# Upper and lower limb tremor in Charcot–Marie–Tooth neuropathy type 1A and the implications for standing balance

## TL;DR

This study explores tremor patterns in CMT1A patients and finds that tremor is common and distinct from essential tremor, with lower limb tremor linked to balance issues.

## Contribution

The study identifies unique tremor characteristics in CMT1A and links lower limb tremor to impaired balance, suggesting potential therapeutic strategies.

## Key findings

- Postural and kinetic upper limb tremors were present in 65% of CMT1A patients.
- Lower limb tremor was associated with impaired balance in CMT1A patients.
- Tremor stability index in CMT1A was significantly higher than in essential tremor.

## Abstract

Neuropathic tremor occurs in Charcot–Marie–Tooth neuropathy type 1A (CMT1A; hereditary motor and sensory neuropathy, HMSN), although the pathophysiological mechanisms remain to be elucidated. Separately, lower limb tremor has not been explored in CMT1A and could be associated with imbalance as in other neuropathies. The present study aimed to determine tremor characteristics in the upper and lower limbs in CMT1A and relate these findings to clinical disability, particularly imbalance.

Tremor and posturography studies were undertaken in phenotyped and genotyped CMT1A patients. Participants underwent detailed clinical assessment, tremor study recordings, and nerve conduction studies. Tremor stability index was calculated for upper limb tremor and compared to essential tremor.

Seventeen patients were enrolled. Postural and kinetic upper limb tremors were evident in 65%, while postural and orthostatic lower limb tremors were seen in 35% of CMT1A patients. Peak upper limb frequencies were lower distally (~ 6 Hz) and higher proximally (~ 9 Hz), were unchanged by weight-loading, and not impacted by fatigue. The tremor stability index was significantly higher in CMT1A than in essential tremor. A 5–6 Hz lower limb tremor was recorded which did not vary along the limb and was unaffected by fatigue. Balance was impaired in patients with postural lower limb tremor. A high frequency peak on posturography was associated with ‘good’ balance.

Tremor is a common clinical feature in CMT1A, distinct from essential tremor, mediated by a complex interaction between peripheral and central mechanisms. Postural lower limb tremor is associated with imbalance; strategies aimed at tremor modulation could be of therapeutic utility.

The online version contains supplementary material available at 10.1007/s00415-023-12124-z.