Clinical Controversies in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis is a devastating neurodegenerative condition with few effective treatments. Current research is gathering momentum into the underlying pathology of this condition and how components of these pathological mechanisms affect individuals differently, leading to the broad manifestations encountered in clinical practice. We are moving away from considering this condition as merely an anterior horn cell disorder into a framework of a multisystem neurodegenerative condition in which early cortical hyperexcitability is key. The deposition of TAR DNA-binding protein 43 is also a relevant finding given the overlap with frontotemporal dysfunction. New techniques have been developed to provide a more accurate diagnosis, earlier in the disease course. This goes beyond the traditional nerve conduction studies and needle electromyography, to cortical excitability studies using transcranial magnetic stimulation, and the use of ultrasound. These ancillary tests are proposed for consideration of future diagnostic paradigms. As we learn more about this disease, future treatments need to ensure efficacy, safety, and a suitable target population to improve outcomes for these patients. In this time of active research into this condition, this paper highlights some of the areas of controversy to induce discussion surrounding these topics.