Multiple Sclerosis Hub

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.

In children with isolated optic neuritis, 3 independent biomarkers are strongly associated with progression to multiple sclerosis, according to a retrospective analysis of 357 children with the condition.

Investigators used multiple Cox proportional regressions to determine the following hazard ratios (HR):

• abnormal cranial magnetic resonance imaging (cMRI), 5.94

• the presence of cerebrosnial fluid immunoglobulin G oligoclonal bands (OCB), 3.69

• age, 1.08 per year of age

• cMRI and OCB positivity combined, 26.84

Neither sex nor laterality (unilateral or bilateral) were associated with an increased rate of disease progression to MS.

Citation: Heussinger N, Kontopantelis E, Gburek-Augustat J, et al; for GRACE-MS (German-speaking Research Alliance for ChildrEn with Multiple Sclerosis). Oligoclonal bands predict multiple sclerosis in children with optic neuritis. Ann Neurol. 2015. doi:10.1002/ana.24409.

In children with isolated optic neuritis, 3 independent biomarkers are strongly associated with progression to multiple sclerosis, according to a retrospective analysis of 357 children with the condition.

Investigators used multiple Cox proportional regressions to determine the following hazard ratios (HR):

• abnormal cranial magnetic resonance imaging (cMRI), 5.94

• the presence of cerebrosnial fluid immunoglobulin G oligoclonal bands (OCB), 3.69

• age, 1.08 per year of age

• cMRI and OCB positivity combined, 26.84

Neither sex nor laterality (unilateral or bilateral) were associated with an increased rate of disease progression to MS.

Citation: Heussinger N, Kontopantelis E, Gburek-Augustat J, et al; for GRACE-MS (German-speaking Research Alliance for ChildrEn with Multiple Sclerosis). Oligoclonal bands predict multiple sclerosis in children with optic neuritis. Ann Neurol. 2015. doi:10.1002/ana.24409.

In children with isolated optic neuritis, 3 independent biomarkers are strongly associated with progression to multiple sclerosis, according to a retrospective analysis of 357 children with the condition.

Investigators used multiple Cox proportional regressions to determine the following hazard ratios (HR):

• abnormal cranial magnetic resonance imaging (cMRI), 5.94

• the presence of cerebrosnial fluid immunoglobulin G oligoclonal bands (OCB), 3.69

• age, 1.08 per year of age

• cMRI and OCB positivity combined, 26.84

Neither sex nor laterality (unilateral or bilateral) were associated with an increased rate of disease progression to MS.

Citation: Heussinger N, Kontopantelis E, Gburek-Augustat J, et al; for GRACE-MS (German-speaking Research Alliance for ChildrEn with Multiple Sclerosis). Oligoclonal bands predict multiple sclerosis in children with optic neuritis. Ann Neurol. 2015. doi:10.1002/ana.24409.

Higher levels of education are associated with a decreased risk of multiple sclerosis (MS) independent of other established risk factors, according to the Environmental Factors in MS (EnvIMS) study. 

The case-control study of 953 MS patients and 1,717 healthy controls reported education level and history of exposure to putative environmental risk factors, including known risk factors of smoking, infective mononucleosis, vitamin D levels, and body size.

In comparison to the lowest level of education, higher levels of education was associated with a decreased MS risk odds ratio of 0.53, a risk that was only moderately reduced after adjusting for other risk factors. The study authors note this suggests factors linked to lower socioeconomic status aside from established risks may play a role in MS.

Citation: Bjørnevik K, Riise T, Cortese M, et al. Level of education and multiple sclerosis risk after adjustment for known risk factors: The EnvIMS study. Mult Scler. 2015. pii:1352458515579444.

Higher levels of education are associated with a decreased risk of multiple sclerosis (MS) independent of other established risk factors, according to the Environmental Factors in MS (EnvIMS) study. 

The case-control study of 953 MS patients and 1,717 healthy controls reported education level and history of exposure to putative environmental risk factors, including known risk factors of smoking, infective mononucleosis, vitamin D levels, and body size.

In comparison to the lowest level of education, higher levels of education was associated with a decreased MS risk odds ratio of 0.53, a risk that was only moderately reduced after adjusting for other risk factors. The study authors note this suggests factors linked to lower socioeconomic status aside from established risks may play a role in MS.

Citation: Bjørnevik K, Riise T, Cortese M, et al. Level of education and multiple sclerosis risk after adjustment for known risk factors: The EnvIMS study. Mult Scler. 2015. pii:1352458515579444.

Higher levels of education are associated with a decreased risk of multiple sclerosis (MS) independent of other established risk factors, according to the Environmental Factors in MS (EnvIMS) study. 

The case-control study of 953 MS patients and 1,717 healthy controls reported education level and history of exposure to putative environmental risk factors, including known risk factors of smoking, infective mononucleosis, vitamin D levels, and body size.

In comparison to the lowest level of education, higher levels of education was associated with a decreased MS risk odds ratio of 0.53, a risk that was only moderately reduced after adjusting for other risk factors. The study authors note this suggests factors linked to lower socioeconomic status aside from established risks may play a role in MS.

Citation: Bjørnevik K, Riise T, Cortese M, et al. Level of education and multiple sclerosis risk after adjustment for known risk factors: The EnvIMS study. Mult Scler. 2015. pii:1352458515579444.

Iron accumulation in the basal ganglia is more pronounced in the early phases of clinically isolated syndrome (CIS) and definite multiple sclerosis (MS), but short-term changes in iron concentration are not associated with disease activity or changes in disability, a longitudinal 3T MRI study of 144 patients reports.

Investigators followed patients both clinically and with 3T MRI for an average of 3 years and found:  

• Subcortical gray matter iron deposition was higher in MS than CIS at baseline.

• In CIS, R2* rates increased in the globus pallidus, putamen, and caudate nucleus, but decreased in the thalamus.

• In MS, R2* rates increased in the putamen, remained stable in the globus pallidus and caudate nucleus, and decreased in the thalamus.

Citation: Khalil M, Langkammer C, Pichler A, et al. Dynamics of brain iron levels in multiple sclerosis: A longitudinal 3T MRI study. Neurology. 2015. pii:10.1212/WNL.0000000000001679. [Epub ahead of print] 

Iron accumulation in the basal ganglia is more pronounced in the early phases of clinically isolated syndrome (CIS) and definite multiple sclerosis (MS), but short-term changes in iron concentration are not associated with disease activity or changes in disability, a longitudinal 3T MRI study of 144 patients reports.

Investigators followed patients both clinically and with 3T MRI for an average of 3 years and found:  

• Subcortical gray matter iron deposition was higher in MS than CIS at baseline.

• In CIS, R2* rates increased in the globus pallidus, putamen, and caudate nucleus, but decreased in the thalamus.

• In MS, R2* rates increased in the putamen, remained stable in the globus pallidus and caudate nucleus, and decreased in the thalamus.

Citation: Khalil M, Langkammer C, Pichler A, et al. Dynamics of brain iron levels in multiple sclerosis: A longitudinal 3T MRI study. Neurology. 2015. pii:10.1212/WNL.0000000000001679. [Epub ahead of print] 

Iron accumulation in the basal ganglia is more pronounced in the early phases of clinically isolated syndrome (CIS) and definite multiple sclerosis (MS), but short-term changes in iron concentration are not associated with disease activity or changes in disability, a longitudinal 3T MRI study of 144 patients reports.

Investigators followed patients both clinically and with 3T MRI for an average of 3 years and found:  

• Subcortical gray matter iron deposition was higher in MS than CIS at baseline.

• In CIS, R2* rates increased in the globus pallidus, putamen, and caudate nucleus, but decreased in the thalamus.

• In MS, R2* rates increased in the putamen, remained stable in the globus pallidus and caudate nucleus, and decreased in the thalamus.

Citation: Khalil M, Langkammer C, Pichler A, et al. Dynamics of brain iron levels in multiple sclerosis: A longitudinal 3T MRI study. Neurology. 2015. pii:10.1212/WNL.0000000000001679. [Epub ahead of print] 

INDIANAPOLIS—Compared with interferon β-1a, daclizumab high-yield process (DAC HYP) may provide greater improvement in the patient-centered outcomes of ambulation and cognition for patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2015 CMSC Annual Meeting.

The results come from a post hoc analysis of results from the DECIDE study. In that randomized, double-blind trial, Michael Kaufman, MD, a neurologist at Cole Neuroscience Center in Knoxville, Tennessee, and colleagues found that DAC HYP reduced clinical and radiographic disease activity in patients with relapsing-remitting MS, compared with interferon β-1a. The researchers incorporated changes in the MS Functional Composite (MSFC) and the Symbol Digit Modalities Test (SDMT) over 96 weeks as tertiary end points in the DECIDE trial to compare the effects of the two therapies on ambulation, hand and arm dexterity, and cognition.

Eligible participants were between ages 18 and 55 and had an Expanded Disability Status Scale (EDSS) score between 0 and 5. Patients were randomized to 150 mg of DAC HYP subcutaneously every four weeks or 30 mg of interferon β-1a once weekly. The study lasted for 144 weeks.

In all, 919 patients received DAC HYP, and 922 participants received interferon β-1a. Mean baseline EDSS was 2.48 for the DAC HYP group and 2.54 for the interferon β-1a group. Over 96 weeks, the median improvement from baseline in MSFC z score was 0.091 for patients receiving DAC HYP, compared with 0.055 for patients receiving interferon β-1a.

The most significant median z score change in an individual component of the MSFC was in the Nine-Hole Peg Test. This change was 0.063 for patients receiving DAC HYP and 0.017 for patients receiving interferon β-1a. Median z score change for the Timed 25-Foot Walk was 0.000 for the DAC HYP group and –0.017 for the interferon β-1a group. Median z score change for the Paced Auditory Serial Addition Test-3 was not different between groups at Week 96, but patients receiving DAC HYP showed earlier improvements in this measure. Mean change in SDMT from baseline over 96 weeks was 4.08 for the DAC HYP group, compared with 2.89 for the interferon β-1a group.

The data suggest that DAC HYP has beneficial effects for cognitive function, “which is extremely important to MS patients,” said Dr. Kaufman. The study “supports the idea that daclizumab may in the future have a place in the therapeutic armamentarium of MS,” he concluded.

—Erik Greb

INDIANAPOLIS—Compared with interferon β-1a, daclizumab high-yield process (DAC HYP) may provide greater improvement in the patient-centered outcomes of ambulation and cognition for patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2015 CMSC Annual Meeting.

The results come from a post hoc analysis of results from the DECIDE study. In that randomized, double-blind trial, Michael Kaufman, MD, a neurologist at Cole Neuroscience Center in Knoxville, Tennessee, and colleagues found that DAC HYP reduced clinical and radiographic disease activity in patients with relapsing-remitting MS, compared with interferon β-1a. The researchers incorporated changes in the MS Functional Composite (MSFC) and the Symbol Digit Modalities Test (SDMT) over 96 weeks as tertiary end points in the DECIDE trial to compare the effects of the two therapies on ambulation, hand and arm dexterity, and cognition.

Eligible participants were between ages 18 and 55 and had an Expanded Disability Status Scale (EDSS) score between 0 and 5. Patients were randomized to 150 mg of DAC HYP subcutaneously every four weeks or 30 mg of interferon β-1a once weekly. The study lasted for 144 weeks.

In all, 919 patients received DAC HYP, and 922 participants received interferon β-1a. Mean baseline EDSS was 2.48 for the DAC HYP group and 2.54 for the interferon β-1a group. Over 96 weeks, the median improvement from baseline in MSFC z score was 0.091 for patients receiving DAC HYP, compared with 0.055 for patients receiving interferon β-1a.

The most significant median z score change in an individual component of the MSFC was in the Nine-Hole Peg Test. This change was 0.063 for patients receiving DAC HYP and 0.017 for patients receiving interferon β-1a. Median z score change for the Timed 25-Foot Walk was 0.000 for the DAC HYP group and –0.017 for the interferon β-1a group. Median z score change for the Paced Auditory Serial Addition Test-3 was not different between groups at Week 96, but patients receiving DAC HYP showed earlier improvements in this measure. Mean change in SDMT from baseline over 96 weeks was 4.08 for the DAC HYP group, compared with 2.89 for the interferon β-1a group.

The data suggest that DAC HYP has beneficial effects for cognitive function, “which is extremely important to MS patients,” said Dr. Kaufman. The study “supports the idea that daclizumab may in the future have a place in the therapeutic armamentarium of MS,” he concluded.

—Erik Greb

INDIANAPOLIS—Compared with interferon β-1a, daclizumab high-yield process (DAC HYP) may provide greater improvement in the patient-centered outcomes of ambulation and cognition for patients with relapsing-remitting multiple sclerosis (MS), according to data presented at the 2015 CMSC Annual Meeting.

The results come from a post hoc analysis of results from the DECIDE study. In that randomized, double-blind trial, Michael Kaufman, MD, a neurologist at Cole Neuroscience Center in Knoxville, Tennessee, and colleagues found that DAC HYP reduced clinical and radiographic disease activity in patients with relapsing-remitting MS, compared with interferon β-1a. The researchers incorporated changes in the MS Functional Composite (MSFC) and the Symbol Digit Modalities Test (SDMT) over 96 weeks as tertiary end points in the DECIDE trial to compare the effects of the two therapies on ambulation, hand and arm dexterity, and cognition.

Eligible participants were between ages 18 and 55 and had an Expanded Disability Status Scale (EDSS) score between 0 and 5. Patients were randomized to 150 mg of DAC HYP subcutaneously every four weeks or 30 mg of interferon β-1a once weekly. The study lasted for 144 weeks.

In all, 919 patients received DAC HYP, and 922 participants received interferon β-1a. Mean baseline EDSS was 2.48 for the DAC HYP group and 2.54 for the interferon β-1a group. Over 96 weeks, the median improvement from baseline in MSFC z score was 0.091 for patients receiving DAC HYP, compared with 0.055 for patients receiving interferon β-1a.

The most significant median z score change in an individual component of the MSFC was in the Nine-Hole Peg Test. This change was 0.063 for patients receiving DAC HYP and 0.017 for patients receiving interferon β-1a. Median z score change for the Timed 25-Foot Walk was 0.000 for the DAC HYP group and –0.017 for the interferon β-1a group. Median z score change for the Paced Auditory Serial Addition Test-3 was not different between groups at Week 96, but patients receiving DAC HYP showed earlier improvements in this measure. Mean change in SDMT from baseline over 96 weeks was 4.08 for the DAC HYP group, compared with 2.89 for the interferon β-1a group.

The data suggest that DAC HYP has beneficial effects for cognitive function, “which is extremely important to MS patients,” said Dr. Kaufman. The study “supports the idea that daclizumab may in the future have a place in the therapeutic armamentarium of MS,” he concluded.

—Erik Greb