BOSTON—Cannabidiol (CBD) as an add-on therapy may reduce drop seizures by 50% in some adults and children with Lennox-Gastaut syndrome (LGS), according to research presented at the 69th Annual Meeting of the American Academy of Neurology. “Our study found that CBD shows great promise, in that it may reduce seizures that are otherwise difficult to control,” said Anup Patel, MD, a pediatric neurologist at Nationwide Children’s Hospital in Columbus, Ohio.

Evaluating CBD in LGS

LGS is a severe form of epilepsy that starts in childhood and causes multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which can lead to serious injuries. To evaluate the efficacy of add-on CBD for the treatment of drop seizures associated with LGS, Dr. Patel and colleagues conducted a randomized, double-blind, placebo-controlled trial.

Eligible participants were between ages 2 and 55 and had a clinical diagnosis of LGS, eight or more drop seizures during a four-week baseline, and documented failures on one or more antiepileptic drugs. Participants received 20 mg/kg/day of CBD, 10 mg/kg/day of CBD, or placebo for 14 weeks, in addition to their current medications. The primary efficacy end point was the percentage change from baseline in drop seizures per month over the course of the study.

Researchers randomized 225 patients; 76 patients received 20 mg/kg/day of CBD, 73 patients received 10 mg/kg/day of CBD, and 76 patients received placebo. At baseline, the participants had a median monthly drop seizure frequency of 85, and they had previously failed a median of six epilepsy drugs. Participants were taking a median of three epilepsy drugs, in addition to CBD or placebo, throughout the study.

CBD Versus Placebo

Investigators observed a significantly greater reduction in drop seizure frequency in patients who received 20 mg/kg/day of CBD (42%) or 10 mg/kg/day of CBD (37%) than in patients who received placebo (17%). In addition, about 40% of patients who received CBD had at least a 50% reduction in drop seizures, compared with 15% of patients who received placebo.

Ninety-four percent of patients who received the higher dose of CBD reported adverse events, compared with 84% of participants who received the lower dose of CBD and 72% of participants who received placebo. The two most commonly reported adverse events were somnolence and decreased appetite. Most adverse events were mild or moderate. Treatment-related serious adverse events occurred in five patients who received 20 mg/kg/day of CBD and in two patients who received 10 mg/kg/day of CBD. No serious adverse events were reported in the placebo group, and no one died in any of the treatment groups.

In addition, patients who received CBD were more likely to report that their overall condition had improved, compared with patients who received placebo. Sixty-six percent of patients who received CBD reported improvement, compared with 44% of patients who received placebo.

“Our results suggest that CBD may be effective for people with Lennox-Gastaut syndrome in treating drop seizures,” said Dr. Patel. “While there were more side effects for those taking CBD, they were mostly well tolerated. I believe that it may become an important new treatment option for these patients.”

This study was supported by GW Pharmaceuticals, the developer of the CBD formulation.

Suggested Reading

Hussain SA, Zhou R, Jacobson C, et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav. 2015;47:138-141.

BOSTON—Cannabidiol (CBD) as an add-on therapy may reduce drop seizures by 50% in some adults and children with Lennox-Gastaut syndrome (LGS), according to research presented at the 69th Annual Meeting of the American Academy of Neurology. “Our study found that CBD shows great promise, in that it may reduce seizures that are otherwise difficult to control,” said Anup Patel, MD, a pediatric neurologist at Nationwide Children’s Hospital in Columbus, Ohio.

Evaluating CBD in LGS

LGS is a severe form of epilepsy that starts in childhood and causes multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which can lead to serious injuries. To evaluate the efficacy of add-on CBD for the treatment of drop seizures associated with LGS, Dr. Patel and colleagues conducted a randomized, double-blind, placebo-controlled trial.

Eligible participants were between ages 2 and 55 and had a clinical diagnosis of LGS, eight or more drop seizures during a four-week baseline, and documented failures on one or more antiepileptic drugs. Participants received 20 mg/kg/day of CBD, 10 mg/kg/day of CBD, or placebo for 14 weeks, in addition to their current medications. The primary efficacy end point was the percentage change from baseline in drop seizures per month over the course of the study.

Researchers randomized 225 patients; 76 patients received 20 mg/kg/day of CBD, 73 patients received 10 mg/kg/day of CBD, and 76 patients received placebo. At baseline, the participants had a median monthly drop seizure frequency of 85, and they had previously failed a median of six epilepsy drugs. Participants were taking a median of three epilepsy drugs, in addition to CBD or placebo, throughout the study.

CBD Versus Placebo

Investigators observed a significantly greater reduction in drop seizure frequency in patients who received 20 mg/kg/day of CBD (42%) or 10 mg/kg/day of CBD (37%) than in patients who received placebo (17%). In addition, about 40% of patients who received CBD had at least a 50% reduction in drop seizures, compared with 15% of patients who received placebo.

Ninety-four percent of patients who received the higher dose of CBD reported adverse events, compared with 84% of participants who received the lower dose of CBD and 72% of participants who received placebo. The two most commonly reported adverse events were somnolence and decreased appetite. Most adverse events were mild or moderate. Treatment-related serious adverse events occurred in five patients who received 20 mg/kg/day of CBD and in two patients who received 10 mg/kg/day of CBD. No serious adverse events were reported in the placebo group, and no one died in any of the treatment groups.

In addition, patients who received CBD were more likely to report that their overall condition had improved, compared with patients who received placebo. Sixty-six percent of patients who received CBD reported improvement, compared with 44% of patients who received placebo.

“Our results suggest that CBD may be effective for people with Lennox-Gastaut syndrome in treating drop seizures,” said Dr. Patel. “While there were more side effects for those taking CBD, they were mostly well tolerated. I believe that it may become an important new treatment option for these patients.”

This study was supported by GW Pharmaceuticals, the developer of the CBD formulation.

Suggested Reading

Hussain SA, Zhou R, Jacobson C, et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav. 2015;47:138-141.

BOSTON—Cannabidiol (CBD) as an add-on therapy may reduce drop seizures by 50% in some adults and children with Lennox-Gastaut syndrome (LGS), according to research presented at the 69th Annual Meeting of the American Academy of Neurology. “Our study found that CBD shows great promise, in that it may reduce seizures that are otherwise difficult to control,” said Anup Patel, MD, a pediatric neurologist at Nationwide Children’s Hospital in Columbus, Ohio.

Evaluating CBD in LGS

LGS is a severe form of epilepsy that starts in childhood and causes multiple kinds of seizures, including drop seizures and tonic-clonic seizures, which can lead to serious injuries. To evaluate the efficacy of add-on CBD for the treatment of drop seizures associated with LGS, Dr. Patel and colleagues conducted a randomized, double-blind, placebo-controlled trial.

Eligible participants were between ages 2 and 55 and had a clinical diagnosis of LGS, eight or more drop seizures during a four-week baseline, and documented failures on one or more antiepileptic drugs. Participants received 20 mg/kg/day of CBD, 10 mg/kg/day of CBD, or placebo for 14 weeks, in addition to their current medications. The primary efficacy end point was the percentage change from baseline in drop seizures per month over the course of the study.

Researchers randomized 225 patients; 76 patients received 20 mg/kg/day of CBD, 73 patients received 10 mg/kg/day of CBD, and 76 patients received placebo. At baseline, the participants had a median monthly drop seizure frequency of 85, and they had previously failed a median of six epilepsy drugs. Participants were taking a median of three epilepsy drugs, in addition to CBD or placebo, throughout the study.

CBD Versus Placebo

Investigators observed a significantly greater reduction in drop seizure frequency in patients who received 20 mg/kg/day of CBD (42%) or 10 mg/kg/day of CBD (37%) than in patients who received placebo (17%). In addition, about 40% of patients who received CBD had at least a 50% reduction in drop seizures, compared with 15% of patients who received placebo.

Ninety-four percent of patients who received the higher dose of CBD reported adverse events, compared with 84% of participants who received the lower dose of CBD and 72% of participants who received placebo. The two most commonly reported adverse events were somnolence and decreased appetite. Most adverse events were mild or moderate. Treatment-related serious adverse events occurred in five patients who received 20 mg/kg/day of CBD and in two patients who received 10 mg/kg/day of CBD. No serious adverse events were reported in the placebo group, and no one died in any of the treatment groups.

In addition, patients who received CBD were more likely to report that their overall condition had improved, compared with patients who received placebo. Sixty-six percent of patients who received CBD reported improvement, compared with 44% of patients who received placebo.

“Our results suggest that CBD may be effective for people with Lennox-Gastaut syndrome in treating drop seizures,” said Dr. Patel. “While there were more side effects for those taking CBD, they were mostly well tolerated. I believe that it may become an important new treatment option for these patients.”

This study was supported by GW Pharmaceuticals, the developer of the CBD formulation.

Suggested Reading

Hussain SA, Zhou R, Jacobson C, et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav. 2015;47:138-141.

NEW ORLEANS—Two studies presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis (MS) Centers examined the impact of MS and treatment among patients who are members of an online social network. Researchers found that, among patients who were taking oral disease-modifying treatments (DMTs), how the drug was taken was the most important factor in selecting the therapy (36% of patients) almost as often as the doctor’s recommendation (40% of patients), according to the results of a patient survey. In a separate study that analyzed comments made on the social network, researchers found that adverse events were the most commonly stated reason for stopping a treatment (56%).

In one study, Terrie Livingston, PharmD, an employee of Biogen in Weston, Massachusetts, and colleagues conducted a patient survey to assess the impact of MS on day-to-day life, self-reported symptoms, patient descriptions of disability progression, trade-offs when deciding which DMT to take, and what health care providers should know to better manage MS.

In November 2014, researchers sent an email invitation to the entire MyMSTeam community, a social network of approximately 25,000 people (currently more than 75,000 people) diagnosed with MS. In all, 1,107 members responded to the survey.

Overall, the most commonly reported symptoms were fatigue (82% of patients), problems with mobility (64%), and poor balance (64%). In addition, weakness, cognitive issues, and depression were common. The respondents defined disability progression as increased limitations on their ability to get around, having to sacrifice normal daily activities, and losing their ability to be independent. Patients measured the efficacy of DMTs by evaluating the treatments’ ability to slow progression, prevent further physical disability, prevent new lesions, and improve quality of life.

In a separate study, Dr. Livingston and colleagues conducted an analysis of organic discussions within MyMSTeam from January 2015 to April 2016. Researchers anonymized, coded, categorized, and analyzed 3,300 verbatim comments by key themes. The analysis focused on 12 DMTs. Discussions were overlaid with patient self-reported data on gender, age, date of diagnosis, MS type, current DMT, and effectiveness ratings.

Common discussion topics included side effects experienced; reasons for stopping treatment; perceived efficacy; questions, hopes, and concerns about starting a new DMT; rituals to mitigate side effects; and insurance or financial hurdles to getting on or staying on treatment.

Discussions about infusion therapies tended to focus on receiving treatment and issues related to progressive multifocal leukoencephalopathy.

When discussing Tysabri (natalizumab), patients most commonly discussed elevated energy levels post infusion around day 14. Patients also reported increased fatigue in the days prior to the next infusion and extreme fatigue on the day of treatment. In addition, patients shared their experiences with managing tolerability issues, most commonly flu-like symptoms with interferons and gastrointestinal effects with Tecfidera (dimethyl fumarate).

Dr. Livingston and colleagues said that their research “will better allow medical professionals to treat the individual holistically, and not just the disease itself. Additionally, helping patients understand MS progression will allow specialists to set realistic expectations for treating the disease and to help their patients better prepare for the future.”

NEW ORLEANS—Two studies presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis (MS) Centers examined the impact of MS and treatment among patients who are members of an online social network. Researchers found that, among patients who were taking oral disease-modifying treatments (DMTs), how the drug was taken was the most important factor in selecting the therapy (36% of patients) almost as often as the doctor’s recommendation (40% of patients), according to the results of a patient survey. In a separate study that analyzed comments made on the social network, researchers found that adverse events were the most commonly stated reason for stopping a treatment (56%).

In one study, Terrie Livingston, PharmD, an employee of Biogen in Weston, Massachusetts, and colleagues conducted a patient survey to assess the impact of MS on day-to-day life, self-reported symptoms, patient descriptions of disability progression, trade-offs when deciding which DMT to take, and what health care providers should know to better manage MS.

In November 2014, researchers sent an email invitation to the entire MyMSTeam community, a social network of approximately 25,000 people (currently more than 75,000 people) diagnosed with MS. In all, 1,107 members responded to the survey.

Overall, the most commonly reported symptoms were fatigue (82% of patients), problems with mobility (64%), and poor balance (64%). In addition, weakness, cognitive issues, and depression were common. The respondents defined disability progression as increased limitations on their ability to get around, having to sacrifice normal daily activities, and losing their ability to be independent. Patients measured the efficacy of DMTs by evaluating the treatments’ ability to slow progression, prevent further physical disability, prevent new lesions, and improve quality of life.

In a separate study, Dr. Livingston and colleagues conducted an analysis of organic discussions within MyMSTeam from January 2015 to April 2016. Researchers anonymized, coded, categorized, and analyzed 3,300 verbatim comments by key themes. The analysis focused on 12 DMTs. Discussions were overlaid with patient self-reported data on gender, age, date of diagnosis, MS type, current DMT, and effectiveness ratings.

Common discussion topics included side effects experienced; reasons for stopping treatment; perceived efficacy; questions, hopes, and concerns about starting a new DMT; rituals to mitigate side effects; and insurance or financial hurdles to getting on or staying on treatment.

Discussions about infusion therapies tended to focus on receiving treatment and issues related to progressive multifocal leukoencephalopathy.

When discussing Tysabri (natalizumab), patients most commonly discussed elevated energy levels post infusion around day 14. Patients also reported increased fatigue in the days prior to the next infusion and extreme fatigue on the day of treatment. In addition, patients shared their experiences with managing tolerability issues, most commonly flu-like symptoms with interferons and gastrointestinal effects with Tecfidera (dimethyl fumarate).

Dr. Livingston and colleagues said that their research “will better allow medical professionals to treat the individual holistically, and not just the disease itself. Additionally, helping patients understand MS progression will allow specialists to set realistic expectations for treating the disease and to help their patients better prepare for the future.”

NEW ORLEANS—Two studies presented at the 31st Annual Meeting of the Consortium of Multiple Sclerosis (MS) Centers examined the impact of MS and treatment among patients who are members of an online social network. Researchers found that, among patients who were taking oral disease-modifying treatments (DMTs), how the drug was taken was the most important factor in selecting the therapy (36% of patients) almost as often as the doctor’s recommendation (40% of patients), according to the results of a patient survey. In a separate study that analyzed comments made on the social network, researchers found that adverse events were the most commonly stated reason for stopping a treatment (56%).

In one study, Terrie Livingston, PharmD, an employee of Biogen in Weston, Massachusetts, and colleagues conducted a patient survey to assess the impact of MS on day-to-day life, self-reported symptoms, patient descriptions of disability progression, trade-offs when deciding which DMT to take, and what health care providers should know to better manage MS.

In November 2014, researchers sent an email invitation to the entire MyMSTeam community, a social network of approximately 25,000 people (currently more than 75,000 people) diagnosed with MS. In all, 1,107 members responded to the survey.

Overall, the most commonly reported symptoms were fatigue (82% of patients), problems with mobility (64%), and poor balance (64%). In addition, weakness, cognitive issues, and depression were common. The respondents defined disability progression as increased limitations on their ability to get around, having to sacrifice normal daily activities, and losing their ability to be independent. Patients measured the efficacy of DMTs by evaluating the treatments’ ability to slow progression, prevent further physical disability, prevent new lesions, and improve quality of life.

In a separate study, Dr. Livingston and colleagues conducted an analysis of organic discussions within MyMSTeam from January 2015 to April 2016. Researchers anonymized, coded, categorized, and analyzed 3,300 verbatim comments by key themes. The analysis focused on 12 DMTs. Discussions were overlaid with patient self-reported data on gender, age, date of diagnosis, MS type, current DMT, and effectiveness ratings.

Common discussion topics included side effects experienced; reasons for stopping treatment; perceived efficacy; questions, hopes, and concerns about starting a new DMT; rituals to mitigate side effects; and insurance or financial hurdles to getting on or staying on treatment.

Discussions about infusion therapies tended to focus on receiving treatment and issues related to progressive multifocal leukoencephalopathy.

When discussing Tysabri (natalizumab), patients most commonly discussed elevated energy levels post infusion around day 14. Patients also reported increased fatigue in the days prior to the next infusion and extreme fatigue on the day of treatment. In addition, patients shared their experiences with managing tolerability issues, most commonly flu-like symptoms with interferons and gastrointestinal effects with Tecfidera (dimethyl fumarate).

Dr. Livingston and colleagues said that their research “will better allow medical professionals to treat the individual holistically, and not just the disease itself. Additionally, helping patients understand MS progression will allow specialists to set realistic expectations for treating the disease and to help their patients better prepare for the future.”

Patients with epilepsy are more likely to develop seizure clusters if they have symptomatic generalized epilepsy, an earlier age of onset of their seizures, or if they have status epilepticus, according to a recent review of medical records that looked at over 4000 adult outpatients with epilepsy. The investigators also found that clustering was more common in patients with symptomatic generalized epilepsy than in those with focal epilepsy or idiopathic generalized epilepsy. 

Chen B, Choi H, Hirsh LJ, et al.  Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133: 98-102.

Patients with epilepsy are more likely to develop seizure clusters if they have symptomatic generalized epilepsy, an earlier age of onset of their seizures, or if they have status epilepticus, according to a recent review of medical records that looked at over 4000 adult outpatients with epilepsy. The investigators also found that clustering was more common in patients with symptomatic generalized epilepsy than in those with focal epilepsy or idiopathic generalized epilepsy. 

Chen B, Choi H, Hirsh LJ, et al.  Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133: 98-102.

Patients with epilepsy are more likely to develop seizure clusters if they have symptomatic generalized epilepsy, an earlier age of onset of their seizures, or if they have status epilepticus, according to a recent review of medical records that looked at over 4000 adult outpatients with epilepsy. The investigators also found that clustering was more common in patients with symptomatic generalized epilepsy than in those with focal epilepsy or idiopathic generalized epilepsy. 

Chen B, Choi H, Hirsh LJ, et al.  Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133: 98-102.

A tiered grading system may help determine which patients with drug-resistant epilepsy are most likely to have resective surgery and become free of seizures. The Epilepsy Surgery Grading Scale used in the study consisted of 3 tiers and included MRI, electroencephalography, concordance between the MRI and EEG, semiology, and IQ. Using the grading system, investigators detected a significant difference between Grade 1 patients, who had a most favorable rating, and Grade 3, who had been classified as least favorable candidates for surgery.

Dugan P, Carlson C, Jette N, et al. Derivation and initial validation of a surgical grading scale for preliminary evaluation of adult patients with drug-resistant focal epilepsy [published online April 4, 2017]. Epilepsia. 2017;doi: 10.1111/epi.13730.

A tiered grading system may help determine which patients with drug-resistant epilepsy are most likely to have resective surgery and become free of seizures. The Epilepsy Surgery Grading Scale used in the study consisted of 3 tiers and included MRI, electroencephalography, concordance between the MRI and EEG, semiology, and IQ. Using the grading system, investigators detected a significant difference between Grade 1 patients, who had a most favorable rating, and Grade 3, who had been classified as least favorable candidates for surgery.

Dugan P, Carlson C, Jette N, et al. Derivation and initial validation of a surgical grading scale for preliminary evaluation of adult patients with drug-resistant focal epilepsy [published online April 4, 2017]. Epilepsia. 2017;doi: 10.1111/epi.13730.

A tiered grading system may help determine which patients with drug-resistant epilepsy are most likely to have resective surgery and become free of seizures. The Epilepsy Surgery Grading Scale used in the study consisted of 3 tiers and included MRI, electroencephalography, concordance between the MRI and EEG, semiology, and IQ. Using the grading system, investigators detected a significant difference between Grade 1 patients, who had a most favorable rating, and Grade 3, who had been classified as least favorable candidates for surgery.

Dugan P, Carlson C, Jette N, et al. Derivation and initial validation of a surgical grading scale for preliminary evaluation of adult patients with drug-resistant focal epilepsy [published online April 4, 2017]. Epilepsia. 2017;doi: 10.1111/epi.13730.

Patients with epilepsy are more likely to develop seizure clusters if they have symptomatic generalized epilepsy, an earlier age of onset of their seizures, or if they have status epilepticus, according to a recent review of medical records that looked at over 4000 adult outpatients with epilepsy. The investigators also found that clustering was more common in patients with symptomatic generalized epilepsy than in those with focal epilepsy or idiopathic generalized epilepsy. 

Chen B, Choi H, Hirsh LJ, et al.  Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133: 98-102.

Patients with epilepsy are more likely to develop seizure clusters if they have symptomatic generalized epilepsy, an earlier age of onset of their seizures, or if they have status epilepticus, according to a recent review of medical records that looked at over 4000 adult outpatients with epilepsy. The investigators also found that clustering was more common in patients with symptomatic generalized epilepsy than in those with focal epilepsy or idiopathic generalized epilepsy. 

Chen B, Choi H, Hirsh LJ, et al.  Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133: 98-102.

Patients with epilepsy are more likely to develop seizure clusters if they have symptomatic generalized epilepsy, an earlier age of onset of their seizures, or if they have status epilepticus, according to a recent review of medical records that looked at over 4000 adult outpatients with epilepsy. The investigators also found that clustering was more common in patients with symptomatic generalized epilepsy than in those with focal epilepsy or idiopathic generalized epilepsy. 

Chen B, Choi H, Hirsh LJ, et al.  Prevalence and risk factors of seizure clusters in adult patients with epilepsy. Epilepsy Res. 2017;133: 98-102.

BOSTON—Siponimod reduces the risk of three-month and six-month confirmed disability progression in patients with secondary progressive multiple sclerosis (MS), according to research described at the 69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate and the number of new lesions. The study is “the largest controlled double-blind study in secondary progressive MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.

Siponimod is a selective sphingosine 1-phosphate receptor-1 and -5 modulator with effects on the CNS and the peripheral nervous system. The treatment may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his colleagues conducted a randomized, double-blind, placebo-controlled, phase III study to compare the effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized patients 2:1 to once-daily siponimod (2 mg) or placebo. Patients were treated for as long as three years in the double-blind phase of the study. In a subsequent extension study, participants were treated for as long as seven years.

The event- and exposure-driven study's primary end point was time to three-month confirmed disability progression, as assessed by the Expanded Disability Status Scale (EDSS). Key secondary end points included time to confirmed worsening of 20% or more from baseline in the Timed 25-Foot Walk test (T25FW) and T2 lesion volume change from baseline. Other secondary end points included six-month confirmed disability progression, annualized relapse rate, 12-item MS Walking Scale (MSWS-12), number of T1 gadolinium-enhancing and T2 lesions, and percent brain volume change.

The investigators randomized 1,651 patients. The population's mean age was 50, and mean EDSS score was 5.5. The sample was typical of the population of patients with secondary progressive MS.

Siponimod reduced the risk of three-month confirmed disability progression by 21% versus placebo. Dr. Kappos and colleagues consistently observed point estimates in favor of siponimod across predefined subgroups, including patients with no relapses in the two years before study initiation and patients without gadolinium-enhancing lesions at baseline.

The risk reduction observed for the T25FW was 6.2%, but was not statistically significant. Siponimod reduced the risk of six-month confirmed disability progression by 26%. In addition, siponimod reduced the annualized relapse rate by 55.5%, the number of T1 gadolinium-enhancing lesions by 86.6%, and the number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume, MSWS-12, and percent brain volume change were 79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod's effects were more pronounced in patients with relapses at baseline, compared with those without, said Dr. Kappos.

—Erik Greb

BOSTON—Siponimod reduces the risk of three-month and six-month confirmed disability progression in patients with secondary progressive multiple sclerosis (MS), according to research described at the 69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate and the number of new lesions. The study is “the largest controlled double-blind study in secondary progressive MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.

Siponimod is a selective sphingosine 1-phosphate receptor-1 and -5 modulator with effects on the CNS and the peripheral nervous system. The treatment may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his colleagues conducted a randomized, double-blind, placebo-controlled, phase III study to compare the effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized patients 2:1 to once-daily siponimod (2 mg) or placebo. Patients were treated for as long as three years in the double-blind phase of the study. In a subsequent extension study, participants were treated for as long as seven years.

The event- and exposure-driven study's primary end point was time to three-month confirmed disability progression, as assessed by the Expanded Disability Status Scale (EDSS). Key secondary end points included time to confirmed worsening of 20% or more from baseline in the Timed 25-Foot Walk test (T25FW) and T2 lesion volume change from baseline. Other secondary end points included six-month confirmed disability progression, annualized relapse rate, 12-item MS Walking Scale (MSWS-12), number of T1 gadolinium-enhancing and T2 lesions, and percent brain volume change.

The investigators randomized 1,651 patients. The population's mean age was 50, and mean EDSS score was 5.5. The sample was typical of the population of patients with secondary progressive MS.

Siponimod reduced the risk of three-month confirmed disability progression by 21% versus placebo. Dr. Kappos and colleagues consistently observed point estimates in favor of siponimod across predefined subgroups, including patients with no relapses in the two years before study initiation and patients without gadolinium-enhancing lesions at baseline.

The risk reduction observed for the T25FW was 6.2%, but was not statistically significant. Siponimod reduced the risk of six-month confirmed disability progression by 26%. In addition, siponimod reduced the annualized relapse rate by 55.5%, the number of T1 gadolinium-enhancing lesions by 86.6%, and the number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume, MSWS-12, and percent brain volume change were 79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod's effects were more pronounced in patients with relapses at baseline, compared with those without, said Dr. Kappos.

—Erik Greb

BOSTON—Siponimod reduces the risk of three-month and six-month confirmed disability progression in patients with secondary progressive multiple sclerosis (MS), according to research described at the 69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate and the number of new lesions. The study is “the largest controlled double-blind study in secondary progressive MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.

Siponimod is a selective sphingosine 1-phosphate receptor-1 and -5 modulator with effects on the CNS and the peripheral nervous system. The treatment may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his colleagues conducted a randomized, double-blind, placebo-controlled, phase III study to compare the effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized patients 2:1 to once-daily siponimod (2 mg) or placebo. Patients were treated for as long as three years in the double-blind phase of the study. In a subsequent extension study, participants were treated for as long as seven years.

The event- and exposure-driven study's primary end point was time to three-month confirmed disability progression, as assessed by the Expanded Disability Status Scale (EDSS). Key secondary end points included time to confirmed worsening of 20% or more from baseline in the Timed 25-Foot Walk test (T25FW) and T2 lesion volume change from baseline. Other secondary end points included six-month confirmed disability progression, annualized relapse rate, 12-item MS Walking Scale (MSWS-12), number of T1 gadolinium-enhancing and T2 lesions, and percent brain volume change.

The investigators randomized 1,651 patients. The population's mean age was 50, and mean EDSS score was 5.5. The sample was typical of the population of patients with secondary progressive MS.

Siponimod reduced the risk of three-month confirmed disability progression by 21% versus placebo. Dr. Kappos and colleagues consistently observed point estimates in favor of siponimod across predefined subgroups, including patients with no relapses in the two years before study initiation and patients without gadolinium-enhancing lesions at baseline.

The risk reduction observed for the T25FW was 6.2%, but was not statistically significant. Siponimod reduced the risk of six-month confirmed disability progression by 26%. In addition, siponimod reduced the annualized relapse rate by 55.5%, the number of T1 gadolinium-enhancing lesions by 86.6%, and the number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume, MSWS-12, and percent brain volume change were 79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod's effects were more pronounced in patients with relapses at baseline, compared with those without, said Dr. Kappos.

—Erik Greb

BOSTON—In older people with multiple sclerosis (MS), fatigue and limited lower leg function are more common in people with MS progression than in those without, according to a preliminary study presented at the 69th Annual Meeting of the American Academy of Neurology.

“Study participants with those symptoms were more likely to progress from relapsing-remitting MS to secondary progressive MS within five years,” said study author Bianca Weinstock-Guttman, MD, a Professor in the Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York. “Better understanding of who is at high risk of getting worse may eventually allow us to tailor more specific treatments to these people.”

Older age at disease onset, high frequency of relapses, and male sex have been found to be predictive of higher risk of conversion to secondary progressive MS. To further define predictors of disease progression, Dr. Weinstock-Guttman and colleagues investigated patient-reported outcomes in an aging cohort of patients with MS.

For the study, 155 people age 50 or older who had had relapsing-remitting MS for at least 15 years were evaluated for symptoms and level of disability at the beginning of the study and five years later, at which point they had been living with MS for an average of 22 years. The study subjects were part of the New York State MS Consortium.

In all, 30.3% of people in the study had progressed to secondary progressive MS by the five-year mark. Those who progressed to secondary progressive MS were older at study enrollment (54.8 vs 52.1) and had a higher Expanded Disability Status Scale score at baseline (3.5 vs 2.6) and at year 5 (5.6 vs 3.0). Those who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%; odds ratio, 3.0) and were more likely to report fatigue (91.5% vs 68.2%; odds ratio, 4.2), compared with those whose disease did not progress. The results were the same after researchers adjusted for other factors that could affect disease progression, such as age, disease duration, and disability severity.

“While more research needs to be done, this study brings us closer to understanding which older adults with MS may be at higher risk of getting worse,” said Dr. Weinstock-Guttman. “With the aging population, this information will be vital as people with MS, their families, and policy makers make decisions about their care.” The investigation was supported by the National MS Society.

—Glenn S. Williams

BOSTON—In older people with multiple sclerosis (MS), fatigue and limited lower leg function are more common in people with MS progression than in those without, according to a preliminary study presented at the 69th Annual Meeting of the American Academy of Neurology.

“Study participants with those symptoms were more likely to progress from relapsing-remitting MS to secondary progressive MS within five years,” said study author Bianca Weinstock-Guttman, MD, a Professor in the Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York. “Better understanding of who is at high risk of getting worse may eventually allow us to tailor more specific treatments to these people.”

Older age at disease onset, high frequency of relapses, and male sex have been found to be predictive of higher risk of conversion to secondary progressive MS. To further define predictors of disease progression, Dr. Weinstock-Guttman and colleagues investigated patient-reported outcomes in an aging cohort of patients with MS.

For the study, 155 people age 50 or older who had had relapsing-remitting MS for at least 15 years were evaluated for symptoms and level of disability at the beginning of the study and five years later, at which point they had been living with MS for an average of 22 years. The study subjects were part of the New York State MS Consortium.

In all, 30.3% of people in the study had progressed to secondary progressive MS by the five-year mark. Those who progressed to secondary progressive MS were older at study enrollment (54.8 vs 52.1) and had a higher Expanded Disability Status Scale score at baseline (3.5 vs 2.6) and at year 5 (5.6 vs 3.0). Those who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%; odds ratio, 3.0) and were more likely to report fatigue (91.5% vs 68.2%; odds ratio, 4.2), compared with those whose disease did not progress. The results were the same after researchers adjusted for other factors that could affect disease progression, such as age, disease duration, and disability severity.

“While more research needs to be done, this study brings us closer to understanding which older adults with MS may be at higher risk of getting worse,” said Dr. Weinstock-Guttman. “With the aging population, this information will be vital as people with MS, their families, and policy makers make decisions about their care.” The investigation was supported by the National MS Society.

—Glenn S. Williams

BOSTON—In older people with multiple sclerosis (MS), fatigue and limited lower leg function are more common in people with MS progression than in those without, according to a preliminary study presented at the 69th Annual Meeting of the American Academy of Neurology.

“Study participants with those symptoms were more likely to progress from relapsing-remitting MS to secondary progressive MS within five years,” said study author Bianca Weinstock-Guttman, MD, a Professor in the Department of Neurology at the Jacobs School of Medicine and Biomedical Sciences at the University of Buffalo in New York. “Better understanding of who is at high risk of getting worse may eventually allow us to tailor more specific treatments to these people.”

Older age at disease onset, high frequency of relapses, and male sex have been found to be predictive of higher risk of conversion to secondary progressive MS. To further define predictors of disease progression, Dr. Weinstock-Guttman and colleagues investigated patient-reported outcomes in an aging cohort of patients with MS.

For the study, 155 people age 50 or older who had had relapsing-remitting MS for at least 15 years were evaluated for symptoms and level of disability at the beginning of the study and five years later, at which point they had been living with MS for an average of 22 years. The study subjects were part of the New York State MS Consortium.

In all, 30.3% of people in the study had progressed to secondary progressive MS by the five-year mark. Those who progressed to secondary progressive MS were older at study enrollment (54.8 vs 52.1) and had a higher Expanded Disability Status Scale score at baseline (3.5 vs 2.6) and at year 5 (5.6 vs 3.0). Those who progressed at year 5 were more likely to report lower limb problems at baseline (53.2% vs 21.5%; odds ratio, 3.0) and were more likely to report fatigue (91.5% vs 68.2%; odds ratio, 4.2), compared with those whose disease did not progress. The results were the same after researchers adjusted for other factors that could affect disease progression, such as age, disease duration, and disability severity.

“While more research needs to be done, this study brings us closer to understanding which older adults with MS may be at higher risk of getting worse,” said Dr. Weinstock-Guttman. “With the aging population, this information will be vital as people with MS, their families, and policy makers make decisions about their care.” The investigation was supported by the National MS Society.

—Glenn S. Williams

Post-ictal generalized EEG suppression (PGES) may signal impending sudden unexpected death in epilepsy (SUDEP), according to a recent analysis of 305 seizures that occurred in 17 patients who had definite or probable SUDEP. Researchers found that PGES duration was shorter in patients who died unexpectedly from epilepsy, when compared to living patients. They also found that earlier nursing intervention was linked to shorter seizures after generalized convulsive seizures and may help reduce the risk of SUDEP.

Kang JY, Rabiei AH, Myint L, Nei M. Equivocal significance of post-ictal generalized EEG suppression as a marker of SUDEP risk. Seizure. 2017;48:28-32.

Post-ictal generalized EEG suppression (PGES) may signal impending sudden unexpected death in epilepsy (SUDEP), according to a recent analysis of 305 seizures that occurred in 17 patients who had definite or probable SUDEP. Researchers found that PGES duration was shorter in patients who died unexpectedly from epilepsy, when compared to living patients. They also found that earlier nursing intervention was linked to shorter seizures after generalized convulsive seizures and may help reduce the risk of SUDEP.

Kang JY, Rabiei AH, Myint L, Nei M. Equivocal significance of post-ictal generalized EEG suppression as a marker of SUDEP risk. Seizure. 2017;48:28-32.

Post-ictal generalized EEG suppression (PGES) may signal impending sudden unexpected death in epilepsy (SUDEP), according to a recent analysis of 305 seizures that occurred in 17 patients who had definite or probable SUDEP. Researchers found that PGES duration was shorter in patients who died unexpectedly from epilepsy, when compared to living patients. They also found that earlier nursing intervention was linked to shorter seizures after generalized convulsive seizures and may help reduce the risk of SUDEP.

Kang JY, Rabiei AH, Myint L, Nei M. Equivocal significance of post-ictal generalized EEG suppression as a marker of SUDEP risk. Seizure. 2017;48:28-32.

BOSTON—Interim results from a small, preliminary study support a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase I study, which was designed to enroll 10 people, were presented at the 69th Annual Meeting of the American Academy of Neurology. “While these results are very preliminary, and much more research is needed, we are excited there were no serious side effects,” said study author Michael P. Pender, MD, PhD, a Professor and Director of the Multiple Sclerosis Research Group at the University of Queensland in Brisbane, Australia.

The study investigated the relationship between MS and the Epstein-Barr virus (EBV). Previous research has suggested a role for EBV in MS pathogenesis. The study involved six people with progressive MS who had moderate to severe disability (ie, Expanded Disability Status Scale scores between 5.0 and 8.0).

In some people with MS, EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T-cell immunity. Elimination of EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with EBV. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients for 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three participants showed symptomatic and objective clinical improvement, starting two to eight weeks after the first infusion.

“One person with secondary progressive MS showed striking improvement,” Professor Pender said. This participant had normalization of lower extremity tone and plantar responses for the first time in 16 years. “This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one-sided assistance. Lower leg spasms that had persisted for years resolved.”

Professor Pender said another participant with primary progressive MS had reduced fatigue, increased productivity, and improved balance. Another responder had improved color vision, visual acuity, and manual dexterity; reduced fatigue; fewer lower extremity spasms; and less urinary urgency. All three responding participants had improvements in fatigue and ability to perform daily activities.  

“The best responses were seen in the two people who received T cells with the highest amount of reactivity to the EBV,” Professor Pender said. None of the six participants had serious side effects.

“Much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings,” Professor Pender said. “But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.”

The study was a collaboration between the QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, and the University of Queensland. The study was supported by MS Queensland, MS Research Australia, QIMR Berghofer Medical Research Institute, and Perpetual Trustee Company Limited.    

—Glenn S. Williams

Suggested Reading

Pender MP, Csurhes PA, Smith C, et al. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014;20(11):1541-1544.

BOSTON—Interim results from a small, preliminary study support a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase I study, which was designed to enroll 10 people, were presented at the 69th Annual Meeting of the American Academy of Neurology. “While these results are very preliminary, and much more research is needed, we are excited there were no serious side effects,” said study author Michael P. Pender, MD, PhD, a Professor and Director of the Multiple Sclerosis Research Group at the University of Queensland in Brisbane, Australia.

The study investigated the relationship between MS and the Epstein-Barr virus (EBV). Previous research has suggested a role for EBV in MS pathogenesis. The study involved six people with progressive MS who had moderate to severe disability (ie, Expanded Disability Status Scale scores between 5.0 and 8.0).

In some people with MS, EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T-cell immunity. Elimination of EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with EBV. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients for 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three participants showed symptomatic and objective clinical improvement, starting two to eight weeks after the first infusion.

“One person with secondary progressive MS showed striking improvement,” Professor Pender said. This participant had normalization of lower extremity tone and plantar responses for the first time in 16 years. “This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one-sided assistance. Lower leg spasms that had persisted for years resolved.”

Professor Pender said another participant with primary progressive MS had reduced fatigue, increased productivity, and improved balance. Another responder had improved color vision, visual acuity, and manual dexterity; reduced fatigue; fewer lower extremity spasms; and less urinary urgency. All three responding participants had improvements in fatigue and ability to perform daily activities.  

“The best responses were seen in the two people who received T cells with the highest amount of reactivity to the EBV,” Professor Pender said. None of the six participants had serious side effects.

“Much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings,” Professor Pender said. “But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.”

The study was a collaboration between the QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, and the University of Queensland. The study was supported by MS Queensland, MS Research Australia, QIMR Berghofer Medical Research Institute, and Perpetual Trustee Company Limited.    

—Glenn S. Williams

Suggested Reading

Pender MP, Csurhes PA, Smith C, et al. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014;20(11):1541-1544.

BOSTON—Interim results from a small, preliminary study support a new type of treatment for progressive multiple sclerosis (MS). Results from the first six people enrolled in the phase I study, which was designed to enroll 10 people, were presented at the 69th Annual Meeting of the American Academy of Neurology. “While these results are very preliminary, and much more research is needed, we are excited there were no serious side effects,” said study author Michael P. Pender, MD, PhD, a Professor and Director of the Multiple Sclerosis Research Group at the University of Queensland in Brisbane, Australia.

The study investigated the relationship between MS and the Epstein-Barr virus (EBV). Previous research has suggested a role for EBV in MS pathogenesis. The study involved six people with progressive MS who had moderate to severe disability (ie, Expanded Disability Status Scale scores between 5.0 and 8.0).

In some people with MS, EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T-cell immunity. Elimination of EBV-infected B cells may reduce the destruction of myelin in MS.

For the study, researchers removed the participants' own T cells and stimulated them to boost their ability to recognize and destroy cells infected with EBV. They then injected participants with infusions of escalating doses of T cells every two weeks for six weeks. They followed the patients for 26 weeks to look for evidence of side effects and possible improvement of symptoms.

Three participants showed symptomatic and objective clinical improvement, starting two to eight weeks after the first infusion.

“One person with secondary progressive MS showed striking improvement,” Professor Pender said. This participant had normalization of lower extremity tone and plantar responses for the first time in 16 years. “This participant had a significant increase in ambulation from 100 yards with a walker at the start of the study, and over the previous five years, to three quarters of a mile, and was now also able to walk shorter distances with only one-sided assistance. Lower leg spasms that had persisted for years resolved.”

Professor Pender said another participant with primary progressive MS had reduced fatigue, increased productivity, and improved balance. Another responder had improved color vision, visual acuity, and manual dexterity; reduced fatigue; fewer lower extremity spasms; and less urinary urgency. All three responding participants had improvements in fatigue and ability to perform daily activities.  

“The best responses were seen in the two people who received T cells with the highest amount of reactivity to the EBV,” Professor Pender said. None of the six participants had serious side effects.

“Much more research needs to be done with larger numbers of participants to confirm and further evaluate these findings,” Professor Pender said. “But the results add to the mounting evidence for a role of the Epstein-Barr virus infection in MS and set the stage for further clinical trials.”

The study was a collaboration between the QIMR Berghofer Medical Research Institute, Royal Brisbane and Women's Hospital, and the University of Queensland. The study was supported by MS Queensland, MS Research Australia, QIMR Berghofer Medical Research Institute, and Perpetual Trustee Company Limited.    

—Glenn S. Williams

Suggested Reading

Pender MP, Csurhes PA, Smith C, et al. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mult Scler. 2014;20(11):1541-1544.

Enhanced Recovery After Surgery (ERAS), a program implemented by Kaiser Permanente Northern California – a multihospital integrated health system – significantly reduced length of stay and complication rates, according to a report published in JAMA Surgery.

Beginning in 2014, when the ERAS program was implemented in 20 Kaiser hospitals, progress was made on the goal of improving inpatient safety, as well as improvements in-hospital mortality, rates of early ambulation, patient nutrition, and reduced opioid use, said Vincent X. Liu, MD, of the division of research, Kaiser Permanente Oakland, and his associates. Those outcomes were studied in the context of a similar group of patients in other, non-ERAS hospitals to determine the degree of change in each area.

shironosov/Thinkstock

Enhanced Recovery After Surgery (ERAS), a program implemented by Kaiser Permanente Northern California – a multihospital integrated health system – significantly reduced length of stay and complication rates, according to a report published in JAMA Surgery.

Beginning in 2014, when the ERAS program was implemented in 20 Kaiser hospitals, progress was made on the goal of improving inpatient safety, as well as improvements in-hospital mortality, rates of early ambulation, patient nutrition, and reduced opioid use, said Vincent X. Liu, MD, of the division of research, Kaiser Permanente Oakland, and his associates. Those outcomes were studied in the context of a similar group of patients in other, non-ERAS hospitals to determine the degree of change in each area.

shironosov/Thinkstock

Enhanced Recovery After Surgery (ERAS), a program implemented by Kaiser Permanente Northern California – a multihospital integrated health system – significantly reduced length of stay and complication rates, according to a report published in JAMA Surgery.

Beginning in 2014, when the ERAS program was implemented in 20 Kaiser hospitals, progress was made on the goal of improving inpatient safety, as well as improvements in-hospital mortality, rates of early ambulation, patient nutrition, and reduced opioid use, said Vincent X. Liu, MD, of the division of research, Kaiser Permanente Oakland, and his associates. Those outcomes were studied in the context of a similar group of patients in other, non-ERAS hospitals to determine the degree of change in each area.

shironosov/Thinkstock