19. Cortical hyperexcitability in ALS: A heterogeneous process

Abstract

Objective Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI) has been identified as an intrinsic feature of amyotrophic lateral sclerosis (ALS). However, in approximately 20% of patients cortical excitability may be normal, suggesting the presence of pathophysiological heterogeneity. Consequently, the present study assessed for the presence of clinical, functional and neurophysiological differences in ALS phenotypes, as defined by cortical hyperexcitability. Methods Cortical excitability was assessed in 62 ALS patients. Clinical, functional and neurophysiological parameters were compared between ALS patients with cortical hyperexcitability (SICI 5.5%) versus those with a “normal” level of cortical excitability (SICI > 5.5%). Results In ALS patients with features of cortical hyperexcitability, there appeared to be an absence of SICI in the early phase (interstimulus interval [ISI] 1–3 ms) with a transition to facilitation at later ISIs (3.5–7 ms). In contrast, ALS patients with normal SICI demonstrated similar levels of inhibition across early and late SICI phases. Of further relevance, ALS patients with abnormal SICI exhibited increased mortality in follow-up. Conclusion Dysfunction in cortical inter-neuronal circuits probed by short latency paired-pulse TMS appears to capture some of the pathophysiological heterogeneity in ALS and may have direct implications for survival.