#AANAM – Follow-up Study of DI-CMTC Patients Shows Progressive Nerve Damage, Gait Deterioration

Patients with dominant intermediate Charcot-Marie-Tooth disease type C (DI-CMTC) experience progressive nerve damage, disability, and gait and quality of life deterioration, according to a follow-up study over 16 years.

The findings, “Prospective 16-year Longitudinal Study of Dominant Intermediate CMT Type C Neuropathy,” were presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, being held through May 10 in Philadelphia.

DI-CMTC is caused by mutations in the YARS gene, which generates an enzyme called tyrosyl-tRNA synthetase. The team at Saint Louis University and Hackensack University Medical Center originally characterized DI-CMTC in a U.S. and a Bulgarian family.

To assess the disease across the lifespan, the researchers repeated the evaluations in 13 of the 21 members from the five-generation U.S. family. They were five women and eight men examined at ages 8–77 in 2000 and 24–93 in 2016.

Specifically, the scientists compared 2000 and 2016 data on neurological symptoms and signs, CMT Neuropathy Score version 2 (CMTNSv2) and the Modified Rankin Score (MRS) — two measures of disability — quality of life, as well as electrodiagnostic studies, which evaluate nerve conduction.

The results showed that although most symptoms and signs progressed, the only statistically significant difference was seen in gait. Unlike MRS, the median CMTNSv2 score significantly increased in the study period from 6.08 in 2000 to 11 in 2016. As for quality of life, the patients experienced significant deterioration in mobility, pain/discomfort, and anxiety/depression.

The median nerve compound muscle action potential (CMAP) amplitudes — the muscle response to nerve fiber stimulation — decreased from 9.35 mV to 6.0 mV, while motor nerve conduction velocities (MNCV) were largely unchanged.

The ulnar (forearm) CMAP amplitudes decreased from 9.24 mV to 6.06 mV. At both timepoints, no adult had peroneal motor response, a frequent type of nerve damage in the lower limb. Over the study period, all sensory nerve amplitudes and conduction velocities diminished. Also, the data indicated a progressive reduction in median and ulnar CMAP amplitudes with age.

“Our study demonstrates that DI-CMTC is a slowly progressive disease with lower greater than upper limb involvement, deteriorating mobility and [quality of life],” the scientists said. The nerve conduction findings support previous results reporting nerve fiber degeneration, they added.