Development and Validation of the Pediatric Charcot–Marie–Tooth Disease Quality of Life Outcome Measure

Ramchandren, Sindhu; Wu, Tong; Finkel, Richard S.; Siskind, Carly E.; Feely, Shawna; Burns, Joshua; Reilly, Mary M.; Estilow, Timothy; Shy, Michael E.

doi:10.1002/ana.25966

Cited by 13 publications

(35 citation statements)

References 48 publications

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“…These patients should therefore be evaluated in early life using pediatric clinical outcome assessments, such as the CMT pediatric and infant scores, and the recently developed pediatric CMT-specific quality of life outcome measure. 28,29,37…”

Section: Discussionmentioning

confidence: 99%

Disease Progression in Charcot–Marie–Tooth Disease Related to MPZ Mutations: A Longitudinal Study

Fridman

Sillau

Bockhorst

et al. 2022

Annals of Neurology

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The paucity of longitudinal natural history studies in MPZ neuropathy remains a barrier to clinical trials. We have completed a longitudinal natural history study in patients with MPZ neuropathies across 13 sites of the Inherited Neuropathies Consortium. Methods: Change in Charcot-Marie-Tooth Examination Score (CMTES) and Rasch modified CMTES (CMTES-R) were evaluated using longitudinal regression over a 5-year period in subjects with MPZ neuropathy. Data from 139 patients with MPZ neuropathy were examined. Results: The average baseline CMTES and CMTES-R were 10.84 (standard deviation [SD] = 6.0, range = 0-28) and 14.60 (SD = 7.56, range = 0-32), respectively. A mixed regression model showed significant change in CMTES at years 2-5 (mean change from baseline of 0.87 points at 2 years, p = 0.008). Subgroup analysis revealed greater change in CMTES at 2 years in subjects with axonal as compared to demyelinating neuropathy (mean change of 1.30 points [p = 0.016] vs 0.06 points [p = 0.889]). Patients with a moderate baseline neuropathy severity also showed more

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Section: Discussionmentioning

confidence: 99%

Disease Progression in Charcot–Marie–Tooth Disease Related to MPZ Mutations: A Longitudinal Study

Fridman

Sillau

Bockhorst

et al. 2022

Annals of Neurology

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“…People with CMT often have physical limitations that can restrict their ability to travel to centers of excellence to perform periodical assessments and to undergo specifically tailored rehabilitation treatment. In addition, recent events such as the COVID-19 pandemic have made even more clear that there is an urgent need for trial OMs that do not require in-clinic visits and can be assessed remotely ( 26 ). Furthermore, an accurate assessment of the functionality of the hand could have important implications in designing a personalized rehabilitation treatment and assessing the possible improvement.…”

Section: Discussionmentioning

confidence: 99%

Quality of life and upper limb disability in Charcot-Marie-Tooth disease: A pilot study

et al. 2022

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Charcot-Marie-Tooth (CMT) patients present mainly lower limbs disability, with slowly progressive distal muscle weakness and atrophy, but hands impairment is a relevant problem affecting the quality of life (QoL). The evaluation of the upper limb is of primary importance. Often these patients present subclinical disorders or report difficulties in manipulating objects, with little evidence in the most used outcome measures. We aim to investigate the impact of hand impairment in the perceived QoL of CMT persons and secondly whether the Disability of Arm, Shoulder and Hand (DASH) scale can be useful in assessing upper limb abilities in CMT. We recruited 23 patients with confirmed genetic diagnosis of CMT. We performed a clinical evaluation with Sollerman Hand Function Test (SHFT), Thumb Opposition Test (TOT) and CMT examination score (CMTES). We completed the clinical assessment with DASH scale and the Short form 36 (SF36) questionnaire for a subjective evaluation of upper limb disability and quality of life. All patients also underwent an instrumental evaluation with a hand-held dynamometer measuring hand grip and tripod pinch and a sensor-engineered glove test (SEGT) to evaluate finger opposition movements in a quantitative spatial-temporal way. As expected, we found significant differences between CMT and control group performances in both clinical and instrumental assessment. Concerning QoL, we found that total score of SF36 and the SF36 Physical Composite Score (PCS) correlate with all clinical and instrumental Outcome Measures (OMs), particularly with Tripod pinch strength and TOT, which are considered major determinants of manual dexterity in CMT. DASH scale correlates with most clinical and instrumental OMs. Not surprisingly, we also found a correlation with DASH work, because CMT affects young patients engaged in work activities. However, we found a low correlation with the TOT and the dynamometer suggesting that DASH may not be the best scale for remote monitoring of upper limb disorders in CMT patients. Nevertheless, the results of our study confirm the usefulness of SF36 in recognizing the impact of upper limb disability in these subjects suggesting its use even in the remote monitoring of physical functioning.

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“…The development of new instruments to assess progression in CMT has therefore become an active area of research. Given that the optimal time for the treatment in CMT is in infancy or early childhood, several early-life clinical outcome assessments (including the CMT pediatric, CMT infant scales, and a pediatric CMT-specific quality of life outcome measure) have been developed [318][319][320].…”

Section: Looking Towards the Future: The Evolving Arena Of Clinical O...mentioning

confidence: 99%

Mechanisms and Treatments in Demyelinating CMT

Fridman

Saporta

2021

Neurotherapeutics

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Demyelinating forms of Charcot-Marie-Tooth disease (CMT) are genetically and phenotypically heterogeneous and result from highly diverse biological mechanisms including gain of function (including dominant negative effects) and loss of function. While no definitive treatment is currently available, rapid advances in defining the pathomechanisms of demyelinating CMT have led to promising pre-clinical studies, as well as emerging clinical trials. Especially promising are the recently completed pre-clinical genetic therapy studies in PMP-22, GJB1, and SH3TC2-associated neuropathies, particularly given the success of similar approaches in humans with spinal muscular atrophy and transthyretin familial polyneuropathy. This article focuses on neuropathies related to mutations in PMP-22, MPZ, and GJB1, which together comprise the most common forms of demyelinating CMT, as well as on select rarer forms for which promising treatment targets have been identified. Clinical characteristics and pathomechanisms are reviewed in detail, with emphasis on therapeutically targetable biological pathways. Also discussed are the challenges facing the CMT research community in its efforts to advance the rapidly evolving biological insights to effective clinical trials. These considerations include the limitations of currently available animal models, the need for personalized medicine approaches/allele-specific interventions for select forms of demyelinating CMT, and the increasing demand for optimal clinical outcome assessments and objective biomarkers.

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Development and Validation of the Pediatric Charcot–Marie–Tooth Disease Quality of Life Outcome Measure

Cited by 13 publications

References 48 publications

Disease Progression in Charcot–Marie–Tooth Disease Related to MPZ Mutations: A Longitudinal Study

Disease Progression in Charcot–Marie–Tooth Disease Related to MPZ Mutations: A Longitudinal Study

Quality of life and upper limb disability in Charcot-Marie-Tooth disease: A pilot study

Mechanisms and Treatments in Demyelinating CMT

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