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

Ann Clin Transl Neurol. 2020 Jan;7(1):15-25. doi: 10.1002/acn3.50953. Epub 2019 Dec 24.


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 (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: Fper 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 Fper 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 Fper values were related to CMTNS (r = 0.69, P = 0.03), while distal muscle Fper and sciatic/tibial nerve MTR values were not related to disability.

Interpretation: Despite the multifocal nature of the HNPP phenotype, muscle Fper measurements relate to disability and exhibit a proximal-to-distal gradient consistent with length-dependent axonal loss, suggesting that Fper may be a viable biomarker of disease progression in HNPP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Adolescent
  • Adult
  • Arthrogryposis / diagnostic imaging*
  • Arthrogryposis / pathology
  • Axons / pathology*
  • Female
  • Hereditary Sensory and Motor Neuropathy / diagnostic imaging*
  • Hereditary Sensory and Motor Neuropathy / pathology
  • Humans
  • Leg / diagnostic imaging*
  • Leg / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle, Skeletal / diagnostic imaging*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Nerve Degeneration / diagnostic imaging*
  • Nerve Degeneration / pathology
  • Sciatic Nerve / diagnostic imaging*
  • Sciatic Nerve / pathology
  • Young Adult

Supplementary concepts

  • Tomaculous neuropathy