Crossover randomized controlled trial of bumetanide to rescue an attack of exercise induced hand weakness in hypokalaemic periodic paralysis.

The aim of this study was to establish whether bumetanide can abort an acute attack of weakness in patients with HypoPP. This was a randomised, double-blind, cross-over, placebo-controlled phase II clinical trial. Focal attack of weakness was induced by isometric exercise of ADM followed by rest (McManis protocol). Participants had two study visits and received either placebo or 2 mg bumetanide at attack onset (defined as 40 % decrement in the abductor digiti minimi CMAP amplitude from peak). CMAP measurements assessed attack severity and duration. Nine participants completed both visits. CMAP percentage of peak amplitudes in the bumetanide (40.6 %) versus placebo (34.9 %) group at 1hr following treatment did not differ significantly (estimated effect difference 5.9 % (95 % CI: (-5.7 %; 17.5 %), p = 0.27, primary outcome). CMAP amplitudes assessed by the area under the curve for early (0-2hr post-treatment) and late (2-4 h post-treatment) efficacy were not statistically different between bumetanide and placebo (early effect estimate 0.043, p = 0.3; late effect estimate 0.085, p = 0.1). Two participants recovered from the attack following bumetanide intake; none recovered following placebo. Bumetanide was well tolerated but not efficacious to rescue a focal attack in an immobilised hand in the majority of patients, although data supports further studies of this agent.

GYG1 causing progressive limb girdle myopathy with onset during teenage years (polyglucosan body myopathy 2).

An 84-year-old lady with slowly progressive limb and axial muscle weakness with onset in her teens was referred for genetic investigations. Targeted next generation sequencing (NGS) revealed a homozygous mutation GYG1 in exon5:c.487delG:p.D163fs, confirming the diagnosis of Polyglucosan Body Myopathy 2 (PGBM2). Retrospective review of muscle pathology revealed a florid vacuolar myopathy with histochemical and ultrastructural features consistent with a polyglucosan storage myopathy. No cardiac symptoms were reported. Our case is consistent with the core phenotype of GYG1-related PGBM2 apart from an early onset of weakness without cardiac symptoms. The presence of α-amylase resistant PAS-positive material in skeletal muscle biopsy of patients with slowly progressive limb girdle muscle weakness should prompt the search for GYG1 mutations. This case highlights the combined role of muscle pathology and NGS in the molecular resolution of patients with undiagnosed neuromuscular conditions.

Misdiagnosis is an important factor for diagnostic delay in McArdle disease.

Diagnosis of McArdle disease is frequently delayed by many years following the first presentation of symptoms to a health professional. The aim of this study was to investigate the importance of misdiagnosis in delaying diagnosis of McArdle disease. The frequency of misdiagnosis, duration of diagnostic delay, categories of misdiagnoses and inappropriate medical interventions were assessed in 50 genetically confirmed patients. The results demonstrated a high frequency of misdiagnosis (90%, n = 45/50) most commonly during childhood years (67%; n = 30/45) compared with teenage years and adulthood (teenage: n = 7/45; adult n = 5/45; not known n = 3/45). The correct diagnosis of McArdle disease was rarely made before adulthood (median age of diagnosis 33 years). Thirty-one patients (62%) reported having received more than one misdiagnosis; the most common were "growing pains" (40%, n = 20) and "laziness/being unfit" (46%, n = 23). A psychiatric/psychological misdiagnosis was significantly more common in females than males (females 6/20; males 1/30; p < 0.01). Of the 45 patients who were misdiagnosed, 21 (47%) received incorrect management. This study shows that most patients with McArdle disease received an incorrect explanation of their symptoms providing evidence that misdiagnosis plays an important part in delaying implementation of appropriate medical advice and management to this group of patients.

Polymyositis without Beneficial Response to Steroid Therapy: Should Miyoshi Myopathy be a Differential Diagnosis?

BACKGROUND Miyoshi myopathy (MM) is an autosomal-recessive muscle disorder caused by mutations in the DYSF gene. Clinical features and histopathological changes in dysferlinopathies may mimic inflammatory myopathies and a high degree of clinical suspicion is required to guide the genetic investigation. CASE REPORT We report the case of a 16-year-old male who presented with severe bilateral calf pain and elevated CK levels (15 000 IU/l) who was on prolonged steroid therapy prompted by the clinical suspicion of inflammatory myopathy. Three years into his illness, he was referred for neuromuscular evaluation presenting with untreatable muscle pain and progressive weakness. The diagnosis of "refractory polymyositis" was revisited. Targeted exome sequencing revealed homozygous pathogenic mutations in the DYSF gene, confirming a diagnosis of Miyoshi myopathy. CONCLUSIONS Our case illustrates that severe muscle pain may be the initial feature of Miyoshi myopathy and should be considered in the differential diagnosis of inflammatory myopathies. Although the described patient reported partial clinical improvement in muscle pain, steroid treatment is not an effective therapy for dysferlinopathy patients and it did not prevent disease progression. In addition, we confirm the utility of next-generation sequencing approaches to myopathies, particularly in complex or unusual cases when muscle biopsy is not available.

Applicability of the Cobb angle measurement in idiopathic scoliosis using scanned imaging / Aplicabilidade da medida do ângulo de Cobb na escoliose idiopática usando imagem digitalizada / Aplicabilidad de la medición del ángulo de Cobb en la escoliosis idiopática usando imagen digitalizada

ABSTRACT Objectives: To compare the measurement of the Cobb angle on printed radiographs and on scanned radiographs viewed through the software "PixViewer". Methods: Preoperative radiographs of 23 patients were evaluated on printed films and through the software "PixViewer". The same evaluator, a spine surgeon, chose the proximal and distal limiting vertebrae of the main curve on printed radiographs, without identification of patients, and measured the Cobb angle based on these parameters. The same parameters and measurements were applied to scanned radiographs. The measurements were compared, as well as the choice of limiting vertebrae. Results: The average variation of the Cobb angle between methods was 1.48 ± 1.73°. The intraclass correlation coefficient (ICC) was 0.99, demonstrating excellent reproducibility. Conclusion: The Cobb method can be used to evaluate scoliosis through the "PixViewer" tool with the same reliability as the classic method on printed radiographs.

RESUMO Objetivo: Comparar a aferição do ângulo de Cobb em radiografias impressas e em radiografias digitalizadas, visualizadas por meio da ferramenta "PixViewer". Métodos: Foram avaliadas as radiografias pré-operatórias de 23 pacientes em filmes impressos e pelo software "PixViewer". O mesmo avaliador, cirurgião de coluna, elegeu as vértebras limites proximal e distal da curva principal nas radiografias impressas, sem identificação dos pacientes, e realizou a aferição do ângulo de Cobb baseado nesses parâmetros. Os mesmos parâmetros e aferições foram aplicados às radiografias digitalizadas. As aferições foram comparadas, assim como a escolha das vértebras limites. Resultados: A variação média do ângulo de Cobb entre os métodos foi de 1,48 ± 1,73°. O coeficiente de correlação intraclasse (CCI) foi de 0,99, demonstrando replicabilidade excelente.. Conclusão: O método de Cobb pode ser utilizado para avaliação da escoliose por meio da ferramenta "PixViewer" com a mesma confiabilidade que pelo método clássico em radiografias impressas.

RESUMEN Objetivo: Comparar la medición del ángulo de Cobb en radiografías impresas y en radiografías digitalizadas vistas a través de la herramienta "PixViewer" . Métodos: Se evaluaron las radiografías preoperatorias de 23 pacientes en películas impresas y a través del software "PixViewer". El mismo evaluador, cirujano de columna, eligió las vértebras proximal y distal límites de la curva principal en las radiografías impresas, sin identificación de los pacientes, y realizó la medición del ángulo de Cobb en base a estos parámetros. Los mismos parámetros y mediciones se aplicaron a las radiografías digitalizadas. Las mediciones fueron comparadas, así como la elección de las vértebras límites. Resultados: La variación promedio del ángulo de Cobb entre los métodos fue de 1,48 ± 1,73°. El coeficiente de correlación intraclase (CCI) fue de 0,99, demostrando reproducibilidad excelente. Conclusión: El método de Cobb puede ser utilizado para la evaluación de la escoliosis a través de la herramienta "PixViewer" con la misma fiabilidad que el método clásico en radiografías impresas.

McArdle Disease Misdiagnosed as Meningitis.

BACKGROUND McArdle disease is a glycogen storage disorder mainly characterized by exercise intolerance. Prolonged muscle contracture is also a feature of this condition and may lead to rhabdomyolysis (RM), which is a serious event characterized by acute skeletal muscle damage.  CASE REPORT A 44-year-old female patient presented with an acute contracture of the posterior neck muscles, causing severe nuchal rigidity. The contracture was induced during a dental extraction as she held her mouth open for a prolonged period, with her neck in a rigid position. She presented with severe pain in her ear and head, as well as fever, vomiting, and confusion. Based on her symptoms, she was initially misdiagnosed with bacterial meningitis and experienced an acute allergic reaction to the systemic penicillin she was subsequently administered. Lumbar puncture results were normal. High serum creatine kinase (CK) levels, recurrent exercise-related muscle symptoms, and a previous history of recurrent myoglobinuria raised the suspicion of an underlying neuromuscular condition. McArdle disease was confirmed by muscle biopsy and a genetic test, which revealed that the patient was homozygous for the R50X mutation in the PYGM gene. CONCLUSIONS This case illustrates that even seemingly innocuous movements, if rapid isotonic or prolonged isometric in nature, can elicit a muscle contracture in McArdle disease patients. Here, we highlight the need for careful management in this patient population even during routine healthcare procedures. The allergic reaction to antibiotics emphasises that misdiagnoses may result in iatrogenic harm.

CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies.

Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n = 6). Symptoms included myalgia (n = 7), exercise intolerance (n = 7) and episodes of rhabdomyolysis (n = 2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients; however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series, immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other "typical" features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes.

Rhabdomyolysis: a genetic perspective.

Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream leading to myoglobinuria and, in severe cases, acute renal failure. Apart from trauma, a wide range of causes have been reported including drug abuse and infections. Underlying genetic disorders are also a cause of RM and can often pose a diagnostic challenge, considering their marked heterogeneity and comparative rarity.In this paper we review the range of rare genetic defects known to be associated with RM. Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach. The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease.

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to 'growing pains' and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.

From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease / De intolerância ao exercício à melhora funcional: o fenômeno second wind na identificação da doença de McArdle

McArdle disease is the most common of the glycogen storage diseases. Onset of symptoms is usually in childhood with muscle pain and restricted exercise capacity. Signs and symptoms are often ignored in children or put down to ‘growing pains’ and thus diagnosis is often delayed. Misdiagnosis is not uncommon because several other conditions such as muscular dystrophy and muscle channelopathies can manifest with similar symptoms. A simple exercise test performed in the clinic can however help to identify patients by revealing the second wind phenomenon which is pathognomonic of the condition. Here a patient is reported illustrating the value of using a simple 12 minute walk test.

A doença de McArdle é o tipo mais frequente das glicogenoses. A apresentação clínica característica na infância inclui mialgia e intolerância aos esforços/exercício físico. Frequentemente, os sinais e sintomas das crianças não são considerados devidamente, sendo muitas vezes interpretados como “dores do crescimento”, retardando o diagnóstico. Erros diagnósticos não são raros uma vez que outras doenças, como distrofia muscular ou canalopatias musculares, podem apresentar sintomas semelhantes. Entretanto, um simples teste de exercício físico realizado no ambulatório/consultório médico pode ajudar a identificar estes pacientes pois evidencia o fenômeno second wind, patognomônico da doença de McArdle. Aqui é descrito um relato de caso de um paciente ilustrando o valor do simples 12 minutes walk test.

Is carpal tunnel syndrome a slow, chronic, progressive nerve entrapment?

OBJECTIVE: The aim of this study is to investigate the presenting profile of patients with carpal tunnel syndrome (CTS) at various ages. METHODS: We performed a cross-sectional study of CTS, analysing the correlation between severity and age. RESULTS: We examined 3108 subjects with CTS, whose frequency increased from 20.9% for the age group 20-29 years to 61.7% for the age group 50-59 years. It remained at almost 50% in people aged over 80 years (49.2%). More than 50% of people younger than 30 years had mild CTS. Severe CTS progressively increased, reaching more than 50% of the CTS diagnoses in people over 80 years. Of the total number of cases, 80.8% of subjects had bilateral CTS. Mild NCS-EMG abnormalities were seen in 74.1% of patients with unilateral involvement, whereas moderate and severe CTS appeared in 70.3% of patients with bilateral involvement. CONCLUSION: There was a clear trend of deterioration with advancing years when comparing severity to age. SIGNIFICANCE: CTS seems to be a chronic condition whose signs and symptoms may vary and progress, becoming worse over time.

Seasonal variation in prevalence of carpal tunnel syndrome.

INTRODUCTION: The influence of cold temperatures on neuropathies has been reported previously, but its impact on carpal tunnel syndrome (CTS) is not well analyzed. METHODS: We analyzed the frequency of CTS among neurophysiological evaluations according to seasonal variation in 9574 consecutive patients (4260 with CTS). RESULTS: A higher frequency of CTS was found in the winter (50.8%), and the lowest number for CTS diagnosis was found in the summer (38.9%). In both autumn and spring the prevalence remained stable at an intermediate level between summer and winter at 42.8% and 43.5%, respectively. CONCLUSION: CTS frequency was much higher in winter in this center.

Risk factors among stroke subtypes in Brazil.

Stroke is a leading cause of mortality and disability in Brazil. Among the risk factors for cerebrovascular disease, some have more influence than others in certain stroke subtypes. Little data are available in the literature on the prevalence of stroke subtypes in Latin America. We analyzed data from 688 patients with acute ischemic stroke (52.3% women; mean age, 65.7 years) who were enrolled in a stroke data bank. Standardized data assessment and stroke subtype classification were used. The most common stroke subtype was large-artery atherosclerosis (n = 223; 32.4%), followed by cardioembolism (n = 195; 28.3%), and microangiopathy (n = 127; 18.5%). Stroke risk factors differ among stroke subtypes. The population of South America is ethnically diverse, and few previous studies have describe the distribution of risk factors among stroke subtypes in this population. In this study, the most important risk factors were hypertension and dyslipidemia.

Febre amarela: Rio Grande do Sul e o risco da reurbanização / Yellow fever: rio grande do sul and the risk of reurbanização

A Febre Amarela e uma doença infecciosa aguda não - contagiosa de curta duração e de gravidade variável. É causada por um flavivírus, para o qual está disponível uma vacina altamente eficaz. A transmissão é feita por intermédio de mosquitos. O surgimento de novos casos de febre amarela, no Brasil é uma ameaça constante. A possível expansão desta doença infecciosa para o Rio Grande do Sul é a preocupação de muitos sanitaristas, uma vez que o vetor está presente nas cidades gaúchas. Em 2001, a vacinação contra a febre amarela em 43 municípios da Região das Missões foi realizada após comprovação de quea febre amarela fora a causa de morte de bugius em muitos municípios, sendo estes classificados como áreas de risco para endemias. Neste contexto, torna-se essencial aos médicos o conhecimento da Febre Amarela: fisiopatologia, áreas de risco, manejo da doença e, sobretudo, mecanismos de prevenção. Cabe lembrar que a Febre Amarela é uma doença de notificação compulsória aos órgãos públicos.

Envelhecimento e alterações na memória: o que é normal e quando suspeitar de demência / Aging and alterations in the memory: what is normal and when to suspect of dementia

Com o aumento da expectativa de vida, médicos de diversas especialidades se deparam com um percentual crescente de pacientes idosos. Queixas quanto a alterações de memória nesta faixa etária são muito prevalentes, gerando uma ansiedade que se estende aos familiares e cuidadores. Entender o processo do envelhecimento e as dificuldades de memória associadas é de suma importância para esclarecer dúvidas, diagnosticar precocemente alterações degenerativas que podem evoluir para demência e orientar um tratamento adequado. Este capítulo visa revisar a abordagem diagnóstica de pacientes com queixas de alterações de memória, enfatizando a identificação do estágio pré-demencial da Doença de Alzheimer, também conhecido como comprometimento cognitivo leve (CCL).

AVC no Hospital São Lucas da PUC, 30 anos depois: "dos heróis de 1977 ao fim do niilismo em 2004": o que realmente mudou? / CVA in the Hospital São Lucas of the PUC, 30 years later: “the heroes of 1977 to the end of the niilismo in 2004”: what's really modified?

Os autores propõem uma revisão sobre o do tratamento do AVC nos últimos 30 anos no Hospital São Lucas da PUCRS