A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis – An explorative study

Mamoei, Sepehr; Jensen, Henrik Boye; Dalgas, Ulrik; Zijdewind, Inge; Pedersen, Andreas Kristian; Nygaard, Mikkel; Eskildsen, Simon Fristed

doi:10.1016/j.jocn.2020.10.034

Cited by 6 publications

(5 citation statements)

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“…Another limitation is related to the long acquisition time, which was the main reason for examining the right sciatic nerve only in this pilot study; a common approach in electrophysiological studies in MS is to examine both sides as a reflection of the global affection of the motor pathways (32)(33)(34). However, multi-modal investigations to extract biophysically meaningful imaging biomarkers related to PNS damage are likely to involve even longer acquisitions and this will need to be accounted for in future study designs.…”

Section: Limitationsmentioning

confidence: 99%

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

et al. 2021

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Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms.Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS.Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS.Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS.Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted.

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Section: Limitationsmentioning

confidence: 99%

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

et al. 2021

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“…Motor evoked potential signals to the VM and TA muscles were facilitated by asking the participants to do a slight voluntary knee extension and dorsiflexion of the ankle, respectively. Electroneuronography (ENG) of the peroneal and tibial nerves was performed using a bipolar surface electrode with pulse durations of 0.1 ms. Electrode placements and distances to the stimulation sites were undertaken using a ruler to ensure reproducibility with the methods applied in the baseline study ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

“…Consequently, the main objectives of this explorative study were to identify if biomarkers, evaluated in a cross-sectional study by Mamoei et al ( 21 ), would remain stable at 1-year follow-up in PwMS with walking impairments, who already were established as responders and non-responders to Fampridine treatment. These biomarkers are applied in the evaluation of disability measures, physical and cognitive performance, neurophysiology, and brain MRI.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03401307.

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“…in persons with MS, yet the pattern of results was heterogenous. Several studies reported no significant associations among neuroimaging and mobility outcomes [23,37,49,61], while some studies reported concurrent associations among specific neuroimaging and mobility outcomes along with no associations among other neuroimaging and mobility outcomes [35,38,39,45,46,[50][51][52]54], as well as cases wherein separate studies reported opposing results [23,24]. Further, there was minimal replication of results such that multiple studies reported different findings using different methodological approaches.…”

Section: Roi: Hippocampusmentioning

confidence: 99%

Neuroimaging Technology in Exercise Neurorehabilitation Research in Persons with MS: A Scoping Review

Sandroff

Rafizadeh

Motl

2023

Sensors

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There is increasing interest in the application of neuroimaging technology in exercise neurorehabilitation research among persons with multiple sclerosis (MS). The inclusion and focus on neuroimaging outcomes in MS exercise training research is critical for establishing a biological basis for improvements in functioning and elevating exercise within the neurologist’s clinical armamentarium alongside disease modifying therapies as an approach for treating the disease and its consequences. Indeed, the inclusion of selective neuroimaging approaches and sensor-based technology among physical activity, mobility, and balance outcomes in such MS research might further allow for detecting specific links between the brain and real-world behavior. This paper provided a scoping review on the application of neuroimaging in exercise training research among persons with MS based on searches conducted in PubMed, Web of Science, and Scopus. We identified 60 studies on neuroimaging-technology-based (primarily MRI, which involved a variety of sequences and approaches) correlates of functions, based on multiple sensor-based measures, which are typically targets for exercise training trials in MS. We further identified 12 randomized controlled trials of exercise training effects on neuroimaging outcomes in MS. Overall, there was a large degree of heterogeneity whereby we could not identify definitive conclusions regarding a consistent neuroimaging biomarker of MS-related dysfunction or singular sensor-based measure, or consistent neural adaptation for exercise training in MS. Nevertheless, the present review provides a first step for better linking correlational and randomized controlled trial research for the development of high-quality exercise training studies on the brain in persons with MS, and this is timely given the substantial interest in exercise as a potential disease-modifying and/or neuroplasticity-inducing behavior in this population.

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A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis – An explorative study

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Cited by 6 publications

References 48 publications

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

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

Neuroimaging Technology in Exercise Neurorehabilitation Research in Persons with MS: A Scoping Review

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