scholarly journals A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores

Neurology ◽  
2020 ◽  
Vol 94 (9) ◽  
pp. e884-e896 ◽  
Author(s):  
Vera Fridman ◽  
Stefan Sillau ◽  
Gyula Acsadi ◽  
Chelsea Bacon ◽  
Kimberly Dooley ◽  
...  
Keyword(s):  
Rasch Analysis ◽  
Clinical Progression ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Mixed Regression ◽  
Longitudinal Regression ◽  
Inherited Neuropathies ◽  
Baseline Disease Severity ◽  
Tooth Disease

ObjectiveTo evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).MethodsPatients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.ResultsBaseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4–87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99–1.97, p < 0.0001, for baseline CMTES-R score 0–9).ConclusionThe CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.ClinicalTrials.gov identifierNCT01193075.

scholarly journals A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands

2018 ◽  
Vol 3 ◽  
pp. 20 ◽  
Author(s):  
Diane L. Sherman ◽  
Peter J. Brophy
Keyword(s):  
Plasma Membrane ◽  
Schwann Cell ◽  
Laminin Receptor ◽  
Cell Plasma Membrane ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
C Terminus ◽  
Cell Plasma ◽  
Inherited Neuropathies ◽  
Tooth Disease

Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin (PRX) gene. Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag). In mice the Prx/Drp2/Dag complex assembles adhesive domains at the interface between the abaxonal surface of the myelin sheath and the cytoplasmic surface of the Schwann cell plasma membrane. Assembly of these appositions causes the formation of cytoplasmic channels called Cajal bands beneath the surface of the Schwann cell plasma membrane. Loss of either Periaxin or Drp2 disrupts the appositions and causes CMT in both mouse and man. In a mouse model of CMT4F, complete loss of Periaxin first prevents normal Schwann cell elongation resulting in abnormally short internodal distances which can reduce nerve conduction velocity, and subsequently precipitates demyelination. Distinct functional domains responsible for Periaxin homodimerization and interaction with Drp2 to form the Prx/Drp2/Dag complex have been identified at the N-terminus of Periaxin. However, CMT4F can also be caused by a mutation that results in the truncation of Periaxin at the extreme C-terminus with the loss of 391 amino acids. By modelling this in mice, we show that loss of the C-terminus of Periaxin results in a surprising reduction in Drp2. This would be predicted to cause the observed instability of both appositions and myelin, and contribute significantly to the clinical phenotype in CMT4F.

Fifteen-year longitudinal follow-up of a patient with severe early-onset Charcot-Marie-Tooth disease type 2A

2018 ◽  
Vol 57 (5) ◽  
pp. E126-E128
Author(s):  
Brett A. McCray ◽  
William Hurst ◽  
Thomas O. Crawford ◽  
Thomas E. Lloyd
Keyword(s):  
Early Onset ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

scholarly journals PROGRESS IN CLINICAL NEUROSCIENCES: Charcot-Marie-Tooth Disease and Related Inherited Peripheral Neuropathies

2001 ◽  
Vol 28 (3) ◽  
pp. 199-214 ◽  
Author(s):  
Timothy J. Benstead ◽  
Ian A. Grant
Keyword(s):  
Molecular Genetic ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathy ◽  
Molecular Aspects ◽  
The Many ◽  
Inherited Neuropathies ◽  
Tooth Disease

The classification of Charcot-Marie-Tooth disease and related hereditary motor and sensory neuropathies has evolved to incorporate clinical, electrophysiological and burgeoning molecular genetic information that characterize the many disorders. For several inherited neuropathies, the gene product abnormality is known and for others, candidate genes have been identified. Genetic testing can pinpoint a specific inherited neuropathy for many patients. However, clinical and electrophysiological assessments continue to be essential tools for diagnosis and management of this disease group. This article reviews clinical, electrophysiological, pathological and molecular aspects of hereditary motor and sensory neuropathies.

Clinical progression in Charcot–Marie-Tooth disease type 1A duplication: clinico-electrophysiological and MRI longitudinal study of a family

2010 ◽  
Vol 257 (10) ◽  
pp. 1633-1641 ◽  
Author(s):  
José Berciano ◽  
Elena Gallardo ◽  
Antonio García ◽  
César Ramón ◽  
Jon Infante ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Disease Type ◽  
Clinical Progression ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Triple Arthrodesis in the Treatment of Fixed Cavovarus Deformity in Adolescent Patients with Charcot-Marie-Tooth Disease

Foot & Ankle ◽  
1992 ◽  
Vol 13 (1) ◽  
pp. 1-6 ◽  
Author(s):  
David C. Mann ◽  
John D. Hsu
Keyword(s):  
Residual Deformity ◽  
Triple Arthrodesis ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Adolescent Patients ◽  
The Face ◽  
Progressive Disorder ◽  
Recurrent Deformity ◽  
Tooth Disease

Ten adolescent patients with Charcot-Marie-Tooth disease (12 feet) were evaluated an average of 7 years, 7 months following triple arthrodesis (TA) for the treatment of cavovarus deformity. The TA was the primary or index bone procedure. At follow-up, five feet were plantigrade, asymptomatic, and radiographically fused at all three joints. Three feet were plantigrade and asymptomatic, but two had talonavicular pseudarthrosis and one had calcaneocuboid pseudarthrosis. Three feet were radiographically fused at all three joints, but in nonplantigrade positions and symptomatic. One foot required a revision TA. In general, TA offers adolescent Charcot-Marie-Tooth patients a stable plantigrade foot in the face of a progressive disorder. The residual deformity, revision, and pseudarthrosis rates are similar to those for adults. Postoperative pain was related to a nonplantigrade foot and not to the presence of pseudarthrosis. It is not known whether a nonplantigrade foot was a result of incomplete surgical correction or recurrent deformity due to progressive muscle imbalance.

scholarly journals Changes of gait pattern in children with Charcot-Marie-Tooth disease type 1A: a 18 months follow-up study

2013 ◽  
Vol 10 (1) ◽  
pp. 65 ◽  
Author(s):  
Maurizio Ferrarin ◽  
Tiziana Lencioni ◽  
Marco Rabuffetti ◽  
Isabella Moroni ◽  
Emanuela Pagliano ◽  
...  
Keyword(s):  
Gait Pattern ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Follow Up Study ◽  
Tooth Disease

Charcot-Marie-Tooth Disease and Related Inherited Neuropathies

Medicine ◽  
1996 ◽  
Vol 75 (5) ◽  
pp. 233-250 ◽  
Author(s):  
Tatsufumi Murakami ◽  
Carlos A. Garcia ◽  
Lawrence T. Reiter ◽  
James R. Lupski
Keyword(s):  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inherited Neuropathies ◽  
Tooth Disease

scholarly journals Atypical presentation of Charcot-Marie-Tooth disease type 1C with a new mutation: a case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Monika Turčanová Koprušáková ◽  
Milan Grofik ◽  
Ema Kantorová ◽  
Petra Jungová ◽  
Ján Chandoga ◽  
...  
Keyword(s):  
New Mutation ◽  
Gene Encoding ◽  
Case Presentation ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Inflammatory Neuropathy ◽  
Inherited Neuropathies ◽  
Partial Effects ◽  
Progressive Weakness ◽  
Tooth Disease

Abstract Background Charcot-Marie-Tooth 1C (CMT1C) is a rare form of dominantly inherited CMT1 neuropathy caused by a mutated gene encoding lipopolysaccharide-induced tumour necrosis alpha factor (LITAF). Case presentation We report a 56-year-old patient with an atypical clinical phenotype of CMT1C, which started as progressive weakness of a single upper limb resembling acquired inflammatory neuropathy. Nerve conduction studies (NCS) and temporarily limited and partial effects of immunotherapy supported the diagnosis of inflammatory neuropathy. Significant progression of polyneuropathy, despite intensive long-lasting immunotherapy, together with repeatedly negative auxiliary investigations (CSF, MRI and antibodies) and genetic testing results finally led to the diagnosis of CMT1C neuropathy. Conclusions CMT1C should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy.

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