New Keys to Early Diagnosis: Muscle Echogenicity, Nerve Ultrasound Patterns, Electrodiagnostic, and Clinical Parameters in 150 Patients with Hereditary Polyneuropathies

Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry’s disease (n = 7). The CMT1A, followed by the CMT1/4 group, had the most homogeneous enlargement of the nerve cross-sectional areas (CSA) in the ultrasound pattern sum (UPSS) and homogeneity score. Entrapment scores were highest in HNPP, ATTRv amyloidosis, and Fabry’s disease patients. In demyelinating neuropathies, the CSA correlated inversely with nerve conduction studies. The muscle echo intensity was significantly highest in the clinically most affected muscles, which was independent from the underlying disease cause and correlated with muscle strength and disease duration. Further correlations were seen with combined clinical (CMTES-2) and electrophysiological (CMTNS-2) scores of disease severity. We conclude that nerve ultrasound is a helpful tool to distinguish different types of hereditary neuropathies by pattern recognition, whereas muscle ultrasound is an objective parameter for disease severity. The implementation of neuromuscular ultrasound might enrich diagnostic procedures both in clinical routines and research.

Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies

Since ancient times, animal models have provided fundamental information in medical knowledge. This also applies for discoveries in the field of inherited peripheral neuropathies (IPNs), where they have been instrumental for our understanding of nerve development, pathogenesis of neuropathy, molecules and pathways involved and to design potential therapies. In this review, we briefly describe how animal models have been used in ancient medicine until the use of rodents as the prevalent model in present times. We then travel along different examples of how rodents have been used to improve our understanding of IPNs. We do not intend to describe all discoveries and animal models developed for IPNs, but just to touch on a few arbitrary and paradigmatic examples, taken from our direct experience or from literature. The idea is to show how strategies have been developed to finally arrive to possible treatments for IPNs.