ICYMI Multiple Sclerosis

In patients with multiple sclerosis (MS), disease progression and disability endpoints can be predicted by time to secondary progression, according to a 50-year follow up of an incidence cohort of 254 MS patients.

The study followed 212 adults with initial relapsing-remitting MS and 42 patients with a monophasic disease course and found:

• Median time to secondary progression was 15 years.

• Median times to Expanded Disability Status Scale 6 (EDSS6) and EDSS7 were 26 and 48 years, respectively.

• The cumulative risk of reaching EDSS6 was 50% at 55 years and 80% at 80 years.

• Age at onset predicted the disease course in men, with a 3 to 6% yearly increase in the risk of reaching disability milestones.

Citation: Tedeholm H, Skoog B, Lisovskaja V, Runmarker B, Nerman O, Andersen O. The outcome spectrum of multiple sclerosis: disability, mortality, and a cluster of predictors from onset. J Neurol. 2015;262(5):1148-1163. doi: 10.1007/s00415-015-7674-y.  

Commentary: Long-term cohort information related to disability outcome and natural history of disease can provide long-term milestones to judge therapy efficacy. MS is a chronic disease with expensive therapies and increasing disability over time. A reliance on short-term studies, relapse rates, and physical examination remains a recipe for economic disaster.  A cumulative risk of half of all patients reaching EDSS6 at age 55 is sobering and reflects the fact that therapy initiation at diagnosis, long-term treatment, and maintaining effective interventions to prevent accumulation of disability are key. Perhaps the long-term benchmark of disease stability with therapy intervention might justify early expenditure. More objective information is needed about disability milestones and reliable predictors of disease change at critical times to justify therapy efficacy for prevention of long-term disability.  A sobering fact that remains is that this disease, despite a greater appearance of benign cases, can still be severe in the long term for many people. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

In patients with multiple sclerosis (MS), disease progression and disability endpoints can be predicted by time to secondary progression, according to a 50-year follow up of an incidence cohort of 254 MS patients.

The study followed 212 adults with initial relapsing-remitting MS and 42 patients with a monophasic disease course and found:

• Median time to secondary progression was 15 years.

• Median times to Expanded Disability Status Scale 6 (EDSS6) and EDSS7 were 26 and 48 years, respectively.

• The cumulative risk of reaching EDSS6 was 50% at 55 years and 80% at 80 years.

• Age at onset predicted the disease course in men, with a 3 to 6% yearly increase in the risk of reaching disability milestones.

Citation: Tedeholm H, Skoog B, Lisovskaja V, Runmarker B, Nerman O, Andersen O. The outcome spectrum of multiple sclerosis: disability, mortality, and a cluster of predictors from onset. J Neurol. 2015;262(5):1148-1163. doi: 10.1007/s00415-015-7674-y.  

Commentary: Long-term cohort information related to disability outcome and natural history of disease can provide long-term milestones to judge therapy efficacy. MS is a chronic disease with expensive therapies and increasing disability over time. A reliance on short-term studies, relapse rates, and physical examination remains a recipe for economic disaster.  A cumulative risk of half of all patients reaching EDSS6 at age 55 is sobering and reflects the fact that therapy initiation at diagnosis, long-term treatment, and maintaining effective interventions to prevent accumulation of disability are key. Perhaps the long-term benchmark of disease stability with therapy intervention might justify early expenditure. More objective information is needed about disability milestones and reliable predictors of disease change at critical times to justify therapy efficacy for prevention of long-term disability.  A sobering fact that remains is that this disease, despite a greater appearance of benign cases, can still be severe in the long term for many people. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

In patients with multiple sclerosis (MS), disease progression and disability endpoints can be predicted by time to secondary progression, according to a 50-year follow up of an incidence cohort of 254 MS patients.

The study followed 212 adults with initial relapsing-remitting MS and 42 patients with a monophasic disease course and found:

• Median time to secondary progression was 15 years.

• Median times to Expanded Disability Status Scale 6 (EDSS6) and EDSS7 were 26 and 48 years, respectively.

• The cumulative risk of reaching EDSS6 was 50% at 55 years and 80% at 80 years.

• Age at onset predicted the disease course in men, with a 3 to 6% yearly increase in the risk of reaching disability milestones.

Citation: Tedeholm H, Skoog B, Lisovskaja V, Runmarker B, Nerman O, Andersen O. The outcome spectrum of multiple sclerosis: disability, mortality, and a cluster of predictors from onset. J Neurol. 2015;262(5):1148-1163. doi: 10.1007/s00415-015-7674-y.  

Commentary: Long-term cohort information related to disability outcome and natural history of disease can provide long-term milestones to judge therapy efficacy. MS is a chronic disease with expensive therapies and increasing disability over time. A reliance on short-term studies, relapse rates, and physical examination remains a recipe for economic disaster.  A cumulative risk of half of all patients reaching EDSS6 at age 55 is sobering and reflects the fact that therapy initiation at diagnosis, long-term treatment, and maintaining effective interventions to prevent accumulation of disability are key. Perhaps the long-term benchmark of disease stability with therapy intervention might justify early expenditure. More objective information is needed about disability milestones and reliable predictors of disease change at critical times to justify therapy efficacy for prevention of long-term disability.  A sobering fact that remains is that this disease, despite a greater appearance of benign cases, can still be severe in the long term for many people. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

Patients with multiple sclerosis are at increased risk of depression and anxiety diagnoses as well as antidepressant and anxiolytic drug use both before and after diagnosis, according to a matched cohort study of 5,084 patients and 24,771 controls from a nationwide sample.

Researchers used logistic regression to estimate odds ratios for pre- and post-MS diagnosis rates of depression and anxiety, and redemption of prescriptions for tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). They found:

Citation: Hoang H, Laursen B, Stenager EN, Stenager E. Psychiatric co-morbidity in multiple sclerosis: the risk of depression and anxiety before and after MS diagnosis. Mult Scler. 2015. pii:1352458515588973. [Epub ahead of print]

Patients with multiple sclerosis are at increased risk of depression and anxiety diagnoses as well as antidepressant and anxiolytic drug use both before and after diagnosis, according to a matched cohort study of 5,084 patients and 24,771 controls from a nationwide sample.

Researchers used logistic regression to estimate odds ratios for pre- and post-MS diagnosis rates of depression and anxiety, and redemption of prescriptions for tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). They found:

Citation: Hoang H, Laursen B, Stenager EN, Stenager E. Psychiatric co-morbidity in multiple sclerosis: the risk of depression and anxiety before and after MS diagnosis. Mult Scler. 2015. pii:1352458515588973. [Epub ahead of print]

Patients with multiple sclerosis are at increased risk of depression and anxiety diagnoses as well as antidepressant and anxiolytic drug use both before and after diagnosis, according to a matched cohort study of 5,084 patients and 24,771 controls from a nationwide sample.

Researchers used logistic regression to estimate odds ratios for pre- and post-MS diagnosis rates of depression and anxiety, and redemption of prescriptions for tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). They found:

Citation: Hoang H, Laursen B, Stenager EN, Stenager E. Psychiatric co-morbidity in multiple sclerosis: the risk of depression and anxiety before and after MS diagnosis. Mult Scler. 2015. pii:1352458515588973. [Epub ahead of print]

A younger age at diagnosis of pediatric-onset multiple sclerosis (POMS) is associated with a greater impairment in information processing speeds in adulthood, compared with those with adult onset MS (AOMS), according to data from the comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study.

Investigators compared 51 POMS and 550 AOMS patients’ scores on Multiple Sclerosis Quality of Life-54 (MSQOL54), Modified Fatigue Impact Scale (MFIS), Center for Epidemiologic Studies Depression Scale (CES-D), and Symbol Digit Modalities Test (SDMT), and found:

• SDMT scores were significantly lower in POMS after adjusting for age, but not after adjusting for disease duration.

• Estimated group difference showed lower normative z scores in POMS than AOMS in unadjusted analysis and after adjusting for disease duration.

• No significant differences in health-related quality-of-life, fatigue, depression, or social support between POMS and AOMS measures.

Citation: Baruch NF, O'Donnell EH, Glanz BI, et al. Cognitive and patient-reported outcomes in adults with pediatric-onset multiple sclerosis. Mult Scler. 2015. pii: 1352458515588781. [Epub ahead of print]

A younger age at diagnosis of pediatric-onset multiple sclerosis (POMS) is associated with a greater impairment in information processing speeds in adulthood, compared with those with adult onset MS (AOMS), according to data from the comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study.

Investigators compared 51 POMS and 550 AOMS patients’ scores on Multiple Sclerosis Quality of Life-54 (MSQOL54), Modified Fatigue Impact Scale (MFIS), Center for Epidemiologic Studies Depression Scale (CES-D), and Symbol Digit Modalities Test (SDMT), and found:

• SDMT scores were significantly lower in POMS after adjusting for age, but not after adjusting for disease duration.

• Estimated group difference showed lower normative z scores in POMS than AOMS in unadjusted analysis and after adjusting for disease duration.

• No significant differences in health-related quality-of-life, fatigue, depression, or social support between POMS and AOMS measures.

Citation: Baruch NF, O'Donnell EH, Glanz BI, et al. Cognitive and patient-reported outcomes in adults with pediatric-onset multiple sclerosis. Mult Scler. 2015. pii: 1352458515588781. [Epub ahead of print]

A younger age at diagnosis of pediatric-onset multiple sclerosis (POMS) is associated with a greater impairment in information processing speeds in adulthood, compared with those with adult onset MS (AOMS), according to data from the comprehensive Longitudinal Investigations in MS at Brigham and Women’s Hospital (CLIMB) study.

Investigators compared 51 POMS and 550 AOMS patients’ scores on Multiple Sclerosis Quality of Life-54 (MSQOL54), Modified Fatigue Impact Scale (MFIS), Center for Epidemiologic Studies Depression Scale (CES-D), and Symbol Digit Modalities Test (SDMT), and found:

• SDMT scores were significantly lower in POMS after adjusting for age, but not after adjusting for disease duration.

• Estimated group difference showed lower normative z scores in POMS than AOMS in unadjusted analysis and after adjusting for disease duration.

• No significant differences in health-related quality-of-life, fatigue, depression, or social support between POMS and AOMS measures.

Citation: Baruch NF, O'Donnell EH, Glanz BI, et al. Cognitive and patient-reported outcomes in adults with pediatric-onset multiple sclerosis. Mult Scler. 2015. pii: 1352458515588781. [Epub ahead of print]

A heavier weight in adolescence is associated with a multiple sclerosis diagnosis at a younger age, according to subgroup cohort of 184 women who provided weight and height information from the age of first menstruation and at age 25.

Investigators calculated BMI and used regression analyses to investigate an association, and found having a higher weight at menarche, weight at age 25, and BMI at age 25 were each significantly related to younger mean age at symptom onset by an average of 5 years:

• overweight: 26.9 years old

• not overweight: 32.1 years old

Citation:  Kavak KS, Teter BE, Hagemeier J, Zakalik K, Weinstock-Guttman B; New York State Multiple Sclerosis Consortium. Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset. Mult Scler. 2015;21(7):858-865. doi:10.1177/1352458514555787.

A heavier weight in adolescence is associated with a multiple sclerosis diagnosis at a younger age, according to subgroup cohort of 184 women who provided weight and height information from the age of first menstruation and at age 25.

Investigators calculated BMI and used regression analyses to investigate an association, and found having a higher weight at menarche, weight at age 25, and BMI at age 25 were each significantly related to younger mean age at symptom onset by an average of 5 years:

• overweight: 26.9 years old

• not overweight: 32.1 years old

Citation:  Kavak KS, Teter BE, Hagemeier J, Zakalik K, Weinstock-Guttman B; New York State Multiple Sclerosis Consortium. Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset. Mult Scler. 2015;21(7):858-865. doi:10.1177/1352458514555787.

A heavier weight in adolescence is associated with a multiple sclerosis diagnosis at a younger age, according to subgroup cohort of 184 women who provided weight and height information from the age of first menstruation and at age 25.

Investigators calculated BMI and used regression analyses to investigate an association, and found having a higher weight at menarche, weight at age 25, and BMI at age 25 were each significantly related to younger mean age at symptom onset by an average of 5 years:

• overweight: 26.9 years old

• not overweight: 32.1 years old

Citation:  Kavak KS, Teter BE, Hagemeier J, Zakalik K, Weinstock-Guttman B; New York State Multiple Sclerosis Consortium. Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset. Mult Scler. 2015;21(7):858-865. doi:10.1177/1352458514555787.

Cervical cord atrophy occurs in clinical isolated syndrome (CIS) as well as more progressive forms of multiple sclerosis (MS), a study of 267 patients with CIS or relapsing-remitting MS (RRMS) and 64 healthy controls reports.

Investigators used structural brain magnetic resonance imaging (MRI) to determine upper cervical cord cross-sectional area (UCCA) at the level of C2/C3 and adjusted for focal MS lesions. They found:

• UCCA was significantly reduced in CIS patients compared to healthy controls.

• Structural variability was higher in patients than in controls, particularly in the case of focal lesions.

• UCCA and the coefficient of variation (CV) were associated with Expanded Disability Status Scale (EDDS) sores and disease duration.

• CV was also associated with hand and arm function.

Citation: Biberacher V, Boucard CC, Schmidt P, et al. Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult Scler. 2015;21(7):875-884. doi:10.1177/1352458514546514.  

Cervical cord atrophy occurs in clinical isolated syndrome (CIS) as well as more progressive forms of multiple sclerosis (MS), a study of 267 patients with CIS or relapsing-remitting MS (RRMS) and 64 healthy controls reports.

Investigators used structural brain magnetic resonance imaging (MRI) to determine upper cervical cord cross-sectional area (UCCA) at the level of C2/C3 and adjusted for focal MS lesions. They found:

• UCCA was significantly reduced in CIS patients compared to healthy controls.

• Structural variability was higher in patients than in controls, particularly in the case of focal lesions.

• UCCA and the coefficient of variation (CV) were associated with Expanded Disability Status Scale (EDDS) sores and disease duration.

• CV was also associated with hand and arm function.

Citation: Biberacher V, Boucard CC, Schmidt P, et al. Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult Scler. 2015;21(7):875-884. doi:10.1177/1352458514546514.  

Cervical cord atrophy occurs in clinical isolated syndrome (CIS) as well as more progressive forms of multiple sclerosis (MS), a study of 267 patients with CIS or relapsing-remitting MS (RRMS) and 64 healthy controls reports.

Investigators used structural brain magnetic resonance imaging (MRI) to determine upper cervical cord cross-sectional area (UCCA) at the level of C2/C3 and adjusted for focal MS lesions. They found:

• UCCA was significantly reduced in CIS patients compared to healthy controls.

• Structural variability was higher in patients than in controls, particularly in the case of focal lesions.

• UCCA and the coefficient of variation (CV) were associated with Expanded Disability Status Scale (EDDS) sores and disease duration.

• CV was also associated with hand and arm function.

Citation: Biberacher V, Boucard CC, Schmidt P, et al. Atrophy and structural variability of the upper cervical cord in early multiple sclerosis. Mult Scler. 2015;21(7):875-884. doi:10.1177/1352458514546514.  

Life expectancy in patients with multiple sclerosis (MS) is approximately 7.5 years shorter than those without MS and comorbidities increase the risk of mortality, according to a population-based study of 5,797 people with MS and 28,807 age- and sex-matched controls.

Investigators used Cox proportional hazards regression to evaluate the association between comorbidity status and mortality and found:

• Median lifespan among MS patients is 75.9 years, compared with 83.4 years in the control group.

• MS was associated with a 2-fold increased risk of mortality.

• Diabetes, ischemic heart disease, and chronic lung disease increased death hazards in both populations, however, the association was lower in the MS group.

• Mortality rates from infectious and respiratory diseases were higher in the MS group.

• The most common cause of death in the MS group was nervous- or circulatory-system diseases.

Citation: Marrie RA, Elliott L, Marriott J, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015. pii:10.1212/WNL.0000000000001718.

Commentary: Multiple Sclerosis is considered a disease of the young. However, the young grow older and accumulate the burdens of living with other illness as well. Having one chronic disease does not prevent you from having another chronic illness and experiencing problems related to both. The more illnesses you accumulate, the harder it becomes to live life without disability and to live a long life. As much as we consider MS a disease that does not shorten life expectancy, that is simply not the case. Those with MS can experience a shorter lifespan and the concurrent complications related to infection and the illness itself clearly can result in a shortened lifespan. This article should reinforce the need and make us double our efforts to diagnose and treat MS early as well as effectively to prevent the long term premature morbidity and mortality of ineffectively and untreated MS. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

Life expectancy in patients with multiple sclerosis (MS) is approximately 7.5 years shorter than those without MS and comorbidities increase the risk of mortality, according to a population-based study of 5,797 people with MS and 28,807 age- and sex-matched controls.

Investigators used Cox proportional hazards regression to evaluate the association between comorbidity status and mortality and found:

• Median lifespan among MS patients is 75.9 years, compared with 83.4 years in the control group.

• MS was associated with a 2-fold increased risk of mortality.

• Diabetes, ischemic heart disease, and chronic lung disease increased death hazards in both populations, however, the association was lower in the MS group.

• Mortality rates from infectious and respiratory diseases were higher in the MS group.

• The most common cause of death in the MS group was nervous- or circulatory-system diseases.

Citation: Marrie RA, Elliott L, Marriott J, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015. pii:10.1212/WNL.0000000000001718.

Commentary: Multiple Sclerosis is considered a disease of the young. However, the young grow older and accumulate the burdens of living with other illness as well. Having one chronic disease does not prevent you from having another chronic illness and experiencing problems related to both. The more illnesses you accumulate, the harder it becomes to live life without disability and to live a long life. As much as we consider MS a disease that does not shorten life expectancy, that is simply not the case. Those with MS can experience a shorter lifespan and the concurrent complications related to infection and the illness itself clearly can result in a shortened lifespan. This article should reinforce the need and make us double our efforts to diagnose and treat MS early as well as effectively to prevent the long term premature morbidity and mortality of ineffectively and untreated MS. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

Life expectancy in patients with multiple sclerosis (MS) is approximately 7.5 years shorter than those without MS and comorbidities increase the risk of mortality, according to a population-based study of 5,797 people with MS and 28,807 age- and sex-matched controls.

Investigators used Cox proportional hazards regression to evaluate the association between comorbidity status and mortality and found:

• Median lifespan among MS patients is 75.9 years, compared with 83.4 years in the control group.

• MS was associated with a 2-fold increased risk of mortality.

• Diabetes, ischemic heart disease, and chronic lung disease increased death hazards in both populations, however, the association was lower in the MS group.

• Mortality rates from infectious and respiratory diseases were higher in the MS group.

• The most common cause of death in the MS group was nervous- or circulatory-system diseases.

Citation: Marrie RA, Elliott L, Marriott J, et al. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015. pii:10.1212/WNL.0000000000001718.

Commentary: Multiple Sclerosis is considered a disease of the young. However, the young grow older and accumulate the burdens of living with other illness as well. Having one chronic disease does not prevent you from having another chronic illness and experiencing problems related to both. The more illnesses you accumulate, the harder it becomes to live life without disability and to live a long life. As much as we consider MS a disease that does not shorten life expectancy, that is simply not the case. Those with MS can experience a shorter lifespan and the concurrent complications related to infection and the illness itself clearly can result in a shortened lifespan. This article should reinforce the need and make us double our efforts to diagnose and treat MS early as well as effectively to prevent the long term premature morbidity and mortality of ineffectively and untreated MS. — Mark Gudesblatt, MD, Medical Director of the Comprehensive MS Care Center at South Shore Neurologic Associates in Islip, NY 

A genetic variant may hinder the effectiveness of interferon-β (IFNβ) in some patients with multiple sclerosis (MS), a genome-wide association study reports.

Researchers found an association between rs9828519, an intronic variant in SLC9A9, and patients with relapsing forms of MS who do not respond to IFNβ treatment. This discovery was then validated in a meta-analysis of 3 independent cohorts.

The study authors suggest the genetic marker can be used as a successful pharmacogenetic screen, creating a more personalized approach to MS treatment.

Citation: Esposito F, Sorosina M, Ottoboni L, et al. A pharmacogenetic study implicates SLC9a9 in multiple sclerosis disease activity. Ann Neurol. 2015. doi:10.1002/ana.24429.

A genetic variant may hinder the effectiveness of interferon-β (IFNβ) in some patients with multiple sclerosis (MS), a genome-wide association study reports.

Researchers found an association between rs9828519, an intronic variant in SLC9A9, and patients with relapsing forms of MS who do not respond to IFNβ treatment. This discovery was then validated in a meta-analysis of 3 independent cohorts.

The study authors suggest the genetic marker can be used as a successful pharmacogenetic screen, creating a more personalized approach to MS treatment.

Citation: Esposito F, Sorosina M, Ottoboni L, et al. A pharmacogenetic study implicates SLC9a9 in multiple sclerosis disease activity. Ann Neurol. 2015. doi:10.1002/ana.24429.

A genetic variant may hinder the effectiveness of interferon-β (IFNβ) in some patients with multiple sclerosis (MS), a genome-wide association study reports.

Researchers found an association between rs9828519, an intronic variant in SLC9A9, and patients with relapsing forms of MS who do not respond to IFNβ treatment. This discovery was then validated in a meta-analysis of 3 independent cohorts.

The study authors suggest the genetic marker can be used as a successful pharmacogenetic screen, creating a more personalized approach to MS treatment.

Citation: Esposito F, Sorosina M, Ottoboni L, et al. A pharmacogenetic study implicates SLC9a9 in multiple sclerosis disease activity. Ann Neurol. 2015. doi:10.1002/ana.24429.