Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons in the motor cortex, brainstem, and spinal cord. The clinical phenotype of ALS is underscored by a combination of upper and lower motor neuron dysfunction. Although this phenotype was observed over 100 years ago, the site of ALS onset and the pathophysiological mechanisms underlying the development of motor neuron degeneration remain to be elucidated. Transcranial magnetic stimulation (TMS) enables noninvasive assessment of the functional integrity of the motor cortex and its corticomotoneuronal projections. To date, TMS studies have established cortical dysfunction in ALS, with cortical hyperexcitability being an early feature in sporadic forms of ALS and preceding the clinical onset of familial ALS. Taken together, a central origin of ALS is supported by TMS studies, with an anterograde dying-forward mechanism implicated in ALS pathogenesis. Of further relevance, TMS techniques reliably distinguish ALS from mimic disorders, despite a compatible peripheral disease burden, thereby suggesting a potential diagnostic utility of TMS in ALS. This chapter reviews the mechanisms underlying the generation of TMS parameters utilized in assessment of cortical excitability, the contribution of TMS in enhancing the understanding of ALS pathophysiology, and the potential diagnostic utility of TMS techniques in ALS.
Keywords: amyotrophic lateral sclerosis; cortical hyperexcitability; dying forward; glutamate excitotoxicity; short-interval intracortical inhibition.
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