Inflammatory demyelination in a patient with CMT1A

Vital, Anne; Vital, C; Lagueny, A; Ferrer, Xavier; Ribière-Bachelier, Catherine; Latour, Philippe; Petry, Klaus G.

doi:10.1002/mus.10404

Cited by 52 publications

(44 citation statements)

References 16 publications

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“…Perturbation of the BNB is a feasible hypothesis for the etiology of at least some of the nerve pathology observed in patients with PMP22-associated neuropathies. Elevated levels of endoneurial macrophages are found in the PMP22-mutant TrJ mice (Misko et al, 2002), and macrophage-associated demyelination is detected in a Charcot-Marie-Tooth disease type IA patient with a PMP22 duplication (Vital et al, 2003). However, similar observations in P0 and connexin-32 mutant mice suggest that macrophage infiltration may be common to several hereditary peripheral neuropathies (Carenini et al, 2001;Kobsar et al, 2002).…”

Section: Discussionmentioning

confidence: 78%

The temporospatial expression of peripheral myelin protein 22 at the developing blood‐nerve and blood‐brain barriers

Roux

Amici

Notterpek

2004

J of Comparative Neurology

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Peripheral myelin protein 22 (PMP22), also known as growth arrest-specific gene 3 (gas3), is a tetraspan membrane protein whose misexpression is associated with demyelinating peripheral neuropathies. Although the function of PMP22 in Schwann cells is unknown, the protein is found at intercellular junctions of various epithelia and endothelia. To begin to elucidate the role of PMP22 at cell junctions, we examined the temporal expression and protein localization during development and maturation of the rat blood-nerve barrier (BNB) and blood-brain barrier (BBB). Developing and adult rat sciatic nerves and brains were coimmunostained for PMP22 and known junctional proteins including zonula occludens-1 (ZO-1), occludin, and claudin-5. Prior to the maturation of the BNB and BBB and detection of the tight junction protein occludin, PMP22 is present at ZO-1 positive endothelial junctions of the sciatic nerve and brain cortex. The subcellular localization of PMP22 in cultured brain endothelia was confirmed by internalization with ZO-1 after EGTA-induced disruption of cell junctions. In choroid epithelia, PMP22 is detected along with occludin and ZO-1 as early as embryonic day 15 (E15). In agreement, PMP22 message is elevated in P1 rat brain microvasculature and choroid epithelia, compared with total cortex. Additionally, neuroepithelial cell junctions in the embryonic rat brain are immunoreactive for PMP22, ZO-1, and beta-catenin but not occludin. Together, these studies identify PMP22 as an early constituent of intercellular junctions in the developing and mature rat BNB and BBB.

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Section: Discussionmentioning

confidence: 78%

The temporospatial expression of peripheral myelin protein 22 at the developing blood‐nerve and blood‐brain barriers

Roux

Amici

Notterpek

2004

J of Comparative Neurology

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“…It has been suggested and accumulating evidence exists [4][5][6][7][8][9] for a superimposed inflammatory process in a subgroup of patients with CMT disease that is not genotype-specific. It could be related to genetic susceptibility or may relate to a disturbance of the normal function of the protein encoded by the affected gene.…”

Section: Figurementioning

confidence: 99%

Clinical Reasoning: A patient with rapidly progressive sensory loss and imbalance

2015

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A 52-year-old man presented with sudden onset of acral paresthesia and imbalance. The patient did not have any recent illness, sick contacts, or travel abroad. He denied weakness, pain, bowel or bladder incontinence, dysphagia, dysarthria, or shortness of breath. On neurologic examination, 1 month into his symptoms, he had reduced muscle strength in his finger spread, extension, and flexion on both sides graded on Medical Research Council scale 42/5 and in toe extensors 24/24 and toe flexors 24/4. The rest of his muscle strength was normal. Reflexes were absent throughout. He had reduced sensation to all modalities in a length-dependent pattern up to his midshin and wrists on both sides. He was severely unsteady when walking and he could not tandem. Romberg was positive. The rest of his neurologic examination was normal apart from high arches and hammertoes. The patient had a family history of Charcot-Marie-Tooth disease type 1A (CMT1A) (PMP22 duplication) and was himself tested, although asymptomatic, and was also found to be carrying the mutation.Questions for consideration:

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“…The study of CIDP within families is impacted by the similarities between CIDP and inherited neuropathies like Charcot-Marie Tooth disease (CMT). Interestingly, there are a number of reports of genetically proven CMT1A with inflammatory changes of nerve biopsy, responsive to treatment with corticosteroids (Dyck, Swanson et al 1982, Vital, Vital et al 2003, Ginsberg, Malik et al 2004). …”

Section: Immunogeneticsmentioning

confidence: 99%

“…Inflammatory changes on nerve biopsy and response to immune therapy have all been seen in proven CMT1A (Dyck, Swanson et al 1982, Vital, Vital et al 2003, Ginsberg, Malik et al 2004. Moreover, GBS has been described in several patients with both axonal and demyelinating forms of CMT and hereditary spastic paraparesis (Odaka, Yuki et al 2003, Alhashel, Alshubaili et al 2004, Münch, Epplen et al 2008.…”

Section: Target Organ Susceptibilitymentioning

confidence: 99%

“…However, there is considerable difficulty in making such a diagnosis because familial demyelinating neuropathy would very likely be diagnosed as a hereditary demyelinating neuropathy. There have been clinical studies that indicate an overlap between hereditary and inflammatory demyelinating neuropathy; some patients with inherited neuropathy are responsive to treatment with corticosteroids, suggesting a super-imposed inflammatory component , some subjects with Charcot Marie Tooth disease (CMT) are found to have inflammatory changes on biopsy (Vital et al, 2003), including seven subjects with CMT1A and one with CMTX (Ginsberg et al, 2004), there is a report of CIDP in a subject with CMT1A (Rajabally et al, 2000) and children with CMT1A have been reported with superimposed inflammatory neuropathy (Desurkar et al, 2009). In GBS, there are reports of GBS in a subject with CMT1A, caused by PMP22 duplication (Munch et al, 2008), in subjects with hereditary neuropathy with pressure palsy, due to PMP22 gene deletion (Korn-Lubetzki et al, 2002;Remiche et al, 2013), and axonal GBS in a patient with axonal Charcot Marie Tooth (CMT) disease (Odaka et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Immunogenetic studies of Guillain - Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy

Blum¹

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Guillain-Barre syndrome (GBS) is an acute inflammatory neuropathy that is frequently triggered by an infectious illness. It is thought to be autoimmune in origin, but differs from other autoimmune diseases in being of male predominance and not showing a HLA-association.Chronic inflammatory demyelinating polyradiculoneuropathy is a chronic inflammatory neuropathy, which shares some pathological features with GBS.We investigated the clinical features of GBS in an Australian cohort of subjects by performing a retrospective chart review. We obtained subjects from several public hospitals and private neurologists in Queensland and New South Wales.We found 335 patients, for 228 of whom electrophysiological data was available. Of these acute inflammatory demyelinating polyradiculoneuropathy (AIDP) with 168 cases was the most common form, whilst axonal and focal forms were rarer. We identified upper respiratory tract infections, occurring predominantly in winter months, as the most frequently named triggering factor for GBS.The illness severity in our cohort was similar to that in earlier Australian studies.Also, we identified a cohort of 78 subjects fulfilling diagnostic criteria for CIDP from similar sources.We investigated a possible underlying genetic susceptibility to develop GBS or CIDP by contacting members of this cohort and collecting their DNA. We embarked on both a candidate gene approach to investigate the killer immunoglobulin-like receptors (KIRs) and their HLA ligands, as well as performing a genome-wide association study (GWAS) of the subjects with GBS as a hypothesis-free method.For the KIR/HLA system, whilst no significant differences were detected in the frequency of KIR genes, HLA-C2 and HLA-B Bw4-T were more frequent in subjects with GBS than controls (p<0.001). The inhibitory pairs of KIR-2DL2/HLA-C2 and KIR-3DL1/HLA-B Bw4-T were more frequent in GBS than controls (p<0.005). Whilst there were some differences between CIDP subjects and controls, interestingly, there were no difference between subjects with GBS and CIDP.This could point to similarities of pathogenesis between these two inflammatory neuropathies.A GWAS was performed on a largely identical cohort of 190 subjects with GBS. Whilst this cohort is relatively small for a modern GWAS and no genome-wide significant results were expected, we were able to identify a number of regions of interest based on clusters of SNPs in linkage disequilibrium of increased significance. These included rs10519519 on Chromosome 2, which is associated with MYT1L, a transcription factor in neuronal development; rs7663689 on Chromosome 4, which is in the promotor region of IL15; rs11151180 on Chromosome 18 which is in a gene-free region; rs17095496 on Chromosome 14, which amongst other genes is associated with DACT1, which encodes a regulator of cell division involved in the NF-κB pathway; and rs2302524 on chromosome 19, associated among other genes with NFKBIB, which encodes an inhibitor of the NF-κB pathway. Relative negatives included the HLA region, a...

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Inflammatory demyelination in a patient with CMT1A

Cited by 52 publications

References 16 publications

The temporospatial expression of peripheral myelin protein 22 at the developing blood‐nerve and blood‐brain barriers

The temporospatial expression of peripheral myelin protein 22 at the developing blood‐nerve and blood‐brain barriers

Clinical Reasoning: A patient with rapidly progressive sensory loss and imbalance

Immunogenetic studies of Guillain - Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy

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