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

OBJECTIVE: Hereditary neuropathy with liability to pressure palsies (HNPP) is caused by heterozygous deletion of the peripheral 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 (F (per)) 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: F (per) values 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 in F (per) was 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 muscle F (per) values were related to CMTNS (r = 0.69, P = 0.03), while distal muscle F (per) and sciatic/tibial nerve MTR values were not related to disability. INTERPRETATION: Despite the multifocal nature of the HNPP phenotype, muscle F (per) measurements relate to disability and exhibit a proximal‐to‐distal gradient consistent with length‐dependent axonal loss, suggesting that F (per) may be a viable biomarker of disease progression in HNPP.