4.6 Article

Clinical, Neurophysiological, and MRI Markers of Fampridine Responsiveness in Multiple Sclerosis-An Explorative Study

Journal

FRONTIERS IN NEUROLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fneur.2021.758710

Keywords

multiple sclerosis; performance test; magnetic resonance imaging; neurodegeneration; demyelination; neurophysiology

Funding

  1. Region of Southern Denmark
  2. University of Southern Denmark
  3. University Hospital of Southern Jutland
  4. Knud and Edith Eriksens Mindefond
  5. charity-event of Rotary Denmark Night of a 1000 drawings in Esbjerg

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In a 1-year longitudinal study, responders and non-responders to Fampridine treatment among persons with multiple sclerosis were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and MRI outcomes. Non-responders were found to have prolonged peripheral motor conduction times compared to responders. The study also showed associations between certain tests and measurements, such as the six spot step test with central motor conduction times and the symbol digit modalities test with T2-weighted lesion characteristics.
Objective: Persons with multiple sclerosis (PwMS), already established as responders or non-responders to Fampridine treatment, were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and magnetic resonance imaging (MRI) outcomes in a 1-year explorative longitudinal study. Materials and Methods: Data from a 1-year longitudinal study were analyzed. Examinations consisted of the timed 25-foot walk test (T25FW), six spot step test (SSST), nine-hole peg test (9-HPT), five times sit-to-stand test (5-STS), symbol digit modalities test (SDMT), transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) examining central motor conduction times (CMCT), peripheral motor conduction times (PMCT) and their amplitudes, electroneuronography (ENG) of the lower extremities, and brain structural MRI measures. Results: Forty-one responders and eight non-responders to Fampridine treatment were examined. There were no intergroup differences except for the PMCT, where non-responders had prolonged conduction times compared to responders to Fampridine. Six spot step test was associated with CMCT throughout the study. After 1 year, CMCT was further prolonged and cortical MEP amplitudes decreased in both groups, while PMCT and ENG did not change. Throughout the study, CMCT was associated with the expanded disability status scale (EDSS) and 12-item multiple sclerosis walking scale (MSWS-12), while SDMT was associated with number of T2-weighted lesions, lesion load, and lesion load normalized to brain volume. Conclusions: Peripheral motor conduction time is prolonged in non-responders to Fampridine when compared to responders. Transcranial magnetic stimulation-elicited MEPs and SDMT can be used as markers of disability progression and lesion activity visualized by MRI, respectively.

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