Dysplastic nevi, cutaneous melanoma, and other skin neoplasms in patients with myotonic dystrophy type 1: a cross-sectional study.

BACKGROUND: Myotonic dystrophy type 1 (MD1) is reported to be associated with internal malignancies. The association of myotonic dystrophy with cutaneous tumors is not fully understood. OBJECTIVE: We sought to explore the total nevi count and the presence of atypical nevi, cutaneous melanoma, and other skin neoplasms in a representative cohort of patients with MD1 and to compare the findings with age- and sex-matched control subjects. METHODS: In all, 90 patients with MD1 and 103 age- and sex-matched control subjects were assessed for cutaneous neoplasms by clinical skin and epiluminescence examination (dermoscopy). Where indicated, subsequent excisions were performed. In patients with MD1, leukocyte n(CTG) expansion was measured. RESULTS: Patients with MD1 showed significantly higher numbers of nevi, dysplastic nevi, and melanomas despite a significantly greater proportion of the control subjects reporting sunburns. In addition, we found a significantly greater number of pilomatrixoma in patients with MD1. LIMITATIONS: Our study is limited by the fact that there is no agreed-upon standardized technique to assess for prior sun exposure. Further research in the association of cutaneous neoplasms and MD1 including vitamin D and molecular biological techniques are also recommended. CONCLUSION: MD1 itself may predispose to development of skin tumors.

Prevalence and clinical correlates of sleep disordered breathing in myotonic dystrophy types 1 and 2.

PURPOSE: Myotonic dystrophy types 1 (DM1) and 2 (DM2) are the most common muscular dystrophies in adulthood. A high prevalence of excessive daytime sleepiness (EDS) and sleep disordered breathing was documented in DM1; however, there are limited data available regarding DM2. Goals of the study were: (1) to evaluate the prevalence of sleep apnea in a large cohort of patients (71 DM1 and 14 DM2) and (2) to analyze correlations among such disorders and clinical features of myotonic dystrophies. METHODS: All patients underwent clinical examination, subjective sleep evaluation, and home based cardiorespiratory monitoring, and most of them performed pulmonary function tests and oropharyngeal-oesophageal scintigraphy (OPES). RESULTS: Almost 45% of patients reported poor sleep quality; only 20% of them referred EDS. Sleep studies documented sleep apnea, mostly obstructive, in 69% DM1 patients and 43% DM2 patients; overall, 28% of cases needed non-invasive ventilation. Neither age, gender, illness duration, body mass index, muscle involvement, OPES respiratory function indexes, nor n(CTG) in leukocytes were predictive of sleep apnea in DM1 patients. Conversely, in DM1 the central apnea-hypopnea index is correlated with the oral transit time estimated by OPES, whereas in DM2 apnea indexes are correlated with pulmonary function parameters. CONCLUSIONS: Sleep apnea is highly prevalent in both forms of myotonic dystrophies. In DM1, no clinical parameters appear to be predictive, while age appears to influence the severity of the obstructive variant; in DM2, the severity of sleep apnea is correlated with the degree of respiratory muscle involvement. Considering the harmful consequences of sleep apnea on cardiorespiratory function, our findings suggest including PSG in the follow-up of myotonic dystrophies.

Neuromuscular function after muscle fatigue in Charcot-Marie-Tooth type 1A patients.

INTRODUCTION: The effect of recovery time on neuromuscular function after a fatiguing task was compared in both the upper and lower limbs between patients with Charcot-Marie-Tooth type 1A (CMT1A) and healthy individuals. METHODS: Torque of elbow flexors and knee extensors and surface electromyography (sEMG) data of biceps brachii and vastus lateralis were recorded from 8 CMT1A patients and 8 matched, healthy individuals during maximal voluntary contraction (MVC) before (pre-fatigue MVC), 10 s after (10-s post-fatigue MVC), and 10 min after (10-min post-fatigue MVC) a fatiguing task at 80% MVC until exhaustion. RESULTS: Only in the lower limb, torque and root mean square of sEMG (RMS) during pre-fatigue MVC were lower (P < 0.05) in patients (91.93 ± 45.95 Nm, 0.11 ± 0.07 mV) than in controls (161.06 ± 75.5 Nm, 0.24 ± 0.16 mV). In the 10-min post-fatigue MVC, muscle-fiber conduction velocity (MFCV) and RMS, expressed as a percentage of pre-fatigue MVC, were lower (P < 0.05) in patients (MFCV 90.3 ± 6.91%, RMS 84.50 ± 9.89%) than in controls (MFCV 100.87 ± 5.1%, RMS 92.71 ± 11.84%). CONCLUSIONS: CMT1A patients are not only weaker than healthy individuals in the knee extensors, but they also have impaired neuromuscular recovery after fatigue.

Ultrasound tissue characterization detects preclinical myocardial structural changes in children affected by Duchenne muscular dystrophy.

Our goal was to identify early changes in myocardial physical properties in children with Duchenne muscular dystrophy (DMDch). Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, which triggers complex molecular and biological events in skeletal and cardiac muscle tissues. Although about 30% of patients display overt signs of cardiomyopathy in the late stage of the disease, it is unknown whether changes in myocardial physical properties can be detected in the early (preclinical) stages of the disease. We performed an ultrasonic tissue characterization (UTC) analysis of myocardium in DMDch with normal systolic myocardial function and no signs of cardiomyopathy. Both the cyclic variation of integrated backscatter (cvIBS) and the calibrated integrated backscatter (cIBS) were assessed in 8 myocardial regions of 20 DMDch, age 7 +/- 2 years (range 4 to 10 years), and in 20 age-matched healthy controls. We found large differences in the UTC data between DMDch and controls; the mean value of cvIBS was 4.4 +/- 1.5 dB versus 8.8 +/- 0.8 dB, whereas the mean value of cIBS was 36.4 +/- 7.1 dB versus 26.9 +/- 2.0 dB (p < 10(-6) for both). In DMDch, all eight sampled segments showed cIBS mean values to be significantly higher and cvIBS mean values to be significantly lower than those in the controls. Finally, interindividual differences were greater in DMDch than in controls for both parameters.The myocardium in DMDch displays UTC features different from those in healthy controls. These results show that lack of dystrophin is commonly associated with changes in myocardial features well before the onset of changes of systolic function and overt cardiomyopathy.

Amount and intensity of daily living activities in Charcot-Marie-Tooth 1A patients.

BACKGROUND: Charcot-Marie-Tooth 1A (CMT1A) patients show a reduction of spontaneous activities of daily living measured by means of questionnaires or pedometers, which are quite inaccurate compared to recent measurement techniques. AIM: The study aimed at quantifying daily living activities in CMT1A patients by means of inertial sensors, which give information not only on the amount but also on the intensity of these activities. MATERIALS AND METHODS: Time and count (amount), and velocity and power (intensity) of 24 h daily living activities were measured in eight patients (20-48 years; Barthel >90; Tinetti >20) and eight healthy individuals, matched for age and gender, by means of a wearable inertial sensor device. RESULTS: There were no differences between patients and controls in the 24-h distance covered and count of steps. However, count of step climbing and sit to stand were lower in patients than in controls (139.93 ± 141.66 vs. 341.06 ± 164.07 n and 58.23 ± 7.82 vs. 65.81 ± 4.75 n, respectively; P < 0.05) as well as mean daily step-climbing and walking velocities (1.07 ± 0.17 vs. 1.21 ± 0.10 m/sec and 1.16 ± 0.31 vs. 1.87 ± 0.50 m/sec, respectively; P < 0.05). In CMT1A patients there was a positive correlation between strength of the knee extensor muscles and both count of steps climbed (R = 0.80) and sit to stand (R = 0.79). DISCUSSION AND CONCLUSION: The reduced ability of CMT1A patients to carry out activities at high intensity, which was correlated with strength, suggests that strength training might be a rehabilitation tool for improving the 1 ability to carry out these activities.

An anterior ankle-foot orthosis improves walking economy in Charcot-Marie-Tooth type 1A patients.

BACKGROUND: Ankle-foot orthoses are commonly prescribed in Charcot-Marie-Tooth type 1A disease to improve quality of walking and reduce the risk of falling due to the foot drop. OBJECTIVES: This study aimed at assessing the effect of an anterior ankle-foot orthosis on walking economy in a group of Charcot-Marie-Tooth type 1A patients. STUDY DESIGN: Within-group comparisons. METHODS: 7 Charcot-Marie-Tooth type 1A patients (four women and three men; 37 ± 11 years; age range = 22-53 years) were asked to walk on a circuit at their self-selected speeds ('slow', 'comfortable' and 'fast') in two walking conditions: (1) with shoes only and (2) with Taloelast(®) anterior elastic ankle-foot orthoses. Speed of walking and metabolic cost of walking energy cost per unit of distance were assessed at the three self-selected speeds of walking for both walking conditions. RESULTS: Speed of walking at the three self-selected speeds did not differ between shoes only and anterior elastic ankle-foot orthoses, whereas walking energy cost per unit of distance at comfortable speed was lower in patients using anterior elastic ankle-foot orthoses with respect to shoes only (2.39 ± 0.22 vs 2.70 ± 0.19 J kg(-1) m(-1); P < 0.05). CONCLUSIONS: In Charcot-Marie-Tooth type 1A patients, the use of anterior elastic ankle-foot orthoses improved walking economy by reducing the energy cost of walking per unit of distance, thus reflecting a lower level of metabolic effort and improved mechanical efficiency in comparison with shoes only. CLINICAL RELEVANCE: From a practical perspective, Charcot-Marie-Tooth type 1A patients with anterior elastic ankle-foot orthoses can walk for a longer duration with a lower level of physical effort. Improvements in walking economy due to ankle-foot orthoses are likely a consequence of the reduction in steppage gait.

Comparison of walking energy cost between an anterior and a posterior ankle-foot orthosis in people with foot drop.

OBJECTIVE: To compare walking energy cost between an anterior and a posterior ankle-foot orthosis in people with foot drop. DESIGN: Within-group comparisons. PARTICIPANTS: Twenty-three adults (14 women, 9 men; mean age 56.8 years (standard deviation 15.4)) with foot drop. METHODS: PARTICIPANTS were asked to walk for 5 min at their self-selected walking speed under 3 conditions: (i) with shoes only; (ii) with a posterior ankle-foot orthosis; (iii) with an anterior ankle-foot orthosis. Spatio-temporal gait para-meters (speed, step length and step frequency) and walking energy cost per unit of distance were assessed for each walking condition. A visual analogue scale was used to quantify participants' level of perceived comfort for the 2 orthosis. RESULTS: Gait spatio-temporal parameters were higher with anterior ankle-foot orthoses than with posterior ankle-foot orthoses or shoes only. Walking energy cost per unit of distance was lower with anterior than posterior ankle-foot orthosis or shoes only ((mean ± standard error) 3.53 ± 1.00 vs 3.94 ± 1.27 and 3.98 ± 1.53 J·kg-1·m-1 respectively; p < 0.05) and level of perceived comfort was higher with anterior ((mean ± standard error) 8.00 ± 1.32) than with posterior ankle-foot orthosis ((mean ± standard error) 4.52 ± 2.57; p < 0.05). CONCLUSION: In people with foot drop the use of anterior ankle-foot orthoses resulted in lower energy costs of walking and higher levels of perceived comfort compared with posterior ankle-foot orthoses. Anterior ankle-foot orthoses may enable people with foot drop to walk further with less physical effort than posterior ankle-foot orthoses.

The role of the prefrontal cortex in the development of muscle fatigue in Charcot-Marie-Tooth 1A patients.

This study aimed at comparing both peripheral and central mechanisms of muscle fatigue between Charcot-Marie-Tooth 1A patients and healthy individuals during a fatiguing voluntary task by simultaneous electromyographic and electroencephalographic recordings. Six Charcot-Marie-Tooth 1A patients (3 females, 40±11 years) and 6-matched healthy individuals performed four blocks of sub-maximal isometric knee extensions. At the beginning of the session and after each block, electrically-evoked maximal single-twitch, maximal voluntary contraction and surface-electromyography of the vastus lateralis muscle were measured. The movement-related-cortical potentials were averaged in early (block 1-2) and late (block 3-4) stages of fatigue. The effect of fatigue was demonstrated at peripheral level by the decline of maximal voluntary contraction, maximal twitch and surface electromyography amplitude and at central level by the larger amplitude of movement-related-cortical-potentials during late than early stage of fatiguing sub-maximal contractions. Charcot-Marie-Tooth 1A patients showed lower motor cortex activity during motor planning, with earlier onset and larger prefrontal cortex activity during the late stage of the fatiguing task than healthy controls. These data demonstrate the key role of the prefrontal cortex in the development of fatigue in Charcot-Marie-Tooth 1A patients, which may be activated as a compensatory mechanism for the low motor cortex activation, thus reflecting high awareness of movement complexity.

Charcot-Marie-Tooth 1A patients with low level of impairment have a higher energy cost of walking than healthy individuals.

The study aimed at quantifying the walking energy cost of a group of Charcot-Marie-Tooth 1A patients (CMT1A), with low severity of walking impairment, in comparison with healthy individuals. Oxygen uptake was measured in 8 patients (age-range 20-48 years; Barthel >90; Tinetti >20) and 8 healthy individuals, matched for age and gender, when walking on a circuit for 5-min at their self-selected speeds ("slow", "comfortable" and "fast"). Both comfortable and fast speeds were lower in patients than in the control group (0.92±0.16 vs 1.16±0.22 and 1.27±0.27 vs 1.61±0.22 m s⁻¹, respectively; P<0.05), whereas walking energy cost per unit of distance was higher in patients than in the control group (P<0.05) at both "comfortable" (2.27±0.35 vs 1.92±0.21 J kg⁻¹m⁻¹) and "fast" speed (3.05±0.35 vs 2.37±0.42 J kg⁻¹m⁻¹). CMT1A patients, therefore, choose to walk slower but with higher metabolic cost compared to healthy individuals, despite no clinically evident walking impairment, which is likely due to altered walking patterns.