The regulatory role of cerebellar degeneration-related protein 1 antisense / 中国医师进修杂志

Circular RNA is a kind of single-stranded RNA ring without 5'capping and 3'polyadenylation.As a new member of non-coding RNA, circular RNA is evolutionally conserved, relatively stable,highly specific and enormously abundant.Instead of liner RNA,circular RNA became the research hotspot.So far,cerebellar degeneration-related protein 1 antisense(CDR1as)is a molecule that has garnered intense research.CDR1as harbors 74 conventional miRNA-7 binding sites.Expression of CDR1as efficiently tethers micro RNA-7, resulting in reduced micro RNA-7 activity and increased levels of micro RNA-7 targeted transcripts consistent with the micro RNA sponge and competing endogenous RNA(ceRNA)hypothesis.Moreover,CDR1as can restore micro RNA-7 and release it at right time.CDR1as can be stabilized in the exosomes.And its level has correlation with many clinical characteristics.

Estudio de las ataxias esporádicas de comienzo en el adulto en el Hospital de Clínicas de Montevideo - Uruguay / Study of sporadic ataxias of adult onset in Hospital de Clínicas de Montevideo - Uruguay / Estudo de ataxias esporádicas de aparecimento de adultos no Hospital de Clínicas de Montevidéu - Uruguai

Resumen: Introducción: El diagnóstico etiológico de las ataxias esporádicas de comienzo en el adulto (AECA) es un desafío clínico pues sus causas posibles son múltiples. No existen en el país estudios a este respecto. Objetivo: Describir las características clínicas, imagenológicas y etiológicas de los pacientes con AECA. Métodos: Estudio prospectivo observacional de los pacientes con AECA que consultaron en el Hospital de Clínicas de Montevideo desde abril de 2010 a marzo de 2014. Se realizó una evaluación clínico-paraclínica protocolizada para llegar al diagnóstico etiológico. Resultados: Se incluyeron 36 pacientes. En 20 de ellos se logró demostrar una etiología definida, siendo las más frecuentes la degeneración cerebelosa alcohólica y la paraneoplásica. La mayoría de los casos en quienes se instauró un tratamiento de dicha etiología lograron un cese de la progresión o mejoría de los síntomas. Discusión y Conclusiones: El estudio protocolizado de los pacientes con AECA logra el diagnóstico etiológico en más de 50% de los casos. Aún así un 44% de los pacientes quedan sin etiología demostrada, principalmente por la incapacidad de acceder a estudios genéticos. Los factores que más se asocian a encontrar una etiología adquirida demostrada fueron: rápida progresión, síndrome vermiano puro y franca asimetría del cuadro.

Abstract: Introduction: Etiological diagnosis of Sporadic Ataxia of Adult Onset (SAAO) is a clinical challenge because its possible causes are multiple. There are no studies of SAAO in our country. Objective: To describe the clinical, imaging and etiological characteristics of patients with SAAO. Methods: Prospective observational study of patients with SAAO who consulted at Hospital de Clínicas de Montevideo from April 2010 to March 2014. A protocolized clinical-paraclinical evaluation was performed to reach the etiological diagnosis. Results: Thirty-six patients were included. In 20 of them an acquired definite etiology was demonstrated. The most frequent were alcoholic and paraneoplastic cerebellar degeneration . The majority of cases in which a treatment of this etiology was instituted resulted in a cessation of the progression or improvement of symptoms. Discussion and Conclusions: The protocolized study of patients with SAAO achieves the etiological diagnosis in more than 50% of the cases. Still, 44% of patients remained without proven etiology, mainly due to the inability to access genetic studies. The factors that are most associated with finding a proven acquired etiology were: rapid progression, pure vermis syndrome and frank asymmetry of symptoms.

Resumo: Introdução: O diagnóstico etiológico da ataxia esporádica do início do adulto (AECA) é um desafio clínico porque suas possíveis causas são múltiplas. Não há estudos neste país. Objetivo: Descrever as características clínicas, imagiológicas e etiológicas de pacientes com AECA. Métodos: estudo prospectivo observacional de pacientes com AECA que consultou no Hospital de Clínicas de Montevidéu de abril de 2010 a março de 2014. Foi realizada uma avaliação clínico-paraclínica para alcançar o diagnóstico etiológico. Resultados: Foram incluídos trinta e seis pacientes. Em 20 deles, foi possível demonstrar uma etiologia definida, sendo a mais frequente a degeneração cerebelar alcoólica e a degeneração paraneoplásica. A maioria dos casos em que o tratamento desta etiologia foi instituído resultou na cessação da progressão ou melhora dos sintomas. Discussão e Conclusões: O estudo protocolizado de pacientes com AECA atinge o diagnóstico etiológico em mais de 50% dos casos. Ainda assim, 44% dos pacientes estão sem etiologia comprovada, principalmente devido à incapacidade de acessar estudos genéticos. Os fatores mais associados com a obtenção de uma etiologia comprovada foram: progressão rápida, síndrome do vermimus puro e assimetria franca da condição.

Alcohol: consumo, consecuencias y complicaciones neurológicas. Resultados del Proyecto Atahualpa / Alcohol: intake, consequences and neurological complications. Results from the Atahualpa Project

RESUMEN La información sobre la prevalencia y consecuencias de la ingesta de alcohol en las comunidades rurales de América Latina es escasa. Este estudio tiene como objetivo evaluar la magnitud de la ingesta de alcohol en Atahualpa, así como sus consecuencias y la prevalencia de complicaciones neurológicas. Se entrevistó a los residentes de sexo masculino mayores de 40 años (n=277) con un cuestionario estructurado diseñado para evaluar la prevalencia, los patrones de consumo y las consecuencias de la ingesta crónica de alcohol. La mayoría eran bebedores actuales y el 40% empezaron a beber por debajo de la edad legal (18 años). El consumo semanal de alcohol fue admitido por el 81% de las personas, el 58% refirió consecuencias físicas relacionadas con la ingesta de alcohol, el 59% tuvo consecuencias sociales y el 51% reconoció la ingesta de alcohol como una carga económica. Las personas que comenzaron a beber por debajo de la edad legal estuvieron más a menudo involucradas en el consumo excesivo y consumieron más alcohol que aquellos que comenzaron a tomar después de los 18 años. La relación entre ingesta de alcohol y degeneración alcohólica cerebelosa se evaluó mediante el uso de la escala BARS, con el 14,6% de individuos con degeneración alcohólica cerebelosa clínicamente relevante. Los modelos predictivos mostraron relaciones significativas entre los márgenes de puntuación de BARS y los años de consumo y la cantidad de ingesta de alcohol. Nuestro estudio también proporcionó pruebas sólidas que favorecen un efecto independiente y sinérgico de la edad y los años de consumo de alcohol en la relación entre degeneración alcohólica cerebelosa y deterioro cognitivo. Este estudio muestra una alta prevalencia de consumo crónico de alcohol en los hombres que habitan en la comunidad de Atahualpa.

ABSTRACT Information about the burden and consequences of alcohol intake in rural communities of Latin America is scarce. This study aims to assess the magnitude of alcohol intake in Atahualpa as well as its consequences and prevalence of neurological complications. Male residents aged ≥40 years (n=277) were interviewed with a structured questionnaire designed to evaluate prevalence, drinking patterns and consequences of chronic alcohol intake. Most of them were current drinkers and 40% started drinking below the legal age (18 years). Weekly binge drinking were admitted by 81% individuals, 58% referred physical consequences related to alcohol intake, 59% had social consequences, and 51% recognized alcohol intake as a major economic burden. Individuals who started drinking below the legal age were more often involved in binge drinking and consumed more alcohol than those aged ≥18 years at first regular drink. The relationship between alcohol intake and alcoholic cerebellar degeneration was evaluated by the use of the BARS scale, with 14.6% of individuals having clinically relevant alcoholic cerebellar degeneration. Predictive models showed significant relationships between BARS score margins and years of drinking and the amount of alcohol intake. Our study also provided robust evidence favoring an independent and synergistic effect of age and years of drinking in the relationship between ACD and cognitive decline. This study shows a high prevalence of chronic alcohol intake in community-dwelling men living in Atahualpa.

Intoxicação por plantas que contêm swainsonina no Brasil / Poisoning by swainsonine-containing plants in Brazil

No Brasil, as plantas que contêm swainsonina compõem um grupo muito importante de plantas tóxicas, incluindo Ipomoea carnea subsp. fistulosa, Ipomoea riedelii, Ipomoea sericophyla, Ipomoea verbascoidea, Turbina cordata e Sida carpinifolia, que causam armazenamento de oligossacarídeos em caprinos e, com menor frequência, em bovinos, equinos, ovinos e cervídeos. Uma característica das plantas que contêm swainsonina é que os animais que iniciam a ingerir essas plantas desenvolvem o hábito de ingeri-las compulsivamente e, por facilitação social, induzem a outros animais da mesma espécie a ingeri-las. Os animais intoxicados apresentam pêlos arrepiados, perda de peso e sinais nervosos associados, principalmente, a lesões cerebelares e do tronco encefálico. Infertilidade, abortos, nascimento de animais fracos e maior susceptibilidade aos parasitas gastrintestinais são descritas tanto em casos agudos quanto em animais que deixaram de ingerir a planta e permanecem com sinais, mesmo que discretos. Atrofia cerebelar pode ser observada macroscopicamente em animais cronicamente afetados. As alterações histológicas caracterizam-se por vacuolização de neurônios, células epiteliais do pâncreas e dos túbulos renais, células foliculares da tireoide, hepatócitos e macrófagos de órgãos linfóides. Para o controle da intoxicação, os animais devem ser retirados imediatamente do local onde ocorre a planta. A única medida profilática consiste em evitar a ingestão da planta, eliminando a mesma das áreas infectadas ou mediante aversão alimentar condicionada.

Swainsonine-containing plants comprise a very important group of toxic plants in Brazil, including Ipomoea carnea subsp. fistulosa, Ipomoea riedelii, Ipomoea sericophyla, Ipomoea verbascoidea, Turbina cordata and Sida carpinifolia, which cause a glycoprotein storage disease in goats, and with less frequency in cattle, horses, sheep, and deer. A characteristic of swainsonine poisoning is that the animals that eat these plants develop the habit of eating them compulsively and, by social facilitation, induce other animals of the same species to eat them. Clinical signs of the poisoning are rough hair coat, weight loss, and nervous signs associated mainly with cerebellar and brain stem lesions. Weight losses or decreased weight gains still occurring also in animals with chronic clinical signs removed from the areas where the plants occur. Reproductive losses are also reported. Chronically affected animals, also without still ingesting the plant, are more susceptible to gastrointestinal parasites. Cerebellar atrophy has been observed grossly in chronic cases. Main histologic lesions are vacuolation of neurons, epithelial cells of the pancreas and kidney, thyroid follicular cells, hepatocytes, and macrophages of lymphoid organs. To control the poisoning animals must be removed immediately from the areas invaded by the plant. The only preventive measure to prevent the ingestion of the plant is their elimination from invaded areas or through conditioned food aversion.

Cerebellar Degeneration Associated with Sjogren's Syndrome

BACKGROUND: Neurologic manifestations of primary Sjogren's syndrome (PSS) have been reported to vary from sensory polyneuropathy to encephalopathy or psychiatric problems. However, marked cerebellar degeneration associated with PSS has rarely been reported. CASE REPORT: We describe a patient with Sjogren's syndrome who exhibited rapidly progressive cerebellar ataxia, nystagmus, cognitive decline, and psychiatric problems. Brain magnetic resonance imaging revealed marked atrophy of the cerebellum, and 18F-fluorodeoxyglucose positron-emission tomography demonstrated glucose hypometabolism of the cerebellum. CONCLUSIONS: Our PSS patient exhibited a progressive course of cerebellar syndrome, as evidenced by cerebellar atrophy on serial brain images.

Intoxicação por Solanum paniculatum (Solanaceae) em bovinos / Poisoning by Solanum paniculatum (Solanaceae) in cattle

Surtos de uma doença neurológica com sinais cerebelares ocorreram em três fazendas da região Agreste do Estado de Pernambuco. A morbidade foi de 3 a 25%, a mortalidade variou de 0 a 20% e a letalidade foi de 0 a 60%. Uma planta que predominava nos pastos das fazendas foi identificada como Solanum paniculatum. Os sinais clínicos apresentados foram de crises periódicas caracterizadas por incoordenação, extensão da cabeça e pescoço, ataxia, hipermetria, tremores de intenção, nistagmo e quedas. As crises eram induzidas pelo teste de levantar a cabeça ou quando os animais eram assustados ou quando aplicado o teste de levantar a cabeça. Alguns animais apresentaram sinais permanentes com alterações posturais, tremores de intenção, andar cambaleante com os membros em abdução e perda progressiva de peso. De dois bovinos que foram necropsiados, um apresentava diminuição de tamanho do cerebelo com marcada atrofia da substância cinzenta. Histologicamente, um dos bovinos apresentou vacuolização fina do pericário das células de Purkinje do cerebelo com marginalização do núcleo. Em algumas áreas havia perda de neurônios de Purkinje com proliferação de astrócitos de Bergmann. Degeneração do tipo Walleriana, com esferoides axonais e vacúolos, alguns contendo macrófagos, foi observada na camada granular do cerebelo, substância branca cerebelar e medula cerebelar. Neurônios vacuolizados e esferóides axonais foram observados também no núcleo gracilis. Em outro bovino com sinais permanentes, que permaneceu por aproximadamente 10 meses sem ter acesso a S. paniculatum, observou-se ausência quase total de células de Purkinje. Havia severa depleção das camadas granular e molecular que se encontravam marcadamente diminuídas de espessura e com rarefação do neurópilo e menor número de células. Considerando que se desconhece o princípio ativo de S. paniculatum e que a planta é largamente utilizada como planta medicinal é necessário alertar para os riscos de intoxicação em humanos.

Outbreaks of a disease of the nervous system are reported in cattle in three farms in the Agreste region of the state of Pernambuco. Morbidity, mortality and fatality rates varied from 3 to 25%, 0 to 20% and 0 to 60%, respectively. A weed found in large amounts in the pastures was identified as Solanum paniculatum. Clinical signs were characterized by transitory, periodic attacks with loss of balance, incoordinated gait, neck and head extension, hypermetria, intention tremors, nystagmus, and falls. The attacks were induced when the animals were disturbed or by the application of the head raising test. Two cows showed permanent signs including ataxia, abnormal posture, staggering gait with limbs in abduction, intention tremors, hypermetria, and progressive weight loss. Histological lesions in one cow were fine vacuolation of the cerebellar Purkinje neurons with marginalization of the nucleus. Loss of Purkinje neurons with proliferation of Bergmann astrocytes and Wallerian degeneration with axonal spheroids in the granular layer and cerebellar white matter were also observed. Neuronal vacuolation and axonal spheroids were observed in the gracillis nucleus. In one cow that stayed for approximately 10 months in an area free of S. paniculatum with permanent signs, there was a severe depletion of Purkinje neurons in the cerebellum. The granular and molecular layers were reduced and depleted of cells. Considering that the toxic compound of S. paniculatum is unknown, and that the plant is largely used as a medical plant, it is necessary to take into account the risk of human poisoning.

Anti-Yo-associated paraneoplastic cerebellar degeneration in a patient with chemotherapy-responsive ovarian cancer: A case report with a review of literatures / 대한산부인과학회지

Paraneoplastic cerebellar degeneration (PCD), the one of rare paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by cancer or its metastasis. PCD is a condition whereby the Purkinje cells of the cerebellar cortex are damaged secondary to an autoimmune process. We report here on the case of PCD of subacute onset in a patient at 7 months after surgery for ovarian cancer. Although the cases of PCD has rarely been reported, the present case appears to be the first in Korea in which PCD was associated with anti-Yo antibody in patient with chemotherapy-responsive ovarian cancer. The clinical significance of PCD associated with anti-Yo antibody is reviewed.

Inhibitory effect of α-tocopherol on methylmercury-induced oxidative steress

<p><b>OBJECTIVES</b>The present study investigated the involvement of oxidative stress in the degeneration of the cerebellum during methylmercury (MeHg) intoxication and the protective effect of α-tocopherol (Vit E) against MeHg toxicity.</p><p><b>METHODS</b>After 5 mg/kg of MeHg was administered to Wistar rats for 12 consecutive days, the cerebellum were examined histopathologically. In addition, the same amount of MeHg was administered to 3 different groups of Wistar rats: rats with a Vit E-deficient diet, rats fed 150 mg/kg of Vit E for 20 consecutive days after initial MeHg administration, and rats with an ordinary diet.</p><p><b>RESULTS</b>Positive immunoreactivity against anti-hydroxynonenal (HNE), a marker of lipid peroxidation, was observed in the cerebellum after MeHg administration. Levels of thiobarbituric acid reactive substance (TBARS), another marker of lipid peroxidation, and those of protein carbonyl, a biomarker for protein oxidation, increased after MeHg administration. In the rats with MeHg and a Vit E-deficient diet, mortality and prevalence of piloerection significantly increased, and in the rats with MeHg and Vit E, mortality, piloerection, retracted and crossed hind leg, and ataxic gait significantly decreased, compared with the rats with MeHg alone. The levels of NO(2) (-) and NO(3) (-) in the serum significantly increased in the rats with MeHg alone 14 days after the initial MeHg administration, but were significantly suppressed by Vit E administration.</p><p><b>CONCLUSIONS</b>Oxidative stress, especially lipid peroxidation, may play an important role in the cerebellar degeneration process during MeHg intoxication and Vit E may play a protective role against MeHg toxicity as an effective antioxidant.</p>

Inhibitory Effect of $\alpha$-Tocopherol on Methylmercury-Induced Oxidative Steress

Objectives: The present study investigated the involvement of oxidative stress in the degeneration of the cerebellum during methylmercury (MeHg) intoxication and the protective effect of α-tocopherol (Vit E) against MeHg toxicity. Methods: After 5 mg/kg of MeHg was administered to Wistar rats for 12 consecutive days, the cerebellum were examined histopathologically. In addition, the same amount of MeHg was administered to 3 different groups of Wistar rats: rats with a Vit E-deficient diet, rats fed 150 mg/kg of Vit E for 20 consecutive days after initial MeHg administration, and rats with an ordinary diet. Results: Positive immunoreactivity against anti-hydroxynonenal (HNE), a marker of lipid peroxidation, was observed in the cerebellum after MeHg administration. Levels of thiobarbituric acid reactive substance (TBARS), another marker of lipid peroxidation, and those of protein carbonyl, a biomarker for protein oxidation, increased after MeHg administration. In the rats with MeHg and a Vit E-deficient diet, mortality and prevalence of piloerection significantly increased, and in the rats with MeHg and Vit E, mortality, piloerection, retracted and crossed hind leg, and ataxic gait significantly decreased, compared with the rats with MeHg alone. The levels of NO2− and NO3− in the serum significantly increased in the rats with MeHg alone 14 days after the initial MeHg administration, but were significantly suppressed by Vit E administration. Conclusions: Oxidative stress, especially lipid peroxidation, may play an important role in the cerebellar degeneration process during MeHg intoxication and Vit E may play a protective role against MeHg toxicity as an effective antioxidant.

Comparison of BAEPs in three different kinds of brainstem disorders / 中华物理医学与康复杂志

Objective To compare the brainstem auditory evoked potential (BAEP) in patients with different kinds of brainstem disorders, so as to offer a significative electrophysiological means for diagnosis and differential diagnosis of different kinds of brainstem disorders. Methods BAEP was recorded from 80 cases of vertebrobasilar arterial insufficiency, 56 cases of acoustic neuroma and 47 cases of chronic cerebellar degeneration and compared with that from 50 healthy people. Results The abnormal rates of the three different case groups were 73.75%, 94.61%, 89.36%, respectively. Each group of patients demonstrated their own characteristics with regard to the BAEP. Conclusion Each of the three brainstem disorders has its own characteristics with BAEP.