Reaching task performance is associated to neuromuscular junction adaptations in rats with induced diabetes mellitus

Upper limb performance is affected by diabetes mellitus (DM). Neuromuscular junction (NMJ) is a key structure to understand the relationship between performance and morphology in DM. The aim of the study was to analyze NMJ plasticity due to DM in an animal model and its relationship with the function of forelimbs in rats. Twelve Wistar rats were divided into control (C) and DM groups. Animals were trained to perform a grasping task, following procedures of habituation, shaping, and reaching task. DM was induced using streptozotocin. Forelimb neuromuscular performance for dexterity was evaluated one day before DM induction and five weeks following induction. After that, biceps, triceps, and finger flexors and extensors were removed. Connective tissue and muscle fiber cross-sectional area (CSA) were measured. NMJ was assessed by its morphometric characteristics (area, perimeter, and maximum diameter), using ImageJ software. Motor performance analyses were made using single pellet retrieval task performance test. Student's t-test was used for comparisons between groups. A significant decrease in all NMJ morphometric parameters was observed in the DM group compared with the C group. Results showed that DM generated NMJ retraction in muscles involved in a reaching task. These alterations are related to signs of muscular atrophy and to poor reaching task performance. In conclusion, induced DM caused NMJ retraction and muscular atrophy in muscles involved in reaching task performance. Induced DM caused significantly lower motor performance, especially in the final moments of evaluation, when DM compromised the tropism of the muscular tissue.

A Case of Sheehan's Syndrome that Manifested as Bilateral Ptosis

Hypothyroidism can cause a variety of signs and symptoms of the neuromuscular system. However, ptosis in a patient with hypothyroidism is very rare. We report here on a case of central hypothyroidism that was due to Sheehan's syndrome and it manifested as bilateral ptosis in a 51-yr-old woman. She complained of exertional dyspnea and weakness. About 25-yr ago, she had a history of severe postpartum vaginal bleeding. The laboratory studies demonstrated hypopituitarism with secondary hypothyroidism. The ptosis was improved by replacement of thyroid hormone. Hypothyroidism should be considered in the differential diagnosis of patients who manifest with ptosis and that prompt replacement of hormone can lead to a complete recovery.

Estudo neurofisiológico na síndrome miastênica congênita do canal lento: relato de caso / Neurophysiological study in slow-channel congenital myasthenic syndrome: case report

A síndrome do canal lento é uma das síndromes miastênicas congênitas atribuída a desordem dinâmica do canal iônico do receptor de acetilcolina da junção neuromuscular. Descrevemos o caso de um homem de 25 anos com progressiva ptose palpebral e limitação da movimentação ocular desde infância, que evoluiu há 6 anos com piora da oftalmoparesia externa e diminuição da força muscular em ombros e mãos. O estudo da condução nervosa motora após estímulo único demonstrou duplo potencial de ação muscular composto (PAMC) com desaparecimento do segundo após esforço de 30 segundos. Ao estímulo repetitivo dos nervos facial e acessório observou-se um decremento da amplitude do PAMC maior que 10 por cento com desaparecimento do segundo potencial. O paciente fez uso de fluoxetina mostrando discreta melhora da força muscular, porém persiste com: ptose palpebral, limitação dos movimentos oculares e PAMC repetitivo ao estudo da condução nervosa motora. As características da doença são discutidas.

Acute axonal polyneuropathy in an unventilated patient with sepsis.

Critical Illness Polyneuropathy (CIP) represents an acute axonal neuropathy that develops during treatment of severely ill patients and remits spontaneously once the critical condition is under control. Except for differences in the predisposing causes, it is difficult to distinguish CIP from axonal Guillain-Barré Syndrome (GBS) on purely clinical grounds. We describe a 70 years lady who developed acute axonal polyneuropathy two weeks following snakebite. She developed this in the background of sepsis but never required ventilatory support. The difficulties in differentiating CIP from axonal GBS are discussed. The hypothesized overlap between both these syndromes is also reviewed.

Evaluation of electrophysiological response to thymectomy in patients with myasthenia gravis.

Clinical response to thymectomy in patients with myasthenia gravis varies in terms of timing and degree of improvement. Electrophysiological test is a reasonably reliable and objective way to evaluate neuromuscular transmission in these patients. The purpose of this study was to evaluate the electrophysiological response before and after thymectomy by repetitive nerve stimulation test in order to estimate the timing of initial improvement, progress and degree of improvement after thymectomy. According to electrophysiological findings, it appeared that neuromuscular transmission in these patients might have begun to improve even as early as one week after thymectomy and steadily improved by the end of one year of the study corresponding to clinical improvement.

Síndrome miasténico de Eaton-Lambert: un reto diagnóstico y terapéutico / Eaton-Lambert myasthenic syndrome: a diagnostic and therapeutic challenge

El síndrome miasténico de Eaton-Lambert (SMEL) es un padecimiento raro de naturaleza autoinmunitaria que afecta la porción presináptica de la unión neuromuscular. ocurre habitualmente en hombres mayores de 60 años; en dos terceras partes de los casos se relaciona con un padecimiento neoplásico y en el resto se considera "idiopático". La producción de autoanticuerpos contra las compuertas de calcio dependientes de voltaje produce falla en la liberación de aceltilcolina. Las manifestaciones clínicas más sobresalientes son debilidad, hiporreflexia y trastornos en la función autonómica. El SMEL puede preceder al cáncer hasta por varios años, en especial el de células pequeñas de pulmón. La prueba de estimulación repetitiva a frecuencias altas muestra en los pacientes con SMEL un incremento característico en el potencial muscular, que es muy típico del padecimiento. El tratamiento debe encaminarse en tres puntos: manejo oncológico, manipulación de la neurotransmisión e inmunomoduladores/inmunosupresores.

Ultrastructure of neuromuscular junction in vacor-induced diabetic rats

OBJECTIVES: Rodenticide Vacor causes a severe peripheral neuropathy in humans. Electrophysiologic studies on a peripheral motor nerve-skeletal system of Vacor-treated rat showed decreased amplitude of muscle action potential without conduction velocity abnormalities. The ultrastructural studies of the neuromuscular junction were performed to clarify the anatomic site of the Vacor-induced peripheral neuropathy in male Wistar rats. METHODS: After oral administration of a single dose of Vacor, 80 mg/kg of body weight, to the experimental animals, neuromuscular junctions within the interosseous muscles of the hind foot were observed in time. RESULTS: No axon terminal change was noted until 24 hours after the administration of Vacor. Remarkable loss of presynaptic vesicles and swollen endoplasmic reticulum in the axon terminal were developed at 3 days after Vacor treatment. Progressive degenerative changes consisting of marked loss of presynaptic vesicles, focal disruption of membrane in the axon terminal with disappearance of the number of the damaged axon terminal appeared, and flattening of postsynaptic folds was also seen. CONCLUSIONS: These results suggest that degenerative changes in axon terminal at neuromuscular junction may contribute to the peripheral neuropathy developed in the early phase of Vacor poisoning.

Anormalidades neuromusculares no desuso, senilidade e caquexia / Neuromuscular abnormalities in disuse, ageing and cachexia

É feita revisäo de literatura sobre as principais alteraçöes do sistema neuromuscular no desuso, senilidade e caquexia no ser humano e em modelos animais. A diminuiçäo do diâmetro das fibras musculares após período de inatividade/imobilidade (desuso) deve-se à perda de miofibrilas periféricas näo ocorrendo formaçäo de core-targetóides ou diminuiçäo da atividade da miofosforilase, próprias da desnervaçäo; mantêm-se a liberaçäo espontânea de acetilcolina e fatores tróficos na junçäo mio-neural; em geral säo afetadas preferencialmente fibras II, que podem assumir forma angular. Existe um processo contínuo intrínseco de envelhecimento de nervos e músculos, com desnervaçäo e reinervaçäo lenta e progressiva; o número de unidades motoras se reduz após 60 anos, sem ocorrência de atividade elétrica desnervatória; a quantidade de acetilcolina liberada nos neurônios terminais e a capacidade máxima de utilizaçäo de oxigênio estäo diminuidas; a reduçäo da capacidade oxidativa mitocondrial pode explicar o aumento de fibras 1, mantendo-se o equilíbrio energético. Após poucas semanas de caquexia as fibras musculares podem ter o diametro reduzido em 30 por cento, essa reduçäo ocorre em ordem decrescente nos músculos dos membros inferiores, superiores e tronco; existe atrofia II preferencial com fibras angulares ocasionais, reduçäo de RNA/síntese proteica, mantendo-se DNA normal

effect of diabetes on neuro muscular transmission

This work included clinical and experimental studies. The clinical study included ten normal females as controls and ten uncontrolled diabetic females who did not receive insulin therapy before. Estimation of fasting blood glucose, fasting serum insulin and measurement of hand grip strength before and after treatment with insulin were done. The results demonstrated that diabetes produce marked weakness of the hand grip strength which improves markedly after insulin therapy. The experimental study was carried on rat phrenic diaphragm preparations taken from normal rats and alloxan diabetic rats. Fasting blood glucose and serum insulin levels were determined, then the time needed to induce neuro muscular block was calculated when indirectly stimulated at a rate of 1 impulse/second and 5 impulses/second. Five experiments were done after addition of insulin to the bath in diabetic rats. It can be concluded that the time is much shortened in diabetic rats and significantly prolonged after addition of insulin to the bath

Neuromuscular transmission studies in human chronic Chagas' disease

Cincuenta y ocho pacientes con edades entre los 1 y 58 años, con diagnóstico de enfermedad de Chagas crónica fueron estudiados para evaluar la transmisión neuromuscular. Se estimuló en forma supramáxima el nervio cubital a nivel de muñeca, con registro de electrodos de superficie en hipotenar. Dicha estimulación se realizó a 3 Hz durante 2 segundos y 10 Hz durante 1 segundo en condiciones basales, trás 4 minutos de ejercicio mecánico, luego de 4 minutos de ejercicio mecánico mas isquemia y trás 2 minutos de liberada la isquemia. Se procedió a medir la amplitud del 3, 5, 6 y 10 potencial, que fueron expresados como variación porcentual con respecto al primero al que se le asignó un valor de 100%. Treinta pacientes no evidenciaron diferencias con respecto a la curva obtenida en 20 sujetos controles, 4 mostraron una caida del potencial evocado muscular, 6 una caida del mismo cuando el estímulo se realizó frecuencias y un incremento cuanto el estímulo fue a altas frecuencias. En los restantes 18 pacientes se observó un incremento del pem. Estos hallazgos susgieren una posible alteración de la transmisión neuromuscular en algunos pacientes que han alcanzado el estadio crónico de la efemedad de Chagas de probable localización pré y/o post-sináptica

Motor unit involvment in human acute Chagas' disease

Treinta e cinco pacientes con el diagnóstico de enfermedad de Chagas en su etapa aguda, todos con parasitemia positiva en el momento de la investigación, fueron sometidos a estudio electromiográfico por técnicas convencionales. En reposo, 12 de ellos mostraron fibrilaciones y/o potenciales positivos. Durante la contracción voluntária, en 7 pacientes los potenciales de unidad motora eran bifásicos de corta duración y polifásicos de baja amplitud. En 20 se encontró disminución de la velocidad de conducción motora y/o sensitiva en uno o mas de los nervios explorados. Finalmente, 12 pacientes mostraron caida de la amplitud del potencial muscular evocado por estímulo nervioso repetitivo supramáximo. Los hallazgos hechos señalan que durante la fase aguda de la enfermedad de Chagas en el hombre puede producirse alteración primária del músculo, neuropatía y compromiso de la transmisión neuromuscular, en forma aislada o combinadas entre si

Alteraçöes da junçäo neuromuscular em miopatias experimentais no camundongo / Neuromuscular junction changes in experimental myopathies in mice

As alteraçöes morfológicas observadas em junçäo neuromuscular de dois modelos de miopatia em camundongos säo estudadas por métodos histoquímicos para demonstrar atividade da enzima acetilcolinesterase e por microscopia eletrônica. Em ambas as situaçöes os resultados obtidos säo similares, indicando que a junçäo neuromuscular permanece intacta mesmo quando a fibra que inerva está sofrendo necrose. Em fibras musculares regeneradas há acentuada simplificaçäo das pregas pós-sinápticas, com reduçäo de até 50% dos valores normais, comprovado por estudos morfométricos. A ausência de reprecussöes fisiológicas ou clinicas detectáveis nesses modelos, apesar da significancia hipotrfia da membrana pós-sináptica, sugere que a exuberante quantidade de pregas pós-sinápticas normalmente encontradas nas junçöes mioneurais pode representar mecanismo anatômico de segurança na transmissäo química neuromuscular

Estudio electrofisiológico de la función neuromuscular en una población intoxicada con plomo / Electrophysiological study of the neuromuscular function in a population with lead poisoning

Un grupo de 12 pacientes con cifras elevadas de plombemia y disminuidas de ALA D fueron estudiados electrofisiológicamente. Se efectuaron las siguientes determinaciones: amplitud de potencial evocado muscular; latencia distal motora; velocidad de conducción motora en los nervios mediano, ciático popliteo externo y radial; velocidad de conducción sensiiva y amplitud del potencial evocado sensitivo de nervio en el mediano; exploración electromiográfica convencional; estudio de la transmisión neuromuscular, mediante estimulación repetitiva del nervio ciático popliteo externo a diversas frecuencias, con registro de la amplitud del potencial en músculo tibial anterior. Los datos obtenidos fueron comparados con controles. Se buscaron correlaciones entre las determinaciones bioquímicas y los diferentes hallazgos electrofisiológicos que a su vez se correlacionaron entre si y también con el tiempo de evolución de la intoxicación. Los hallazgos pusieron de manifiesto la presencia de neuropatía axonal junto a moderada desmielinización. La exploración de la transmisión neuromuscular mostró ocasional decremento o incremento de la amplitud del potencial muscular evocado, hechos que suponen cierta participación de la unión neuromuscular. Se halló correlación solamente entre disminución de ALA D y la disminución de las amplitudes del potencial sensitivo del mediano y el evocado muscular del mismo nervio y con la disminución de la VCM del nervio radial. Una débil relación se observó entre el tiempo de exposición y la disminución de las VCS del nervio mediano y VCM del radial. Las determinaciones bioquímicas y el tiempo de exposición transcurridos no probaron ser parámetros sensibles para determinar el grado de afectación del sistema nervioso periférico. El conjunto de hallazgos sugiere que el desarrollo de la neuropatía puede estar ligado a factores individuales de predisposición al daño nervioso