Central and Peripheral Nervous System Changes as Markers of Disease Progression in Multiple Sclerosis
This project aims to investigate neurodegeneration and demyelination in the central (CNS) and peripheral nervous system (PNS) in multiple sclerosis (MS). Furthermore, links to disease progression and mechanisms that can explain different responses to Fampridine treatment in MS patients with walking disability will be investigated.
Participants will undergo MRI, blood samples, neurophysiologic examinations and functional testing in order to evaluate response to treatment with Fampridine and the evaluation of disease progression markers.
This study will add to the understanding of neurodegeneration and demyelination in CNS and PNS in patients with MS having walking disability. This will impact clinical decision-making by improving organization of immunomodulatory treatment, identifying biomarkers thus facilitating earlier treatment and improving patient control, information and education.
Walking impairment is one of the most common symptoms of MS and has been reported as one of the most impactful symptoms on quality of life. MS patients with walking impairments receive the potassium-channel blocker, Fampridine, if they respond to this treatment. It has been established that approximately 35% of MS patients with walking disabilities are responders to this treatment, and thus have improvements in their walking speed and acceleration. The response status is established using the functional test T25FW. Antibodies affecting the PNS and thus aggravating walking abilities have been studied, but their links to MS remain to be investigated.
MS patients undergo neurodegeneration in the CNS with progressive neurological disability associated with axonal and neuronal damage, which is a major contributor to walking impairment. The involvement of the PNS in the dysfunction of the lower extremities as well as the role of the PNS as a potential marker of disease progression in MS remains to be fully elucidated. The effect of Fampridine in relation to the PNS has also not been examined and the mechanism behind non-response to Fampridine treatment and conversion from response to non-response remains to be elucidated.
Description of the cohort
Participants in this cohort will be recruited from the four Multiple Sclerosis Centers in the Region of Southern Denmark (Sønderborg, Odense, Kolding and Esbjerg), which (as of January 2016) have approximately 3600 patients with MS. At least 82 patients with MS are expected to be enrolled.
Participants, who are classified as responders to Fampridine treatment, have already been identified in the MS-centers in the Region of Southern Denmark, where they undergo outpatient treatment and clinical controls.
Data and biological material
- Imaging (Magnetic Resonance Imaging of the Brain)
- Biological Material (Blood)
- Neurophysiologic examinations (Motor Evoked Potential and Electroneuronography)
- Questionnaire (Twelve Item MS Walking Scale and Guy's Neurological Disability Scale)
- Functional testing (Timed 25-Foot Walk Test, The Six Spot Step Test, 5 Times Sit to Stand Test, 9-Hole Peg Test, Symbol Digit Modalities Test)
Collaborating researchers and departments
University of Southern Denmark and Sydjysk Skleroseklinik (Sønderborg, Esbjerg, Vejle), Department of Neurology, Sønderborg Hospital
Department of Neurology, Odense University Hospital, Skleroseklinikken and Institute of Regional Health Science Research, University of Southern Denmark
- Consultant Henrik Boye Jensen, PhD
Department of Public Health, and Section of Sport Science, Aarhus University
- Associate Professor Ulrik Dalgas, PhD
Institute of Molecular Medicine/Neurobiology Research, University of Southern Denmark
- Associate Professor Åsa Fex Svenningsen
Department of Neurology, Odense University Hospital
- Leading consultant Mads Ravnborg
Department of Neurology, Sygehus Sønderjylland
Department of Radiology, Sygehus Sønderjylland
Neurological Research Unit, Aabenraa
- Statistician Anders Bo Bojesen