Sensory neuropathy in amyotrophic lateral sclerosis: a systematic review

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of both upper and lower motoneurons, leading to motor and non-motor symptoms. Recent evidence suggests that ALS is indeed a multisystem disorder, associated with cognitive impairment, dysautonomia, pain and fatigue, excess of secretions, and sensory symptoms. To evaluate whether sensory neuropathy could broaden its spectrum, we systematically reviewed its presence and characteristics in ALS, extracting data on epidemiological, clinical, neurophysiological, neuropathological, and genetic features. Sensory neuropathy can be found in up to 20% of ALS patients, affecting both large and small fibers, although there is a great heterogeneity related to different techniques used for its detection (electromyography vs skin biopsy vs nerve biopsy). Moreover, the association between CIDP-like neuropathy and ALS needs to be better explored, although it could be interpreted as part of the neuroinflammatory process in the latter disease. Sensory neuropathy in ALS may be associated with a spinal onset and might be more frequent in SOD1 patients. Moreover, it seems mutually exclusive with cognitive impairment. No associations with sex and other genetic mutation were observed. All these data in the literature reveal the importance of actively looking for sensory neuropathy in ALS patients, and suggest including sensory neuropathy among ALS non-motor features, as it may explain sensory symptoms frequently reported throughout the course of the disease. Its early identification could help avoid diagnostic delays and improve patients' treatment and quality of life.

Keywords: Amyotrophic lateral sclerosis; Neurodegeneration; Non-motor symptoms; Sensory neuropathy; Systematic review.

Fig. 1

PRISMA flowchart of the included studies

Fig. 2

Timeline of ALS and sensory neuropathy. In this figure we can observe the temporal correlation between the onset of ALS and of sensory neuropathy: in spinal onset ALS patients neuropathy could appear before (C), after (A) o together (B) with ALS symptoms. If sensory neuropathy precedes ALS there is usually a delay in ALS diagnosis. Sensory neuropathy does not seem to be associated with bulbar onset of ALS. SN Sensory neuropathy