Intraepineurial Fat Quantification and Cross-sectional Area Analysis of the Sciatic Nerve Using MRI in Charcot-Marie-Tooth Disease Type 1A Patients

Abstract The objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p < 0.0001). Comparisons among levels showed significantly higher FF for levels 2 and 3 than for level 1 and significantly larger CSA for level 2 compared with level 1 in CMT1A patients. CSA at level 3 correlated positively with the CMT Neuropathy Score version 2 (CMTNSv2). In conclusion, the sciatic nerve FF of CMT1A patients was significantly higher on level 3 compared with both the controls and the measurements taken on more proximal levels, suggesting the possibility of increased intraepineurial fat within the sciatic nerves of CMT1A patients, with a possible distal tendency. Sciatic nerve CSA at level 3 correlated significantly and positively with CMTNSv2, suggesting its potential value as an imaging marker for clinical severity.

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Intraepineurial fat quantification and cross-sectional area analysis of the sciatic nerve using MRI in Charcot-Marie-Tooth disease type 1A patients

Scientific Reports ◽

10.1038/s41598-021-00819-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hyun Su Kim ◽

Ji Hyun Lee ◽

Young Cheol Yoon ◽

Min Jae Cha ◽

Soo Hyun Nam ◽

...

Keyword(s):

Sciatic Nerve ◽

Disease Type ◽

Sectional Area ◽

Fat Quantification ◽

Cross Sectional ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Level 3 ◽

Level 1 ◽

Tooth Disease

AbstractThe objectives of this study were to assess the fat fraction (FF) and cross-sectional area (CSA) of the sciatic nerve in Charcot-Marie-Tooth disease type 1A (CMT1A) patients using Dixon-based proton density fat quantification MRI and to elucidate its potential association with clinical parameters. Thigh MRIs of 18 CMT1A patients and 18 age- and sex-matched volunteers enrolled for a previous study were reviewed. Analyses for FF and CSA of the sciatic nerve were performed at three levels (proximal to distal). CSA and FF were compared between the two groups and among the different levels within each group. The relationship between the MRI parameters and clinical data were assessed in the CMT1A patients. The CMT1A patients showed significantly higher FF at level 3 (p = 0.0217) and significantly larger CSA at all three levels compared with the control participants (p < 0.0001). Comparisons among levels showed significantly higher FF for levels 2 and 3 than for level 1 and significantly larger CSA for level 2 compared with level 1 in CMT1A patients. CSA at level 3 correlated positively with the CMT neuropathy score version 2 (CMTNSv2). In conclusion, the sciatic nerve FF of CMT1A patients was significantly higher on level 3 compared with both the controls and the measurements taken on more proximal levels, suggesting the possibility of increased intraepineurial fat within the sciatic nerves of CMT1A patients, with a possible distal tendency. Sciatic nerve CSA at level 3 correlated significantly and positively with CMTNSv2, suggesting its potential value as an imaging marker for clinical severity.

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Expression profiling of sciatic nerve in a Charcot-Marie-Tooth disease type 1a mouse model

Journal of Neuroscience Research ◽

10.1002/jnr.20406 ◽

2005 ◽

Vol 79 (6) ◽

pp. 825-835 ◽

Cited By ~ 7

Author(s):

Anneloor L.M.A. ten Asbroek ◽

Camiel Verhamme ◽

Marjon van Groenigen ◽

Ruud Wolterman ◽

Maryla M. de Kok-Nazaruk ◽

...

Keyword(s):

Sciatic Nerve ◽

Mouse Model ◽

Expression Profiling ◽

Disease Type ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Tooth Disease

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The α-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model of Charcot–Marie–Tooth disease type 1A and alters myelin gene expression in cultured Schwann cells

Neurobiology of Disease ◽

10.1016/j.nbd.2008.11.014 ◽

2009 ◽

Vol 33 (3) ◽

pp. 448-458 ◽

Cited By ~ 15

Author(s):

Elena M. Barbaria ◽

Bianca Kohl ◽

Bettina A. Buhren ◽

Kerstin Hasenpusch-Theil ◽

Fabian Kruse ◽

...

Keyword(s):

Gene Expression ◽

Sciatic Nerve ◽

Mouse Model ◽

Schwann Cells ◽

Disease Type ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Cultured Schwann Cells ◽

Myelin Gene ◽

Tooth Disease

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Ndrg1-Deficient Mice Exhibit a Progressive Demyelinating Disorder of Peripheral Nerves

Molecular and Cellular Biology ◽

10.1128/mcb.24.9.3949-3956.2004 ◽

2004 ◽

Vol 24 (9) ◽

pp. 3949-3956 ◽

Cited By ~ 89

Author(s):

Tomohiko Okuda ◽

Yujiro Higashi ◽

Koichi Kokame ◽

Chihiro Tanaka ◽

Hisato Kondoh ◽

...

Keyword(s):

Sciatic Nerve ◽

Schwann Cells ◽

Peripheral Nerves ◽

Sensory Neuropathy ◽

Disease Type ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Hind Limbs ◽

Deficient Mice ◽

Tooth Disease

ABSTRACT NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. In this study, we generated mice lacking Ndrg1 to analyze its function and elucidate the pathogenesis of Charcot-Marie-Tooth disease type 4D. Histological analysis showed that the sciatic nerve of Ndrg1-deficient mice degenerated with demyelination at about 5 weeks of age. However, myelination of Schwann cells in the sciatic nerve was normal for 2 weeks after birth. Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained. In wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells rather than the myelin sheath. These results indicate that NDRG1 deficiency leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for maintenance of the myelin sheaths in peripheral nerves. These mice will be used for future analyses of the mechanisms of myelin maintenance.

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Faculty Opinions recommendation of Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11064957.12018055 ◽

2011 ◽

Author(s):

Davide Pareyson ◽

Chiara Marchesi

Keyword(s):

Disease Type ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Tooth Disease

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Faculty Opinions recommendation of Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1160853.622273 ◽

2009 ◽

Author(s):

Davide Pareyson ◽

Chiara Marchesi

Keyword(s):

Ascorbic Acid ◽

Disease Type ◽

Efficacy Trial ◽

Double Blind ◽

Safety And Efficacy ◽

Double Blind Placebo ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Tooth Disease

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PRENATAL DETECTION OF A 17P11.2 DUPLICATION RESULTING FROM A RARE RECOMBINATION EVENT AND NOVEL PCR-BASED STRATEGY FOR MOLECULAR IDENTIFICATION OF CHARCOT-MARIE-TOOTH DISEASE TYPE 1A

Journal of the Peripheral Nervous System ◽

10.1046/j.1529-8027.2000.00022-16.x ◽

2000 ◽

Vol 5 (4) ◽

pp. 240-240

Author(s):

R Bernard ◽

V Labelle ◽

P Negre ◽

S Tardieu ◽

Jp Azulay ◽

...

Keyword(s):

Molecular Identification ◽

Recombination Event ◽

Disease Type ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Prenatal Detection ◽

Tooth Disease

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Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A

Communications Biology ◽

10.1038/s42003-021-01839-2 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Suzan Boutary ◽

Marie Caillaud ◽

Mévidette El Madani ◽

Jean-Michel Vallat ◽

Julien Loisel-Duwattez ◽

...

Keyword(s):

Mouse Models ◽

Disease Type ◽

Major Step ◽

Charcot Marie Tooth ◽

Charcot Marie Tooth Disease ◽

Protein Levels ◽

Positive Effects ◽

Severity Of The Disease ◽

Tooth Disease

AbstractCharcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease. Pathological studies demonstrated the regeneration of myelinated axons and myelin compaction, one major step in restoring function of myelin sheaths. The normalization of sciatic nerve Krox20, Sox10 and neurofilament levels reflected the regeneration of both myelin and axons. Importantly, the positive effects of siRNA PMP22-SQ NPs lasted for three weeks, and their renewed administration resulted in full functional recovery. Beyond CMT1A, our findings can be considered as a potent therapeutic strategy for inherited peripheral neuropathies. They provide the proof of concept for a new precision medicine based on the normalization of disease gene expression by siRNA.

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