Clinical and Histologic Findings in ACTA1-Related Nemaline Myopathy: Case Series and Review of the Literature

BACKGROUND: Nemaline myopathy is a rare congenital disease of skeletal muscle characterized by muscle weakness and hypotonia, as well as the diagnostic presence of nemaline rods in skeletal muscle fibers. Nemaline myopathy is genetically and phenotypically heterogeneous and, so far, mutations in 11 different genes have been associated with this disease. Dominant mutations in ACTA1 are the second most frequent genetic cause of nemaline myopathy and can lead to a variety of clinical and histologic phenotypes. PATIENTS AND METHODS: We present a series of ACTA1-related cases from a Brazilian cohort of 23 patients with nemaline myopathy, diagnosed after Sanger sequencing the entire coding region of ACTA1, and review the literature on ACTA1-related nemaline myopathy. RESULTS: The study confirmed ACTAI mutations in four patients, including one with intranuclear rods, one with large intracytoplasmic aggregates, and two with nemaline intracytoplasmic rods. A repeat muscle biopsy in one patient did not show histological progression. CONCLUSION: Despite the recognized phenotypic variability in ACTA1-related nemaline myopathy, clinical and histological presentations appear to correlate with the position of the mutation, which confirms emerging genotype/phenotype correlations and better predict the prognosis of affected patients.Univ Sao Paulo FMUSP, Med Sch, Dept Neurol, Sao Paulo, BrazilNINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USAUniv Fed Sao Paulo, Dept Neurol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Neurol, Sao Paulo, BrazilWeb of Scienc

Post-polio syndrome: renaissance of poliomyelitis?

Poliomyelitis is an acute and infectious viral disease, transmitted primarily through oral-fecal contact or directly, person to person. Approximately 90% of the individuals infected by the polio virus do not present symptoms; however, the affected individuals can show a variety of symptoms if the virus reaches the bloodstream. In up to 2% of cases, the virus reaches the central nervous system  preferably infecting and destroying the motor neurons, resulting in muscular weakness and acute flaccid paralysis. Despite the expressive reduction in the number of cases, many people live with the consequences of the acute illness, thus representing a burden to the public healthcare systems. Many of these people present new manifestations as signs and symptoms that are called post-polio syndrome. It can be defined and characterized by new neuromuscular symptoms, which occur at least 15 years after a period of clinical and functional stability in patients with previous history of symptomatic poliomyelitis. The signs and symptoms characterizing the post-polio syndrome include new muscular weakness, muscular fatigue and atrophy, pain in joints and muscles, sleep disorders, intolerance to cold, respiratory and swallowing difficulties, and recent weight gain. Therefore, the aim of this review is to present the physiological changes caused by the new manifestation of symptoms in individuals with poliomyelitis

Funcao pulmonar em pessoas com sindrome pos-poliomielite: um estudo transversal

OBJECTIVE:To compare lung function between patients with post-poliomyelitis syndrome and those with sequelae of paralytic poliomyelitis (without any signs or symptoms of post-poliomyelitis syndrome), as well as between patients with post-poliomyelitis syndrome and healthy controls.METHODS:Twenty-nine male participants were assigned to one of three groups: control; poliomyelitis (comprising patients who had had paralytic poliomyelitis but had not developed post-poliomyelitis syndrome); and post-poliomyelitis syndrome. Volunteers underwent lung function measurements (spirometry and respiratory muscle strength assessment). RESULTS:The results of the spirometric assessment revealed no significant differences among the groups except for an approximately 27% lower mean maximal voluntary ventilation in the post-poliomyelitis syndrome group when compared with the control group (p = 0.0127). Nevertheless, the maximal voluntary ventilation values for the post-poliomyelitis group were compared with those for the Brazilian population and were found to be normal. No significant differences were observed in respiratory muscle strength among the groups.CONCLUSIONS:With the exception of lower maximal voluntary ventilation, there was no significant lung function impairment in outpatients diagnosed with post-poliomyelitis syndrome when compared with healthy subjects and with patients with sequelae of poliomyelitis without post-poliomyelitis syndrome. This is an important clinical finding because it shows that patients with post-poliomyelitis syndrome can have preserved lung function.OBJETIVO:Comparar a função pulmonar de pacientes com síndrome pós-poliomielite à de pacientes com sequelas de poliomielite paralítica (sem quaisquer sinais ou sintomas de síndrome pós-poliomielite) e à de sujeitos saudáveis. MÉTODOS:Vinte e nove sujeitos do sexo masculino foram divididos em três grupos: controle, poliomielite (pacientes que sofreram de poliomielite paralítica, mas que não apresentaram síndrome pós-poliomielite) e síndrome pós-poliomielite. Os voluntários foram submetidos a avaliações da função pulmonar (espirometria e avaliação da força muscular respiratória).RESULTADOS:Os resultados da espirometria não revelaram diferenças significantes entre os grupos, à exceção da ventilação voluntária máxima, cuja média no grupo síndrome pós-poliomielite foi aproximadamente 27% mais baixa que no grupo controle (p = 0,0127). No entanto, os valores de ventilação voluntária máxima observados no grupo pós-poliomielite foram comparados aos da população brasileira e se apresentaram dentro da faixa normal. Não foram observadas diferenças significantes entre os grupos no tocante à força muscular respiratória. CONCLUSÕES:À exceção da ventilação voluntária máxima mais baixa, não houve comprometimento significante da função pulmonar em pacientes ambulatoriais com diagnóstico de síndrome pós-poliomielite quando comparados a pacientes com sequelas de poliomielite, mas sem a síndrome pós-poliomielite e a sujeitos saudáveis. Trata-se de um importante achado clínico, pois mostra que pacientes com síndrome pós-poliomielite podem apresentar função pulmonar preservada.Federal University of Goias at JataiMcGill UniversitySanta Casa de São Paulo Faculdade de Ciencias MedicasFederal University of São Paulo Department of PhysiologyFederal University of São Paulo Department of Neurology and NeurosurgeryUNIFESP, Department of PhysiologyUNIFESP, Department of Neurology and NeurosurgerySciEL

Respiratory physiotherapy in ALS patients in Brazil during COVID-19

ISSN 25269747Si

Centronuclear myopathy: histopathological aspects in ten patients with chilfhood onset Miopatia centronuclear: aspectos histopatológicos em dez pacientes com a forma clínica de início na infância

Centronuclear myopathy is a rare congenital myopathy. According to the period of onset of signs and symptoms and the degree of muscular involvement three clinical forms are distinguished: severe neonatal; childhood onset; and adult onset. We describe herein the muscle biopsy findings of ten patients with the childhood onset form of the disease including three cases with ultrastructural study. The biopsies disclosed increased nuclear centralization that varied from 25 to 90% of the fibers, type 1 predominance, great variability in fiber diameters, involvement in the internal fiber's architecture, and focal areas of myofilament disorganization. The main histopathologic differential diagnoses included type I fiber predominance, congenital fiber type disproportion, and myotonic dystrophy. The histologic abnormalities in centronuclear myopathy may be due to an arrest of maturation on the fetal myotubular stage. The cause of this arrest remains elusive.<br>A miopatia centronuclear (MCN) é uma forma rara de miopatia congênita. De acordo com a época do início dos sinais e sintomas e com o grau de envolvimento muscular são distinguidas três formas clínicas: forma neonatal severa; forma de início na infância; e de início na vida adulta. São apresentados neste estudo os achados histopatológicos de dez pacientes portadores da forma de início na infância da MCN. Os fragmentos musculares foram processados através de colorações de rotina e histoquímica, e em três casos foi realizado estudo ultraestrutural. Dentre os resultados obtidos, destacou-se o aumento da centralização nuclear na fibra muscular, que variou de 25 a 90%. Adicionalmente, foram observadas predominância de fibras do tipo I, variabilidade entre o diâmetro das fibras musculares, alterações da arquitetura interna das fibras musculares e presença de áreas focais de desorganização dos miofilamentos. Devido a estes aspectos, os principais diagnósticos diferenciais considerados foram as miopatias por predominância de fibras e por desproporção de fibras, e a distrofia miotônica. As anormalidades histológicas observadas na MCN podem ser devidas a uma parada no processo maturacional do músculo esquelético na fase miotubular fetal. A causa deste defeito ainda permanece sem explicação completa