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– Among patients with relapsing-remitting multiple sclerosis (MS), cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test, according to a retrospective analysis of data from a phase 3 trial. Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months, researchers reported at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York
Jake Remaly/MDedge News
Dr. Maria Petracca

Investigators have found that demyelination in MS tends to occur in the cerebellum, and cerebellar atrophy contributes to clinical impairment in patients with the disease. In addition, cerebellar volume loss over one year may predict disease worsening in patients with progressive MS, said Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York, and her research colleagues. Prior studies, however, had not tested in a large group of patients whether baseline cerebellar volume predicts disability in relapsing-remitting MS.

To examine this question, Dr. Petracca and her colleagues analyzed MRI data from 838 of 1,008 patients in the phase 3 CombiRx trial. Patients in the multicenter, randomized trial had relapsing-remitting MS and received immunomodulatory treatment with glatiramer acetate, interferon beta-1a, or both. The researchers used an MRI analysis package to measure whole brain and cerebellar T2 and gadolinium-enhancing lesions, and they used statistical parametric mapping to measure gray matter fraction and cerebellar volume. Expanded Disability Status Scale (EDSS) scores and scores on the Multiple Sclerosis Functional Composite (MSFC) and its subcomponents were assessed at baseline and 36 months. The investigators assessed changes in clinical scores using repeated measure analysis of variance. They examined the relationship between MRI metrics and clinical disability at baseline and follow-up using ordinal and hierarchical multiple linear regression analysis.


At baseline, patients had a mean age of 37.7, and 72% were female. Median EDSS score was 2, and average cerebellar gray matter volume was 109.78 mL.

A regression model that included T2 and gadolinium-enhancing lesion volume, supratentorial gray matter volume, and cerebellar gray matter volume explained about 15% of the variance in EDSS and MSFC scores at baseline. Cerebellar volume was a significant predictor of MSFC (beta = 0.188).

The 25-foot walk test was the only clinical score that significantly worsened during follow-up – from an average of 4.94 seconds at baseline to 5.09 seconds at follow-up. “Baseline cerebellar gray matter volume was the only MRI metric to significantly predict 25-foot walk test scores at follow-up (beta = –0.172),” the researchers reported. “These results suggest that cerebellar volume is an independent predictor of clinical disability in MS patients as measured by 25-foot walk test.”

The researchers had no disclosures.

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– Among patients with relapsing-remitting multiple sclerosis (MS), cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test, according to a retrospective analysis of data from a phase 3 trial. Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months, researchers reported at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York
Jake Remaly/MDedge News
Dr. Maria Petracca

Investigators have found that demyelination in MS tends to occur in the cerebellum, and cerebellar atrophy contributes to clinical impairment in patients with the disease. In addition, cerebellar volume loss over one year may predict disease worsening in patients with progressive MS, said Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York, and her research colleagues. Prior studies, however, had not tested in a large group of patients whether baseline cerebellar volume predicts disability in relapsing-remitting MS.

To examine this question, Dr. Petracca and her colleagues analyzed MRI data from 838 of 1,008 patients in the phase 3 CombiRx trial. Patients in the multicenter, randomized trial had relapsing-remitting MS and received immunomodulatory treatment with glatiramer acetate, interferon beta-1a, or both. The researchers used an MRI analysis package to measure whole brain and cerebellar T2 and gadolinium-enhancing lesions, and they used statistical parametric mapping to measure gray matter fraction and cerebellar volume. Expanded Disability Status Scale (EDSS) scores and scores on the Multiple Sclerosis Functional Composite (MSFC) and its subcomponents were assessed at baseline and 36 months. The investigators assessed changes in clinical scores using repeated measure analysis of variance. They examined the relationship between MRI metrics and clinical disability at baseline and follow-up using ordinal and hierarchical multiple linear regression analysis.


At baseline, patients had a mean age of 37.7, and 72% were female. Median EDSS score was 2, and average cerebellar gray matter volume was 109.78 mL.

A regression model that included T2 and gadolinium-enhancing lesion volume, supratentorial gray matter volume, and cerebellar gray matter volume explained about 15% of the variance in EDSS and MSFC scores at baseline. Cerebellar volume was a significant predictor of MSFC (beta = 0.188).

The 25-foot walk test was the only clinical score that significantly worsened during follow-up – from an average of 4.94 seconds at baseline to 5.09 seconds at follow-up. “Baseline cerebellar gray matter volume was the only MRI metric to significantly predict 25-foot walk test scores at follow-up (beta = –0.172),” the researchers reported. “These results suggest that cerebellar volume is an independent predictor of clinical disability in MS patients as measured by 25-foot walk test.”

The researchers had no disclosures.

– Among patients with relapsing-remitting multiple sclerosis (MS), cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test, according to a retrospective analysis of data from a phase 3 trial. Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months, researchers reported at ACTRIMS Forum 2019, the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York
Jake Remaly/MDedge News
Dr. Maria Petracca

Investigators have found that demyelination in MS tends to occur in the cerebellum, and cerebellar atrophy contributes to clinical impairment in patients with the disease. In addition, cerebellar volume loss over one year may predict disease worsening in patients with progressive MS, said Maria Petracca, MD, PhD, a postdoctoral fellow at Icahn School of Medicine at Mount Sinai, New York, and her research colleagues. Prior studies, however, had not tested in a large group of patients whether baseline cerebellar volume predicts disability in relapsing-remitting MS.

To examine this question, Dr. Petracca and her colleagues analyzed MRI data from 838 of 1,008 patients in the phase 3 CombiRx trial. Patients in the multicenter, randomized trial had relapsing-remitting MS and received immunomodulatory treatment with glatiramer acetate, interferon beta-1a, or both. The researchers used an MRI analysis package to measure whole brain and cerebellar T2 and gadolinium-enhancing lesions, and they used statistical parametric mapping to measure gray matter fraction and cerebellar volume. Expanded Disability Status Scale (EDSS) scores and scores on the Multiple Sclerosis Functional Composite (MSFC) and its subcomponents were assessed at baseline and 36 months. The investigators assessed changes in clinical scores using repeated measure analysis of variance. They examined the relationship between MRI metrics and clinical disability at baseline and follow-up using ordinal and hierarchical multiple linear regression analysis.


At baseline, patients had a mean age of 37.7, and 72% were female. Median EDSS score was 2, and average cerebellar gray matter volume was 109.78 mL.

A regression model that included T2 and gadolinium-enhancing lesion volume, supratentorial gray matter volume, and cerebellar gray matter volume explained about 15% of the variance in EDSS and MSFC scores at baseline. Cerebellar volume was a significant predictor of MSFC (beta = 0.188).

The 25-foot walk test was the only clinical score that significantly worsened during follow-up – from an average of 4.94 seconds at baseline to 5.09 seconds at follow-up. “Baseline cerebellar gray matter volume was the only MRI metric to significantly predict 25-foot walk test scores at follow-up (beta = –0.172),” the researchers reported. “These results suggest that cerebellar volume is an independent predictor of clinical disability in MS patients as measured by 25-foot walk test.”

The researchers had no disclosures.

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REPORTING FROM ACTRIMS FORUM 2019

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Publish date: April 1, 2019
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Key clinical point: In patients with relapsing-remitting MS, cerebellar volume may independently predict clinical disability as measured by the 25-foot walk test.

Major finding: Baseline cerebellar gray matter volume was the only MRI metric that significantly predicted 25-foot walk test results at 36 months (Beta = –0.172).

Study details: A retrospective analysis of MRI data from 838 patients in the phase 3 CombiRx trial.

Disclosures: The researchers had no disclosures.

Source: Petracca M et al. ACTRIMS Forum 2019, Abstract 160.

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