Esclerose lateral amiotrófica: novas possibilidades terapêuticas em um arcabouço fisiopatológico ainda em construção / Amyotrophic lateral sclerosis: new therapeutic possibilities in a pathophysiological framework still under construction

Introdução: A Esclerose Lateral Amiotrófica (ELA) é definida como uma doença neurológica progressiva e inexorável, com cerca de 80% dos casos de etiologia desconhecida. Novos medicamentos têm emergido no tratamento de doenças neurodegenerativas, inclusive na ELA, redesenhando o modelo fisiopatológico. Dentre eles, destacam-se o uso da: Edaravone, Vitamina K2, Serina, Metilcobalamina, Pirroloquinolina quinona (PQQ), Ubiquinol e Glutationa. Especificamente na ELA, alguns já foram validados em estudos randomizados-controlados. Metodologia: Atualização da literatura (PUBMED, Medline) sobre a utilização desses fármacos em doenças neurológicas degenerativas, com enfoque para a Doença do Neurônio Motor (DNM-ELA), nos idiomas Português, Inglês, Espanhol e Francês, compreendidos entre os anos de (2010-2017). Discussão: A associação desses medicamentos tem mostrado resultados positivos em inúmeras doenças neurológicas. Alguns, como, por exemplo, a Metilcobalamina e o Edaravone,exerceriam mecanismos de ação capazes de interferir no processo de depleção dos neurônios motores da ponta anterior e do feixe piramidal em pacientes com ELA. Conclusão: Seria precipitado concluir que o uso associado desses fármacos poderia modificar ou mesmo restaurar os danos às unidades motoras; entretanto, faz-se necessário destacar seus mecanismos de ação e potencial capacidade de intervir na evolução da doença, principalmente, a partir de estudos em modelos fisiopatológico que culminam na degeneração dos neurônios motores.(AU)

Introduction: Amyotrophic Lateral Sclerosis (ALS) is defined as a progressive and inexorable neurological disease, with about 80% of cases of unknown etiology. New drugs have emerged in the treatment of neurodegenerative diseases, including ALS, redesigning the pathophysiological model. Among them, the use of: Edaravone, Vitamin K2, Serine, Methylcobalamin, Pyrroloquinoline quinone (PQQ), Ubiquinol and Glutathione are noteworthy. Specifically in ALS, some have been validated in randomized controlled trials. Methodology: Update of the literature (PUBMED, Medline) on the use of these drugs in degenerative neurological diseases, with a focus on Motor Neuron Disease (DNM-ELA) in the Portuguese, English, Spanish and French languages, of (2010-2017). Discussion: The association of these drugs has shown positive results in neurological diseases. Some, such as Methylcobalamin and Edaravone, would exert mechanisms of action capable of interfering in the process of depletion of the motor neurons of the anterior horn and pyramidal tracts in patients with ALS. Conclusion: It would be precipitate to conclude that the associated use of these drugs could modify or even restore damage to motor units; however, it is necessary to highlight its mechanisms of action and potential ability to intervene in the evolution of the disease, mainly from studies in pathophysiological models that culminate in the degeneration of motor neurons (AU)

Síndrome de Guillain-Barré: relato de caso da neuropatia sensitivo-motora axonal aguda em criança / Guillain-Barré syndrome: case report of a child with acute axonal sensorimotor neuropathy

A forma sensitivo-motora axonal aguda da Síndrome de Guillain-Barré (SBG) é uma apresentação rara, a qual pode apresentar um comprometimento neurológico mais grave. O diagnóstico desta morbidade é realizado através da avaliação clínica associada à eletroneuromiografia. Neste artigo, reportamos o caso de um paciente de 13 anos, submetido a medidas de suporte isoladamente, com evolução neurológica favorável. Em crianças e adolescentes, a melhor abordagem terapêutica para esta condição ainda carece de evidência científica (AU)

The acute axonal sensorimotor form of Guillain-Barre Syndrome (GBS) is a rare presentation which may have a more severe neurological impairment. The diagnosis of this condition is made by clinical evaluation associated with electroneuromyography. In this paper we report the case of a 13-year-old patient who underwent supportive measures alone, with a favorable neurological outcome. In children and adolescents, the best therapeutic approach for this condition still lacks scientific evidence (AU)

Esclerosis lateral amiotrófica: ¿es el astrocito la célula primariamente dañada? / [Amyotrophic lateral sclerosis: is the astrocyte the cell primarily involved?].

So far, amyotrophic lateral sclerosis (ALS) is thought as due to a primary insult of the motor neurons. None of its pathogenic processes proved to be the cause of the illness, nor can be blamed environmental agents. Motor neurons die by apoptosis, leaving the possibility that their death might be due to an unfriendly environment, unable to sustain their health, rather than being directly targeted themselves. These reasons justify an examination of the astrocytes, because they have the most important role controlling the neurons’ environment. It is known that astrocytes are plastic, enslaving their functions to the requirements of the neurons to which they are related. Each population of astrocytes is unique, and if it were affected the consequences would reach the neurons that it normally sustains. In regard to the motor neurons, this situation would lead to a disturbed production and release of astrocytic neurotransmitters and transporters, impairing nutritional and trophic support as well. For explaining the spreading of muscle symptoms in ALS, correlated with the type of spreading observed at the cortical and spinal motor neurons pools, the present hypotheses suggests that the illness-causing process is spreading among astrocytes, through their gap junctions, depriving the motor neurons of their support. Also it is postulated that a normal astrocytic protein becomes misfolded and infectious, inducing the misfolding of its wild type, travelling from one protoplasmatic astrocyte to another and to the fibrous astrocytes encircling the pyramidal pathway which joints the upper and lower motoneurones.

Is magnetic resonance imaging a plausible biomarker for upper motor neuron degeneration in amyotrophic lateral sclerosis/primary lateral sclerosis or merely a useful paraclinical tool to exclude mimic syndromes? A critical review of imaging applicability in clinical routine / A ressonância magnética é um biomarcador aceitável da degeneração do neurônio motor superior em esclerose lateral amiotrófica/esclerose lateral primária ou apenas um instrumento paraclínico útil para a exclusão das síndromes mimetizadoras? Uma revisão crítica da aplicabilidade da imagem na rotina clínica

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons in the cerebral cortex, brainstem, and spinal cord, brain regions in which conventional magnetic resonance imaging is often uninformative. Although the mean time from symptom onset to diagnosis is estimated to be about one year, the current criteria only prescribe magnetic resonance imaging to exclude "ALS mimic syndromes". Extensive application of non-conventional magnetic resonance imaging (MRI) to the study of ALS has improved our understanding of the in vivo pathological mechanisms involved in the disease. These modern imaging techniques have recently been added to the list of potential ALS biomarkers to aid in both diagnosis and monitoring of disease progression. This article provides a comprehensive review of the clinical applicability of the neuroimaging progress that has been made over the past two decades towards establishing suitable diagnostic tools for upper motor neuron (UMN) degeneration in ALS.

A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa fatal que afeta os neurônios motores em regiões nas quais a ressonância magnética (RM) é frequentemente pouco informativa. Embora o tempo médio desde a manifestação inicial até o diagnóstico esteja em torno de um ano, os critérios atuais apenas recomendam o emprego da RM para excluir as "síndromes mimetizadoras da ELA". A maior aplicação da RM não convencional tem melhorado nossa compreensão sobre os mecanismos patológicos in vivo envolvidos na ELA. Estas modernas técnicas de imagem foram adicionadas à lista de potenciais biomarcadores da ELA, contribuindo para o diagnóstico e para a monitorização da progressão da doença. Esta é uma revisão detalhada da aplicabilidade clínica dos recentes avanços da neuroimagem, que visa apontar as ferramentas mais apropriadas para o diagnóstico da degeneração do neurônio motor superior (NMS).

Obesity Affects Median Nerve Conduction - A Study in Armed Forces Individuals.

Background: Obesity, a growing public health concern, is associated with various disorders. Studies have suggested obesity as an independent risk factor that influences the prevalence of carpal tunnel syndrome (CTS) among active workers. The present study is an attempt to establish relationship between median nerve conduction velocity and obesity in people who do not have any other contributory factor for CTS other than obesity. CTS is the commonest entrapment neuropathy where the median nerve is compressed. Methods: The study was conducted in 15 obese subjects with Body Mass Index (BMI)>30 (group III) and 15 overweight subjects with BMI between 25&29.9 (group II) and 15 control subjects with BMI <25 (group I). The subjects were personnel from armed forces. Their body density was estimated using hydro-densitometry and the body fat percentage was calculated from density. The distal motor latency (DML) and the sensory conduction velocity (SCV) across the wrist on stimulation of median nerve at wrist 3cm proximal to distal crease were assessed in all subjects. Results: The mean values of DML in group I, II, and III were 3.52±0.25 ms, 3.50±0.30 ms and 3.65±0.20 ms respectively. Mean value of SCV among these groups were 48.99±3.23 m/s, 49.32±3.35 m/s and 48.69±4.00 m/s. Conclusion: No relationship could be established between BMI and DML as well as BMI and SCV. The relationship between percentage body fat and DML and SCV also found to be statistically insignificant. However, there was a correlation between BMI and body fat percentage. Carpal tunnel syndrome is uncommon even in obese armed forces personnel, which might be due to their regular body and hand exercise thereby having increased tone in hand muscles.

Motor Unit Number Estimation in Evaluating Disease Progression in Patients with Amyotrophic Lateral Sclerosis

We investigated the availability of motor unit number estimation (MUNE) as a quantitative method to assess the severity and clinical progression of amyotrophic lateral sclerosis (ALS). The 143 ALS patients were evaluated by statistical MUNE and the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). By using mean values of MUNE according to disease duration, regression equation between mean MUNE and disease duration was presented as a formula. The individual MUNE ratio was calculated by dividing individual MUNE value by mean MUNE value. All patients were classified into 2 groups (MUNE ratio or =1) according to the MUNE ratio. Comparison between the 2 groups revealed that the patients in MUNE ratio or =1 group were respectively assigned to rapid progression or slow progression. We recommended informative mean values of MUNE and best regression equation in ALS patients according to disease duration. These values allow us to evaluate the severity and rapidity of progression in ALS.

Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report

The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an unusual but important complication of hematopoietic stem cell transplantation (HSCT) rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinating polyradiculoneuropathy; muscle and nerve biopsy were compatible with CIDP.

A polirradiculoneuropatia desmielinizante inflamatória crônica (CIDP) é uma incomum, porém, importante complicação do transplante de células hematopoiéticas (HSCT) raramente relatada até a data. Nós descrevemos uma mulher de 17 anos com diagnóstico de leucemia mielóide aguda por anemia de Fanconi que foi submetida à HSCT e desenvolveu CIDP como parte da doença do enxerto contra o hospedeiro. A investigação mostrou elevação na proteína no líquor; estudo eletrofisiológico revelando polirradiculoneuropatia desmielinizante sensitivo-motora; e biópsia de músculo e nervo compatível com CIDP.

Early nerve damage in leprosy: an electrophysiological study of ulnar and median nerves in patients with and without clinical neural deficits.

BACKGROUND: Peripheral nerve trunk involvement in leprosy is very common. However, by the time it becomes clinically manifest, the damage is quite advanced. If the preclinical nerve damage can be detected early, the deformities and disabilities can be prevented to a large extent. AIMS: To assess the electrophysiological functions of the ulnar and median nerve trunks in cases of clinically manifest leprosy with and without manifest nerve damage at different durations of nerve damage. MATERIALS AND METHODS: Electrophysiological functions of ulnar and median nerves were studied in leprosy patients, both normal and at different stages of disease and damage. PB cases, having disease for six months or less, without neurological symptoms and clinically normal appearing nerve. STATISTICAL METHODS: Mean was taken of different values. The changes in values of different parameters were expressed as percentage change with reference to the control values (increase or decrease). RESULTS: Reduced nerve conduction velocities and changes in latency and amplitude were observed. Changes in sensory nerve conduction were more pronounced. Sensory latencies and amplitude changes were more severe than motor latencies and amplitudes in cases with manifest muscle palsies. Changes in MB cases were less marked. CONCLUSIONS: Further studies are needed to identify parameters likely to be helpful in the diagnosis of early nerve damage.

Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown etiology, affects motor neurons leading to atrophy of skeletal muscles, paralysis and death. There is evidence for the accumulation of neurofilaments (NF) in motor neurons of the spinal cord in ALS cases. NF are major structural elements of the neuronal cytoskeleton. They play an important role in cell architecture and differentiation and in the determination and maintenance of fiber caliber. They are composed of three different polypeptides: light (NF-L), medium (NF-M) and heavy (NF-H) subunits. In the present study, we performed a morphological and quantitative immunohistochemical analysis to evaluate the accumulation of NF and the presence of each subunit in control and ALS cases. Spinal cords from patients without neurological disease and from ALS patients were obtained at autopsy. In all ALS cases there was a marked loss of motor neurons, besides atrophic neurons and preserved neurons with cytoplasmic inclusions, and extensive gliosis. In control cases, the immunoreaction in the cytoplasm of neurons was weak for phosphorylated NF-H, strong for NF-M and weak for NF-L. In ALS cases, anterior horn neurons showed intense immunoreactivity in focal regions of neuronal perikarya for all subunits, although the difference in the integrated optical density was statistically significant only for NF-H. Furthermore, we also observed dilated axons (spheroids), which were immunopositive for NF-H but negative for NF-M and NF-L. In conclusion, we present qualitative and quantitative evidence of NF-H subunit accumulation in neuronal perikarya and spheroids, which suggests a possible role of this subunit in the pathogenesis of ALS.

Progressive bulbur paralysis (Fazio-Londe disease).

Progressive bulbar paralysis of childhood is characterised by progressive paralysis of muscles innervated by cranial nerves. The authors report a case of progressive bulbar paralysis of childhood in a 12-year-old child. Child was admitted with the complaints of drooping of eyelids, difficulty in swallowing and hoarse voice. She had involvement of III, VII, IX, X, XI and XII cranial nerves and the corticospinal tracts. Electromyography revealed spontaneous activity in the form of fasciculations, giant motor unit potential and discrete recruitment of motor neurons suggestive of denervation pattern. Hearing assessment was normal. Muscle biopsy was also suggestive of neurogenic atrophy.

Protective effect of interleukin-1beta on motor neurons after sciatic nerve injury in rats / 华中科技大学学报（医学）（英德文版）

Protective effect of interleukin-1beta (IL-1beta) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 microl 1 ng/ml IL-1beta and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal alpha motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too (P < 0.01). These results suggest that exogenous IL-1beta protects alpha-motor neurons from degeneration and necrosis after peripheral nerve injury.

Sindrome das cinturas dos membros / Limb Girdle Syndrome

Enfatizando que a sindrome da cintura dos membros pode se apresentar em varias afeccoes miopaticas ou do sistema nervoso periferico, os AA relatam como fazer o diagnostico diferencial dessas afeccoes, com auxilio da anamnese, do exame neurologico, da eletroneuromiografia, da biopsia muscular inclusive com histoquimica, com exames bioquimicos do sangue (enzimas musculares, prova de atividade inflamatoria, dosagens hormonais, lactacidemia e Kalemia) da imunohistoquimica e finalmente dos exames genetico atraves da biologia molecular e ou da pesquisa de produtos genicos como a distrofina

Neuropatia motora mutifocal / Multifocal motor neuropathy

A Neuropatia Motora Multifocal apresenta um quadro clínico superponível ao das doenças do neurônio motor, mas uma avaliaçäo eletroneuromiográfica cuidadosa revela indícios de desmielinizaçäo focal das fibras motoras, permitindo a individualizaçäo desta afecçäo e autorizando terapia imunossupresora

Envelhecimento e o aumento das doenças abiotróficas: epidemiologia das doenças (crônicas) das células do corno anterior da medula / Agind and the increasing of abistrophic diseases: epidemiology of the anterior born diseases

É considerada a hipótese da degeneraçäo prematura de células/tecidos geneticamente determinada com precipitaçäo ou näo por um outro agente como a etiologia de algumas doenças neurológicas. Entre estas doenças, estuda-se a esclerose lateral amiotrófica, protótipo das doenças do corno anterior da medula e das doenças do neurônio motor. Essa hipótese é correlacionada à literatura revisada e aos dados epidemiológicos de mortalidade apresentados, baseados e m declaraçöes de óbito, nos anos de 1979 a 1986, na cidade do Rio de Janeiro, e em 1986, também em Porto Alegre, Recife, Belém e Goiânia. No Rio, os resultados säo similares aos da literatura; predomínio de óbitos acima dos 5a anos (77%), e em homens (1,7 x 1), embora com coeficientes dos menores do mundo (0,4/100.00). Nas outras cidades estudadas, os coeficientes säo ainda menores do que os do Rio, mas, com a melhor definiçäo dos casos e crescimento da populaçäo idosa, supöe-se que ocorrerá maior notificaçäo dessas doenças

Histopathologic study on muscle diseases among Koreans (274 muscle biopsy analysis)

All the diagnostic muscle biopsy cases were collected from the file of Department of Pathology, Seoul National University Hospital during June 1976 to December 1978. Slides were reviewed and correlated with clinical informations. Two hundred seventy four cases showed pathological changes, which were classified into six large groups (Table 1). Neurogenic atrophy was most common, 97 cases (35%), including 71 cases of motor neuron disease and 22 cases of peripheral neuropathy. Muscular dystrophy was seen in 92 cases (34%), and Duchenne type was the commonest among them (51 cases). Fifty seven cases showed inflammatory myopathy, making 20% of all cases. There were four cases of congenital myopathy and 13 cases showed various muscle diseases.

El virus HTLV-I como posible causa de la paraparesia espastica del pacifico / The HTLV-I virus as possible cause of spastic paraparesia in the pacific

Se describe un foco de prevalencia elevada de paraparesia espastica tropical en la porcion sur de la costa del Pacifico de Colombia. Como todos los pacientes vivian en las llanuras costeras, este sindrome se denomino paraparesia espastica del Pacifico. Los sintomas y signos son los de un sindrome de neurona motora superior, propio solo de adultos de ambos sexos. La prevalencia del sindorme (98/100.000) en Tumaco, pequeno puerto colombiano, excede la prevalencia actual de la enfermedad de neurona motora en Guam y en la Peninsula Kii. Se dan los criterios diagnosticos minimos. De casi 100 casos que se encontraron, se incluyeron 77 en este trabajo y de ellos 20, con el cuadro clasico, se llevaron desde la costa del Pacifico al Hospital Universitario del Valle en Cali, donde se les hicieron estudios completos neurologicos y de laboratorio. Los hallaza positivos fueron: parasitismo multiple (85%), eosinofilia (50%), megaloblastosis (40%), serologia positiva para VDRL (75%), y la misma cifra de positividad para FTA-abs en el liquido cefalorraquideo. Las pruebas virologicas para HTLV-I mostraron tasas altas de anticuerpos en 100% de los sueros y en 72.7% de los LCR. Todos los sueros y LCR de controles fueron negativos para HTLV-I y HTLV-III. Estos resultados sugieren un proceso infeccioso como la causa de la paraparesia espastica tropical. La transmision sexual podria explicar el hecho que la enfermedad ataca solo a los adultos