Multiple Sclerosis

Patients who continue smoking after they have been diagnosed with multiple sclerosis (MS) may progress to secondary progressive MS earlier than patients who quit smoking, according to research published online ahead of print September 8 in JAMA Neurology. The findings suggest that physicians should advise patients to stop smoking to avoid aggravating MS-related disability, said Jan Hillert, MD, PhD, of the Karolinska Institutet at Karolinska University Hospital Solna in Stockholm.

“Evidence clearly supports advising patients with MS who smoke to quit,” said Dr. Hillert and colleagues. “Health care services for patients with MS should be organized to support such a lifestyle change.”

A Cross-Sectional Analysis

Cigarette smoking is a known risk factor for MS, with an odds ratio between 1.2 and 1.5, but investigators had not assessed whether quitting smoking after diagnosis affects the course of the disease. To clarify the impact of smoking continuation and cessation on time to conversion from relapsing-remitting MS to secondary progressive MS, Dr. Hillert and colleagues performed a cross-sectional study of patients in the Genes and Environment in Multiple Sclerosis (GEMS) Study in Sweden, a population-based case–control study that includes patients with prevalent MS from the Swedish National MS Registry. Researchers included in their main analysis 728 patients who smoked at diagnosis and who completed questionnaires from November 2009 to March 2011 about their smoking habits.

Researchers categorized 332 of these patients as continuous smokers (ie, they averaged at least one cigarette per day every year from the year after diagnosis) and 118 as quitters. Intermittent smokers were not considered in the primary outcome. An optimized accelerated failure time survival model showed that each additional year of smoking after diagnosis accelerated the time to conversion to secondary progressive MS by 4.7%. Uncorrected Kaplan–Meier plots showed that those who continued to smoke each year after diagnosis converted to secondary progressive MS at a median age of 48, compared with a median age of 56 for those who quit smoking, said the researchers. Smoking measured by pack-years had similar associations with time to conversion as years of active smoking, suggesting that these measures may be approximate proxies of each other.

Potential Confounder

Confounders can exist in any association study, and there might be variables associated with smoking that were not captured in this study, the researchers said.

While the groups were well balanced across most measures, those who quit smoking had shorter time to MS treatment than those who continued smoking, which is a potential confounder in the difference in time of secondary progressive MS onset, said Myla D. Goldman, MD, of the University of Virginia in Charlottesville, and Olaf Stüve, MD, PhD, of the University of Texas Southwestern Medical Center at Dallas, in an editorial commentary published with the study.

In addition, the broad categories of patient smoking levels “unfortunately prohibited any granularity about any dose effect of smoking on progression,” Drs. Goldman and Stüve said. “Thus, it remains unclear whether simply cutting back on the amount one is smoking could provide any benefit.”

A Risk Factor Worth Modifying

About 60% of Swedish patients with MS are smokers, reflecting a potentially large overall health benefit to smoking cessation efforts, Dr. Hillert and colleagues said.

“Most importantly, [this study] provides the first evidence, to our knowledge, that quitting smoking appears to delay onset of secondary progressive MS and provide protective benefit,” said Drs. Goldman and Stüve. “Therefore, even after MS diagnosis, smoking is a risk factor worth modifying.”

—Jake Remaly

Patients who continue smoking after they have been diagnosed with multiple sclerosis (MS) may progress to secondary progressive MS earlier than patients who quit smoking, according to research published online ahead of print September 8 in JAMA Neurology. The findings suggest that physicians should advise patients to stop smoking to avoid aggravating MS-related disability, said Jan Hillert, MD, PhD, of the Karolinska Institutet at Karolinska University Hospital Solna in Stockholm.

“Evidence clearly supports advising patients with MS who smoke to quit,” said Dr. Hillert and colleagues. “Health care services for patients with MS should be organized to support such a lifestyle change.”

A Cross-Sectional Analysis

Cigarette smoking is a known risk factor for MS, with an odds ratio between 1.2 and 1.5, but investigators had not assessed whether quitting smoking after diagnosis affects the course of the disease. To clarify the impact of smoking continuation and cessation on time to conversion from relapsing-remitting MS to secondary progressive MS, Dr. Hillert and colleagues performed a cross-sectional study of patients in the Genes and Environment in Multiple Sclerosis (GEMS) Study in Sweden, a population-based case–control study that includes patients with prevalent MS from the Swedish National MS Registry. Researchers included in their main analysis 728 patients who smoked at diagnosis and who completed questionnaires from November 2009 to March 2011 about their smoking habits.

Researchers categorized 332 of these patients as continuous smokers (ie, they averaged at least one cigarette per day every year from the year after diagnosis) and 118 as quitters. Intermittent smokers were not considered in the primary outcome. An optimized accelerated failure time survival model showed that each additional year of smoking after diagnosis accelerated the time to conversion to secondary progressive MS by 4.7%. Uncorrected Kaplan–Meier plots showed that those who continued to smoke each year after diagnosis converted to secondary progressive MS at a median age of 48, compared with a median age of 56 for those who quit smoking, said the researchers. Smoking measured by pack-years had similar associations with time to conversion as years of active smoking, suggesting that these measures may be approximate proxies of each other.

Potential Confounder

Confounders can exist in any association study, and there might be variables associated with smoking that were not captured in this study, the researchers said.

While the groups were well balanced across most measures, those who quit smoking had shorter time to MS treatment than those who continued smoking, which is a potential confounder in the difference in time of secondary progressive MS onset, said Myla D. Goldman, MD, of the University of Virginia in Charlottesville, and Olaf Stüve, MD, PhD, of the University of Texas Southwestern Medical Center at Dallas, in an editorial commentary published with the study.

In addition, the broad categories of patient smoking levels “unfortunately prohibited any granularity about any dose effect of smoking on progression,” Drs. Goldman and Stüve said. “Thus, it remains unclear whether simply cutting back on the amount one is smoking could provide any benefit.”

A Risk Factor Worth Modifying

About 60% of Swedish patients with MS are smokers, reflecting a potentially large overall health benefit to smoking cessation efforts, Dr. Hillert and colleagues said.

“Most importantly, [this study] provides the first evidence, to our knowledge, that quitting smoking appears to delay onset of secondary progressive MS and provide protective benefit,” said Drs. Goldman and Stüve. “Therefore, even after MS diagnosis, smoking is a risk factor worth modifying.”

—Jake Remaly

Patients who continue smoking after they have been diagnosed with multiple sclerosis (MS) may progress to secondary progressive MS earlier than patients who quit smoking, according to research published online ahead of print September 8 in JAMA Neurology. The findings suggest that physicians should advise patients to stop smoking to avoid aggravating MS-related disability, said Jan Hillert, MD, PhD, of the Karolinska Institutet at Karolinska University Hospital Solna in Stockholm.

“Evidence clearly supports advising patients with MS who smoke to quit,” said Dr. Hillert and colleagues. “Health care services for patients with MS should be organized to support such a lifestyle change.”

A Cross-Sectional Analysis

Cigarette smoking is a known risk factor for MS, with an odds ratio between 1.2 and 1.5, but investigators had not assessed whether quitting smoking after diagnosis affects the course of the disease. To clarify the impact of smoking continuation and cessation on time to conversion from relapsing-remitting MS to secondary progressive MS, Dr. Hillert and colleagues performed a cross-sectional study of patients in the Genes and Environment in Multiple Sclerosis (GEMS) Study in Sweden, a population-based case–control study that includes patients with prevalent MS from the Swedish National MS Registry. Researchers included in their main analysis 728 patients who smoked at diagnosis and who completed questionnaires from November 2009 to March 2011 about their smoking habits.

Researchers categorized 332 of these patients as continuous smokers (ie, they averaged at least one cigarette per day every year from the year after diagnosis) and 118 as quitters. Intermittent smokers were not considered in the primary outcome. An optimized accelerated failure time survival model showed that each additional year of smoking after diagnosis accelerated the time to conversion to secondary progressive MS by 4.7%. Uncorrected Kaplan–Meier plots showed that those who continued to smoke each year after diagnosis converted to secondary progressive MS at a median age of 48, compared with a median age of 56 for those who quit smoking, said the researchers. Smoking measured by pack-years had similar associations with time to conversion as years of active smoking, suggesting that these measures may be approximate proxies of each other.

Potential Confounder

Confounders can exist in any association study, and there might be variables associated with smoking that were not captured in this study, the researchers said.

While the groups were well balanced across most measures, those who quit smoking had shorter time to MS treatment than those who continued smoking, which is a potential confounder in the difference in time of secondary progressive MS onset, said Myla D. Goldman, MD, of the University of Virginia in Charlottesville, and Olaf Stüve, MD, PhD, of the University of Texas Southwestern Medical Center at Dallas, in an editorial commentary published with the study.

In addition, the broad categories of patient smoking levels “unfortunately prohibited any granularity about any dose effect of smoking on progression,” Drs. Goldman and Stüve said. “Thus, it remains unclear whether simply cutting back on the amount one is smoking could provide any benefit.”

A Risk Factor Worth Modifying

About 60% of Swedish patients with MS are smokers, reflecting a potentially large overall health benefit to smoking cessation efforts, Dr. Hillert and colleagues said.

“Most importantly, [this study] provides the first evidence, to our knowledge, that quitting smoking appears to delay onset of secondary progressive MS and provide protective benefit,” said Drs. Goldman and Stüve. “Therefore, even after MS diagnosis, smoking is a risk factor worth modifying.”

—Jake Remaly

Greater cumulative exposure to subcutaneous interferon beta-1a (IFN–beta-1a) may cause better outcomes in treatment of relapsing-remitting multiple sclerosis, according to Ludwig Kappos, Ph.D., of the departments of neurology, medicine, clinical research, biomedicine and biomedical engineering, University Hospital Basel, Switzerland, and his associates.

In the study, 290 patients received varying doses of subcutaneous IFN–beta-1a over a 15-year time period, and their MS progression was monitored. Patients in the maximum-dosage quartile had two fewer relapses on average: 5.8 versus 7.8 in the minimum-dosage quartile. About 57% of patients in the maximum-dosage group experienced five or fewer relapses, compared with only 40% in the minimum-dosage group.

designer491/Thinkstock

Average progression on the Expanded Disability Status Scale was lower in the maximum-dosage group, which also had fewer patients experience progression than the minimum-dosage group. Conversion rate to secondary-progressive MS was also lower in the maximum-dosage group, with a hazard ratio of 0.31, compared with the minimum-dosage group.

In a related editorial, Dr. Fedor Heidenreich of the department of neurology and clinical neurophysiology, Diakoniekrankenhaus Henriettenstiftung in Hannover, Germany, said the study results “should prompt MS specialists to encourage patients to continue with IFN–beta-1a (or glatiramer acetate) treatment more resolutely instead of frequently switching their therapeutic regime.”

Find the full study and editorial online in the Sept. 16 Journal of Neurology, Neurosurgery, and Psychiatry.

lfranki@frontlinemedcom.com

Greater cumulative exposure to subcutaneous interferon beta-1a (IFN–beta-1a) may cause better outcomes in treatment of relapsing-remitting multiple sclerosis, according to Ludwig Kappos, Ph.D., of the departments of neurology, medicine, clinical research, biomedicine and biomedical engineering, University Hospital Basel, Switzerland, and his associates.

In the study, 290 patients received varying doses of subcutaneous IFN–beta-1a over a 15-year time period, and their MS progression was monitored. Patients in the maximum-dosage quartile had two fewer relapses on average: 5.8 versus 7.8 in the minimum-dosage quartile. About 57% of patients in the maximum-dosage group experienced five or fewer relapses, compared with only 40% in the minimum-dosage group.

designer491/Thinkstock

Average progression on the Expanded Disability Status Scale was lower in the maximum-dosage group, which also had fewer patients experience progression than the minimum-dosage group. Conversion rate to secondary-progressive MS was also lower in the maximum-dosage group, with a hazard ratio of 0.31, compared with the minimum-dosage group.

In a related editorial, Dr. Fedor Heidenreich of the department of neurology and clinical neurophysiology, Diakoniekrankenhaus Henriettenstiftung in Hannover, Germany, said the study results “should prompt MS specialists to encourage patients to continue with IFN–beta-1a (or glatiramer acetate) treatment more resolutely instead of frequently switching their therapeutic regime.”

Find the full study and editorial online in the Sept. 16 Journal of Neurology, Neurosurgery, and Psychiatry.

lfranki@frontlinemedcom.com

Greater cumulative exposure to subcutaneous interferon beta-1a (IFN–beta-1a) may cause better outcomes in treatment of relapsing-remitting multiple sclerosis, according to Ludwig Kappos, Ph.D., of the departments of neurology, medicine, clinical research, biomedicine and biomedical engineering, University Hospital Basel, Switzerland, and his associates.

In the study, 290 patients received varying doses of subcutaneous IFN–beta-1a over a 15-year time period, and their MS progression was monitored. Patients in the maximum-dosage quartile had two fewer relapses on average: 5.8 versus 7.8 in the minimum-dosage quartile. About 57% of patients in the maximum-dosage group experienced five or fewer relapses, compared with only 40% in the minimum-dosage group.

designer491/Thinkstock

Average progression on the Expanded Disability Status Scale was lower in the maximum-dosage group, which also had fewer patients experience progression than the minimum-dosage group. Conversion rate to secondary-progressive MS was also lower in the maximum-dosage group, with a hazard ratio of 0.31, compared with the minimum-dosage group.

In a related editorial, Dr. Fedor Heidenreich of the department of neurology and clinical neurophysiology, Diakoniekrankenhaus Henriettenstiftung in Hannover, Germany, said the study results “should prompt MS specialists to encourage patients to continue with IFN–beta-1a (or glatiramer acetate) treatment more resolutely instead of frequently switching their therapeutic regime.”

Find the full study and editorial online in the Sept. 16 Journal of Neurology, Neurosurgery, and Psychiatry.

lfranki@frontlinemedcom.com

Patients with multiple sclerosis who continued to smoke after diagnosis had faster disease progression in a population-based, case-control study.

Each additional year of smoking after diagnosis accelerated the time to conversion to secondary progressive multiple sclerosis (SPMS) by 4.7%, and those who smoked continuously each year after diagnosis converted to SPMS an estimated 8 years earlier than did those who quit smoking at diagnosis, according to Ryan Ramanujam, Ph.D., and his colleagues.

©American Heart Association

They analyzed data from a survey of 2,538 MS patients living in Sweden, including 728 who smoked at diagnosis, 1,012 who never had smoked, and 618 who had smoked prior to having been diagnosed. The group of smokers included 118 who stopped smoking during the year after diagnosis, 332 who continued smoking, and 278 who smoked intermittently, meaning they continued smoking for at least 1 year after being diagnosed with MS and were not smoking for at least 1 year after diagnosis.

“This study demonstrates that smoking after MS diagnosis has a negative impact on the progression of the disease, whereas reduced smoking may improve patient quality of life, with more years before the development of SP disease,” the investigators wrote.

“We suggest that these results should be regarded as sufficient to recommend smoking cessation to patients,” they added.

Read the full study in JAMA Neurology (doi: 10.1001/jamaneurol.2015.1788).

klennon@frontlinemedcom.com

Patients with multiple sclerosis who continued to smoke after diagnosis had faster disease progression in a population-based, case-control study.

Each additional year of smoking after diagnosis accelerated the time to conversion to secondary progressive multiple sclerosis (SPMS) by 4.7%, and those who smoked continuously each year after diagnosis converted to SPMS an estimated 8 years earlier than did those who quit smoking at diagnosis, according to Ryan Ramanujam, Ph.D., and his colleagues.

©American Heart Association

They analyzed data from a survey of 2,538 MS patients living in Sweden, including 728 who smoked at diagnosis, 1,012 who never had smoked, and 618 who had smoked prior to having been diagnosed. The group of smokers included 118 who stopped smoking during the year after diagnosis, 332 who continued smoking, and 278 who smoked intermittently, meaning they continued smoking for at least 1 year after being diagnosed with MS and were not smoking for at least 1 year after diagnosis.

“This study demonstrates that smoking after MS diagnosis has a negative impact on the progression of the disease, whereas reduced smoking may improve patient quality of life, with more years before the development of SP disease,” the investigators wrote.

“We suggest that these results should be regarded as sufficient to recommend smoking cessation to patients,” they added.

Read the full study in JAMA Neurology (doi: 10.1001/jamaneurol.2015.1788).

klennon@frontlinemedcom.com

Patients with multiple sclerosis who continued to smoke after diagnosis had faster disease progression in a population-based, case-control study.

Each additional year of smoking after diagnosis accelerated the time to conversion to secondary progressive multiple sclerosis (SPMS) by 4.7%, and those who smoked continuously each year after diagnosis converted to SPMS an estimated 8 years earlier than did those who quit smoking at diagnosis, according to Ryan Ramanujam, Ph.D., and his colleagues.

©American Heart Association

They analyzed data from a survey of 2,538 MS patients living in Sweden, including 728 who smoked at diagnosis, 1,012 who never had smoked, and 618 who had smoked prior to having been diagnosed. The group of smokers included 118 who stopped smoking during the year after diagnosis, 332 who continued smoking, and 278 who smoked intermittently, meaning they continued smoking for at least 1 year after being diagnosed with MS and were not smoking for at least 1 year after diagnosis.

“This study demonstrates that smoking after MS diagnosis has a negative impact on the progression of the disease, whereas reduced smoking may improve patient quality of life, with more years before the development of SP disease,” the investigators wrote.

“We suggest that these results should be regarded as sufficient to recommend smoking cessation to patients,” they added.

Read the full study in JAMA Neurology (doi: 10.1001/jamaneurol.2015.1788).

klennon@frontlinemedcom.com

High-dose oral methylprednisolone was noninferior to intravenous steroids for improving disability after multiple sclerosis relapse, according to a study published online in The Lancet.

The findings “support the use of oral methylprednisolone 1,000 mg per day for 3 days to treat MS relapses,” wrote Dr. Emmanuelle Le Page of Rennes (France) University Hospital and her associates. “Oral delivery is simpler and less invasive, more convenient for a quick primary and community care response, and allows obvious savings in cost and logistics,” they added. This also was the first trial with enough power to detect a difference between comparable doses of steroids begun early after relapse onset, they said.

©solitude72/iStockphoto

Intravenous methylprednisolone is recommended as first-line treatment for MS relapses, but can be expensive and inconvenient, the investigators said. Authors of a recent Cochrane review found no differences in recovery between patients given high-dose oral or IV methylprednisolone, but concluded that the studies were underpowered. Based on their suggestions, Dr. Le Page and associates randomized 199 adults with relapsing-remitting MS to receive 1,000 mg oral or IV methylprednisolone once daily for 3 days, starting within a week of relapse onset. The researchers powered the study based on a predetermined efficacy margin of 15%. The primary efficacy endpoint was the percentage of patients who improved on day 28 by at least 1 point on their most affected score of the Kurtzke Functional System Scale, without needing more steroids (Lancet 2015;386[9997]:974-81).

In all, 81% of patients who received oral steroids and 80% of those who received IV therapy met this endpoint. Rates of treatment-associated adverse events also were similar between the two groups, except that patients were more likely to report insomnia on oral therapy (77% vs. 64%; P = .039). “This was also reported in the meta-analysis, and might be due to prolonged bioavailability,” the researchers wrote. They recommended giving oral methylprednisolone in the morning to help avert the problem.

The French Health Ministry, Ligue Française contre la Sclérose En Plaques, and Teva Pharmaceutical Industries funded the study. Dr. Le Page reported receiving consulting fees and grant funding from Novartis, Biogen, Teva, and Genzyme Sanofi Aventis. Five coauthors reported financial relationships with several public entities, foundations, and pharmaceutical companies. The other four coauthors declared no competing interests.

High-dose oral methylprednisolone was noninferior to intravenous steroids for improving disability after multiple sclerosis relapse, according to a study published online in The Lancet.

The findings “support the use of oral methylprednisolone 1,000 mg per day for 3 days to treat MS relapses,” wrote Dr. Emmanuelle Le Page of Rennes (France) University Hospital and her associates. “Oral delivery is simpler and less invasive, more convenient for a quick primary and community care response, and allows obvious savings in cost and logistics,” they added. This also was the first trial with enough power to detect a difference between comparable doses of steroids begun early after relapse onset, they said.

©solitude72/iStockphoto

Intravenous methylprednisolone is recommended as first-line treatment for MS relapses, but can be expensive and inconvenient, the investigators said. Authors of a recent Cochrane review found no differences in recovery between patients given high-dose oral or IV methylprednisolone, but concluded that the studies were underpowered. Based on their suggestions, Dr. Le Page and associates randomized 199 adults with relapsing-remitting MS to receive 1,000 mg oral or IV methylprednisolone once daily for 3 days, starting within a week of relapse onset. The researchers powered the study based on a predetermined efficacy margin of 15%. The primary efficacy endpoint was the percentage of patients who improved on day 28 by at least 1 point on their most affected score of the Kurtzke Functional System Scale, without needing more steroids (Lancet 2015;386[9997]:974-81).

In all, 81% of patients who received oral steroids and 80% of those who received IV therapy met this endpoint. Rates of treatment-associated adverse events also were similar between the two groups, except that patients were more likely to report insomnia on oral therapy (77% vs. 64%; P = .039). “This was also reported in the meta-analysis, and might be due to prolonged bioavailability,” the researchers wrote. They recommended giving oral methylprednisolone in the morning to help avert the problem.

The French Health Ministry, Ligue Française contre la Sclérose En Plaques, and Teva Pharmaceutical Industries funded the study. Dr. Le Page reported receiving consulting fees and grant funding from Novartis, Biogen, Teva, and Genzyme Sanofi Aventis. Five coauthors reported financial relationships with several public entities, foundations, and pharmaceutical companies. The other four coauthors declared no competing interests.

High-dose oral methylprednisolone was noninferior to intravenous steroids for improving disability after multiple sclerosis relapse, according to a study published online in The Lancet.

The findings “support the use of oral methylprednisolone 1,000 mg per day for 3 days to treat MS relapses,” wrote Dr. Emmanuelle Le Page of Rennes (France) University Hospital and her associates. “Oral delivery is simpler and less invasive, more convenient for a quick primary and community care response, and allows obvious savings in cost and logistics,” they added. This also was the first trial with enough power to detect a difference between comparable doses of steroids begun early after relapse onset, they said.

©solitude72/iStockphoto

Intravenous methylprednisolone is recommended as first-line treatment for MS relapses, but can be expensive and inconvenient, the investigators said. Authors of a recent Cochrane review found no differences in recovery between patients given high-dose oral or IV methylprednisolone, but concluded that the studies were underpowered. Based on their suggestions, Dr. Le Page and associates randomized 199 adults with relapsing-remitting MS to receive 1,000 mg oral or IV methylprednisolone once daily for 3 days, starting within a week of relapse onset. The researchers powered the study based on a predetermined efficacy margin of 15%. The primary efficacy endpoint was the percentage of patients who improved on day 28 by at least 1 point on their most affected score of the Kurtzke Functional System Scale, without needing more steroids (Lancet 2015;386[9997]:974-81).

In all, 81% of patients who received oral steroids and 80% of those who received IV therapy met this endpoint. Rates of treatment-associated adverse events also were similar between the two groups, except that patients were more likely to report insomnia on oral therapy (77% vs. 64%; P = .039). “This was also reported in the meta-analysis, and might be due to prolonged bioavailability,” the researchers wrote. They recommended giving oral methylprednisolone in the morning to help avert the problem.

The French Health Ministry, Ligue Française contre la Sclérose En Plaques, and Teva Pharmaceutical Industries funded the study. Dr. Le Page reported receiving consulting fees and grant funding from Novartis, Biogen, Teva, and Genzyme Sanofi Aventis. Five coauthors reported financial relationships with several public entities, foundations, and pharmaceutical companies. The other four coauthors declared no competing interests.

Disease duration, clinical course, age, and gender contribute to the dynamic nature of white matter MS pathology, according to an analysis of 1,220 tissue blocks from 120 patients with MS. Researchers found:

• Active plaques were most often found in early disease.

• In later stages, smoldering, inactive, and shadow plaques predominated.

• Early active plaques rapidly declined with disease duration.

• Plaque type distribution differed significantly by clinical course.

• The majority of plaques in acute monophasic  and relapsing-remitting MS were active.

• In secondary progressive MS (SPMS) with attacks, all plaque types could be distinguished.

• In SPMS without attacks, inactive plaques predominated.

• Smoldering plaques were found almost exclusively in progressive MS.

• At 47 years of age, equilibrium was seen between active and inactive plaques and smoldering plaques began to peak.

• Men displayed a higher proportion of smoldering plaques.

Citation: Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. [Published online ahead of print August 3, 2015]. Ann Neurol. doi: 10.1002/ana.24497.

Disease duration, clinical course, age, and gender contribute to the dynamic nature of white matter MS pathology, according to an analysis of 1,220 tissue blocks from 120 patients with MS. Researchers found:

• Active plaques were most often found in early disease.

• In later stages, smoldering, inactive, and shadow plaques predominated.

• Early active plaques rapidly declined with disease duration.

• Plaque type distribution differed significantly by clinical course.

• The majority of plaques in acute monophasic  and relapsing-remitting MS were active.

• In secondary progressive MS (SPMS) with attacks, all plaque types could be distinguished.

• In SPMS without attacks, inactive plaques predominated.

• Smoldering plaques were found almost exclusively in progressive MS.

• At 47 years of age, equilibrium was seen between active and inactive plaques and smoldering plaques began to peak.

• Men displayed a higher proportion of smoldering plaques.

Citation: Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. [Published online ahead of print August 3, 2015]. Ann Neurol. doi: 10.1002/ana.24497.

Disease duration, clinical course, age, and gender contribute to the dynamic nature of white matter MS pathology, according to an analysis of 1,220 tissue blocks from 120 patients with MS. Researchers found:

• Active plaques were most often found in early disease.

• In later stages, smoldering, inactive, and shadow plaques predominated.

• Early active plaques rapidly declined with disease duration.

• Plaque type distribution differed significantly by clinical course.

• The majority of plaques in acute monophasic  and relapsing-remitting MS were active.

• In secondary progressive MS (SPMS) with attacks, all plaque types could be distinguished.

• In SPMS without attacks, inactive plaques predominated.

• Smoldering plaques were found almost exclusively in progressive MS.

• At 47 years of age, equilibrium was seen between active and inactive plaques and smoldering plaques began to peak.

• Men displayed a higher proportion of smoldering plaques.

Citation: Frischer JM, Weigand SD, Guo Y, et al. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. [Published online ahead of print August 3, 2015]. Ann Neurol. doi: 10.1002/ana.24497.

Dyschromatopsia in the non-optic neuritis eyes (NON-eyes) of MS patients is due to damage of retinal ganglion cells (RGC), according to a study of 106 patients with MS. Researchers found:

• There were moderate, significant correlations between color vision and macular retinal nerve fiber layer, ganglion cell complex (GCC), thalamus, and lesion volume within the optic radiations.

• Only GCC remained significant in a logistic regression model.

• In the final model including lesion load, and normalized brain parenchymal volume (NBPV) as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia, an association that remained significant when sex, age, and disease duration were added as covariates.

Citation: Lampert EJ, Andorra M, Torres-Torres R, et al. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. [Published online ahead of print August 11, 2015]. J Neurol. doi: 10.1007/s00415-015-7876-3.

Dyschromatopsia in the non-optic neuritis eyes (NON-eyes) of MS patients is due to damage of retinal ganglion cells (RGC), according to a study of 106 patients with MS. Researchers found:

• There were moderate, significant correlations between color vision and macular retinal nerve fiber layer, ganglion cell complex (GCC), thalamus, and lesion volume within the optic radiations.

• Only GCC remained significant in a logistic regression model.

• In the final model including lesion load, and normalized brain parenchymal volume (NBPV) as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia, an association that remained significant when sex, age, and disease duration were added as covariates.

Citation: Lampert EJ, Andorra M, Torres-Torres R, et al. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. [Published online ahead of print August 11, 2015]. J Neurol. doi: 10.1007/s00415-015-7876-3.

Dyschromatopsia in the non-optic neuritis eyes (NON-eyes) of MS patients is due to damage of retinal ganglion cells (RGC), according to a study of 106 patients with MS. Researchers found:

• There were moderate, significant correlations between color vision and macular retinal nerve fiber layer, ganglion cell complex (GCC), thalamus, and lesion volume within the optic radiations.

• Only GCC remained significant in a logistic regression model.

• In the final model including lesion load, and normalized brain parenchymal volume (NBPV) as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia, an association that remained significant when sex, age, and disease duration were added as covariates.

Citation: Lampert EJ, Andorra M, Torres-Torres R, et al. Color vision impairment in multiple sclerosis points to retinal ganglion cell damage. [Published online ahead of print August 11, 2015]. J Neurol. doi: 10.1007/s00415-015-7876-3.

Mixed amphetamine salts, extended release (MAS-XR) may be a potential treatment for MS patients with demonstrated processing speed (PS) impairment, according to a study of 52 patients randomized to MAS-XR 5 mg, MAS-XR 10 mg, or placebo. Researchers found:

• At baseline, mean score on the symbol digit modalities test (SDMT) was 43.3 and mean score on the paced auditory serial addition test (PASAT) was 34.8.

• 48.1% of patients were classified as impaired at baseline.

• After treatment, the MAS-XR 10 mg group showed significant improvement on SDMT score, improving 5.2 points vs 0.6 point improvement in the placebo group.

• Change on the PASAT was not significantly different in either treatment group.

Citation: Morrow SA, Rosehart H. Effects of single dose mixed amphetamine salts - extended release on processing speed in multiple sclerosis: a double blind placebo controlled study. [Published online ahead of print August 21, 2015]. Psychopharmacology. doi: 10.1007/s00213-015-4051-6.

Mixed amphetamine salts, extended release (MAS-XR) may be a potential treatment for MS patients with demonstrated processing speed (PS) impairment, according to a study of 52 patients randomized to MAS-XR 5 mg, MAS-XR 10 mg, or placebo. Researchers found:

• At baseline, mean score on the symbol digit modalities test (SDMT) was 43.3 and mean score on the paced auditory serial addition test (PASAT) was 34.8.

• 48.1% of patients were classified as impaired at baseline.

• After treatment, the MAS-XR 10 mg group showed significant improvement on SDMT score, improving 5.2 points vs 0.6 point improvement in the placebo group.

• Change on the PASAT was not significantly different in either treatment group.

Citation: Morrow SA, Rosehart H. Effects of single dose mixed amphetamine salts - extended release on processing speed in multiple sclerosis: a double blind placebo controlled study. [Published online ahead of print August 21, 2015]. Psychopharmacology. doi: 10.1007/s00213-015-4051-6.

Mixed amphetamine salts, extended release (MAS-XR) may be a potential treatment for MS patients with demonstrated processing speed (PS) impairment, according to a study of 52 patients randomized to MAS-XR 5 mg, MAS-XR 10 mg, or placebo. Researchers found:

• At baseline, mean score on the symbol digit modalities test (SDMT) was 43.3 and mean score on the paced auditory serial addition test (PASAT) was 34.8.

• 48.1% of patients were classified as impaired at baseline.

• After treatment, the MAS-XR 10 mg group showed significant improvement on SDMT score, improving 5.2 points vs 0.6 point improvement in the placebo group.

• Change on the PASAT was not significantly different in either treatment group.

Citation: Morrow SA, Rosehart H. Effects of single dose mixed amphetamine salts - extended release on processing speed in multiple sclerosis: a double blind placebo controlled study. [Published online ahead of print August 21, 2015]. Psychopharmacology. doi: 10.1007/s00213-015-4051-6.

Patients with MS have a lower increase in serum 25-hyroxyvitamin D (25(OH)D) levels with supplementation, even after accounting for putative confounders, according to a study of 27 female relapsing-remitting MS patients aged 18 to 60 years and 30 healthy controls. Researchers found:

• At baseline, there were no significant differences in 25(OH)D levels or demographics, except a higher body mass index (BMI) in the MS group.

• In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l lower increase in 25(OH)D levels compared with controls.

Citation: Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. [Published online ahead of print August 18, 2015]. Mult Scler. doi:10.1177/1352458515600248.

Patients with MS have a lower increase in serum 25-hyroxyvitamin D (25(OH)D) levels with supplementation, even after accounting for putative confounders, according to a study of 27 female relapsing-remitting MS patients aged 18 to 60 years and 30 healthy controls. Researchers found:

• At baseline, there were no significant differences in 25(OH)D levels or demographics, except a higher body mass index (BMI) in the MS group.

• In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l lower increase in 25(OH)D levels compared with controls.

Citation: Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. [Published online ahead of print August 18, 2015]. Mult Scler. doi:10.1177/1352458515600248.

Patients with MS have a lower increase in serum 25-hyroxyvitamin D (25(OH)D) levels with supplementation, even after accounting for putative confounders, according to a study of 27 female relapsing-remitting MS patients aged 18 to 60 years and 30 healthy controls. Researchers found:

• At baseline, there were no significant differences in 25(OH)D levels or demographics, except a higher body mass index (BMI) in the MS group.

• In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l lower increase in 25(OH)D levels compared with controls.

Citation: Bhargava P, Steele SU, Waubant E, et al. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls. [Published online ahead of print August 18, 2015]. Mult Scler. doi:10.1177/1352458515600248.

Rates of mortality and several comorbidities are higher in an MS versus non-MS cohort, according to a study of 15, 864 patients with MS and 78,420 people without MS. Researchers found that in the MS cohort compared with the non-MS cohort:

• All-causes mortality was 2.9 times higher.

• Relative risks of mortality were: infectious disease (6.2), diseases of the nervous system (5.8), respiratory system (5.0), circulatory system (2.1), and suicide (2.6).

• Relative risks of comorbidities were: sepsis (5.7), ischemic stroke (3.8), attempted suicide (2.4), and ulcerative colitis (2.0).

• The rate of cancers was higher: lymphoproliferative disorders (2.2) and melanoma (1.7). 

Citation: Capkur G, Dahlke F, Lahoz R, et al. Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US department of defense administrative claims database. [Published online ahead of print August 18, 2015]. Mul Scler Rel Dis. doi: http://dx.doi.org/10.1016/j.msard.2015.08.005.

Comment: Multiple sclerosis (MS) is not a benign disease; people with MS die at a rate higher than those without MS. This study reinforces the importance of early effective treatment to reduce disease burden and treat symptomatic problems in people who have MS. It is also just as important to identify and treat other significant comorbidities in those we treat for MS.—Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY

Rates of mortality and several comorbidities are higher in an MS versus non-MS cohort, according to a study of 15, 864 patients with MS and 78,420 people without MS. Researchers found that in the MS cohort compared with the non-MS cohort:

• All-causes mortality was 2.9 times higher.

• Relative risks of mortality were: infectious disease (6.2), diseases of the nervous system (5.8), respiratory system (5.0), circulatory system (2.1), and suicide (2.6).

• Relative risks of comorbidities were: sepsis (5.7), ischemic stroke (3.8), attempted suicide (2.4), and ulcerative colitis (2.0).

• The rate of cancers was higher: lymphoproliferative disorders (2.2) and melanoma (1.7). 

Citation: Capkur G, Dahlke F, Lahoz R, et al. Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US department of defense administrative claims database. [Published online ahead of print August 18, 2015]. Mul Scler Rel Dis. doi: http://dx.doi.org/10.1016/j.msard.2015.08.005.

Comment: Multiple sclerosis (MS) is not a benign disease; people with MS die at a rate higher than those without MS. This study reinforces the importance of early effective treatment to reduce disease burden and treat symptomatic problems in people who have MS. It is also just as important to identify and treat other significant comorbidities in those we treat for MS.—Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY

Rates of mortality and several comorbidities are higher in an MS versus non-MS cohort, according to a study of 15, 864 patients with MS and 78,420 people without MS. Researchers found that in the MS cohort compared with the non-MS cohort:

• All-causes mortality was 2.9 times higher.

• Relative risks of mortality were: infectious disease (6.2), diseases of the nervous system (5.8), respiratory system (5.0), circulatory system (2.1), and suicide (2.6).

• Relative risks of comorbidities were: sepsis (5.7), ischemic stroke (3.8), attempted suicide (2.4), and ulcerative colitis (2.0).

• The rate of cancers was higher: lymphoproliferative disorders (2.2) and melanoma (1.7). 

Citation: Capkur G, Dahlke F, Lahoz R, et al. Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US department of defense administrative claims database. [Published online ahead of print August 18, 2015]. Mul Scler Rel Dis. doi: http://dx.doi.org/10.1016/j.msard.2015.08.005.

Comment: Multiple sclerosis (MS) is not a benign disease; people with MS die at a rate higher than those without MS. This study reinforces the importance of early effective treatment to reduce disease burden and treat symptomatic problems in people who have MS. It is also just as important to identify and treat other significant comorbidities in those we treat for MS.—Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY

Genetically reduced vitamin D levels were “strongly associated” with increased risk of multiple sclerosis (MS) in a study of European populations.

The researchers used patients’ levels of 25-hydroxyvitamin D (25OHD) to determine genetically reduced vitamin D levels. They conducted a Mendelian randomization study “to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study,” which comprised 14,498 MS patients and 24,091 healthy controls.

“Each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a twofold increase in the odds of MS (95% confidence interval; 1.7-2.5; P = 7.7 X 10^-12; I² = 63%, 95% CI: 0-88%),” according to Dr. J. Brent Richards of McGill University, Montreal, and his colleagues. This provided “strong evidence” that vitamin D played “a causal role” in the patients’ susceptibility to MS.

“Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials,” the researchers wrote.

Read the full study in PLOS Medicine (doi:10.1371/journal.pmed.1001866).

klennon@frontlinemedcom.com

Genetically reduced vitamin D levels were “strongly associated” with increased risk of multiple sclerosis (MS) in a study of European populations.

The researchers used patients’ levels of 25-hydroxyvitamin D (25OHD) to determine genetically reduced vitamin D levels. They conducted a Mendelian randomization study “to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study,” which comprised 14,498 MS patients and 24,091 healthy controls.

“Each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a twofold increase in the odds of MS (95% confidence interval; 1.7-2.5; P = 7.7 X 10^-12; I² = 63%, 95% CI: 0-88%),” according to Dr. J. Brent Richards of McGill University, Montreal, and his colleagues. This provided “strong evidence” that vitamin D played “a causal role” in the patients’ susceptibility to MS.

“Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials,” the researchers wrote.

Read the full study in PLOS Medicine (doi:10.1371/journal.pmed.1001866).

klennon@frontlinemedcom.com

Genetically reduced vitamin D levels were “strongly associated” with increased risk of multiple sclerosis (MS) in a study of European populations.

The researchers used patients’ levels of 25-hydroxyvitamin D (25OHD) to determine genetically reduced vitamin D levels. They conducted a Mendelian randomization study “to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study,” which comprised 14,498 MS patients and 24,091 healthy controls.

“Each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a twofold increase in the odds of MS (95% confidence interval; 1.7-2.5; P = 7.7 X 10^-12; I² = 63%, 95% CI: 0-88%),” according to Dr. J. Brent Richards of McGill University, Montreal, and his colleagues. This provided “strong evidence” that vitamin D played “a causal role” in the patients’ susceptibility to MS.

“Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials,” the researchers wrote.

Read the full study in PLOS Medicine (doi:10.1371/journal.pmed.1001866).

klennon@frontlinemedcom.com