TY - JOUR
T1 - Length-dependent MRI of hereditary neuropathy with liability to pressure palsies
AU - Pridmore, Michael
AU - Castoro, Ryan
AU - McCollum, Megan Simmons
AU - Kang, Hakmook
AU - Li, Jun
AU - Dortch, Richard
N1 - Funding Information:
Funding Information This research is supported by grants from National Institutes of Health/NINDS, R01NS066927 (J.L.) and R01NS097821 (R.D.), the Muscular Dystrophy Association, and the National Center for Advancing Translational Sciences (UL1TR000445). We thank Teresa Turner for outreach and recruitment of HNPP subjects. We also thank the MRI technologists at VUIIS (Chris Thompson, Leslie McIntosh, Clair Jones) for their ongoing support and expertise. This research is supported by grants from National Institutes of Health/NINDS, R01 NS066927 (J.L.) and R01 NS097821 (R.D.), the Muscular Dystrophy Association, and the National Center for Advancing Translational Sciences (UL1TR000445).
Funding Information:
We thank Teresa Turner for outreach and recruitment of HNPP subjects. We also thank the MRI technologists at VUIIS (Chris Thompson, Leslie McIntosh, Clair Jones) for their ongoing support and expertise. This research is supported by grants from National Institutes of Health/NINDS, R01 NS066927 (J.L.) and R01 NS097821 (R.D.), the Muscular Dystrophy Association, and the National Center for Advancing Translational Sciences (UL1TR000445).
Publisher Copyright:
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
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 (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.
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U2 - 10.1002/acn3.50953
DO - 10.1002/acn3.50953
M3 - Article
C2 - 31872979
AN - SCOPUS:85076928467
SN - 2328-9503
VL - 7
SP - 15
EP - 25
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 1
ER -