Utility of Transcranial Magnetic Simulation in Studying Upper Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis

Nimeshan Geevasinga,Mehdi Van Den Bos,Parvathi Menon,Steve Vucic

doi:10.3390/brainsci11070906

Nimeshan Geevasinga, Mehdi Van Den Bos + Show 2 more

Open Access

https://doi.org/10.3390/brainsci11070906

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Journal: Brain sciences	Publication Date: Jul 9, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Western Sydney University, University of Sydney

Abstract

Amyotrophic lateral sclerosis (ALS) is characterised by progressive dysfunction of the upper and lower motor neurons. The disease can evolve over time from focal limb or bulbar onset to involvement of other regions. There is some clinical heterogeneity in ALS with various phenotypes of the disease described, from primary lateral sclerosis, progressive muscular atrophy and flail arm/leg phenotypes. Whilst the majority of ALS patients are sporadic in nature, recent advances have highlighted genetic forms of the disease. Given the close relationship between ALS and frontotemporal dementia, the importance of cortical dysfunction has gained prominence. Transcranial magnetic stimulation (TMS) is a noninvasive neurophysiological tool to explore the function of the motor cortex and thereby cortical excitability. In this review, we highlight the utility of TMS and explore cortical excitability in ALS diagnosis, pathogenesis and insights gained from genetic and variant forms of the disease.

Highlights

Dysfunction in Amyotrophic LateralAmyotrophic lateral sclerosis is a progressive neurodegenerative disorder first described by Charcot [1,2]
A split-leg and a split-elbow phenomenon were reported as specific clinical features of Amyotrophic lateral sclerosis (ALS) and attributed to cortical dysfunction [68,69]
Cortical hyperexcitability is heralded by development of cortical disinhibition and increases in activity of cortical facilitatory circuits with evolution of the disease course

Summary

Introduction

Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder first described by Charcot [1,2]. The majority of ALS patients (65–75%) present with asymmetrical weakness, leading to wasting of the limb muscles, typically spreading along the neuroaxis and affecting contiguous motor neurons [7,8,9]. Cortical hyperexcitability appears to be an early feature of ALS, highlighting the importance of the UMN dysfunction in the disease process [2,12]. Cortical hyperexcitability is a unique and specific feature of ALS, differentiating the pathophysiological processes in ALS from other mimic disorders such as Kennedy’s disease, oculopharyngeal muscular dystrophy, multifocal motor neuropathy and spinal muscular atrophy [12,14]. Supporting the notion for the importance of UMN dysfunction in ALS, recent clinical, neurophysiological, radiological and genetic advances, have suggested the importance of cortical hyperexcitability in ALS pathogenesis. We highlight the utility of TMS in identifying cortical hyperexcitability in ALS, furthering the understanding of the pathophysiological processes driving ALS, aiding in the diagnosis of this condition and the utility cortical hyperexcitability as a diagnostic biomarker in this progressive and invariably fatal disease

Cortical Hyperexcitability

The Split-Hand Pattern

Insights Gathered from Studying Cortical Excitability in Familial ALS

The Role of TMS in Aiding Diagnosis

Utilising TMS to Differentiate between Clinical Disorders

Findings

Conclusions