Clinical and radiological profile of patients with spinal muscular atrophy type 4.

BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is the most important cause of motor neuron disease in childhood, and continues to represent the leading genetic cause of infant death. Adulthood-onset SMA (SMA type 4) is rare, with few isolated cases reported. The objective of the present study was to describe a cohort of patients with SMA type 4. METHODS: A cross-sectional study was conducted to characterize clinical, genetic, radiological and neurophysiological features of patients with adulthood-onset SMA. Correlation analysis of functional assessment with genetic, radiological and neurophysiological data was performed. RESULTS: Twenty patients with SMA type 4 were identified in a Brazilian cohort of 227 patients with SMA. The most common clinical symptom was limb-girdle muscle weakness, observed in 15 patients (75%). The most frequent neurological findings were absent tendon reflexes in 18 (90%) and fasciculations in nine patients (45%). Sixteen patients (80%) had the homozygous deletion of exon 7 in the SMN1 gene, with 12 patients (60%) showing four copies of the SMN2 gene. The functional scales Hammersmith Functional Motor Scale Expanded, Amyotrophic Lateral Sclerosis Functional Rating Scale Revised, Revised Upper Limb Module and Spinal Muscular Atrophy Functional Rating Scale, as well as the six-minute walk and the Time Up and Go tests showed a correlation with duration of disease. Motor Unit Number Index was correlated both with duration of disease and with performance in functional assessment. Radiological studies exhibited a typical pattern, with involvement of biceps femoris short head and gluteus minimus in all patients. CONCLUSION: This study represents the largest cohort of patients with SMA type 4 and provides functional, genetic, radiological and neurophysiological features that can be used as potential biomarkers for the new specific genetic therapies for SMA.

Atypical Motor Neuron Disease variants: Still a diagnostic challenge in Neurology.

Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice.

New findings in facial-onset sensory and motor neuronopathy (FOSMN) syndrome.

Facial-onset sensory and motor neuronopathy (FOSMN) syndrome represents a rare, slowly progressive, lower motor neuron disease with sensory compromise, involving mainly the face, bulbar region and upper limbs. However, non-motor symptoms and neurogenetic studies have rarely been evaluated in large case series. In the present study, 10 unrelated Brazilian patients with FOSMN syndrome underwent extensive clinical, laboratory, neurophysiological and neurogenetic assessment. Median age at symptom onset was 52.1 years, and men and women were equally affected. Patients presented with hemifacial or bilateral facial paresthesia and weakness, which evolved with dysphagia, dysphonia, and facial and tongue atrophy and, finally, a dropped-head, upper limb weakness and syringomyelia-like sensory disturbances in the upper limbs. All 10 patients showed chronic diffuse neurogenic compromise of bulbar, cervical and thoracic myotomes, and abnormal blink reflex tests. A positive family history of neurodegeneration was identified in six cases, and revealed pathogenic gene variants in three families (involving VCP, TARDBP and CHCHD10). Thus, our case series has revealed new findings regarding FOSMN syndrome: (i) its clinical course is not always benign, with poorer prognoses associated with dropped-head syndrome and early bulbar compromise; (ii) FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; and (iii) a definite genetic basis may be observed in some cases.

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy.

Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption ( V ˙ O 2 ) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO.

Post-polio syndrome: epidemiologic and prognostic aspects in Brazil.

OBJECTIVES: To describe the clinical and epidemiological aspects of post-polio syndrome (PPS) and identify predictors of its severity. MATERIALS AND METHODS: 132 patients with PPS were selected at the Neuromuscular Disease Outpatient Clinic of the Federal University of São Paulo. Descriptive analysis was carried out and predictors of PPS severe forms were investigated using an unconditional logistic regression. RESULTS: The average age at onset was 39.4 years. The most common symptoms were fatigue (87.1%), muscle pain (82.4%) and joint pain (72.0%); 50.4% of the cases were severe. The following were associated with PPS severity: a < or =4-year period of neurological recovery (OR 2.8), permanent damage in two limbs (OR 3.6) and residence at the time of acute polio in a city with more advanced medical assistance (OR 2.5). CONCLUSIONS: Health professionals should carefully evaluate polio survivors for PPS and be aware of the implications of muscle overuse in the neurological recovery period.

Fukuyama-type congenital muscular dystrophy: a case report in the Japanese population living in Brazil.

INTRODUCTION: We present herein clinical, histological and magnetic resonance imaging (MRI) findings in a patient with Fukuyama-type congenital muscular dystrophy (FCMD). He is the first case report in the Japanese population living in Brazil. CASE REPORT: The child presented with neonatal hypotonia, delayed motor abilities and speech, seizures, cerebral and cerebellar gyrus abnormalities with signal intensity change in the white matter by MRI, high serum level of creatinephosphokinase (CK), and dystrophic skeletal muscle with normal merosin, alpha-sarcoglycan and dystrophin expression. The fukutin gene study showed one founder 3-kb retrotransposal insertion in the 3'-non-coding region, and in the other allele no mutation was detected after screening all exons and flanking introns by sequencing. DISCUSSION: This case report emphasizes the importance to consider FCMD in Japanese people living in other countries.

Polineuropatia nutricional entre índios Xavantes / Polyneuropathy deficiency among Xavante indians

Os autores apresentam dois casos de polineuropatia carencial (PC) entre os índios Xavantes, em que o arroz era o alimento exclusivo no caso 1 e quase exclusivo no caso 2. O arroz consumido por esses índios era o beneficiado ou despolpado. A intoxicaçao pelo cianeto da mandioca ou de outros vegetais foi afastada. Relato dos Casos. Foram observados em suas aldeias dois índios com 18 e 25 anos, com história progressiva de fraqueza, diminuiçao da força muscular e emagrecimento. Removidos ao Hospital Sao Paulo, notou-se, no exame neurológico do caso 1, atrofia da musculatura distal dos membros superiores e inferiores, déficit motor distalmente com grau zero na musculatura flexora, reflexos profundos abolidos, reflexo cutâneo plantar sem resposta bilateralmente, sensibilidade, táctil, dolorosa e palestésica diminuída distalmente nos membros inferiores. No exame neurológico do caso 2, notou-se hiporreflexia proximal nos membros superiores, areflexia nas porçoes distais dos membros superiores e inferiores, hipoestesia táctil e dolorosa nos pés, hipoacusia à direita. As eletroneuromiografias mostraram anormalidades compatíveis com polineuropatia sensitivo-motora simétrica de padrao axonal desmielinizante no caso 1 e de predomínio desmielinizante no caso 2. Os exames de líquor foram normais. Discussao. A polineuropatia foi caracterizada pela história clínica, pelos exames neurológicos, eletroneuromiográficos e líquor. O diagnóstico de PC ficou estabelecido pela história clínica e pelos exames eletroneuromiográficos sugestivos de polineuropatia periférica de causa nutricional. Esta PC nao se enquadra nas mieloneuropatias como a neuropatia atáxica tropical, a paraparesia espástica e a neuropatia de Cuba. Conclusao. A PC dos Xavantes deve-se à deficiência da tiamina (vitamina B1), sendo o beribéri seco, tendo como causa o consumo do arroz beneficiado industrialmente como alimento exclusivo ou quase exclusivo. A polineuropatia dos Xavantes é diferente da neuropatia verificada ente os índios Kreen-Akrore e a observada entre os adolescentes índios do Parque do Xingu.

Expression of HLA-DR in pheripheral nerve of amyotrophic lateral sclerosis

Para investigar a possibilidade de comprometimento auto imune no nervo perifárico de pacientes com esclerose lateral amiotrófica (ELA) 83 biópsias do nervo periférico de 79 pacientes (51 sexo masculino, 28 sexo feminino) com média de idade de 62 anos (variaçäo de 19 a 82) foram congelada e coradas para demonstraçäo de HLA-DR usando anticorpo monoclonal. Quarenta amostras (48 por cento) mostraram expressäo nitidamente aumentada de HLA-DR na regiäo endoneural. Usando proteínas S-100 como marcador, demonstramos que HLA-DR se expressava principalmente nas células de Schwann. Näo encontramos co-expressäo com HLA-DR usando anticorpos antineurofilamento ou antimielina, mas detectamos co-expressäo de HLA-DR e antireceptor de fator de crescimento nervoso na maioria das células HLA-DR positivas. Células inflamatórias foram encontradas ocasionalmente, sendo detectadas em somente 11 casos, predominantemente ao redor de vasos sanguíneos epineurais. Biopsias de nervo sensitivo e motor feitas simultaneamente mostraram maior expressäo de HLA-DR em nervos motores de 2 dos 4 pacientes. A significância desses achados ainda näo é clara. A presença de células endoneurais expressando HLA-DR sugere que mecanismos auto imunes podem estar envolvidos na ELA tendo a célula de Schwann como um dos principais alvos

Distrofia muscular congênita: estudo clínico de 17 pacientes / Congenital muscular dystrophy: clinical study of 17 patients

Descrevemos 17 pacientes (12m, 5f) com idades que variaram de 1 a 24 anos (mediana 6 anos) com distrofia muscular congênita (DMC), que foram estudados do ponto de vista genético, clínico, laboratorial, eletrofisiológico e anátomo-patológico. A apresentaçäo segundo a herança foi a forma esporádica (76,5%) ou possivelmente autossômica recessiva (23,5%). A diminuiçäo da movimentaçäo fetal intra-uterina foi referida em 57% dos casos, hipotomia neonatal em 82% e retardo no desenvolvimento motor em 88,2%. Fraqueza muscular, diminuiçäo dos reflexos profundos e contraturas articulares estavam presentes em todos os casos. A piora na funçäo motora estava muito relacionada ao aumento ou aparecimento de novas retraçöes articulares. A CK nuna ultrapassou valores acima de 8 vezes o normal. O EN MG foi de padräo miopático em 73,3%, neuropático em 13,3% e normal em 13,3% dos casos. Aspectos tomográficos com hipodensidade da substância branca subcortical foram vistos em 8 casos. Ao tratamento impôs-se fisioterapia adequada e cirurgia corretiva das deformidades articulares. Novas contraturas desenvolveram-se mais tarde e estavam relacionadas freqüêntemente a fisioterapia insuficiente

Miopatia mitocondrial: relato de 12 casos com estudo histoquímico do músculo esquelético / Mitochondrial myopathy: report of 12 cases with histochemical study of the skeletal muscle

Säo relatados 12 pacientes com o diagnóstico de MM definidos histoquimicamente. Nove pacientes eram do sexo masculino e tres do sexo feminino. A idade de início dos sintomas variou desde o período neonatal até os 35 anos de idade (mediana 14 anos). Foram identificadas como características principais a fraqueza muscular, oftalmoplegia e ptose palpebral em 10 pacientes. Um paciente apresentou quadro de intolerância aos exercícios e outro além da fraqueza muscular, alteraçäo do comportamento. Säo discutidos aspectos clínicos e o diagnóstico diferencial de nossos pacientes

Distrofia muscular congênita: apresentaçäo de oito casos com evidência de comprometimento do SNC / Congenital muscular dystrophy. Report of 8 cases with evidence of central nervous system involvement

Doze pacientes portadores de distrofia muscular congênita (DMC) diagnosticados segundo critérios clínicos-laboratoriais foram submetidos a tomografia computadorizada. Em oito deles observou-se hipodensidade da substância branca bilateral e difusamente predominando nos lobos frontais. Nossos achados do sistema nervoso central em pacientes com DMC sugee que a herança esteja ligada a um gene autossômico recessivo polimórfico, responsável pelo envolvimento dos sistema nervoso central e musculatura esquelética

Miosite lúpica pseudogranulomatosa / Pseudogranulomatoues lupic myositis

Os autores relatam um caso de LES, cuja sintomatologia principal era dada por uma importante miopatia. Pela primeira vez na literatura, estudou-se a biópsia muscular por técnicas histoquímicas, concluindo-se por uma miosite lúpica pseudogranulomatosa. Discute-se a raridade do achado, bem como os diagnósticos diferenciais com a PAN, dermatopolimiosite e polimiosite, tendo em vista critérios histológicos