PMID- 31872979
OWN - NLM
STAT- MEDLINE
DCOM- 20210201
LR  - 20210329
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 7
IP  - 1
DP  - 2020 Jan
TI  - Length-dependent MRI of hereditary neuropathy with liability to pressure palsies.
PG  - 15-25
LID - 10.1002/acn3.50953 [doi]
AB  - 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.
CI  - (c) 2019 The Authors. Annals of Clinical and Translational Neurology published by 
      Wiley Periodicals, Inc on behalf of American Neurological Association.
FAU - Pridmore, Michael
AU  - Pridmore M
AUID- ORCID: 0000-0002-9879-7147
AD  - Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
FAU - Castoro, Ryan
AU  - Castoro R
AD  - Department of Neurology, Division of Neuromuscular Medicine, Wake Forest School 
      of Medicine, Winston-Salem, North Carolina, USA.
FAU - McCollum, Megan Simmons
AU  - McCollum MS
AD  - Department of Neurology, Vanderbilt University Medical Center, Nashville, 
      Tennessee, USA.
FAU - Kang, Hakmook
AU  - Kang H
AD  - Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
FAU - Li, Jun
AU  - Li J
AD  - Department of Neurology, Wayne State University School of Medicine, Detroit, 
      Michigan, USA.
FAU - Dortch, Richard
AU  - Dortch R
AD  - Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
AD  - Department of Biomedical Engineering, Vanderbilt University, Nashville, 
      Tennessee, USA.
AD  - Department of Radiology and Radiological Sciences, Vanderbilt University Medical 
      Center, Nashville, Tennessee, USA.
LA  - eng
GR  - UL1 TR000445/TR/NCATS NIH HHS/United States
GR  - R01 NS097821/NS/NINDS NIH HHS/United States
GR  - R01 NS066927/NS/NINDS NIH HHS/United States
GR  - Muscular Dystrophy Association/International
GR  - UL1TR000445/TR/NCATS NIH HHS/United States
GR  - R01 NS066927/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20191224
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
RN  - Tomaculous neuropathy
SB  - IM
MH  - *Adiposity
MH  - Adolescent
MH  - Adult
MH  - Arthrogryposis/*diagnostic imaging/pathology
MH  - Axons/*pathology
MH  - Female
MH  - Hereditary Sensory and Motor Neuropathy/*diagnostic imaging/pathology
MH  - Humans
MH  - Leg/*diagnostic imaging/pathology
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Muscle, Skeletal/*diagnostic imaging/metabolism/pathology
MH  - Nerve Degeneration/*diagnostic imaging/pathology
MH  - Sciatic Nerve/*diagnostic imaging/pathology
MH  - Young Adult
PMC - PMC6952310
COIS- No authors in this manuscript have any conflict of interest to disclose.
EDAT- 2019/12/25 06:00
MHDA- 2021/02/02 06:00
PMCR- 2019/12/24
CRDT- 2019/12/25 06:00
PHST- 2019/07/23 00:00 [received]
PHST- 2019/11/06 00:00 [revised]
PHST- 2019/11/07 00:00 [accepted]
PHST- 2019/12/25 06:00 [pubmed]
PHST- 2021/02/02 06:00 [medline]
PHST- 2019/12/25 06:00 [entrez]
PHST- 2019/12/24 00:00 [pmc-release]
AID - ACN350953 [pii]
AID - 10.1002/acn3.50953 [doi]
PST - ppublish
SO  - Ann Clin Transl Neurol. 2020 Jan;7(1):15-25. doi: 10.1002/acn3.50953. Epub 2019 
      Dec 24.