Clinical and preclinical evidence of somatosensory involvement in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron neurodegenerative disease. Although it has been classically considered as a disease limited to the motor system, there is increasing evidence for the involvement of other neural and non‐neuronal systems. In this review, we will discuss currently existing literature regarding the involvement of the sensory system in ALS. Human studies have reported intradermic small fibre loss, sensory axonal predominant neuropathy, as well as somatosensory cortex hyperexcitability. In line with this, ALS animal studies have demonstrated the involvement of several sensory components. Specifically, they have highlighted the impairment of sensory–motor networks as a potential mechanism for the disease. The elucidation of these “non‐motor” systems involvement, which might also be part of the degeneration process, should prompt the scientific community to re‐consider ALS as a pure motor neuron disease, which may in turn result in more holistic research approaches. LINKED ARTICLES This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc

Recent advances in the pathogenesis and therapeutics of amyotrophic lateral sclerosis

“…In a second review, Riancho and coworkers addressed ALS from the perspective of a disease beyond the motor system, with emphasis on the sensory system. They combined information coming from patients and from animal models and highlighted the impairment of sensory‐motor networks as an important event in this disease that has been frequently ignored or undervalued (Riancho, Paz‐Fajardo, & López de Munaín, 2020).…”

Diagnostics of Amyotrophic Lateral Sclerosis: Up to Date

“…In human studies, predominant intradermal small fibre loss and axonal sensory neuropathy have been reported [ 18 ]. This observation of non-motor system involvement should lead to re-considering ALS as not only a pure motor neuron disease [ 19 ].…”

Moving Toward Patient-Tailored Treatment in ALS and FTD: The Potential of Genomic Assessment as a Tool for Biological Discovery and Trial Recruitment

“…It is classically characterized by progressive degeneration of both upper motor neurons (UMN) of the motor cortex and lower motor neurons (LMN) of the brainstem and spinal cord at disease onset. Although motor neuron damage is predominating in ALS, other neurons in the fronto-executive circuits, temporal and parietal cortical regions, basal ganglia, and dorsal root ganglia are also involved in some patients (Bede et al, 2013;Westeneng et al, 2016;Cykowski et al, 2017;Omer et al, 2017;Nakamura-Shindo et al, 2020;Riancho et al, 2020). ALS is considered a rare "orphan" disease.…”