Multiple Sclerosis Hub

COPENHAGEN—The many drugs in development for multiple sclerosis (MS) have various modes of action and could increase patients’ treatment options, according to an overview presented at the 29th Congress of the European Committee for Treatment and Research in MS. If these drugs reach the market, they may make it difficult for neurologists to stratify patients to various treatment regimens, but they will open new possibilities such as combination therapies, said Tobias Derfuss, MD.

Laquinimod Reduced Disability Progression
Two recently completed phase III trials found that laquinimod, a drug that appeared to promote remyelination in animal models, reduced patients’ annualized relapse rate by 20%. The drug also was associated with a “surprising” 46% reduction in disability progression, said Dr. Derfuss, Cohead of the Outpatient Care Unit and the Neuroimmunological Research Group at the University Hospital Basel. “You expect this effect on disability progression only if you also have a strong effect on the inflammatory components or [if] the drug has an impact on neuroprotection,” he said.

In addition, laquinimod reduced patients’ rate of brain atrophy by 30% during a 24-month period, which indicated that the drug might have a neuroprotective effect. New trials are required to identify the optimal dose and determine whether the drug could be part of a combination therapy.

Siponimod Decreased the Number of Unique Active Lesions
Siponimod is an oral compound in development that acts on the sphingosine-1-phosphate receptor. A phase II trial that compared siponimod to placebo in patients with relapsing-remitting MS suggested that 2 mg was the most effective dose of the drug. Compared with placebo, siponimod reduced unique active lesions at three months.

Investigators are recruiting participants for a phase III trial of siponimod in patients with secondary progressive MS. The trial will continue until a certain number of patients have three-month confirmed disability progression, which is the primary end point. When patients have six-month confirmed disability progression, they will be given the option of switching to open-label treatment. “This trial is a very good option for patients with secondary progressive MS,” said Dr. Derfuss.

Simvastatin May Reduce Brain Atrophy
Researchers have investigated the efficacy of statins in treating relapsing-remitting MS, and a double blind placebo-controlled trial in 2012 evaluated the efficacy of 80 mg/day of simvastatin in patients with secondary progressive MS. The drug was associated with significant reduction in brain atrophy, as well as with reductions in Expanded Disability Status Scale score and the MS Impact Scale, a patient-related outcome.

The results are surprising, in light of the trial’s small patient population, said Dr. Derfuss. In all, 140 patients participated in the trial, which lasted for two years. “We know from other trials in secondary progressive MS [that] it might take longer to see the effect,” said Dr. Derfuss. But because simvastatin no longer has patent protection, he added, pharmaceutical companies may be unwilling to conduct larger phase III trials, which means that MS societies and independent research organizations may have to provide the necessary funding.

Monoclonal Antibodies May Improve Patients’ Outcomes
Several monoclonal anti­bodies in development also show promise for the treatment of MS. Investigators recently completed a phase II trial that tested two doses of daclizumab, an IL-2 receptor antagonist, for one year. Compared with placebo, daclizumab reduced patients’ annualized relapse rate by more than 50%. An extension study and another phase IIb trial have supported the treatment’s efficacy. Daclizumab is a “promising drug” that has an “impressive effect on disability progression” within a short time, said Dr. Derfuss.

Secukinumab is a fully humanized antibody against the IL-17A cytokine. Patients in a small trial received 10 mg/kg/day of secukinumab. Despite the trial’s brief duration, researchers observed a significant reduction in new gadolinium-enhancing lesions among patients receiving secukinumab. Patients in the treatment arm also had a reduction in relapse rates, but it was not statistically significant. Investigators are recruiting patients for a second, larger phase II trial.

Ocrelizumab, a third antibody, depletes the body’s B-cells. A recent phase II trial compared ocrelizumab with interferon beta-1a and placebo. After eight weeks, patients who received ocrelizumab had a significant reduction in gadolinium-enhancing lesions, compared with patients receiving placebo and those receiving interferon. Ocrelizumab also reduced relapse rates. Two phase III trials are studying ocrelizumab for primary progressive MS, and one trial is evaluating ocrelizumab as a treatment for relapsing-remitting MS.

—Erik Greb
Senior Associate Editor

COPENHAGEN—The many drugs in development for multiple sclerosis (MS) have various modes of action and could increase patients’ treatment options, according to an overview presented at the 29th Congress of the European Committee for Treatment and Research in MS. If these drugs reach the market, they may make it difficult for neurologists to stratify patients to various treatment regimens, but they will open new possibilities such as combination therapies, said Tobias Derfuss, MD.

Laquinimod Reduced Disability Progression
Two recently completed phase III trials found that laquinimod, a drug that appeared to promote remyelination in animal models, reduced patients’ annualized relapse rate by 20%. The drug also was associated with a “surprising” 46% reduction in disability progression, said Dr. Derfuss, Cohead of the Outpatient Care Unit and the Neuroimmunological Research Group at the University Hospital Basel. “You expect this effect on disability progression only if you also have a strong effect on the inflammatory components or [if] the drug has an impact on neuroprotection,” he said.

In addition, laquinimod reduced patients’ rate of brain atrophy by 30% during a 24-month period, which indicated that the drug might have a neuroprotective effect. New trials are required to identify the optimal dose and determine whether the drug could be part of a combination therapy.

Siponimod Decreased the Number of Unique Active Lesions
Siponimod is an oral compound in development that acts on the sphingosine-1-phosphate receptor. A phase II trial that compared siponimod to placebo in patients with relapsing-remitting MS suggested that 2 mg was the most effective dose of the drug. Compared with placebo, siponimod reduced unique active lesions at three months.

Investigators are recruiting participants for a phase III trial of siponimod in patients with secondary progressive MS. The trial will continue until a certain number of patients have three-month confirmed disability progression, which is the primary end point. When patients have six-month confirmed disability progression, they will be given the option of switching to open-label treatment. “This trial is a very good option for patients with secondary progressive MS,” said Dr. Derfuss.

Simvastatin May Reduce Brain Atrophy
Researchers have investigated the efficacy of statins in treating relapsing-remitting MS, and a double blind placebo-controlled trial in 2012 evaluated the efficacy of 80 mg/day of simvastatin in patients with secondary progressive MS. The drug was associated with significant reduction in brain atrophy, as well as with reductions in Expanded Disability Status Scale score and the MS Impact Scale, a patient-related outcome.

The results are surprising, in light of the trial’s small patient population, said Dr. Derfuss. In all, 140 patients participated in the trial, which lasted for two years. “We know from other trials in secondary progressive MS [that] it might take longer to see the effect,” said Dr. Derfuss. But because simvastatin no longer has patent protection, he added, pharmaceutical companies may be unwilling to conduct larger phase III trials, which means that MS societies and independent research organizations may have to provide the necessary funding.

Monoclonal Antibodies May Improve Patients’ Outcomes
Several monoclonal anti­bodies in development also show promise for the treatment of MS. Investigators recently completed a phase II trial that tested two doses of daclizumab, an IL-2 receptor antagonist, for one year. Compared with placebo, daclizumab reduced patients’ annualized relapse rate by more than 50%. An extension study and another phase IIb trial have supported the treatment’s efficacy. Daclizumab is a “promising drug” that has an “impressive effect on disability progression” within a short time, said Dr. Derfuss.

Secukinumab is a fully humanized antibody against the IL-17A cytokine. Patients in a small trial received 10 mg/kg/day of secukinumab. Despite the trial’s brief duration, researchers observed a significant reduction in new gadolinium-enhancing lesions among patients receiving secukinumab. Patients in the treatment arm also had a reduction in relapse rates, but it was not statistically significant. Investigators are recruiting patients for a second, larger phase II trial.

Ocrelizumab, a third antibody, depletes the body’s B-cells. A recent phase II trial compared ocrelizumab with interferon beta-1a and placebo. After eight weeks, patients who received ocrelizumab had a significant reduction in gadolinium-enhancing lesions, compared with patients receiving placebo and those receiving interferon. Ocrelizumab also reduced relapse rates. Two phase III trials are studying ocrelizumab for primary progressive MS, and one trial is evaluating ocrelizumab as a treatment for relapsing-remitting MS.

—Erik Greb
Senior Associate Editor

COPENHAGEN—The many drugs in development for multiple sclerosis (MS) have various modes of action and could increase patients’ treatment options, according to an overview presented at the 29th Congress of the European Committee for Treatment and Research in MS. If these drugs reach the market, they may make it difficult for neurologists to stratify patients to various treatment regimens, but they will open new possibilities such as combination therapies, said Tobias Derfuss, MD.

Laquinimod Reduced Disability Progression
Two recently completed phase III trials found that laquinimod, a drug that appeared to promote remyelination in animal models, reduced patients’ annualized relapse rate by 20%. The drug also was associated with a “surprising” 46% reduction in disability progression, said Dr. Derfuss, Cohead of the Outpatient Care Unit and the Neuroimmunological Research Group at the University Hospital Basel. “You expect this effect on disability progression only if you also have a strong effect on the inflammatory components or [if] the drug has an impact on neuroprotection,” he said.

In addition, laquinimod reduced patients’ rate of brain atrophy by 30% during a 24-month period, which indicated that the drug might have a neuroprotective effect. New trials are required to identify the optimal dose and determine whether the drug could be part of a combination therapy.

Siponimod Decreased the Number of Unique Active Lesions
Siponimod is an oral compound in development that acts on the sphingosine-1-phosphate receptor. A phase II trial that compared siponimod to placebo in patients with relapsing-remitting MS suggested that 2 mg was the most effective dose of the drug. Compared with placebo, siponimod reduced unique active lesions at three months.

Investigators are recruiting participants for a phase III trial of siponimod in patients with secondary progressive MS. The trial will continue until a certain number of patients have three-month confirmed disability progression, which is the primary end point. When patients have six-month confirmed disability progression, they will be given the option of switching to open-label treatment. “This trial is a very good option for patients with secondary progressive MS,” said Dr. Derfuss.

Simvastatin May Reduce Brain Atrophy
Researchers have investigated the efficacy of statins in treating relapsing-remitting MS, and a double blind placebo-controlled trial in 2012 evaluated the efficacy of 80 mg/day of simvastatin in patients with secondary progressive MS. The drug was associated with significant reduction in brain atrophy, as well as with reductions in Expanded Disability Status Scale score and the MS Impact Scale, a patient-related outcome.

The results are surprising, in light of the trial’s small patient population, said Dr. Derfuss. In all, 140 patients participated in the trial, which lasted for two years. “We know from other trials in secondary progressive MS [that] it might take longer to see the effect,” said Dr. Derfuss. But because simvastatin no longer has patent protection, he added, pharmaceutical companies may be unwilling to conduct larger phase III trials, which means that MS societies and independent research organizations may have to provide the necessary funding.

Monoclonal Antibodies May Improve Patients’ Outcomes
Several monoclonal anti­bodies in development also show promise for the treatment of MS. Investigators recently completed a phase II trial that tested two doses of daclizumab, an IL-2 receptor antagonist, for one year. Compared with placebo, daclizumab reduced patients’ annualized relapse rate by more than 50%. An extension study and another phase IIb trial have supported the treatment’s efficacy. Daclizumab is a “promising drug” that has an “impressive effect on disability progression” within a short time, said Dr. Derfuss.

Secukinumab is a fully humanized antibody against the IL-17A cytokine. Patients in a small trial received 10 mg/kg/day of secukinumab. Despite the trial’s brief duration, researchers observed a significant reduction in new gadolinium-enhancing lesions among patients receiving secukinumab. Patients in the treatment arm also had a reduction in relapse rates, but it was not statistically significant. Investigators are recruiting patients for a second, larger phase II trial.

Ocrelizumab, a third antibody, depletes the body’s B-cells. A recent phase II trial compared ocrelizumab with interferon beta-1a and placebo. After eight weeks, patients who received ocrelizumab had a significant reduction in gadolinium-enhancing lesions, compared with patients receiving placebo and those receiving interferon. Ocrelizumab also reduced relapse rates. Two phase III trials are studying ocrelizumab for primary progressive MS, and one trial is evaluating ocrelizumab as a treatment for relapsing-remitting MS.

—Erik Greb
Senior Associate Editor

AUSTIN—Adjusting the ketogenic diet is helpful in one of five children with epilepsy, researchers reported at the 2013 Annual Meeting of the Child Neurology Society.

“Medication adjustment and dietary modification lead to similar outcomes,” stated Eric Kossoff, MD, Assistant Professor of Neurology and Pediatrics at Johns Hopkins Children’s Center in Baltimore, and colleagues. “Therefore, both [tactics] can be tried if the ketogenic diet is not meeting seizure-control expectations.”

The findings are based on a retrospective review of 200 children with epilepsy who had begun the ketogenic diet at the Johns Hopkins Hospital between October 2007 and June 2013. Dr. Kossoff’s group identified 10 commonly implemented dietary and supplement changes among the children. The investigators also reviewed medication adjustments in the children, as well as patient records during the course of adherence to the ketogenic diet for as many as four interventions per child. Greater than 50% seizure reduction after a change was defined as success, according to the study authors.

A total of 156 children (78%) had at least one intervention, and 391 distinct and occasionally concurrent interventions were recorded, of which 265 were made specifically for seizure control, noted Dr. Kossoff.

“Overall, there was an 18% chance that any intervention would be successful, but only a 3% chance of resultant seizure freedom,” reported the researchers. “The likelihood of success did not decrease with each subsequent intervention. There was a trend toward medication adjustments being more successful than dietary modifications (24% vs 15%, respectively).”

Analgesic Overuse May Worsen Chronic Post-Traumatic Headaches in Adolescents With Concussion
Excessive use of analgesics may exacerbate post-traumatic headaches among adolescents who have had a concussion, investigators reported.

“Analgesics should be minimized or discontinued when headaches continue several weeks following concussion,” recommended Geoffrey L. Heyer, MD, of the Division of Pediatric Neurology, Nationwide Children’s Hospital in Columbus, Ohio, and colleagues.

The researchers conducted a retrospective review of 104 adolescents with concussion who had been referred to a pediatric headache clinic for chronic post-traumatic headaches of three to 12 months in duration. The study authors compared concussion symptoms, headache symptoms before and after concussion, demographic data, and headache outcomes between patients who had probable medication-overuse headache and those who did not have probable medication-overuse headache.

A total of 77 patients had chronic post-traumatic headache between three and 12 months, and 54 patients (70%) met the criteria for probable medication-overuse headache. The investigators found that patients with medication overuse were more likely to have had daily headaches, to be female, to have had nausea or throbbing associated with their headaches, to have had increased irritability following concussion, and to have had a longer interval between injury and neurologic evaluation.

“Of the patients with medication overuse, 37 (68.5%) had resolution of headaches or improvements to preconcussion headache patterns after discontinuing analgesics, seven (13%) had no change in headaches or worsening of headaches after discontinuing analgesics, and 10 (18.5%) did not discontinue analgesics or were lost to follow-up,” stated Dr. Heyer.

2010 McDonald Criteria Are Effective for Early Diagnosis of Pediatric MS
The 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) may have a higher sensitivity for diagnosing pediatric MS, compared with the 2005 criteria. The revised criteria thus could allow for earlier initiation of disease-modifying therapy, researchers reported.

Mitchel T. Williams, MD, Pediatric Neurologist at the Children’s Hospital of Michigan in Detroit, and colleagues conducted a retrospective study of 25 children who had been diagnosed with MS at the Children’s Hospital of Michigan from 2005 through early 2013.

The researchers applied the 2005 and 2010 McDonald criteria based on neuroimaging findings as well as initial clinical presentation. The investigators also analyzed demographic data and compared those data with those of previous pediatric MS cohorts.

The median age at presentation, sex ratio, clinical symptoms, and relapse rate among the participants were comparable to those in previously published data, except for a high rate of African Americans (64%) among the 25 children.

The researchers found that the initial MS diagnosis rate based on the 2005 McDonald criteria was 32%, compared with a rate of 92% using the 2010 McDonald criteria. The mean time after initial symptom presentation until the 2005 criteria for MS were met was 5.0 months, compared with 0.7 months for the 2010 McDonald criteria.

“[Our findings] suggest that the 2010 McDonald criteria are a more appropriate tool for the timely diagnosis of pediatric MS,” concluded the researchers.

—Colby Stong
Editor

AUSTIN—Adjusting the ketogenic diet is helpful in one of five children with epilepsy, researchers reported at the 2013 Annual Meeting of the Child Neurology Society.

“Medication adjustment and dietary modification lead to similar outcomes,” stated Eric Kossoff, MD, Assistant Professor of Neurology and Pediatrics at Johns Hopkins Children’s Center in Baltimore, and colleagues. “Therefore, both [tactics] can be tried if the ketogenic diet is not meeting seizure-control expectations.”

The findings are based on a retrospective review of 200 children with epilepsy who had begun the ketogenic diet at the Johns Hopkins Hospital between October 2007 and June 2013. Dr. Kossoff’s group identified 10 commonly implemented dietary and supplement changes among the children. The investigators also reviewed medication adjustments in the children, as well as patient records during the course of adherence to the ketogenic diet for as many as four interventions per child. Greater than 50% seizure reduction after a change was defined as success, according to the study authors.

A total of 156 children (78%) had at least one intervention, and 391 distinct and occasionally concurrent interventions were recorded, of which 265 were made specifically for seizure control, noted Dr. Kossoff.

“Overall, there was an 18% chance that any intervention would be successful, but only a 3% chance of resultant seizure freedom,” reported the researchers. “The likelihood of success did not decrease with each subsequent intervention. There was a trend toward medication adjustments being more successful than dietary modifications (24% vs 15%, respectively).”

Analgesic Overuse May Worsen Chronic Post-Traumatic Headaches in Adolescents With Concussion
Excessive use of analgesics may exacerbate post-traumatic headaches among adolescents who have had a concussion, investigators reported.

“Analgesics should be minimized or discontinued when headaches continue several weeks following concussion,” recommended Geoffrey L. Heyer, MD, of the Division of Pediatric Neurology, Nationwide Children’s Hospital in Columbus, Ohio, and colleagues.

The researchers conducted a retrospective review of 104 adolescents with concussion who had been referred to a pediatric headache clinic for chronic post-traumatic headaches of three to 12 months in duration. The study authors compared concussion symptoms, headache symptoms before and after concussion, demographic data, and headache outcomes between patients who had probable medication-overuse headache and those who did not have probable medication-overuse headache.

A total of 77 patients had chronic post-traumatic headache between three and 12 months, and 54 patients (70%) met the criteria for probable medication-overuse headache. The investigators found that patients with medication overuse were more likely to have had daily headaches, to be female, to have had nausea or throbbing associated with their headaches, to have had increased irritability following concussion, and to have had a longer interval between injury and neurologic evaluation.

“Of the patients with medication overuse, 37 (68.5%) had resolution of headaches or improvements to preconcussion headache patterns after discontinuing analgesics, seven (13%) had no change in headaches or worsening of headaches after discontinuing analgesics, and 10 (18.5%) did not discontinue analgesics or were lost to follow-up,” stated Dr. Heyer.

2010 McDonald Criteria Are Effective for Early Diagnosis of Pediatric MS
The 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) may have a higher sensitivity for diagnosing pediatric MS, compared with the 2005 criteria. The revised criteria thus could allow for earlier initiation of disease-modifying therapy, researchers reported.

Mitchel T. Williams, MD, Pediatric Neurologist at the Children’s Hospital of Michigan in Detroit, and colleagues conducted a retrospective study of 25 children who had been diagnosed with MS at the Children’s Hospital of Michigan from 2005 through early 2013.

The researchers applied the 2005 and 2010 McDonald criteria based on neuroimaging findings as well as initial clinical presentation. The investigators also analyzed demographic data and compared those data with those of previous pediatric MS cohorts.

The median age at presentation, sex ratio, clinical symptoms, and relapse rate among the participants were comparable to those in previously published data, except for a high rate of African Americans (64%) among the 25 children.

The researchers found that the initial MS diagnosis rate based on the 2005 McDonald criteria was 32%, compared with a rate of 92% using the 2010 McDonald criteria. The mean time after initial symptom presentation until the 2005 criteria for MS were met was 5.0 months, compared with 0.7 months for the 2010 McDonald criteria.

“[Our findings] suggest that the 2010 McDonald criteria are a more appropriate tool for the timely diagnosis of pediatric MS,” concluded the researchers.

—Colby Stong
Editor

AUSTIN—Adjusting the ketogenic diet is helpful in one of five children with epilepsy, researchers reported at the 2013 Annual Meeting of the Child Neurology Society.

“Medication adjustment and dietary modification lead to similar outcomes,” stated Eric Kossoff, MD, Assistant Professor of Neurology and Pediatrics at Johns Hopkins Children’s Center in Baltimore, and colleagues. “Therefore, both [tactics] can be tried if the ketogenic diet is not meeting seizure-control expectations.”

The findings are based on a retrospective review of 200 children with epilepsy who had begun the ketogenic diet at the Johns Hopkins Hospital between October 2007 and June 2013. Dr. Kossoff’s group identified 10 commonly implemented dietary and supplement changes among the children. The investigators also reviewed medication adjustments in the children, as well as patient records during the course of adherence to the ketogenic diet for as many as four interventions per child. Greater than 50% seizure reduction after a change was defined as success, according to the study authors.

A total of 156 children (78%) had at least one intervention, and 391 distinct and occasionally concurrent interventions were recorded, of which 265 were made specifically for seizure control, noted Dr. Kossoff.

“Overall, there was an 18% chance that any intervention would be successful, but only a 3% chance of resultant seizure freedom,” reported the researchers. “The likelihood of success did not decrease with each subsequent intervention. There was a trend toward medication adjustments being more successful than dietary modifications (24% vs 15%, respectively).”

Analgesic Overuse May Worsen Chronic Post-Traumatic Headaches in Adolescents With Concussion
Excessive use of analgesics may exacerbate post-traumatic headaches among adolescents who have had a concussion, investigators reported.

“Analgesics should be minimized or discontinued when headaches continue several weeks following concussion,” recommended Geoffrey L. Heyer, MD, of the Division of Pediatric Neurology, Nationwide Children’s Hospital in Columbus, Ohio, and colleagues.

The researchers conducted a retrospective review of 104 adolescents with concussion who had been referred to a pediatric headache clinic for chronic post-traumatic headaches of three to 12 months in duration. The study authors compared concussion symptoms, headache symptoms before and after concussion, demographic data, and headache outcomes between patients who had probable medication-overuse headache and those who did not have probable medication-overuse headache.

A total of 77 patients had chronic post-traumatic headache between three and 12 months, and 54 patients (70%) met the criteria for probable medication-overuse headache. The investigators found that patients with medication overuse were more likely to have had daily headaches, to be female, to have had nausea or throbbing associated with their headaches, to have had increased irritability following concussion, and to have had a longer interval between injury and neurologic evaluation.

“Of the patients with medication overuse, 37 (68.5%) had resolution of headaches or improvements to preconcussion headache patterns after discontinuing analgesics, seven (13%) had no change in headaches or worsening of headaches after discontinuing analgesics, and 10 (18.5%) did not discontinue analgesics or were lost to follow-up,” stated Dr. Heyer.

2010 McDonald Criteria Are Effective for Early Diagnosis of Pediatric MS
The 2010 Revised McDonald Diagnostic Criteria for Multiple Sclerosis (MS) may have a higher sensitivity for diagnosing pediatric MS, compared with the 2005 criteria. The revised criteria thus could allow for earlier initiation of disease-modifying therapy, researchers reported.

Mitchel T. Williams, MD, Pediatric Neurologist at the Children’s Hospital of Michigan in Detroit, and colleagues conducted a retrospective study of 25 children who had been diagnosed with MS at the Children’s Hospital of Michigan from 2005 through early 2013.

The researchers applied the 2005 and 2010 McDonald criteria based on neuroimaging findings as well as initial clinical presentation. The investigators also analyzed demographic data and compared those data with those of previous pediatric MS cohorts.

The median age at presentation, sex ratio, clinical symptoms, and relapse rate among the participants were comparable to those in previously published data, except for a high rate of African Americans (64%) among the 25 children.

The researchers found that the initial MS diagnosis rate based on the 2005 McDonald criteria was 32%, compared with a rate of 92% using the 2010 McDonald criteria. The mean time after initial symptom presentation until the 2005 criteria for MS were met was 5.0 months, compared with 0.7 months for the 2010 McDonald criteria.

“[Our findings] suggest that the 2010 McDonald criteria are a more appropriate tool for the timely diagnosis of pediatric MS,” concluded the researchers.

—Colby Stong
Editor

Dot Test May Gauge the Progression of Dopamine Loss in Parkinson’s Disease
A simple dot test could help gauge the extent of dopamine loss in individuals with Parkinson’s disease, according to a pilot study by a multidisciplinary team of investigators. “It is difficult now to assess the extent of dopamine loss—a hallmark of Parkinson’s disease—in people with the disease,” said Katherine R. Gamble, a doctoral student in psychology at Georgetown University in Washington, DC. “This test, called the Triplets Learning Task (TLT), may provide some help for physicians who treat people with Parkinson’s disease, but we still have much work to do to better understand its utility,” she added.

The TLT tests implicit learning, which occurs without awareness or intent and relies on the caudate nucleus, an area of the brain affected by loss of dopamine. The test is a sequential learning task that does not require complex motor skills. In the TLT, participants see four open circles, and then two red dots appear. Patients are asked to respond when they see a green dot appear. Unknown to them, the location of the first red dot predicts the location of the green dot. Participants learn implicitly where the green dot will appear, and their responses become faster and more accurate.

Previous studies have shown that the caudate region in the brain underlies implicit learning. In the study, participants with Parkinson’s disease implicitly learned the dot pattern with training, but a loss of dopamine appears to negatively affect that learning. “Their performance began to decline toward the end of training, suggesting that people with Parkinson’s disease lack the neural resources in the caudate, such as dopamine, to complete the learning task,” said Ms. Gamble. The current study included 27 patients with Parkinson’s disease. The research team is now testing how implicit learning may differ by different stages of Parkinson’s disease and drug doses.

The Eyes May Help Diagnose Alzheimer’s Disease
The loss of a particular layer of retinal cells may reveal the presence of Alzheimer’s disease and provide a new way to track disease progression, according to an international team of researchers. The investigators examined retinas from the eyes of mice genetically engineered to develop Alzheimer’s disease.

“The retina is an extension of the brain, so it makes sense to see if the same pathologic processes found in an Alzheimer’s brain are also found in the eye,” said R. Scott Turner, MD, PhD, Director of the Memory Disorders Program at Georgetown University Medical Center in Washington, DC. “We know there’s an association between glaucoma and Alzheimer’s disease, in that both are characterized by loss of neurons, but the mechanisms are not clear.” Many researchers increasingly view glaucoma as a neurodegenerative disorder similar to Alzheimer’s disease, he added.

Most of the research to date examining the relationship between glaucoma and Alzheimer’s disease focused on the retinal ganglion cell layer, which transmits visual information via the optic nerve into the brain. Before that transmission happens, though, the retinal ganglion cells receive information from another layer in the retina—the inner nuclear layer.

The researchers examined the thickness of the retina, including the inner nuclear layer (which had not been studied previously in this setting) and the retinal ganglion cell layer. They found a significant loss of thickness in both layers. The inner nuclear layer had a 37% loss of neurons, and the retinal ganglion cell layer had a 49% loss of neurons, compared with healthy, age-matched control mice.

In humans, the structure and thickness of the retina can be readily measured using optical coherence tomography. This new tool is finding an increasing number of applications in research and clinical care, said Dr. Turner.

“This study suggests another path forward in understanding the disease process and could lead to new ways to diagnose or predict Alzheimer’s that could be as simple as looking into the eyes,” said Dr. Turner. “Parallel disease mechanisms suggest that new treatments developed for Alzheimer’s disease may also be useful for glaucoma.”

Research Suggests Warning Signs and Potential Treatments for MS
Recent research is increasing clinicians’ understanding of multiple sclerosis (MS) and may lead to new treatments and management strategies, said investigators. One study has shed light on the way in which antibodies in the bloodstream break through the blood–brain barrier to attack the optic nerves, spinal cord, and brain, causing the symptoms of neuromyelitis optica. Understanding how the antibodies bypass the blood–brain barrier could provide new approaches to treating the disease.

A protein involved in blood clotting might serve as an early biomarker for MS before symptoms occur, said Katerina Akassoglou, PhD, Professor in Residence of Neurology at the University of California, San Francisco School of Medicine. Early detection of the disease could lead to more effective early treatments.

In another study, low levels of a cholesterol protein correlated with the severity of MS. The finding suggests that the protein, which protects against inflammation, may protect against developing MS and may help regenerate damaged neurons, said Lidia Gardner, PhD, Assistant Professor of Neurology at the University of Tennessee in Memphis. Cholesterol drugs thus may be potential treatments for MS.

Researchers found that a type of immune system cell directly targets and damages nerve cell axons, just as MS does. This cell may be a target for new disease-modifying therapies. In addition, researchers have found that when exosomes—tiny, naturally occurring nanovesicles—are produced by dendritic cells and applied to the brain, they can deliver a mixture of proteins and RNAs that promote the regeneration of protective myelin sheaths and guard against MS symptoms.

Dot Test May Gauge the Progression of Dopamine Loss in Parkinson’s Disease
A simple dot test could help gauge the extent of dopamine loss in individuals with Parkinson’s disease, according to a pilot study by a multidisciplinary team of investigators. “It is difficult now to assess the extent of dopamine loss—a hallmark of Parkinson’s disease—in people with the disease,” said Katherine R. Gamble, a doctoral student in psychology at Georgetown University in Washington, DC. “This test, called the Triplets Learning Task (TLT), may provide some help for physicians who treat people with Parkinson’s disease, but we still have much work to do to better understand its utility,” she added.

The TLT tests implicit learning, which occurs without awareness or intent and relies on the caudate nucleus, an area of the brain affected by loss of dopamine. The test is a sequential learning task that does not require complex motor skills. In the TLT, participants see four open circles, and then two red dots appear. Patients are asked to respond when they see a green dot appear. Unknown to them, the location of the first red dot predicts the location of the green dot. Participants learn implicitly where the green dot will appear, and their responses become faster and more accurate.

Previous studies have shown that the caudate region in the brain underlies implicit learning. In the study, participants with Parkinson’s disease implicitly learned the dot pattern with training, but a loss of dopamine appears to negatively affect that learning. “Their performance began to decline toward the end of training, suggesting that people with Parkinson’s disease lack the neural resources in the caudate, such as dopamine, to complete the learning task,” said Ms. Gamble. The current study included 27 patients with Parkinson’s disease. The research team is now testing how implicit learning may differ by different stages of Parkinson’s disease and drug doses.

The Eyes May Help Diagnose Alzheimer’s Disease
The loss of a particular layer of retinal cells may reveal the presence of Alzheimer’s disease and provide a new way to track disease progression, according to an international team of researchers. The investigators examined retinas from the eyes of mice genetically engineered to develop Alzheimer’s disease.

“The retina is an extension of the brain, so it makes sense to see if the same pathologic processes found in an Alzheimer’s brain are also found in the eye,” said R. Scott Turner, MD, PhD, Director of the Memory Disorders Program at Georgetown University Medical Center in Washington, DC. “We know there’s an association between glaucoma and Alzheimer’s disease, in that both are characterized by loss of neurons, but the mechanisms are not clear.” Many researchers increasingly view glaucoma as a neurodegenerative disorder similar to Alzheimer’s disease, he added.

Most of the research to date examining the relationship between glaucoma and Alzheimer’s disease focused on the retinal ganglion cell layer, which transmits visual information via the optic nerve into the brain. Before that transmission happens, though, the retinal ganglion cells receive information from another layer in the retina—the inner nuclear layer.

The researchers examined the thickness of the retina, including the inner nuclear layer (which had not been studied previously in this setting) and the retinal ganglion cell layer. They found a significant loss of thickness in both layers. The inner nuclear layer had a 37% loss of neurons, and the retinal ganglion cell layer had a 49% loss of neurons, compared with healthy, age-matched control mice.

In humans, the structure and thickness of the retina can be readily measured using optical coherence tomography. This new tool is finding an increasing number of applications in research and clinical care, said Dr. Turner.

“This study suggests another path forward in understanding the disease process and could lead to new ways to diagnose or predict Alzheimer’s that could be as simple as looking into the eyes,” said Dr. Turner. “Parallel disease mechanisms suggest that new treatments developed for Alzheimer’s disease may also be useful for glaucoma.”

Research Suggests Warning Signs and Potential Treatments for MS
Recent research is increasing clinicians’ understanding of multiple sclerosis (MS) and may lead to new treatments and management strategies, said investigators. One study has shed light on the way in which antibodies in the bloodstream break through the blood–brain barrier to attack the optic nerves, spinal cord, and brain, causing the symptoms of neuromyelitis optica. Understanding how the antibodies bypass the blood–brain barrier could provide new approaches to treating the disease.

A protein involved in blood clotting might serve as an early biomarker for MS before symptoms occur, said Katerina Akassoglou, PhD, Professor in Residence of Neurology at the University of California, San Francisco School of Medicine. Early detection of the disease could lead to more effective early treatments.

In another study, low levels of a cholesterol protein correlated with the severity of MS. The finding suggests that the protein, which protects against inflammation, may protect against developing MS and may help regenerate damaged neurons, said Lidia Gardner, PhD, Assistant Professor of Neurology at the University of Tennessee in Memphis. Cholesterol drugs thus may be potential treatments for MS.

Researchers found that a type of immune system cell directly targets and damages nerve cell axons, just as MS does. This cell may be a target for new disease-modifying therapies. In addition, researchers have found that when exosomes—tiny, naturally occurring nanovesicles—are produced by dendritic cells and applied to the brain, they can deliver a mixture of proteins and RNAs that promote the regeneration of protective myelin sheaths and guard against MS symptoms.

Dot Test May Gauge the Progression of Dopamine Loss in Parkinson’s Disease
A simple dot test could help gauge the extent of dopamine loss in individuals with Parkinson’s disease, according to a pilot study by a multidisciplinary team of investigators. “It is difficult now to assess the extent of dopamine loss—a hallmark of Parkinson’s disease—in people with the disease,” said Katherine R. Gamble, a doctoral student in psychology at Georgetown University in Washington, DC. “This test, called the Triplets Learning Task (TLT), may provide some help for physicians who treat people with Parkinson’s disease, but we still have much work to do to better understand its utility,” she added.

The TLT tests implicit learning, which occurs without awareness or intent and relies on the caudate nucleus, an area of the brain affected by loss of dopamine. The test is a sequential learning task that does not require complex motor skills. In the TLT, participants see four open circles, and then two red dots appear. Patients are asked to respond when they see a green dot appear. Unknown to them, the location of the first red dot predicts the location of the green dot. Participants learn implicitly where the green dot will appear, and their responses become faster and more accurate.

Previous studies have shown that the caudate region in the brain underlies implicit learning. In the study, participants with Parkinson’s disease implicitly learned the dot pattern with training, but a loss of dopamine appears to negatively affect that learning. “Their performance began to decline toward the end of training, suggesting that people with Parkinson’s disease lack the neural resources in the caudate, such as dopamine, to complete the learning task,” said Ms. Gamble. The current study included 27 patients with Parkinson’s disease. The research team is now testing how implicit learning may differ by different stages of Parkinson’s disease and drug doses.

The Eyes May Help Diagnose Alzheimer’s Disease
The loss of a particular layer of retinal cells may reveal the presence of Alzheimer’s disease and provide a new way to track disease progression, according to an international team of researchers. The investigators examined retinas from the eyes of mice genetically engineered to develop Alzheimer’s disease.

“The retina is an extension of the brain, so it makes sense to see if the same pathologic processes found in an Alzheimer’s brain are also found in the eye,” said R. Scott Turner, MD, PhD, Director of the Memory Disorders Program at Georgetown University Medical Center in Washington, DC. “We know there’s an association between glaucoma and Alzheimer’s disease, in that both are characterized by loss of neurons, but the mechanisms are not clear.” Many researchers increasingly view glaucoma as a neurodegenerative disorder similar to Alzheimer’s disease, he added.

Most of the research to date examining the relationship between glaucoma and Alzheimer’s disease focused on the retinal ganglion cell layer, which transmits visual information via the optic nerve into the brain. Before that transmission happens, though, the retinal ganglion cells receive information from another layer in the retina—the inner nuclear layer.

The researchers examined the thickness of the retina, including the inner nuclear layer (which had not been studied previously in this setting) and the retinal ganglion cell layer. They found a significant loss of thickness in both layers. The inner nuclear layer had a 37% loss of neurons, and the retinal ganglion cell layer had a 49% loss of neurons, compared with healthy, age-matched control mice.

In humans, the structure and thickness of the retina can be readily measured using optical coherence tomography. This new tool is finding an increasing number of applications in research and clinical care, said Dr. Turner.

“This study suggests another path forward in understanding the disease process and could lead to new ways to diagnose or predict Alzheimer’s that could be as simple as looking into the eyes,” said Dr. Turner. “Parallel disease mechanisms suggest that new treatments developed for Alzheimer’s disease may also be useful for glaucoma.”

Research Suggests Warning Signs and Potential Treatments for MS
Recent research is increasing clinicians’ understanding of multiple sclerosis (MS) and may lead to new treatments and management strategies, said investigators. One study has shed light on the way in which antibodies in the bloodstream break through the blood–brain barrier to attack the optic nerves, spinal cord, and brain, causing the symptoms of neuromyelitis optica. Understanding how the antibodies bypass the blood–brain barrier could provide new approaches to treating the disease.

A protein involved in blood clotting might serve as an early biomarker for MS before symptoms occur, said Katerina Akassoglou, PhD, Professor in Residence of Neurology at the University of California, San Francisco School of Medicine. Early detection of the disease could lead to more effective early treatments.

In another study, low levels of a cholesterol protein correlated with the severity of MS. The finding suggests that the protein, which protects against inflammation, may protect against developing MS and may help regenerate damaged neurons, said Lidia Gardner, PhD, Assistant Professor of Neurology at the University of Tennessee in Memphis. Cholesterol drugs thus may be potential treatments for MS.

Researchers found that a type of immune system cell directly targets and damages nerve cell axons, just as MS does. This cell may be a target for new disease-modifying therapies. In addition, researchers have found that when exosomes—tiny, naturally occurring nanovesicles—are produced by dendritic cells and applied to the brain, they can deliver a mixture of proteins and RNAs that promote the regeneration of protective myelin sheaths and guard against MS symptoms.

ORLANDO—For patients with relapsing-remitting multiple sclerosis (MS), MRI activity unaccompanied by any other clinical event may be the strongest predictor of switching from a first-line disease-modifying therapy (DMT), according to research presented at the Fifth Cooperative Meeting of the Consortium of MS Centers and the Americas Committee for Treatment and Research in MS. Individuals with MRI worsening alone may be 6.3 times as likely to switch DMTs than patients with one relapse.

In addition, worsening on the Expanded Disability Status Scale (EDSS) alone or EDSS and MRI worsening nearly tripled the odds of switching DMTs, compared with having one relapse, said Barbara Teter, PhD, Director of Research and Development at the New York State MS Consortium in Buffalo. Patients with two or more relapses as a first event following DMT initiation were 2.8 times as likely to switch DMTs, compared with patients with a single relapse.

A Retrospective Analysis of Longitudinal Registry Data
To identify clinical and demographic characteristics that predict switching to a new DMT among patients with relapsing-remitting MS, Dr. Teter and her colleagues conducted a retrospective study of longitudinal registry data from 14 MS Centers or neurology practices in the state of New York. The researchers analyzed data for patients enrolled in the registry from 1996 to 2009, and nine MS treatment centers participated in chart review follow-up.

Eligible study participants had three or more years of follow-up and used interferon beta or glatiramer acetate as an initial DMT. Suboptimal response to the first DMT was defined as a relapse, EDSS worsening, MRI worsening (eg, new gadolinium-enhancing or T2 lesions), or a combination of these events. Patients who discontinued their initial DMT and started another DMT within six to 12 months after the first MS event were considered to have switched therapies. The investigators used regression modeling to identify predictors of DMT switching.

Patients Who Switched DMTs Were More Likely to Be Younger
Patients who switched therapies were more likely to be younger at symptom onset and younger at DMT initiation than patients who did not switch. Among patients with MRI worsening alone, the mean time between DMT initiation and first MS event was longer among patients who switched DMTs (62.3 months) than among patients who did not switch (38.5 months).

Patients were less likely to switch therapies if they experienced combinations of one relapse plus EDSS worsening and one relapse plus EDSS worsening plus MRI worsening than if they had one relapse alone, said Dr. Teter. Combinations of two or more relapses plus EDSS worsening or MRI worsening did not predict a DMT switch, but the sample size was small.

“The likelihood and drivers of therapy switch may change with expanding therapy options,” said Dr. Teter. “At the time of this study, few therapy options were available.”

—Erik Greb
Senior Associate Editor

ORLANDO—For patients with relapsing-remitting multiple sclerosis (MS), MRI activity unaccompanied by any other clinical event may be the strongest predictor of switching from a first-line disease-modifying therapy (DMT), according to research presented at the Fifth Cooperative Meeting of the Consortium of MS Centers and the Americas Committee for Treatment and Research in MS. Individuals with MRI worsening alone may be 6.3 times as likely to switch DMTs than patients with one relapse.

In addition, worsening on the Expanded Disability Status Scale (EDSS) alone or EDSS and MRI worsening nearly tripled the odds of switching DMTs, compared with having one relapse, said Barbara Teter, PhD, Director of Research and Development at the New York State MS Consortium in Buffalo. Patients with two or more relapses as a first event following DMT initiation were 2.8 times as likely to switch DMTs, compared with patients with a single relapse.

A Retrospective Analysis of Longitudinal Registry Data
To identify clinical and demographic characteristics that predict switching to a new DMT among patients with relapsing-remitting MS, Dr. Teter and her colleagues conducted a retrospective study of longitudinal registry data from 14 MS Centers or neurology practices in the state of New York. The researchers analyzed data for patients enrolled in the registry from 1996 to 2009, and nine MS treatment centers participated in chart review follow-up.

Eligible study participants had three or more years of follow-up and used interferon beta or glatiramer acetate as an initial DMT. Suboptimal response to the first DMT was defined as a relapse, EDSS worsening, MRI worsening (eg, new gadolinium-enhancing or T2 lesions), or a combination of these events. Patients who discontinued their initial DMT and started another DMT within six to 12 months after the first MS event were considered to have switched therapies. The investigators used regression modeling to identify predictors of DMT switching.

Patients Who Switched DMTs Were More Likely to Be Younger
Patients who switched therapies were more likely to be younger at symptom onset and younger at DMT initiation than patients who did not switch. Among patients with MRI worsening alone, the mean time between DMT initiation and first MS event was longer among patients who switched DMTs (62.3 months) than among patients who did not switch (38.5 months).

Patients were less likely to switch therapies if they experienced combinations of one relapse plus EDSS worsening and one relapse plus EDSS worsening plus MRI worsening than if they had one relapse alone, said Dr. Teter. Combinations of two or more relapses plus EDSS worsening or MRI worsening did not predict a DMT switch, but the sample size was small.

“The likelihood and drivers of therapy switch may change with expanding therapy options,” said Dr. Teter. “At the time of this study, few therapy options were available.”

—Erik Greb
Senior Associate Editor

ORLANDO—For patients with relapsing-remitting multiple sclerosis (MS), MRI activity unaccompanied by any other clinical event may be the strongest predictor of switching from a first-line disease-modifying therapy (DMT), according to research presented at the Fifth Cooperative Meeting of the Consortium of MS Centers and the Americas Committee for Treatment and Research in MS. Individuals with MRI worsening alone may be 6.3 times as likely to switch DMTs than patients with one relapse.

In addition, worsening on the Expanded Disability Status Scale (EDSS) alone or EDSS and MRI worsening nearly tripled the odds of switching DMTs, compared with having one relapse, said Barbara Teter, PhD, Director of Research and Development at the New York State MS Consortium in Buffalo. Patients with two or more relapses as a first event following DMT initiation were 2.8 times as likely to switch DMTs, compared with patients with a single relapse.

A Retrospective Analysis of Longitudinal Registry Data
To identify clinical and demographic characteristics that predict switching to a new DMT among patients with relapsing-remitting MS, Dr. Teter and her colleagues conducted a retrospective study of longitudinal registry data from 14 MS Centers or neurology practices in the state of New York. The researchers analyzed data for patients enrolled in the registry from 1996 to 2009, and nine MS treatment centers participated in chart review follow-up.

Eligible study participants had three or more years of follow-up and used interferon beta or glatiramer acetate as an initial DMT. Suboptimal response to the first DMT was defined as a relapse, EDSS worsening, MRI worsening (eg, new gadolinium-enhancing or T2 lesions), or a combination of these events. Patients who discontinued their initial DMT and started another DMT within six to 12 months after the first MS event were considered to have switched therapies. The investigators used regression modeling to identify predictors of DMT switching.

Patients Who Switched DMTs Were More Likely to Be Younger
Patients who switched therapies were more likely to be younger at symptom onset and younger at DMT initiation than patients who did not switch. Among patients with MRI worsening alone, the mean time between DMT initiation and first MS event was longer among patients who switched DMTs (62.3 months) than among patients who did not switch (38.5 months).

Patients were less likely to switch therapies if they experienced combinations of one relapse plus EDSS worsening and one relapse plus EDSS worsening plus MRI worsening than if they had one relapse alone, said Dr. Teter. Combinations of two or more relapses plus EDSS worsening or MRI worsening did not predict a DMT switch, but the sample size was small.

“The likelihood and drivers of therapy switch may change with expanding therapy options,” said Dr. Teter. “At the time of this study, few therapy options were available.”

—Erik Greb
Senior Associate Editor

COPENHAGEN—Dysfunction within the pyramidal system may be the strongest independent clinical predictor of disability progression in patients with clinically isolated syndrome (CIS), according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Older age at CIS onset, however, may be a poor prognostic indicator. Factors that predict disability progression in patients with relapsing-remitting MS may also predict the same outcome in patients with CIS.

Natural history studies indicate that high T2 lesion burden is a poor prognostic indicator, but “in our study, this [finding] is confounded by treatment,” said Vilija Jokubaitis, PhD, researcher in the Department of Medicine at the University of Melbourne. Dr. Jokubaitis and colleagues found that high T2 lesion load was associated with earlier and longer treatment exposure.

The researchers also observed that exposure to disease-modifying therapies (DMTs) significantly delayed the accumulation of disability. The investigators found an association between increase in treatment exposure and a decrease in the hazard of progression. “Our data suggest that the early and consistent use of DMTs is key in delaying the accumulation of MS-related disability,” said Dr. Jokubaitis.

Monitoring for Disability Progression
Dr. Jokubaitis and colleagues analyzed data from the MSBase Incidence Study, an investigator-initiated, prospective, observational cohort study of patients with CIS. The study began collecting data in 17 countries in 2004. Persons who had been diagnosed with CIS within 12 months of onset were enrolled into this study.

At baseline, the researchers collected demographic information, Expanded Disability Status Scale (EDSS) scores, Kurtzke functional scores (KFS), and cerebral MRI. Baseline MRI scans were available for 89% of the patients. At follow-up, the investigators collected EDSS scores, KFS, relapse information, and information about changes in treatments. The study’s primary end point was disability progression events, which were defined as an EDSS score increase of at least one point above a minimum baseline EDSS score of 1. The increase had to be maintained for a particular period of time. The study focused on disability progression events at three months and at 12 months.

A total of 1,989 patients had at least three EDSS scores spanning a minimum of nine months. Of these patients, 391 had a three-month confirmed disability progression event, and the event was maintained for at least 12 months in 307 patients.

First-Line Drugs Had Equivalent Efficacy
Approximately 71% of patients were female. Patients’ average age at CIS onset was 33, and their median EDSS score at baseline was 1.5. About 9% of patients had fewer than three T2 lesions on cerebral MRI.

Hazard regression analysis indicated that every 10 years of age were associated with a 1.17 increase in the hazard of disease progression. A KFS of 2 or greater was associated with roughly a 1.5-fold increase in the risk of disability progression, compared with patients who had a pyramidal KFS of 0 or 1.

To assess the effect of treatment, the researchers compared patients who were treated before the accumulation of disability with patients who were untreated before the accumulation of disability. All first-line injectable drugs decreased patients’ risk of progression by approximately 50%.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Dysfunction within the pyramidal system may be the strongest independent clinical predictor of disability progression in patients with clinically isolated syndrome (CIS), according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Older age at CIS onset, however, may be a poor prognostic indicator. Factors that predict disability progression in patients with relapsing-remitting MS may also predict the same outcome in patients with CIS.

Natural history studies indicate that high T2 lesion burden is a poor prognostic indicator, but “in our study, this [finding] is confounded by treatment,” said Vilija Jokubaitis, PhD, researcher in the Department of Medicine at the University of Melbourne. Dr. Jokubaitis and colleagues found that high T2 lesion load was associated with earlier and longer treatment exposure.

The researchers also observed that exposure to disease-modifying therapies (DMTs) significantly delayed the accumulation of disability. The investigators found an association between increase in treatment exposure and a decrease in the hazard of progression. “Our data suggest that the early and consistent use of DMTs is key in delaying the accumulation of MS-related disability,” said Dr. Jokubaitis.

Monitoring for Disability Progression
Dr. Jokubaitis and colleagues analyzed data from the MSBase Incidence Study, an investigator-initiated, prospective, observational cohort study of patients with CIS. The study began collecting data in 17 countries in 2004. Persons who had been diagnosed with CIS within 12 months of onset were enrolled into this study.

At baseline, the researchers collected demographic information, Expanded Disability Status Scale (EDSS) scores, Kurtzke functional scores (KFS), and cerebral MRI. Baseline MRI scans were available for 89% of the patients. At follow-up, the investigators collected EDSS scores, KFS, relapse information, and information about changes in treatments. The study’s primary end point was disability progression events, which were defined as an EDSS score increase of at least one point above a minimum baseline EDSS score of 1. The increase had to be maintained for a particular period of time. The study focused on disability progression events at three months and at 12 months.

A total of 1,989 patients had at least three EDSS scores spanning a minimum of nine months. Of these patients, 391 had a three-month confirmed disability progression event, and the event was maintained for at least 12 months in 307 patients.

First-Line Drugs Had Equivalent Efficacy
Approximately 71% of patients were female. Patients’ average age at CIS onset was 33, and their median EDSS score at baseline was 1.5. About 9% of patients had fewer than three T2 lesions on cerebral MRI.

Hazard regression analysis indicated that every 10 years of age were associated with a 1.17 increase in the hazard of disease progression. A KFS of 2 or greater was associated with roughly a 1.5-fold increase in the risk of disability progression, compared with patients who had a pyramidal KFS of 0 or 1.

To assess the effect of treatment, the researchers compared patients who were treated before the accumulation of disability with patients who were untreated before the accumulation of disability. All first-line injectable drugs decreased patients’ risk of progression by approximately 50%.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Dysfunction within the pyramidal system may be the strongest independent clinical predictor of disability progression in patients with clinically isolated syndrome (CIS), according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Older age at CIS onset, however, may be a poor prognostic indicator. Factors that predict disability progression in patients with relapsing-remitting MS may also predict the same outcome in patients with CIS.

Natural history studies indicate that high T2 lesion burden is a poor prognostic indicator, but “in our study, this [finding] is confounded by treatment,” said Vilija Jokubaitis, PhD, researcher in the Department of Medicine at the University of Melbourne. Dr. Jokubaitis and colleagues found that high T2 lesion load was associated with earlier and longer treatment exposure.

The researchers also observed that exposure to disease-modifying therapies (DMTs) significantly delayed the accumulation of disability. The investigators found an association between increase in treatment exposure and a decrease in the hazard of progression. “Our data suggest that the early and consistent use of DMTs is key in delaying the accumulation of MS-related disability,” said Dr. Jokubaitis.

Monitoring for Disability Progression
Dr. Jokubaitis and colleagues analyzed data from the MSBase Incidence Study, an investigator-initiated, prospective, observational cohort study of patients with CIS. The study began collecting data in 17 countries in 2004. Persons who had been diagnosed with CIS within 12 months of onset were enrolled into this study.

At baseline, the researchers collected demographic information, Expanded Disability Status Scale (EDSS) scores, Kurtzke functional scores (KFS), and cerebral MRI. Baseline MRI scans were available for 89% of the patients. At follow-up, the investigators collected EDSS scores, KFS, relapse information, and information about changes in treatments. The study’s primary end point was disability progression events, which were defined as an EDSS score increase of at least one point above a minimum baseline EDSS score of 1. The increase had to be maintained for a particular period of time. The study focused on disability progression events at three months and at 12 months.

A total of 1,989 patients had at least three EDSS scores spanning a minimum of nine months. Of these patients, 391 had a three-month confirmed disability progression event, and the event was maintained for at least 12 months in 307 patients.

First-Line Drugs Had Equivalent Efficacy
Approximately 71% of patients were female. Patients’ average age at CIS onset was 33, and their median EDSS score at baseline was 1.5. About 9% of patients had fewer than three T2 lesions on cerebral MRI.

Hazard regression analysis indicated that every 10 years of age were associated with a 1.17 increase in the hazard of disease progression. A KFS of 2 or greater was associated with roughly a 1.5-fold increase in the risk of disability progression, compared with patients who had a pyramidal KFS of 0 or 1.

To assess the effect of treatment, the researchers compared patients who were treated before the accumulation of disability with patients who were untreated before the accumulation of disability. All first-line injectable drugs decreased patients’ risk of progression by approximately 50%.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Serum vitamin D level early in the course of multiple sclerosis (MS) may predict a patient’s rate of long-term progression, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Vitamin D level appears to have an inverse correlation with the number of relapses, the amount of MRI activity, the number of new active lesions, and the amount of brain atrophy over five years.

The study results suggest that vitamin D supplementation may have a role in the early treatment of MS, particularly for patients who have vitamin D insufficiency or deficiency, said Alberto Ascherio, MD, Professor of Epidemiology and Nutrition at the Harvard School of Public Health in Boston. For the purposes of the study, a serum vitamin D level of 50 nmol/L or higher was considered sufficient.

The BENEFIT Trial
To determine whether serum vitamin D levels predict disease activity after clinically isolated syndrome (CIS), Dr. Ascherio and colleagues examined data from the BENEFIT study, a randomized trial that compared the effects of early and delayed treatment with interferon beta-1b in patients with CIS. A total of 468 patients were randomized. The BENEFIT investigators measured participants’ serum 25(OH)D concentrations at baseline, six months, 12 months, and 24 months and performed clinical and MRI assessments at established intervals. At 24 months, patients entered the trial’s open phase and were offered treatment with interferon beta. Clinical and MRI follow-up lasted for five years.

Dr. Ascherio and colleagues created Cox proportional hazard models or generalized mixed effects models to analyze the data. They adjusted the data analysis for sex, age, initial randomization group, and baseline T2 lesion scores to relate season-adjusted serum 25(OH)D levels to MS outcomes.

High Vitamin D Levels Predicted Reduced Disease Activity
Most patients had a vitamin D level lower than 50 nmol/L, said Dr. Ascherio. At baseline, the number of T2 lesions was higher in patients with vitamin D deficiency than in patients with sufficient vitamin D. Higher 25(OH)D levels were correlated with slower conversion from CIS to MS, reduced MS activity, and a slower rate of progression. The associations were stronger when the researchers used seasonally asynchronous blood samples to assess long-term average 25(OH)D levels.

A 50-nmol/L increment in average serum 25(OH)D levels at 12 months predicted a 57% lower rate of new active lesions, a 57% lower relapse rate, a 25% lower increase in T2 lesion volume, and a 0.41% lower annual loss of brain volume from 12 to 60 months. Compared with serum 25(OH)D levels lower than 50 nmol/L at 12 months, serum 25(OH)D levels of 50 nmol/L or more at 12 months predicted fewer active lesions on MRI, a lower increase in T2 lesion volume, a lower rate of brain loss, and lower disability, as measured by Expanded Disability Status Scale score, during the following four years.

Patient Population Was Ethnically Homogeneous
Dr. Ascherio identified several limitations to the study. Almost all of the patients were Caucasians of European ancestry, so the researchers did not draw conclusions about patients of other ethnicities. In addition, most patients eventually were treated with interferon beta, so it is unclear whether the association between disease activity and vitamin D results from an additive effect of interferon beta and vitamin D. It also is uncertain whether researchers would observe a similar beneficial effect of vitamin D in patients treated with other disease-modifying therapies.

Dr. Ascherio’s group did not see a ceiling effect of vitamin D, so it is unclear whether vitamin D supplementation would provide additional benefit to the patients. A prospective trial could give more definitive information about the therapeutic value of increasing vitamin D levels in patients with sufficient vitamin D. Neurologists should strongly consider the detection and treatment of vitamin D insufficiency and deficiency, Dr. Ascherio concluded.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Serum vitamin D level early in the course of multiple sclerosis (MS) may predict a patient’s rate of long-term progression, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Vitamin D level appears to have an inverse correlation with the number of relapses, the amount of MRI activity, the number of new active lesions, and the amount of brain atrophy over five years.

The study results suggest that vitamin D supplementation may have a role in the early treatment of MS, particularly for patients who have vitamin D insufficiency or deficiency, said Alberto Ascherio, MD, Professor of Epidemiology and Nutrition at the Harvard School of Public Health in Boston. For the purposes of the study, a serum vitamin D level of 50 nmol/L or higher was considered sufficient.

The BENEFIT Trial
To determine whether serum vitamin D levels predict disease activity after clinically isolated syndrome (CIS), Dr. Ascherio and colleagues examined data from the BENEFIT study, a randomized trial that compared the effects of early and delayed treatment with interferon beta-1b in patients with CIS. A total of 468 patients were randomized. The BENEFIT investigators measured participants’ serum 25(OH)D concentrations at baseline, six months, 12 months, and 24 months and performed clinical and MRI assessments at established intervals. At 24 months, patients entered the trial’s open phase and were offered treatment with interferon beta. Clinical and MRI follow-up lasted for five years.

Dr. Ascherio and colleagues created Cox proportional hazard models or generalized mixed effects models to analyze the data. They adjusted the data analysis for sex, age, initial randomization group, and baseline T2 lesion scores to relate season-adjusted serum 25(OH)D levels to MS outcomes.

High Vitamin D Levels Predicted Reduced Disease Activity
Most patients had a vitamin D level lower than 50 nmol/L, said Dr. Ascherio. At baseline, the number of T2 lesions was higher in patients with vitamin D deficiency than in patients with sufficient vitamin D. Higher 25(OH)D levels were correlated with slower conversion from CIS to MS, reduced MS activity, and a slower rate of progression. The associations were stronger when the researchers used seasonally asynchronous blood samples to assess long-term average 25(OH)D levels.

A 50-nmol/L increment in average serum 25(OH)D levels at 12 months predicted a 57% lower rate of new active lesions, a 57% lower relapse rate, a 25% lower increase in T2 lesion volume, and a 0.41% lower annual loss of brain volume from 12 to 60 months. Compared with serum 25(OH)D levels lower than 50 nmol/L at 12 months, serum 25(OH)D levels of 50 nmol/L or more at 12 months predicted fewer active lesions on MRI, a lower increase in T2 lesion volume, a lower rate of brain loss, and lower disability, as measured by Expanded Disability Status Scale score, during the following four years.

Patient Population Was Ethnically Homogeneous
Dr. Ascherio identified several limitations to the study. Almost all of the patients were Caucasians of European ancestry, so the researchers did not draw conclusions about patients of other ethnicities. In addition, most patients eventually were treated with interferon beta, so it is unclear whether the association between disease activity and vitamin D results from an additive effect of interferon beta and vitamin D. It also is uncertain whether researchers would observe a similar beneficial effect of vitamin D in patients treated with other disease-modifying therapies.

Dr. Ascherio’s group did not see a ceiling effect of vitamin D, so it is unclear whether vitamin D supplementation would provide additional benefit to the patients. A prospective trial could give more definitive information about the therapeutic value of increasing vitamin D levels in patients with sufficient vitamin D. Neurologists should strongly consider the detection and treatment of vitamin D insufficiency and deficiency, Dr. Ascherio concluded.

—Erik Greb
Senior Associate Editor

COPENHAGEN—Serum vitamin D level early in the course of multiple sclerosis (MS) may predict a patient’s rate of long-term progression, according to research presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Vitamin D level appears to have an inverse correlation with the number of relapses, the amount of MRI activity, the number of new active lesions, and the amount of brain atrophy over five years.

The study results suggest that vitamin D supplementation may have a role in the early treatment of MS, particularly for patients who have vitamin D insufficiency or deficiency, said Alberto Ascherio, MD, Professor of Epidemiology and Nutrition at the Harvard School of Public Health in Boston. For the purposes of the study, a serum vitamin D level of 50 nmol/L or higher was considered sufficient.

The BENEFIT Trial
To determine whether serum vitamin D levels predict disease activity after clinically isolated syndrome (CIS), Dr. Ascherio and colleagues examined data from the BENEFIT study, a randomized trial that compared the effects of early and delayed treatment with interferon beta-1b in patients with CIS. A total of 468 patients were randomized. The BENEFIT investigators measured participants’ serum 25(OH)D concentrations at baseline, six months, 12 months, and 24 months and performed clinical and MRI assessments at established intervals. At 24 months, patients entered the trial’s open phase and were offered treatment with interferon beta. Clinical and MRI follow-up lasted for five years.

Dr. Ascherio and colleagues created Cox proportional hazard models or generalized mixed effects models to analyze the data. They adjusted the data analysis for sex, age, initial randomization group, and baseline T2 lesion scores to relate season-adjusted serum 25(OH)D levels to MS outcomes.

High Vitamin D Levels Predicted Reduced Disease Activity
Most patients had a vitamin D level lower than 50 nmol/L, said Dr. Ascherio. At baseline, the number of T2 lesions was higher in patients with vitamin D deficiency than in patients with sufficient vitamin D. Higher 25(OH)D levels were correlated with slower conversion from CIS to MS, reduced MS activity, and a slower rate of progression. The associations were stronger when the researchers used seasonally asynchronous blood samples to assess long-term average 25(OH)D levels.

A 50-nmol/L increment in average serum 25(OH)D levels at 12 months predicted a 57% lower rate of new active lesions, a 57% lower relapse rate, a 25% lower increase in T2 lesion volume, and a 0.41% lower annual loss of brain volume from 12 to 60 months. Compared with serum 25(OH)D levels lower than 50 nmol/L at 12 months, serum 25(OH)D levels of 50 nmol/L or more at 12 months predicted fewer active lesions on MRI, a lower increase in T2 lesion volume, a lower rate of brain loss, and lower disability, as measured by Expanded Disability Status Scale score, during the following four years.

Patient Population Was Ethnically Homogeneous
Dr. Ascherio identified several limitations to the study. Almost all of the patients were Caucasians of European ancestry, so the researchers did not draw conclusions about patients of other ethnicities. In addition, most patients eventually were treated with interferon beta, so it is unclear whether the association between disease activity and vitamin D results from an additive effect of interferon beta and vitamin D. It also is uncertain whether researchers would observe a similar beneficial effect of vitamin D in patients treated with other disease-modifying therapies.

Dr. Ascherio’s group did not see a ceiling effect of vitamin D, so it is unclear whether vitamin D supplementation would provide additional benefit to the patients. A prospective trial could give more definitive information about the therapeutic value of increasing vitamin D levels in patients with sufficient vitamin D. Neurologists should strongly consider the detection and treatment of vitamin D insufficiency and deficiency, Dr. Ascherio concluded.

—Erik Greb
Senior Associate Editor