Early Peripheral Nerve Involvement at the Time of Coughing in Patients With Intronic Expansion.

OBJECTIVES

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome results from variations in and is mostly caused by intronic biallelic pathogenic expansions (RE-). Refractory chronic cough (RCC) is frequently observed for years to decades preceding ataxia onset. Whether peripheral nerves are involved in the presymptomatic phase characterized by RCC is uncertain.

METHODS

Here, patients previously screened for RCC and identified as having at least one RE- intronic expansion underwent a comprehensive clinical and neurophysiologic assessment and were screened for additional exonic variations.

RESULTS

Fourteen patients with RCC and RE- were investigated. Seven patients presented with biallelic RE- (Bi-RE-) while 7 presented with monoallelic RE- (Mono-RE-). In patients with Mono-RE-, no additional exonic variation was identified, and clinical examinations were normal. Most of the patients with Bi-RE- presented with subtle neurologic impairment, mainly exhibiting decreased lower limb vibration sense (85.7%). Nerve conduction studies revealed that all patients with Bi-RE- exhibited lower sensory sum scores than patients with Mono-RE- (median 20.2 µV vs 84.9 µV, = 0.0012). In addition, the radial-to-sural sensory ratios were null or inverted (>0.5) in all patients but one with Bi-RE-, which is consistent with sensory neuronopathy.

DISCUSSION

Patients with Bi-RE-RFC1 already exhibit widespread sensory neuron involvement at the time of apparently isolated RCC.