Hypoglossal Neuropathy in the Pathogenesis of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography to Explore the Frequency of Clinical and Subclinical Neuropathy in a Pilot Dysphagia Trial.

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All 13 patients with late-RAD (median 8.3 years post-RT) who consecutively underwent needle EMG had neurophysiological evidence of hypoglossal neuropathy, while 31% of neuropathy cases were subclinical without clear clinical signs of denervation. Exploratory subgroup analyses revealed worse function and fibrosis among late-RAD cases whose neuropathy had progressed to clinical stages.

Conclusions: Findings suggest that hypoglossal neuropathy is universally present in patients with fibrosis-related late-RAD, supporting a hypothesis that cranial neuropathy is in the mechanistic pathway. Subclinical hypoglossal neuropathy is evident on EMG assessment before clinical presentation at earlier stages of functional impairment.