Multiple Sclerosis Hub

A higher sodium intake is associated with increased clinical and radiologic disease activity among patients with multiple sclerosis (MS), according to research published online ahead of print August 28 in the Journal of Neurology, Neurosurgery, and Psychiatry.

Mauricio F. Farez, MD, from the Department of Neurology at Raúl Carrea Institute for Neurological Research in Buenos Aires, and colleagues conducted an observational study of 70 patients with relapsing-remitting MS who were followed for two years. The researchers estimated sodium intake from sodium excretion in urine samples and used regression analysis to estimate the effect of sodium intake on MS disease activity. The findings were subsequently replicated in a separate group of 52 patients with MS.

Dr. Farez’s group found a positive correlation between exacerbation rates and sodium intake in a multivariate model after adjusting for age, gender, disease duration, smoking status, vitamin D level, BMI, and treatment. The exacerbation rate was 2.75-fold higher in patients with medium or high sodium intake, compared with the rate in subjects who had a low sodium intake.

In addition, participants with a high sodium intake had a 3.4-fold greater risk of having a new lesion revealed by MRI. This group also had, on average, eight more T2 lesions on MRI than other participants. The investigators observed a similar relationship in the independent replication group.

The authors noted several study limitations, including a small cohort size and the inability to exclude potential confounders such as diet, role of commensal microbiota, stress, and other behavior that may affect food preference and treatment compliance or healthy overall behavior.

“Thus, even though an association between increased sodium intake and increased disease activity was shown, we cannot claim causality and we cannot exclude the possibility of reverse causation: individuals with more relapses received more steroids, and thus their salt intake and excretion is increased because they have higher disease activity, and not the other way around,” stated the researchers. “Another possible caveat relates to changes in salt consumption over time. We tried to overcome this [variation] by retesting the same patients at different time points, finding no significant changes.”

The investigators also noted that although studies have found that dietary salt has a role in regulating blood pressure, the effects of sodium on the risk of MS may involve additional factors. For example, sodium chloride has been shown to have pleiotropic effects on kidney homeostasis and T-cell function, and other evidence suggests a reciprocal relationship between sodium chloride and the immune system.

“Whether high blood pressure interacts with the typical autoimmune mechanisms associated with MS is an interesting question that remains to be answered,” commented Dr. Farez and colleagues. “Nevertheless, our findings suggest that clinical trials with a salt intake reduction as an intervention are needed to establish whether sodium intake control benefits patients with MS.”

—Colby Stong

A higher sodium intake is associated with increased clinical and radiologic disease activity among patients with multiple sclerosis (MS), according to research published online ahead of print August 28 in the Journal of Neurology, Neurosurgery, and Psychiatry.

Mauricio F. Farez, MD, from the Department of Neurology at Raúl Carrea Institute for Neurological Research in Buenos Aires, and colleagues conducted an observational study of 70 patients with relapsing-remitting MS who were followed for two years. The researchers estimated sodium intake from sodium excretion in urine samples and used regression analysis to estimate the effect of sodium intake on MS disease activity. The findings were subsequently replicated in a separate group of 52 patients with MS.

Dr. Farez’s group found a positive correlation between exacerbation rates and sodium intake in a multivariate model after adjusting for age, gender, disease duration, smoking status, vitamin D level, BMI, and treatment. The exacerbation rate was 2.75-fold higher in patients with medium or high sodium intake, compared with the rate in subjects who had a low sodium intake.

In addition, participants with a high sodium intake had a 3.4-fold greater risk of having a new lesion revealed by MRI. This group also had, on average, eight more T2 lesions on MRI than other participants. The investigators observed a similar relationship in the independent replication group.

The authors noted several study limitations, including a small cohort size and the inability to exclude potential confounders such as diet, role of commensal microbiota, stress, and other behavior that may affect food preference and treatment compliance or healthy overall behavior.

“Thus, even though an association between increased sodium intake and increased disease activity was shown, we cannot claim causality and we cannot exclude the possibility of reverse causation: individuals with more relapses received more steroids, and thus their salt intake and excretion is increased because they have higher disease activity, and not the other way around,” stated the researchers. “Another possible caveat relates to changes in salt consumption over time. We tried to overcome this [variation] by retesting the same patients at different time points, finding no significant changes.”

The investigators also noted that although studies have found that dietary salt has a role in regulating blood pressure, the effects of sodium on the risk of MS may involve additional factors. For example, sodium chloride has been shown to have pleiotropic effects on kidney homeostasis and T-cell function, and other evidence suggests a reciprocal relationship between sodium chloride and the immune system.

“Whether high blood pressure interacts with the typical autoimmune mechanisms associated with MS is an interesting question that remains to be answered,” commented Dr. Farez and colleagues. “Nevertheless, our findings suggest that clinical trials with a salt intake reduction as an intervention are needed to establish whether sodium intake control benefits patients with MS.”

—Colby Stong

A higher sodium intake is associated with increased clinical and radiologic disease activity among patients with multiple sclerosis (MS), according to research published online ahead of print August 28 in the Journal of Neurology, Neurosurgery, and Psychiatry.

Mauricio F. Farez, MD, from the Department of Neurology at Raúl Carrea Institute for Neurological Research in Buenos Aires, and colleagues conducted an observational study of 70 patients with relapsing-remitting MS who were followed for two years. The researchers estimated sodium intake from sodium excretion in urine samples and used regression analysis to estimate the effect of sodium intake on MS disease activity. The findings were subsequently replicated in a separate group of 52 patients with MS.

Dr. Farez’s group found a positive correlation between exacerbation rates and sodium intake in a multivariate model after adjusting for age, gender, disease duration, smoking status, vitamin D level, BMI, and treatment. The exacerbation rate was 2.75-fold higher in patients with medium or high sodium intake, compared with the rate in subjects who had a low sodium intake.

In addition, participants with a high sodium intake had a 3.4-fold greater risk of having a new lesion revealed by MRI. This group also had, on average, eight more T2 lesions on MRI than other participants. The investigators observed a similar relationship in the independent replication group.

The authors noted several study limitations, including a small cohort size and the inability to exclude potential confounders such as diet, role of commensal microbiota, stress, and other behavior that may affect food preference and treatment compliance or healthy overall behavior.

“Thus, even though an association between increased sodium intake and increased disease activity was shown, we cannot claim causality and we cannot exclude the possibility of reverse causation: individuals with more relapses received more steroids, and thus their salt intake and excretion is increased because they have higher disease activity, and not the other way around,” stated the researchers. “Another possible caveat relates to changes in salt consumption over time. We tried to overcome this [variation] by retesting the same patients at different time points, finding no significant changes.”

The investigators also noted that although studies have found that dietary salt has a role in regulating blood pressure, the effects of sodium on the risk of MS may involve additional factors. For example, sodium chloride has been shown to have pleiotropic effects on kidney homeostasis and T-cell function, and other evidence suggests a reciprocal relationship between sodium chloride and the immune system.

“Whether high blood pressure interacts with the typical autoimmune mechanisms associated with MS is an interesting question that remains to be answered,” commented Dr. Farez and colleagues. “Nevertheless, our findings suggest that clinical trials with a salt intake reduction as an intervention are needed to establish whether sodium intake control benefits patients with MS.”

—Colby Stong

BOSTON—Age and any exposure to disease-modifying therapy may independently affect the likelihood of conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), according to the results of a large prospective cohort study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.



The findings could have important implications for treatment initiation in patients at higher risk of conversion, said Tim Spelman, of the University of Melbourne in Parkville, Australia. These results suggest the potential utility of developing a risk calculator that considers the values for the predictors identified in this study and helps identify patients who may benefit from closer monitoring and early treatment intervention.



Patients were recruited from 50 clinics in 22 countries, contributing a total of 5,379 patient years of data with more than 30,000 observation points.


Of 3,296 patients with CIS who were enrolled in the MSBase Incident Study (MSBASIS) subset of the MSBase global registry, 1,953 (59%) experienced a second attack, marking the conversion to clinically definite MS. Age was significantly associated with conversion to MS; for every additional five years of age at the time of CIS, the likelihood of relapse was reduced by 10%, said Mr. Spelman.



Relapse risk was also lower in patients with any exposure to disease-modifying therapy, compared with those with no such exposure (hazard ratio, 0.57), and in those with increasing proportion of follow-up time on disease-modifying therapy (hazard ratio, 0.35).

Having at least one T1 gadolinium-enhancing lesion on cerebral MRI was associated with an increased risk of relapse, compared with having no such lesions (hazard ratio, 1.25). In addition, having at least one infratentorial and at least one juxtacortical lesion on cerebral MRI also were associated with an increased risk of relapse, compared with having no such lesions (hazard ratios of 1.23 and 1.21, respectively).



The presence of oligoclonal bands on baseline CSF examination also was associated with an increased risk of relapse (hazard ratio, 1.52). Baseline spinal MRI lesion frequency was co-linear with oligoclonal banding in the CSF, said Mr. Spelman.



—Sharon Worcester

BOSTON—Age and any exposure to disease-modifying therapy may independently affect the likelihood of conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), according to the results of a large prospective cohort study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.



The findings could have important implications for treatment initiation in patients at higher risk of conversion, said Tim Spelman, of the University of Melbourne in Parkville, Australia. These results suggest the potential utility of developing a risk calculator that considers the values for the predictors identified in this study and helps identify patients who may benefit from closer monitoring and early treatment intervention.



Patients were recruited from 50 clinics in 22 countries, contributing a total of 5,379 patient years of data with more than 30,000 observation points.


Of 3,296 patients with CIS who were enrolled in the MSBase Incident Study (MSBASIS) subset of the MSBase global registry, 1,953 (59%) experienced a second attack, marking the conversion to clinically definite MS. Age was significantly associated with conversion to MS; for every additional five years of age at the time of CIS, the likelihood of relapse was reduced by 10%, said Mr. Spelman.



Relapse risk was also lower in patients with any exposure to disease-modifying therapy, compared with those with no such exposure (hazard ratio, 0.57), and in those with increasing proportion of follow-up time on disease-modifying therapy (hazard ratio, 0.35).

Having at least one T1 gadolinium-enhancing lesion on cerebral MRI was associated with an increased risk of relapse, compared with having no such lesions (hazard ratio, 1.25). In addition, having at least one infratentorial and at least one juxtacortical lesion on cerebral MRI also were associated with an increased risk of relapse, compared with having no such lesions (hazard ratios of 1.23 and 1.21, respectively).



The presence of oligoclonal bands on baseline CSF examination also was associated with an increased risk of relapse (hazard ratio, 1.52). Baseline spinal MRI lesion frequency was co-linear with oligoclonal banding in the CSF, said Mr. Spelman.



—Sharon Worcester

BOSTON—Age and any exposure to disease-modifying therapy may independently affect the likelihood of conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (MS), according to the results of a large prospective cohort study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.



The findings could have important implications for treatment initiation in patients at higher risk of conversion, said Tim Spelman, of the University of Melbourne in Parkville, Australia. These results suggest the potential utility of developing a risk calculator that considers the values for the predictors identified in this study and helps identify patients who may benefit from closer monitoring and early treatment intervention.



Patients were recruited from 50 clinics in 22 countries, contributing a total of 5,379 patient years of data with more than 30,000 observation points.


Of 3,296 patients with CIS who were enrolled in the MSBase Incident Study (MSBASIS) subset of the MSBase global registry, 1,953 (59%) experienced a second attack, marking the conversion to clinically definite MS. Age was significantly associated with conversion to MS; for every additional five years of age at the time of CIS, the likelihood of relapse was reduced by 10%, said Mr. Spelman.



Relapse risk was also lower in patients with any exposure to disease-modifying therapy, compared with those with no such exposure (hazard ratio, 0.57), and in those with increasing proportion of follow-up time on disease-modifying therapy (hazard ratio, 0.35).

Having at least one T1 gadolinium-enhancing lesion on cerebral MRI was associated with an increased risk of relapse, compared with having no such lesions (hazard ratio, 1.25). In addition, having at least one infratentorial and at least one juxtacortical lesion on cerebral MRI also were associated with an increased risk of relapse, compared with having no such lesions (hazard ratios of 1.23 and 1.21, respectively).



The presence of oligoclonal bands on baseline CSF examination also was associated with an increased risk of relapse (hazard ratio, 1.52). Baseline spinal MRI lesion frequency was co-linear with oligoclonal banding in the CSF, said Mr. Spelman.



—Sharon Worcester

BOSTON—An electronic version of the Expanded Disability Status Scale (EDSS), the eEDSS, an algorithm-based, tablet-driven tool, is superior to the standard paper version in providing consistent assessments, according to the results of a validation study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.

“By reducing noise, the eEDSS should have a positive impact on the accuracy of individual assessments and statistical power in clinical trials,” said Marcus D’Souza, MD, from the Department of Neurology, University Hospital, Basel, Switzerland, and colleagues.

The EDSS is the most widely used disability rating scale in multiple sclerosis (MS), but has been criticized for its low reliability. To improve reliability, a standardized version of the EDSS (Neurostatus) was established during the last two decades and is used in most major clinical studies, including many of the pivotal trials for regulatory approval of MS drugs.

To further improve EDSS reliability, Dr. D’Souza and colleagues developed the electronic capturing and real-time feedback EDSS (eEDSS), an algorithm-based evaluation performed with a tablet computer (iPad). The eEDSS provides immediate feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. To validate their tool, the researchers compared results obtained with the standardized EDSS paper version (pEDSS) and the eEDSS.

Three certified EDSS raters who received training in the use of the eEDSS examined 100 patients with MS with varying degrees of neurologic deficits. Each patient was assessed twice. The first rater began by using the pEDSS and then switched to the eEDSS after seeing a third of the study population.

In parallel, the second EDSS rater assessed the same patients on the same day using the eEDSS and switched accordingly. pEDSS and eEDSS were compared for the frequency of inconsistencies in the assignment of the functional systems, ambulation score, and EDSS using generalized mixed-effects models and the exact McNemar test. Calculation of functional system scores based on Neurostatus Subscores were then checked by a third EDSS rater who was blinded for type of assessment, EDSS examiner, and patient.

For all examined end points, errors were more likely when using the pEDSS, compared with using the eEDSS. Examiners were three times as likely to make an error of any type when using the pEDSS, compared with using eEDSS (odds ratio, 2.93). Functional systems errors were more likely when pEDSS was used, compared with eEDSS (odds ratio, 2.54).

Errors were much more likely to occur for patients with low EDSS scores (3.5 or lower) than for those with high EDSS scores (3.5 or higher), with an odds ratio of 5.32. Errors in calculation of functional systems after exclusion of the cerebral functional system were much more likely when pEDSS was used, compared with eEDSS (odds ratio, 3.107). Ambulation score errors and EDSS errors were rare, and the differences between the pEDSS and eEDSS in the rates of these errors were not statistically significant.

—Glenn S. Williams

BOSTON—An electronic version of the Expanded Disability Status Scale (EDSS), the eEDSS, an algorithm-based, tablet-driven tool, is superior to the standard paper version in providing consistent assessments, according to the results of a validation study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.

“By reducing noise, the eEDSS should have a positive impact on the accuracy of individual assessments and statistical power in clinical trials,” said Marcus D’Souza, MD, from the Department of Neurology, University Hospital, Basel, Switzerland, and colleagues.

The EDSS is the most widely used disability rating scale in multiple sclerosis (MS), but has been criticized for its low reliability. To improve reliability, a standardized version of the EDSS (Neurostatus) was established during the last two decades and is used in most major clinical studies, including many of the pivotal trials for regulatory approval of MS drugs.

To further improve EDSS reliability, Dr. D’Souza and colleagues developed the electronic capturing and real-time feedback EDSS (eEDSS), an algorithm-based evaluation performed with a tablet computer (iPad). The eEDSS provides immediate feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. To validate their tool, the researchers compared results obtained with the standardized EDSS paper version (pEDSS) and the eEDSS.

Three certified EDSS raters who received training in the use of the eEDSS examined 100 patients with MS with varying degrees of neurologic deficits. Each patient was assessed twice. The first rater began by using the pEDSS and then switched to the eEDSS after seeing a third of the study population.

In parallel, the second EDSS rater assessed the same patients on the same day using the eEDSS and switched accordingly. pEDSS and eEDSS were compared for the frequency of inconsistencies in the assignment of the functional systems, ambulation score, and EDSS using generalized mixed-effects models and the exact McNemar test. Calculation of functional system scores based on Neurostatus Subscores were then checked by a third EDSS rater who was blinded for type of assessment, EDSS examiner, and patient.

For all examined end points, errors were more likely when using the pEDSS, compared with using the eEDSS. Examiners were three times as likely to make an error of any type when using the pEDSS, compared with using eEDSS (odds ratio, 2.93). Functional systems errors were more likely when pEDSS was used, compared with eEDSS (odds ratio, 2.54).

Errors were much more likely to occur for patients with low EDSS scores (3.5 or lower) than for those with high EDSS scores (3.5 or higher), with an odds ratio of 5.32. Errors in calculation of functional systems after exclusion of the cerebral functional system were much more likely when pEDSS was used, compared with eEDSS (odds ratio, 3.107). Ambulation score errors and EDSS errors were rare, and the differences between the pEDSS and eEDSS in the rates of these errors were not statistically significant.

—Glenn S. Williams

BOSTON—An electronic version of the Expanded Disability Status Scale (EDSS), the eEDSS, an algorithm-based, tablet-driven tool, is superior to the standard paper version in providing consistent assessments, according to the results of a validation study presented at the 2014 Joint ACTRIMS–ECTRIMS Meeting.

“By reducing noise, the eEDSS should have a positive impact on the accuracy of individual assessments and statistical power in clinical trials,” said Marcus D’Souza, MD, from the Department of Neurology, University Hospital, Basel, Switzerland, and colleagues.

The EDSS is the most widely used disability rating scale in multiple sclerosis (MS), but has been criticized for its low reliability. To improve reliability, a standardized version of the EDSS (Neurostatus) was established during the last two decades and is used in most major clinical studies, including many of the pivotal trials for regulatory approval of MS drugs.

To further improve EDSS reliability, Dr. D’Souza and colleagues developed the electronic capturing and real-time feedback EDSS (eEDSS), an algorithm-based evaluation performed with a tablet computer (iPad). The eEDSS provides immediate feedback, based on the Neurostatus definitions, indicating inconsistencies in the scoring of parts of the neurologic examination, functional systems, ambulation score, and EDSS. The final decision on the correct scores remains with the physician, who can overrule the algorithm. To validate their tool, the researchers compared results obtained with the standardized EDSS paper version (pEDSS) and the eEDSS.

Three certified EDSS raters who received training in the use of the eEDSS examined 100 patients with MS with varying degrees of neurologic deficits. Each patient was assessed twice. The first rater began by using the pEDSS and then switched to the eEDSS after seeing a third of the study population.

In parallel, the second EDSS rater assessed the same patients on the same day using the eEDSS and switched accordingly. pEDSS and eEDSS were compared for the frequency of inconsistencies in the assignment of the functional systems, ambulation score, and EDSS using generalized mixed-effects models and the exact McNemar test. Calculation of functional system scores based on Neurostatus Subscores were then checked by a third EDSS rater who was blinded for type of assessment, EDSS examiner, and patient.

For all examined end points, errors were more likely when using the pEDSS, compared with using the eEDSS. Examiners were three times as likely to make an error of any type when using the pEDSS, compared with using eEDSS (odds ratio, 2.93). Functional systems errors were more likely when pEDSS was used, compared with eEDSS (odds ratio, 2.54).

Errors were much more likely to occur for patients with low EDSS scores (3.5 or lower) than for those with high EDSS scores (3.5 or higher), with an odds ratio of 5.32. Errors in calculation of functional systems after exclusion of the cerebral functional system were much more likely when pEDSS was used, compared with eEDSS (odds ratio, 3.107). Ambulation score errors and EDSS errors were rare, and the differences between the pEDSS and eEDSS in the rates of these errors were not statistically significant.

—Glenn S. Williams

Baseline MRI measures of lesion volume and brain atrophy predict distinct long-term clinical changes in patients with early multiple sclerosis (MS), according to a small study published online ahead of print July 23 in Multiple Sclerosis and Related Disorders.

The study identified several interesting potential biomarkers that are strongly associated with clinical worsening in early MS, said Amir-Hadi Maghzi, MD, postdoctoral research fellow at the University of California, San Francisco, and his associates.

The study included 43 patients with early MS, of whom 22 completed the three-year assessment. The patients had participated in a randomized, double-blind, placebo-controlled trial at two centers that assessed the possible neuroprotective effects of riluzole in combination with intramuscular interferon beta-1a. T2 lesion volume, as measured on MRI, significantly predicted longitudinal changes in the Paced Auditory Serial Addition Test, the authors reported.

In addition, three baseline measures of atrophy—brain parenchymal volume and normal-appearing white and gray matter volumes—predicted longitudinal changes in the MS Functional Composite score and the Timed 25-Foot Walk. The different findings for lesion and brain volume could reflect distinct disease processes, said the investigators.

Dr. Maghzi and his colleagues calculated longitudinal changes in brain volume by using the Structural Image Evaluation Using Normalization of Atrophy analysis. The researchers counted T2 and contrast-enhancing lesions by visualizing T2 and T1 images simultaneously before and after enhancement. Most MRI measures did not correlate with clinical outcomes at baseline, the researchers noted.

In longitudinal analyses, every 1% decrease in brain volume was associated with a 1.14-point decrease on the Symbol Digit Modalities Test (SDMT). For patients with MS, a four- to five-point decrease in SDMT score is associated with job loss, according to the authors. For every 1% decrease in brain volume, low-contrast letter acuity also declined by an average of nearly 1.5 letters, the investigators said.

—Amy Karon

Baseline MRI measures of lesion volume and brain atrophy predict distinct long-term clinical changes in patients with early multiple sclerosis (MS), according to a small study published online ahead of print July 23 in Multiple Sclerosis and Related Disorders.

The study identified several interesting potential biomarkers that are strongly associated with clinical worsening in early MS, said Amir-Hadi Maghzi, MD, postdoctoral research fellow at the University of California, San Francisco, and his associates.

The study included 43 patients with early MS, of whom 22 completed the three-year assessment. The patients had participated in a randomized, double-blind, placebo-controlled trial at two centers that assessed the possible neuroprotective effects of riluzole in combination with intramuscular interferon beta-1a. T2 lesion volume, as measured on MRI, significantly predicted longitudinal changes in the Paced Auditory Serial Addition Test, the authors reported.

In addition, three baseline measures of atrophy—brain parenchymal volume and normal-appearing white and gray matter volumes—predicted longitudinal changes in the MS Functional Composite score and the Timed 25-Foot Walk. The different findings for lesion and brain volume could reflect distinct disease processes, said the investigators.

Dr. Maghzi and his colleagues calculated longitudinal changes in brain volume by using the Structural Image Evaluation Using Normalization of Atrophy analysis. The researchers counted T2 and contrast-enhancing lesions by visualizing T2 and T1 images simultaneously before and after enhancement. Most MRI measures did not correlate with clinical outcomes at baseline, the researchers noted.

In longitudinal analyses, every 1% decrease in brain volume was associated with a 1.14-point decrease on the Symbol Digit Modalities Test (SDMT). For patients with MS, a four- to five-point decrease in SDMT score is associated with job loss, according to the authors. For every 1% decrease in brain volume, low-contrast letter acuity also declined by an average of nearly 1.5 letters, the investigators said.

—Amy Karon

Baseline MRI measures of lesion volume and brain atrophy predict distinct long-term clinical changes in patients with early multiple sclerosis (MS), according to a small study published online ahead of print July 23 in Multiple Sclerosis and Related Disorders.

The study identified several interesting potential biomarkers that are strongly associated with clinical worsening in early MS, said Amir-Hadi Maghzi, MD, postdoctoral research fellow at the University of California, San Francisco, and his associates.

The study included 43 patients with early MS, of whom 22 completed the three-year assessment. The patients had participated in a randomized, double-blind, placebo-controlled trial at two centers that assessed the possible neuroprotective effects of riluzole in combination with intramuscular interferon beta-1a. T2 lesion volume, as measured on MRI, significantly predicted longitudinal changes in the Paced Auditory Serial Addition Test, the authors reported.

In addition, three baseline measures of atrophy—brain parenchymal volume and normal-appearing white and gray matter volumes—predicted longitudinal changes in the MS Functional Composite score and the Timed 25-Foot Walk. The different findings for lesion and brain volume could reflect distinct disease processes, said the investigators.

Dr. Maghzi and his colleagues calculated longitudinal changes in brain volume by using the Structural Image Evaluation Using Normalization of Atrophy analysis. The researchers counted T2 and contrast-enhancing lesions by visualizing T2 and T1 images simultaneously before and after enhancement. Most MRI measures did not correlate with clinical outcomes at baseline, the researchers noted.

In longitudinal analyses, every 1% decrease in brain volume was associated with a 1.14-point decrease on the Symbol Digit Modalities Test (SDMT). For patients with MS, a four- to five-point decrease in SDMT score is associated with job loss, according to the authors. For every 1% decrease in brain volume, low-contrast letter acuity also declined by an average of nearly 1.5 letters, the investigators said.

—Amy Karon

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—Alemtuzumab may prevent disease activity for as long as three years in patients with active relapsing-remitting multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology.

The drug appears to suppress gadolinium-enhancing activity and new or enlarging T2 lesions efficiently among treatment-naïve patients and patients who have relapsed on previous therapy. In addition, alemtuzumab reduces brain volume loss to a rate similar to that associated with normal aging, said Douglas Arnold, MD, a neurologist at the Montreal Neurological Institute and Hospital.

Dr. Arnold and colleagues presented three-year MRI outcomes from the Comparison of Alemtuzumab and Rebif Efficacy in MS (CARE-MS) I and II trials, which lasted for two years. CARE-MS I included treatment-naïve participants, and CARE-MS II included participants who had relapsed on prior therapy. In both trials, patients with MS were randomized to alemtuzumab or interferon beta-1a. Patients randomized to alemtuzumab received 12 mg at baseline and at one year. In CARE-MS I, alemtuzumab reduced relapse rates, compared with interferon beta-1a. In CARE-MS II, alemtuzumab reduced relapse rates and sustained accumulation of disability, compared with interferon beta-1a.

Alemtuzumab Slowed the Rate of Brain Atrophy
A total of 349 participants in CARE-MS I and 393 participants in CARE-MS II entered the extension trial. At year three, the researchers administered alemtuzumab again to patients with recurrence of disease activity. Approximately 18% of patients in CARE-MS I and 20% of patients in CARE-MS II had recurrence. Fewer than 3% of patients had taken any other therapy at year three.

“At year three, patients maintained approximately 90% suppression of gadolinium-enhancing activity and about 75% suppression of new or enlarging T2 lesion formation,” said Dr. Arnold. Similar proportions of patients had new or active gadolinium-enhancing lesions at year three and at year two (9.6% and 7.1%, respectively). Also, similar proportions of patients had new and enlarging T2 lesions at year three and at year two (27.4% and 23.1%, respectively). Approximately 75% of patients in both trials had no MRI activity.

The rate of change in brain volume slowed progressively from year one to year three. At year three, the rate of change was 0.19% per year in CARE-MS I and 0.1% per year in CARE-MS II.

Positive Outcomes Despite Two-Year Lack of Treatment
“These findings provide strong support for the efficacy of alemtuzumab in treatment-naïve patients and patients who have relapsed on prior therapy,” said Dr. Arnold. “It is important to note that the majority of patients in this three-year follow-up received no treatment for two years, since they received their second course of alemtuzumab at the beginning of year two. Despite being treatment-free for two years, they had these remarkable outcomes on MRI.”

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—After a patient with relapsing-remitting multiple sclerosis (MS) has been on a first-line drug for two years, the factors that most influence neurologists’ decision to consider changing therapies are clinical measures such as relapse rate and Expanded Disability Status Scale (EDSS) score and subclinical measures such as MRI, according to research presented at the 66th Annual Meeting of the American Academy of Neurology. In contrast, quality-of-life measures do not contribute significantly to treatment decisions, the researchers said.

Stephan Schmidt, MD, PhD, a neurologist at Neurologische Gemeinschaftspraxis in Bonn, Germany, and colleagues performed an interim analysis of data from EPIDEM, an ongoing retrospective, noninterventional study that collects cross-sectional data for 5,000 patients at 150 sites in Germany. Eligible patients had received immunomodulatory treatment (ie, interferon beta or glatiramer acetate) continuously during the two years before enrollment. The researchers collected information about demographics, immunomodulatory treatment, EDSS score, MRI, John Cunningham virus (JCV) status, and quality of life (using MSQoL-54).

During the study, the participants’ neurologists were asked whether they were considering a switch to a second-line therapy, and the researchers performed χ² homogeneity analysis to identify factors that influenced this treatment decision. The study did not document whether patients switched to a second-line therapy, however.

Most Patients Had No Relapses or MRI Activity
The interim analysis included 2,500 patients from October 2011 to April 2013. Patients’ mean EDSS score was 2.2 at the beginning of the period and remained stable. Approximately 65% of patients had been relapse-free during the previous 24 months, and about 35% of patients had had at least one relapse.

MRI data were available for two-thirds of the participants. The mean duration between the documentation visit and the last MRI was 9.4 months. Approximately 74% of patients had neither increased T2 lesion load nor new gadolinium-enhancing T1 lesions, compared with the last MRI. About 23% of patients had increased MRI activity, compared with the last MRI.

The STRATIFY-JCV assay to determine JCV antibody status became available in Germany in May 2011. Neurologists determined the JCV antibody status of 6.1% of participants, and 56.9% of reported test results were positive.

Most Patients Reported Good Health
A total of 2,018 patients underwent MSQoL-54, and 74% of patients rated their general state of health as good to excellent. In addition, 21% of participants rated their overall health as fair, and 2% rated their health as poor.

Neurologists described the course of disease as stable in 81% of patients, improved in 3% of patients, and worse in 15% of patients. In contrast, 57% of patients described their course of disease as stable, 17% as improved, and 24% as worse.

Neurologists considered changing the current treatment regimen for 11% of the patients. The availability of JCV-antibody test results, relapse rate, EDSS score, and MRI activity had the strongest influence when considering second-line therapies. Quality-of-life parameters, treatment duration, disease duration, and number of previous disease-modifying therapies had little or no influence on therapeutic considerations.

—Erik Greb

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—Cannabis is used by 8.6% of patients with multiple sclerosis (MS), making it the second most commonly used alternative therapy in this patient population, according to research reported at the 66th Annual Meeting of the American Academy of Neurology.

Patients with MS most frequently used marijuana for such symptoms as fatigue, heat sensitivity, and numbness, tingling, and pain. Massage was the leading alternative therapy used by patients with MS, reported by 12% of this group, said Stanley Cohan, MD, PhD, and his research colleagues.

The researchers sent surveys with questions related to demographics, symptoms of MS, disability status, quality of life, use of MS medications, and alternative therapies to patients with MS (ages 18 and older) who were enrolled in the Pacific Northwest MS Registry. Oregon and Washington are among the 20 states that allow the use of marijuana for medicinal purposes, and Washington is one of two states that have legalized marijuana for recreational use.

The investigators conducted analyses to determine the percentage of responders who reported cannabis use for MS symptoms and compared the data with those of nonusers according to demographic characteristics, score on the MS Impact Scale, responses on the Patient Determined Disease Steps questionnaire, and current symptoms using χ² and t-tests.

A total of 1,701 surveys (70%) were returned by patients in the registry; 8.6% of respondents reported current use of medical marijuana for their MS symptoms. The investigators found that patients who had used marijuana for MS were more likely to be younger, have more progressive disease or greater disability, be male, be unable to work due to MS, and smoke tobacco.

“There were no significant differences between cannabis users and nonusers in the use of MS medications, mean disease duration, or seeing a neurologist for treatment of MS,” stated Dr. Cohan, who is a neurologist and Medical Director of the Providence MS Center in Portland, Oregon.

Other complementary or alternative therapies used for MS included “other” (reported by 7.5% of survey responders), chiropractic (7.1%), acupuncture or acupressure (6.9%), naturopathy (3.8%), and biofeedback (0.6%). Regarding which MS symptoms were targeted by marijuana users, 82.2% used marijuana for fatigue, 76% for heat sensitivity, 74.7% for numbness, tingling, or pain, 68.5% for problems with thinking or memory, 67.1% for stiffness, spasms, or tremors in limbs, 62.3% for difficulty walking or maintaining balance, 58.2% for pain related to MS, 47.9% for impaired coordination, and 47.3% for depression and for problems with urination.

“Participants who used cannabis for their symptom management also reported higher unemployment due to MS, a higher impact of MS on quality of life, and greater disability,” Dr. Cohan commented. “The results highlight the need for in-depth studies on the impact of medical marijuana for management of MS symptoms. Follow-up studies will investigate the patient-reported impact of cannabis on symptom management.”

—Colby Stong

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.