Carpal tunnel syndrome (CTS) has an incidence of > 1 million people/year in the US. While carpal tunnel release (CTR) typically restores sensation effectively, the ability to regain lost motor function is limited. The Bland Criteria, a diagnostic tool for CTS based on nerve conduction studies, does not predict post-operative recovery of symptoms or function of patients with early or advanced CTS.
Moreover, the molecular determinants of early and advanced denervation in CTS and their impacts on functional recovery remain unknown in humans. This study aims to correlate nerve conduction studies, thenar ultrasound, and molecular pathways associated with denervation atrophy in CTS with self-reported functional outcomes.
Tissue biopsies were harvested from the abductor pollicis brevis (APB) muscle in 50 patients, with Bland Grades ranging from 2 to 6, during open CTR. Total RNA extraction, followed by analysis using quantitative real-time PCR (qRT-PCR) of genes implicated in muscle atrophy was performed. Patients completed a Boston Carpal Tunnel Questionnaire (BCTQ) and thenar muscle ultrasound immediately before surgery and 3 months postoperatively. The minimally clinically important difference (MCID) was determined as 0.46 and 0.28 relative to the preoperative Symptom Severity Scale (SSS) and Functional Status Scale (FSS), respectively for the BCTQ. Receiver operator characteristic (ROC) curves evaluated the prognostic value of atrophy-related genes for symptomatic and functional recovery, with an area under the curve (AUC) exceeding 0.7 indicating predictive value.
ResultsPatients with a higher Bland Grade had a clinically significant improvement in functional status (AUC = 0.9375, CI: (0.7239, 1.000)), likely due to poorer baseline function. However, Bland Grade did not correspond with improvement in symptom severity. Genes such as Myogenin, MyoD, Foxo-3, Nf-kB, FASN, a-SMA, and Decorin corresponded with significant functional improvement, suggesting their role in muscle atrophy before surgery. Only Foxo-3 corresponded with improvement in symptom severity, suggesting its gene expression is crucial during early denervation. Importantly, gene expression outliers were seen who had a lower Bland Grade with more severe muscle changes than expected correlating with less functional recovery.
ConclusionsUnveiling the key molecular players in early and severe denervation atrophy is vital for devising novel interventions to enhance functional recovery and optimize surgical timing in CTS patients. Early identification of patients with muscle changes exceeding changes predicted by electrodiagnostic grading will allow for appropriately timed surgical intervention for this critical patient population.
