Corticospinal conduction in RFC1-related disease: a transcranial magnetic stimulation study

Area of Science:

• Neurology
• Neurophysiology

Background:

• Biallelic intronic expansions in RFC1 gene cause cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS).
• CANVAS may present with hyperreflexia, yet the mechanism of this apparent corticospinal involvement alongside sensory neuropathy is unclear.

Purpose of the Study:

• To assess corticospinal tract integrity using transcranial magnetic stimulation (TMS) in patients with RFC1-related disease.
• To investigate the relationship between hyperreflexia and TMS findings in RFC1-related disease.

Main Methods:

• Transcranial magnetic stimulation (TMS) was used to evaluate corticospinal tract integrity in 18 patients with genetically confirmed RFC1-related disease.
• Measurements included resting motor threshold (RMT), central motor conduction time (CMCT), and motor evoked potential/compound muscle action potential (MEP/CMAP) amplitude ratios.
• Clinical phenotype, neuroimaging, peripheral neurophysiology, and medication use were reviewed.

Main Results:

• Among 18 patients, 5 (28%) exhibited clinical hyperreflexia.
• No significant differences in RMT, CMCT, or MEP/CMAP ratios were found between patients with and without hyperreflexia.
• Neuroimaging did not reveal structural central nervous system causes in most cases.

Conclusions:

• Standard TMS measures did not significantly differ based on hyperreflexia status in RFC1-related disease.
• Hyperreflexia can occur in RFC1-related disease without detectable abnormalities in conventional TMS metrics.
• Subtle corticospinal dysfunction cannot be ruled out, considering sample size and potential medication effects.