New Method to Assess Nerve Fiber Loss Seen to Accurately Measure CMT1 Disability

Researchers in France have found that a new technique to assess muscle electrical activity, called Motor Unit Number Index (MUNIX), correlates with clinical disability in Charcot-Marie-Tooth disease type 1 (CMT1) and can be used to monitor disease progression.

The study, “Motor unit number index correlates with disability in Charcot-Marie-Tooth disease,” appeared in the journal Clinical Neurophysiology.

CMT1A is the most common type of CMT1. It typically begins in adolescence with muscle weakness and atrophy of the lower legs, followed by hand weakness and reduced sensations.

Although CMT1A has been the subject of clinical trials in the last decade, the definition of appropriate stages to monitor small, disease-related changes over time remains an important challenge.

Studies have shown that clinical disability correlates with the loss of nerve fibers, which together with the loss of their insulating layer, called myelin, is a hallmark feature of CMT.

MUNIX is a new method to assess the dysfunction of motor nerve fibers, which conduct impulses to muscle cells. It provides a score linked to the number of functional motor units in a muscle and is faster, simpler, and less invasive than other methods, the study’s authors noted.

Previous studies analyzed MUNIX in amyotrophic lateral sclerosis and other debilitating disorders, but not CMT.

The researchers performed the MUNIX technique on 56 CMT patients and 53 healthy controls. They also assessed the potential correlation of MUNIX results with clinical scales.

The method was performed in the abductor pollicis brevis (APB, a muscle in the hand located between the wrist and the base of the thumb), the abductor digiti minimi (ADM, the lateral side of the foot), and the tibialis anterior (TA, the lateral side of the lower leg), which are all typically involved in CMT.

The scientists calculated a MUNIX sum score by adding the results of the three muscles. Muscle strength and weakness were assessed with appropriate scales.

Of 41 patients with available genetic results, 34 had CMT1A, four had CMT1B, one had CMT4C, and two had other CMT-related gene mutations. All other patients had a typical CMT phenotype, with peripheral nerve damage and muscle atrophy in the lower limbs, with foot deformities.

In CMT1 patients, results showed a correlation between the MUNIX scores of the ADM, APB, and TA muscles and the scale score of the corresponding muscle. MUNIX values decreased in patients with CMT compared to healthy controls, which is due to the loss of motor nerve fibers, researchers observed. These findings concur with those seen in ALS.

The MUNIX sum score also correlated with the functional scales of clinical impairment, CMTNSv2 and ONLS. Of note, assessment of each muscle took less than 20 minutes and was well-tolerated, the scientists reported.

“This study showed that MUNIX correlated with motor impairment and clinical disability in patients with CMT disease, and could provide a new tool to follow up these patients in trials,” the researchers wrote.

Additional studies are required to confirm the findings in larger patient groups, they said.