Multiple Sclerosis Hub

PARIS—Clinical efficacy of alemtuzumab was maintained for seven years in patients who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial two courses of alemtuzumab, according to study data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, 44% of patients showed improvement in disability, researchers reported. “These findings suggest that alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multiple sclerosis (RRMS), offering durable efficacy in the absence of continuous treatment,” said Barry Singer, MD, Director of the MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis.

Alemtuzumab Treatment: Then

In the CARE-MS II trial, alemtuzumab significantly improved clinical outcomes compared with subcutaneous interferon beta-1a over two years in patients with active RRMS and an inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over six years in a completed extension study in the absence of continuous treatment. Patients in the CARE-MS II study received two courses of alemtuzumab 12 mg/day (five days of therapy at baseline and three days of therapy 12 months later). In the extension study, patients could receive as-needed alemtuzumab retreatment (12 mg/day on three consecutive days at least 12 months after a previous course for relapse or MRI activity) or other disease-modifying therapy per investigator discretion. Patients completing at least 48 months of the extension could enroll in the five-year TOPAZ study for further long-term evaluation.

Alemtuzumab Treatment: Now

The goal of the TOPAZ study was to evaluate the seven-year efficacy and safety of alemtuzumab in patients with RRMS who received alemtuzumab in the CARE-MS II trial. In TOPAZ, patients could receive alemtuzumab retreatment 12 months or more after a previous course or other disease-modifying therapy at any time point (both per investigator discretion; no criteria). MRI scans were done annually. Annualized relapse rate, six-month confirmed disability worsening, six-month confirmed disability improvement, no evidence of disease activity (NEDA), and adverse events were analyzed in TOPAZ.

In total, 338 of 393 (86%) CARE-MS II patients who entered the extension remained on study until the end of year six and then entered TOPAZ; 317 (94%) remained on study through year seven. Annualized release rate remained low (0.14 at year seven) and the proportion of patients with stable or improved Expanded Disability Status Scale score remained high (73% at year seven). Through year seven, 69% of patients were free from six-month confirmed disability worsening, 44% achieved six-month confirmed disability improvement, and the majority achieved NEDA each year. These effects were achieved with 47% of patients receiving no additional treatment (alemtuzumab or other disease-modifying treatment) after their initial two courses of alemtuzumab. Incidences of overall adverse events, infusion-associated reactions, and infections decreased over time and were reduced, compared with those in the two-year core study. Thyroid adverse events incidence peaked at year three and then declined.

PARIS—Clinical efficacy of alemtuzumab was maintained for seven years in patients who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial two courses of alemtuzumab, according to study data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, 44% of patients showed improvement in disability, researchers reported. “These findings suggest that alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multiple sclerosis (RRMS), offering durable efficacy in the absence of continuous treatment,” said Barry Singer, MD, Director of the MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis.

Alemtuzumab Treatment: Then

In the CARE-MS II trial, alemtuzumab significantly improved clinical outcomes compared with subcutaneous interferon beta-1a over two years in patients with active RRMS and an inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over six years in a completed extension study in the absence of continuous treatment. Patients in the CARE-MS II study received two courses of alemtuzumab 12 mg/day (five days of therapy at baseline and three days of therapy 12 months later). In the extension study, patients could receive as-needed alemtuzumab retreatment (12 mg/day on three consecutive days at least 12 months after a previous course for relapse or MRI activity) or other disease-modifying therapy per investigator discretion. Patients completing at least 48 months of the extension could enroll in the five-year TOPAZ study for further long-term evaluation.

Alemtuzumab Treatment: Now

The goal of the TOPAZ study was to evaluate the seven-year efficacy and safety of alemtuzumab in patients with RRMS who received alemtuzumab in the CARE-MS II trial. In TOPAZ, patients could receive alemtuzumab retreatment 12 months or more after a previous course or other disease-modifying therapy at any time point (both per investigator discretion; no criteria). MRI scans were done annually. Annualized relapse rate, six-month confirmed disability worsening, six-month confirmed disability improvement, no evidence of disease activity (NEDA), and adverse events were analyzed in TOPAZ.

In total, 338 of 393 (86%) CARE-MS II patients who entered the extension remained on study until the end of year six and then entered TOPAZ; 317 (94%) remained on study through year seven. Annualized release rate remained low (0.14 at year seven) and the proportion of patients with stable or improved Expanded Disability Status Scale score remained high (73% at year seven). Through year seven, 69% of patients were free from six-month confirmed disability worsening, 44% achieved six-month confirmed disability improvement, and the majority achieved NEDA each year. These effects were achieved with 47% of patients receiving no additional treatment (alemtuzumab or other disease-modifying treatment) after their initial two courses of alemtuzumab. Incidences of overall adverse events, infusion-associated reactions, and infections decreased over time and were reduced, compared with those in the two-year core study. Thyroid adverse events incidence peaked at year three and then declined.

PARIS—Clinical efficacy of alemtuzumab was maintained for seven years in patients who had inadequate response to prior therapy, despite 47% receiving no additional treatment since the initial two courses of alemtuzumab, according to study data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. In addition, 44% of patients showed improvement in disability, researchers reported. “These findings suggest that alemtuzumab may provide a unique treatment approach for patients with relapsing-remitting multiple sclerosis (RRMS), offering durable efficacy in the absence of continuous treatment,” said Barry Singer, MD, Director of the MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis.

Alemtuzumab Treatment: Then

In the CARE-MS II trial, alemtuzumab significantly improved clinical outcomes compared with subcutaneous interferon beta-1a over two years in patients with active RRMS and an inadequate response to prior therapy. Durable efficacy of alemtuzumab was demonstrated over six years in a completed extension study in the absence of continuous treatment. Patients in the CARE-MS II study received two courses of alemtuzumab 12 mg/day (five days of therapy at baseline and three days of therapy 12 months later). In the extension study, patients could receive as-needed alemtuzumab retreatment (12 mg/day on three consecutive days at least 12 months after a previous course for relapse or MRI activity) or other disease-modifying therapy per investigator discretion. Patients completing at least 48 months of the extension could enroll in the five-year TOPAZ study for further long-term evaluation.

Alemtuzumab Treatment: Now

The goal of the TOPAZ study was to evaluate the seven-year efficacy and safety of alemtuzumab in patients with RRMS who received alemtuzumab in the CARE-MS II trial. In TOPAZ, patients could receive alemtuzumab retreatment 12 months or more after a previous course or other disease-modifying therapy at any time point (both per investigator discretion; no criteria). MRI scans were done annually. Annualized relapse rate, six-month confirmed disability worsening, six-month confirmed disability improvement, no evidence of disease activity (NEDA), and adverse events were analyzed in TOPAZ.

In total, 338 of 393 (86%) CARE-MS II patients who entered the extension remained on study until the end of year six and then entered TOPAZ; 317 (94%) remained on study through year seven. Annualized release rate remained low (0.14 at year seven) and the proportion of patients with stable or improved Expanded Disability Status Scale score remained high (73% at year seven). Through year seven, 69% of patients were free from six-month confirmed disability worsening, 44% achieved six-month confirmed disability improvement, and the majority achieved NEDA each year. These effects were achieved with 47% of patients receiving no additional treatment (alemtuzumab or other disease-modifying treatment) after their initial two courses of alemtuzumab. Incidences of overall adverse events, infusion-associated reactions, and infections decreased over time and were reduced, compared with those in the two-year core study. Thyroid adverse events incidence peaked at year three and then declined.

New data confirm cladribine’s efficacy as a treatment for relapsing-remitting multiple sclerosis (MS), according to results published online ahead of print August 1 in Multiple Sclerosis Journal. The drug’s effect on relapses is comparable to that of fingolimod, and its effect on disability accumulation is comparable to those of interferon β and fingolimod. Compared with interferon, fingolimod, and natalizumab, cladribine may be associated with superior recovery from disability.

A phase III trial demonstrated that, compared with placebo, cladribine reduced relapse rate and increased the likelihood of remaining free from three-month confirmed disability progression in patients with relapsing-remitting MS. The European Medicines Agency approved the therapy in August 2017. Cladribine’s potential position in the treatment landscape is unclear, however, because no direct comparisons of cladribine with other MS therapies are available.

An Analysis of Matched Cohorts

Tomas Kalincik, MD, PhD, Professor of Medicine at Royal Melbourne Hospital in Australia, and colleagues conducted a propensity score–matched analysis of observational data from MSBase, including patients from the Australian Cladribine Product Familiarization Program, to compare the effectiveness of cladribine to that of interferon β, fingolimod, and natalizumab. Eligible participants had relapsing-remitting MS, received one of the study medications as monotherapy for one or more years, and had no prior exposure to alemtuzumab, mitoxantrone, rituximab, or hematopoietic stem cell transplantation.

Patients received 3.5 mg/kg of oral cladribine, 44 μg of subcutaneous interferon β-1a three times weekly, 0.5 mg/day of oral fingolimod, or 300 μg of IV natalizumab every four weeks. Data were recorded during routine clinical practice. The primary end points were the proportion of patients free from relapses, disability accumulation, and disability improvement while on study therapy.

Cladribine Was Associated With Superior Disability Improvement

The researchers included 37 patients treated with cladribine, 1,940 patients treated with interferon β, 1,892 patients treated with fingolimod, and 1,410 patients treated with natalizumab in their analysis. The investigators noted only small differences in baseline characteristics between the matched cohorts.

Compared with participants receiving interferon β, patients receiving cladribine were less likely to have a relapse during the first year of treatment (hazard ratio [HR], 0.6). The proportion of relapse-free patients was 86% in the cladribine group and 70% in the interferon β group. The probability of disability accumulation was similar for these drugs (HR, 0.41), but the cladribine group was more likely to have disability improvement (HR, 15).

The proportion of relapse-free patients at one year was 79% in the cladribine and fingolimod groups, and cumulative hazards of a relapse did not differ between the two groups (HR, 1.2). The probability of disability accumulation was similar for cladribine and fingolimod (HR, 1.8), but the probability of disability improvement was greater for cladribine (HR, 3.9).

The probability of relapse was higher with cladribine than with natalizumab (HR, 1.8), but the proportions of relapse-free patients at the end of year one were 80% and 81%, respectively. The probability of disability accumulation was greater in the cladribine group than in the natalizumab group (HR, 2.5). The probability of disability improvement was greater among patients receiving cladribine than among those receiving natalizumab (HR, 4). Sensitivity analyses largely confirmed the results of the primary analyses.

“Six-month confirmed improvement of disability was observed in 10%–20% of the cladribine cohort during the first year, which was superior to all three comparator therapies. This [finding] is of interest in the context of the comparison to natalizumab, which is known to be associated with a marked improvement in disability early after its commencement,” said Dr. Kalincik and colleagues. “Improvement in disability in a cohort with this profile is unexpected.”

The study’s main limitation is the small size of the cladribine cohort, said the authors. Another limitation is the brief duration of follow-up for the cladribine group, which precludes conclusions about long-term outcomes. Nevertheless, the comparative effectiveness results “represent timely information about the role of cladribine in the management of MS,” Dr. Kalincik concluded.

—Erik Greb

Suggested Reading

Kalincik T, Jokubaitis V, Spelman T, et al. Cladribine versus fingolimod, natalizumab and interferon β for multiple sclerosis. Mult Scler. 2017 Aug 1 [Epub ahead of print].

New data confirm cladribine’s efficacy as a treatment for relapsing-remitting multiple sclerosis (MS), according to results published online ahead of print August 1 in Multiple Sclerosis Journal. The drug’s effect on relapses is comparable to that of fingolimod, and its effect on disability accumulation is comparable to those of interferon β and fingolimod. Compared with interferon, fingolimod, and natalizumab, cladribine may be associated with superior recovery from disability.

A phase III trial demonstrated that, compared with placebo, cladribine reduced relapse rate and increased the likelihood of remaining free from three-month confirmed disability progression in patients with relapsing-remitting MS. The European Medicines Agency approved the therapy in August 2017. Cladribine’s potential position in the treatment landscape is unclear, however, because no direct comparisons of cladribine with other MS therapies are available.

An Analysis of Matched Cohorts

Tomas Kalincik, MD, PhD, Professor of Medicine at Royal Melbourne Hospital in Australia, and colleagues conducted a propensity score–matched analysis of observational data from MSBase, including patients from the Australian Cladribine Product Familiarization Program, to compare the effectiveness of cladribine to that of interferon β, fingolimod, and natalizumab. Eligible participants had relapsing-remitting MS, received one of the study medications as monotherapy for one or more years, and had no prior exposure to alemtuzumab, mitoxantrone, rituximab, or hematopoietic stem cell transplantation.

Patients received 3.5 mg/kg of oral cladribine, 44 μg of subcutaneous interferon β-1a three times weekly, 0.5 mg/day of oral fingolimod, or 300 μg of IV natalizumab every four weeks. Data were recorded during routine clinical practice. The primary end points were the proportion of patients free from relapses, disability accumulation, and disability improvement while on study therapy.

Cladribine Was Associated With Superior Disability Improvement

The researchers included 37 patients treated with cladribine, 1,940 patients treated with interferon β, 1,892 patients treated with fingolimod, and 1,410 patients treated with natalizumab in their analysis. The investigators noted only small differences in baseline characteristics between the matched cohorts.

Compared with participants receiving interferon β, patients receiving cladribine were less likely to have a relapse during the first year of treatment (hazard ratio [HR], 0.6). The proportion of relapse-free patients was 86% in the cladribine group and 70% in the interferon β group. The probability of disability accumulation was similar for these drugs (HR, 0.41), but the cladribine group was more likely to have disability improvement (HR, 15).

The proportion of relapse-free patients at one year was 79% in the cladribine and fingolimod groups, and cumulative hazards of a relapse did not differ between the two groups (HR, 1.2). The probability of disability accumulation was similar for cladribine and fingolimod (HR, 1.8), but the probability of disability improvement was greater for cladribine (HR, 3.9).

The probability of relapse was higher with cladribine than with natalizumab (HR, 1.8), but the proportions of relapse-free patients at the end of year one were 80% and 81%, respectively. The probability of disability accumulation was greater in the cladribine group than in the natalizumab group (HR, 2.5). The probability of disability improvement was greater among patients receiving cladribine than among those receiving natalizumab (HR, 4). Sensitivity analyses largely confirmed the results of the primary analyses.

“Six-month confirmed improvement of disability was observed in 10%–20% of the cladribine cohort during the first year, which was superior to all three comparator therapies. This [finding] is of interest in the context of the comparison to natalizumab, which is known to be associated with a marked improvement in disability early after its commencement,” said Dr. Kalincik and colleagues. “Improvement in disability in a cohort with this profile is unexpected.”

The study’s main limitation is the small size of the cladribine cohort, said the authors. Another limitation is the brief duration of follow-up for the cladribine group, which precludes conclusions about long-term outcomes. Nevertheless, the comparative effectiveness results “represent timely information about the role of cladribine in the management of MS,” Dr. Kalincik concluded.

—Erik Greb

Suggested Reading

Kalincik T, Jokubaitis V, Spelman T, et al. Cladribine versus fingolimod, natalizumab and interferon β for multiple sclerosis. Mult Scler. 2017 Aug 1 [Epub ahead of print].

New data confirm cladribine’s efficacy as a treatment for relapsing-remitting multiple sclerosis (MS), according to results published online ahead of print August 1 in Multiple Sclerosis Journal. The drug’s effect on relapses is comparable to that of fingolimod, and its effect on disability accumulation is comparable to those of interferon β and fingolimod. Compared with interferon, fingolimod, and natalizumab, cladribine may be associated with superior recovery from disability.

A phase III trial demonstrated that, compared with placebo, cladribine reduced relapse rate and increased the likelihood of remaining free from three-month confirmed disability progression in patients with relapsing-remitting MS. The European Medicines Agency approved the therapy in August 2017. Cladribine’s potential position in the treatment landscape is unclear, however, because no direct comparisons of cladribine with other MS therapies are available.

An Analysis of Matched Cohorts

Tomas Kalincik, MD, PhD, Professor of Medicine at Royal Melbourne Hospital in Australia, and colleagues conducted a propensity score–matched analysis of observational data from MSBase, including patients from the Australian Cladribine Product Familiarization Program, to compare the effectiveness of cladribine to that of interferon β, fingolimod, and natalizumab. Eligible participants had relapsing-remitting MS, received one of the study medications as monotherapy for one or more years, and had no prior exposure to alemtuzumab, mitoxantrone, rituximab, or hematopoietic stem cell transplantation.

Patients received 3.5 mg/kg of oral cladribine, 44 μg of subcutaneous interferon β-1a three times weekly, 0.5 mg/day of oral fingolimod, or 300 μg of IV natalizumab every four weeks. Data were recorded during routine clinical practice. The primary end points were the proportion of patients free from relapses, disability accumulation, and disability improvement while on study therapy.

Cladribine Was Associated With Superior Disability Improvement

The researchers included 37 patients treated with cladribine, 1,940 patients treated with interferon β, 1,892 patients treated with fingolimod, and 1,410 patients treated with natalizumab in their analysis. The investigators noted only small differences in baseline characteristics between the matched cohorts.

Compared with participants receiving interferon β, patients receiving cladribine were less likely to have a relapse during the first year of treatment (hazard ratio [HR], 0.6). The proportion of relapse-free patients was 86% in the cladribine group and 70% in the interferon β group. The probability of disability accumulation was similar for these drugs (HR, 0.41), but the cladribine group was more likely to have disability improvement (HR, 15).

The proportion of relapse-free patients at one year was 79% in the cladribine and fingolimod groups, and cumulative hazards of a relapse did not differ between the two groups (HR, 1.2). The probability of disability accumulation was similar for cladribine and fingolimod (HR, 1.8), but the probability of disability improvement was greater for cladribine (HR, 3.9).

The probability of relapse was higher with cladribine than with natalizumab (HR, 1.8), but the proportions of relapse-free patients at the end of year one were 80% and 81%, respectively. The probability of disability accumulation was greater in the cladribine group than in the natalizumab group (HR, 2.5). The probability of disability improvement was greater among patients receiving cladribine than among those receiving natalizumab (HR, 4). Sensitivity analyses largely confirmed the results of the primary analyses.

“Six-month confirmed improvement of disability was observed in 10%–20% of the cladribine cohort during the first year, which was superior to all three comparator therapies. This [finding] is of interest in the context of the comparison to natalizumab, which is known to be associated with a marked improvement in disability early after its commencement,” said Dr. Kalincik and colleagues. “Improvement in disability in a cohort with this profile is unexpected.”

The study’s main limitation is the small size of the cladribine cohort, said the authors. Another limitation is the brief duration of follow-up for the cladribine group, which precludes conclusions about long-term outcomes. Nevertheless, the comparative effectiveness results “represent timely information about the role of cladribine in the management of MS,” Dr. Kalincik concluded.

—Erik Greb

Suggested Reading

Kalincik T, Jokubaitis V, Spelman T, et al. Cladribine versus fingolimod, natalizumab and interferon β for multiple sclerosis. Mult Scler. 2017 Aug 1 [Epub ahead of print].

PARIS—The Expanded Timed Get Up and Go (ETGUG) may be a more sensitive predictor of disability in multiple sclerosis (MS) than the Timed 25-Foot Walk (T25FW), according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting.

The 355 study participants were part of the New York State MS Consortium, a 20-year longitudinal registry. The researchers compared the ETGUG, T25FW, and Expanded Disability Status Scale (EDSS) using Spearman’s Rank correlations. They performed receiver operating characteristic (ROC) analyses with 80% specificity to determine the ETGUG and T25FW cutoff score and associated sensitivity predicting an EDSS score of 4.0 or greater.

Of the 355 participants, 121 (34.1%) had an EDSS score of 4.0 or higher. Both ETGUG and T25FW were highly correlated with EDSS. Correlations with EDSS were stronger for ETGUG and T25FW among subjects with an EDSS score of 4.0 or greater than among people with MS with EDSS scores of less than 4.0. At the predetermined specificity, an ETGUG score of 23.5 seconds or more had a 91.7% sensitivity of identifying subjects with an EDSS of 4.0 or greater. Completing the T25FW in 6.4 seconds or more, however, had a lower sensitivity of 82.7%.

“Prospectively captured data are required to determine the sensitivity of the ETGUG to longitudinal change and its usefulness in predicting disability progression and risk of falling, especially in the patients with higher disability,” said the researchers.

PARIS—The Expanded Timed Get Up and Go (ETGUG) may be a more sensitive predictor of disability in multiple sclerosis (MS) than the Timed 25-Foot Walk (T25FW), according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting.

The 355 study participants were part of the New York State MS Consortium, a 20-year longitudinal registry. The researchers compared the ETGUG, T25FW, and Expanded Disability Status Scale (EDSS) using Spearman’s Rank correlations. They performed receiver operating characteristic (ROC) analyses with 80% specificity to determine the ETGUG and T25FW cutoff score and associated sensitivity predicting an EDSS score of 4.0 or greater.

Of the 355 participants, 121 (34.1%) had an EDSS score of 4.0 or higher. Both ETGUG and T25FW were highly correlated with EDSS. Correlations with EDSS were stronger for ETGUG and T25FW among subjects with an EDSS score of 4.0 or greater than among people with MS with EDSS scores of less than 4.0. At the predetermined specificity, an ETGUG score of 23.5 seconds or more had a 91.7% sensitivity of identifying subjects with an EDSS of 4.0 or greater. Completing the T25FW in 6.4 seconds or more, however, had a lower sensitivity of 82.7%.

“Prospectively captured data are required to determine the sensitivity of the ETGUG to longitudinal change and its usefulness in predicting disability progression and risk of falling, especially in the patients with higher disability,” said the researchers.

PARIS—The Expanded Timed Get Up and Go (ETGUG) may be a more sensitive predictor of disability in multiple sclerosis (MS) than the Timed 25-Foot Walk (T25FW), according to research presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting.

The 355 study participants were part of the New York State MS Consortium, a 20-year longitudinal registry. The researchers compared the ETGUG, T25FW, and Expanded Disability Status Scale (EDSS) using Spearman’s Rank correlations. They performed receiver operating characteristic (ROC) analyses with 80% specificity to determine the ETGUG and T25FW cutoff score and associated sensitivity predicting an EDSS score of 4.0 or greater.

Of the 355 participants, 121 (34.1%) had an EDSS score of 4.0 or higher. Both ETGUG and T25FW were highly correlated with EDSS. Correlations with EDSS were stronger for ETGUG and T25FW among subjects with an EDSS score of 4.0 or greater than among people with MS with EDSS scores of less than 4.0. At the predetermined specificity, an ETGUG score of 23.5 seconds or more had a 91.7% sensitivity of identifying subjects with an EDSS of 4.0 or greater. Completing the T25FW in 6.4 seconds or more, however, had a lower sensitivity of 82.7%.

“Prospectively captured data are required to determine the sensitivity of the ETGUG to longitudinal change and its usefulness in predicting disability progression and risk of falling, especially in the patients with higher disability,” said the researchers.

PARIS—Among patients with neuromyelitis optica (NMO), early disability predicts late disability, consistent with favorable effects of early treatment on disability, according to a literature review presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Additionally, outcomes are worse in nonwhite patients and Hispanic patients. Visual outcomes are worse in young-onset NMO, and motor outcomes are worse in late-onset NMO.

Noting that there is limited literature regarding long-term outcomes in NMO spectrum disorder (NMOSD) since the discovery of aquaporin-4 immunoglobulin G (AQP4–IgG), Zahra Nasr, a medical student at Isfahan University of Medical Sciences in Isfahan, Iran, and colleagues sought to perform a systematic literature review on long-term outcomes in NMOSD in the era of AQP4-IgG.

The researchers conducted a database search that included studies in Cochrane Collaboration Database, PubMed, SCOPUS, Web of Knowledge, and Embase through April 2017. They used the search terms “neuromyelitis optica” or “Devic’s disease,” and “clinical features,” “outcome,” “natural history,” “prognosis,” “mortality,” “morbidity,” “incidence,” “prevalence,” “epidemiology,” and “demography.” They included in their analysis English language studies that used 1999, 2006, or 2015 Wingerchuk criteria and reported AQP4-IgG status.

Twenty percent to 30% of patients had residual motor and visual disability after the initial attack; early disability was positively associated with long-term disability. After five to six years, 11% to 18% of individuals had visual acuity of 20/200 or less in at least one eye, and 7% to 23% were wheelchair confined.

Nonwhite patients and Hispanic patients had higher relapse rates and worse outcomes. Younger patients and men had worse visual outcomes, whereas older patients had poor motor outcomes. In addition, long-term immunosuppressive treatment reduced attack-related disability. AQP4-IgG serostatus was not associated with outcome.

Survival improved in contemporary studies (91% to 98% survival after five years), compared with survival reported prior to the discovery of AQP4-IgG (68% to 75% survival). A higher attack frequency during the first two years, older age at onset, lack of recovery from first attack, blindness, and history of other autoimmune disease were associated with higher mortality rates, but race, gender, and type of attack at onset were not.

The researchers concluded that contemporary studies report more favorable outcomes than pre-AQP4-IgG series.

PARIS—Among patients with neuromyelitis optica (NMO), early disability predicts late disability, consistent with favorable effects of early treatment on disability, according to a literature review presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Additionally, outcomes are worse in nonwhite patients and Hispanic patients. Visual outcomes are worse in young-onset NMO, and motor outcomes are worse in late-onset NMO.

Noting that there is limited literature regarding long-term outcomes in NMO spectrum disorder (NMOSD) since the discovery of aquaporin-4 immunoglobulin G (AQP4–IgG), Zahra Nasr, a medical student at Isfahan University of Medical Sciences in Isfahan, Iran, and colleagues sought to perform a systematic literature review on long-term outcomes in NMOSD in the era of AQP4-IgG.

The researchers conducted a database search that included studies in Cochrane Collaboration Database, PubMed, SCOPUS, Web of Knowledge, and Embase through April 2017. They used the search terms “neuromyelitis optica” or “Devic’s disease,” and “clinical features,” “outcome,” “natural history,” “prognosis,” “mortality,” “morbidity,” “incidence,” “prevalence,” “epidemiology,” and “demography.” They included in their analysis English language studies that used 1999, 2006, or 2015 Wingerchuk criteria and reported AQP4-IgG status.

Twenty percent to 30% of patients had residual motor and visual disability after the initial attack; early disability was positively associated with long-term disability. After five to six years, 11% to 18% of individuals had visual acuity of 20/200 or less in at least one eye, and 7% to 23% were wheelchair confined.

Nonwhite patients and Hispanic patients had higher relapse rates and worse outcomes. Younger patients and men had worse visual outcomes, whereas older patients had poor motor outcomes. In addition, long-term immunosuppressive treatment reduced attack-related disability. AQP4-IgG serostatus was not associated with outcome.

Survival improved in contemporary studies (91% to 98% survival after five years), compared with survival reported prior to the discovery of AQP4-IgG (68% to 75% survival). A higher attack frequency during the first two years, older age at onset, lack of recovery from first attack, blindness, and history of other autoimmune disease were associated with higher mortality rates, but race, gender, and type of attack at onset were not.

The researchers concluded that contemporary studies report more favorable outcomes than pre-AQP4-IgG series.

PARIS—Among patients with neuromyelitis optica (NMO), early disability predicts late disability, consistent with favorable effects of early treatment on disability, according to a literature review presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Additionally, outcomes are worse in nonwhite patients and Hispanic patients. Visual outcomes are worse in young-onset NMO, and motor outcomes are worse in late-onset NMO.

Noting that there is limited literature regarding long-term outcomes in NMO spectrum disorder (NMOSD) since the discovery of aquaporin-4 immunoglobulin G (AQP4–IgG), Zahra Nasr, a medical student at Isfahan University of Medical Sciences in Isfahan, Iran, and colleagues sought to perform a systematic literature review on long-term outcomes in NMOSD in the era of AQP4-IgG.

The researchers conducted a database search that included studies in Cochrane Collaboration Database, PubMed, SCOPUS, Web of Knowledge, and Embase through April 2017. They used the search terms “neuromyelitis optica” or “Devic’s disease,” and “clinical features,” “outcome,” “natural history,” “prognosis,” “mortality,” “morbidity,” “incidence,” “prevalence,” “epidemiology,” and “demography.” They included in their analysis English language studies that used 1999, 2006, or 2015 Wingerchuk criteria and reported AQP4-IgG status.

Twenty percent to 30% of patients had residual motor and visual disability after the initial attack; early disability was positively associated with long-term disability. After five to six years, 11% to 18% of individuals had visual acuity of 20/200 or less in at least one eye, and 7% to 23% were wheelchair confined.

Nonwhite patients and Hispanic patients had higher relapse rates and worse outcomes. Younger patients and men had worse visual outcomes, whereas older patients had poor motor outcomes. In addition, long-term immunosuppressive treatment reduced attack-related disability. AQP4-IgG serostatus was not associated with outcome.

Survival improved in contemporary studies (91% to 98% survival after five years), compared with survival reported prior to the discovery of AQP4-IgG (68% to 75% survival). A higher attack frequency during the first two years, older age at onset, lack of recovery from first attack, blindness, and history of other autoimmune disease were associated with higher mortality rates, but race, gender, and type of attack at onset were not.

The researchers concluded that contemporary studies report more favorable outcomes than pre-AQP4-IgG series.

PARIS—Benign multiple sclerosis (MS) appears to be rare. Its estimated prevalence is less than 4%, according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting.

The existence of benign MS has been proposed, but it remains controversial. Neurologists are uncertain about the frequency and pathologic explanation for a favorable outcome in MS. Identifying and studying individuals with benign MS would have “considerable implications for patient management and for our understanding of the biology of the disease,” said Emma Tallantyre, BMBS, PhD, Clinical Senior Lecturer in the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University in the United Kingdom, and colleagues.

Most definitions of benign MS are focused on walking ability after 10 or 15 years, despite the far wider effects of MS on ability. Dr. Tallantyre and colleagues screened a prevalent population of more than 2,000 people with MS and found 275 individuals who had unlimited walking ability after 15 or more years from onset. The investigators undertook detailed assessments of 56 of the individuals within this group (ie, those recorded to have unlimited walking ability after the longest disease durations). Assessment incorporated scores of cognition, fatigue, mood, vision, bladder symptoms, and arm and leg function.

All patients were considered to have relapsing-remitting MS, but they showed a wide range of relapse frequency and severity. In a group of 32 patients who fulfilled a contemporary definition of benign MS based on the Expanded Disability Status Scale, the researchers considered less than 25% to be truly benign, which was defined as having normal function in all domains. Patient-reported scores of MS impact correlated strongly with the outcomes of clinical assessment, but patients’ own perceptions of their condition was more benign than clinicians’ perceptions.

MR imaging was used to explore the biology underlying benign MS using a global approach and a tract-based approach. The study provides early insights into the phenotypic and imaging characteristics of benign MS and could provide information about the biologic mechanisms of a favorable outcome in MS, said Dr. Tallantyre.

PARIS—Benign multiple sclerosis (MS) appears to be rare. Its estimated prevalence is less than 4%, according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting.

The existence of benign MS has been proposed, but it remains controversial. Neurologists are uncertain about the frequency and pathologic explanation for a favorable outcome in MS. Identifying and studying individuals with benign MS would have “considerable implications for patient management and for our understanding of the biology of the disease,” said Emma Tallantyre, BMBS, PhD, Clinical Senior Lecturer in the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University in the United Kingdom, and colleagues.

Most definitions of benign MS are focused on walking ability after 10 or 15 years, despite the far wider effects of MS on ability. Dr. Tallantyre and colleagues screened a prevalent population of more than 2,000 people with MS and found 275 individuals who had unlimited walking ability after 15 or more years from onset. The investigators undertook detailed assessments of 56 of the individuals within this group (ie, those recorded to have unlimited walking ability after the longest disease durations). Assessment incorporated scores of cognition, fatigue, mood, vision, bladder symptoms, and arm and leg function.

All patients were considered to have relapsing-remitting MS, but they showed a wide range of relapse frequency and severity. In a group of 32 patients who fulfilled a contemporary definition of benign MS based on the Expanded Disability Status Scale, the researchers considered less than 25% to be truly benign, which was defined as having normal function in all domains. Patient-reported scores of MS impact correlated strongly with the outcomes of clinical assessment, but patients’ own perceptions of their condition was more benign than clinicians’ perceptions.

MR imaging was used to explore the biology underlying benign MS using a global approach and a tract-based approach. The study provides early insights into the phenotypic and imaging characteristics of benign MS and could provide information about the biologic mechanisms of a favorable outcome in MS, said Dr. Tallantyre.

PARIS—Benign multiple sclerosis (MS) appears to be rare. Its estimated prevalence is less than 4%, according to a study described at the Seventh Joint ECTRIMS–ACTRIMS Meeting.

The existence of benign MS has been proposed, but it remains controversial. Neurologists are uncertain about the frequency and pathologic explanation for a favorable outcome in MS. Identifying and studying individuals with benign MS would have “considerable implications for patient management and for our understanding of the biology of the disease,” said Emma Tallantyre, BMBS, PhD, Clinical Senior Lecturer in the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University in the United Kingdom, and colleagues.

Most definitions of benign MS are focused on walking ability after 10 or 15 years, despite the far wider effects of MS on ability. Dr. Tallantyre and colleagues screened a prevalent population of more than 2,000 people with MS and found 275 individuals who had unlimited walking ability after 15 or more years from onset. The investigators undertook detailed assessments of 56 of the individuals within this group (ie, those recorded to have unlimited walking ability after the longest disease durations). Assessment incorporated scores of cognition, fatigue, mood, vision, bladder symptoms, and arm and leg function.

All patients were considered to have relapsing-remitting MS, but they showed a wide range of relapse frequency and severity. In a group of 32 patients who fulfilled a contemporary definition of benign MS based on the Expanded Disability Status Scale, the researchers considered less than 25% to be truly benign, which was defined as having normal function in all domains. Patient-reported scores of MS impact correlated strongly with the outcomes of clinical assessment, but patients’ own perceptions of their condition was more benign than clinicians’ perceptions.

MR imaging was used to explore the biology underlying benign MS using a global approach and a tract-based approach. The study provides early insights into the phenotypic and imaging characteristics of benign MS and could provide information about the biologic mechanisms of a favorable outcome in MS, said Dr. Tallantyre.

Age at onset, exposure to disease-modifying drugs (DMDs), disability at onset, MRI criteria, and oligoclonal bands affect the likelihood of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS), according to research published in the September issue of Multiple Sclerosis Journal. The study results corroborate and augment previous research into factors that predict clinical conversion, said the authors.

In addition, the researchers developed and validated a nomogram intended to predict individualized risk of relapse after CIS. The nomogram’s estimated probabilities of conversion to MS had high concordance with observed rates of conversion.

An Analysis of Prospective Data

Tim Spelman, MBBS, PhD, Head of Statistics at the Melbourne Brain Center at the Royal Melbourne Hospital, and colleagues examined data for 3,296 patients with CIS who were enrolled in the prospective MSBase Incident Study, a substudy of the MSBase Registry. Participants presented to 50 clinics in 22 countries. At each visit, investigators recorded participants’ Expanded Disability Status Scale (EDSS) score, date of relapse onset, and dates of DMD initiation and discontinuation. The primary outcome was the time to first relapse following CIS. The researchers defined clinically definite MS according to the Poser criteria. Patients were followed up until first relapse after CIS or last recorded clinic visit.

Dr. Spelman and colleagues used Cox proportional hazards regression to examine the correlation between previously identified predictors and time to first relapse after CIS. They used their baseline-adjusted data modeling to create a nomogram to predict conversion to clinically definite MS.

Drug Exposure Reduced Risk

Approximately 43% of participants initiated intramuscular interferon β-1a, 34% initiated subcutaneous interferon β-1a, 18% initiated interferon β-1b, and 14% initiated glatiramer acetate. In all, 1,953 patients (59%) had a relapse during a median follow-up of 1.92 years.

Older age at CIS was associated with a 10% reduction in the risk of clinical conversion. Every one-point increase in baseline EDSS score was associated with 1.16 times the rate of subsequent conversion. Compared with the optic pathway, first symptom location in the brainstem was associated with 1.17 times the rate of second attack, and first symptom location in the supratentorial region was associated with 1.29 times the rate of second attack. Any exposure to DMD during follow-up was associated with a 42% rate reduction in time to first relapse, compared with nonexposure.

CSF-restricted oligoclonal bands were associated with 1.52 times the rate of relapse, compared with the absence of oligoclonal bands. Having at least one T1 gadolinium-enhancing lesion was associated with 1.24 times the rate of relapse. Having three or more periventricular lesions was associated with 1.68 times the rate of relapse, compared with no lesions. Having at least one infratentorial and at least one juxtacortical lesion on brain MRI were associated with 1.21 times and 1.21 times the rate of first post-CIS relapse, respectively, compared with no lesions.

“This multinational, prospective study represents the largest post-CIS cohort reported to date,” said Dr. Spelman. “Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD treatment intervention, [thus] facilitating more favorable patient outcomes.”

—Erik Greb

Suggested Reading

Spelman T, Meyniel C, Rojas JI, et al. Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice. Mult Scler. 2017;23(10):1346-1357.

Age at onset, exposure to disease-modifying drugs (DMDs), disability at onset, MRI criteria, and oligoclonal bands affect the likelihood of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS), according to research published in the September issue of Multiple Sclerosis Journal. The study results corroborate and augment previous research into factors that predict clinical conversion, said the authors.

In addition, the researchers developed and validated a nomogram intended to predict individualized risk of relapse after CIS. The nomogram’s estimated probabilities of conversion to MS had high concordance with observed rates of conversion.

An Analysis of Prospective Data

Tim Spelman, MBBS, PhD, Head of Statistics at the Melbourne Brain Center at the Royal Melbourne Hospital, and colleagues examined data for 3,296 patients with CIS who were enrolled in the prospective MSBase Incident Study, a substudy of the MSBase Registry. Participants presented to 50 clinics in 22 countries. At each visit, investigators recorded participants’ Expanded Disability Status Scale (EDSS) score, date of relapse onset, and dates of DMD initiation and discontinuation. The primary outcome was the time to first relapse following CIS. The researchers defined clinically definite MS according to the Poser criteria. Patients were followed up until first relapse after CIS or last recorded clinic visit.

Dr. Spelman and colleagues used Cox proportional hazards regression to examine the correlation between previously identified predictors and time to first relapse after CIS. They used their baseline-adjusted data modeling to create a nomogram to predict conversion to clinically definite MS.

Drug Exposure Reduced Risk

Approximately 43% of participants initiated intramuscular interferon β-1a, 34% initiated subcutaneous interferon β-1a, 18% initiated interferon β-1b, and 14% initiated glatiramer acetate. In all, 1,953 patients (59%) had a relapse during a median follow-up of 1.92 years.

Older age at CIS was associated with a 10% reduction in the risk of clinical conversion. Every one-point increase in baseline EDSS score was associated with 1.16 times the rate of subsequent conversion. Compared with the optic pathway, first symptom location in the brainstem was associated with 1.17 times the rate of second attack, and first symptom location in the supratentorial region was associated with 1.29 times the rate of second attack. Any exposure to DMD during follow-up was associated with a 42% rate reduction in time to first relapse, compared with nonexposure.

CSF-restricted oligoclonal bands were associated with 1.52 times the rate of relapse, compared with the absence of oligoclonal bands. Having at least one T1 gadolinium-enhancing lesion was associated with 1.24 times the rate of relapse. Having three or more periventricular lesions was associated with 1.68 times the rate of relapse, compared with no lesions. Having at least one infratentorial and at least one juxtacortical lesion on brain MRI were associated with 1.21 times and 1.21 times the rate of first post-CIS relapse, respectively, compared with no lesions.

“This multinational, prospective study represents the largest post-CIS cohort reported to date,” said Dr. Spelman. “Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD treatment intervention, [thus] facilitating more favorable patient outcomes.”

—Erik Greb

Suggested Reading

Spelman T, Meyniel C, Rojas JI, et al. Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice. Mult Scler. 2017;23(10):1346-1357.

Age at onset, exposure to disease-modifying drugs (DMDs), disability at onset, MRI criteria, and oligoclonal bands affect the likelihood of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS), according to research published in the September issue of Multiple Sclerosis Journal. The study results corroborate and augment previous research into factors that predict clinical conversion, said the authors.

In addition, the researchers developed and validated a nomogram intended to predict individualized risk of relapse after CIS. The nomogram’s estimated probabilities of conversion to MS had high concordance with observed rates of conversion.

An Analysis of Prospective Data

Tim Spelman, MBBS, PhD, Head of Statistics at the Melbourne Brain Center at the Royal Melbourne Hospital, and colleagues examined data for 3,296 patients with CIS who were enrolled in the prospective MSBase Incident Study, a substudy of the MSBase Registry. Participants presented to 50 clinics in 22 countries. At each visit, investigators recorded participants’ Expanded Disability Status Scale (EDSS) score, date of relapse onset, and dates of DMD initiation and discontinuation. The primary outcome was the time to first relapse following CIS. The researchers defined clinically definite MS according to the Poser criteria. Patients were followed up until first relapse after CIS or last recorded clinic visit.

Dr. Spelman and colleagues used Cox proportional hazards regression to examine the correlation between previously identified predictors and time to first relapse after CIS. They used their baseline-adjusted data modeling to create a nomogram to predict conversion to clinically definite MS.

Drug Exposure Reduced Risk

Approximately 43% of participants initiated intramuscular interferon β-1a, 34% initiated subcutaneous interferon β-1a, 18% initiated interferon β-1b, and 14% initiated glatiramer acetate. In all, 1,953 patients (59%) had a relapse during a median follow-up of 1.92 years.

Older age at CIS was associated with a 10% reduction in the risk of clinical conversion. Every one-point increase in baseline EDSS score was associated with 1.16 times the rate of subsequent conversion. Compared with the optic pathway, first symptom location in the brainstem was associated with 1.17 times the rate of second attack, and first symptom location in the supratentorial region was associated with 1.29 times the rate of second attack. Any exposure to DMD during follow-up was associated with a 42% rate reduction in time to first relapse, compared with nonexposure.

CSF-restricted oligoclonal bands were associated with 1.52 times the rate of relapse, compared with the absence of oligoclonal bands. Having at least one T1 gadolinium-enhancing lesion was associated with 1.24 times the rate of relapse. Having three or more periventricular lesions was associated with 1.68 times the rate of relapse, compared with no lesions. Having at least one infratentorial and at least one juxtacortical lesion on brain MRI were associated with 1.21 times and 1.21 times the rate of first post-CIS relapse, respectively, compared with no lesions.

“This multinational, prospective study represents the largest post-CIS cohort reported to date,” said Dr. Spelman. “Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD treatment intervention, [thus] facilitating more favorable patient outcomes.”

—Erik Greb

Suggested Reading

Spelman T, Meyniel C, Rojas JI, et al. Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice. Mult Scler. 2017;23(10):1346-1357.

PARIS—Oligoclonal bands, together with symptomatic lesions disseminated in space, increase the risk of multiple sclerosis (MS), according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. MRI dissemination in space (DIS) at any time plus positive oligoclonal bands should be considered as an additional criterion for MS diagnosis, according to the researchers.

Previous research has suggested that the presence of oligoclonal bands in typical clinically isolated syndromes (CIS) increases the risk of a second attack independently of MRI findings. Georgina Arrambide, MD, PhD, a neurologist at Vall d’Hebron University Hospital in Barcelona, and colleagues studied an ongoing CIS cohort to explore whether oligoclonal bands would be a valuable criterion for MS diagnosis in the context of the 2010 McDonald criteria.

An Examination of MRIs

The investigators obtained MRIs at three to five months after CIS diagnosis, at one year, and at every five years. Oligoclonal bands were determined by isoelectric focusing combined with immunoblotting. Dr. Arrambide and colleagues selected 565 patients with oligoclonal band determination and sufficient data on baseline brain MRI to assess 2010 DIS and dissemination in time (DIT) considering the symptomatic lesions. They excluded 167 participants (29.6%) who already fulfilled DIS and DIT criteria and divided the remaining 398 participants into groups with no DIS and no DIT (n = 218), DIS only (n = 164), and DIT only (n = 16).

Next, the researchers performed Cox proportional hazards regression models with 2010 McDonald as the outcome, using no DIS no DIT with no lesions (n = 107) as the reference for no DIS no DIT with one or more lesion, DIS only, and DIT only. To assess performance, Dr. Arrambide’s group selected cases with a follow-up of three or more years or a second attack within three years of the CIS (n = 305). These participants were divided into groups with no DIS and no DIT (n = 165), DIS only (n = 129), and DIT only (n = 11). The investigators classified participants with no DIS and no DIT with one or more lesion (n = 93) and DIS only according to their oligoclonal band status. They assessed sensitivity, specificity, accuracy, positive predictive value, and negative predictive value with 2010 McDonald at three years as the outcome.

Oligoclonal Bands Increased Risk of Conversion to MS

The adjusted hazard ratios of second attack were 2.8 for no DIS and no DIT with one or more lesion and negative oligoclonal bands, 6.4 for no DIS and no DIT with one or more lesion and positive oligoclonal bands, 9.7 for DIS only with negative oligoclonal bands, 14.8 for DIS only with positive oligoclonal bands, and 7.9 for DIT only. Regarding performance, specificity was 77.6 for no DIS no DIT with one or more lesion and negative oligoclonal bands, 89.1 for no DIS no DIT with one or more lesion and positive oligoclonal bands, 92.5 for DIS only and negative oligoclonal bands, 88.1 for DIS only and positive oligoclonal bands, and 97.8 for DIT only. DIS only with positive oligoclonal bands had the highest sensitivity (46.2), accuracy (64.6), and positive predictive value (83.2).

PARIS—Oligoclonal bands, together with symptomatic lesions disseminated in space, increase the risk of multiple sclerosis (MS), according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. MRI dissemination in space (DIS) at any time plus positive oligoclonal bands should be considered as an additional criterion for MS diagnosis, according to the researchers.

Previous research has suggested that the presence of oligoclonal bands in typical clinically isolated syndromes (CIS) increases the risk of a second attack independently of MRI findings. Georgina Arrambide, MD, PhD, a neurologist at Vall d’Hebron University Hospital in Barcelona, and colleagues studied an ongoing CIS cohort to explore whether oligoclonal bands would be a valuable criterion for MS diagnosis in the context of the 2010 McDonald criteria.

An Examination of MRIs

The investigators obtained MRIs at three to five months after CIS diagnosis, at one year, and at every five years. Oligoclonal bands were determined by isoelectric focusing combined with immunoblotting. Dr. Arrambide and colleagues selected 565 patients with oligoclonal band determination and sufficient data on baseline brain MRI to assess 2010 DIS and dissemination in time (DIT) considering the symptomatic lesions. They excluded 167 participants (29.6%) who already fulfilled DIS and DIT criteria and divided the remaining 398 participants into groups with no DIS and no DIT (n = 218), DIS only (n = 164), and DIT only (n = 16).

Next, the researchers performed Cox proportional hazards regression models with 2010 McDonald as the outcome, using no DIS no DIT with no lesions (n = 107) as the reference for no DIS no DIT with one or more lesion, DIS only, and DIT only. To assess performance, Dr. Arrambide’s group selected cases with a follow-up of three or more years or a second attack within three years of the CIS (n = 305). These participants were divided into groups with no DIS and no DIT (n = 165), DIS only (n = 129), and DIT only (n = 11). The investigators classified participants with no DIS and no DIT with one or more lesion (n = 93) and DIS only according to their oligoclonal band status. They assessed sensitivity, specificity, accuracy, positive predictive value, and negative predictive value with 2010 McDonald at three years as the outcome.

Oligoclonal Bands Increased Risk of Conversion to MS

The adjusted hazard ratios of second attack were 2.8 for no DIS and no DIT with one or more lesion and negative oligoclonal bands, 6.4 for no DIS and no DIT with one or more lesion and positive oligoclonal bands, 9.7 for DIS only with negative oligoclonal bands, 14.8 for DIS only with positive oligoclonal bands, and 7.9 for DIT only. Regarding performance, specificity was 77.6 for no DIS no DIT with one or more lesion and negative oligoclonal bands, 89.1 for no DIS no DIT with one or more lesion and positive oligoclonal bands, 92.5 for DIS only and negative oligoclonal bands, 88.1 for DIS only and positive oligoclonal bands, and 97.8 for DIT only. DIS only with positive oligoclonal bands had the highest sensitivity (46.2), accuracy (64.6), and positive predictive value (83.2).

PARIS—Oligoclonal bands, together with symptomatic lesions disseminated in space, increase the risk of multiple sclerosis (MS), according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. MRI dissemination in space (DIS) at any time plus positive oligoclonal bands should be considered as an additional criterion for MS diagnosis, according to the researchers.

Previous research has suggested that the presence of oligoclonal bands in typical clinically isolated syndromes (CIS) increases the risk of a second attack independently of MRI findings. Georgina Arrambide, MD, PhD, a neurologist at Vall d’Hebron University Hospital in Barcelona, and colleagues studied an ongoing CIS cohort to explore whether oligoclonal bands would be a valuable criterion for MS diagnosis in the context of the 2010 McDonald criteria.

An Examination of MRIs

The investigators obtained MRIs at three to five months after CIS diagnosis, at one year, and at every five years. Oligoclonal bands were determined by isoelectric focusing combined with immunoblotting. Dr. Arrambide and colleagues selected 565 patients with oligoclonal band determination and sufficient data on baseline brain MRI to assess 2010 DIS and dissemination in time (DIT) considering the symptomatic lesions. They excluded 167 participants (29.6%) who already fulfilled DIS and DIT criteria and divided the remaining 398 participants into groups with no DIS and no DIT (n = 218), DIS only (n = 164), and DIT only (n = 16).

Next, the researchers performed Cox proportional hazards regression models with 2010 McDonald as the outcome, using no DIS no DIT with no lesions (n = 107) as the reference for no DIS no DIT with one or more lesion, DIS only, and DIT only. To assess performance, Dr. Arrambide’s group selected cases with a follow-up of three or more years or a second attack within three years of the CIS (n = 305). These participants were divided into groups with no DIS and no DIT (n = 165), DIS only (n = 129), and DIT only (n = 11). The investigators classified participants with no DIS and no DIT with one or more lesion (n = 93) and DIS only according to their oligoclonal band status. They assessed sensitivity, specificity, accuracy, positive predictive value, and negative predictive value with 2010 McDonald at three years as the outcome.

Oligoclonal Bands Increased Risk of Conversion to MS

The adjusted hazard ratios of second attack were 2.8 for no DIS and no DIT with one or more lesion and negative oligoclonal bands, 6.4 for no DIS and no DIT with one or more lesion and positive oligoclonal bands, 9.7 for DIS only with negative oligoclonal bands, 14.8 for DIS only with positive oligoclonal bands, and 7.9 for DIT only. Regarding performance, specificity was 77.6 for no DIS no DIT with one or more lesion and negative oligoclonal bands, 89.1 for no DIS no DIT with one or more lesion and positive oligoclonal bands, 92.5 for DIS only and negative oligoclonal bands, 88.1 for DIS only and positive oligoclonal bands, and 97.8 for DIT only. DIS only with positive oligoclonal bands had the highest sensitivity (46.2), accuracy (64.6), and positive predictive value (83.2).

PARIS—Secondary progressive multiple sclerosis (MS) is at least partly a consequence of early inflammation, and the risk of conversion from relapsing-remitting MS to secondary progressive MS is modifiable over five years with existing disease-modifying therapies (DMTs), according to research described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. High-efficacy therapies such as alemtuzumab and natalizumab reduce the risk to a greater extent than do other DMTs.

Current immunotherapies do not slow secondary progressive MS after disease onset. The extent to which secondary progressive MS reflects early inflammation is not certain. Also unclear is whether conversion to secondary progressive MS might be modified by immunomodulatory DMTs during the relapsing-remitting phase.

Using an objective definition of secondary progressive MS published by Lorscheider et al in 2016, J. William L. Brown, MD, of the Queen Square MS Center at University College of London Institute of Neurology, and colleagues examined whether DMTs delay or reduce conversion from relapsing-remitting MS to secondary progressive MS. They examined patients with relapsing-remitting MS who participated in the MSBase database and were treated with a single DMT with at least four years of on-treatment follow-up. In all, 240 patients received injectables (ie, interferons or glatiramer acetate), 109 took fingolimod, 93 received natalizumab, and 44 took alemtuzumab.

Participants were each propensity matched to untreated patients with relapsing-remitting MS from a historical cohort (n = 622; mean follow-up, 9.2 years) and then matched to different DMT groups. Patients were matched on gender, baseline age, annualized-relapse rate, Expanded Disability Status Scale (EDSS) score, and disease duration. The researchers used weighted conditional proportional hazards models adjusted for EDSS frequency with pairwise censoring to compare the proportions of patients in each group who were free from conversion to secondary progressive MS.

Because lower-efficacy drug groups may have been biased towards participants with milder disease through excluding patients with multiple DMTs (such as treatment escalators), the investigators limited the injectables group to patients followed up before higher-efficacy drugs became available in 2006.

All DMTs reduced the hazard of conversion to secondary progressive MS, compared with different groups of matched untreated patients, in a series of pairwise analyses. For injectables, the hazard ratio (HR) of conversion to secondary progressive MS was 0.31 (median censored on-treatment follow-up, 7.9 years). For fingolimod, the HR was 0.23 (follow-up, 4.6 years). Natalizumab was associated with an HR of 0.50 (follow-up, 4.9 years). Alemtuzumab had an HR of 0.60 (follow-up, 7.2 years).

When the investigators matched patients between the treated cohorts, they found no significant difference in rate of conversion to secondary progressive MS between alemtuzumab and natalizumab. Alemtuzumab and natalizumab were therefore combined in a category of high-efficacy therapies (n = 118) and matched and compared with the injectables group (n = 236). High-efficacy therapies conferred greater protection against conversion to secondary progressive MS than injectables did (HR, 0.65; follow-up, 5.7 years).

PARIS—Secondary progressive multiple sclerosis (MS) is at least partly a consequence of early inflammation, and the risk of conversion from relapsing-remitting MS to secondary progressive MS is modifiable over five years with existing disease-modifying therapies (DMTs), according to research described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. High-efficacy therapies such as alemtuzumab and natalizumab reduce the risk to a greater extent than do other DMTs.

Current immunotherapies do not slow secondary progressive MS after disease onset. The extent to which secondary progressive MS reflects early inflammation is not certain. Also unclear is whether conversion to secondary progressive MS might be modified by immunomodulatory DMTs during the relapsing-remitting phase.

Using an objective definition of secondary progressive MS published by Lorscheider et al in 2016, J. William L. Brown, MD, of the Queen Square MS Center at University College of London Institute of Neurology, and colleagues examined whether DMTs delay or reduce conversion from relapsing-remitting MS to secondary progressive MS. They examined patients with relapsing-remitting MS who participated in the MSBase database and were treated with a single DMT with at least four years of on-treatment follow-up. In all, 240 patients received injectables (ie, interferons or glatiramer acetate), 109 took fingolimod, 93 received natalizumab, and 44 took alemtuzumab.

Participants were each propensity matched to untreated patients with relapsing-remitting MS from a historical cohort (n = 622; mean follow-up, 9.2 years) and then matched to different DMT groups. Patients were matched on gender, baseline age, annualized-relapse rate, Expanded Disability Status Scale (EDSS) score, and disease duration. The researchers used weighted conditional proportional hazards models adjusted for EDSS frequency with pairwise censoring to compare the proportions of patients in each group who were free from conversion to secondary progressive MS.

Because lower-efficacy drug groups may have been biased towards participants with milder disease through excluding patients with multiple DMTs (such as treatment escalators), the investigators limited the injectables group to patients followed up before higher-efficacy drugs became available in 2006.

All DMTs reduced the hazard of conversion to secondary progressive MS, compared with different groups of matched untreated patients, in a series of pairwise analyses. For injectables, the hazard ratio (HR) of conversion to secondary progressive MS was 0.31 (median censored on-treatment follow-up, 7.9 years). For fingolimod, the HR was 0.23 (follow-up, 4.6 years). Natalizumab was associated with an HR of 0.50 (follow-up, 4.9 years). Alemtuzumab had an HR of 0.60 (follow-up, 7.2 years).

When the investigators matched patients between the treated cohorts, they found no significant difference in rate of conversion to secondary progressive MS between alemtuzumab and natalizumab. Alemtuzumab and natalizumab were therefore combined in a category of high-efficacy therapies (n = 118) and matched and compared with the injectables group (n = 236). High-efficacy therapies conferred greater protection against conversion to secondary progressive MS than injectables did (HR, 0.65; follow-up, 5.7 years).

PARIS—Secondary progressive multiple sclerosis (MS) is at least partly a consequence of early inflammation, and the risk of conversion from relapsing-remitting MS to secondary progressive MS is modifiable over five years with existing disease-modifying therapies (DMTs), according to research described at the Seventh Joint ECTRIMS–ACTRIMS Meeting. High-efficacy therapies such as alemtuzumab and natalizumab reduce the risk to a greater extent than do other DMTs.

Current immunotherapies do not slow secondary progressive MS after disease onset. The extent to which secondary progressive MS reflects early inflammation is not certain. Also unclear is whether conversion to secondary progressive MS might be modified by immunomodulatory DMTs during the relapsing-remitting phase.

Using an objective definition of secondary progressive MS published by Lorscheider et al in 2016, J. William L. Brown, MD, of the Queen Square MS Center at University College of London Institute of Neurology, and colleagues examined whether DMTs delay or reduce conversion from relapsing-remitting MS to secondary progressive MS. They examined patients with relapsing-remitting MS who participated in the MSBase database and were treated with a single DMT with at least four years of on-treatment follow-up. In all, 240 patients received injectables (ie, interferons or glatiramer acetate), 109 took fingolimod, 93 received natalizumab, and 44 took alemtuzumab.

Participants were each propensity matched to untreated patients with relapsing-remitting MS from a historical cohort (n = 622; mean follow-up, 9.2 years) and then matched to different DMT groups. Patients were matched on gender, baseline age, annualized-relapse rate, Expanded Disability Status Scale (EDSS) score, and disease duration. The researchers used weighted conditional proportional hazards models adjusted for EDSS frequency with pairwise censoring to compare the proportions of patients in each group who were free from conversion to secondary progressive MS.

Because lower-efficacy drug groups may have been biased towards participants with milder disease through excluding patients with multiple DMTs (such as treatment escalators), the investigators limited the injectables group to patients followed up before higher-efficacy drugs became available in 2006.

All DMTs reduced the hazard of conversion to secondary progressive MS, compared with different groups of matched untreated patients, in a series of pairwise analyses. For injectables, the hazard ratio (HR) of conversion to secondary progressive MS was 0.31 (median censored on-treatment follow-up, 7.9 years). For fingolimod, the HR was 0.23 (follow-up, 4.6 years). Natalizumab was associated with an HR of 0.50 (follow-up, 4.9 years). Alemtuzumab had an HR of 0.60 (follow-up, 7.2 years).

When the investigators matched patients between the treated cohorts, they found no significant difference in rate of conversion to secondary progressive MS between alemtuzumab and natalizumab. Alemtuzumab and natalizumab were therefore combined in a category of high-efficacy therapies (n = 118) and matched and compared with the injectables group (n = 236). High-efficacy therapies conferred greater protection against conversion to secondary progressive MS than injectables did (HR, 0.65; follow-up, 5.7 years).

PARIS—When faced with patients with clinically isolated syndrome (CIS) or primary progressive multiple sclerosis (PPMS), diagnosis can be challenging. The 2010 McDonald criteria and the 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria offer sound guidance for relapsing-remitting multiple sclerosis (MS), but for special patient populations, these criteria may fall short. At the Seventh Joint ECTRIMS–ACTRIMS Meeting, two studies looked at the suitability of diagnostic criteria for special MS populations.

Clinically Isolated Syndrome

The recently proposed MAGNIMS dissemination in space criteria include lesions in the optic nerve, cortex, and symptomatic region, in addition to an increase in the required number of periventricular lesions from one to three. Raquel Lamas Pérez, MD, and colleagues aimed to compare the diagnostic performance of the 2010 McDonald and 2016 MAGNIMS MRI criteria for dissemination in space in predicting the conversion to clinically definite MS in patients with CIS. Dr. Lamas Pérez is affiliated with the Hospital Universitario Virgen del Rocío in Sevilla, Spain.

Study inclusion criteria included CIS suggestive of CNS demyelination (since 2008), clinical assessment and baseline brain MRI within six months of CIS onset, availability of spinal cord MRI if patients presented with spinal cord syndrome, and clinical follow-up of at least 24 months.

The researchers included 161 patients with CIS (113 women) with a mean age at onset of 34. After a mean follow-up of 58 months, 102 (63.4%) patients had a diagnosis of MS according to the 2010 McDonald criteria. The overall conversion rate to clinically definite MS was 48.4%. Forty-six (45%) patients initiated a disease-modifying treatment before the second clinical event. The 2010 McDonald dissemination in space criteria were met in 100 (62.1%) and the 2016 MAGNIMS dissemination in space criteria in 95 (59%) patients with CIS. Six patients with one periventricular lesion fulfilled the 2010 McDonald criteria but not the 2016 MAGNIMS criteria. In contrast, when symptomatic infratentorial or spinal cord lesions were included, two more patients met the 2016 dissemination in space criteria than met the 2010 McDonald criteria. The sensitivity, specificity, and positive and negative predictive values of 2010 McDonald criteria were 80.7%, 55.4%, 63%, and 75.4%, respectively, and those for the 2016 MAGNIMS criteria were 75.6%, 56.6%, 62.1%, and 71.2%, respectively. Both dissemination in space criteria identified a subset of patients with CIS who were at high early risk of developing clinically definite MS (hazard ratio: 2.17 for McDonald and 2.07 for MAGNIMS).

“In our CIS patient cohort, 2016 MAGNIMS MRI criteria for dissemination in space showed lower sensitivity with similar specificity than 2010 McDonald criteria in predicting conversion to clinically definite MS, probably related to the increase in the required number of periventricular lesions,” Dr. Lamas Pérez said. “Because disease-modifying therapy can delay or prevent the conversion to clinically definite MS, the high number of patients that initiated these therapies before the second relapse would explain the intermediate specificity values obtained with both MRI criteria.”

Primary Progressive MS

The 2010 McDonald criteria for PPMS have not been fully validated, while 2016 MAGNIMS MRI guidelines have not been studied in PPMS yet.

To assess the sensitivity and specificity of 2010 McDonald and 2016 MAGNIMS criteria for patients with PPMS, Alberto Gajofatto, MD, PhD, Assistant Professor in Neurology in the Department of Neurological and Movement Sciences at the University of Verona in Italy, and colleagues applied the criteria to two retrospective cohorts.

Patients who were seen at the University of California San Francisco and Verona University MS Centers for suspected PPMS were retrospectively identified from existing databases between November 2015 and October 2016. Data were obtained from review of patient charts with adequate documentation of clinical, MRI, and CSF status to determine the fulfillment of 2010 McDonald criteria for PPMS and 2016 MAGNIMS guidelines for dissemination in space at first visit at study centers. PPMS diagnosis was confirmed at last available visit using stringent criteria (ie, dissemination in space according to 2005 McDonald criteria, dissemination in time according to 2001 McDonald criteria, and exclusion of a better explanation).

Dr. Gajofatto and colleagues included 108 patients with a mean follow-up duration of 10.1 years. The 2010 McDonald criteria had a sensitivity for PPMS of 92.1% and a specificity of 57.9%. The highest combined values of sensitivity and specificity (91.8% and 72.2%) were achieved by combining 2016 MAGNIMS dissemination in space criteria and the presence of oligoclonal bands or increased IgG index in the CSF.

“Our findings suggest that 2010 McDonald criteria for PPMS diagnosis have high sensitivity, while specificity appears to be modest,” Dr. Gajofatto said. “The substitution of 2016 MAGNIMS criteria for dissemination in space plus the incorporation of CSF status increased specificity without compromising sensitivity.”

PARIS—When faced with patients with clinically isolated syndrome (CIS) or primary progressive multiple sclerosis (PPMS), diagnosis can be challenging. The 2010 McDonald criteria and the 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria offer sound guidance for relapsing-remitting multiple sclerosis (MS), but for special patient populations, these criteria may fall short. At the Seventh Joint ECTRIMS–ACTRIMS Meeting, two studies looked at the suitability of diagnostic criteria for special MS populations.

Clinically Isolated Syndrome

The recently proposed MAGNIMS dissemination in space criteria include lesions in the optic nerve, cortex, and symptomatic region, in addition to an increase in the required number of periventricular lesions from one to three. Raquel Lamas Pérez, MD, and colleagues aimed to compare the diagnostic performance of the 2010 McDonald and 2016 MAGNIMS MRI criteria for dissemination in space in predicting the conversion to clinically definite MS in patients with CIS. Dr. Lamas Pérez is affiliated with the Hospital Universitario Virgen del Rocío in Sevilla, Spain.

Study inclusion criteria included CIS suggestive of CNS demyelination (since 2008), clinical assessment and baseline brain MRI within six months of CIS onset, availability of spinal cord MRI if patients presented with spinal cord syndrome, and clinical follow-up of at least 24 months.

The researchers included 161 patients with CIS (113 women) with a mean age at onset of 34. After a mean follow-up of 58 months, 102 (63.4%) patients had a diagnosis of MS according to the 2010 McDonald criteria. The overall conversion rate to clinically definite MS was 48.4%. Forty-six (45%) patients initiated a disease-modifying treatment before the second clinical event. The 2010 McDonald dissemination in space criteria were met in 100 (62.1%) and the 2016 MAGNIMS dissemination in space criteria in 95 (59%) patients with CIS. Six patients with one periventricular lesion fulfilled the 2010 McDonald criteria but not the 2016 MAGNIMS criteria. In contrast, when symptomatic infratentorial or spinal cord lesions were included, two more patients met the 2016 dissemination in space criteria than met the 2010 McDonald criteria. The sensitivity, specificity, and positive and negative predictive values of 2010 McDonald criteria were 80.7%, 55.4%, 63%, and 75.4%, respectively, and those for the 2016 MAGNIMS criteria were 75.6%, 56.6%, 62.1%, and 71.2%, respectively. Both dissemination in space criteria identified a subset of patients with CIS who were at high early risk of developing clinically definite MS (hazard ratio: 2.17 for McDonald and 2.07 for MAGNIMS).

“In our CIS patient cohort, 2016 MAGNIMS MRI criteria for dissemination in space showed lower sensitivity with similar specificity than 2010 McDonald criteria in predicting conversion to clinically definite MS, probably related to the increase in the required number of periventricular lesions,” Dr. Lamas Pérez said. “Because disease-modifying therapy can delay or prevent the conversion to clinically definite MS, the high number of patients that initiated these therapies before the second relapse would explain the intermediate specificity values obtained with both MRI criteria.”

Primary Progressive MS

The 2010 McDonald criteria for PPMS have not been fully validated, while 2016 MAGNIMS MRI guidelines have not been studied in PPMS yet.

To assess the sensitivity and specificity of 2010 McDonald and 2016 MAGNIMS criteria for patients with PPMS, Alberto Gajofatto, MD, PhD, Assistant Professor in Neurology in the Department of Neurological and Movement Sciences at the University of Verona in Italy, and colleagues applied the criteria to two retrospective cohorts.

Patients who were seen at the University of California San Francisco and Verona University MS Centers for suspected PPMS were retrospectively identified from existing databases between November 2015 and October 2016. Data were obtained from review of patient charts with adequate documentation of clinical, MRI, and CSF status to determine the fulfillment of 2010 McDonald criteria for PPMS and 2016 MAGNIMS guidelines for dissemination in space at first visit at study centers. PPMS diagnosis was confirmed at last available visit using stringent criteria (ie, dissemination in space according to 2005 McDonald criteria, dissemination in time according to 2001 McDonald criteria, and exclusion of a better explanation).

Dr. Gajofatto and colleagues included 108 patients with a mean follow-up duration of 10.1 years. The 2010 McDonald criteria had a sensitivity for PPMS of 92.1% and a specificity of 57.9%. The highest combined values of sensitivity and specificity (91.8% and 72.2%) were achieved by combining 2016 MAGNIMS dissemination in space criteria and the presence of oligoclonal bands or increased IgG index in the CSF.

“Our findings suggest that 2010 McDonald criteria for PPMS diagnosis have high sensitivity, while specificity appears to be modest,” Dr. Gajofatto said. “The substitution of 2016 MAGNIMS criteria for dissemination in space plus the incorporation of CSF status increased specificity without compromising sensitivity.”

PARIS—When faced with patients with clinically isolated syndrome (CIS) or primary progressive multiple sclerosis (PPMS), diagnosis can be challenging. The 2010 McDonald criteria and the 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria offer sound guidance for relapsing-remitting multiple sclerosis (MS), but for special patient populations, these criteria may fall short. At the Seventh Joint ECTRIMS–ACTRIMS Meeting, two studies looked at the suitability of diagnostic criteria for special MS populations.

Clinically Isolated Syndrome

The recently proposed MAGNIMS dissemination in space criteria include lesions in the optic nerve, cortex, and symptomatic region, in addition to an increase in the required number of periventricular lesions from one to three. Raquel Lamas Pérez, MD, and colleagues aimed to compare the diagnostic performance of the 2010 McDonald and 2016 MAGNIMS MRI criteria for dissemination in space in predicting the conversion to clinically definite MS in patients with CIS. Dr. Lamas Pérez is affiliated with the Hospital Universitario Virgen del Rocío in Sevilla, Spain.

Study inclusion criteria included CIS suggestive of CNS demyelination (since 2008), clinical assessment and baseline brain MRI within six months of CIS onset, availability of spinal cord MRI if patients presented with spinal cord syndrome, and clinical follow-up of at least 24 months.

The researchers included 161 patients with CIS (113 women) with a mean age at onset of 34. After a mean follow-up of 58 months, 102 (63.4%) patients had a diagnosis of MS according to the 2010 McDonald criteria. The overall conversion rate to clinically definite MS was 48.4%. Forty-six (45%) patients initiated a disease-modifying treatment before the second clinical event. The 2010 McDonald dissemination in space criteria were met in 100 (62.1%) and the 2016 MAGNIMS dissemination in space criteria in 95 (59%) patients with CIS. Six patients with one periventricular lesion fulfilled the 2010 McDonald criteria but not the 2016 MAGNIMS criteria. In contrast, when symptomatic infratentorial or spinal cord lesions were included, two more patients met the 2016 dissemination in space criteria than met the 2010 McDonald criteria. The sensitivity, specificity, and positive and negative predictive values of 2010 McDonald criteria were 80.7%, 55.4%, 63%, and 75.4%, respectively, and those for the 2016 MAGNIMS criteria were 75.6%, 56.6%, 62.1%, and 71.2%, respectively. Both dissemination in space criteria identified a subset of patients with CIS who were at high early risk of developing clinically definite MS (hazard ratio: 2.17 for McDonald and 2.07 for MAGNIMS).

“In our CIS patient cohort, 2016 MAGNIMS MRI criteria for dissemination in space showed lower sensitivity with similar specificity than 2010 McDonald criteria in predicting conversion to clinically definite MS, probably related to the increase in the required number of periventricular lesions,” Dr. Lamas Pérez said. “Because disease-modifying therapy can delay or prevent the conversion to clinically definite MS, the high number of patients that initiated these therapies before the second relapse would explain the intermediate specificity values obtained with both MRI criteria.”

Primary Progressive MS

The 2010 McDonald criteria for PPMS have not been fully validated, while 2016 MAGNIMS MRI guidelines have not been studied in PPMS yet.

To assess the sensitivity and specificity of 2010 McDonald and 2016 MAGNIMS criteria for patients with PPMS, Alberto Gajofatto, MD, PhD, Assistant Professor in Neurology in the Department of Neurological and Movement Sciences at the University of Verona in Italy, and colleagues applied the criteria to two retrospective cohorts.

Patients who were seen at the University of California San Francisco and Verona University MS Centers for suspected PPMS were retrospectively identified from existing databases between November 2015 and October 2016. Data were obtained from review of patient charts with adequate documentation of clinical, MRI, and CSF status to determine the fulfillment of 2010 McDonald criteria for PPMS and 2016 MAGNIMS guidelines for dissemination in space at first visit at study centers. PPMS diagnosis was confirmed at last available visit using stringent criteria (ie, dissemination in space according to 2005 McDonald criteria, dissemination in time according to 2001 McDonald criteria, and exclusion of a better explanation).

Dr. Gajofatto and colleagues included 108 patients with a mean follow-up duration of 10.1 years. The 2010 McDonald criteria had a sensitivity for PPMS of 92.1% and a specificity of 57.9%. The highest combined values of sensitivity and specificity (91.8% and 72.2%) were achieved by combining 2016 MAGNIMS dissemination in space criteria and the presence of oligoclonal bands or increased IgG index in the CSF.

“Our findings suggest that 2010 McDonald criteria for PPMS diagnosis have high sensitivity, while specificity appears to be modest,” Dr. Gajofatto said. “The substitution of 2016 MAGNIMS criteria for dissemination in space plus the incorporation of CSF status increased specificity without compromising sensitivity.”

PARIS—McArdle’s sign, a rapidly reversible motor weakness induced by head flexion in patients with suspected multiple sclerosis (MS), may facilitate diagnosis in certain clinical situations, according to a study presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. “McArdle’s sign, when defined as a greater than 10% neck flexion-induced reduction using isoinertial finger extension on a measurement device, is highly specific and moderately sensitive for a diagnosis of MS,” said Brian G. Weinshenker, MD, and colleagues. Dr. Weinshenker is Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.

Dr. Weinshenker and colleagues quantified McArdle’s sign in finger extensors using a torque measuring device and assessed its specificity for MS. They enrolled 25 healthy controls and 76 patients with detectable finger extensor weakness, 52 with MS, 24 with other myelopathies, and five with peripheral nerve lesions. Patients were not selected for having McArdle’s sign. Dr. Weinshenker and his team evaluated McArdle’s sign blinded to diagnosis by measuring change in finger extensor strength in successive trials of head extension and flexion, first clinically and then with a torque measuring device. McArdle’s sign was clinically rated from zero (absent) to three (marked). In the quantitative measurement, the patient applied maximum extension strength of four fingers on a bar using isometric (against fixed object) and isoinertial (against a constant resistance) maneuvers. The researchers then averaged the percentage decrease in strength over four trials.

Baseline strength was similar in the three patient groups. The median clinical McArdle’s sign was one (range, zero to three) in patients with MS, zero (range, zero to two) in other myelopathies, zero (range, zero to one) in healthy controls, and zero in all patients with peripheral nerve lesions. The isometric and isoinertial maneuvers provided similar quantitative results, but the isoinertial maneuver had superior diagnostic performance. Head flexion resulted in 17% (± 17%) isoinertial strength reduction in patients with MS versus 1% (± 6%) in other myelopathies, 1% (± 5%) in healthy controls and -3% (± 10%) in patients with peripheral nerve lesions.

A multivariate regression analysis eliminated confounding by baseline strength. Receiver operator curves were generated to assess the diagnostic properties of the test; the area under the curve was 0.82 in patients with MS versus healthy controls and 0.83 in patients with MS versus other myelopathies for isoinertial testing. A 10% drop in strength with flexion was 100% specific and 62% sensitive for MS compared with other myelopathies and a 6% drop, 92% specific and 73% sensitive, for MS compared with healthy controls. Quantitative McArdle’s sign correlated with clinical McArdle’s sign by referring physician and technician (r = 0.58). McArdle’s sign correlated with Expanded Disability Status Scale (r = 0.41) and pyramidal score (r = 0.49) in patients with MS, but was evident in some patients in very early phases of MS and minor disability.

PARIS—McArdle’s sign, a rapidly reversible motor weakness induced by head flexion in patients with suspected multiple sclerosis (MS), may facilitate diagnosis in certain clinical situations, according to a study presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. “McArdle’s sign, when defined as a greater than 10% neck flexion-induced reduction using isoinertial finger extension on a measurement device, is highly specific and moderately sensitive for a diagnosis of MS,” said Brian G. Weinshenker, MD, and colleagues. Dr. Weinshenker is Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.

Dr. Weinshenker and colleagues quantified McArdle’s sign in finger extensors using a torque measuring device and assessed its specificity for MS. They enrolled 25 healthy controls and 76 patients with detectable finger extensor weakness, 52 with MS, 24 with other myelopathies, and five with peripheral nerve lesions. Patients were not selected for having McArdle’s sign. Dr. Weinshenker and his team evaluated McArdle’s sign blinded to diagnosis by measuring change in finger extensor strength in successive trials of head extension and flexion, first clinically and then with a torque measuring device. McArdle’s sign was clinically rated from zero (absent) to three (marked). In the quantitative measurement, the patient applied maximum extension strength of four fingers on a bar using isometric (against fixed object) and isoinertial (against a constant resistance) maneuvers. The researchers then averaged the percentage decrease in strength over four trials.

Baseline strength was similar in the three patient groups. The median clinical McArdle’s sign was one (range, zero to three) in patients with MS, zero (range, zero to two) in other myelopathies, zero (range, zero to one) in healthy controls, and zero in all patients with peripheral nerve lesions. The isometric and isoinertial maneuvers provided similar quantitative results, but the isoinertial maneuver had superior diagnostic performance. Head flexion resulted in 17% (± 17%) isoinertial strength reduction in patients with MS versus 1% (± 6%) in other myelopathies, 1% (± 5%) in healthy controls and -3% (± 10%) in patients with peripheral nerve lesions.

A multivariate regression analysis eliminated confounding by baseline strength. Receiver operator curves were generated to assess the diagnostic properties of the test; the area under the curve was 0.82 in patients with MS versus healthy controls and 0.83 in patients with MS versus other myelopathies for isoinertial testing. A 10% drop in strength with flexion was 100% specific and 62% sensitive for MS compared with other myelopathies and a 6% drop, 92% specific and 73% sensitive, for MS compared with healthy controls. Quantitative McArdle’s sign correlated with clinical McArdle’s sign by referring physician and technician (r = 0.58). McArdle’s sign correlated with Expanded Disability Status Scale (r = 0.41) and pyramidal score (r = 0.49) in patients with MS, but was evident in some patients in very early phases of MS and minor disability.

PARIS—McArdle’s sign, a rapidly reversible motor weakness induced by head flexion in patients with suspected multiple sclerosis (MS), may facilitate diagnosis in certain clinical situations, according to a study presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. “McArdle’s sign, when defined as a greater than 10% neck flexion-induced reduction using isoinertial finger extension on a measurement device, is highly specific and moderately sensitive for a diagnosis of MS,” said Brian G. Weinshenker, MD, and colleagues. Dr. Weinshenker is Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.

Dr. Weinshenker and colleagues quantified McArdle’s sign in finger extensors using a torque measuring device and assessed its specificity for MS. They enrolled 25 healthy controls and 76 patients with detectable finger extensor weakness, 52 with MS, 24 with other myelopathies, and five with peripheral nerve lesions. Patients were not selected for having McArdle’s sign. Dr. Weinshenker and his team evaluated McArdle’s sign blinded to diagnosis by measuring change in finger extensor strength in successive trials of head extension and flexion, first clinically and then with a torque measuring device. McArdle’s sign was clinically rated from zero (absent) to three (marked). In the quantitative measurement, the patient applied maximum extension strength of four fingers on a bar using isometric (against fixed object) and isoinertial (against a constant resistance) maneuvers. The researchers then averaged the percentage decrease in strength over four trials.

Baseline strength was similar in the three patient groups. The median clinical McArdle’s sign was one (range, zero to three) in patients with MS, zero (range, zero to two) in other myelopathies, zero (range, zero to one) in healthy controls, and zero in all patients with peripheral nerve lesions. The isometric and isoinertial maneuvers provided similar quantitative results, but the isoinertial maneuver had superior diagnostic performance. Head flexion resulted in 17% (± 17%) isoinertial strength reduction in patients with MS versus 1% (± 6%) in other myelopathies, 1% (± 5%) in healthy controls and -3% (± 10%) in patients with peripheral nerve lesions.

A multivariate regression analysis eliminated confounding by baseline strength. Receiver operator curves were generated to assess the diagnostic properties of the test; the area under the curve was 0.82 in patients with MS versus healthy controls and 0.83 in patients with MS versus other myelopathies for isoinertial testing. A 10% drop in strength with flexion was 100% specific and 62% sensitive for MS compared with other myelopathies and a 6% drop, 92% specific and 73% sensitive, for MS compared with healthy controls. Quantitative McArdle’s sign correlated with clinical McArdle’s sign by referring physician and technician (r = 0.58). McArdle’s sign correlated with Expanded Disability Status Scale (r = 0.41) and pyramidal score (r = 0.49) in patients with MS, but was evident in some patients in very early phases of MS and minor disability.