Multiple Sclerosis

An experimental procedure that attempts to improve venous blood flow may cause significant damage or death in patients with multiple sclerosis, according to an alert issued by the Food and Drug Administration.

"Liberation therapy," which involves balloon angioplasty or stenting of veins in the neck and chest, has been used but not proven as a treatment for chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by stenosis of the veins draining blood from the brain and upper spinal cord. Despite the lack of a definitive link between CCSVI and multiple sclerosis (MS), the former has been suggested as a cause of or contributing factor in the development of the progressive, immune-mediated neurologic disorder (Ann. Neurol. 2010;67:286-90).

Since its introduction in 2009 (J. Vasc. Surg. 2009;50:1348-58), the liberation procedure has been linked to multiple complications, including stroke, stent detachment and migration, impairment of the treated vein, cranial nerve damage, blood clots, abdominal bleeding, and death, according to a statement issued by the FDA. The complications have been reported through the agency’s Safety Information and Adverse Event Reporting Program.

In the absence of rigorous, targeted research establishing an association between the two conditions or reliable evidence from controlled clinical trials demonstrating the efficacy of liberation-type procedures in MS, "patients are encouraged to discuss the potential risks and benefits of this procedure with a neurologist or other physician who is familiar with MS and CCSVI, including the CCSVI procedures and their outcomes," Dr. William Maisel, chief scientist in the FDA’s Center for Devices and Radiological Health, emphasized in the alert.

The statement also stresses that physicians and clinical investigators considering or conducting trials of devices to treat CCSVI are obligated to comply with regulations for investigational devices.

Currently, no devices for use in liberation therapy have received FDA approval for that indication, although doctors can and have offered the procedure to their patients, Dr. Maisel said in an interview. "We don’t know exactly how many individuals have had the treatment, because there is no central patient registry."

An experimental procedure that attempts to improve venous blood flow may cause significant damage or death in patients with multiple sclerosis, according to an alert issued by the Food and Drug Administration.

"Liberation therapy," which involves balloon angioplasty or stenting of veins in the neck and chest, has been used but not proven as a treatment for chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by stenosis of the veins draining blood from the brain and upper spinal cord. Despite the lack of a definitive link between CCSVI and multiple sclerosis (MS), the former has been suggested as a cause of or contributing factor in the development of the progressive, immune-mediated neurologic disorder (Ann. Neurol. 2010;67:286-90).

Since its introduction in 2009 (J. Vasc. Surg. 2009;50:1348-58), the liberation procedure has been linked to multiple complications, including stroke, stent detachment and migration, impairment of the treated vein, cranial nerve damage, blood clots, abdominal bleeding, and death, according to a statement issued by the FDA. The complications have been reported through the agency’s Safety Information and Adverse Event Reporting Program.

In the absence of rigorous, targeted research establishing an association between the two conditions or reliable evidence from controlled clinical trials demonstrating the efficacy of liberation-type procedures in MS, "patients are encouraged to discuss the potential risks and benefits of this procedure with a neurologist or other physician who is familiar with MS and CCSVI, including the CCSVI procedures and their outcomes," Dr. William Maisel, chief scientist in the FDA’s Center for Devices and Radiological Health, emphasized in the alert.

The statement also stresses that physicians and clinical investigators considering or conducting trials of devices to treat CCSVI are obligated to comply with regulations for investigational devices.

Currently, no devices for use in liberation therapy have received FDA approval for that indication, although doctors can and have offered the procedure to their patients, Dr. Maisel said in an interview. "We don’t know exactly how many individuals have had the treatment, because there is no central patient registry."

An experimental procedure that attempts to improve venous blood flow may cause significant damage or death in patients with multiple sclerosis, according to an alert issued by the Food and Drug Administration.

"Liberation therapy," which involves balloon angioplasty or stenting of veins in the neck and chest, has been used but not proven as a treatment for chronic cerebrospinal venous insufficiency (CCSVI), a condition characterized by stenosis of the veins draining blood from the brain and upper spinal cord. Despite the lack of a definitive link between CCSVI and multiple sclerosis (MS), the former has been suggested as a cause of or contributing factor in the development of the progressive, immune-mediated neurologic disorder (Ann. Neurol. 2010;67:286-90).

Since its introduction in 2009 (J. Vasc. Surg. 2009;50:1348-58), the liberation procedure has been linked to multiple complications, including stroke, stent detachment and migration, impairment of the treated vein, cranial nerve damage, blood clots, abdominal bleeding, and death, according to a statement issued by the FDA. The complications have been reported through the agency’s Safety Information and Adverse Event Reporting Program.

In the absence of rigorous, targeted research establishing an association between the two conditions or reliable evidence from controlled clinical trials demonstrating the efficacy of liberation-type procedures in MS, "patients are encouraged to discuss the potential risks and benefits of this procedure with a neurologist or other physician who is familiar with MS and CCSVI, including the CCSVI procedures and their outcomes," Dr. William Maisel, chief scientist in the FDA’s Center for Devices and Radiological Health, emphasized in the alert.

The statement also stresses that physicians and clinical investigators considering or conducting trials of devices to treat CCSVI are obligated to comply with regulations for investigational devices.

Currently, no devices for use in liberation therapy have received FDA approval for that indication, although doctors can and have offered the procedure to their patients, Dr. Maisel said in an interview. "We don’t know exactly how many individuals have had the treatment, because there is no central patient registry."

NEW ORLEANS – Higher vitamin D levels are associated with slightly less disability and greater preservation of gray matter in patients with multiple sclerosis, according to a 5-year observational study.

The researchers assessed 25-hydroxyvitamin D levels, clinical disability, and MRI brain volumes annually in 469 patients with relapsing-remitting multiple sclerosis (MS) or clinically isolated syndrome, all members of a longitudinal MS cohort study at the University of California, San Francisco.

They found that for every 10-ng/mL increase in 25-hydroxyvitamin D levels, subsequent EDSS (Expanded Disability Status Scale) scores were 0.05 points lower (95% confidence interval –0.091 to –0.003; P = .037), and subsequent normalized gray matter volume was 7 cc higher (95% CI 2.4, 11.5; P = .003). The results were adjusted for age, sex, ethnicity, smoking status, body mass index, and use of MS treatments.

Based on the results and a growing body of literature suggesting a role for vitamin D in MS, lead investigator Dr. Ellen Mowry, an assistant professor of neuroimmunology at Johns Hopkins University, Baltimore, often supplements her patients to a vitamin D level of 40-60 ng/mL, which usually takes 2,000-4,000 international units a day.

"The preponderance of the observational evidence is in favor of supplementing, and I think those levels are the most strongly supported by the data. Above 60 ng/mL, there are very few data to say whether or not the effect remains the same," she said at the annual meeting of the American Academy of Neurology.

Dr. Mowry said she is careful to tell her MS patients that although observational studies suggest vitamin D is safe and helpful, ongoing randomized trials may prove otherwise.

The average age of patients in her study was 42 years; their median disease duration was 5 years, and about two-thirds were women. Their baseline vitamin D levels were low at around 28 ng/mL.

Mean EDSS scores were about 1.5 at the start of the study, and about 2 at its end. Mean normalized gray matter volumes were 985 cc at baseline and 964 cc at the end of 4 years. Only 9% of the subjects took vitamin D supplements at the start of the study, but almost half (43%) took them at its end.

Trends were favorable for an association between vitamin D levels and preservation of brain parenchymal volume, but the results were not statistically significant.

The results are in line with a 2006 study that found an inverse association between vitamin D levels and the risk for developing MS (JAMA 2006;296:2832-8).

Previously, Dr. Mowry and other researchers have demonstrated that vitamin D levels are inversely associated with MS relapse risk in both children and adults (Ann. Neurol. 2010;67:618-24; Ann. Neurol. 2010;68:193-203).

Dr. Mowry is the principal investigator in a randomized treatment trial that will assess the impact of high- and low-dose vitamin D supplementation on attack rates, numbers of new lesions, and changes in brain volume in relapsing-remitting MS.

The study was funded by a grant from the National Institutes of Health and by GlaxoSmithKline and Biogen Idec. Dr. Mowry reported receiving research support from Teva Pharmaceuticals.

NEW ORLEANS – Higher vitamin D levels are associated with slightly less disability and greater preservation of gray matter in patients with multiple sclerosis, according to a 5-year observational study.

The researchers assessed 25-hydroxyvitamin D levels, clinical disability, and MRI brain volumes annually in 469 patients with relapsing-remitting multiple sclerosis (MS) or clinically isolated syndrome, all members of a longitudinal MS cohort study at the University of California, San Francisco.

They found that for every 10-ng/mL increase in 25-hydroxyvitamin D levels, subsequent EDSS (Expanded Disability Status Scale) scores were 0.05 points lower (95% confidence interval –0.091 to –0.003; P = .037), and subsequent normalized gray matter volume was 7 cc higher (95% CI 2.4, 11.5; P = .003). The results were adjusted for age, sex, ethnicity, smoking status, body mass index, and use of MS treatments.

Based on the results and a growing body of literature suggesting a role for vitamin D in MS, lead investigator Dr. Ellen Mowry, an assistant professor of neuroimmunology at Johns Hopkins University, Baltimore, often supplements her patients to a vitamin D level of 40-60 ng/mL, which usually takes 2,000-4,000 international units a day.

"The preponderance of the observational evidence is in favor of supplementing, and I think those levels are the most strongly supported by the data. Above 60 ng/mL, there are very few data to say whether or not the effect remains the same," she said at the annual meeting of the American Academy of Neurology.

Dr. Mowry said she is careful to tell her MS patients that although observational studies suggest vitamin D is safe and helpful, ongoing randomized trials may prove otherwise.

The average age of patients in her study was 42 years; their median disease duration was 5 years, and about two-thirds were women. Their baseline vitamin D levels were low at around 28 ng/mL.

Mean EDSS scores were about 1.5 at the start of the study, and about 2 at its end. Mean normalized gray matter volumes were 985 cc at baseline and 964 cc at the end of 4 years. Only 9% of the subjects took vitamin D supplements at the start of the study, but almost half (43%) took them at its end.

Trends were favorable for an association between vitamin D levels and preservation of brain parenchymal volume, but the results were not statistically significant.

The results are in line with a 2006 study that found an inverse association between vitamin D levels and the risk for developing MS (JAMA 2006;296:2832-8).

Previously, Dr. Mowry and other researchers have demonstrated that vitamin D levels are inversely associated with MS relapse risk in both children and adults (Ann. Neurol. 2010;67:618-24; Ann. Neurol. 2010;68:193-203).

Dr. Mowry is the principal investigator in a randomized treatment trial that will assess the impact of high- and low-dose vitamin D supplementation on attack rates, numbers of new lesions, and changes in brain volume in relapsing-remitting MS.

The study was funded by a grant from the National Institutes of Health and by GlaxoSmithKline and Biogen Idec. Dr. Mowry reported receiving research support from Teva Pharmaceuticals.

NEW ORLEANS – Higher vitamin D levels are associated with slightly less disability and greater preservation of gray matter in patients with multiple sclerosis, according to a 5-year observational study.

The researchers assessed 25-hydroxyvitamin D levels, clinical disability, and MRI brain volumes annually in 469 patients with relapsing-remitting multiple sclerosis (MS) or clinically isolated syndrome, all members of a longitudinal MS cohort study at the University of California, San Francisco.

They found that for every 10-ng/mL increase in 25-hydroxyvitamin D levels, subsequent EDSS (Expanded Disability Status Scale) scores were 0.05 points lower (95% confidence interval –0.091 to –0.003; P = .037), and subsequent normalized gray matter volume was 7 cc higher (95% CI 2.4, 11.5; P = .003). The results were adjusted for age, sex, ethnicity, smoking status, body mass index, and use of MS treatments.

Based on the results and a growing body of literature suggesting a role for vitamin D in MS, lead investigator Dr. Ellen Mowry, an assistant professor of neuroimmunology at Johns Hopkins University, Baltimore, often supplements her patients to a vitamin D level of 40-60 ng/mL, which usually takes 2,000-4,000 international units a day.

"The preponderance of the observational evidence is in favor of supplementing, and I think those levels are the most strongly supported by the data. Above 60 ng/mL, there are very few data to say whether or not the effect remains the same," she said at the annual meeting of the American Academy of Neurology.

Dr. Mowry said she is careful to tell her MS patients that although observational studies suggest vitamin D is safe and helpful, ongoing randomized trials may prove otherwise.

The average age of patients in her study was 42 years; their median disease duration was 5 years, and about two-thirds were women. Their baseline vitamin D levels were low at around 28 ng/mL.

Mean EDSS scores were about 1.5 at the start of the study, and about 2 at its end. Mean normalized gray matter volumes were 985 cc at baseline and 964 cc at the end of 4 years. Only 9% of the subjects took vitamin D supplements at the start of the study, but almost half (43%) took them at its end.

Trends were favorable for an association between vitamin D levels and preservation of brain parenchymal volume, but the results were not statistically significant.

The results are in line with a 2006 study that found an inverse association between vitamin D levels and the risk for developing MS (JAMA 2006;296:2832-8).

Previously, Dr. Mowry and other researchers have demonstrated that vitamin D levels are inversely associated with MS relapse risk in both children and adults (Ann. Neurol. 2010;67:618-24; Ann. Neurol. 2010;68:193-203).

Dr. Mowry is the principal investigator in a randomized treatment trial that will assess the impact of high- and low-dose vitamin D supplementation on attack rates, numbers of new lesions, and changes in brain volume in relapsing-remitting MS.

The study was funded by a grant from the National Institutes of Health and by GlaxoSmithKline and Biogen Idec. Dr. Mowry reported receiving research support from Teva Pharmaceuticals.

Every patient should get an electrocardiogram prior to and 6 hours after the first dose of fingolimod, and hourly blood pressure and heart rate measurements in between, to assess for bradycardia, according to revised labeling released by the Food and Drug Administration on May 9.

Patients with prolonged QTc intervals during the observation period should be observed overnight with continuous ECG monitoring, labeling now states.

The revisions come after more than a dozen reports of sudden or unexplained deaths in the United States and Europe following the drug’s 2010 approval for relapsing forms of multiple sclerosis, and months-long talks between the FDA and Novartis, the maker of fingolimod (Gilenya). Previous labeling recommended baseline ECGs only "in those at higher risk of bradyarrhythmia."

--------------------------------------------------------------------------------------------------

• 

     Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod)

--------------------------------------------------------------------------------------------------

Novartis noted in a press release that fingolimod has been used in more than 36,000 patients.

Labeling also now calls for overnight, continuous ECG monitoring in a medical facility for patients with preexisting heart conditions, cerebrovascular disease, recurrent syncope, or severe untreated sleep apnea; patients on beta-blockers or other drugs that slow heart rate or atrioventricular (AV) conduction; and patients with prolonged QTc intervals, whether due to drugs or medical conditions. ECG monitoring is also warranted, in some cases, for patients restarting the drug after a pause.

"Isolated delayed onset events, including transient asystole and unexplained death, have occurred within 24 hours of the first dose," the revised labeling notes, although the relationship with fingolimod is "uncertain."

The new label contraindicates the drug in patients who, in the last 6 months, have had a heart attack, unstable angina, stroke, transient ischemic attack, second- or third-degree AV block, decompensated heart failure requiring hospitalization, sick sinus syndrome with no pacemaker, baseline QTc interval of 500 ms or longer, and treatment with class Ia or class III antiarrhythmic drugs. Previous labeling had no contraindications.

Those and other changes come shortly after the annual meeting of the American Academy of Neurology, where Novartis released the results of its recent 2-year, double-blind, placebo-controlled, multicenter, phase III trial of fingolimod in 1,083 patients with relapsing-remitting multiple sclerosis.

At month 24, 0.5 mg of fingolimod once daily significantly reduced patients’ annualized relapse rates by 48% versus placebo. Fingolimod patients also had a statistically significant reduction in brain volume loss.

Those results are consistent with previous trials of the drug (N. Engl. J. Med. 2010;362:387-401; N. Engl. J. Med. 2006;355:1124-40). But in contrast to those studies, fingolimod did not show a statistically significant benefit over placebo on 2-year EDSS (Expanded Disability Status Scale) disability progression.

Overall, "there were probably not any new [safety] signals" in the recent trial, "but some of the old signals came back," said lead investigator Dr. Peter Calabresi, professor of neurology at Johns Hopkins University in Baltimore.

"There were some second-degree AV blocks in a small proportion of patients," 1-3%, he said. There were also dose-dependent, mostly reversible increases in liver function test results during treatment.

"Hypertension was more frequent in this study," as well, Dr. Calabresi said, perhaps because patients had a higher body mass index than in previous trials. The drug’s new labeling notes that about 5% of patients have an approximately 2 mm Hg rise in systolic pressure and 1 mm Hg rise in diastolic pressure after the first month of treatment.

Basal cell carcinoma, macular edema, and herpes zoster and lower respiratory infections were also slightly more frequent in fingolimod patients. Although two patients died in previous trials, there were no deaths in the most recent trial.

It’s "an individual conversation between the doctor and the patient" whether or not to use the drug. "Hopefully the doctor knows that patient well. If you already have hypertension or a history of MI or stroke, you shouldn’t go on this drug. The drug’s known to cause bradycardia and, in some cases, first- and second-degree AV block," Dr. Calabresi said.

Dr. Calabresi reported that he has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, Vertex, Abbott, Genentech, and Merck Serono, and that he has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer.

Every patient should get an electrocardiogram prior to and 6 hours after the first dose of fingolimod, and hourly blood pressure and heart rate measurements in between, to assess for bradycardia, according to revised labeling released by the Food and Drug Administration on May 9.

Patients with prolonged QTc intervals during the observation period should be observed overnight with continuous ECG monitoring, labeling now states.

The revisions come after more than a dozen reports of sudden or unexplained deaths in the United States and Europe following the drug’s 2010 approval for relapsing forms of multiple sclerosis, and months-long talks between the FDA and Novartis, the maker of fingolimod (Gilenya). Previous labeling recommended baseline ECGs only "in those at higher risk of bradyarrhythmia."

--------------------------------------------------------------------------------------------------

• 

     Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod)

--------------------------------------------------------------------------------------------------

Novartis noted in a press release that fingolimod has been used in more than 36,000 patients.

Labeling also now calls for overnight, continuous ECG monitoring in a medical facility for patients with preexisting heart conditions, cerebrovascular disease, recurrent syncope, or severe untreated sleep apnea; patients on beta-blockers or other drugs that slow heart rate or atrioventricular (AV) conduction; and patients with prolonged QTc intervals, whether due to drugs or medical conditions. ECG monitoring is also warranted, in some cases, for patients restarting the drug after a pause.

"Isolated delayed onset events, including transient asystole and unexplained death, have occurred within 24 hours of the first dose," the revised labeling notes, although the relationship with fingolimod is "uncertain."

The new label contraindicates the drug in patients who, in the last 6 months, have had a heart attack, unstable angina, stroke, transient ischemic attack, second- or third-degree AV block, decompensated heart failure requiring hospitalization, sick sinus syndrome with no pacemaker, baseline QTc interval of 500 ms or longer, and treatment with class Ia or class III antiarrhythmic drugs. Previous labeling had no contraindications.

Those and other changes come shortly after the annual meeting of the American Academy of Neurology, where Novartis released the results of its recent 2-year, double-blind, placebo-controlled, multicenter, phase III trial of fingolimod in 1,083 patients with relapsing-remitting multiple sclerosis.

At month 24, 0.5 mg of fingolimod once daily significantly reduced patients’ annualized relapse rates by 48% versus placebo. Fingolimod patients also had a statistically significant reduction in brain volume loss.

Those results are consistent with previous trials of the drug (N. Engl. J. Med. 2010;362:387-401; N. Engl. J. Med. 2006;355:1124-40). But in contrast to those studies, fingolimod did not show a statistically significant benefit over placebo on 2-year EDSS (Expanded Disability Status Scale) disability progression.

Overall, "there were probably not any new [safety] signals" in the recent trial, "but some of the old signals came back," said lead investigator Dr. Peter Calabresi, professor of neurology at Johns Hopkins University in Baltimore.

"There were some second-degree AV blocks in a small proportion of patients," 1-3%, he said. There were also dose-dependent, mostly reversible increases in liver function test results during treatment.

"Hypertension was more frequent in this study," as well, Dr. Calabresi said, perhaps because patients had a higher body mass index than in previous trials. The drug’s new labeling notes that about 5% of patients have an approximately 2 mm Hg rise in systolic pressure and 1 mm Hg rise in diastolic pressure after the first month of treatment.

Basal cell carcinoma, macular edema, and herpes zoster and lower respiratory infections were also slightly more frequent in fingolimod patients. Although two patients died in previous trials, there were no deaths in the most recent trial.

It’s "an individual conversation between the doctor and the patient" whether or not to use the drug. "Hopefully the doctor knows that patient well. If you already have hypertension or a history of MI or stroke, you shouldn’t go on this drug. The drug’s known to cause bradycardia and, in some cases, first- and second-degree AV block," Dr. Calabresi said.

Dr. Calabresi reported that he has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, Vertex, Abbott, Genentech, and Merck Serono, and that he has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer.

Every patient should get an electrocardiogram prior to and 6 hours after the first dose of fingolimod, and hourly blood pressure and heart rate measurements in between, to assess for bradycardia, according to revised labeling released by the Food and Drug Administration on May 9.

Patients with prolonged QTc intervals during the observation period should be observed overnight with continuous ECG monitoring, labeling now states.

The revisions come after more than a dozen reports of sudden or unexplained deaths in the United States and Europe following the drug’s 2010 approval for relapsing forms of multiple sclerosis, and months-long talks between the FDA and Novartis, the maker of fingolimod (Gilenya). Previous labeling recommended baseline ECGs only "in those at higher risk of bradyarrhythmia."

--------------------------------------------------------------------------------------------------

• 

     Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod)

--------------------------------------------------------------------------------------------------

Novartis noted in a press release that fingolimod has been used in more than 36,000 patients.

Labeling also now calls for overnight, continuous ECG monitoring in a medical facility for patients with preexisting heart conditions, cerebrovascular disease, recurrent syncope, or severe untreated sleep apnea; patients on beta-blockers or other drugs that slow heart rate or atrioventricular (AV) conduction; and patients with prolonged QTc intervals, whether due to drugs or medical conditions. ECG monitoring is also warranted, in some cases, for patients restarting the drug after a pause.

"Isolated delayed onset events, including transient asystole and unexplained death, have occurred within 24 hours of the first dose," the revised labeling notes, although the relationship with fingolimod is "uncertain."

The new label contraindicates the drug in patients who, in the last 6 months, have had a heart attack, unstable angina, stroke, transient ischemic attack, second- or third-degree AV block, decompensated heart failure requiring hospitalization, sick sinus syndrome with no pacemaker, baseline QTc interval of 500 ms or longer, and treatment with class Ia or class III antiarrhythmic drugs. Previous labeling had no contraindications.

Those and other changes come shortly after the annual meeting of the American Academy of Neurology, where Novartis released the results of its recent 2-year, double-blind, placebo-controlled, multicenter, phase III trial of fingolimod in 1,083 patients with relapsing-remitting multiple sclerosis.

At month 24, 0.5 mg of fingolimod once daily significantly reduced patients’ annualized relapse rates by 48% versus placebo. Fingolimod patients also had a statistically significant reduction in brain volume loss.

Those results are consistent with previous trials of the drug (N. Engl. J. Med. 2010;362:387-401; N. Engl. J. Med. 2006;355:1124-40). But in contrast to those studies, fingolimod did not show a statistically significant benefit over placebo on 2-year EDSS (Expanded Disability Status Scale) disability progression.

Overall, "there were probably not any new [safety] signals" in the recent trial, "but some of the old signals came back," said lead investigator Dr. Peter Calabresi, professor of neurology at Johns Hopkins University in Baltimore.

"There were some second-degree AV blocks in a small proportion of patients," 1-3%, he said. There were also dose-dependent, mostly reversible increases in liver function test results during treatment.

"Hypertension was more frequent in this study," as well, Dr. Calabresi said, perhaps because patients had a higher body mass index than in previous trials. The drug’s new labeling notes that about 5% of patients have an approximately 2 mm Hg rise in systolic pressure and 1 mm Hg rise in diastolic pressure after the first month of treatment.

Basal cell carcinoma, macular edema, and herpes zoster and lower respiratory infections were also slightly more frequent in fingolimod patients. Although two patients died in previous trials, there were no deaths in the most recent trial.

It’s "an individual conversation between the doctor and the patient" whether or not to use the drug. "Hopefully the doctor knows that patient well. If you already have hypertension or a history of MI or stroke, you shouldn’t go on this drug. The drug’s known to cause bradycardia and, in some cases, first- and second-degree AV block," Dr. Calabresi said.

Dr. Calabresi reported that he has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, Vertex, Abbott, Genentech, and Merck Serono, and that he has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer.

Short-Term Outcomes After Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients With MS
A minimally invasive endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) is safe and may produce “significant,” short-term improvement in the physical– and mental health–related quality of life in patients with multiple sclerosis (MS), according to researchers.

“Traditional theories surrounding treatment for MS in large part focus on autoimmune causes for brain pathology and neurologic symptoms. Based on this, treatment has been predominantly medications by mouth or injection,” stated Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center in New York.

“Interventional radiologists, pioneers in the field of minimally invasive therapies, have been performing … angioplasty for years to treat blocked or narrowed arteries and veins. We have been using angioplasty to open jugular and azygos veins in the neck and chest, respectively, to improve blood flow in people with MS. On follow-up, we have seen many of these individuals report significant symptom relief.”

MS subtypes within the Albany study group included 96 individuals with relapsing-remitting MS, 66 with secondary-progressive MS, and 30 with primary-progressive MS. The study population included those who underwent angioplasty alone and three who underwent angioplasty with a stent placement.

“Results of the study were quite exciting and promising,” stated Dr. Mandato. “We can attest to significant physical improvements reported in greater than 75% of those with relapsing-remitting and primary-progressive forms of MS. Additionally, mental health scores improved in greater than 70% of individuals studied. People with secondary-progressive MS showed statistically significant improvements in both physical and mental health scores at a rate of 59% and 50%, respectively,” he added.

“During a four-month period, we treated 213 individuals; 192 of these patients (141 women; average age, 49) responded to a standard questionnaire that evaluated key quality-of-life components, including changes in physical abilities, health perception, energy/fatigue, sexual function, emotional well-being, cognition, and pain,” explained coauthor Meridith J. Englander, MD, an interventional radiologist at the Albany Medical Center. “We ultimately broke these data down into physical and mental health scores for each person and found improvement in both components of quality of life,” she added. “In addition, we found a trend that patients undergoing this treatment more than 10 years after diagnosis did not respond as well as those with a more recent diagnosis.”

“To address the needs and concerns of those with MS who feel they cannot wait until definitive studies are completed, many doctors are currently offering treatments with the hope of helping individuals with hard-to-manage symptoms of MS,” said Dr. Mandato. “Physicians who perform these treatments hope that this work will provide insights into the design of a prospective, randomized trial that is needed to rigorously evaluate the role of this treatment in MS,” he added.

“As we are still early in fully understanding the condition and its relation to treatment of CCSVI, it is our hope that future double-blinded prospective studies will be performed to further assess the durability of these results,” Dr. Mandato concluded.

Managing Chronic Cerebrospinal Venous Insufficiency in Patients With MS
Performing angioplasty on veins in the neck and chest is safe and may be an effective way to treat the venous abnormalities and provide symptom relief in patients with multiple sclerosis (MS), investigators reported in a second study.

“Our results are important, because there are an estimated 400,000 individuals affected by MS in the United States, some of whom experience symptoms that limit their quality of life in several ways. For many, it can be quite debilitating,” said lead investigator Hector Ferral, MD, an interventional radiologist at NorthShore University HealthSystem in Evanston, Illinois. “These early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life.

“Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,” Dr. Ferral continued. “Based on follow-up that included ultrasound one week postprocedure and clinic visits every three months, our results showed that people who have this treatment are not exposed to fatal risks. Portraying venous angioplasty of the azygos and jugular veins as a high-risk procedure is a widespread misconception that needs to be addressed and corrected. In addition to these significant safety findings, we noted that angioplasty provided symptomatic benefit in 55% of the individuals we treated.”

The retrospective review examined results of 105 procedures performed in 94 patients with MS (59 women; age range, 26 to 67). About 50% of participants had relapsing-remitting MS, 39% had secondary-progressive MS, 6.4% had primary-progressive MS, and 4.2% were unknown. Jugular and azygos veins were evaluated with selective venography and intravascular ultrasound. Angioplasty was performed if the imaging confirmed reflux, allowing blood to flow backward, or a greater than 50% decrease in the vessel’s diameter. If necessary, stents were then used to treat nonresponsive lesions or blockages. These individuals were given blood-thinning medications for six weeks after the treatment.

Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study.

“These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral. “As interventional radiologists, our biggest challenge is to bring to the attention of other specialists, especially those physicians specialized in MS, the evidence that venous lesions, often classified CCSVI, may be a true entity that deserves further attention and serious research,” he explained.

In 2011, members of a Society of Interventional Radiology Foundation’s Research Consensus Panel noted that evaluating patients with MS who have narrowed jugular and azygos veins—and examining the value of widening those veins with angioplasty—warranted careful, well-designed research. The multidisciplinary panel indicated that the “mandatory goal” should be conducting large-scale, pivotal, multicenter trials to explore CCSVI.                     

Short-Term Outcomes After Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients With MS
A minimally invasive endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) is safe and may produce “significant,” short-term improvement in the physical– and mental health–related quality of life in patients with multiple sclerosis (MS), according to researchers.

“Traditional theories surrounding treatment for MS in large part focus on autoimmune causes for brain pathology and neurologic symptoms. Based on this, treatment has been predominantly medications by mouth or injection,” stated Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center in New York.

“Interventional radiologists, pioneers in the field of minimally invasive therapies, have been performing … angioplasty for years to treat blocked or narrowed arteries and veins. We have been using angioplasty to open jugular and azygos veins in the neck and chest, respectively, to improve blood flow in people with MS. On follow-up, we have seen many of these individuals report significant symptom relief.”

MS subtypes within the Albany study group included 96 individuals with relapsing-remitting MS, 66 with secondary-progressive MS, and 30 with primary-progressive MS. The study population included those who underwent angioplasty alone and three who underwent angioplasty with a stent placement.

“Results of the study were quite exciting and promising,” stated Dr. Mandato. “We can attest to significant physical improvements reported in greater than 75% of those with relapsing-remitting and primary-progressive forms of MS. Additionally, mental health scores improved in greater than 70% of individuals studied. People with secondary-progressive MS showed statistically significant improvements in both physical and mental health scores at a rate of 59% and 50%, respectively,” he added.

“During a four-month period, we treated 213 individuals; 192 of these patients (141 women; average age, 49) responded to a standard questionnaire that evaluated key quality-of-life components, including changes in physical abilities, health perception, energy/fatigue, sexual function, emotional well-being, cognition, and pain,” explained coauthor Meridith J. Englander, MD, an interventional radiologist at the Albany Medical Center. “We ultimately broke these data down into physical and mental health scores for each person and found improvement in both components of quality of life,” she added. “In addition, we found a trend that patients undergoing this treatment more than 10 years after diagnosis did not respond as well as those with a more recent diagnosis.”

“To address the needs and concerns of those with MS who feel they cannot wait until definitive studies are completed, many doctors are currently offering treatments with the hope of helping individuals with hard-to-manage symptoms of MS,” said Dr. Mandato. “Physicians who perform these treatments hope that this work will provide insights into the design of a prospective, randomized trial that is needed to rigorously evaluate the role of this treatment in MS,” he added.

“As we are still early in fully understanding the condition and its relation to treatment of CCSVI, it is our hope that future double-blinded prospective studies will be performed to further assess the durability of these results,” Dr. Mandato concluded.

Managing Chronic Cerebrospinal Venous Insufficiency in Patients With MS
Performing angioplasty on veins in the neck and chest is safe and may be an effective way to treat the venous abnormalities and provide symptom relief in patients with multiple sclerosis (MS), investigators reported in a second study.

“Our results are important, because there are an estimated 400,000 individuals affected by MS in the United States, some of whom experience symptoms that limit their quality of life in several ways. For many, it can be quite debilitating,” said lead investigator Hector Ferral, MD, an interventional radiologist at NorthShore University HealthSystem in Evanston, Illinois. “These early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life.

“Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,” Dr. Ferral continued. “Based on follow-up that included ultrasound one week postprocedure and clinic visits every three months, our results showed that people who have this treatment are not exposed to fatal risks. Portraying venous angioplasty of the azygos and jugular veins as a high-risk procedure is a widespread misconception that needs to be addressed and corrected. In addition to these significant safety findings, we noted that angioplasty provided symptomatic benefit in 55% of the individuals we treated.”

The retrospective review examined results of 105 procedures performed in 94 patients with MS (59 women; age range, 26 to 67). About 50% of participants had relapsing-remitting MS, 39% had secondary-progressive MS, 6.4% had primary-progressive MS, and 4.2% were unknown. Jugular and azygos veins were evaluated with selective venography and intravascular ultrasound. Angioplasty was performed if the imaging confirmed reflux, allowing blood to flow backward, or a greater than 50% decrease in the vessel’s diameter. If necessary, stents were then used to treat nonresponsive lesions or blockages. These individuals were given blood-thinning medications for six weeks after the treatment.

Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study.

“These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral. “As interventional radiologists, our biggest challenge is to bring to the attention of other specialists, especially those physicians specialized in MS, the evidence that venous lesions, often classified CCSVI, may be a true entity that deserves further attention and serious research,” he explained.

In 2011, members of a Society of Interventional Radiology Foundation’s Research Consensus Panel noted that evaluating patients with MS who have narrowed jugular and azygos veins—and examining the value of widening those veins with angioplasty—warranted careful, well-designed research. The multidisciplinary panel indicated that the “mandatory goal” should be conducting large-scale, pivotal, multicenter trials to explore CCSVI.                     

Short-Term Outcomes After Endovascular Treatment for Chronic Cerebrospinal Venous Insufficiency in Patients With MS
A minimally invasive endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) is safe and may produce “significant,” short-term improvement in the physical– and mental health–related quality of life in patients with multiple sclerosis (MS), according to researchers.

“Traditional theories surrounding treatment for MS in large part focus on autoimmune causes for brain pathology and neurologic symptoms. Based on this, treatment has been predominantly medications by mouth or injection,” stated Kenneth Mandato, MD, an interventional radiologist at the Albany Medical Center in New York.

“Interventional radiologists, pioneers in the field of minimally invasive therapies, have been performing … angioplasty for years to treat blocked or narrowed arteries and veins. We have been using angioplasty to open jugular and azygos veins in the neck and chest, respectively, to improve blood flow in people with MS. On follow-up, we have seen many of these individuals report significant symptom relief.”

MS subtypes within the Albany study group included 96 individuals with relapsing-remitting MS, 66 with secondary-progressive MS, and 30 with primary-progressive MS. The study population included those who underwent angioplasty alone and three who underwent angioplasty with a stent placement.

“Results of the study were quite exciting and promising,” stated Dr. Mandato. “We can attest to significant physical improvements reported in greater than 75% of those with relapsing-remitting and primary-progressive forms of MS. Additionally, mental health scores improved in greater than 70% of individuals studied. People with secondary-progressive MS showed statistically significant improvements in both physical and mental health scores at a rate of 59% and 50%, respectively,” he added.

“During a four-month period, we treated 213 individuals; 192 of these patients (141 women; average age, 49) responded to a standard questionnaire that evaluated key quality-of-life components, including changes in physical abilities, health perception, energy/fatigue, sexual function, emotional well-being, cognition, and pain,” explained coauthor Meridith J. Englander, MD, an interventional radiologist at the Albany Medical Center. “We ultimately broke these data down into physical and mental health scores for each person and found improvement in both components of quality of life,” she added. “In addition, we found a trend that patients undergoing this treatment more than 10 years after diagnosis did not respond as well as those with a more recent diagnosis.”

“To address the needs and concerns of those with MS who feel they cannot wait until definitive studies are completed, many doctors are currently offering treatments with the hope of helping individuals with hard-to-manage symptoms of MS,” said Dr. Mandato. “Physicians who perform these treatments hope that this work will provide insights into the design of a prospective, randomized trial that is needed to rigorously evaluate the role of this treatment in MS,” he added.

“As we are still early in fully understanding the condition and its relation to treatment of CCSVI, it is our hope that future double-blinded prospective studies will be performed to further assess the durability of these results,” Dr. Mandato concluded.

Managing Chronic Cerebrospinal Venous Insufficiency in Patients With MS
Performing angioplasty on veins in the neck and chest is safe and may be an effective way to treat the venous abnormalities and provide symptom relief in patients with multiple sclerosis (MS), investigators reported in a second study.

“Our results are important, because there are an estimated 400,000 individuals affected by MS in the United States, some of whom experience symptoms that limit their quality of life in several ways. For many, it can be quite debilitating,” said lead investigator Hector Ferral, MD, an interventional radiologist at NorthShore University HealthSystem in Evanston, Illinois. “These early results show that performing angioplasty on azygos and jugular vein lesions may have a positive impact on the symptoms of those individuals with MS and also could be an effective palliative treatment geared toward improving their quality of life.

“Our experience showed that 95% of the individuals we evaluated had venous obstructions, supporting the concept that venous lesions are common in individuals with MS,” Dr. Ferral continued. “Based on follow-up that included ultrasound one week postprocedure and clinic visits every three months, our results showed that people who have this treatment are not exposed to fatal risks. Portraying venous angioplasty of the azygos and jugular veins as a high-risk procedure is a widespread misconception that needs to be addressed and corrected. In addition to these significant safety findings, we noted that angioplasty provided symptomatic benefit in 55% of the individuals we treated.”

The retrospective review examined results of 105 procedures performed in 94 patients with MS (59 women; age range, 26 to 67). About 50% of participants had relapsing-remitting MS, 39% had secondary-progressive MS, 6.4% had primary-progressive MS, and 4.2% were unknown. Jugular and azygos veins were evaluated with selective venography and intravascular ultrasound. Angioplasty was performed if the imaging confirmed reflux, allowing blood to flow backward, or a greater than 50% decrease in the vessel’s diameter. If necessary, stents were then used to treat nonresponsive lesions or blockages. These individuals were given blood-thinning medications for six weeks after the treatment.

Dr. Ferral’s team reported symptomatic improvement in 55% of the individuals treated, and 38% reported no improvement. Seven percent of patients did not comply with their follow-up visits and were considered to be lost to follow-up. Close to 60% of those with relapsing-remitting MS reported improvement in symptoms, the highest of all the subgroups in this study.

“These important results revealed that for people with MS who experience debilitating symptoms, minimally invasive interventional radiology treatments can be an effective, palliative treatment that also may improve their quality of life,” said Dr. Ferral. “As interventional radiologists, our biggest challenge is to bring to the attention of other specialists, especially those physicians specialized in MS, the evidence that venous lesions, often classified CCSVI, may be a true entity that deserves further attention and serious research,” he explained.

In 2011, members of a Society of Interventional Radiology Foundation’s Research Consensus Panel noted that evaluating patients with MS who have narrowed jugular and azygos veins—and examining the value of widening those veins with angioplasty—warranted careful, well-designed research. The multidisciplinary panel indicated that the “mandatory goal” should be conducting large-scale, pivotal, multicenter trials to explore CCSVI.                     

Adults with a higher level of daily physical activity may have a decreased risk of Alzheimer’s disease, according to research published in the online April 18 Neurology. Researchers objectively measured the continuous exercise and nonexercise physical activity of 716 older subjects without dementia by using actigraphy monitoring for up to 10 days. During an average follow-up of four years, 71 persons were diagnosed with clinical Alzheimer’s disease, and the investigators identified an inverse association between total daily physical activity and Alzheimer’s disease (hazard ratio, 0.477) after adjusting for age, sex, and education. This association remained following further adjustments for self-reported physical, social, and cognitive activities; APOE allele status; and current level of motor function, depressive symptoms, and chronic health conditions. “A higher level of total daily physical activity is associated with reduced risk of Alzheimer’s disease,” the investigators concluded.

The herpes zoster vaccine is associated with a small increased risk of allergic reactions in the week following vaccination but is generally safe and well tolerated, according to a study published in the May Journal of Internal Medicine. Researchers analyzed data from 193,083 persons ages 50 and older who had received a zoster vaccine from January 2007 to December 2008 and who were included in the Vaccine Safety Datalink project. A case-centered approach and a self-controlled case series approach were used for analysis. Although results showed that risk of allergic reaction significantly increased within one to seven days of vaccination (RR, 2.13), the investigators identified no increased risk for cerebrovascular or cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay–Hunt syndrome, or Bell’s palsy. According to the study authors, this research supports the safety results from the zoster vaccine’s prelicensure clinical trials.

Consumption of low-fat dairy products may reduce the risk of stroke, according to research published in the online April 19 Stroke. In a prospective cohort study, researchers followed 74,961 Swedish women and men who were free from cancer and cardiovascular disease. During a mean 10.2-year follow-up, 4,089 cases of stroke were recorded among the cohort, including 3,159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Analysis showed an inverse association between consumption of low-fat dairy food and risk of total stroke and cerebral infarction, with multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption of .88 for total stroke and .87 for cerebral infarction. “These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke,” the researchers concluded.

Cognitive abilities decline more rapidly at the end of life than before the terminal period, and late-life participation in mentally stimulating activities might enhance cognitive functioning, according to two studies published in the online April 4 Neurology. In one study, 174 persons without dementia completed a battery of cognitive performance tests at annual intervals for six to 15 years prior to death, after which researchers assessed participants’ brains for evidence of Alzheimer’s disease. Although cognitive decline prior to the terminal period was relatively gradual, cognition declined rapidly during the terminal period. In the second study, 1,076 dementia-free older persons annually completed clinical evaluations (mean, 4.9 years) regarding cognitive performance as well as participation in mentally stimulating activities. Investigators found that cognitive activity participation and cognitive functioning declined at moderately correlative rates. “The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning,” the researchers stated.

Patients with chronic temporal lobe epilepsy have extensive brain abnormalities and age-accelerated ventricular expansion that may have a significant neurodevelopmental impact, according to research published in the online April 3 Epilepsia. Investigators compared differences in brain structure as well as patterns of age-related change in 55 patients with chronic temporal lobe epilepsy with childhood or adolescent onset and 53 healthy controls. Using MRI studies, the researchers identified extensive anatomic abnormalities in patients with chronic temporal lobe epilepsy. Furthermore, participants with epilepsy showed age-accelerated changes in the third and lateral ventricles, though age-related changes in other regions of interest were mostly comparable with those of controls. “These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years,” the study authors said.

Treatment with omega-3 fatty acid supplements is not correlated with reduction in disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to a study published in the online April 16 issue of Archives of Neurology. From 2004 to 2008, investigators conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of 96 patients ages 18 to 55 with active relapsing-remitting MS. Half the participants were randomized to placebo, half were randomized to receive omega-3 fatty acids, and, after six months of treatment, all patients received 44 µg of interferon beta-1a three times per week for another 18 months. Results showed that MRI measurements of gadolinium-enhancing lesions were similar among groups in the first six months, and no difference in relapse rate was found after six or 24 months.

Patients with Parkinson’s disease often have persistent ocular tremors that prevent eye stability during fixation, which suggests that modern, precise oculomotor testing of this feature could serve as a biomarker for early diagnosis of Parkinson’s disease, researchers reported in the online April 9 Archives of Neurology. The investigators conducted a case-control study with 112 patients with Parkinson’s disease, 18 de novo, untreated patients, and 60 age-matched controls. Patients’ oculomotor parameters were assessed with precise eye-tracking technology, and oculomotor function between groups during fixation was compared with oculomotor function while tracking a randomly displaced target on a computer monitor. All 112 patients with Parkinson’s disease showed oscillatory fixation instability. “The pervasiveness and specificity of [ocular tremor] suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson’s disease,” the study authors concluded.

Wrist-worn biosensors that continuously record the sympathetically mediated electrodermal activity (EDA) of patients with epilepsy show autonomic correlates of postictal EEG suppression that may serve as biomarkers for risk of sudden death in epilepsy, according to research published in the online April 25 Neurology. Researchers recorded a total of 34 seizures (22 complex partial; 12 tonic-clonic) in patients with refractory epilepsy who wore the wrist sensors. Analysis of the postictal period showed heightened heart rate and a surge in EDA at the same time as persistent suppression of parasympathetic-modulated high-frequency (HF) power of heart rate. In addition, increased EDA response amplitude was associated with increased duration of EEG suppression (r = 0.81), and decreased HF power was associated with increased duration of EEG suppression (r = -0.87). “The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures,” the investigators stated.

The suggested immobilization test (SIT) may assist clinicians in diagnosing restless legs syndrome (RLS) in patients with Parkinson’s disease, according to research published in the March 21 online Movement Disorders. The investigators compared SIT scores and polysomnography measures of 50 patients with Parkinson’s disease (25 with RLS), 25 patients with primary RLS, and 25 controls matched for age and sex. Results indicated that patients with Parkinson’s disease and RLS had increased mean leg discomfort scores and high leg discomfort at the end of the test compared with patients with Parkinson’s disease but without RLS. In addition, the SIT showed sensitivity of 91% and specificity of 72% for RLS diagnosis in patients with Parkinson’s disease during symptomatic time intervals. “The sensory SIT is a simple test that may help diagnose RLS in patients with Parkinson’s disease,” the researchers concluded. 

Adults with a higher level of daily physical activity may have a decreased risk of Alzheimer’s disease, according to research published in the online April 18 Neurology. Researchers objectively measured the continuous exercise and nonexercise physical activity of 716 older subjects without dementia by using actigraphy monitoring for up to 10 days. During an average follow-up of four years, 71 persons were diagnosed with clinical Alzheimer’s disease, and the investigators identified an inverse association between total daily physical activity and Alzheimer’s disease (hazard ratio, 0.477) after adjusting for age, sex, and education. This association remained following further adjustments for self-reported physical, social, and cognitive activities; APOE allele status; and current level of motor function, depressive symptoms, and chronic health conditions. “A higher level of total daily physical activity is associated with reduced risk of Alzheimer’s disease,” the investigators concluded.

The herpes zoster vaccine is associated with a small increased risk of allergic reactions in the week following vaccination but is generally safe and well tolerated, according to a study published in the May Journal of Internal Medicine. Researchers analyzed data from 193,083 persons ages 50 and older who had received a zoster vaccine from January 2007 to December 2008 and who were included in the Vaccine Safety Datalink project. A case-centered approach and a self-controlled case series approach were used for analysis. Although results showed that risk of allergic reaction significantly increased within one to seven days of vaccination (RR, 2.13), the investigators identified no increased risk for cerebrovascular or cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay–Hunt syndrome, or Bell’s palsy. According to the study authors, this research supports the safety results from the zoster vaccine’s prelicensure clinical trials.

Consumption of low-fat dairy products may reduce the risk of stroke, according to research published in the online April 19 Stroke. In a prospective cohort study, researchers followed 74,961 Swedish women and men who were free from cancer and cardiovascular disease. During a mean 10.2-year follow-up, 4,089 cases of stroke were recorded among the cohort, including 3,159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Analysis showed an inverse association between consumption of low-fat dairy food and risk of total stroke and cerebral infarction, with multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption of .88 for total stroke and .87 for cerebral infarction. “These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke,” the researchers concluded.

Cognitive abilities decline more rapidly at the end of life than before the terminal period, and late-life participation in mentally stimulating activities might enhance cognitive functioning, according to two studies published in the online April 4 Neurology. In one study, 174 persons without dementia completed a battery of cognitive performance tests at annual intervals for six to 15 years prior to death, after which researchers assessed participants’ brains for evidence of Alzheimer’s disease. Although cognitive decline prior to the terminal period was relatively gradual, cognition declined rapidly during the terminal period. In the second study, 1,076 dementia-free older persons annually completed clinical evaluations (mean, 4.9 years) regarding cognitive performance as well as participation in mentally stimulating activities. Investigators found that cognitive activity participation and cognitive functioning declined at moderately correlative rates. “The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning,” the researchers stated.

Patients with chronic temporal lobe epilepsy have extensive brain abnormalities and age-accelerated ventricular expansion that may have a significant neurodevelopmental impact, according to research published in the online April 3 Epilepsia. Investigators compared differences in brain structure as well as patterns of age-related change in 55 patients with chronic temporal lobe epilepsy with childhood or adolescent onset and 53 healthy controls. Using MRI studies, the researchers identified extensive anatomic abnormalities in patients with chronic temporal lobe epilepsy. Furthermore, participants with epilepsy showed age-accelerated changes in the third and lateral ventricles, though age-related changes in other regions of interest were mostly comparable with those of controls. “These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years,” the study authors said.

Treatment with omega-3 fatty acid supplements is not correlated with reduction in disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to a study published in the online April 16 issue of Archives of Neurology. From 2004 to 2008, investigators conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of 96 patients ages 18 to 55 with active relapsing-remitting MS. Half the participants were randomized to placebo, half were randomized to receive omega-3 fatty acids, and, after six months of treatment, all patients received 44 µg of interferon beta-1a three times per week for another 18 months. Results showed that MRI measurements of gadolinium-enhancing lesions were similar among groups in the first six months, and no difference in relapse rate was found after six or 24 months.

Patients with Parkinson’s disease often have persistent ocular tremors that prevent eye stability during fixation, which suggests that modern, precise oculomotor testing of this feature could serve as a biomarker for early diagnosis of Parkinson’s disease, researchers reported in the online April 9 Archives of Neurology. The investigators conducted a case-control study with 112 patients with Parkinson’s disease, 18 de novo, untreated patients, and 60 age-matched controls. Patients’ oculomotor parameters were assessed with precise eye-tracking technology, and oculomotor function between groups during fixation was compared with oculomotor function while tracking a randomly displaced target on a computer monitor. All 112 patients with Parkinson’s disease showed oscillatory fixation instability. “The pervasiveness and specificity of [ocular tremor] suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson’s disease,” the study authors concluded.

Wrist-worn biosensors that continuously record the sympathetically mediated electrodermal activity (EDA) of patients with epilepsy show autonomic correlates of postictal EEG suppression that may serve as biomarkers for risk of sudden death in epilepsy, according to research published in the online April 25 Neurology. Researchers recorded a total of 34 seizures (22 complex partial; 12 tonic-clonic) in patients with refractory epilepsy who wore the wrist sensors. Analysis of the postictal period showed heightened heart rate and a surge in EDA at the same time as persistent suppression of parasympathetic-modulated high-frequency (HF) power of heart rate. In addition, increased EDA response amplitude was associated with increased duration of EEG suppression (r = 0.81), and decreased HF power was associated with increased duration of EEG suppression (r = -0.87). “The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures,” the investigators stated.

The suggested immobilization test (SIT) may assist clinicians in diagnosing restless legs syndrome (RLS) in patients with Parkinson’s disease, according to research published in the March 21 online Movement Disorders. The investigators compared SIT scores and polysomnography measures of 50 patients with Parkinson’s disease (25 with RLS), 25 patients with primary RLS, and 25 controls matched for age and sex. Results indicated that patients with Parkinson’s disease and RLS had increased mean leg discomfort scores and high leg discomfort at the end of the test compared with patients with Parkinson’s disease but without RLS. In addition, the SIT showed sensitivity of 91% and specificity of 72% for RLS diagnosis in patients with Parkinson’s disease during symptomatic time intervals. “The sensory SIT is a simple test that may help diagnose RLS in patients with Parkinson’s disease,” the researchers concluded. 

Adults with a higher level of daily physical activity may have a decreased risk of Alzheimer’s disease, according to research published in the online April 18 Neurology. Researchers objectively measured the continuous exercise and nonexercise physical activity of 716 older subjects without dementia by using actigraphy monitoring for up to 10 days. During an average follow-up of four years, 71 persons were diagnosed with clinical Alzheimer’s disease, and the investigators identified an inverse association between total daily physical activity and Alzheimer’s disease (hazard ratio, 0.477) after adjusting for age, sex, and education. This association remained following further adjustments for self-reported physical, social, and cognitive activities; APOE allele status; and current level of motor function, depressive symptoms, and chronic health conditions. “A higher level of total daily physical activity is associated with reduced risk of Alzheimer’s disease,” the investigators concluded.

The herpes zoster vaccine is associated with a small increased risk of allergic reactions in the week following vaccination but is generally safe and well tolerated, according to a study published in the May Journal of Internal Medicine. Researchers analyzed data from 193,083 persons ages 50 and older who had received a zoster vaccine from January 2007 to December 2008 and who were included in the Vaccine Safety Datalink project. A case-centered approach and a self-controlled case series approach were used for analysis. Although results showed that risk of allergic reaction significantly increased within one to seven days of vaccination (RR, 2.13), the investigators identified no increased risk for cerebrovascular or cardiovascular events, meningitis, encephalitis, encephalopathy, Ramsay–Hunt syndrome, or Bell’s palsy. According to the study authors, this research supports the safety results from the zoster vaccine’s prelicensure clinical trials.

Consumption of low-fat dairy products may reduce the risk of stroke, according to research published in the online April 19 Stroke. In a prospective cohort study, researchers followed 74,961 Swedish women and men who were free from cancer and cardiovascular disease. During a mean 10.2-year follow-up, 4,089 cases of stroke were recorded among the cohort, including 3,159 cerebral infarctions, 583 hemorrhagic strokes, and 347 unspecified strokes. Analysis showed an inverse association between consumption of low-fat dairy food and risk of total stroke and cerebral infarction, with multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption of .88 for total stroke and .87 for cerebral infarction. “These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke,” the researchers concluded.

Cognitive abilities decline more rapidly at the end of life than before the terminal period, and late-life participation in mentally stimulating activities might enhance cognitive functioning, according to two studies published in the online April 4 Neurology. In one study, 174 persons without dementia completed a battery of cognitive performance tests at annual intervals for six to 15 years prior to death, after which researchers assessed participants’ brains for evidence of Alzheimer’s disease. Although cognitive decline prior to the terminal period was relatively gradual, cognition declined rapidly during the terminal period. In the second study, 1,076 dementia-free older persons annually completed clinical evaluations (mean, 4.9 years) regarding cognitive performance as well as participation in mentally stimulating activities. Investigators found that cognitive activity participation and cognitive functioning declined at moderately correlative rates. “The results suggest that more frequent mental stimulation in old age leads to better cognitive functioning,” the researchers stated.

Patients with chronic temporal lobe epilepsy have extensive brain abnormalities and age-accelerated ventricular expansion that may have a significant neurodevelopmental impact, according to research published in the online April 3 Epilepsia. Investigators compared differences in brain structure as well as patterns of age-related change in 55 patients with chronic temporal lobe epilepsy with childhood or adolescent onset and 53 healthy controls. Using MRI studies, the researchers identified extensive anatomic abnormalities in patients with chronic temporal lobe epilepsy. Furthermore, participants with epilepsy showed age-accelerated changes in the third and lateral ventricles, though age-related changes in other regions of interest were mostly comparable with those of controls. “These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years,” the study authors said.

Treatment with omega-3 fatty acid supplements is not correlated with reduction in disease activity in patients with relapsing-remitting multiple sclerosis (MS), according to a study published in the online April 16 issue of Archives of Neurology. From 2004 to 2008, investigators conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of 96 patients ages 18 to 55 with active relapsing-remitting MS. Half the participants were randomized to placebo, half were randomized to receive omega-3 fatty acids, and, after six months of treatment, all patients received 44 µg of interferon beta-1a three times per week for another 18 months. Results showed that MRI measurements of gadolinium-enhancing lesions were similar among groups in the first six months, and no difference in relapse rate was found after six or 24 months.

Patients with Parkinson’s disease often have persistent ocular tremors that prevent eye stability during fixation, which suggests that modern, precise oculomotor testing of this feature could serve as a biomarker for early diagnosis of Parkinson’s disease, researchers reported in the online April 9 Archives of Neurology. The investigators conducted a case-control study with 112 patients with Parkinson’s disease, 18 de novo, untreated patients, and 60 age-matched controls. Patients’ oculomotor parameters were assessed with precise eye-tracking technology, and oculomotor function between groups during fixation was compared with oculomotor function while tracking a randomly displaced target on a computer monitor. All 112 patients with Parkinson’s disease showed oscillatory fixation instability. “The pervasiveness and specificity of [ocular tremor] suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing Parkinson’s disease,” the study authors concluded.

Wrist-worn biosensors that continuously record the sympathetically mediated electrodermal activity (EDA) of patients with epilepsy show autonomic correlates of postictal EEG suppression that may serve as biomarkers for risk of sudden death in epilepsy, according to research published in the online April 25 Neurology. Researchers recorded a total of 34 seizures (22 complex partial; 12 tonic-clonic) in patients with refractory epilepsy who wore the wrist sensors. Analysis of the postictal period showed heightened heart rate and a surge in EDA at the same time as persistent suppression of parasympathetic-modulated high-frequency (HF) power of heart rate. In addition, increased EDA response amplitude was associated with increased duration of EEG suppression (r = 0.81), and decreased HF power was associated with increased duration of EEG suppression (r = -0.87). “The magnitude of both sympathetic activation and parasympathetic suppression increases with duration of EEG suppression after tonic-clonic seizures,” the investigators stated.

The suggested immobilization test (SIT) may assist clinicians in diagnosing restless legs syndrome (RLS) in patients with Parkinson’s disease, according to research published in the March 21 online Movement Disorders. The investigators compared SIT scores and polysomnography measures of 50 patients with Parkinson’s disease (25 with RLS), 25 patients with primary RLS, and 25 controls matched for age and sex. Results indicated that patients with Parkinson’s disease and RLS had increased mean leg discomfort scores and high leg discomfort at the end of the test compared with patients with Parkinson’s disease but without RLS. In addition, the SIT showed sensitivity of 91% and specificity of 72% for RLS diagnosis in patients with Parkinson’s disease during symptomatic time intervals. “The sensory SIT is a simple test that may help diagnose RLS in patients with Parkinson’s disease,” the researchers concluded. 

Patients with an apparent first demyelinating event who are treated early with subcutaneous interferon beta-1a experience a significantly longer time until progression to multiple sclerosis, compared with those whose treatment is initiated after diagnosis with clinically definite MS, according to 3-year results from the ongoing phase III, double-blind REFLEX extension trial.

The best results from the REFLEXION trial occurred in those treated early with a 44-mcg dose given three times weekly.

The findings provide additional evidence that treating early makes a difference in the long run, lead investigator Dr. Mark Freedman said in an interview. Dr. Freedman will present the results April 25 at the annual meeting of the American Academy of Neurology.

"What we saw at 2 years [in the REFLEXION trial] is definitely still there at 3 years. Treating early is the best opportunity for getting control of the disease," he said.

Not only do the findings show that early treatment matters, they show that the dose matters – even at the start of treatment, said Dr. Freedman, director of the multiple sclerosis research unit at the Ottawa (Ont.) Hospital and professor of neurology at the University of Ottawa. "The one question that remained after all the other interferon trials was the question about the dose," and now the answer is 44 mcg three times weekly.

In the REFLEX trial, 517 patients with a first demyelinating event were randomized to receive placebo; 44-mcg of interferon beta-1a three times weekly; or an off-label, 44-mcg dose of interferon beta-1a once weekly. They received treatment for 24 months or until they were diagnosed with clinically definite multiple sclerosis (CDMS), at which time they were switched to the three-times-weekly interferon dose. Both doses of interferon, when given early, significantly delayed CDMS and MS based on the more MRI-dependent McDonald criteria, compared with placebo. For MS diagnosed with the McDonald criteria, the three-times-weekly interferon dose was associated with significantly greater delay than the once-weekly dose.

All patients from the REFLEX trial were eligible for REFLEXION; 402 (78%) participated. All those originally on placebo who did not reach CDMS were switched to interferon three times weekly, and those in the initial interferon once- or three-times-weekly groups who did not reach CDMS remained in their original treatment group.

Integrated data from the two trials, analyzed by original group, showed that the 36-month cumulative probability of CDMS was 41.3% for the placebo/delayed-treatment group, 27.6% for the once-weekly interferon group, and 27.1% for the three-times-weekly interferon group. The 36-month probability of McDonald-criteria MS was 87% for placebo/delayed treatment, 79% for the once-weekly interferon group, and 67% for the three times weekly interferon group.

As in the REFLEX trial, the difference in time to progression was statistically significant for both interferon groups compared with placebo based on both clinical and MRI-based criteria, and for the three-times-weekly interferon group compared with the once-weekly interferon group based on McDonald criteria, Dr. Freedman said.

The REFLEX and REFLEXION trials were conducted using a human serum albumin-free formulation of interferon beta-1a that is available in numerous countries worldwide but not in the United States. Participants had a first clinical episode suggestive of a demyelinating event, including symptoms such as tingling, numbness, muscle weakness, or balance problems. They also had at least two clinically silent brain lesions detected on MRI.

CDMS was diagnosed in those experiencing a second clinical attack or a sustained increase of more than 1.5 in the Expanded Disability Status Scale score. Those who initially received placebo but who did not develop CDMS – and who therefore switched to interferon only after entering the REFLEXION trial – started interferon treatment an average of 58 days following their initial symptoms.

An added benefit of starting with this higher dose is that, compared with the lower dose, it was associated with a reduction in the persistent flulike symptoms known to be associated with interferon beta-1a, Dr. Freedman said.

The REFLEXION trial, which is sponsored by Merck Serono S.A., will continue for a total of 5 years, he said.

Dr. Freedman had no other disclosures to report.

Patients with an apparent first demyelinating event who are treated early with subcutaneous interferon beta-1a experience a significantly longer time until progression to multiple sclerosis, compared with those whose treatment is initiated after diagnosis with clinically definite MS, according to 3-year results from the ongoing phase III, double-blind REFLEX extension trial.

The best results from the REFLEXION trial occurred in those treated early with a 44-mcg dose given three times weekly.

The findings provide additional evidence that treating early makes a difference in the long run, lead investigator Dr. Mark Freedman said in an interview. Dr. Freedman will present the results April 25 at the annual meeting of the American Academy of Neurology.

"What we saw at 2 years [in the REFLEXION trial] is definitely still there at 3 years. Treating early is the best opportunity for getting control of the disease," he said.

Not only do the findings show that early treatment matters, they show that the dose matters – even at the start of treatment, said Dr. Freedman, director of the multiple sclerosis research unit at the Ottawa (Ont.) Hospital and professor of neurology at the University of Ottawa. "The one question that remained after all the other interferon trials was the question about the dose," and now the answer is 44 mcg three times weekly.

In the REFLEX trial, 517 patients with a first demyelinating event were randomized to receive placebo; 44-mcg of interferon beta-1a three times weekly; or an off-label, 44-mcg dose of interferon beta-1a once weekly. They received treatment for 24 months or until they were diagnosed with clinically definite multiple sclerosis (CDMS), at which time they were switched to the three-times-weekly interferon dose. Both doses of interferon, when given early, significantly delayed CDMS and MS based on the more MRI-dependent McDonald criteria, compared with placebo. For MS diagnosed with the McDonald criteria, the three-times-weekly interferon dose was associated with significantly greater delay than the once-weekly dose.

All patients from the REFLEX trial were eligible for REFLEXION; 402 (78%) participated. All those originally on placebo who did not reach CDMS were switched to interferon three times weekly, and those in the initial interferon once- or three-times-weekly groups who did not reach CDMS remained in their original treatment group.

Integrated data from the two trials, analyzed by original group, showed that the 36-month cumulative probability of CDMS was 41.3% for the placebo/delayed-treatment group, 27.6% for the once-weekly interferon group, and 27.1% for the three-times-weekly interferon group. The 36-month probability of McDonald-criteria MS was 87% for placebo/delayed treatment, 79% for the once-weekly interferon group, and 67% for the three times weekly interferon group.

As in the REFLEX trial, the difference in time to progression was statistically significant for both interferon groups compared with placebo based on both clinical and MRI-based criteria, and for the three-times-weekly interferon group compared with the once-weekly interferon group based on McDonald criteria, Dr. Freedman said.

The REFLEX and REFLEXION trials were conducted using a human serum albumin-free formulation of interferon beta-1a that is available in numerous countries worldwide but not in the United States. Participants had a first clinical episode suggestive of a demyelinating event, including symptoms such as tingling, numbness, muscle weakness, or balance problems. They also had at least two clinically silent brain lesions detected on MRI.

CDMS was diagnosed in those experiencing a second clinical attack or a sustained increase of more than 1.5 in the Expanded Disability Status Scale score. Those who initially received placebo but who did not develop CDMS – and who therefore switched to interferon only after entering the REFLEXION trial – started interferon treatment an average of 58 days following their initial symptoms.

An added benefit of starting with this higher dose is that, compared with the lower dose, it was associated with a reduction in the persistent flulike symptoms known to be associated with interferon beta-1a, Dr. Freedman said.

The REFLEXION trial, which is sponsored by Merck Serono S.A., will continue for a total of 5 years, he said.

Dr. Freedman had no other disclosures to report.

Patients with an apparent first demyelinating event who are treated early with subcutaneous interferon beta-1a experience a significantly longer time until progression to multiple sclerosis, compared with those whose treatment is initiated after diagnosis with clinically definite MS, according to 3-year results from the ongoing phase III, double-blind REFLEX extension trial.

The best results from the REFLEXION trial occurred in those treated early with a 44-mcg dose given three times weekly.

The findings provide additional evidence that treating early makes a difference in the long run, lead investigator Dr. Mark Freedman said in an interview. Dr. Freedman will present the results April 25 at the annual meeting of the American Academy of Neurology.

"What we saw at 2 years [in the REFLEXION trial] is definitely still there at 3 years. Treating early is the best opportunity for getting control of the disease," he said.

Not only do the findings show that early treatment matters, they show that the dose matters – even at the start of treatment, said Dr. Freedman, director of the multiple sclerosis research unit at the Ottawa (Ont.) Hospital and professor of neurology at the University of Ottawa. "The one question that remained after all the other interferon trials was the question about the dose," and now the answer is 44 mcg three times weekly.

In the REFLEX trial, 517 patients with a first demyelinating event were randomized to receive placebo; 44-mcg of interferon beta-1a three times weekly; or an off-label, 44-mcg dose of interferon beta-1a once weekly. They received treatment for 24 months or until they were diagnosed with clinically definite multiple sclerosis (CDMS), at which time they were switched to the three-times-weekly interferon dose. Both doses of interferon, when given early, significantly delayed CDMS and MS based on the more MRI-dependent McDonald criteria, compared with placebo. For MS diagnosed with the McDonald criteria, the three-times-weekly interferon dose was associated with significantly greater delay than the once-weekly dose.

All patients from the REFLEX trial were eligible for REFLEXION; 402 (78%) participated. All those originally on placebo who did not reach CDMS were switched to interferon three times weekly, and those in the initial interferon once- or three-times-weekly groups who did not reach CDMS remained in their original treatment group.

Integrated data from the two trials, analyzed by original group, showed that the 36-month cumulative probability of CDMS was 41.3% for the placebo/delayed-treatment group, 27.6% for the once-weekly interferon group, and 27.1% for the three-times-weekly interferon group. The 36-month probability of McDonald-criteria MS was 87% for placebo/delayed treatment, 79% for the once-weekly interferon group, and 67% for the three times weekly interferon group.

As in the REFLEX trial, the difference in time to progression was statistically significant for both interferon groups compared with placebo based on both clinical and MRI-based criteria, and for the three-times-weekly interferon group compared with the once-weekly interferon group based on McDonald criteria, Dr. Freedman said.

The REFLEX and REFLEXION trials were conducted using a human serum albumin-free formulation of interferon beta-1a that is available in numerous countries worldwide but not in the United States. Participants had a first clinical episode suggestive of a demyelinating event, including symptoms such as tingling, numbness, muscle weakness, or balance problems. They also had at least two clinically silent brain lesions detected on MRI.

CDMS was diagnosed in those experiencing a second clinical attack or a sustained increase of more than 1.5 in the Expanded Disability Status Scale score. Those who initially received placebo but who did not develop CDMS – and who therefore switched to interferon only after entering the REFLEXION trial – started interferon treatment an average of 58 days following their initial symptoms.

An added benefit of starting with this higher dose is that, compared with the lower dose, it was associated with a reduction in the persistent flulike symptoms known to be associated with interferon beta-1a, Dr. Freedman said.

The REFLEXION trial, which is sponsored by Merck Serono S.A., will continue for a total of 5 years, he said.

Dr. Freedman had no other disclosures to report.

Adipose tissue in patients with multiple sclerosis is marked by an activated lipolytic metabolic state.

AMSTERDAM—Patients with multiple sclerosis (MS) have an altered metabolic flexibility after glucose load, both at rest and during exercise, researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Persons with MS had a higher baseline respiratory quotient at rest than healthy controls did, which may indicate that the former have a higher rate of carbohydrate oxidation and a lower rate of lipid oxidation than the latter do. Also, after 40 minutes of light exercise, patients with MS showed greater energy expenditure than controls did.

Measuring Metabolismin Patients With MS
One symptom of MS is an intolerance to exercise, but it is not clear whether this symptom results from a metabolic change. To test the hypothesis that altered metabolic flexibility contributes to exercise intolerance in patients with MS, Anja Mähler, a nutritionist at the Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine, Berlin, and colleagues conducted a prospective study of 16 patients (eight men), with MS who were taking glatiramer acetate.

The patients’ mean age was 45, their mean BMI was 25.2, and they had had MS for a median of 133 months. Eight healthy men and eight healthy women also were studied as controls. The mean age of members of the control group was 40, and their mean BMI was 23.3.

In two separate tests, the researchers compared the groups’ postprandial and exercise activity metabolism with their resting metabolism, both after an oral glucose load. Blood marker metabolites and calorimetry were used to study systemic metabolism, and adipose tissue and skeletal muscle microdialysis were used to examine local metabolism.

Altered Metabolic Flexibility Could Result From MS
After an oral glucose load, patients with MS expended slightly less postprandial energy than controls did. Baseline and postprandial respiratory quotients, however, were higher in patients with MS than in controls, which indicated that the patients had higher carbohydrate and lower lipid oxidation rates than did controls. In addition, higher baseline and postprandial levels of dialysate glucose and lactate in adipose tissue in patients with MS indicated an activated lipolytic metabolic state.

The respiratory quotient kinetics were different in patients with MS than in controls during exercise, according to the study. Respiratory quotient did not reach a plateau in patients with MS as it did in controls.

The altered metabolic flexibility in patients with MS at rest and during exercise “might be attributed to an autonomic dysfunction,” said the investigators. The activated lipolytic metabolic state seen in the adipose tissue of patients with MS “could be caused by local monocyte/macrophage infiltration due to systemic inflammation,” they remarked. Future studies should investigate whether these two factors contribute to mitochondrial dysfunction in patients with MS, the investigators concluded.   

Adipose tissue in patients with multiple sclerosis is marked by an activated lipolytic metabolic state.

AMSTERDAM—Patients with multiple sclerosis (MS) have an altered metabolic flexibility after glucose load, both at rest and during exercise, researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Persons with MS had a higher baseline respiratory quotient at rest than healthy controls did, which may indicate that the former have a higher rate of carbohydrate oxidation and a lower rate of lipid oxidation than the latter do. Also, after 40 minutes of light exercise, patients with MS showed greater energy expenditure than controls did.

Measuring Metabolismin Patients With MS
One symptom of MS is an intolerance to exercise, but it is not clear whether this symptom results from a metabolic change. To test the hypothesis that altered metabolic flexibility contributes to exercise intolerance in patients with MS, Anja Mähler, a nutritionist at the Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine, Berlin, and colleagues conducted a prospective study of 16 patients (eight men), with MS who were taking glatiramer acetate.

The patients’ mean age was 45, their mean BMI was 25.2, and they had had MS for a median of 133 months. Eight healthy men and eight healthy women also were studied as controls. The mean age of members of the control group was 40, and their mean BMI was 23.3.

In two separate tests, the researchers compared the groups’ postprandial and exercise activity metabolism with their resting metabolism, both after an oral glucose load. Blood marker metabolites and calorimetry were used to study systemic metabolism, and adipose tissue and skeletal muscle microdialysis were used to examine local metabolism.

Altered Metabolic Flexibility Could Result From MS
After an oral glucose load, patients with MS expended slightly less postprandial energy than controls did. Baseline and postprandial respiratory quotients, however, were higher in patients with MS than in controls, which indicated that the patients had higher carbohydrate and lower lipid oxidation rates than did controls. In addition, higher baseline and postprandial levels of dialysate glucose and lactate in adipose tissue in patients with MS indicated an activated lipolytic metabolic state.

The respiratory quotient kinetics were different in patients with MS than in controls during exercise, according to the study. Respiratory quotient did not reach a plateau in patients with MS as it did in controls.

The altered metabolic flexibility in patients with MS at rest and during exercise “might be attributed to an autonomic dysfunction,” said the investigators. The activated lipolytic metabolic state seen in the adipose tissue of patients with MS “could be caused by local monocyte/macrophage infiltration due to systemic inflammation,” they remarked. Future studies should investigate whether these two factors contribute to mitochondrial dysfunction in patients with MS, the investigators concluded.   

Adipose tissue in patients with multiple sclerosis is marked by an activated lipolytic metabolic state.

AMSTERDAM—Patients with multiple sclerosis (MS) have an altered metabolic flexibility after glucose load, both at rest and during exercise, researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in MS.

Persons with MS had a higher baseline respiratory quotient at rest than healthy controls did, which may indicate that the former have a higher rate of carbohydrate oxidation and a lower rate of lipid oxidation than the latter do. Also, after 40 minutes of light exercise, patients with MS showed greater energy expenditure than controls did.

Measuring Metabolismin Patients With MS
One symptom of MS is an intolerance to exercise, but it is not clear whether this symptom results from a metabolic change. To test the hypothesis that altered metabolic flexibility contributes to exercise intolerance in patients with MS, Anja Mähler, a nutritionist at the Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Charité University Medicine, Berlin, and colleagues conducted a prospective study of 16 patients (eight men), with MS who were taking glatiramer acetate.

The patients’ mean age was 45, their mean BMI was 25.2, and they had had MS for a median of 133 months. Eight healthy men and eight healthy women also were studied as controls. The mean age of members of the control group was 40, and their mean BMI was 23.3.

In two separate tests, the researchers compared the groups’ postprandial and exercise activity metabolism with their resting metabolism, both after an oral glucose load. Blood marker metabolites and calorimetry were used to study systemic metabolism, and adipose tissue and skeletal muscle microdialysis were used to examine local metabolism.

Altered Metabolic Flexibility Could Result From MS
After an oral glucose load, patients with MS expended slightly less postprandial energy than controls did. Baseline and postprandial respiratory quotients, however, were higher in patients with MS than in controls, which indicated that the patients had higher carbohydrate and lower lipid oxidation rates than did controls. In addition, higher baseline and postprandial levels of dialysate glucose and lactate in adipose tissue in patients with MS indicated an activated lipolytic metabolic state.

The respiratory quotient kinetics were different in patients with MS than in controls during exercise, according to the study. Respiratory quotient did not reach a plateau in patients with MS as it did in controls.

The altered metabolic flexibility in patients with MS at rest and during exercise “might be attributed to an autonomic dysfunction,” said the investigators. The activated lipolytic metabolic state seen in the adipose tissue of patients with MS “could be caused by local monocyte/macrophage infiltration due to systemic inflammation,” they remarked. Future studies should investigate whether these two factors contribute to mitochondrial dysfunction in patients with MS, the investigators concluded.   

Low levels of vitamin D can increase MS risk but low gestational levels of 25(OH)D have no effect on MS risk.

AMSTERDAM—Levels of vitamin D greater than or equal to 75 nmol/L are associated with a 61% lower risk for multiple sclerosis (MS), researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Gestational vitamin D levels do not affect the risk for MS in children, however.

Jonatan Salzer, a graduate student in clinical neuroscience at Umeå University in Sweden, and associates conducted a study to estimate the risk for MS by examining levels of 25(OH)D in prospectively collected blood samples from patients with MS and controls. The investigators also sought to evaluate the risk for MS in children by studying levels of 25(OH)D during pregnancy.

The researchers created a database of MS cases and mothers of patients with MS in the four northern counties of Sweden. The database was cross-linked to various biobanks that contained serum and plasma samples taken between 1976 and 2005. The researchers found 192 MS cases with prospectively collected samples for their study of risk factors of MS, and 37 gestational samples taken during pregnancies in which the offspring had later developed MS, as the basis for their inquiry into gestational risk factors of MS. Controls were matched for sex, biobank, sampling date, and age.

Decreasing Levels of Vitamin D
Analysis showed that 3.6% of MS cases and 7.8% of controls had levels of 25(OH)D ≥75 nmol/L, which is the cutoff for normal levels, as defined by the American Endocrine Society. The investigators found a negative correlation between 25(OH)D levels and sampling year for samples collected from May through October (ie, the 25(OH)D levels were lower in later samples).

Also, the risk for 25(OH)D levels <75 nmol/L in controls was three times higher in samples taken after 1985 than it was in samples taken before 1985. Overall, the risk of having 25(OH)D levels <75 nmol/L increased from 1976 to 2005, according to Mr. Salzer.

Changes in the population’s summer behavior, including increasing use of sunscreen, wearing clothes that cover more of the body, and a reduction in time spent outdoors, could explain the overall decrease in vitamin D levels, said Mr. Salzer. “If this finding can be replicated in other cohorts, and applies to the time before 1976, perhaps it is the key to why MS incidence is increasing,” he added.

No effect on MS risk was observed when the investigators grouped 25(OH)D levels into other categories, such as median, tertiles, and quintiles. This result occurred “because of the high prevalence of 25(OH)D levels <75 nmol/L in northern Sweden” and “suggests that higher levels are needed to protect against MS,” said Mr. Salzer.

The results contradict the findings of the 2011 diet questionnaire study conducted by Mirzaei et al. The investigators noted that their results “must be treated with caution,” however, because of the small sample size. “There is a need for expanded study material on vitamin D levels, in which samples are collected from gestation through adolescence,” Mr. Salzer said.

A Call to Revise Recommended Doses of Vitamin D
It may be reasonable to “adjust the supplementation recommendations to increase the doses and include the entire population, with the goal of no one having levels below 75 nmol/L” concluded Mr. Salzer.   

Low levels of vitamin D can increase MS risk but low gestational levels of 25(OH)D have no effect on MS risk.

AMSTERDAM—Levels of vitamin D greater than or equal to 75 nmol/L are associated with a 61% lower risk for multiple sclerosis (MS), researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Gestational vitamin D levels do not affect the risk for MS in children, however.

Jonatan Salzer, a graduate student in clinical neuroscience at Umeå University in Sweden, and associates conducted a study to estimate the risk for MS by examining levels of 25(OH)D in prospectively collected blood samples from patients with MS and controls. The investigators also sought to evaluate the risk for MS in children by studying levels of 25(OH)D during pregnancy.

The researchers created a database of MS cases and mothers of patients with MS in the four northern counties of Sweden. The database was cross-linked to various biobanks that contained serum and plasma samples taken between 1976 and 2005. The researchers found 192 MS cases with prospectively collected samples for their study of risk factors of MS, and 37 gestational samples taken during pregnancies in which the offspring had later developed MS, as the basis for their inquiry into gestational risk factors of MS. Controls were matched for sex, biobank, sampling date, and age.

Decreasing Levels of Vitamin D
Analysis showed that 3.6% of MS cases and 7.8% of controls had levels of 25(OH)D ≥75 nmol/L, which is the cutoff for normal levels, as defined by the American Endocrine Society. The investigators found a negative correlation between 25(OH)D levels and sampling year for samples collected from May through October (ie, the 25(OH)D levels were lower in later samples).

Also, the risk for 25(OH)D levels <75 nmol/L in controls was three times higher in samples taken after 1985 than it was in samples taken before 1985. Overall, the risk of having 25(OH)D levels <75 nmol/L increased from 1976 to 2005, according to Mr. Salzer.

Changes in the population’s summer behavior, including increasing use of sunscreen, wearing clothes that cover more of the body, and a reduction in time spent outdoors, could explain the overall decrease in vitamin D levels, said Mr. Salzer. “If this finding can be replicated in other cohorts, and applies to the time before 1976, perhaps it is the key to why MS incidence is increasing,” he added.

No effect on MS risk was observed when the investigators grouped 25(OH)D levels into other categories, such as median, tertiles, and quintiles. This result occurred “because of the high prevalence of 25(OH)D levels <75 nmol/L in northern Sweden” and “suggests that higher levels are needed to protect against MS,” said Mr. Salzer.

The results contradict the findings of the 2011 diet questionnaire study conducted by Mirzaei et al. The investigators noted that their results “must be treated with caution,” however, because of the small sample size. “There is a need for expanded study material on vitamin D levels, in which samples are collected from gestation through adolescence,” Mr. Salzer said.

A Call to Revise Recommended Doses of Vitamin D
It may be reasonable to “adjust the supplementation recommendations to increase the doses and include the entire population, with the goal of no one having levels below 75 nmol/L” concluded Mr. Salzer.   

Low levels of vitamin D can increase MS risk but low gestational levels of 25(OH)D have no effect on MS risk.

AMSTERDAM—Levels of vitamin D greater than or equal to 75 nmol/L are associated with a 61% lower risk for multiple sclerosis (MS), researchers reported at the Fifth Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis. Gestational vitamin D levels do not affect the risk for MS in children, however.

Jonatan Salzer, a graduate student in clinical neuroscience at Umeå University in Sweden, and associates conducted a study to estimate the risk for MS by examining levels of 25(OH)D in prospectively collected blood samples from patients with MS and controls. The investigators also sought to evaluate the risk for MS in children by studying levels of 25(OH)D during pregnancy.

The researchers created a database of MS cases and mothers of patients with MS in the four northern counties of Sweden. The database was cross-linked to various biobanks that contained serum and plasma samples taken between 1976 and 2005. The researchers found 192 MS cases with prospectively collected samples for their study of risk factors of MS, and 37 gestational samples taken during pregnancies in which the offspring had later developed MS, as the basis for their inquiry into gestational risk factors of MS. Controls were matched for sex, biobank, sampling date, and age.

Decreasing Levels of Vitamin D
Analysis showed that 3.6% of MS cases and 7.8% of controls had levels of 25(OH)D ≥75 nmol/L, which is the cutoff for normal levels, as defined by the American Endocrine Society. The investigators found a negative correlation between 25(OH)D levels and sampling year for samples collected from May through October (ie, the 25(OH)D levels were lower in later samples).

Also, the risk for 25(OH)D levels <75 nmol/L in controls was three times higher in samples taken after 1985 than it was in samples taken before 1985. Overall, the risk of having 25(OH)D levels <75 nmol/L increased from 1976 to 2005, according to Mr. Salzer.

Changes in the population’s summer behavior, including increasing use of sunscreen, wearing clothes that cover more of the body, and a reduction in time spent outdoors, could explain the overall decrease in vitamin D levels, said Mr. Salzer. “If this finding can be replicated in other cohorts, and applies to the time before 1976, perhaps it is the key to why MS incidence is increasing,” he added.

No effect on MS risk was observed when the investigators grouped 25(OH)D levels into other categories, such as median, tertiles, and quintiles. This result occurred “because of the high prevalence of 25(OH)D levels <75 nmol/L in northern Sweden” and “suggests that higher levels are needed to protect against MS,” said Mr. Salzer.

The results contradict the findings of the 2011 diet questionnaire study conducted by Mirzaei et al. The investigators noted that their results “must be treated with caution,” however, because of the small sample size. “There is a need for expanded study material on vitamin D levels, in which samples are collected from gestation through adolescence,” Mr. Salzer said.

A Call to Revise Recommended Doses of Vitamin D
It may be reasonable to “adjust the supplementation recommendations to increase the doses and include the entire population, with the goal of no one having levels below 75 nmol/L” concluded Mr. Salzer.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.   

Symptoms of migraine aura may resemble those of multiple sclerosis (MS) relapse, and some MS drugs may cause headache.

STOWE, VT—Migraine and multiple sclerosis (MS) can have similar symptoms and often are comorbid diseases, according to Angela Applebee, MD, who spoke at the Headache Cooperative of New England’s 22nd Annual Headache Symposium. Neurologists should know which MS therapies can contribute to headache and which migraine drugs to prescribe with caution if a patient is taking certain new MS therapies, said Dr. Applebee, Assistant Professor of Neurology at the University of Vermont in Burlington.

The Link Between Migraine and MS
“The most convincing study of the link between migraine and MS” is the Nursing Health Study, said Dr. Applebee. That prospective study, during which investigators at New York University sent surveys to 116,000 nurses from 1989 to 1995, found that patients with migraine had a 39% higher risk of developing MS than nonmigraneurs. The absolute risk of developing MS was 0.15% higher, which means that migraine is a modest predictor of MS. Stronger predictors of MS include factors such as DRB1*1501 haplotype or history of infectious mononucleosis.

The study also found that patients with MS had a 33% greater chance of being diagnosed with migraine during follow-up. This difference was nonsignificant, however, said Dr. Applebee.

Differentiating Between Migraine Aura and MS Relapse
Migraine aura and MS relapse may have similar symptoms, but several principles can help neurologists distinguish between the two. First, aura tends not to last as long as MS relapse. In general, migraine aura lasts from five to 60 minutes, with the exception of the rare hemiplegic migraine variant. In MS relapse, on the other hand, new or worsening previous symptoms usually occur for 24 hours. “When I’m doing a history on a new patient, I’m trying to determine whether the symptom is always there, or whether it comes and goes, to help determine whether it could be a relapse or an aura,” Dr. Applebee explained.

Second, the symptoms of migraine aura tend to be consistent, but those of MS relapse tend to vary. A stress such as an infection, however, can cause an MS relapse characterized by a recurrence of old symptoms.

Also, each occurrence of migraine usually is related to the same areas of the brain. In contrast, each MS relapse, by definition, affects a different area of the brain than the previous MS relapse had affected. “If the optic nerve is first involved [in a relapse], another area of the brain should be next involved,” said Dr. Applebee. “Different areas of the brain don’t have to be involved in migraine,” she added.

Between 20% and 30% of auras entail visual and sensory disturbance. If an MS relapse entails a visual disturbance, it tends to include the symptoms of optic neuritis, such as pain when moving the eye and cloudy vision. MS relapses also may be associated with nystagmus or diplopia, said Dr. Applebee.

Drugs for MS May Cause Headache
Several drugs used to treat MS may cause headache. Natalizumab, a once-per-month infusion, can cause a postinfusion headache that lasts 24 hours before resolving itself completely. “If you premedicate prior to the infusion, this tends not to be an issue, and I haven’t seen that patients with migraine are more predisposed to having headaches with natalizumab,” advised Dr. Applebee.

Interferon therapies, which are given by subcutaneous or intramuscular injection, sometimes cause flulike symptoms that last from three to six months after the start of therapy. “If you teach patients to premedicate prior to their injections, it can minimize the flulike symptoms,” said Dr. Applebee. “Patients with migraine tend to have more difficulty in controlling their migraines when they first go on interferon therapy.” This difficulty, however, is not a contraindication for using interferon therapies in these patients, she added.

A patient with MS also may experience headache for the first four weeks after starting to take fingolimod, which the FDA approved in 2010. After four weeks, the headache usually resolves itself. Initiating treatment with fingolimod sometimes causes a pounding headache in patients with no previous history of headache. The drug also may make it difficult for patients with migraine to control their headache, but pulse steroids can provide relief, said Dr. Applebee.

Monitoring Fingolimod Use in Patients With Comorbid Cardiac Problems
Because fingolimod acts on the S1P1 receptors, patients may have a decreased heart rate within the first six hours of their first dose of the drug. The drug may lead to first- and second-degree heart block.

“When we dose these patients, we do a baseline ECG in our office, monitor them for six hours with vitals every hour, and then have a second ECG performed prior to exit,” noted Dr. Applebee. Patients with abnormal ECGs should be admitted to the hospital to ensure that they can tolerate the medication, she observed.

“In general, calcium-channel blockers and beta-blockers, if possible, should be avoided for migraine prophylactic therapy in these patients because of the possible interaction with fingolimod,” advised Dr. Applebee.

A recent study found that a beta-blocker in combination with fingolimod decreased heart rate to a statistically significant degree. A calcium-channel blocker did not have this effect, however, when it was administered with fingolimod. If a patient with MS and cardiac problems is taking fingolimod, a neurologist should consult his or her primary care doctor to determine the most appropriate medication for prophylaxis, concluded Dr. Applebee.