Pharmacological Treatments and Therapeutic Targets in Muscle Dystrophies Generated by Alterations in Dystrophin-Associated Proteins.

Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)-the most common type of MD-and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.

Ambient floor vibration sensing advances the accessibility of functional gait assessments for children with muscular dystrophies.

Muscular dystrophies (MD) are a group of genetic neuromuscular disorders that cause progressive weakness and loss of muscles over time, influencing 1 in 3500-5000 children worldwide. New and exciting treatment options have led to a critical need for a clinical post-marketing surveillance tool to confirm the efficacy and safety of these treatments after individuals receive them in a commercial setting. For MDs, functional gait assessment is a common approach to evaluate the efficacy of the treatments because muscle weakness is reflected in individuals' walking patterns. However, there is little incentive for the family to continue to travel for such assessments due to the lack of access to specialty centers. While various existing sensing devices, such as cameras, force plates, and wearables can assess gait at home, they are limited by privacy concerns, area of coverage, and discomfort in carrying devices, which is not practical for long-term, continuous monitoring in daily settings. In this study, we introduce a novel functional gait assessment system using ambient floor vibrations, which is non-invasive and scalable, requiring only low-cost and sparsely deployed geophone sensors attached to the floor surface, suitable for in-home usage. Our system captures floor vibrations generated by footsteps from patients while they walk around and analyzes such vibrations to extract essential gait health information. To enhance interpretability and reliability under various sensing scenarios, we translate the signal patterns of floor vibration to pathological gait patterns related to MD, and develop a hierarchical learning algorithm that aggregates insights from individual footsteps to estimate a person's overall gait performance. When evaluated through real-world experiments with 36 subjects (including 15 patients with MD), our floor vibration sensing system achieves a 94.8% accuracy in predicting functional gait stages for patients with MD. Our approach enables accurate, accessible, and scalable functional gait assessment, bringing MD progressive tracking into real life.

Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy / Desempenho funcional e força muscular em portadoras sintomáticas de distrofia muscular de Duchenne

Abstract Duchenne muscular dystrophy (DMD) usually affects men. However, women are also affected in rare instances. Approximately 8% of female DMD carriers have muscle weakness and cardiomyopathy. The early identification of functional and motor impairments can support clinical decision making. Objective: To investigate the motor and functional impairments of 10 female patients with dystrophinopathy diagnosed with clinical, pathological, genetic and immunohistochemical studies. Methods: A descriptive study of a sample of symptomatic female carriers of DMD mutations. The studied variables were muscular strength and functional performance. Results: The prevalence was 10/118 (8.4%) symptomatic female carriers. Deletions were found in seven patients. The age of onset of symptoms in female carriers of DMD was quite variable. Pseudohypertrophy of calf muscles, muscular weakness, compensatory movements and longer timed performance on functional tasks were observed in most of the cases. Differently from males with DMD, seven female patients showed asymmetrical muscular weakness. The asymmetric presentation of muscle weakness was frequent and affected posture and functionality in some cases. The functional performance presents greater number of compensatory movements. Time of execution of activities was not a good biomarker of functionality for this population, because it does not change in the same proportion as the number of movement compensations. Conclusion: Clinical manifestation of asymmetrical muscle weakness and compensatory movements, or both can be found in female carriers of DMD mutations, which can adversely affect posture and functional performance of these patients.

Resumo A distrofia muscular de Duchenne (DMD) geralmente afeta indivíduos do sexo masculino. No entanto, mulheres também são acometidas em casos raros. Aproximadamente 8% das portadoras de DMD têm fraqueza muscular ou cardiomiopatia. A identificação precoce das alterações funcionais e motoras pode alterar a tomada de decisão clínica. Objetivo: Investigar as deficiências motoras e funcionais de 10 pacientes do sexo feminino com distrofinopatia diagnosticada por estudos clínicos, patológicos, genéticos e imuno-histoquímicos. Método: Estudo descritivo de uma amostra de portadoras sintomáticas de mutações DMD. As variáveis estudadas foram força muscular e desempenho funcional. Resultados: A prevalência foi de 10/118 (8,4%) de portadoras sintomáticas de DMD. Foram encontradas deleções em sete pacientes. A idade de início dos sintomas em portadoras de DMD foi variável. Pseudo-hipertrofia de panturrilhas, movimentos compensatórios, fraqueza muscular e aumento no tempo de execução de tarefas funcionais foram observados na maioria dos casos. Diferentemente dos homens com DMD, sete pacientes apresentaram fraqueza muscular assimétrica. A apresentação assimétrica da fraqueza muscular foi frequente, podendo afetar a postura e a funcionalidade. O desempenho funcional geralmente apresenta aumento no número de movimentos compensatórios. Não podemos sempre considerar o tempo como um bom marcador de funcionalidade para essa população, uma vez que não muda na mesma proporção que o número de compensações em todas essas pacientes. Conclusão: Fraqueza muscular assimétrica e movimentos compensatórios, ou ambos, podem ser encontrados em portadoras sintomáticas de DMD, o que pode afetar a postura e a funcionalidade dessas pacientes.

Fisioterapia aquática no tratamento de criança com distrofia muscular congênita merosina negativa: relato de caso / Aquatic physical therapy in the treatment of a child with merosin-deficient congenital muscular dystrophy: case report

Este relato de caso descreve um programa de fisioterapia aquática para uma criança com distrofia muscular congênita (DMC) merosina negativa. Objetivo: Verificar a interferência da fisioterapia aquática na velocidade e no índice de gasto energético durante o deslocamento sentado em superfície plana, e no alcance funcional com os membros superiores devido a fraqueza proximal que acomete estes pacientes visando maior independência. Métodos: Como instrumentos de avaliação foram utilizados a Medida da Função Motora (MFM); o Functional Reach Test (FRT); foi verificado o Índice de Gasto Energético (IGE) no deslocamento sentado; assim como o tempo gasto neste deslocamento e a ativação muscular com a eletromiografia (EMG). O programa durou 12 semanas e a intervenção incluiu atividades para melhorar a mobilidade e a agilidade no deslocamento sentado e o alcance na postura sentada. Resultados: Na MFM a variação no escore das duas dimensões (D2 e D3) focadas na terapia foi de 6,8%. O alcance funcional melhorou 16 centímetros (cm) e o tempo do deslocamento sentado diminuiu 19 segundos (s). O gasto energético diminuiu 252,31 batimentos por minuto (bpm). Conclusão: A fisioterapia aquática foi eficaz para melhora da agilidade no deslocamento sentado e na funcionalidade de membros superiores (MMSS) de uma criança com DMC merosina negativa

This case report describes an aquatic therapy program for a child with Merosin-Deficient Congenital Muscular Dystrophy. Objective: This study sought to investigate the effect of aquatic physical therapy on the speed and the rate of energy expenditure while moving around on a flat surface, in addition to the functional reach of the upper limbs suffering from the proximal weakness that affects these patients seeking greater independence. Methods: The Motor Function Measurement (MFM) and the Functional Reach Test (FRT) were used as assessment tools; the Energy Expenditure Index (EEI) was measured in seated locomotion, as well as the time spent, and muscle activation was measured via electromyography (EMG). The program lasted 12 weeks and included activities to improve mobility and agility as well as reaching from the seated position. Results: In the MFM the change in the score of the two dimensions (D2 and D3) that the treatment focused on was 6.8%. The functional reach improved by 16 centimeters (cm) and the amount of time moving while sitting decreased by 19 seconds (s). Energy expenditure decreased by 252.31 beats per minute (bpm). Conclusion: The aquatic physical therapy was effective for agility improvement in seated locomotion and upper limb functionality of a 6-year-old child with Merosin-Deficient Congenital Muscular Dystrophy

Síndrome d'embòlia grassa en un pacient afectat de distròfiamuscular de Duchenne. Més risc en aquesta població? / Síndrome de embolia grasa en un paciente afecto de distrofia muscular de Duchenne. Mayor riesgo en esta población? / Fat embolism syndrome in two patients with Duchenne muscular dystrophy. Is there an increased risk in this population?

Introducció: la distròfia muscular de Duchenne és la distròfia muscular més comuna en la població pediàtrica. Aquests pacients presenten una mineralització òssia deficient i les fractures són freqüents. La síndrome d'embòlia grassa és una de les complicacions difícils de diagnosticar si no existeix una alta sospita, ja que moltes vegades es presenta de forma subclínica. Observació clínica: es presenten dos pacients de 12 i 15 anys amb malaltia de Duchenne que després d'una caiguda presenten al cap de 3 i 16 hores, respectivament, un quadre d'inici sobtat de dificultat respiratòria. En tots dos casos les radiografies mostren fractura de fèmur i s'orienten com una síndrome d'embòlia grassa. Comentaris: l'embòlia grassa és l'obstrucció d'un vas per un èmbol gras, la majoria de casos secundari a fractures d'ossos llargs, que contenen trioleïnes; aquestes penetren amb facilitat al torrent sanguini i provoquen microinfarts i hemorràgies. Entre el 15 i el 44% dels infants afectats per la malaltia de Duchenne tindran alguna fractura. En alguns casos, aquestes fractures donaran lloc a una síndrome d'embòlia grassa. Tenint en compte que la majoria de vegades es presenta de forma subclínica, és una entitat que cal considerar en aquests pacients quan presenten símptomes respiratoris i/o neurològics després d'un traumatisme amb fractura, encara que aquesta sigui no desplaçada

Introducción. La distrofia muscular de Duchenne es la distrofia muscular más común en la población pediátrica. Estos pacientes presentan una mineralización ósea deficiente y las fracturas son frecuentes. El síndrome de embolia grasa es una de las posibles complicaciones de difícil diagnóstico si no existe una alta sospecha, dado que muchas veces se presenta de forma subclínica. Observación clínica. Se presentan dos pacientes de 12 y 15 años con enfermedad de Duchenne que tras caída presentan a las 3 y 16 horas, respectivamente, un cuadro de inicio súbito de dificultad respiratoria. En ambos casos las radiografías muestran fractura de fémur y se orientan como un síndrome de embolia grasa. Comentarios. La embolia grasa es la obstrucción de un vaso por un émbolo graso, secundario en la mayoría de ocasiones a fracturas de huesos largos, que contienen trioleínas; estas penetran con facilidad al torrente sanguíneo provocando microinfartos y hemorragias. Entre el 15 y el 44% de los niños afectos de Duchenne padecen fracturas. En algunos casos esas fracturas darán lugar a un síndrome de embolia grasa. Dado que en la mayoría de ocasiones se presenta de forma subclínica, es una entidad a tener en cuenta en estos pacientes cuando presenten síntomas respiratorios y/o neurológicos tras traumatismos con fracturas, incluso no desplazadas (AU)

Introduction. Duchenne muscular dystrophy is the most common muscular dystrophy in the pediatric population. Patients with Duchenne dystrophy have poor bone mineralization, and fractures are frequent. Fat embolism syndrome is one of the possible complications; it commonly presents subclinically and in the absence of high level of suspicion, the diagnosis is difficult. Clinical observation. We present two patients aged 12 and 15 years with Duchenne dystrophy who presented with acute onset of respiratory distress hours after a fall. In both cases the X-rays showed femur fractures and were diagnosed as having a fat embolism syndrome. Comments. Fat embolism is the obstruction of a vessel due to fat emboli, which occurs as result of a long bone fracture. Long bones are rich in trioleines, which in the setting of a fracture can easily reach the blood stream and cause micro infarctions and hemorrhages. Between 15% and 44% of children with Duchenne dystrophy suffer from bone fractures, which in some cases could lead to the development of fat embolism syndrome. Since it usually presents subclinically, fat embolism syndrome needs to be considered in patients with Duchenne dystrophy presenting with acute respiratory or neurological symptoms after a trauma with a fracture (AU)

Overexpression of caveolin-3-enhanced protein synthesis rather than proteolysis inhibition in C2C12 myoblasts: relationship with myostatin activity

Caveolin-3 (cav-3), which is involved in the regulation of signal transduction and vesicular trafficking, could interact with activin receptor IIB to inhibit myostatin (MSTN) activity and may therefore play a role in muscle development and hypertrophy. MSTN is a member of the transforming growth factor-Beta family, identified as a negative regulator of skeletal muscle mass. The expression of MSTN is fiber-type specific and the greatest amount of MSTN is present in fiber, which is composed of myosin heavy chain (MHC) type IIb. MSTN acts through the activin receptor IIB to activate smad2/3 which leads to an increase in gene transcription involved in muscle atrophy. Muscle hypertrophy is a consequence of two mechanisms: (1) the inhibition of proteolysis such as the calcium-dependent proteolytic system calpains and calpastatin and (2) an increase in protein synthesis through theAkt/mTOR/p70s6K pathway. In order to determine which of the two processes predominates in inhibition of MSTN activity in a cav-3 context, we transfected a C2C12 cell line with plasmids containing mstn or cav-3 wild genes. The results reported in this study demonstrate that inhibition of MSTN activity by overexpression of cav-3 induces an activation of protein synthesis rather than an inhibition of proteolysis through the calcium proteolytic system. The inhibition of phosphorylation of smad-3 due to overexpression of cav-3 causes an increase in the phosphorylation of the ribosomal protein S6, promoting the synthesis of MHC type II, probably through activation of Akt/mTOR/p70s6K. These data highlight the role of protein synthesis as the predominant mechanism in muscle hypertrophy observed when the expression of MSTN is altered and confirm the value of studying the physiological role of MSTN in the growing processes of skeletal muscle (AU)

Calcificación distrófica postraumática aislada de músculo sartorio / Post-traumatic dystrophic calcification isolated from the sartorius muscle

Presentamos un caso de calcificación distrófica muscular tras traumatismos repetidos y revisamos las diferentes causas de calcificaciones de partes blandas y de osificación heterotópica

We present a case of muscular dystrophic calcification after repeated traumas and review the different cases of calcifications of the soft parts and heterotopic ossification

Anestesia en enfermedades neuromusculares raras / Anaesthesia in neuromuscular uncommon diseases

Se estima, tras una revisión de 150 artículos publicados, que el riesgo de padecer una enfermedad neuromuscular durante la infancia tardía o en estado adulto es de 1:3.500, llegando a ser superior a 1:3.000 cuando se manifiesta en edades tempranas o se trata de formas raras de distrofia y miopatía. Los trastornos neuromusculares constituyen un grupo heterogéneo de enfermedades que afectan a cualquiera de los componentes de la unidad motora, es decir, la unidad funcional constituida por el cuerpo de la motoneurona del asta anterior de la médula, su axón y todas las fibras inervadas por aquella. En el grupo de anestesiólogos interesados, creado para revisar las enfermedades de rara aparición, realizamos, no sin dificultades debido a la poca frecuencia y a la no muy abundante bibliografía, una completa revisión sobre los aspectos relacionados con la anestesia en estas enfermedades. Este es uno de los artículos que dimanan de dicho estudio, en el que revisamos esquemáticamente las enfermedades neuromusculares raras y sus implicaciones anestésicas (AU)

After a detais review of 150 articles, the risk of having a neuromuscular disorder in the paediatric and adult age is 1:3,500. It is even 1:3,000 with uncommon muscular dystrophy and myopathy. The neuromuscular disorders are a heterogeneous group of the neuromuscular junction components (motoneuron, spinal cord, axon and nervous fibres). We schematically review the uncommon diseases and their anaesthetic implications (AU)

Análisis de la marcha y del movimiento de las extremidades superiores en distrofias musculares / Analysis of gait and movement of upper limbs in muscular dystrophies

Introducción. El objetivo del estudio es analizar y comparar la marcha y el movimiento de las extremidades superiores en una muestra de individuos sanos y con diferentes tipos de distrofias musculares y determinar la relación entre las variables obtenidas y el patrón de afectación muscular. Pacientes y métodos. Se analizó la marcha y el movimiento de las extremidades superiores a través de un sistema de fotogrametria tridimensional a una muestra de 28 voluntarios sanos, 40 pacientes con distrofia miotónica (DM). 9 pacientes con distrofia facioescapulohumeral (DMFEH) y 14 pacientes con distrofia muscular de cinturas tipo 2A (LGM02A). Se analizaron variables espacio-temporales y cinemáticas. Resultados. Los pacientes presentaron una menor velocidad, cadencia y menor duración de la zancada que los sujetos sanos. Las variables cinemáticas se correlacionaron con una afectación muscular proximal en los pacientes con LGM02A y con anomalías en la musculatura distal en pacientes con OM. Los hallazgos más característicos en los pacientes con OMFEH se relacionaron con una debilidad de la musculatura dorsiflexora del pie. Se encontró también correlación entre la alteración de algunas variables y el estadio funcional de los pacientes. Conclusiones. Este análisis permite establecer una correlación entre las alteraciones de las variables espaciotemporales y cinemáticas de la marcha y el movimiento de los miembros superiores y el fenotipo de cada una de las distrofias musculares examinadas. La utilización de este análisis en la práctica clínica para evaluar la progresión de la enfermedad o los efectos potenciales de diferentes intervenciones requiere estudios adicionales

Introduction. The objective is to analyze gait and upper extremity movement in a sample of healthy individuals and patients with different muscular dystrophies and to determine the relationship of the obtained variables with the pattern of muscular involvement. Subjects and methods. Gait and upper limb movement was analyzed with a three-dimensional phtogrammetry system. Convenience sample of 28 healthy volunteers, 40 patients with myotonic dystrophy (MD), 9 patients with facioscapulohumeral dystrophy (FSHD) and 14 patients with limb-girdle muscular dystrophy type 2A (LGMD2A). Spatio-temporal and kinematic variables were analyzed. Results. Patients had lower velocity, cadence and shorter stride duration than healthy subjects. Gait and upper extremity kinematic variables suggested proximal muscular involvement in LGMD2A patients and distal muscular abnormalities in MD patients. The most characteristic finding in FSHD patients was related with dorsiflexor muscles' weakness. Some of the variables were also correlated to the patients' functional stage. Conclusions. This analysis allows the distinction of kinematic and spatio-temporal patterns of gait and upper extremity movement that correlate with muscular dystrophy's phenotype. The use of this analysis in the clinical setting to assess disease progression or the potential effects of treatments requires further studies

Avaliação da função motora em crianças com distrofia muscular congênita com deficiência da merosina / Motor function evaluation in merosin-deficient congenital muscular dystrophy children

A distrofia muscular congênita (DMC) compõe um grupo de miopatias caracterizadas por hipotonia e fraqueza muscular notadas até o primeiro ano de vida. Em torno de 40 por cento a 50 por cento dos casos são decorrentes de deficiência primária da proteína merosina (DM), os quais apresentam um fenótipo mais homogêneo, com grave comprometimento motor e respiratório. Foram avaliadas neste estudo onze crianças com diagnóstico clínico e histológico de DMC-DM, com idade de 3 a 15 anos, através de exame de força muscular ("Medical Research Council"), análise goniométrica, avaliação das habilidades motoras e das atividades de vida diária (AVDs) (indicador de Barthel), com o objetivo de caracterizar as principais limitações funcionais motoras. Os grupos musculares mais comprometidos foram os flexores cervicais, paravertebrais e proximais dos membros. Os grupos musculares dos membros superiores estavam tão comprometidos quanto os dos membros inferiores, enquanto que os extensores encontravam-se mais comprometidos que os flexores. Todas as crianças apresentavam importantes retrações musculares nos quadris, joelhos e cotovelos. Outras deformidades freqüentes foram escoliose e pés eqüino-varo. Nenhuma criança possuía a habilidade motora necessária para engatinhar, ficar de pé ou andar; e todas foram classificadas como dependentes ou semidependentes para a maioria das AVDs estudadas. Nossos achados confirmam o envolvimento difuso e intenso da musculatura esquelética na DMC-DM, acarretando graves limitações funcionais motoras e deformidades músculo-esqueléticas.

Mialgias post ejercicios como forma de presentación de una distrofinopatía / Post exercise myalgias as form of dystrophynopathy

Cramps and myalgias are frequent presentations of many disorders whose diagnosis is generally difficult. Among the unusual causes stand the milder phenotypes of dystrophinopathies, which are caused, just as Duchenne and BeckerÕs dystrophy, by mutations in the dystrophin gene. An 8 year-old boy presented severe muscle pain on exercise and serum rise in creatine kinase over 1000 U/l. He had normal muscle power and mild calf hypertrophy. The molecular analysis by polymerase chain reaction (PCR) of the dystrophin gene showed deletions of exons 45 to 51. Dystrophin analysis by Western blot revealed a dystrophin of reduced quantity and molecular weight. Emphasis is made to include dystrophinopathies in the differential diagnosis of myalgias and the usefulness of molecular genetic techniques in the identification of these disorders

Tardanza en el diagnóstico de la distrofia muscular de Duchenne en Chile / Delayed diagnosis of Duchenne muscular dystrophy in Chile

Background: Duchenne muscular dystrophy is the most frequent neuromuscular disease in children. Aim: To determine the causes of delayed diagnosis of the disease. Patients and methods: The clinical records of 61 children diagnosed as Duchenne progressive muscular dystrophy were analyzed. Results: the first symptoms of the disease were noticed at a mean age of 1.5 years. Parents consulted at the mean age of 3 years, but the accurate diagnosis was made at a mean age of 5.7 years. In only 15 percent of children, the disease was diagnosed in the first four years of age. Less than 20 percent of children were referred for an adequate study and the rest were managed mainly as flat feet. Conclusions: Duchenne dystrophy is the most common neuromuscular disorder in children, with an incidence of 1 in 3679 male newborns. The lack of recognition of non specific symptoms such as retardation in independent walking and frequent falls as forms of presentation, is probably the most important cause of diagnostic delay. Strong recommendation is made to measure creatinphosphokinase and to study every male child that is not walking independently by the age of 18 months

Teste de esforço cardiopulmonar na avaliaçäo de doenças musculares / Cardiopulmonary exercise testing for evaluation of muscle diseases

Objetivo: Analisar o teste de esforço cardiopulmonar (TECP) no diagnóstico de miopatias. Métodos: 27 pacientes com miopatia realizaram TECP (protocolo de bicicleta em rampa, máximo, interrompido por sintoma). Resultados: Pacientes distróficos e pacientes com mitocondriopatias mostraram diferenças significativas em relaçao aos controles para as variáveis potência do trabalho desenvolvido (watt) e pico do consumo de oxigênio (VO2máx). Pacientes com mitocondriopatias mostraram diminuiçao significativa do limiar anaeróbio em relaçao aos controles, além de elevaçao dos valores do quociente respiratório (QR) do pico do exercício em relaçao aos demais grupos. Conclusoes: TECP pode ser útil na avaliaçao evolutiva do grau de limitaçao física dos pacientes com miopatia. As variáveis potência do trabalho desenvolvido, VO2 máx, limiar anaeróbio e QR do pico do exercício podem sugerir o diagnóstico de miopatia e seus subtipos, excluindo quadros psicológicos.

Importância do camundongo mdx na fisiopatologia da distrofia muscular de Duchenne / The importance of mdx mouse in the pathophysiology of Duchenne's muscular distrophy

O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X (locus Xp21.1) e näo expressa distrofina. Embora näo apresente intensa fibrose do tecido muscular e acúmulo de tecido adiposo, é considerado o modelo animal mais adequado da distrofia muscular de Duchenne. As alteraçäes estruturais no tecido muscular associadas à mionecrose e presença do infiltrado inflamatório com predomínio de linfócitos e monócitos/macrófagos sugerem uma participaçäo do sistema imunológico nesta miopatia. Além disso a modulaçäo na expressäo dos componentes da matriz extracelular no microambiente muscular nas vßrias fases da doença (início, mionecrose, regeneraçäo) indicam um papel importante do conjuntivo no direcionamento das células inflamatórias para o foco da lesäo muscular. O camundongo mdx coloca-se como um excelente modelo para o estudo dos mecanismos patogenéticos da mionecrose e regeneraçäo na distrofia muscular de Duchenne, possibilitando inclusive o desenvolvimento de estratégias terapêuticas mais adequadas.

Esophageal motility disorders in Mexican patioents with Duchenne's muscular dystrophy

Objetive: Myopathies are entities tahat mainly involve strieted muscle. In Duchenne's muscular dystrophy (DMD) there have been reported smooth muscle alterations in the pre-oral phase of swallowing, in gastric emptying, and pseudoobstruction. Nevertheless, esophageal motility alterations are not concluding. The objetive of this work was to determine if there are motor esophageal alterations is this patients, and if this alterations are related to the clinical manifestations of disease. Study design: nine consecutive patients with DMD (mean age 8, range 6-11 years; males) were evaluated, comparing clinical and manometric findings. Results: esophageal manometry alterations were found in all patients, mainly simultaneous non-peristaltic waves (60.86 percent) of diminished amplitude, in both striated and smooth muscle. Seventy seven percent presented with upper and lower gastrointestinal symptoms (dysphagia, regurgitation, epigastric pain, constipation, and distention). No correlation was found between esophageal motility alterations and gastrointestinal symptoms, nor with the clinical stage of disease in accordance to Brook (r=0.27). Conclusion: these results show that patients with DMD present esophageal motor disorders in both striated and smooth muscle, as well as upper and lower gastrointestinal symptoms. Specialized motility studies, could yield a better understanding of disease, and, possibly with adequate treatment, provide for a better quality of life in children with DMD.

Esophageal motility disorders in Mexican patioents with Duchennes muscular dystrophy

Objetive: Myopathies are entities tahat mainly involve strieted muscle. In Duchennes muscular dystrophy (DMD) there have been reported smooth muscle alterations in the pre-oral phase of swallowing, in gastric emptying, and pseudoobstruction. Nevertheless, esophageal motility alterations are not concluding. The objetive of this work was to determine if there are motor esophageal alterations is this patients, and if this alterations are related to the clinical manifestations of disease. Study design: nine consecutive patients with DMD (mean age 8, range 6-11 years; males) were evaluated, comparing clinical and manometric findings. Results: esophageal manometry alterations were found in all patients, mainly simultaneous non-peristaltic waves (60.86 percent) of diminished amplitude, in both striated and smooth muscle. Seventy seven percent presented with upper and lower gastrointestinal symptoms (dysphagia, regurgitation, epigastric pain, constipation, and distention). No correlation was found between esophageal motility alterations and gastrointestinal symptoms, nor with the clinical stage of disease in accordance to Brook (r=0.27). Conclusion: these results show that patients with DMD present esophageal motor disorders in both striated and smooth muscle, as well as upper and lower gastrointestinal symptoms. Specialized motility studies, could yield a better understanding of disease, and, possibly with adequate treatment, provide for a better quality of life in children with DMD. (AU)

La Retina en la Enfermedad de Duchenne. Estudio Electrorretinografico / Retina in duchenne disease. Electroretinographic study

La distrofia muscular pseudohipertrofica o enfermedad de Duchenne es una miopatia congenita en cuyo fenotipo no se describen alteraciones oftalmologicas. Esta enfermedad es producto de un fallo en la zona Xp2.13 donde se codifica la proteina distrofina relacionada con la contraccion muscular. Los autores estudian el estado funcional de la retina mediante examen de la funcion visual, fondo de ojo y electrorretinograma en 40 sujetos con esta enfermedad. En ellos detectan alteraciones del electrorretinograma (ERG) en 35 de ellos, con un patron de respuesta similar; estas alteraciones consistieron en evidente disminucion de onda b y relativa conservacion de onda a, dando un ERG de tipo negativo (relacion b/a menor de 1) y disminucion de los potenciales oscilatorios. Estos hallazgos no guardan relacion significativa con la edad, estadio clinico ni patron de herencia. Las alteraciones del ERG detectadas plantean una posible disfuncion en la trasmision sinaptica al nivel de plexiforme externa, esto coincide con los recientes hallazgos de distrofina en la capa plexiforme externa de la retina, lo que sugiere un posible rol conductivo en la trasmision nerviosa en esta enigmatica proteina