Differences in high-resolution nerve ultrasound (HRUS) results could help distinguish patients with Charcot-Marie-Tooth disease type 1A (CMT1A) from those with other disease types characterized by the loss of myelin, a study reports.
More than 80 genes have been reported as causing Charcot-Marie-Tooth (CMT) disease. CMT1 represents about 80% of all genetically confirmed cases of this disorder. Autosomal dominant CMT1A, associated with the duplication of the PMP22 gene, is the most common, occurring in more than 60% of patients. Autosomal dominant means the mutated gene is a dominant gene located on a nonsex chromosome.
HRUS is a noninvasive imaging tool that helps differentiate between demyelinating neuropathies, characterized by the loss of myelin (the protective layer of nerve fibers, or axons) and a larger nerve cross-sectional area (CSA), from axonal neuropathies, which exhibit slower nerve conduction and normal CSA.
To date, HRUS studies on demyelinating CMT considered it to be genetically and pathologically homogeneous or they only focused on CMT1A. Data on other subtypes is still scarce, and researchers also lack information on whether different genetic subtypes have different HRUS results, which could help diagnosis and represent an advantage over the more invasive nerve conduction study.
Aiming to address these gaps, a research team in Italy compared HRUS findings between patients with CMT1A, CMTX, CMT1B and CMT4C, all demyelinating CMTs. The scientists specifically looked at the median (in the arm and hand), ulnar (arm), and peroneal nerves (lower leg), as well as the brachial plexus, a network of nerves sending signals from the spinal cord to the shoulder, arm, and hand.
The study included 65 patients, 34 of whom were women, with a mean age 44.1 years (ranging from 7-75), from 51 families — 44 with CMT1A, nine with CMT1B, eight with CMTX, and four with CMT4C.
Results revealed that the conduction velocity of median, ulnar, and peroneal nerves was significantly different across the CMT subtypes. Specifically, CMTX differed from the other subtypes for the median and ulnar nerves, and from CMT1A and CMT1B for the peroneal nerve.
When comparing CMT1A to the combination of CMTX, CMT1B, and CMT4C, only the ulnar and radial (a branch of the brachial plexus) nerve impulses — or sensory nerve action potentials (SNAPs) — differed, as they were smaller in CMT1A. However, SNAPs could not be obtained in about 80% of patients, limiting the clinical value of this result, the scientists cautioned.
CSA showed marked enlargement at all sites except the wrist in CMT1A patients, but only slight enlargement or normal range in the other CMTs. This difference between CMT1A and the other subtypes was statistically significant.
In some CMT1A patients, CSA largely overlapped that of other CMTs, as shown in five CMT1A patients with similar brachial plexus and peroneal nerve CSA at all sites assessed.
“Future studies should focus on this subset of CMT1A patients, to explore whether they have different clinical phenotypes and/or may predict clinical course,” the team wrote.
The data also showed an effect of age on the CSA of the peroneal nerve only — the older the patient, the larger the CSA — which is in opposition with prior data on CMT1B only. No right-to-left difference was found.
Also, a combination of three median CSA measures (right and left median nerve forearm, left median nerve elbow) could differentiate CMT1A from other demyelinating CMTs. This result needs to be confirmed in larger, multicenter studies, the investigators said.
“Taken together, these findings indicate heterogeneous nerve HRUS findings in demyelinating CMTs and a possible differential diagnostic role of this technique,” the researchers wrote.
Among the study’s limitations, the investigators mentioned the small number of patients with CMT1B, CMTX and CMT4C and the lack of other genetic subtypes of demyelinating CMTs.
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