Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis.

OBJECTIVES: To present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis. METHODS: Suspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non-CMS molecular diagnosis. RESULTS: Seventy-nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty-one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non-CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS. CONCLUSIONS: Stricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes.

A case of mitochondrial DNA depletion syndrome type 11 - expanding the genotype and phenotype.

Mitochondrial DNA depletion syndrome type 11 (MTDPS11) is caused by pathogenic variants in MGME1 gene. We report a woman, 40-year-old, who presented slow progressive drop eyelid at 11-year-old with, learning difficulty and frequent falls. Phisical examination revealed: mild scoliosis, elbow hyperextensibility, flat feet, chronic progressive external ophthalmoplegia with upper eyelid ptosis, diffuse hypotonia, and weakness of arm abduction and neck flexion. Investigation evidenced mild serum creatine kinase increase and glucose intolerance; second-degree atrioventricular block; mild mixed-type respiratory disorder and atrophy and granular appearance of the retinal pigment epithelium. Brain magnetic resonance showed cerebellar atrophy. Muscle biopsy was compatible with mitochondrial myopathy. Genetic panel revealed a homozygous pathogenic variant in the MGME1 gene, consistent with MTDPS11 (c.862C>T; p.Gln288*). This case of MTDPS11 can contribute to the phenotypic characterization of this ultra-rare mitochondrial disorder, presenting milder respiratory and nutritional involvement than the previously reported cases, with possible additional features.

X-linked spinal and bulbar muscular atrophy (Kennedy's disease) with long-term electrophysiological evaluation: case report.

X-linked spinal and bulbar muscular atrophy or Kennedy's disease is an adult-onset motor neuronopathy caused by a CAG repeat expansion within the first exon of an androgen receptor gene. We report the case of a 66-year-old man, previously diagnosed with motor neuron disease (MND), who presented acute and reversible left vocal fold (dysphonia) and pharyngeal paresis, followed by a slowly progressive weakness and also bouts of weakness, wasting and fasciculation on tongue, masseter, face, pharyngeal, and some proximal more than distal upper limb muscles, associated to bilateral hand tremor and mild gynecomastia. There were 5 electroneuromyography exams between 1989 and 2003 that revealed chronic reinnervation, some fasciculations (less than clinically observed) and rare fibrillation potentials, and slowly progressive sensory nerve action potentials (SNAP) abnormality, leading to absent/low amplitude potentials. PCR techniques of DNA analysis showed an abnormal number of CAG repeats, found to be 44 (normal 11-34). Our case revealed an acute and asymmetric clinical presentation related to bulbar motoneurons; low amplitude/absent SNAP with mild asymmetry; a sub-clinical or subtle involvement of proximal/distal muscles of both upper and lower limbs; and a probable evolution with bouts of acute dennervation, followed by an efficient reinnervation.

[Analysis of the expression of collagen VI in congenital muscular dystrophy]. / Análise da expressão do colágeno VI na distrofia muscular congênita.

Congenital muscular dystrophy (CMD) composes a group of disorders characterized by hypotonia and muscular weakness noticed in the first year of life. The Ullrich's form is characterized by proximal joint contractures and distal hiperextensibility. About 40% of these patients present mutations in one of the genes that codify the sub-units of the collagen VI protein (COL6), producing total or partial deficiency of the protein expression. We analyzed, through immunohistochemistry, the expression of COL6 in muscle fragments of 50 patients with CMD; 20 of them presented merosin expression deficiency. We identified 4 cases with total COL6 deficiency (8% of the total), representing 13% of the cases with normal merosin expression. The histological findings of patients with deficiency of COL6 were indistinguishable from other forms of CMD, but milder than that abnormalities observed in merosin deficient patients. In three COL6 deficient patients were observed hypotonia and weakness in the neonatal period, delayed of motor milestones, muscular retractions of knees and elbows, distal joint hiperextensibility and congenital hip dislocation (two patients). One patient lost the ability to walk; and one died due to respiratory problems. The analysis of COL6 expression, as well as merosin expression, in the muscle tissue from CMD patients, can be important for identification and phenotypic characterization of different CMD subtypes.

Comunicação alternativa ampliada na esclerose lateral amiotrófica: a tecnologia a favor da reabilitação / Augmentative and alternative communication in amyotrophic lateral sclerosis: technology for rehabilitation

Introdução:A Esclerose Lateral Amiotrófica (ELA), doença caracterizada por deterioração de neurônios motores causa paralisia progressiva de músculos esqueléticos, comprometendo a motricidade dos membros, da deglutição, da respiração e da fala. O comprometimento da fala tem papel fundamental na qualidade de vida do paciente bem como na de seu cuidador. A Comunicação Alternativa Ampliada (CAA) surge como uma oportunidade para amenizar as limitações de comunicação impostas pela doença. Objetivo: Avaliar a eficácia da Comunicação Alternativa Ampliada em pacientes com Esclerose Lateral Amiotrófica. Casuística e Métodos: Estudo quantitativo, descritivo e transversal com 13 pacientes, realizado em São José do Rio Preto ­ SP, Brasil, nos anos de 2015 e 2016. Instrumentos: questionários sócio-demográfico elaborado pelos pesquisadores; questionário de avaliação da ELA (Amyotrophic Lateral Sclerosis Assessment Questionnaire; ALSAQ-40); questionário de qualidade de vida em voz (QVV); e questionário de eficácia dos meios de comunicaçãoalternativa (Vox4All ou HeadMouse). O questionário sócio-demográfico, o ALSAQ-40e o questionário de qualidade de vida em voz foram aplicados antes da intervenção. A intervenção com a Comunicação Alternativa Ampliada foi aplicada durante seis atendimentos individuais com duração de 50 minutos cada, uma a duas vezes por semana com a ajuda do profissional da saúde. Apóso término das sessões, os pacientes responderam ao questionário sobre a eficácia dos meios de comunicação alternativa.A associação entre as variáveis foi medida utilizando o teste exato de Fisher. Resultados: A idade dos pacientes foi de 60,07±11,17 anos (média ± desvio padrão), e 76,92% apresentava cuidador familiar. Cem por cento dos pacientes apresentavam dificuldades na comunicação. Após a intervenção com a Comunicação Alternativa Ampliada os pacientes relataram melhora na comunicação (p<0,05) e consideraram esses métodos eficazes para o uso diário. Conclusão: A Comunicação Alternativa Ampliada pode ser considerada uma intervenção facilitadora na interação social e na qualidade de vida de pacientes com Esclerose Lateral Amiotrófica

Introduction:Amyotrophic Lateral Sclerosis (ALS), a disease characterized by deterioration of upper and lower motor neurons causes progressive paralysis in all skeletal muscles. It compromises limb motility, swallowing, breathing, and speech. Speech impairment plays a key role in both the patient and the caregiver's quality of life. Augmentative and Alternative Communication (AAC) emerges as an opportunity to alleviate the communication limitations imposed by the disease. Objective: Assess the effectiveness of Augmentative and Alternative Communication in patients with Amyotrophic Lateral Sclerosis. Patients and Methods:We carried out a descriptive, quantitative and cross-sectional study conducted with 13 patients in SP, Brazil from 2015 to 2016. We used a questionnaire designed by the researcher to assess sociodemographic characteristics; an Amyotrophic Lateral Sclerosis assessment questionnaire (ALSAQ-40); voice-related quality of life (V-RQOL); and a questionnaire to assess the effectiveness of alternative communication (Vox4All or HeadMouse). The sociodemographic questionnaire, the Amyotrophic Lateral Sclerosis assessment questionnaire and the voice-related quality of life survey were applied before the intervention. The intervention with Augmentative and Alternative Communication was applied during six individual visits lasting 50 minutes each, once or twice a week with the help of the health professional. After the end of the sessions, the patients answered the questionnaire on the effectiveness of the alternative means of communication. The association between variables was measured using the Fisher's exact test. Results: The mean age was 60.07 ± 11.17, and 76.92% of the patients had family caregivers. All the patients exhibited communication difficulties caused by voice-related quality of life. After Augmentative and Alternative Communication intervention, patients reported improved communication (p<0.05), and they considered these methods effective for daily use. Conclusion:Augmentative and Alternative Communication can be considered a facilitating intervention for social interaction and quality of life of patients with amyotrophic lateral sclerosis.

X-linked spinal and bulbar muscular atrophy (Kennedy's disease) with long-term electrophysiological evaluation: case report

Atrofia muscular bulbo-espinal ligada ao cromossomo X (doença de Kennedy) é uma neuronopatia motora em adultos causada por expansões na repetição CAG no gene do receptor andrógeno. Neste relato, descreve-se o caso de homem de 66 anos, com diagnóstico prévio de doença do neurônio motor (DNM) que apresentou quadro agudo e reversível de paresia de prega vocal (disfonia) e de músculos faríngeos à esquerda; posteriormente seguiram-se surtos de fraqueza lentamente progressiva, atrofia e fasciculações em língua, masseter, face, faringe e membros superiores predominantemente proximal, associada a tremor bilateral de mãos e ginecomastia leve. Foram realizadas 5 eletroneuromiografias entre 1989 e 2003 que mostraram reinervação crônica, algumas fasciculações, raras fibrilações e redução progressiva de amplitude ou ausência dos potenciais de ação dos nervos sensitivos (PANS). Técnica de PCR para análise de DNA revelou expansão anormal de repetições CAG, sendo encontrado 44 (normal, 11-34). Este caso teve apresentação clínica aguda e assimétrica relacionada aos motoneurônios bulbares; PANS ausentes ou de baixa amplitude com leve assimetria; envolvimento subclínico ou leve de músculos proximais e distais tanto de membros superiores como inferiores; e, provável evolução com surtos agudos de desnervação aguda, seguida por reinervação eficiente.

Análise da expressão do colágeno VI na distrofia muscular congênita / Analysis of the expression of collagen VI in congenital muscular dystrophy

A distrofia muscular congênita (DMC) compõe um grupo de miopatias caracterizadas por hipotonia e fraqueza muscular notadas já no primeiro ano de vida. A forma de Ullrich é caracterizada por retrações musculares proximais e hiperextensibilidade distal. Cerca de 40 por cento destes pacientes apresentam mutações em um dos genes que codificam as três sub-unidades do colágeno VI (COL6), acarretando deficiência total ou parcial na marcação da proteína. Analisamos, através de imunofluorescência, a marcação do COL6 em fragmentos musculares de 50 pacientes com DMC, 20 deles com ausência da marcação para merosina. Identificamos 4 casos com deficiência total da marcação do COL6 (8 por cento do total), representando 13 por cento dos casos com marcação normal para merosina. As alterações histológicas musculares dos pacientes com COL6 deficiente eram indistinguíveis das outras formas de DMC, porém mais brandas que as observadas na DMC com deficiência de merosina. Em três dos pacientes com COL6 deficiente observou-se hipotonia e fraqueza muscular, notadas já no período neonatal, atraso do desenvolvimento motor, retrações musculares em joelhos e cotovelos, hiperextensibilidade distal e luxação congênita do quadril (dois pacientes). Um paciente perdeu a capacidade para a marcha, e outro faleceu por problemas respiratórios. A análise da marcação do COL6, assim como da merosina, no tecido muscular de pacientes com DMC pode auxiliar na identificação e caracterização fenotípica dos diversos subtipos de DMC.

Comparison of nerve conduction techniques in 95 mild carpal tunnel syndrome hands

Electrodiagnosis of carpal tunnel syndrome (CTS) were prospectively studied in 95 hands. The following techniques were studied in all hands when at least one abnormal value was found (onset-measured), it was included on results: 1. wrist-index finger latency (WIF), abnormal = 2.8 ms, 140 mm; 2. palm-wrist latency (PW), abnormal = 1.8 ms, 80 mm; 3. comparison median/ulnar palm-wrist latency (CPW), abnormal = 0.4 ms; 4. comparison median/ulnar latency, wrist-ring finger (CMU), abnormal = 0.5 ms, 140 mm; 5. comparison median/radial latency, wrist-thumb (CMR), abnormal = 0.4 ms, 100 mm. All 95 CTS hands selected have the WIF = 3.5 ms (mild CTS). We found the CMR (97.8 per cent) technique the most sensitive for mild CTS electrodiagnosis and the only comparative method with all potentials recordable when compared to CPW (88.4 per cent). PW (84.2 per cent), CMU (72.6 per cent) and WIF (68.4 per cent).

Myasthenia gravis in children: analysis of 18 patients

Myasthenia gravis (MG) in childhood is rare comprising 10 to 20 percent of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1). Eleven patients (61 percent) presented moderate or severe generalized disease and 4 (22 percent) had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47 percent) out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6 percent (9 out of 11 tested) and the levels had no relation to clinical severity. Nine out of 16 patients (56 percent) worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia). Three patients (75 percent) improved markedly after thymectomy and one (25 percent) worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child

Fatal rhabdomyolysis after acute sodium monensin (Rumensin) toxicity: case report

Myoglobinuria or rhabdomyolysis occurs when myoglobin escapes into the blood and then into the urine after acute muscle necrosis. It can be a serious medical condition leading to renal failure and death. There are many causes including exertion, crush syndromes, ischaemia, metabolic disorders, exogenous toxins and drugs, heat stroke and hereditary disorders such as malignant hyperthermia. We report the case of a 17 year-old boy who developed myoglobinuria, renal failure and death 11 days after ingesting sodium monensin, possibly with the intention of developing muscles. Sodium monensin, the active principle of Rumensin®, is a dietary additive used as a growth promoter for confined cattle. There are no previous reports of human intoxication. Accidental or experimental sodium monensin intoxication in animals produces similar findings to those seen in this case

Acidose tubular renal distal manifestando-se com rabdomiólise / Distal renal tubular acidosis manifesting with rhabdomyolysis

A hipocalemia severa é causa incomum de rabdomiólise. Descreve-se ocaso de uma paciente de 28 anos com acidose tubular renal distal, que desenvolveu hipocalemia severa com consequente rabdomiólise. O estudo histológico do músculo evidenciou áreas focais de necrose muscular predominando em fibras do tipo II, com discreta reaçäo macrofágica. A melhota clínica e laboratorial apresentada pela paciente ocorreu após a normalizaçäo do potássio sérico, tendo sido fundamental, neste caso, a correçäo da acidose metabólica

Isolated and painless infraspinatus atrophy in top-level volleyball players: report of two cases and review of the literature

Atrofia isolada e näo dolorosa do músculo infraespinhoso e fraqueza säo descritas em 2 jogadores de voleibol. EMG mostrou desnervaçäo isolada do músculo infraespinoso. Um dos atletas continuou jogando e näo foi notada qualquer alteraçäo no quadro clínico. O outro, após cessar as suas atividades esportivas, recuperou progressivamente a força e o trofismo muscular. Estes dados sugerem íntima relaçäo entre comprometimento do músculo infraespinhoso e atividade intensa da articulaçäo do ombro, mas sem qualquer trauma direto. Näo consideramos estes casos como verdadeiros exemplos de neuropatia por compressäo. Patogênese foi relacionada à traçäo dos ramos distais do nervo supraescapular durante o ato da recepçäo da bola ("Manchete")

Paralisia periódica: estudo anátomo-patológico do músculo esquelético de 14 pacientes / Periodic paralysis: anatomo-pathological study of musculoskeletal of 14 patients

A paralisia periódica é entidade caracterizada por crises de fraqueza muscular relacionadas com alteraçöes do nível sérico de potássio. A biópsia muscular pode mostrar alteraçöes específicas ou inespecíficas. Nosso estudo tem como objetivo a análise de 18 biópsias musculares de 14 pacientes com paralisia periódica (14 hipocalêmica, 2 hipercalêmica). Todas as biópsias mostraram alguma alteraçäo histopatológica. Quatorze biópsias apresentavam vacúolos, que se caracterizavam por serem únicos, de localizaçäo periférica, de aparecimento frequente e preferentemente em fibras do tipo I. Os vacúolos eram mais visualizados naqueles pacientes com longa evoluçäo e sem relaçäo com a frequência de crises. Os agregados tubulares foram encontrados em 10 biópsias principalmente naqueles pacientes com crises frequentes e doença de longa evoluçäo. Em 3 pacientes foram realizadas 2 biópsias, notando-se piora das alteraçöes em 2. Um paciente evoluiu com quadro clínico de miopatia permanente, confirmado pela biópsia muscular. Alteraçöes inespecíficas foram encontradas em graus variáveis em 15 biópsias. Nosso estudo mostra que os vacúolos e os agregados tubulares säo achado frequentes na paralisia periódica, constituindo importante auxílio diagnóstico. Alteraçöes miopáticas evidentes à biópsia sugerem o aparecimento de miopatia permanente, quadro decorrente de doença de longa evoluçäo ou crises severas

Body mass index and carpal tunnel syndrome

Carpal tunnel syndrome (CTS) has been correlated to body mass index (BMI) increase. The present study was done in a Brazilian population to compare BMI values in the following groups: first, CTS vs. controls subjects, and, second CTS groups of increasing median sensory latency (MSL). According to MSL33.7 ms (wrist-index finger, 14 cm), median/ulnar sensory latency difference30.5 ms (ring finger, 14 cm) or median palm-to-wrist (8 cm) latency32.3 ms (all peak-measured), 141 cases (238 hands) had CTS confirmation. All were symptomatic; previous surgery and polyneuropathy were excluded; mean age 50.3; 90.8 prcent female. Controls subjects (n=243; mean age 43.0; 96.7 percent female) and CTS cases had BMI calculated (kg/m2). Controls subjects had a mean BMI of 25.43 +/- 4.80 versus 28.38 +/- 4.69 of all CTS cases, a statistically significant difference (p<0.001). The CTS groups of increasing MSL severity do not show additional increase in BMI (28.44 for incipient, 28.27 for mild, 28.75 for moderate and 29.0 for severe). We conclude that CTS cases have a significant correlation with higher BMI when compared to controls subjects; however, higher BMI do not represent a statistically significant increasing risk for more severe MSL.

Síndrome do túnel do carpo / Carpal tunnel syndrome

Síndrome do túnel do carpo (STC) é a neuropatía compressíva mais comum do ser humano; o nervo mediano sofre efeitos pressóricos no túnel do carpo, 3-4 cm dístal à prega do pulso, com desmielinização nodal ou segmentar nas fases iniciais. O complexo sintomático incluí dor, dormância e fomigamento,noturnolpostural nas mãos, freqüentemente bilateral e mais comum em mulheres entre 40 e 60 anos. Fatores pessoais repre- sentam risco mais importante do que os ocupacionais, particularmente o aumento da idade, do índice de massa corporal e do índice do pulso (pulsos quadrados'@, várias condições nosológicas podem estar associadas a STC. Ressonância magnética da região carpal pode ser útil em casos selecionados e atípicos. A descompressão cirúrgica representa a melhor alternativa terapêutica com benefícios indiscutíveis, apesar de controvérsías com relação a seleção dos pacientes, tratamento conservador por meio de talas, retirada de fatores desencadeantes e uso de medicações sintomáticas podem ser utilizados nas fases iniciais com achados eletrofisioiógícos leves. O estudo da condução nervosa é o método complementar mais adequado para diagnóstico da STC, observan- do-se aumento das fatências dístais sensitivas e motoras do nervo mediano (redução da velocidade de condução na região carpal).(au)