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 ACTA1 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.

Sleep, lung function, and quality of life in patients with myasthenia gravis: A cross-sectional study.

The purpose of this study was to investigate the physiological variables of lung function, respiratory muscle strength, and sleep in clinically stable patients with myasthenia gravis. This was a prospective cross-sectional study conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Patients adhering to the eligibility criteria were consecutively recruited from the Research Department of Neuromuscular Diseases at the Federal University of Sao Paulo and the Department of Neurology at Santa Casa de Misericordia of Sao Paulo and were referred to the Nove de Julho University Sleep Laboratory (Sao Paulo, Brazil). The study included 25 patients (21 female) with a mean age of 45.28 ± 12.33 years. Only one patient exhibited a restrictive ventilatory pattern. The maximum ventilatory pressures observed were considerably reduced in most patients as compared to reference values. In sleep studies, the patients exhibited significantly reduced oxygen saturation, reduced rapid eye movement sleep time, increased non-rapid eye movement stage 3 sleep, and considerable apnoea/hypopnoea indexes. Clinically stable patients with myasthenia gravis exhibit a high prevalence of sleep-disordered breathing, significant reductions in maximum ventilatory pressures, and impairment of health-related quality of life.

Sleep disorders in patients with myasthenia gravis: a systematic review.

[Purpose] This systematic review evaluated the presence of sleep-disordered breathing in patients with myasthenia gravis and clarified the role of physiotherapy. [Subjects and Methods] We followed the PRISMA declaration criteria. The evaluation was performed in accordance with the STROBE statement for observational and cross-sectional studies and the CONSORT checklist for clinical trials. Searches were followed by hand on MEDLINE, EMBASE, SciELO, PubMed Central, and the Cochrane Central Register of Controlled Trials. [Results] Our searches yielded a total of 36 studies published between 1970 and 2014. The number of patients involved ranged from 9-490. Of the 36 studies, 19 articles were excluded because they did not meet the inclusion criteria. Therefore, 17 observational, cross-sectional, or clinical studies assessing the quality of sleep and prevalence of sleep disorders in patients with myasthenia gravis were eligible for our review. [Conclusion] Some studies of patients with MG show that patients with MG are associated with poor sleep quality, excessive daytime sleepiness, presence of restless syndrome, and a higher incidence of SDB, while other studies do not report such associations. Therefore, given the current inconclusive evidence and limited literature, further study of sleep disturbances in patients with MG is needed.

Peroneal nerve palsy due to compartment syndrome after facial plastic surgery.

A 25-year-old white man, right after bilateral rhytidoplasty, presented with agitation, necessitating use of haloperidol. Some hours after, he developed severe pain in his legs and a diagnosis of neuroleptic malignant syndrome (NMS) was considered. Even with treatment for NMS he still complained of pain. A diagnosis of lower limb compartment syndrome (CS) was done only 12 hours after the initial event, being submitted to fasciotomy in both legs, disclosing very pale muscles, due to previous ischemia. This syndrome was not explained only by facial surgery, his position and duration of the procedure. It can be explained by a sequence of events. He had a history of pain in his legs during physical exercises, usually seen in chronic compartment syndrome. He used to take anabolizant and venlafaxine, not previously related, and the agitation could be related to serotoninergic syndrome caused by interaction between venlafaxine and haloperidol. Rhabdomyolysis could lead to oedema and ischemia in both anterior leg compartment. This report highlights the importance of early diagnosis of compartment syndrome, otherwise, even after fasciotomy, a permanent disability secondary to peripheral nerve compression could occur.

Peroneal nerve palsy due to compartment syndrome after facial plastic surgery

A 25-year-old white man, right after bilateral rhytidoplasty, presented with agitation, necessiting use of haloperidol. Some hours after, he developed severe pain in his legs and a diagnosis of neuroleptic malignant syndrome (NMS) was considered. Even with treatment for NMS he still complained of pain. A diagnosis of lower limb compartment syndrome (CS) was done only 12 hours after the initial event, being submitted to fasciotomy in both legs, disclosing very pale muscles, due to previous ischemia. This syndrome was not explained only by facial surgery, his position and duration of the procedure. It can be explained by a sequence of events. He had a history of pain in his legs during physical exercises, usually seen in chronic compartment syndrome. He used to take anabolizant and venlafaxine, not previously related, and the agitation could be related to serotoninergic syndrome caused by interaction between venlafaxine and haloperidol. Rhabdomyolisis could lead to oedema and ischmemia in both anterior leg compartment. This report highlights the importance of early diagnosis of compartment syndrome, otherwise, even after fasciotomy, a permanent disability secondary to peripheral nerve compression could occur.

Logo após ritidoplastia bilateral, um jovem de 25 anos apresentou agitação, necessitando uso de haloperidol. Algumas horas após, desenvolveu dor intensa em membros inferiores, e o diagnóstico de síndrome neuroléptica maligna foi considerado. Mesmo com o tratamento para tal, persistiu com dor. Após 12 horas do início do quadro, foi realizado o diagnóstico de síndrome compartimental de membros inferiores e o jovem foi submetido a fasciotomia bilateral. Uma seqüência de eventos desencadeou esta síndrome, já que sua ocorrência dificilmente seria justificada pela cirurgia facial e/ou posição do paciente durante o procedimento. O jovem apresentava previamente dor em membros inferiores aos exercícios, sugerindo a ocorrência de uma síndrome compartimental crônica. Ele fazia uso de anabolizantes e venlafaxina, não relatado no início do quadro, e a agitação poderia ser explicada por uma síndrome serotoninérgia desencadeada pela interação deste último medicamento e haloperidol. A rabdomiólise secundária a estes eventos causou edema e isquemia nos compartimentos anteriores de ambos os membros inferiores, levando a uma compressão secundária do nervo fibular. O caso em questão ilustra a importância do diagnóstico precoce da síndrome compartimental pois, caso contrário, mesmo com fasciotomia, uma complicação permanente devido à compressão de nervos periféricos pode se estabelecer.