. When following up for an average of 6.1 years on patients who had the procedure, researchers found it reduced seizures by a median average of 70%. Twenty-nine percent of patients had at least 1 seizure free period that lasted at least 6 months and 15% had at least 1 seizure free period lasting at least 1 year.

Geller EB, Skarpaas TL, Gross RE, et al. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy [published online April 11, 2017]. Epilepsia. doi: 10.1111/epi.13740

Brain-responsive neurostimulation may be an effective treatment option for patients with mesial temporal lobe epilepsy, according to a recent study of 111 subjects. When following up for an average of 6.1 years on patients who had the procedure, researchers found it reduced seizures by a median average of 70%. Twenty-nine percent of patients had at least 1 seizure free period that lasted at least 6 months and 15% had at least 1 seizure free period lasting at least 1 year.

Geller EB, Skarpaas TL, Gross RE, et al. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy [published online April 11, 2017]. Epilepsia. doi: 10.1111/epi.13740

Brain-responsive neurostimulation may be an effective treatment option for patients with mesial temporal lobe epilepsy, according to a recent study of 111 subjects. When following up for an average of 6.1 years on patients who had the procedure, researchers found it reduced seizures by a median average of 70%. Twenty-nine percent of patients had at least 1 seizure free period that lasted at least 6 months and 15% had at least 1 seizure free period lasting at least 1 year.

Geller EB, Skarpaas TL, Gross RE, et al. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy [published online April 11, 2017]. Epilepsia. doi: 10.1111/epi.13740

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].

Obesity and underweight status are associated with an increased risk of migraine, according to research published online ahead of print April 12 in Neurology. Age and sex are important covariates of this association.

“As obesity and being underweight are potentially modifiable risk factors for migraine, awareness of these risk factors is vital for both people with migraine and doctors,” said B. Lee Peterlin, DO, Director of Headache Research at Johns Hopkins University School of Medicine in Baltimore. “More research is needed to determine whether efforts to help people lose or gain weight could lower their risk for migraine.”

Previous studies have suggested an association between obesity and increased risk of migraine. These studies differed, however, in the populations they included, the way in which they categorized obesity status, and the way in which they were designed and conducted.

To further evaluate this possible association, Dr. Peterlin and colleagues searched the peer-reviewed literature for studies related to body composition status, as estimated by BMI and World Health Organization (WHO) physical status categories, and migraine. Their meta-analysis included 12 studies that encompassed data from 288,981 participants between ages 18 and 98.

After adjusting for age and sex, Dr. Peterlin and colleagues found that risk of migraine in people with obesity was increased by 27%, compared with people of normal weight. The risk remained increased after multivariate adjustments. Similarly, the age- and sex-adjusted risk of migraine was increased among overweight participants, but the result was not significant after multivariate adjustments were performed. The age- and sex-adjusted risk of migraine in underweight people was increased by 13%, compared with people of normal weight, and remained increased after multivariate adjustments.

“It is not clear how body composition could affect migraine,” said Dr. Peterlin. “Adipose tissue, or fatty tissue, secretes a wide range of molecules that could play a role in developing or triggering migraine. It is also possible that other factors such as changes in physical activity, medications, or other conditions such as depression play a role in the relationship between migraine and body composition.”

Half of the studies included in the meta-analysis relied on self-report of migraine and did not use International Classification of Headache Disorders criteria, thus introducing the potential for recall bias. Furthermore, eight of the studies used self-report of BMI. Previous data have indicated that people with migraine are more likely to underestimate their BMI.

One of the meta-analysis’s strengths, however, is its large sample size. Another is its use of uniform and consistent obesity status categories based on the WHO physical status categories for non-Asian populations.

Additional research could “advance our understanding of migraine and lead to the development of targeted therapeutic strategies based on obesity status,” Dr. Peterlin and colleagues concluded.

—Erik Greb

Suggested Reading

Gelaye B, Sacco S, Brown WJ, et al. Body composition status and the risk of migraine: a meta-analysis. Neurology. 2017 April 12 [Epub ahead of print].