Quality of life in hereditary neuropathy with liability to pressure palsies is as impaired as in Charcot-Marie-Tooth disease type 1A.

To date, only one study assessed quality of life (QoL) in patients with hereditary neuropathy with liability to pressure palsies (HNPP). We aimed to fill in this gap by investigating QoL in a cohort of patients with HNPP compared to Charcot-Marie-Tooth type 1A (CMT1A) patients, as well as to analyze sociodemographic and clinical features associated with QoL in HNPP. Eighteen genetically confirmed HNPP patients were age-and gender-matched with 18 CMT1A patients. SF-36 questionnaire was used to assess QoL. Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale Score (ONLS), Falls Efficacy Score (FES), Visual Analog Pain Scale, Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) were also used in our study. Although HNPP patients were less clinically impaired, no difference was observed in these two cohorts regarding SF-36 scores. Worse QoL in HNPP patients was associated with lower education (p < 0.01), physical work (p < 0.05), higher number of clinically affected nerves during the disease course (p < 0.01), worse MRC-SS score (p < 0.01), worse ONLS score (p < 0.01), and with more severe pain (p < 0.01), depression (p < 0.01), and fatigue (p < 0.01). Worse pain at the moment of testing appeared as a significant independent predictor of worse QoL in HNPP patients (ß = - 0.93, p < 0.001). QoL was similarly impaired in patients with HNPP and patients with CMT1A. We identified different factors associated with QoL in HNPP, and many of these factors are amenable to treatment which is of special interest in these still incurable disease.

Patient-reported impact of Charcot-Marie-Tooth disease: protocol for a real-world digital lifestyle study.

Charcot-Marie-Tooth disease (CMT) is a rare, chronic, progressive motor and sensory neuropathy affecting the peripheral nervous system. This study will explore the real-world impact of CMT. The trial is a digital study of approximately 2000 people in 6 countries with CMT ≥18 years. Participants will use a smartphone application to check eligibility, provide consent and contribute data. The dataset will include a personal profile, covering demographics, lifestyle, diagnosis and treatment and a selection of validated generic and disease-specific instruments. Participants will provide data for up to 2 years. Data analysis will be conducted upon registration of the 1000th participant and at 12-month intervals from launch. This study is designed to help researchers and clinicians understand the real-world impact of CMT and the unmet needs of patients. ClinicalTrials.gov identifier: NCT03782883.

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

OBJECTIVE: Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL), especially in children. Defining QOL in pediatric CMT can help physicians monitor disease burden clinically and in trials. We identified items pertaining to QOL in children with CMT and conducted validation studies to develop a pediatric CMT-specific QOL outcome measure (pCMT-QOL). METHODS: Development and validation of the pCMT-QOL patient-reported outcome measure were iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing. Testing was conducted in children with CMT seen at participating sites from the USA, United Kingdom, and Australia. RESULTS: We conducted systematic literature reviews and analysis of generic QOL measures to identify 6 domains relevant to QOL in children with CMT. Sixty items corresponding to those domains were developed de novo, or identified from literature review and CMT-specific modification of items from the pediatric Neuro-QOL measures. The draft version underwent prospective feasibility and face content validity assessments to develop a working version of the pCMT-QOL measure. From 2010 to 2016, the pCMT-QOL working version was administered to 398 children aged 8 to 18 years seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, item response theory analysis, and longitudinal analysis, to develop the final pCMT-QOL patient-reported outcome measure. INTERPRETATION: The pCMT-QOL patient-reported outcome measure is a reliable, valid, and sensitive measure of health-related QOL for children with CMT. ANN NEUROL 2021;89:369-379.

Living With Charcot-Marie-Tooth, Charlie, and Change.

Charcot-Marie-Tooth (CMT) is a hereditary condition that affects the myelin sheath of peripheral nerves causing muscle weakness, atrophy, and peripheral neuropathy. This is a firsthand reflection of living with CMT disease from my personal experience and through my family. I hope this provides informative education to practitioners or individuals who may not be familiar with CMT.

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

BACKGROUND: Only several studies analyzed the characteristics of neuropathic pain (NeP) more extensively in patients with Charcot-Marie-Tooth type 1A (CMT1A). Therefore, we sought to determine the frequency and features of NeP in CMT1A patients and to assess the association between NeP and sociodemographic and clinical characteristics of patients with CMT1A. METHODS: Our research included 51 genetically diagnosed CMT1A patients. The International Association for the Study of Pain (IASP) criteria were used for diagnosis of NeP. PainDETECT questionnaire (PD-Q) was used to assess NeP features. The Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale (ONLS) score, and Beck Depression Inventory were also used. RESULTS: NeP was present in 15 (29.4%) patients with CMT1A. The average intensity of pain was 5.7 ± 2.2 out of 10. The most sensitive neuropathic symptoms were numbness, then tingling, and burning sensations, while the most specific symptom was allodynia. Patients with NeP more frequently reported pain in the back (p < 0.01) and the trunk (p < 0.05). Patients with NeP had more pronounced disability of the upper extremities and overall disability, as assessed by the ONLS score (p < 0.05). Depression was more frequent in patients with NeP compared with patients without NeP (66.7 to 13.9%, p < 0.01). CONCLUSION: NeP was present in almost one-third of the patients with CMT1A and it was moderate on average. Presence of NeP was associated with worse functional disability and depression.

Treadmill training in patients affected by Charcot-Marie-Tooth neuropathy: results of a multicenter, prospective, randomized, single-blind, controlled study.

BACKGROUND AND PURPOSE: Muscle-strengthening, stretching or proprioceptive treatments may slow symptom progression in Charcot-Marie-Tooth (CMT) neuropathy. The aim of the study was to evaluate safety and efficacy of treadmill training in CMT1A. METHODS: We planned a multicenter, prospective, randomized, single-blind, controlled study. We recruited 53 outpatients affected by CMT1A and randomized them into two treatment groups: one underwent stretching and proprioceptive exercise, whereas the other was additionally treated with treadmill training (TreSPE). Primary outcome measures (OMs) were the walking evaluations and secondary OM was the balance assessment. All participants were assessed at baseline and after 3 and 6 months of treatment. RESULTS: Most patients showed an improvement in at least one OM after 3 months [42/47 (89.4%)] and 6 months [38/40 (95%)] of treatment. No adverse events were reported in either group. CONCLUSIONS: The most important finding was that both stretching and proprioceptive exercise and treadmill training had an objective benefit on patients affected by CMT disease, without causing overwork weakness. We had a low rate of drop out and did not find deterioration in motor performance. Our results also confirm that applying evidence-based medicine methods to rehabilitative research is the correct way to test the efficacy of a treatment.

Body composition and its association with physical performance, quality of life, and clinical indictors in Charcot-Marie-Tooth disease: a pilot study.

AIM: To investigate whether the amount and distribution of lean body mass and fat mass is associated with disease severity in adults with Charcot-Marie Tooth. METHODS: Ten participants (age 46 ± 13 y, height 1.7 ± 0.1 m, and body mass 77 ± 17 kg) with Charcot-Marie Tooth disease were involved in this study. Participants were evaluated for quality of life, falls efficacy, balance, mobility, muscle strength, and power. Body composition was measured using dual energy x-ray absorptiometry. Statistical analyses were conducted on subsets of all participants. RESULTS: Better static balance was associated with higher lean body mass of the lower leg (r = 0.73, p = 0.03), while superior leg press strength and power was associated with greater lean body mass of the leg and lower leg (r ≥ 0.80, p ≤ 0.01). Faster habitual walking speed and enhanced quality of life was associated with lower fat mass of several regions. CONCLUSION: Our study seems to suggest that assessing of body composition could assist with monitoring of disease progression in people with Charcot-Marie Tooth; however these findings need to be substantiated in a larger cohort. Implications for Rehabilitation Higher lean body mass and lower fat mass of the legs is associated with better physical performances in people with Charcot-Marie-Tooth disease. Lower fat mass is related to greater quality of life and reduced clinical symptoms in people with Charcot-Marie-Tooth disease. Optimising favorable body composition profiles (higher lean body mass and lower fat mass) in people with Charcot-Marie-Tooth disease may be highly clinically relevant.

A Rasch Analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) in a Cohort of Charcot-Marie-Tooth Type 1A Patients.

The Charcot-Marie-Tooth Neuropathy Score (CMTNS) was developed as a main efficacy endpoint for application in clinical trials of Charcot-Marie-Tooth disease type 1A (CMT1A). However, the sensitivity of the CMTNS for measuring disease severity and progression in CMT1A patients has been questioned. Here, we applied a Rasch analysis in a French cohort of patients to evaluate the psychometrical properties of the CMTNS. Overall, our analysis supports the validity of the CMTNS for application to CMT1A patients though with some limitations such as certain items of the CMTNS being more suitable for moderate to severe forms of the disease, and some items being disordered. We suggest that additional items and/or categories be considered to better assess mild-to-moderate patients.

Do Psychosocial Interventions Improve Quality of Life and Wellbeing in Adults with Neuromuscular Disorders? A Systematic Review and Narrative Synthesis.

Quality of life and well-being are frequently restricted in adults with neuromuscular disorders. As such, identification of appropriate interventions is imperative. The objective of this paper was to systematically review and critically appraise quantitative studies (RCTs, controlled trials and cohort studies) of psychosocial interventions designed to improve quality of life and well-being in adults with neuromuscular disorders. A systematic review of the published and unpublished literature was conducted. Studies meeting inclusion criteria were appraised using a validated quality assessment tool and results presented in a narrative synthesis. Out of 3,136 studies identified, ten studies met criteria for inclusion within the review. Included studies comprised a range of interventions including: cognitive behavioural therapy, dignity therapy, hypnosis, expressive disclosure, gratitude lists, group psychoeducation and psychologically informed rehabilitation. Five of the interventions were for patients with Amyotrophic Lateral Sclerosis (ALS). The remainder were for patients with post-polio syndrome, muscular dystrophies and mixed disorders, such as Charcot-Marie-Tooth disease, myasthenia gravis and myotonic dystrophy. Across varied interventions and neuromuscular disorders, seven studies reported a short-term beneficial effect of intervention on quality of life and well-being. Whilst such findings are encouraging, widespread issues with the methodological quality of these studies significantly compromised the results. There is no strong evidence that psychosocial interventions improve quality of life and well-being in adults with neuromuscular disorders, due to a paucity of high quality research in this field. Multi-site, randomised controlled trials with active controls, standardised outcome measurement and longer term follow-ups are urgently required.

Relationship between physical performance and quality of life in Charcot-Marie-Tooth disease: a pilot study.

Charcot-Marie-Tooth (CMT) is a rare inherited peripheral neuropathy in which quality of life (QoL) is reduced compared with the general population. This paper investigates the relationship between QoL and physical performance in people with CMT with the aim of identifying avenues for future research into rehabilitation strategies. Cross-sectional data was obtained from 10 participants (5 men, 5 women, age 46 ± 13 years, height 1.7 ± 0.1 m, body mass 77 ± 17 kg) with CMT (CMT1A n = 5; CMT-X n = 3; unknown genetic origin n = 2). Participants were evaluated for QoL, falls efficacy (FES), balance, mobility, muscle strength, and power. Physical component score (PCS) of the Short Form-36 (SF-36) was significantly and directly related to higher leg press power (r = 0.75, p = 0.02). Better FES scores were significantly related to faster habitual gait speed (r = -0.70, p = 0.02), left hip abduction, and seated row strength (r = -0.68, p = 0.03; r = -0.73, p = 0.03, respectively). Future research should aim to substantiate these preliminary findings in a larger cohort and investigate whether interventions targeting muscle strength and power can improve QoL and mobility outcomes in people with CMT.

Sport activity in Charcot-Marie-Tooth disease: A case study of a Paralympic swimmer.

This study reports the positive physical, emotional and psychosocial changes induced by sport activity in a Paralympic swimmer with Charcot-Marie-Tooth (CMT) type 4A. When we compared evaluations before initiating sport activity with those after five years of competitive activity, we found: i) increased proximal muscles strength of upper limbs; ii) augmented ability to propel wheelchair independently; iii) improved quality of life; iv) reduced trait anxiety and striking improvement of depression; v) enhanced self-esteem. Longitudinal studies in large cohorts to evaluate the positive effects of sport activity are needed to support provision of evidence-based advice to patients and families.

Efficacy of focal mechanic vibration treatment on balance in Charcot-Marie-Tooth 1A disease: a pilot study.

Patients affected by Charcot-Marie-Tooth (CMT) disease experience an impaired balance. Although the causes of the postural instability are not fully understood, somatosensory system seems to play a key role. Mechanical vibration seems to act on the somatosensory system and to improve its function. The aim of our study was to evaluate the effects of focal mechanical vibration (fMV) on the balance of CMT 1A patients. We enrolled 14 genetically confirmed CMT 1A patients (8 female and 6 male, mean age 492 years, range 32-74, mean duration of disease: 13 years, range 1-30). Patients underwent a 3-day fMV treatment on quadriceps and triceps surae and were evaluated before the treatment as well as 1 week and 1 month after the end of the treatment. The primary outcome measure was the Berg Balance Scale (BBS) and the secondary were the Dynamic Gait Index (DGI), the 6 Min Walking Test (6MWT), the muscular strength of lower limbs, the Quality of Life (QoL) questionnaire and the stabilometric variables. The statistical analysis showed a significant modification of the BBS due to the effect of treatment (p < 0.05). A significant modification was also found in the DGI (p < 0.05). Concerning the stabilometric variables we found significant changes only for the eyes closed condition; in particular, a significant decrease was found in VelocityML (p < 0.05) and Sway path length (p < 0.05). The fMV treatment applied on lower limbs of CMT 1A patients determined an improvement of balance as detected by the BBS. The concurrent improvement of stabilometric variables in the eyes closed condition only suggests that fMV acts mostly on somatosensory afferences. Further studies are needed to confirm these data on a larger sample of CMT patients.

Exploratory study of physical activity in persons with Charcot-Marie-Tooth disease.

OBJECTIVES: To explore and describe the perceived facilitators and barriers to physical activity, and to examine the physical activity correlates in people with Charcot-Marie-Tooth (CMT) disease. DESIGN: Cross-sectional survey study. SETTING: Community-living subjects. PARTICIPANTS: Swedish people with CMT disease (N=44; men, 54.5%; median age, 59.5 y [interquartile range, 45.3-64.8 y]). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The survey included open-ended questions and standardized self-reported scales measuring physical activity, fatigue, activity limitation, self-efficacy for physical activity, fall-related self-efficacy, social support, and enjoyment of physical activity. Physical activity was measured by the Physical Activity Disability Survey-Revised. RESULTS: Qualitative content analysis revealed that personal factors such as fatigue, poor balance, muscle weakness, and pain were important barriers for physical activity behavior. Facilitators of physical activity were self-efficacy for physical activity, activity-related factors, and assistive devices. Multiple regression analysis showed that self-efficacy for physical activity (ß=.41) and fatigue (ß=-.30) explained 31.8% of the variation in physical activity (F2,40=10.78, P=.000). CONCLUSIONS: Despite the well-known benefits of physical activity, physical activity in people with CMT disease is very sparsely studied. These new results contribute to the understanding of factors important for physical activity behavior in people with CMT disease and can guide health professionals to facilitate physical activity behavior in this group of patients.

Quality-of-life in Charcot-Marie-Tooth disease: the patient's perspective.

This study determines the impact of symptoms associated with Charcot-Marie-Tooth disease on quality-of-life. Charcot-Marie-Tooth patients in the Inherited Neuropathies Consortium Rare Diseases Clinical Research Network Contact Registry were surveyed. The survey inquired about 214 symptoms and 20 themes previously identified as important to Charcot-Marie-Tooth patients through patient interviews. Symptom population impact was calculated as the prevalence multiplied by the relative importance of each symptom identified. Prevalence and symptom impact were analyzed by age, symptom duration, gender, Charcot-Marie-Tooth type, and employment status. 407 participants returned the survey, identifying foot and ankle weakness (99.7%) and impaired balance (98.6%) as the most prevalent themes. Foot and ankle weakness and limitations with mobility were the themes with the highest impact. Both symptom prevalence and impact gradually increased with age and symptom duration. Several themes were more prevalent in women with Charcot-Marie-Tooth, including activity limitations, pain, fatigue, hip-thigh weakness, and gastrointestinal issues. All of the themes, except emotional or body image issues, were more prevalent among unemployed individuals. There were minimal differences in symptom prevalence between Charcot-Marie-Tooth types. There are multiple symptoms that impact Charcot-Marie-Tooth quality-of-life in adults. These symptoms have different levels of importance, are readily recognized by patients, and represent critical areas of Charcot-Marie-Tooth health.

Charcot-Marie-Tooth disease, psychiatric indicators and quality of life: a systematic review.

This study is aimed to conduct a systematic literature review regarding the associations between psychiatric symptoms, functional impairments, and quality of life in patients with CMT (Charcot-Marie-Tooth). The PUBMED, PsycInfo, SCIELO, and LILACS electronic databases were used, and the following search terms were employed: CMT, HMSN (hereditary motor and sensory neuropathy), mental disorder, quality of life, psychiatry, psychiatric, and psychological without the use of time-limit filters. According to the adopted inclusion criteria, 20 studies were included and appraised. These studies indicated that patients with CMT exhibited an increased trend toward depressive symptoms compared with the general population. In addition, CMT patients were exposed to a higher risk of reduced quality of life and significant sleep impairment. Considering the comorbidity of CMT with other psychiatric disorders, the heterogeneity of the instruments used to evaluate the psychiatric symptoms compromised the ability to compare the studies examined. Our results indicate a need for a systematic evaluation of these conditions to minimize the impairments and decreased quality of life caused by CMT.

Lower urinary tract functions in a series of Charcot-Marie-Tooth neuropathy patients.

OBJECTIVES: To evaluate lower urinary tract (LUT), bowel, and sexual dysfunctions in a series of patients with Charcot-Marie-Tooth disease (CMT). MATERIALS AND METHODS: A cohort of 58 patients and 54 healthy controls filled out the International Prostate Symptoms Score (IPSS) and the International Consultation on Incontinence Modular (ICIQ) Questionnaires to assess their symptoms and their impact on the patient's quality of life. RESULTS: On the IPSS questionnaire, CMT patients reported a significantly higher score compared with the healthy controls in 7 of 8 questions. The ICIQ-male LUT symptoms questionnaire revealed a significantly higher score in 7 of 26 questions. In the ICIQ-female LUT questionnaire, a significantly higher score was observed in 13 of 24 questions. When assessing the bowel function in CMT patients using the ICIQ-bowel questionnaire, a significantly higher score in 30 of 40 questions was noted. No differences in sexual function were found in either group. CONCLUSIONS: The occurrence of the LUT symptoms and bowel dysfunctions in CMT patients was significantly higher when compared with an age-matched control group. The symptoms were more frequent in female patients. The findings suggest that autonomic dysfunction should be evaluated and included in the diagnostic approach and care of CMT patients.

Clinical spectrum and gender differences in a large cohort of Charcot-Marie-Tooth type 1A patients.

INTRODUCTION: Heterogeneous clinical presentation and gender differences were reported in Charcot-Marie-Tooth disease type 1A (CMT1A). METHODS: This report examined demographic and clinical data collected during a randomised controlled trial, to describe the clinical spectrum of a large and well-defined cohort of CMT1A patients. RESULTS: Among the 189 symptomatic patients screened, three patients (1.6%) reported first symptoms in the upper limbs, which may be misleading when establishing the clinical diagnosis. The quality of life (QoL) of patients was significantly deteriorated compared to the standard population, and slightly better compared to multiple sclerosis patients. According to the literature, patients reported several disorders which may be associated with CMT1A, including auditory dysfunction (7.9%), Carpal Tunnel Syndrome (CTS) (7.9%) or sleep apnoea (4.2%). Compared to available data, we reported more patients with CTS and fewer patients with sleep apnoea. Women were more affected by CTS than men (11% and 2.8%, respectively). Women also reported an earlier onset of symptoms than men (8.6±9.5 years and 13.1±14 years, respectively), higher deterioration of their QoL and higher disability of their upper limb, assessed by Overall Neuropathy Limitation Scale (p=0.023). CONCLUSIONS: This information will be useful for better understanding of this disease and for designing future clinical studies.

Patient identification of the symptomatic impact of charcot-marie-tooth disease type 1A.

OBJECTIVE: The burden of Charcot-Marie-Tooth type 1A (CMT1A), the most common inherited peripheral neuropathy, including impact on patient quality of life (QOL) is not well understood. This study aims to qualitatively describe the range of symptoms associated with CMT1A and impact on QOL. METHODS: We performed qualitative interviews with 16 adult CMT1A patients. Each interview was analyzed using a qualitative framework technique to identify and index symptoms by theme. RESULTS: Sixteen patients provided 656 quotes. One hundred forty-five symptoms of importance were identified representing 20 symptomatic themes. Symptoms associated with difficulty with mobility and ambulation, specific activity impairment, and emotional distress were the most frequently mentioned. CONCLUSIONS: Multiple symptoms contribute to CMT1A disease burden, some previously underrecognized. Improved recognition of underrecognized symptoms will optimize patient care and QOL.

Quality of life in patients with Charcot-Marie-Tooth disease type 1A.

We assessed the functional impairment in Charcot-Marie-Tooth resulting from 17p11.2-p12 duplication (CMT1A) patients using the Short-Form Health Survey (SF-36), which is a quality of life questionnaire. Twenty-five patients of both genders aged ≥10 years with a positive molecular diagnosis of CMT1A were selected. Age- and gender-matched Control Group (without family history of neuropathy), and the sociodemographic and professional conditions similar to the patients' group were selected to compare the SF-36 results between them. The results showed that the majority quality of life impairments in CMT1A patients occurred in the social and emotional domains. Functional capacity also tended to be significantly affected; other indicators of physical impairment were preserved. In conclusion, social and emotional aspects are mostly neglected in the assistance provided to CMT1A Brazilian patients, and they should be better understood in order to offer global health assistance with adequate quality of life as a result.