[Subjective oral health, malocclusions and oral health related quality of life in patients with Duchenne muscular dystrophy]. / De subjectieve mondgezondheid, malocclusies en orale kwaliteit van leven van patiënten met Duchenne-spierdystrofie.

Duchenne muscular dystrophy is a hereditary progressive neuromuscular disorder. Deterioration and weakening of the muscles is also present in orofacial muscles. Both weakness of the muscles and the fact that patients become more dependent of care, can make oral care more difficult. At this moment, it is unknown how patients with Duchenne muscular dystrophy experience their oral health and which problems regarding oral health and oral care may impact their oral health related quality of life. In this cross-sectional study, we found that, despite a high percentage of gingivitis, a high percentage of patients who experience halitosis and a high percentage of malocclusions, patients score their oral health related quality of life as good.

Orofacial muscles may be affected in early stages of Becker muscular dystrophy: A preliminary study.

BACKGROUND: Dysphagia is reported in patients with Duchenne or Becker muscular dystrophy. Our clinical experience suggests that, compared with Duchenne patients, impaired mastication and swallowing occur early in Becker patients relative to their skeletal muscle involvement. The aim of this study was to assess dysphagia in Duchenne and Becker patients in relation to ambulatory capacity. METHODS: In patients in the early ambulatory stage, clinical symptoms, quantitative muscle ultrasound of the orofacial muscles, and maximum bite force were assessed. The 6-Minute Walk Test (6MWT) was used to measure ambulatory capacity. RESULTS: Eleven Duchenne and 11 Becker patients were included. Although Becker patients had a greater 6MWT distance than Duchenne patients, the occurrence of mastication and swallowing difficulties was similar. The temporalis muscle was significantly thicker in Becker patients. CONCLUSIONS: Clinicians should be aware of dysphagia in both groups, even when ambulation is still well preserved.

Growing patients with Duchenne muscular dystrophy: longitudinal changes in their dentofacial morphology and orofacial functional capacities.

Aim: The aim of this study was to describe the longitudinal changes in facial morphology, dental arch alterations and oral functional capacities that occur in growing patients with Duchenne muscular dystrophy (DMD) in order to identify the effects of the progression of the disease. Subjects and Methods: Twelve DMD patients (6.5-17.5 years of age) and 12 matched controls were screened on two different occasions (T1 and T2), 2 years apart. Dental casts, lateral cephalometric radiographs, maximal posterior bite force and labial force were measured to determine changes in their functional capacities and dentofacial morphology. Furthermore, the thickness and echogenicity of the masseter muscle were measured during clenching. Statistical evaluation: Unpaired t-tests were performed to evaluate the differences between the DMD patients and their healthy matched controls; paired t-tests were used to assess the changes that occurred within each group between T1 and T2. Results: Between T1 and T2 the following changes were observed: widening of the lower dental arch for the DMD patients of 2.6mm (±0.9mm) compared to a slight reduction of -0.1mm (±0.8mm) for the control group (P = 0.001). We found a statistically significant reduction of the sagittal skeletal intermaxillary relationship (ANB-angle) of 2.0° (±2.0°) in the DMD group (P = 0.012). In T1 and T2, the maximal posterior bite force and the labial force were lower for the DMD patients compared to the control group (P = 0.001), who showed an increase during this period. Conclusion: The results indicate that DMD influences the facial morphology, dental arch dimensions and oral functional capacities. The longitudinal perspective of this study revealed that the worsening of most of the measured parameters is associated with the progression of the disease. Besides the expected deterioration of the functional measurements, we found in all patients, a marked transverse increase of the posterior part of the dental arches, more in the lower than in the upper, resulting in posterior crossbites, as well as a tendency towards a skeletal Class III relationship.

Anaesthetic Management in a Duchennne Muscle Dystrophy Patient for Treatment of Recurrent Pneumothorax.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is an x linked recessive disorder. Long term prognosis is ominous, with development of respiratory distress and cardiomyopathy in advanced stage of the disease and expected death in the teens-to-mid 20s due to respiratory or cardiac failure. Peri-operative management of this patients is challenging due to difficult airway anatomy (macroglossia, limited neck and mandibular mobility). Additionally, they are at risk of developing malignant hyperthermia, rhabdomyolysis and hyperkalemic cardiac arrest when exposed to halogenated inhalational anaesthetics and depolarizing muscle relaxants. METHODS: We describe a case of DMD proposed to a thoracotomy for treatment of recurrent pneumothorax and its anaesthetic approach. RESULTS: A 22-year-old male patient with DMD presented at emergency department due dyspnoea starting at 3 days associated with right scapular pain, enhanced by breathing. The patient already presents with mild cardiomyopathy (ejection fraction of 55%, mild mitral and tricuspid regurgitation), severe restrictive respiratory defect, requiring continuous BiPAP. The patient was markedly denourished (BMI of 12 kg/m2) and presented with nearly absent breathing sounds on the right side. Chest radiography showed large pneumothorax on the right side with no signs of tension. Drainage was performed. Despite initial success, recurrence of pneumothorax occurred on the several attempts of clamping. A bronchopleural fistula was suspected and operative treatment was considered. Considering the comorbidities, he was graded ASA IV with a difficult airway due to macroglossia, limited neck and mandibular mobility. Oro-tracheal intubation was performed with slight sedation (propofol, without neuromuscular blocks). Difficult airway anatomy (direct laryngoscopy - Cormack 4) successfully approached with a bougie and Mccoy blade. Fibreoptic intubation approach was immediately available in the operating room, if required. Total intravenous anaesthesia was decided (remifentanil and propofol, administered by continuous infusion, without neuromuscular blockers). Volume controlled protective ventilation as used (tidal volume 6-8ml/kg, respiratory frequency of 14-16/ min; FiO2: 0,5). No bronchopleural fistula was detected and pleurodesis was performed with biologic glue. Patient remained intubated and was transferred to the ICU for monitoring, having been discharged on the 2nd day to the ward. Despite this, pneumothorax recurrence occurred, and surgery was performed again, using the same anaesthetic approach, this time with successful closure of the bronchopleural fistula. CONCLUSION: Total intravenous anaesthesia, without neuromuscular blockers, is a safe and effective option for DMD patients. Anaesthesiologists must consider the possibility of cardio-pulmonary disabilities, difficult airway management, as well as the high risk of malignant hyperthermia in these patients.

Orthodontic treatment of a patient with Duchenne muscular dystrophy and macroglossia: how informed consent was critical to success.

This article describes the complex orthodontic treatment of a 22-year-old patient with Duchenne muscular dystrophy and macroglossia. His orthodontic treatment hinged on providing proper informed consent and management of the malocclusion with glossectomy, extractions, fixed appliances, and elastics. Challenges to traditional treatment are outlined, and compromises to both process and outcome are discussed from an informed consent point of view because of the serious risks involved. The treatment objectives were met, and the outcome was considered a success.

[Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses].

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Open Bite Malocclusion and Orofacial Dysfunction in Patients with Myotonic Dystrophy Type 1 and Duchenne Muscular Dystrophy.

Open bite (OB) is a common malocclusion in individuals with orofacial dysfunction and syndromes, especially in neuromuscular diseases. OBJECTIVES: The objectives were to explore the prevalence of OB in myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and to create and compare orofacial dysfunction profiles. METHODS: In this database study, 143 individuals with DM1 and 99 with DMD were included. The Mun-H-Center questionnaire and observation chart were used together with the Nordic Orofacial Test -Screening (NOT-S) to create orofacial dysfunction profiles. OB was categorised as: lateral (LOB); anterior (AOB); severe anterior (AOBS); or both types of anterior OB (AOBTot). Descriptive and multivariate statistics were used to compare the OB prevalence and to study associations with orofacial variables, respectively. RESULTS: There was a statistically significant difference in OB prevalence between the DM1 (37%) and DMD (49%) groups (p = 0.048). LOB was seen in < 1% of DM1 and 18% of DMD. LOB was associated with macroglossia and closed mouth posture, AOB with hypotonic lips, and open mouth posture and AOBS with hypotonic jaw muscles. The orofacial dysfunction profiles showed similar patterns, although the mean NOT-S total scores for DM1 and DMD were 4.2±2.8 (median 4.0, min-max 1-8) and 2.3±2.0 (median 2.0, min-max 0-8), respectively. LIMITATIONS: The two groups were not age- or gender-matched. CONCLUSION: OB malocclusion is common in patients with DM1 and DMD and is associated with different types of orofacial dysfunction. This study highlights the need for multi-disciplinary assessments to support tailored treatment strategies that improve or sustain orofacial functions.

Membrane sealant Poloxamer P188 protects against isoproterenol induced cardiomyopathy in dystrophin deficient mice.

BACKGROUND: Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy. METHODS: Three month old female mdx mice were exposed to the ß(1) receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining. RESULTS: BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers. CONCLUSIONS: This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.

Dystrophic heart failure blocked by membrane sealant poloxamer.

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy. Heart failure is the second leading cause of fatalities in DMD. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease. Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy.

Alleviation of masticatory disturbance with an occlusal splint in a Duchenne muscular dystrophy patient.

AIM: To present an occlusal splint effective for alleviating masticatory disturbance in Duchenne muscular dystrophy (DMD). CASE REPORT: A 13-year-old male DMD patient with masticatory disturbance presented with an open bite, with occlusal contact only between the first and second molars bilaterally and reduced masticatory performance. We applied an occlusal splint that achieved occlusal contact for all teeth and monitored its effects on masticatory function over 6 years. The occlusal splint increased occlusal contact points from 11 to 60. Although occlusal force remained at 13.9-16 kg, masticatory performance increased, and the number of mastication strokes increased from 124 to 169. Masseter muscle activity decreased from 76.8% to 33.4% maximum voluntary contraction (MVC) and digastric muscle activity increased from 8.7% to 18.0% MVC. Time from start of peanut mastication to swallowing decreased, and the vertical mastication cycle diameter and its width on the habitual side increased. CONCLUSIONS: Masticatory disturbance in a DMD patient was alleviated using an occlusal splint. The number of mastication strokes and the digastric to masseter muscle activity ratio were increased. Furthermore, the mastication cycle was enlarged, which increased masticatory movement. As masseter muscle activity during mastication decreased, the occlusal splint likely reduced muscle fatigue during masticatory movement.

Interventions for increasing ankle range of motion in patients with neuromuscular disease.

BACKGROUND: Reduced ankle dorsiflexion range of motion, or ankle equinus, is a common and disabling problem for patients with neuromuscular disease. Clinicians devote considerable time and resources implementing interventions to correct this problem although few of these interventions have been subject to rigorous empirical investigation. OBJECTIVES: To assess the effect of interventions to reduce or resolve ankle equinus in people with neuromuscular disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Specialized Register (August 2009), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2009), MEDLINE (1966 to August 2009), EMBASE (1980 to August 2009), CINAHL 1982 to August 2009), AMED (1985 to August 2009) and The Physiotherapy Evidence Database (PEDro) (1929 to August 2009). We searched the reference lists of identified articles and also contacted known experts in the field to identify additional or unpublished data. SELECTION CRITERIA: Randomised controlled trials evaluating interventions for increasing ankle dorsiflexion range of motion in neuromuscular disease. Outcomes included ankle dorsiflexion range of motion, functional improvement, foot alignment, foot and ankle muscle strength, health-related quality of life, satisfaction with the intervention and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, assessed trial quality and extracted data. MAIN RESULTS: Four studies involving 149 participants met inclusion criteria for this review. Two studies assessed the effect of night splinting in a total of 26 children and adults with Charcot-Marie-Tooth disease type 1A. There were no statistically or clinically significant differences between wearing a night splint and not wearing a night splint. One study assessed the efficacy of prednisone treatment in 103 boys with Duchenne muscular dystrophy. While a daily dose of prednisone at 0.75 mg/kg/day resulted in significant improvements in some strength and function parameters compared with placebo, there was no significant difference in ankle range of motion between groups. Increasing the prednisone dose to 1.5 mg/kg/day had no significant effect on ankle range of motion. One study evaluated early surgery in 20 young boys with Duchenne muscular dystrophy. Surgery resulted in increased ankle dorsiflexion range at 12 months but functional outcomes favoured the control group. By 24 months, many boys in the surgical group experienced a relapse of achilles tendon contractures. AUTHORS' CONCLUSIONS: There is no evidence of significant benefit from any intervention for increasing ankle range of motion in Charcot-Marie-Tooth disease type 1A or Duchenne muscular dystrophy. Further research is required.

Range of motion exercise of temporo-mandibular joint with hot pack increases occlusal force in patients with Duchenne muscular dystrophy.

The purpose of this study is to evaluate whether the range of motion exercise of the temporo-mandibular joint (jaw ROM exercise) with a hot pack and massage of the masseter muscle improve biting disorder in Duchenne muscular dystrophy (DMD). The subjects were 18 DMD patients (21.3+/- 4.1 years old). The jaw ROM exercise consisted of therapist-assisted training (2 times a week) and self-training (before each meal every day). The therapist-assisted training consisted of the application of a hot pack on the cheek of the masseter muscle region (15 minutes), the massage of the masseter (10 minutes), and jaw ROM exercise (5 minutes). The self-training involved jaw ROM exercise by opening the mouth to the maximum degree, ten times. These trainings continued for six months. Outcomes were evaluated by measuring the greatest occlusal force and the distance at the maximum degree of mouth opening between an incisor of the top and that of the bottom. Six months later, the greatest occlusal force had increased significantly compared with that at the start of jaw ROM exercise (intermediate values: from 73.8N to 97.3N) (p = 0.005) as determined by the Friedman test and Scheffi's nonparametric test. The patients' satisfaction with meals increased. However, the maximum degree of mouth opening did not change after six months of jaw ROM exercise. Jaw ROM exercise in DMD is effective for increasing the greatest occlusal force.

Management of the dentoalveolar effects of tongue hypertrophy in patients with Duchenne muscular dystrophy: A pilot study.

Subjects affected by Duchenne muscular dystrophy (DMD) develop severe malocclusions with the progression of the disease, due to changes in orofacial musculature and function, including tongue hypertrophy. We aimed to evaluate the benefits of maintaining mandibular interarch width with the help of a simple fixed orthodontic appliance. Three adolescent DMD boys were selected consecutively to receive a passive rigid mandibular lingual arch, and followed for 4-5 years. An untreated age-matched control group was chosen and followed for a similar period. Study casts were obtained at baseline and after follow-up. Outcomes measured were overjet, overbite, maxillary and mandibular intermolar widths, mandibular arch depth, molar relationships, and the presence of lateral crossbites and anterior or lateral openbites. Changes in measurements obtained between the two time points were compared in each age-matched pair. There was a clinically important increase in the mandibular intermolar width in the non-treated children ranging from 2.5 mm to 9 mm, but not in those treated. Malocclusions generally deteriorated in untreated children while they remained stable in treated children. The use of a rigid mandibular lingual arch in boys with DMD can help slow down the rapid deterioration of the developing malocclusions that accompanies the progression of the disease.

Walking and weakness in children: a narrative review of gait and functional ambulation in paediatric neuromuscular disease.

BACKGROUND: Weakness is the primary impairment in paediatric neuromuscular diseases, impacting gait and gait-related functional activities in ambulant children affected by these rare and often degenerative diseases. Gait speed is an indicator of health and disability, yet gait is a complex, multi-faceted activity. Using the International Classification of Function, Health and Disability (ICF) model, assessment of gait and functional ambulation should consider the impairments, activity limitations and participation restrictions due to disease, and factors related to the environment and the individual person. METHODS: This narrative review involved a literature search of databases including Medline, Embase and Pubmed from 1946 to October 2019. Inclusion criteria included assessments of gait, endurance and ambulatory function in paediatric (0-18 years) neuromuscular diseases. RESULTS: Fifty-two papers were identified reporting assessments of gait speed, timed function, endurance and ambulatory capacity, gait-related balance and qualitative descriptive assessments of gait function and effect of disease on gait and gait-related activities. Gait speed is an indicator of disability and children with neuromuscular disease walk slower than typically developing peers. Increasing disease severity and age were associated with slower walking in children with Duchenne muscular dystrophy and Charcot-Marie-Tooth disease. The six-minute walk test is used widely as a test of endurance and ambulatory capacity; six-minute walk distance was substantially reduced across all paediatric neuromuscular diseases. Endurance and ambulatory capacity was more limited in children with spinal muscular atrophy type 3, congenital muscular dystrophy and older boys with Duchenne muscular dystrophy. Only a few papers considered normalisation of gait parameters accounting for the effect on gait of height in heterogeneous groups of children and linear growth in longitudinal studies. Balance related to gait was considered in five papers, mainly in children with Charcot-Marie-Tooth disease. There was limited investigation of factors including distance requirements and terrain in children's typical environments and personal factors related to self-perception of disease effect on gait and gait-related function. CONCLUSION: Assessments of gait and functional ambulation are important considerations in documenting disease progression and treatment efficacy in the clinical setting; and in clinical trials of disease-modifying agents and physiotherapeutic interventions in paediatric neuromuscular diseases. There is a need for expert consensus on core gait and functional ambulation assessments for use in clinical and research settings.

Rehabilitation interventions for foot drop in neuromuscular disease.

BACKGROUND: "Foot drop" or "Floppy foot drop" is the term commonly used to describe weakness or contracture of the muscles around the ankle joint. It may arise from many neuromuscular diseases. OBJECTIVES: To conduct a systematic review of randomised trials for the treatment of foot drop resulting from neuromuscular disease. SEARCH STRATEGY: In this update, we searched the Cochrane Neuromuscular Disease Group Trials Register (April 2009), MEDLINE (January 1966 to April 24 2009), EMBASE January 1980 to April 24 2009), CINAHL (January 1982 to May 6 2009), AMED (January 1985 to April 24 2009), the British Nursing Index (January 1985 to January 2008) and Royal College of Nursing Journal of Databases (January 1985 to January 2008). SELECTION CRITERIA: Randomised and quasi-randomised trials of physical, orthotic and surgical treatments for foot drop resulting from lower motor neuron or muscle disease and related contractures were included. People with primary joint disease were excluded. Interventions included a 'wait and see' approach, physiotherapy, orthoses, surgery and pharmacological therapy. The primary outcome measure was quantified ability to walk whilst secondary outcome measures included range of movement, dorsiflexor torque and strength, measures of activity and participation, quality of life and adverse effects. DATA COLLECTION AND ANALYSIS: Methodological quality was evaluated by two authors using the van Tulder criteria. Four studies with a total of n = 152 participants were included in the update to the original review. Heterogeneity of the studies precluded pooling the data. MAIN RESULTS: Early surgery did not significantly affect walking speed in a trial including 20 children with Duchenne muscular dystrophy. Both groups deteriorated during the 12 months follow-up. After one year, the mean difference (MD) of the 28 feet walking time was 0.00 seconds (95% confidence interval (CI) -0.83 to 0.83) and the MD of the 150 feet walking time was -2.88 seconds, favouring the control group (95% CI -8.18 to 2.42). Night splinting of the ankle did not significantly affect muscle force or range of movement about the ankle in a trial of 26 participants with Charcot-Marie-Tooth disease. Improvements were observed in both the splinting and control groups. In a trial of 26 participants with Charcot-Marie-Tooth disease and 28 participants with myotonic dystrophy, 24 weeks of strength training significantly improved six-metre timed walk in the Charcot-Marie-Tooth group compared to the control group (MD 0.70 seconds, favouring strength training, 95% CI 0.23 to 1.17), but not in the myotonic dystrophy group (MD -0.20 seconds, favouring the control group, 95% CI -0.79 to 0.39). No significant differences were observed for the 50 metre timed walk in the Charcot-Marie-Tooth disease group (MD 1.90 seconds, favouring the training group, 95% CI -0.29 to 4.09) or the myotonic dystrophy group (MD -0.80 seconds, favouring the control group, 95% CI -5.29 to 3.69). In a trial of 65 participants with facioscapulohumeral muscular dystrophy, 26 weeks of strength training did not significantly affect ankle strength. After one year, the mean difference in maximum voluntary isometric contraction was -0.43 kg, favouring the control group (95%CI -2.49 to 1.63) and the mean difference in dynamic strength was 0.44 kg, favouring the training group (95%CI -0.89 to 1.77). AUTHORS' CONCLUSIONS: Only one study, involving people with Charcot-Marie-Tooth disease, demonstrated a statistically significant positive effect of strength training. No effect of strength training was found in people with either myotonic dystrophy or facioscapulohumeral muscular dystrophy. Surgery had no significant effect in children with Duchenne muscular dystrophy and night splinting of the ankle had no significant effect in people with Charcot-Marie-Tooth disease. More evidence generated by methodologically sound trials is required.

Charcot-Marie-Tooth neuropathy type 1A combined with Duchenne muscular dystrophy.

We report a 24-year-old male with an unusual combination of two inherited neuromuscular disorders--Charcot-Marie-Tooth (CMT) disease type 1A and Duchenne muscular dystrophy (DMD). A phenotypic presentation of this patient included features of both these disorders. Nerve conduction studies revealed demyelinating peripheral neuropathy. Electromyography showed a profound myogenic pattern. The serum creatine kinase level was highly elevated. Muscle biopsy revealed a dystrophic picture with deficient dystrophin immunostaining. CMT1A duplication on chromosome 17p11.2 was found. The frame-shift mutation c.3609-3612delTAAAinsCTT (p.K1204LfsX11) was detected in the dystrophin gene by analysing mRNA isolated from the muscle tissue. The patient inherited both these mutations from his mother. The combination of CMT1A and DMD has not been reported as yet.

Rehabilitation interventions for foot drop in neuromuscular disease.

BACKGROUND: "Foot drop" or "Floppy foot drop" is the term commonly used to describe weakness or contracture of the muscles around the ankle joint. It may arise from many neuromuscular diseases. OBJECTIVES: To conduct a systematic review of randomised trials of treatment for footdrop resulting from neuromuscular disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (July 2005), MEDLINE (January 1966 to July 2005), EMBASE (January 1980 to July 2005), AMED (January 1985 to July 2005) and CINAHL databases (January 1982 to July 2005). SELECTION CRITERIA: Randomised and quasi-randomised trials of physical, orthotic and surgical treatments for footdrop resulting from lower motor neuron or muscle disease and related contractures were included. People with primary joint disease were excluded. Interventions included a 'wait and see' approach, physiotherapy, orthotics, surgery and pharmacological therapy. The primary outcome measure was ability to walk whilst secondary outcome measures included dorsiflexor torque and strength, measures of 'activity' and 'participation' and adverse effects. DATA COLLECTION AND ANALYSIS: Methodological quality was evaluated by two authors using the van Tulder criteria. Three studies with altogether 139 participants were included in the review. Heterogeneity of the studies precluded pooling the data. MAIN RESULTS: Early surgery did not significantly affect walking speed in a trial including 20 children with Duchenne muscular dystrophy. After one year, the mean difference (MD) of the 28 feet walking time was 0.00 seconds (95% confidence interval (CI) -0.83 to 0.83) and the MD of the 150 feet walking time was -2.88 seconds, (95% CI -8.18 to 2.42). In a trial with altogether 26 participants with Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy), long-term strength training significantly increased walking speed on a 6 metre timed walk (MD -0.70 seconds, 95% CI -1.17 to -0.23) but not on a 50 metre timed walk (MD -1.9 seconds, 95% CI -4.09 to 0.29). In a trial of a 24-week strength training programme in 28 participants with myotonic dystrophy, there was no significant change in walking speed on either a 6 or 50 metre walk. AUTHORS' CONCLUSIONS: Using the primary outcome of ability to walk, only one study demonstrated a positive effect and that was an exercise programme for people with Charcot-Marie-Tooth disease. Surgery was not significantly effective in children with Duchenne Muscular Dystrophy. More evidence generated by methodologically sound trials is required.

Effect of pyridostigmine on in vivo and in vitro respiratory muscle of mdx mice.

The current work was conducted to verify the contribution of neuromuscular transmission defects at the neuromuscular junction to Duchenne Muscular Dystrophy disease progression and respiratory dysfunction. We tested pyridostigmine and pyridostigmine encapsulated in liposomes (liposomal PYR), an acetylcholinesterase inhibitor to improve muscular contraction on respiratory muscle function in mdx mice at different ages. We evaluated in vivo with the whole-body plethysmography, the ventilatory response to hypercapnia, and measured in vitro diaphragm strength in each group. Compared to C57BL10 mice, only 17 and 22 month-old mdx presented blunted ventilatory response, under normocapnia and hypercapnia. Free pyridostigmine (1mg/kg) was toxic to mdx mice, unlike liposomal PYR, which did not show any side effect, confirming that the encapsulation in liposomes is effective in reducing the toxic effects of this drug. Treatment with liposomal PYR, either acute or chronic, did not show any beneficial effect on respiratory function of this DMD experimental model. The encapsulation in liposomes is effective to abolish toxic effects of drugs.

Mouthpiece ventilation in Duchenne muscular dystrophy: a rescue strategy for noncompliant patients.

OBJECTIVE:: To evaluate mouthpiece ventilation (MPV) in patients with Duchenne muscular dystrophy (DMD) who are noncompliant with noninvasive ventilation (NIV). METHODS:: We evaluated four young patients with DMD who had previously refused to undergo NIV. Each patient was reassessed and encouraged to try MPV. RESULTS:: The four patients tolerated MPV well and were compliant with NIV at home. MPV proved to be preferable and more comfortable than NIV with any other type of interface. Two of the patients required overnight NIV and eventually agreed to use a nasal mask during the night. CONCLUSIONS:: The advantages of MPV over other types of NIV include fewer speech problems, better appearance, and less impact on the patient, eliminating the risk of skin breakdown, gastric distension, conjunctivitis, and claustrophobia. The use of a mouthpiece interface should be always considered in patients with DMD who need to start NIV, in order to promote a positive approach and a rapid acceptance of NIV. Using MPV during the daytime makes patients feel safe and more likely to use NIV at night. In addition, MPV increases treatment compliance for those who refuse to use other types of interfaces. OBJETIVO:: Avaliar a ventilação bucal (VB) em pacientes com distrofia muscular de Duchenne (DMD) não aderentes à ventilação não invasiva (VNI). MÉTODOS:: Foram avaliados quatro pacientes jovens com DMD que anteriormente recusaram-se a se submeter à VNI. Cada paciente foi reavaliado e encorajado a tentar VB. RESULTADOS:: Os quatro pacientes toleraram bem a VB e aderiram ao uso de VNI em casa. O uso de VB provou ser uma alternativa preferível e mais confortável que o uso de VNI com qualquer outro tipo de interface. Dois dos pacientes necessitaram de VNI noturna e eventualmente aceitaram utilizar uma máscara nasal durante a noite. CONCLUSÕES:: As vantagens da VB sobre outros tipos de VNI incluem menores problemas na fala, melhor aparência e menor impacto no paciente, eliminando o risco de lesões na pele, distensão gástrica, conjuntivite e claustrofobia. O uso da interface bucal sempre deve ser considerado em pacientes com DMD que necessitam iniciar VNI a fim de promover uma abordagem positiva e uma rápida aceitação da VNI. O uso diurno de VB faz com que os pacientes sintam-se seguros e mais propensos a utilizar VNI à noite. Além disso, a VB aumenta a adesão ao tratamento naqueles pacientes que se recusam a utilizar outros tipos de interfaces.