Multiple Sclerosis Hub

Two randomized, double-blind clinical trials of oral laquinimod in relapsing–remitting multiple sclerosis (MS) have been completed. The BRAVO study failed to meet its primary end point, a significant decrease in annualized relapse rate (ARR), until a prespecified readjustment was carried out because of an imbalance in baseline characteristics. The ALLEGRO study, however, satisfied this end point.

Despite the adjustments, the effect of laquinimod on a reduction in ARR was only 21.3%, its effect on decrease in Expanded Disability Status Scale (EDSS) was 33.5%, and its effect on decrease in brain volume loss was 27.5%. No significant decrease in ARR or disability progression was found comparing placebo to interferon b-1a. Comparisons between interferon and laquinimod have not yet been published.

A post hoc analysis of the combined studies yielded results similar to those of the individual studies. Although it is dangerous to do a cross-study comparison, the laquinimod results compared unfavorably to those of other phase 3 trials in effect on ARR reduction, or decrease in Gad+ or new T2 lesions. The major positive findings were the effects of laquinimod in reducing sustained EDSS progression and loss of brain volume. This result raises the possibility that laquinimod may have a mechanism of action other than as an anti-inflammatory agent.

In considering any drug in MS, assessment of progression can be difficult. Progression may occur slowly and may be secondary to clinical or MRI relapses. Even sustained progression is difficult to assess and may reverse itself after study completion.

It is of interest that comparing decrease in three-month EDSS progression in all completed phase III oral trials (ie, of five drugs), a mean clustering of decrease in sustained three-month disease progression was found in a fairly narrow range between 30% and 34%. Measurements of brain-volume loss can also be confounded by the degree and timing of inflammation. If inflammation occurs later in a study, there can be an impression that brain-volume loss is lessened due to an increase in brain volume seen with inflammation (ie, pseudohypertrophy).

Two randomized, double-blind clinical trials of oral laquinimod in relapsing–remitting multiple sclerosis (MS) have been completed. The BRAVO study failed to meet its primary end point, a significant decrease in annualized relapse rate (ARR), until a prespecified readjustment was carried out because of an imbalance in baseline characteristics. The ALLEGRO study, however, satisfied this end point.

Despite the adjustments, the effect of laquinimod on a reduction in ARR was only 21.3%, its effect on decrease in Expanded Disability Status Scale (EDSS) was 33.5%, and its effect on decrease in brain volume loss was 27.5%. No significant decrease in ARR or disability progression was found comparing placebo to interferon b-1a. Comparisons between interferon and laquinimod have not yet been published.

A post hoc analysis of the combined studies yielded results similar to those of the individual studies. Although it is dangerous to do a cross-study comparison, the laquinimod results compared unfavorably to those of other phase 3 trials in effect on ARR reduction, or decrease in Gad+ or new T2 lesions. The major positive findings were the effects of laquinimod in reducing sustained EDSS progression and loss of brain volume. This result raises the possibility that laquinimod may have a mechanism of action other than as an anti-inflammatory agent.

In considering any drug in MS, assessment of progression can be difficult. Progression may occur slowly and may be secondary to clinical or MRI relapses. Even sustained progression is difficult to assess and may reverse itself after study completion.

It is of interest that comparing decrease in three-month EDSS progression in all completed phase III oral trials (ie, of five drugs), a mean clustering of decrease in sustained three-month disease progression was found in a fairly narrow range between 30% and 34%. Measurements of brain-volume loss can also be confounded by the degree and timing of inflammation. If inflammation occurs later in a study, there can be an impression that brain-volume loss is lessened due to an increase in brain volume seen with inflammation (ie, pseudohypertrophy).

Two randomized, double-blind clinical trials of oral laquinimod in relapsing–remitting multiple sclerosis (MS) have been completed. The BRAVO study failed to meet its primary end point, a significant decrease in annualized relapse rate (ARR), until a prespecified readjustment was carried out because of an imbalance in baseline characteristics. The ALLEGRO study, however, satisfied this end point.

Despite the adjustments, the effect of laquinimod on a reduction in ARR was only 21.3%, its effect on decrease in Expanded Disability Status Scale (EDSS) was 33.5%, and its effect on decrease in brain volume loss was 27.5%. No significant decrease in ARR or disability progression was found comparing placebo to interferon b-1a. Comparisons between interferon and laquinimod have not yet been published.

A post hoc analysis of the combined studies yielded results similar to those of the individual studies. Although it is dangerous to do a cross-study comparison, the laquinimod results compared unfavorably to those of other phase 3 trials in effect on ARR reduction, or decrease in Gad+ or new T2 lesions. The major positive findings were the effects of laquinimod in reducing sustained EDSS progression and loss of brain volume. This result raises the possibility that laquinimod may have a mechanism of action other than as an anti-inflammatory agent.

In considering any drug in MS, assessment of progression can be difficult. Progression may occur slowly and may be secondary to clinical or MRI relapses. Even sustained progression is difficult to assess and may reverse itself after study completion.

It is of interest that comparing decrease in three-month EDSS progression in all completed phase III oral trials (ie, of five drugs), a mean clustering of decrease in sustained three-month disease progression was found in a fairly narrow range between 30% and 34%. Measurements of brain-volume loss can also be confounded by the degree and timing of inflammation. If inflammation occurs later in a study, there can be an impression that brain-volume loss is lessened due to an increase in brain volume seen with inflammation (ie, pseudohypertrophy).

NEW ORLEANS—Laquinimod, an oral, CNS-active therapy for multiple sclerosis (MS), significantly slows disability progression and brain atrophy, compared with placebo, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. The drug’s safety profile suggests that “it may have an important role in the long-term management of MS,” said Timothy Vollmer, MD, Professor of Neurology and Director of Clinical Research at the University of Colorado School of Medicine in Aurora.

Laquinimod reduced the probability of three-month sustained disability by 34% with a hazard ratio of 0.658 and a highly significant P value. “From an exploratory standpoint, if you extend this definition to a six-month sustained disability progression, you get an even larger effect of 46%, again with a significant P value and a hazard ratio of 0.54,” said Dr. Vollmer.

After 24 months, laquinimod reduced the rate of cerebral atrophy by 30%, compared with placebo. “This effect was actually visible at month 12 and was already statistically significant,” observed Dr. Vollmer.

“This effect on disability seems somewhat out of proportion to what we would expect, based on the reduction of the inflammatory phase of the disease,” he continued. After 24 months, patients on laquinimod had a 21% lower annualized relapse rate than patients on placebo. At months 12 and 24, the researchers observed a 30% reduction in the number of gadolinium-enhancing lesions and a 24% reduction in new T2 lesions. These three results were highly statistically significant, but their effects were “modest,” said Dr. Vollmer.

Pooled Analyses of Two Trials
Dr. Vollmer and his colleagues performed pooled analyses of data from the Safety and Efficacy of Orally Administered Laquinimod Versus Placebo for Treatment of Relapsing Remitting Multiple Sclerosis (ALLEGRO) and Laquinimod Double Blind Placebo Controlled Study in RRMS Patients With a Rater Blinded Reference Arm of Interferon b-1a (BRAVO) phase III trials to assess the effect of laquinimod on relapse, disability, and brain atrophy in patients with MS. The ALLEGRO trial was a randomized, double-blinded, placebo-controlled study comparing 0.6 mg of laquinimod to placebo in patients with relapsing MS. The BRAVO trial was a randomized study that compared the same dose of laquinimod and placebo, but included an open-label comparator arm that was analyzed using a rater-blinded method. The two trials had similar study designs and shared the same primary outcome, secondary outcome, and exploratory end point.

The two patient data sets included almost 2,000 patients, approximately 50% of whom were randomized to laquinimod. About 21% of patients in the placebo arm ultimately were excluded from analysis, and 19% of patients in the laquinimod arm were excluded from analysis, mostly because of withdrawal of consent or failure to reconsent. Approximately 6.4% of the laquinimod group withdrew because of adverse events (primarily gastrointestinal side effects and abdominal pain), compared with 4.7% of the placebo group. About 80% of patients in both groups completed the protocol.

Trials Show Laquinimod’sPositive Safety Profile
Laquinimod was well tolerated among patients in the ALLEGRO and BRAVO trials. Approximately 9% of laquinimod and placebo patients reported experiencing serious adverse events. Six patients receiving laquinimod experienced appendicitis, the most commonly reported serious adverse event, compared with one patient on placebo. Three patients on laquinimod experienced malignant breast neoplasms, compared with one patient on placebo.

Overall, nearly 82% of patients receiving laquinimod experienced adverse events, compared with 76% of patients receiving placebo. Compared with control patients, those receiving laquinimod experienced higher rates of headache (15.1% vs 18.2%), back pain (8.2% vs 13.6%), arthralgia (6.0% vs 7.2%), increased liver enzymes (2.7% vs 5.9%), urinary tract infection (4.2% vs 5.7%), cough (3.1% vs 5.2%), and abdominal pain (2.6% vs 5.0%).

“Laquinimod’s toxicity-related liver function was very mild—0.7% of patients on laquinimod had elevated liver transaminase, compared with 0.4% of placebo,” Dr. Vollmer noted. “In all cases, they were mild elevations and resolved despite patients staying on therapy,” he added.  

NEW ORLEANS—Laquinimod, an oral, CNS-active therapy for multiple sclerosis (MS), significantly slows disability progression and brain atrophy, compared with placebo, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. The drug’s safety profile suggests that “it may have an important role in the long-term management of MS,” said Timothy Vollmer, MD, Professor of Neurology and Director of Clinical Research at the University of Colorado School of Medicine in Aurora.

Laquinimod reduced the probability of three-month sustained disability by 34% with a hazard ratio of 0.658 and a highly significant P value. “From an exploratory standpoint, if you extend this definition to a six-month sustained disability progression, you get an even larger effect of 46%, again with a significant P value and a hazard ratio of 0.54,” said Dr. Vollmer.

After 24 months, laquinimod reduced the rate of cerebral atrophy by 30%, compared with placebo. “This effect was actually visible at month 12 and was already statistically significant,” observed Dr. Vollmer.

“This effect on disability seems somewhat out of proportion to what we would expect, based on the reduction of the inflammatory phase of the disease,” he continued. After 24 months, patients on laquinimod had a 21% lower annualized relapse rate than patients on placebo. At months 12 and 24, the researchers observed a 30% reduction in the number of gadolinium-enhancing lesions and a 24% reduction in new T2 lesions. These three results were highly statistically significant, but their effects were “modest,” said Dr. Vollmer.

Pooled Analyses of Two Trials
Dr. Vollmer and his colleagues performed pooled analyses of data from the Safety and Efficacy of Orally Administered Laquinimod Versus Placebo for Treatment of Relapsing Remitting Multiple Sclerosis (ALLEGRO) and Laquinimod Double Blind Placebo Controlled Study in RRMS Patients With a Rater Blinded Reference Arm of Interferon b-1a (BRAVO) phase III trials to assess the effect of laquinimod on relapse, disability, and brain atrophy in patients with MS. The ALLEGRO trial was a randomized, double-blinded, placebo-controlled study comparing 0.6 mg of laquinimod to placebo in patients with relapsing MS. The BRAVO trial was a randomized study that compared the same dose of laquinimod and placebo, but included an open-label comparator arm that was analyzed using a rater-blinded method. The two trials had similar study designs and shared the same primary outcome, secondary outcome, and exploratory end point.

The two patient data sets included almost 2,000 patients, approximately 50% of whom were randomized to laquinimod. About 21% of patients in the placebo arm ultimately were excluded from analysis, and 19% of patients in the laquinimod arm were excluded from analysis, mostly because of withdrawal of consent or failure to reconsent. Approximately 6.4% of the laquinimod group withdrew because of adverse events (primarily gastrointestinal side effects and abdominal pain), compared with 4.7% of the placebo group. About 80% of patients in both groups completed the protocol.

Trials Show Laquinimod’sPositive Safety Profile
Laquinimod was well tolerated among patients in the ALLEGRO and BRAVO trials. Approximately 9% of laquinimod and placebo patients reported experiencing serious adverse events. Six patients receiving laquinimod experienced appendicitis, the most commonly reported serious adverse event, compared with one patient on placebo. Three patients on laquinimod experienced malignant breast neoplasms, compared with one patient on placebo.

Overall, nearly 82% of patients receiving laquinimod experienced adverse events, compared with 76% of patients receiving placebo. Compared with control patients, those receiving laquinimod experienced higher rates of headache (15.1% vs 18.2%), back pain (8.2% vs 13.6%), arthralgia (6.0% vs 7.2%), increased liver enzymes (2.7% vs 5.9%), urinary tract infection (4.2% vs 5.7%), cough (3.1% vs 5.2%), and abdominal pain (2.6% vs 5.0%).

“Laquinimod’s toxicity-related liver function was very mild—0.7% of patients on laquinimod had elevated liver transaminase, compared with 0.4% of placebo,” Dr. Vollmer noted. “In all cases, they were mild elevations and resolved despite patients staying on therapy,” he added.  

NEW ORLEANS—Laquinimod, an oral, CNS-active therapy for multiple sclerosis (MS), significantly slows disability progression and brain atrophy, compared with placebo, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. The drug’s safety profile suggests that “it may have an important role in the long-term management of MS,” said Timothy Vollmer, MD, Professor of Neurology and Director of Clinical Research at the University of Colorado School of Medicine in Aurora.

Laquinimod reduced the probability of three-month sustained disability by 34% with a hazard ratio of 0.658 and a highly significant P value. “From an exploratory standpoint, if you extend this definition to a six-month sustained disability progression, you get an even larger effect of 46%, again with a significant P value and a hazard ratio of 0.54,” said Dr. Vollmer.

After 24 months, laquinimod reduced the rate of cerebral atrophy by 30%, compared with placebo. “This effect was actually visible at month 12 and was already statistically significant,” observed Dr. Vollmer.

“This effect on disability seems somewhat out of proportion to what we would expect, based on the reduction of the inflammatory phase of the disease,” he continued. After 24 months, patients on laquinimod had a 21% lower annualized relapse rate than patients on placebo. At months 12 and 24, the researchers observed a 30% reduction in the number of gadolinium-enhancing lesions and a 24% reduction in new T2 lesions. These three results were highly statistically significant, but their effects were “modest,” said Dr. Vollmer.

Pooled Analyses of Two Trials
Dr. Vollmer and his colleagues performed pooled analyses of data from the Safety and Efficacy of Orally Administered Laquinimod Versus Placebo for Treatment of Relapsing Remitting Multiple Sclerosis (ALLEGRO) and Laquinimod Double Blind Placebo Controlled Study in RRMS Patients With a Rater Blinded Reference Arm of Interferon b-1a (BRAVO) phase III trials to assess the effect of laquinimod on relapse, disability, and brain atrophy in patients with MS. The ALLEGRO trial was a randomized, double-blinded, placebo-controlled study comparing 0.6 mg of laquinimod to placebo in patients with relapsing MS. The BRAVO trial was a randomized study that compared the same dose of laquinimod and placebo, but included an open-label comparator arm that was analyzed using a rater-blinded method. The two trials had similar study designs and shared the same primary outcome, secondary outcome, and exploratory end point.

The two patient data sets included almost 2,000 patients, approximately 50% of whom were randomized to laquinimod. About 21% of patients in the placebo arm ultimately were excluded from analysis, and 19% of patients in the laquinimod arm were excluded from analysis, mostly because of withdrawal of consent or failure to reconsent. Approximately 6.4% of the laquinimod group withdrew because of adverse events (primarily gastrointestinal side effects and abdominal pain), compared with 4.7% of the placebo group. About 80% of patients in both groups completed the protocol.

Trials Show Laquinimod’sPositive Safety Profile
Laquinimod was well tolerated among patients in the ALLEGRO and BRAVO trials. Approximately 9% of laquinimod and placebo patients reported experiencing serious adverse events. Six patients receiving laquinimod experienced appendicitis, the most commonly reported serious adverse event, compared with one patient on placebo. Three patients on laquinimod experienced malignant breast neoplasms, compared with one patient on placebo.

Overall, nearly 82% of patients receiving laquinimod experienced adverse events, compared with 76% of patients receiving placebo. Compared with control patients, those receiving laquinimod experienced higher rates of headache (15.1% vs 18.2%), back pain (8.2% vs 13.6%), arthralgia (6.0% vs 7.2%), increased liver enzymes (2.7% vs 5.9%), urinary tract infection (4.2% vs 5.7%), cough (3.1% vs 5.2%), and abdominal pain (2.6% vs 5.0%).

“Laquinimod’s toxicity-related liver function was very mild—0.7% of patients on laquinimod had elevated liver transaminase, compared with 0.4% of placebo,” Dr. Vollmer noted. “In all cases, they were mild elevations and resolved despite patients staying on therapy,” he added.  

To read the accompanying article, please click here.

To read the accompanying article, please click here.

To read the accompanying article, please click here.

NEW ORLEANS—Among treatment-naïve patients with relapsing–remitting multiple sclerosis (MS), alemtuzumab reduced the relapse rate by 55%, compared with interferon beta-1a, said Alasdair Coles, PhD, member of the Department of Clinical Neurosciences at Cambridge University in the United Kingdom, at the 64th Annual Meeting of the American Academy of Neurology. Eight percent of patients receiving alemtuzumab experienced sustained accumulation of disability, compared with 11% of patients receiving Rebif, but this difference was not statistically significant, according to findings from the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) study.

“Perhaps most significantly,” the study provided evidence for alemtuzumab’s superiority “on reducing the rate of tissue loss, as measured by MRI, compared to the active drug Rebif,” said Dr. Coles. Alemtuzumab also had a superior effect on measures of neurologic impairment and on MRI measures of new inflammatory lesions, compared with that of Rebif.

In the two-year phase III trial, Dr. Coles and his colleagues randomized 581 treatment-naïve patients from 98 centers in 16 countries to alemtuzumab or interferon beta-1a to compare the clinical efficacy and safety outcomes of the two drugs. All patients had highly active relapsing–remitting MS but had not yet accumulated disability. Participants’ mean age was 33, and their mean Expanded Disability Status Scale (EDSS) score was 2. EDSS raters were blinded to treatment, and all relapses were adjudicated by an independent end point panel.

The annualized relapse rate was 0.18 for patients receiving alemtuzumab, compared with 0.39 for patients receiving interferon beta-1a. Approximately 78% of patients receiving alemtuzumab were relapse-free, compared with nearly 59% of patients receiving interferon beta-1a.

Alemtuzumab was associated with more adverse events than was interferon beta-1a, including infusion-associated symptoms such as headache, pyrexia, and rash. Premedication and further treatment with antihistamines and antipyretics ameliorated these symptoms.

“As we have come to expect, there was an excess of thyroid autoimmunities following alemtuzumab,” said Dr. Coles. In addition, three cases of idiopathic thrombocytopenic purpura occurred in the alemtuzumab arm, and one case occurred in the interferon beta-1a arm. The study’s risk-minimization program identified all cases, and appropriate treatment restored patients’ platelet counts and prevented sequelae.

NEW ORLEANS—Among treatment-naïve patients with relapsing–remitting multiple sclerosis (MS), alemtuzumab reduced the relapse rate by 55%, compared with interferon beta-1a, said Alasdair Coles, PhD, member of the Department of Clinical Neurosciences at Cambridge University in the United Kingdom, at the 64th Annual Meeting of the American Academy of Neurology. Eight percent of patients receiving alemtuzumab experienced sustained accumulation of disability, compared with 11% of patients receiving Rebif, but this difference was not statistically significant, according to findings from the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) study.

“Perhaps most significantly,” the study provided evidence for alemtuzumab’s superiority “on reducing the rate of tissue loss, as measured by MRI, compared to the active drug Rebif,” said Dr. Coles. Alemtuzumab also had a superior effect on measures of neurologic impairment and on MRI measures of new inflammatory lesions, compared with that of Rebif.

In the two-year phase III trial, Dr. Coles and his colleagues randomized 581 treatment-naïve patients from 98 centers in 16 countries to alemtuzumab or interferon beta-1a to compare the clinical efficacy and safety outcomes of the two drugs. All patients had highly active relapsing–remitting MS but had not yet accumulated disability. Participants’ mean age was 33, and their mean Expanded Disability Status Scale (EDSS) score was 2. EDSS raters were blinded to treatment, and all relapses were adjudicated by an independent end point panel.

The annualized relapse rate was 0.18 for patients receiving alemtuzumab, compared with 0.39 for patients receiving interferon beta-1a. Approximately 78% of patients receiving alemtuzumab were relapse-free, compared with nearly 59% of patients receiving interferon beta-1a.

Alemtuzumab was associated with more adverse events than was interferon beta-1a, including infusion-associated symptoms such as headache, pyrexia, and rash. Premedication and further treatment with antihistamines and antipyretics ameliorated these symptoms.

“As we have come to expect, there was an excess of thyroid autoimmunities following alemtuzumab,” said Dr. Coles. In addition, three cases of idiopathic thrombocytopenic purpura occurred in the alemtuzumab arm, and one case occurred in the interferon beta-1a arm. The study’s risk-minimization program identified all cases, and appropriate treatment restored patients’ platelet counts and prevented sequelae.

NEW ORLEANS—Among treatment-naïve patients with relapsing–remitting multiple sclerosis (MS), alemtuzumab reduced the relapse rate by 55%, compared with interferon beta-1a, said Alasdair Coles, PhD, member of the Department of Clinical Neurosciences at Cambridge University in the United Kingdom, at the 64th Annual Meeting of the American Academy of Neurology. Eight percent of patients receiving alemtuzumab experienced sustained accumulation of disability, compared with 11% of patients receiving Rebif, but this difference was not statistically significant, according to findings from the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) study.

“Perhaps most significantly,” the study provided evidence for alemtuzumab’s superiority “on reducing the rate of tissue loss, as measured by MRI, compared to the active drug Rebif,” said Dr. Coles. Alemtuzumab also had a superior effect on measures of neurologic impairment and on MRI measures of new inflammatory lesions, compared with that of Rebif.

In the two-year phase III trial, Dr. Coles and his colleagues randomized 581 treatment-naïve patients from 98 centers in 16 countries to alemtuzumab or interferon beta-1a to compare the clinical efficacy and safety outcomes of the two drugs. All patients had highly active relapsing–remitting MS but had not yet accumulated disability. Participants’ mean age was 33, and their mean Expanded Disability Status Scale (EDSS) score was 2. EDSS raters were blinded to treatment, and all relapses were adjudicated by an independent end point panel.

The annualized relapse rate was 0.18 for patients receiving alemtuzumab, compared with 0.39 for patients receiving interferon beta-1a. Approximately 78% of patients receiving alemtuzumab were relapse-free, compared with nearly 59% of patients receiving interferon beta-1a.

Alemtuzumab was associated with more adverse events than was interferon beta-1a, including infusion-associated symptoms such as headache, pyrexia, and rash. Premedication and further treatment with antihistamines and antipyretics ameliorated these symptoms.

“As we have come to expect, there was an excess of thyroid autoimmunities following alemtuzumab,” said Dr. Coles. In addition, three cases of idiopathic thrombocytopenic purpura occurred in the alemtuzumab arm, and one case occurred in the interferon beta-1a arm. The study’s risk-minimization program identified all cases, and appropriate treatment restored patients’ platelet counts and prevented sequelae.

NEW ORLEANS—Compared with interferon beta-1a, alemtuzumab reduced the annualized relapse rate by 49% among patients with relapsing–remitting multiple sclerosis (MS) who had relapsed on previous therapy, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. Approximately 65% of patients taking alemtuzumab were relapse-free, compared with 47% of patients taking interferon beta-1a, per results from the phase III Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II (CARE-MS II) study.

In addition, patients with relapsing–remitting MS taking alemtuzumab had a 12.7% risk of sustained accumulation of disability, while patients taking interferon had a 21% risk, said Jeffrey A. Cohen, MD, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center. This reduction represents a hazard ratio of 0.58, or 42% treatment effect, he noted.

During a two-year period, the average Expanded Disability Status Scale (EDSS) score decreased by 0.17 steps among patients taking alemtuzumab, compared with an increase of 0.24 steps among patients taking interferon. The net difference of 0.41 EDSS steps between the two groups after two years was statistically significant, said Dr. Cohen, as were the differences between each group’s scores at baseline and at 12 months.

Patients receiving alemtuzumab also experienced a 29% chance of sustained reduction of disability. Patients receiving interferon, in contrast, experienced a 13% chance of this outcome.

Comparing the Same Drugs in a New Patient Population
The results of the study were consistent with those of a previous phase III trial—Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) (see sidebar). The two-year CARE-MS II trial, conducted by Dr. Cohen and colleagues, compared the effects of alemtuzumab and interferon beta-1a in patients who had relapsed on prior therapy. The study’s two primary efficacy end points were relapse rate and time to six-month sustained accumulation of disability. Additional end points included EDSS change from baseline and sustained reduction of disability, MRI lesion analyses, and normalized whole-brain volume, as measured by brain parenchymal fraction.

Eligible patients ages 18 to 55 were randomized to receive either 12 mg of alemtuzumab for five days at month 0 and for three days at month 12, or 44 µg of subcutaneous interferon beta-1a three times per week. To prevent side effects, the alemtuzumab patients received three days of IV methylprednisolone with each infusion course, and the same therapy was administered annually to the interferon patients. “Because of the distinct mode of administration and side-effect profiles, we felt that blinding of participants and treating clinicians was not feasible,” said Dr. Cohen.

The patients’ average EDSS score was 2.7, and participants had had an average of 1.5 relapses in the previous year. Approximately 80% of patients had previously received interferon therapy, 30% had received glatiramer acetate, and 20% had received both therapies.

Alemtuzumab Reduces the Number of T2 Lesions
Approximately 46% of patients receiving alemtuzumab had new or enlarging T2 lesions over two years, compared with 68% of patients receiving interferon. Although T2 lesion volume decreased in both patient groups, the difference was not statistically significant. Patients taking alemtuzumab experienced 23% less brain volume loss over two years, as measured by brain parenchymal fraction, compared with patients taking interferon beta-1a.

The overall incidence of adverse events was similar in both groups, as was the incidence of serious adverse events. Infections such as nasopharyngitis, sinusitis, and upper respiratory infection were somewhat more common among patients receiving alemtuzumab, as were serious infections such as pneumonia, appendicitis, and herpes zoster.

“This study showed superior efficacy of alemtuzumab, compared with interferon beta-1a, across multiple outcomes,” said Dr. Cohen. “This is now the third study demonstrating superior efficacy of alemtuzumab, and it’s important to note [that] all three of those studies were against an active comparator—subcutaneous interferon beta-1a—which itself is effective against relapses, disability, and MRI. The adverse event profile was consistent with [that of] previous studies, and a comprehensive monitoring program was successful in early detection, facilitating early treatment,” he concluded.

To hear an audiocast related to this news article, please click here.

To read a commentary on this news article, please click here.

NEW ORLEANS—Compared with interferon beta-1a, alemtuzumab reduced the annualized relapse rate by 49% among patients with relapsing–remitting multiple sclerosis (MS) who had relapsed on previous therapy, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. Approximately 65% of patients taking alemtuzumab were relapse-free, compared with 47% of patients taking interferon beta-1a, per results from the phase III Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II (CARE-MS II) study.

In addition, patients with relapsing–remitting MS taking alemtuzumab had a 12.7% risk of sustained accumulation of disability, while patients taking interferon had a 21% risk, said Jeffrey A. Cohen, MD, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center. This reduction represents a hazard ratio of 0.58, or 42% treatment effect, he noted.

During a two-year period, the average Expanded Disability Status Scale (EDSS) score decreased by 0.17 steps among patients taking alemtuzumab, compared with an increase of 0.24 steps among patients taking interferon. The net difference of 0.41 EDSS steps between the two groups after two years was statistically significant, said Dr. Cohen, as were the differences between each group’s scores at baseline and at 12 months.

Patients receiving alemtuzumab also experienced a 29% chance of sustained reduction of disability. Patients receiving interferon, in contrast, experienced a 13% chance of this outcome.

Comparing the Same Drugs in a New Patient Population
The results of the study were consistent with those of a previous phase III trial—Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) (see sidebar). The two-year CARE-MS II trial, conducted by Dr. Cohen and colleagues, compared the effects of alemtuzumab and interferon beta-1a in patients who had relapsed on prior therapy. The study’s two primary efficacy end points were relapse rate and time to six-month sustained accumulation of disability. Additional end points included EDSS change from baseline and sustained reduction of disability, MRI lesion analyses, and normalized whole-brain volume, as measured by brain parenchymal fraction.

Eligible patients ages 18 to 55 were randomized to receive either 12 mg of alemtuzumab for five days at month 0 and for three days at month 12, or 44 µg of subcutaneous interferon beta-1a three times per week. To prevent side effects, the alemtuzumab patients received three days of IV methylprednisolone with each infusion course, and the same therapy was administered annually to the interferon patients. “Because of the distinct mode of administration and side-effect profiles, we felt that blinding of participants and treating clinicians was not feasible,” said Dr. Cohen.

The patients’ average EDSS score was 2.7, and participants had had an average of 1.5 relapses in the previous year. Approximately 80% of patients had previously received interferon therapy, 30% had received glatiramer acetate, and 20% had received both therapies.

Alemtuzumab Reduces the Number of T2 Lesions
Approximately 46% of patients receiving alemtuzumab had new or enlarging T2 lesions over two years, compared with 68% of patients receiving interferon. Although T2 lesion volume decreased in both patient groups, the difference was not statistically significant. Patients taking alemtuzumab experienced 23% less brain volume loss over two years, as measured by brain parenchymal fraction, compared with patients taking interferon beta-1a.

The overall incidence of adverse events was similar in both groups, as was the incidence of serious adverse events. Infections such as nasopharyngitis, sinusitis, and upper respiratory infection were somewhat more common among patients receiving alemtuzumab, as were serious infections such as pneumonia, appendicitis, and herpes zoster.

“This study showed superior efficacy of alemtuzumab, compared with interferon beta-1a, across multiple outcomes,” said Dr. Cohen. “This is now the third study demonstrating superior efficacy of alemtuzumab, and it’s important to note [that] all three of those studies were against an active comparator—subcutaneous interferon beta-1a—which itself is effective against relapses, disability, and MRI. The adverse event profile was consistent with [that of] previous studies, and a comprehensive monitoring program was successful in early detection, facilitating early treatment,” he concluded.

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NEW ORLEANS—Compared with interferon beta-1a, alemtuzumab reduced the annualized relapse rate by 49% among patients with relapsing–remitting multiple sclerosis (MS) who had relapsed on previous therapy, according to research presented at the 64th Annual Meeting of the American Academy of Neurology. Approximately 65% of patients taking alemtuzumab were relapse-free, compared with 47% of patients taking interferon beta-1a, per results from the phase III Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis II (CARE-MS II) study.

In addition, patients with relapsing–remitting MS taking alemtuzumab had a 12.7% risk of sustained accumulation of disability, while patients taking interferon had a 21% risk, said Jeffrey A. Cohen, MD, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center. This reduction represents a hazard ratio of 0.58, or 42% treatment effect, he noted.

During a two-year period, the average Expanded Disability Status Scale (EDSS) score decreased by 0.17 steps among patients taking alemtuzumab, compared with an increase of 0.24 steps among patients taking interferon. The net difference of 0.41 EDSS steps between the two groups after two years was statistically significant, said Dr. Cohen, as were the differences between each group’s scores at baseline and at 12 months.

Patients receiving alemtuzumab also experienced a 29% chance of sustained reduction of disability. Patients receiving interferon, in contrast, experienced a 13% chance of this outcome.

Comparing the Same Drugs in a New Patient Population
The results of the study were consistent with those of a previous phase III trial—Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis I (CARE-MS I) (see sidebar). The two-year CARE-MS II trial, conducted by Dr. Cohen and colleagues, compared the effects of alemtuzumab and interferon beta-1a in patients who had relapsed on prior therapy. The study’s two primary efficacy end points were relapse rate and time to six-month sustained accumulation of disability. Additional end points included EDSS change from baseline and sustained reduction of disability, MRI lesion analyses, and normalized whole-brain volume, as measured by brain parenchymal fraction.

Eligible patients ages 18 to 55 were randomized to receive either 12 mg of alemtuzumab for five days at month 0 and for three days at month 12, or 44 µg of subcutaneous interferon beta-1a three times per week. To prevent side effects, the alemtuzumab patients received three days of IV methylprednisolone with each infusion course, and the same therapy was administered annually to the interferon patients. “Because of the distinct mode of administration and side-effect profiles, we felt that blinding of participants and treating clinicians was not feasible,” said Dr. Cohen.

The patients’ average EDSS score was 2.7, and participants had had an average of 1.5 relapses in the previous year. Approximately 80% of patients had previously received interferon therapy, 30% had received glatiramer acetate, and 20% had received both therapies.

Alemtuzumab Reduces the Number of T2 Lesions
Approximately 46% of patients receiving alemtuzumab had new or enlarging T2 lesions over two years, compared with 68% of patients receiving interferon. Although T2 lesion volume decreased in both patient groups, the difference was not statistically significant. Patients taking alemtuzumab experienced 23% less brain volume loss over two years, as measured by brain parenchymal fraction, compared with patients taking interferon beta-1a.

The overall incidence of adverse events was similar in both groups, as was the incidence of serious adverse events. Infections such as nasopharyngitis, sinusitis, and upper respiratory infection were somewhat more common among patients receiving alemtuzumab, as were serious infections such as pneumonia, appendicitis, and herpes zoster.

“This study showed superior efficacy of alemtuzumab, compared with interferon beta-1a, across multiple outcomes,” said Dr. Cohen. “This is now the third study demonstrating superior efficacy of alemtuzumab, and it’s important to note [that] all three of those studies were against an active comparator—subcutaneous interferon beta-1a—which itself is effective against relapses, disability, and MRI. The adverse event profile was consistent with [that of] previous studies, and a comprehensive monitoring program was successful in early detection, facilitating early treatment,” he concluded.

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Multiple sclerosis (MS) treatments have been available for more than a decade. Several disease-modifying therapies are approved and routinely used with various degrees of effectiveness, tolerability, and compliance. Treatment options have continued to evolve in effectiveness, frequency of administration, and routes of delivery, but more targeted, effective, and safe options are still needed.

The alemtuzumab clinical trial outcome data are exciting. Alemtuzumab represents another effective therapeutic option that will help MS clinicians treat their patients more effectively. This novel agent has demonstrated significant improvement in effectiveness not only for reduced relapse rates and MRI disease activity suppression, but also for reduction of accumulated disability. These impressive and significant gains across multiple outcomes have been accomplished when compared not to placebo, but to one of our mainstays in available treatment. This improved ability to deliver more effective treatment safely and easily, without the worry of ongoing compliance concerns, represents a great advantage in our ongoing fight to limit the damage that this disease causes to our patients, friends, and colleagues.

Multiple sclerosis (MS) treatments have been available for more than a decade. Several disease-modifying therapies are approved and routinely used with various degrees of effectiveness, tolerability, and compliance. Treatment options have continued to evolve in effectiveness, frequency of administration, and routes of delivery, but more targeted, effective, and safe options are still needed.

The alemtuzumab clinical trial outcome data are exciting. Alemtuzumab represents another effective therapeutic option that will help MS clinicians treat their patients more effectively. This novel agent has demonstrated significant improvement in effectiveness not only for reduced relapse rates and MRI disease activity suppression, but also for reduction of accumulated disability. These impressive and significant gains across multiple outcomes have been accomplished when compared not to placebo, but to one of our mainstays in available treatment. This improved ability to deliver more effective treatment safely and easily, without the worry of ongoing compliance concerns, represents a great advantage in our ongoing fight to limit the damage that this disease causes to our patients, friends, and colleagues.

Multiple sclerosis (MS) treatments have been available for more than a decade. Several disease-modifying therapies are approved and routinely used with various degrees of effectiveness, tolerability, and compliance. Treatment options have continued to evolve in effectiveness, frequency of administration, and routes of delivery, but more targeted, effective, and safe options are still needed.

The alemtuzumab clinical trial outcome data are exciting. Alemtuzumab represents another effective therapeutic option that will help MS clinicians treat their patients more effectively. This novel agent has demonstrated significant improvement in effectiveness not only for reduced relapse rates and MRI disease activity suppression, but also for reduction of accumulated disability. These impressive and significant gains across multiple outcomes have been accomplished when compared not to placebo, but to one of our mainstays in available treatment. This improved ability to deliver more effective treatment safely and easily, without the worry of ongoing compliance concerns, represents a great advantage in our ongoing fight to limit the damage that this disease causes to our patients, friends, and colleagues.

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. 

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.