Neurophysiological impairments in multiple sclerosis—Central and peripheral motor pathways

Abstract

A systematic review of the literature was conducted comparing neurophysiological outcomes in persons with multiple sclerosis (PwMS) to healthy controls (HC), in studies of the central nervous system (CNS) function comprising motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) and in studies of the peripheral nervous system (PNS) function comprising electroneuronography (ENG) outcomes elicited by peripheral nerve stimulation. Studies comparing neuromuscular function, assessed during maximal voluntary contraction (MVC) of muscle, were included if they reported muscle strength along with muscle activation by use of electromyography (EMG) and/or interpolated twitch technique (ITT). Studies investigating CNS function showed prolonged central motor conduction times, asymmetry of nerve conduction motor pathways, and prolonged latencies in PwMS when compared to HC. Resting motor threshold, amplitude, and cortical silent periods showed conflicting results. CNS findings generally correlated with disabilities. Studies of PNS function showed near significant prolongation in motor latency of the median nerve, reduced nerve conduction velocities in the tibial and peroneal nerves, and decreased compound muscle action potential amplitudes of the tibial nerve in PwMS. ENG findings did not correlate with clinical severity of disabilities. Studies of neuromuscular function showed lower voluntary muscle activation and increased central fatigue in PwMS, whereas EMG showed divergent muscle activation (ie, EMG amplitude) during MVC. When comparing the existing literature on neurophysiological motor examinations in PwMS and HC, consistent and substantial impairments of CNS function were seen in PwMS, whereas impairments of the PNS were less pronounced and inconsistent. In addition, impairments in muscle activation were observed in PwMS.

Distinguishing between Fatigue and Fatigability in Multiple Sclerosis

“…Although these studies have been able to characterize differences in motor function between people with MS and healthy controls, they typically fail to capture the substantial influence of the extra demands on the nervous system of persons with MS when performing prescribed tasks. 33,[117][118][119][120][121][122][123][124][125][126][127] Critically, the reduced capacity of the central nervous system in persons with MS to generate an adequate level of voluntary activation is significantly correlated with the self-reported level of fatigue. 71,121,128,129 One example of this effect is shown in Figure 3, which compares the increase in rating of perceived exertion (RPE) for 2 groups of participants during the intermittent fatiguing contractions shown in Figure 2.…”

“…33,[117][118][119][120][121][122][123][124][125][126][127] Critically, the reduced capacity of the central nervous system in persons with MS to generate an adequate level of voluntary activation is significantly correlated with the self-reported level of fatigue. 71,121,128,129 One example of this effect is shown in Figure 3, which compares the increase in rating of perceived exertion (RPE) for 2 groups of participants during the intermittent fatiguing contractions shown in Figure 2. Despite similar declines in MVC force immediately after the 60 intermittent contractions (MS: À16 ± 19 N•m; Control: À13 ± 16 N•m), we found that RPE scores increased more rapidly during the task for MS participants.…”

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

“…Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease affecting myelinated axons in the central nervous system (CNS) and it is the leading cause of nontraumatic disability in young adults (1). Demyelination impairs neural conduction (2)(3)(4)(5) leading to various motor, sensory, sphincter, visual, and cognitive symptoms among others (6).…”

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

“…[14] However, MRI estimates of brain volume, grey matter volume, white matter diffusion, and T2-weighted lesion volumes are over time correlated with clinical disabilities in PwMS. [15] When corticospinal tracts are affected by MS lesions, motor evoked potentials (MEPs) are highly capable of detecting and monitoring clinical and subclinical motor nerve conduction alterations, [16] especially in lower extremities. [17] Multimodal evoked potentials can predict future advancement of neurological disabilities in PwMS.…”

“…[17] However, the current knowledge about the use of MEP in determining MS disease course is limited. [16,18] Furthermore, electroneurographic (ENG) studies of the PNS in PwMS are few, variable in methodology, and inconclusive. [16,19] Taken together, no studies could be located examining PNS involvement in walking impaired PwMS and its relationship with Fampridine responsiveness, clinical disability measures, nerve conduction in central corticospinal pathways, and MRI outcomes, which was therefore the purpose of the present study.…”