Work

Length‐dependent MRI of hereditary neuropathy with liability to pressure palsies

Year: 2019

Type: article

Abstract: Objective Hereditary neuropathy with liability to pressure palsies (HNPP) is caused by heterozygous deletion of theperipheral myelin protein 22 (PMP22)gene. Patients with HNPP present multifocal, reversible sensory/motor deficits due to increased susceptibility to mechanical pressure. Additionally, age‐dependent axonal degeneration is reported. We hypothesize that length‐dependent axonal loss can be revealed by MRI, irrespective of the multifocal phenotype in HNPP. Methods Nerve and muscle MRI data were acquired in the proximal and distal leg of patients with HNPP (n = 10) and matched controls (n = 7). More specifically, nerve magnetization transfer ratios (MTR) were evaluated to assay proximal‐to‐distal gradients in nerve degeneration, while intramuscular fat percentages (Fper) were evaluated to assay muscle fat replacement following denervation. Neurological disabilities were assessed via the Charcot‐Marie‐Tooth neuropathy score (CMTNS) for correlation with MRI. Results Fpervalues were elevated in HNPP proximal muscle (9.8 ± 2.2%,P = 0.01) compared to controls (6.9 ± 1.0%). We observed this same elevation of HNPP distal muscles (10.5 ± 2.5%,P < 0.01) relative to controls (6.3 ± 1.1%). Additionally, the amplitude of the proximal‐to‐distal gradient inFperwas more significant in HNPP patients than controls (P < 0.01), suggesting length‐dependent axonal loss. In contrast, nerve MTR values were similar between HNPP subjects (sciatic/tibial nerves = 39.4 ± 2.0/34.2 ± 2.5%) and controls (sciatic/tibial nerves = 37.6 ± 3.8/35.5 ± 1.2%). Proximal muscleFpervalues were related to CMTNS (r = 0.69,P = 0.03), while distal muscleFperand sciatic/tibial nerve MTR values were not related to disability. Interpretation Despite the multifocal nature of the HNPP phenotype, muscleFpermeasurements relate to disability and exhibit a proximal‐to‐distal gradient consistent with length‐dependent axonal loss, suggesting thatFpermay be a viable biomarker of disease progression in HNPP.

Source: Annals of Clinical and Translational Neurology

DOI: 10.1002/acn3.50953

Authors: Michael Pridmore, Ryan Castoro, Megan Simmons McCollum, Hakmook Kang, Jun Li, Richard Dortch