Myelin abnormality in Charcot–Marie–Tooth type 4J recapitulates features of acquired demyelination

Hu, Bo; Mccollum, Megan; Ravi, Vignesh; Arpag, Sezgi; Moiseev, Daniel; Castoro, Ryan; Mobley, Bret; Burnette, Bryan W.; Siskind, Carly E.; Day, John W.; Yawn, Robin; Feely, Shawna; Li, Yuebing; Yan, Qing; Shy, Michael E.; Li, Jun

doi:10.1002/ana.25198

Cited by 30 publications

(33 citation statements)

References 51 publications

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“…Conduction blocks in CMT may be related to marked hypoexcitability of nerves but superimposed inflammation cannot certainly be excluded. Non‐uniform slowing of conduction velocities, conduction blocks, and temporal dispersion, together with pathological features resembling those of CIDP were also observed in patients with CMT4J . Moreover, hereditary amyloidosis caused by TTR gene mutations may be misdiagnosed with CIDP, especially in cases with late onset, absent family history, and lack of dysautonomia and heart involvement .…”

Section: Discussionmentioning

confidence: 98%

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Campagnolo

Taioli

Cacciavillani³

et al. 2020

J Peripheral Nervous Sys

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Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.

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Section: Discussionmentioning

confidence: 98%

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Campagnolo

Taioli

Cacciavillani³

et al. 2020

J Peripheral Nervous Sys

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“…The rightmost images ( C and F ) were enlarged from B and E , respectively. CMT4J is a rare subtype of the inherited neuropathy caused by recessive genetic mutations with the loss of FIG4 protein which results in demyelination in peripheral nerves 64 . Even though the significantly enlarged sciatic nerve cross-sectional area is a change in a number of peripheral neuropathies, it is not possible to differentiate demyelination versus axonal degeneration using the magnitude images (or other forms of conventional imaging such as proton density–weighted, T1-weighted, or T2-weighted imaging).…”

Section: Peripheral Nerve Magnetic Resonance Imagingmentioning

confidence: 99%

Peripheral nerve magnetic resonance imaging

Chen

Haacke

2019

F1000Res

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Magnetic resonance imaging (MRI) has been used extensively in revealing pathological changes in the central nervous system. However, to date, MRI is very much underutilized in evaluating the peripheral nervous system (PNS). This underutilization is generally due to two perceived weaknesses in MRI: first, the need for very high resolution to image the small structures within the peripheral nerves to visualize morphological changes; second, the lack of normative data in MRI of the PNS and this makes reliable interpretation of the data difficult. This article reviews current state-of-the-art capabilities in in vivo MRI of human peripheral nerves. It aims to identify areas where progress has been made and those that still require further improvement. In particular, with many new therapies on the horizon, this review addresses how MRI can be used to provide non-invasive and objective biomarkers in the evaluation of peripheral neuropathies. Although a number of techniques are available in diagnosing and tracking pathologies in the PNS, those techniques typically target the distal peripheral nerves, and distal nerves may be completely degenerated during the patient’s first clinic visit. These techniques may also not be able to access the proximal nerves deeply embedded in the tissue. Peripheral nerve MRI would be an alternative to circumvent these problems. In order to address the pressing clinical needs, this review closes with a clinical protocol at 3T that will allow high-resolution, high-contrast, quantitative MRI of the proximal peripheral nerves.

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“…Even though there is no compelling evidence for a causal relationship between SC dedifferentiation and demyelination, the systematic coincidence of the two processes indicates that the molecular mechanism of phenotypic transition of SC into DSC is tightly related to that of SC dedifferentiation. By further investigating how mechanisms of SC dedifferentiation-such as MAP kinases and c-Jun (Hu et al, 2018;Lee, Shin, & Park, 2014a;Napoli et al, 2012)drive DSC phenotype acquisition, we might be able to better understand the molecular processes of demyelination in peripheral neuropathies.…”

Section: Demyelinating Schwann Cells In Inflammatory Segmental Demymentioning

confidence: 99%

“…how mechanisms of SC dedifferentiation-such as MAP kinases and c-Jun(Hu et al, 2018;Lee, Shin, & Park, 2014a;Napoli et al, 2012)drive DSC phenotype acquisition, we might be able to better understand the molecular processes of demyelination in peripheral neuropathies.ACKNOWLEDGMENTSThis research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (2016R1A5A2007009) to HTP. NT is grateful for the support of European Research Council (FP7-IDEAS-ERC 311610) and ATIP-Avenir Program.…”

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confidence: 99%

The conceptual introduction of the “demyelinating Schwann cell” in peripheral demyelinating neuropathies

Park

Kim

Tricaud

2018

Glia

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Myelinating Schwann cells undergo irreversible demyelination in many demyelinating neuropathies that show complete demyelination of the internode. Dedifferentiation, reprogramming, and myelin clearance processes—which are specifically discussed in this article—appear to be shared by various demyelinating peripheral conditions, such as Wallerian degeneration, immune‐mediated, and toxic demyelinating diseases. We propose to introduce the concept of the “demyelinating Schwann cell (DSC)” as a novel cell phenotype, which has specific properties required for myelin sheath clearance. We anticipate that the introduction of the DSC concept will provide a significant advance in understanding the pathophysiological mechanisms of demyelinating peripheral neuropathies.

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Myelin abnormality in Charcot–Marie–Tooth type 4J recapitulates features of acquired demyelination

Cited by 30 publications

References 51 publications

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Peripheral nerve magnetic resonance imaging

The conceptual introduction of the “demyelinating Schwann cell” in peripheral demyelinating neuropathies

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