Neuropathic pain in patients with Charcot-Marie-Tooth type 1A

Bjelica, Bogdan; Perić, Stojan; Basta, Ivana; Božović, Ivo; Kačar, Aleksandra; Marjanovic, Ana; Ivanovic, Vukan; Branković, Miloš; Janković, Milena; Novaković, Ivana; Stojanović, Vidosava Rakočević

doi:10.1007/s10072-019-04142-5

Cited by 16 publications

(20 citation statements)

References 26 publications

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“…CMT is a length-dependent polyneuropathy involving the motor and sensory large myelinated fibers causing distal weakness/atrophy and sensory impairment with gait imbalance, reduced manual dexterity, and equinovarus foot deformities. Pain, a frequent and debilitating symptom, may have a dual nature: nociceptive pain is obviously related to joint deformities; neuropathic pain (NP) is increasingly recognized and attributed to an impairment of small nerve fibers (Bjelica et al, 2020;Carter et al, 1998;Duchesne et al, 2018;Gemignani et al, 2004;Laurà et al, 2014;Nolano et al, 2015;Padua et al, 2008;Pazzaglia et al, 2010;Ribiere et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Peretti

Squintani

Taioli

et al. 2022

European Journal of Pain

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Background: Pain, either nociceptive or neuropathic (NP), is a common symptom in Charcot-Marie-Tooth (CMT) disease. Methods:We investigated small fibers involvement and its correlation with pain in different CMT subtypes through a systematic clinical and neurophysiological study. We enrolled 50 patients: 19 with duplication of PMP22 (CMT1A), 11 with mutation of MPZ (CMT1B, CMT2I/J, or CMTDID), 12 with mutation of GJB1 (CMTX1), and 8 with mutation of MFN2 (CMT2A and CMT2A2B). Pain was rated with the 11-point Numerical Rating Scale and characterized through Neuropathic Pain Symptoms Inventory. Laser-evoked potentials (LEPs) were recorded after right foot and hand stimulation and N2-P2 complex amplitude and latency were compared with those of 41 controls.Results: Overall pain prevalence was 36%. NP was present in 14.6% of patients, with a length-dependent distribution in 85.7% of cases, and it was significantly more frequent in CMT1A (p < 0.001). Aδ fibers involvement greatly varies between CMT subtypes, reflecting differences in molecular pathology and pathophysiologic mechanisms. Prolonged N2 latency from foot stimulation was noted in 11 CMT1A patients, 5 of which report NP. MPZ-CMTs displayed different neurophysiological phenotypes and a very low prevalence of NP. LEPs were normal in all but one CMTX1 patients, although lower limbs N2-P2 amplitude was significantly reduced in males (p = 0.043). MFN2-CMTs were NP free and LEPs recordings were all normal. NP strictly correlated with LEPs alterations (p = 0.017).Conclusions: NP prevalence varies among CMTs subtypes and is mainly related to Aδ fibers impairment.Significance: Neuropathic pain is a frequent finding in Charcot-Marie Tooth disease and is related to Aδ fibers impairment. Patients at higher risk are those belonging to certain genetic subtypes (i.e. CMT1A and CMT2J) or with laserevoked potentials abnormalities. While managing this disease, clinicians should be aware of this symptom in order to offer best treatment options to their patients.

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Section: Introductionmentioning

confidence: 99%

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Peretti

Squintani

Taioli

et al. 2022

European Journal of Pain

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“… 20 Human chromosome 17 is a small, gene‐rich chromosome associated with several well‐known duplication syndromes. So far the duplication region of 17p13.3p11.2 includes chromosome 17p13.3 duplication syndrome[OMIM:613215], 20 Charcot Marie Tooth Syndrome Type 1A (CMT1A), 21 and Potocki Lupski syndrome (17p11.2 duplication syndrome). 22 Among these, 17p13.3 duplication syndrome 23 and Potocki‐Lupski syndrome 22 were reported to be related with CCA.…”

Section: Discussionmentioning

confidence: 99%

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

She

Tang

Cui

et al. 2021

Clinical Laboratory Analysis

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Background Corpus callosum abnormality (CCA) can lead to epilepsy, moderate severe neurologic or mental retardation. The prognosis of CCA is closely related to genetic etiology. However, copy number variations (CNVs) associated with fetal CCA are still limited and need to be further identified. Only a few scattered cases have been reported to diagnose CCA by whole exome sequencing (WES). Methods Karyotyping analysis, copy number variation sequencing (CNV‐seq), chromosomal microarray analysis (CMA) and WES were parallelly performed for prenatal diagnosis of 19 CCA cases. Results The total detection rate of karyotyping analysis, CMA (or CNV‐seq) and WES were 15.79% (3/19), 21.05% (4/19) and 40.00% (2/5), respectively. Two cases (case 11 and case 15) were diagnosed as aneuploidy (47, XY, + 13 and 47, XX, + 21) by karyotyping analysis and CNV‐seq. Karyotyping analysis revealed an unknown origin fragment (46,XY,add(13)(p11.2)) in case 3, which was further confirmed to originate from p13.3p11.2 of chromosome 17 by CNV‐seq. CMA revealed arr1q43q44 (238923617–246964774) × 1(8.04 Mb) in case 8 with a negative result of chromosome karyotype. WES revealed that 2 of 5 cases with negative results of karyotyping and CNV‐seq or CMA carried pathogenic genes ALDH7A1 and ARID1B. Conclusion Parallel genetic tests showed that CNV‐seq and CMA are able to identify additional, clinically significant cytogenetic information of CCA compared to karyotyping; WES significantly improves the detection rate of genetic etiology of CCA. For the patients with a negative results of CNV‐seq or CMA, further WES test is recommended.

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“…Pain is a frequent complaint in CMT (reported by 23–85% of patients) and may be biomechanical–nociceptive in nature, linked to skeletal deformities of the foot and spine, leading to altered posture and arthropathic degeneration or a true neuropathic pain [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. It usually has mild-to-moderate intensity: the mean visual analogue scale (VAS) score for pain value in 272 CMT1A patients recruited in the ascorbic acid trial was 3.7 ± 3.0 on a 0–10 scale [ 11 ].…”

Section: Current Managementmentioning

confidence: 99%

“…More than one-third of CMT patients make use of analgesic drugs [ 9 ], mainly non-steroid anti-inflammatory drugs (NSAIDs) and paracetamol/acetaminophen, and less commonly opioids [ 5 ]. About 18–30% of patients complain of neuropathic pain [ 4 , 6 ], which should be treated according to evidence-based medicine by choosing first-line and second-line treatments among tricyclic antidepressants, SSRI drugs, anticonvulsants (pregabalin, gabapentin, carbamazepine, etc. ), and local capsaicin, avoiding the use of opioids [ 12 , 13 ].…”

Section: Current Managementmentioning

confidence: 99%

Challenges in Treating Charcot-Marie-Tooth Disease and Related Neuropathies: Current Management and Future Perspectives

2021

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There is still no effective drug treatment available for Charcot-Marie-Tooth neuropathies (CMT). Current management relies on rehabilitation therapy, surgery for skeletal deformities, and symptomatic treatment of pain; fatigue and cramps are frequent complaints that are difficult to treat. The challenge is to find disease-modifying therapies. Several approaches, including gene silencing, to counteract the PMP22 gene overexpression in the most frequent CMT1A type are under investigation. PXT3003 is the compound in the most advanced phase for CMT1A, as a second-phase III trial is ongoing. Gene therapy to substitute defective genes or insert novel ones and compounds acting on pathways important for different CMT types are being developed and tested in animal models. Modulation of the Neuregulin pathway determining myelin thickness is promising for both hypo-demyelinating and hypermyelinating neuropathies; intervention on Unfolded Protein Response seems effective for rescuing misfolded myelin proteins such as P0 in CMT1B. HDAC6 inhibitors improved axonal transport and ameliorated phenotypes in different CMT models. Other potential therapeutic strategies include targeting macrophages, lipid metabolism, and Nav1.8 sodium channel in demyelinating CMT and the P2X7 receptor, which regulates calcium influx into Schwann cells, in CMT1A. Further approaches are aimed at correcting metabolic abnormalities, including the accumulation of sorbitol caused by biallelic mutations in the sorbitol dehydrogenase (SORD) gene and of neurotoxic glycosphingolipids in HSN1.

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Neuropathic pain in patients with Charcot-Marie-Tooth type 1A

Cited by 16 publications

References 26 publications

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Neuropathic pain in Charcot–Marie‐Tooth disease: A clinical and laser‐evoked potential study

Prenatal genetic testing in 19 fetuses with corpus callosum abnormality

Challenges in Treating Charcot-Marie-Tooth Disease and Related Neuropathies: Current Management and Future Perspectives

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