# Sensory dysfunction in SMA type 2 and 3 - adaptive mechanism or concomitant target of damage?

## TL;DR

This study investigates sensory dysfunction in adults with SMA types 2 and 3, finding signs of sensory nerve hyperactivity and possible demyelination.

## Contribution

The study provides new electrophysiological evidence of sensory system involvement in SMA, suggesting adaptive mechanisms and early demyelination.

## Key findings

- SMA patients showed higher sensory nerve action potential amplitudes compared to controls, especially in type 2 patients.
- SMA patients had longer sensory latency and slower conduction velocity, indicating possible demyelination.
- Cold pain thresholds were higher and warm dispersion larger in SMA patients, suggesting sensory fiber damage.

## Abstract

The motor neuron survival protein performs numerous cellular functions; hence, spinal muscular atrophy (SMA) is considered to be a multi-organ disease with possible sensory system damage. The controversy surrounding the presence of sensory disturbances, prompted us to conduct standard electrophysiological studies and assess the sensory thresholds for different modalities in adults with SMA types 2 and 3. The study group consisted of 44 adult SMA patients (types 2 and 3). All patients underwent neurological examination using the Hammersmith Functional Motor Scale – Expanded (HFMSE). Standard sensory electrophysiological studies in the ulnar nerve and the estimation of vibratory, temperature, and warm- and cold-induced pain thresholds with temperature dispersion assessment were performed using quantitative sensory testing (QST).

The most repeatable result was the high amplitude of the sensory nerve action potentials (SNAP) in SMA patients compared to controls. This was higher in type 2 patients compared to type 3a and 3b patients and patients with low HFSME scores. Patients with SMA, especially type 3b presented a longer sensory latency and slower conduction velocity than did controls. Cold pain threshold was higher and warm dispersion larger in SMA. The vibratory limit was higher in patients with high HFSME scores.

A high SNAP amplitude suggests sensory fibre hyperactivity, which may be based on overactivation of metabolic pathways as an adaptive mechanism in response to SMN protein deficiency with additionally coexisting small C- and A-delta fibre damage. SMA patients seem to have a concomitant, mild demyelinating process present at the early SMA stage.