Clinical, histological and radiological responses to methylprednisolone in HIV-associated rod myopathy.

Skeletal muscle involvement as a neurologic manifestation in individuals with HIV is rare, especially as rod myopathy. We describe a 41-year-old male with HIV infection who presented progressive proximal muscle weakness and limb-girdle atrophy. A muscle magnetic resonance image showed bilateral fatty infiltration and post-contrast enhancement in the arm and thigh muscles. The muscle biopsy revealed intracytoplasmic aggregates with appearance of nemaline rod bodies with Gomori trichrome staining and electron microscopy in most fibers. The patient underwent six cycles of intravenous methylprednisolone pulses, presenting clinical improvement. Post-treatment muscle biopsy showed fewer nemaline bodies and muscle magnetic resonance image depicted a pronounced reduction of muscular edema. These findings corroborate that deposition of nemaline bodies in these patients might be related to an immune response triggered by the virus.

[Inclusion body myositis: series of 30 cases from a Brazilian tertiary center]. / Miosite de corpos de inclusão: série de 30 casos de um centro terciário brasileiro.

OBJECTIVES: To describe a series of 30 consecutive patients with inclusion body myositis (IBM) from our tertiary center, from 1982 to 2012. MATERIALS AND METHODS: All patients fulfilled the criteria of Griggs et al. (1995) for IBM. RESULTS: The mean age of patients at disease onset was 60.8 � 11.9 years with disease duration of 8.0 � 5.2 years. Eighty % of patients were Caucasian, with similar distribution between genders. Weight loss in early disease was present in less than a quarter of cases. The main symptom was proximal weakness of the lower limbs followed by weakness of the upper (proximal and/or distal) limbs. One third of patients had dysphagia, whereas dysphonia was present in 16.7%, arthralgias in 6.7%, moderate dyspnea symptoms in 3.3% of cases. All patients received prednisone (1mg/kg/day). Several immunosuppressives were used as corticosteroid-sparing according to tolerance, side effects and/or refractoriness. Half of the patients still in follow-up remained stable according to clinical and laboratory data during the study. There were four cases of cancer, four cases associated with viral infections (HIV and hepatitis C virus) and three deaths (two because of sepsis secondary to community bronchopneumonia, and one because of congestive heart failure). CONCLUSIONS: This is the first Brazilian series of cases involving large sample of IBM. The profile of the patients analyzed in this study was comparable to those profiles described in literature, except that of IBM cases of our population are equally distributed in both genders and the interval between symptoms onset and diagnosis of the disease was relatively short. It is relevant to note the high frequency of neoplastic diseases and chronic viral infections in our population, reinforcing the need for specific epidemiological studies to verify these associations, once it is poorly described in the literature.

Phenotypic and immunohistochemical characterization of sarcoglycanopathies.

INTRODUCTION: Limb-girdle muscular dystrophy presents with heterogeneous clinical and molecular features. The primary characteristic of this disorder is proximal muscular weakness with variable age of onset, speed of progression, and intensity of symptoms. Sarcoglycanopathies, which are a subgroup of the limb-girdle muscular dystrophies, are caused by mutations in sarcoglycan genes. Mutations in these genes cause secondary deficiencies in other proteins, due to the instability of the dystrophin-glycoprotein complex. Therefore, determining the etiology of a given sarcoglycanopathy requires costly and occasionally inaccessible molecular methods. OBJECTIVE: The aim of this study was to identify phenotypic differences among limb-girdle muscular dystrophy patients who were grouped according to the immunohistochemical phenotypes for the four sarcoglycans. METHODS: To identify phenotypic differences among patients with different types of sarcoglycanopathies, a questionnaire was used and the muscle strength and range of motion of nine joints in 45 patients recruited from the Department of Neurology--HC-FMUSP (Clinics Hospital of the Faculty of Medicine of the University of São Paulo) were evaluated. The findings obtained from these analyses were compared with the results of the immunohistochemical findings. RESULTS: The patients were divided into the following groups based on the immunohistochemical findings: α-sarcoglycanopathies (16 patients), ß-sarcoglycanopathies (1 patient), γ-sarcoglycanopathies (5 patients), and nonsarcoglycanopathies (23 patients). The muscle strength analysis revealed significant differences for both upper and lower limb muscles, particularly the shoulder and hip muscles, as expected. No pattern of joint contractures was found among the four groups analyzed, even within the same family. However, a high frequency of tiptoe gait was observed in patients with α-sarcoglycanopathies, while calf pseudo-hypertrophy was most common in patients with non-sarcoglycanopathies. The α-sarcoglycanopathy patients presented with more severe muscle weakness than did γ-sarcoglycanopathy patients. CONCLUSION: The clinical differences observed in this study, which were associated with the immunohistochemical findings, may help to prioritize the mutational investigation of sarcoglycan genes.

Phenotypic and immunohistochemical characterization of sarcoglycanopathies

INTRODUCTION: Limb-girdle muscular dystrophy presents with heterogeneous clinical and molecular features. The primary characteristic of this disorder is proximal muscular weakness with variable age of onset, speed of progression, and intensity of symptoms. Sarcoglycanopathies, which are a subgroup of the limb-girdle muscular dystrophies, are caused by mutations in sarcoglycan genes. Mutations in these genes cause secondary deficiencies in other proteins, due to the instability of the dystrophin-glycoprotein complex. Therefore, determining the etiology of a given sarcoglycanopathy requires costly and occasionally inaccessible molecular methods. OBJECTIVE: The aim of this study was to identify phenotypic differences among limb-girdle muscular dystrophy patients who were grouped according to the immunohistochemical phenotypes for the four sarcoglycans. METHODS: To identify phenotypic differences among patients with different types of sarcoglycanopathies, a questionnaire was used and the muscle strength and range of motion of nine joints in 45 patients recruited from the Department of Neurology - HC-FMUSP (Clinics Hospital of the Faculty of Medicine of the University of São Paulo) were evaluated. The findings obtained from these analyses were compared with the results of the immunohistochemical findings. RESULTS: The patients were divided into the following groups based on the immunohistochemical findings: a-sarcoglycanopathies (16 patients), b-sarcoglycanopathies (1 patient), y-sarcoglycanopathies (5 patients), and nonsarcoglycanopathies (23 patients). The muscle strength analysis revealed significant differences for both upper and lower limb muscles, particularly the shoulder and hip muscles, as expected. No pattern of joint contractures was found among the four groups analyzed, even within the same family. However, a high frequency of tiptoe gait was observed in patients with a-sarcoglycanopathies, while calf pseudo-hypertrophy was most common in patients with non-sarcoglycanopathies. The a-sarcoglycanopathy patients presented with more severe muscle weakness than did y-sarcoglycanopathy patients. CONCLUSION: The clinical differences observed in this study, which were associated with the immunohistochemical findings, may help to prioritize the mutational investigation of sarcoglycan genes.

Congenital muscular dystrophy with merosin deficiency: 1H MR spectroscopy and diffusion-weighted MR imaging.

PURPOSE: To prospectively use hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopy and apparent diffusion coefficient (ADC) maps to try to explain the discrepancy between the extensive white matter (WM) abnormalities observed at MR imaging and the relatively mild neurocognitive decline in patients with merosin-deficient congenital muscular dystrophy (CMD). MATERIALS AND METHODS: The hospital ethics committee approved this study, and informed consent was obtained. Nine patients (five boys, four girls; age range, 3-9 years; mean, 6 years +/- 2 [standard deviation]) with merosin-deficient CMD underwent T1-weighted, T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted MR imaging and (1)H MR spectroscopy, which was performed in the parieto-occipital WM (POWM) and frontal WM (FWM) by using stimulated-echo acquisition mode. Metabolite (N-acetylaspartate [NAA], choline-containing compounds [Cho], and myo-inositol [mI]) ratios were calculated in relation to creatine/phosphocreatine (Cr) and water (H(2)O). NAA/Cho was also calculated. ADCs were calculated in approximately the same locations that were studied with spectroscopy. For comparison, (1)H MR spectroscopy (n = 10) and ADC mapping (n = 7) were also performed in 10 healthy age- and sex-matched control subjects (three boys, seven girls; age range, 4-9 years; mean, 6 years +/- 1). Statistical analysis involved the t test for comparison between different groups; correlation between ADC and spectroscopy results was studied with the Pearson test. RESULTS: MR imaging revealed evidence of bilateral WM involvement in all patients. Whereas their NAA/Cr and Cho/Cr were normal, their mI/Cr was slightly increased compared with that in control subjects (P = .03 in FWM and P = .07 in POWM), and their NAA/Cho was decreased in POWM (P = .03). NAA/H(2)O, Cr/H(2)O, Cho/H(2)O, and mI/H(2)O were considerably decreased (P < .05 for all) and ADC values were increased (P < .001) in WM in all patients versus these values in WM in control subjects. There was significant correlation between ADC values and metabolite/water ratios (r = -0.777 to -0.967, P < .05). CONCLUSION: ADC mapping and (1)H MR spectroscopy reveal abnormally high free-water concentrations in the WM of patients with merosin-deficient CMD.

Merosin-deficient congenital muscular dystrophy (CMD): a study of 25 Brazilian patients using MRI.

BACKGROUND: Merosin-deficient congenital muscular dystrophy (CMD) is characterized clinically by hypotonia and muscular weakness and, on imaging studies, by white matter (WM) abnormality. OBJECTIVE: To evaluate MRI findings in Brazilian patients with merosin-deficient CMD. MATERIALS AND METHODS: Twenty-five patients were evaluated using MRI. Three patients presented with partial merosin deficiency and 22 with total merosin deficiency. Follow-up examinations were done in 7 cases. T1- and T2-weighted images were performed in all examinations, and fluid-attenuated inversion recovery (FLAIR) was performed in 15. Enhanced images were done in 11 cases. The WM involvement was classified according to location and severity. RESULTS: From 1991 to 2004, 32 MRI examinations were performed. Severe involvement was found in 23 patients in the frontal and temporal lobes, in 18 patients in the parietal lobes, and in 7 patients in the occipital lobes. The brain stem (n=5), cerebellum (n=6), internal capsules (n=1), and external capsules (n=5) were also affected. One patient had occipital pachygyria, and one had cerebellar vermian hypoplasia. No gadolinium enhancement was noted. Follow-up MRI showed no interval change (n=4), progression (n=1), or improvement of the findings (n=2). CONCLUSION: This series of patients demonstrated that there was no correlation between the extent of WM abnormality on MRI and the clinical status and degree of merosin deficiency (partial or total). Bilateral WM involvement was seen to be more prominent in the parietal, frontal, and temporal regions of the brain. The brain stem and internal and external capsules were less affected. Cerebellar WM involvement is rare. Changes on follow-up imaging studies did not correlate with the clinical status of the patient.

Kearns-Sayre Sundrome "plus": classical clinical findings and dystonia

We present a boy of eight years of age with symptoms of Kearns-Sayre syndrome (KSS) characterised by ophthalmoparesis, palpebral ptosis, mitochondrial myopathy, pigmentous retinitis, associated to short stature, cerebellar signs, cardiac blockade, diabetes melitus, elevated cerebrospinal fluid protein concentration, and focal hand and foot dystonia. The skeletal muscle biopsy demonstrated ragged red fibers, cytochrome C oxidase-negative and succinate dehydrogenase-positive fibers. The magnetic resonance imaging showed symmetrical signal alteration in tegmentum of brain stem, pallidum and thalamus. Mitochondrial DNA analysis from skeletal muscle showed a deletion in heteroplasmic condition. The association of dystonia to KSS, confirmed by molecular analysis, is first described in this case, and the importance of oxidative phosphorylation defects in the physiopathogenesis of this type of movement disorder is stressed.

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.

Miotonia congênita: relato de sete pacientes / Congenital myotonia: report of 7 patients

Miotonia é o fenômeno da diminuiçao da velocidade de relaxamento muscular após contraçao, estímulo mecânico ou elétrico. As miotonias congênitas sao afecçoes hereditárias e nao apresentam distrofla muscular. Atualmente, a tendência é agrupá-las como doenças de canais iônicos, juntamente com as paralisias periódicas. Foram acompanhados sete pacientes, seis do sexo masculino e um do sexo feminino, com idade entre 16 e 48 anos (média 27 anos) e início dos sintomas entre 1 e 10 anos (média 5 anos), que apresentavam fenômeno miotônico desencadeado por contraçao intensa e hipertrofia muscular global. Três pacientes foram diagnosticados como miotonia generalizada tipo Becker por apresentarem herança autossômica recessiva e/ou episódios transitórios de fraqueza muscular. Dois pacientes correspondiam à miotonia congênita de Thomsen, com padrao de herança autossômica dominante e/ou ausência de episódios de fraqueza ou fatores de piora. Dois pacientes apresentavam miotonia flutuante, piorando com o frio e/ou ingestao de potássio. O diagnóstico clínico foi confirmado através de exames complementares (eletroneuromiografia, biópsia muscular e estudo do DNA). Cada paciente fez uso de diferentes drogas, no sentido de procurar o máximo de melhora da miotonia. Houve cinco relatos de melhora com difenil-hidantoína, um com carbamazepina, três com acetazolamida, um com bloqueador de canal de cálcio, um com beta-adrenérgico, um com tiazídico e nenhum com quinidina/procainamida.

Amiotrofia espinal crônica juvenil simulando distrofia muscular / The chronic spinal muscular atrophy juvenile simulating muscular dystrophy

A amiotrofia espinal crônica proximal juvenil constitui uma entidade de doença distinta mas, parece ser pouco conhecida desde que é geralmente confundida com distrofia muscular**(9,10). Os autores descrevem um caso clínico isolado de amiotrofia espinal crônica proximal juvenil comprovado pela eletromiografia, porém com características clínicas, laboratoriais e histológicas sugestivas de distrofia muscular, alertando, assim, para os casos de amiotrofia espinal progressiva de evoluçäo longa, erroneamente diagnosticados como distrofia muscular

Miopatia nemalínica com corpos intracitoplasmáticos esferóides: relato de caso / Nemalinic myopathy with intracytoplasmic spheroid bodies: a case report

Os autores relatam o caso de paciente do sexo feminino de 18 anos de idade com fraqueza lentamente progressiva nos quatro membros desde a infância, sem antecedentes relevantes. O exame neurológico mostrou déficit motor discreto proximal e distal com retraçao muscular leve ao nível de ombros, cotovelos, articulaçoes coxo-femurais, joelhos e tornozelos; hipotrofia muscular nas pernas e pés: reflexos presentes e sensibilidade normal. Creatinofosfoquinase com aumento de uma vez e meia o valor normal. Eletroneuromiografia: diminuiçao de amplitude e duraçao dos potenciais de açao e traçado de interferência paradoxal, compatíveis com afecçao muscular primária. Biópsia muscular em congelaçao (HE, Gomori, PAS, ATPases, NADH, SDH, fosfatases ácida e alcalina, citocromo-c-oxidase e Oil-red-O) revelou afecçao muscular primária caracterizada pela presença de corpos nemalínicos e corpos intracitoplasmáticos esferóides. Os corpos nemalínicos podem ser encontrados com diferentes alteraçoes das fibras musculares, porém essa associaçao é rara. Este é o segundo relato da associaçao entre corpos nemalínicos e esferóides.