SGK1 as a therapeutic target for central nervous system diseases / 生理学报

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.

Bacopa monnieri: historical aspects to promising pharmacological actions for the treatment on central nervous system diseases / Bacopa monnieri: aspectos históricos de las acciones farmacológicas prometedoras para el tratamiento de enfermedades del sistema nervioso central

Bacopa monnieri(L.) Wettst. (Plantaginaceae), also known as Brahmi, has been used to improve cognitive processes and intellectual functions that are related to the preservation of memory. The objective of this research is to review the ethnobotanical applications, phytochemical composition, toxicity and activity of B. monnieri in the central nervous system. It reviewed articles on B. monnieri using Google Scholar, SciELO, Science Direct, Lilacs, Medline, and PubMed. Saponins are the main compounds in extracts of B. monnieri. Pharmacological studies showed that B. monnieri improves learning and memory and presents biological effects against Alzheimer's disease, Parkinson's disease, epilepsy, and schizophrenia. No preclinical acute toxicity was reported. However, gastrointestinal side effects were reported in some healthy elderly individuals. Most studies with B. monnieri have been preclinical evaluations of cellular mechanisms in the central nervous system and further translational clinical research needs to be performed to evaluate the safety and efficacy of the plant.

Bacopa monnieri (L.) Wettst. (Plantaginaceae), también conocida como Brahmi, se ha utilizado para mejorar los procesos cognitivos y las funciones intelectuales que están relacionadas con la preservación de la memoria. El objetivo de esta investigación es revisar las aplicaciones etnobotánicas, composición fitoquímica, toxicidad y actividad de B. monnieri en el sistema nervioso central. Se revisaron artículos sobre B. monnieri utilizando Google Scholar, SciELO, Science Direct, Lilacs, Medline y PubMed. Las saponinas son los principales compuestos de los extractos de B. monnieri. Los estudios farmacológicos mostraron que B. monnieri mejora el aprendizaje y la memoria y presenta efectos biológicos contra la enfermedad de Alzheimer, la enfermedad de Parkinson, la epilepsia y la esquizofrenia. No se informó toxicidad aguda preclínica. Sin embargo, se informaron efectos secundarios gastrointestinales en algunos ancianos sanos. La mayoría de los estudios con B. monnieri han sido evaluaciones preclínicas de los mecanismos celulares en el sistema nervioso central y es necesario realizar más investigaciones clínicas traslacionales para evaluar la seguridad y eficacia de la planta.

Neurosarcoidosis: guidance for the general neurologist / Neurosarcoidose: orientações para o neurologista geral

Neurosarcoidosis (NS) more commonly occurs in the setting of systemic disease. The diagnosis is based on a clinical history suggestive of NS, presence of noncaseating granulomas, and supportive evidence of sarcoid pathology, laboratory, and imaging studies. NS could involve any part of the nervous system and often demands high doses of steroids for symptom control. It presents low response to isolated steroids administration and frequently requires immunosuppressive agents. In NS, lymphocytes are polarized toward an excessive Th1 response, leading to overproduction of TNF-alpha and INF-gama, as well as lL-2 and IL-15. Infliximab, a chimeric monoclonal antibody that neutralizes the biological activity of TNF-alpha, is a new option in the NS treatment. We revised pathophysiology, clinical manifestations, diagnostic work up, and treatment of NS as guidance for the general neurologist.

A neurosarcoidose (NS) ocorre frequentemente no contexto de doença sistêmica. O diagnóstico é baseado na história clínica sugestiva de NS, presença de granulomas não-caseosos e achados anatomopatológicos, laboratoriais e radiológicos de sarcoidose. A NS causa manifestações neurológicas variadas, que apresentam, em geral, baixa resposta ao corticoide isoladamente e, portanto, necessitam uso de imunossupressores. Na NS, os linfócitos estão polarizados para resposta Th1 excessiva, levando à produção aumentada de TNF-alfa e IFN-gama, assim como IL-2 e IL-15. Infliximabe, um anticorpo monoclonal quimérico que neutraliza a atividade biológica do TNF-alfa, é uma nova opção no tratamento da NS. Revisou-se a fisiopatologia, as manifestações clínicas, o diagnóstico e o tratamento da NS para orientar neurologistas gerais.

Isolated Spinal Cord Neurosarcoidosis Diagnosed by Cord Biopsy and Thalidomide Trial

We report a case of 54-yr-old woman who presented with 4-extremities weakness and sensory changes, followed by cervical spinal cord lesion in magnetic resonance imaging. Based on the suspicion of spinal tumor, spinal cord biopsy was performed, and the histology revealed multinucleated giant cells, lymphocytes and aggregated histiocytes within granulomatous inflammation, consistent with non-caseating granuloma seen in sarcoidosis. The patient was treated with corticosteroid, immunosuppressant and thalidomide for years. Our case indicates that diagnosis of spinal cord sarcoidosis is challenging and may require histological examination, and high-dose corticosteroid and immunosuppressant will be a good choice in the treatment of spinal cord sarcoidosis, and the thalidomide has to be debated in the spinal cord sarcoidosis.

Tumores del sistema nervioso central en el primer año de vida / Tumors of the central nervous system in the first year of life

Se efectuó un estudio descriptivo, longitudinal y retrospectivo de los 8 pacientes con tumores del sistema nervioso central en el primer año de vida, diagnosticados en el Hospital Infantil Sur de Santiago de Cuba desde 1987 hasta 2008, de los cuales 5 (62,5 por ciento) habían fallecido cuando se elaboró el presente artículo. Los tratamientos indicados en este caso son la resección de la masa tumoral, lo más radical que permitan su tamaño y localización, así como la quimioterapia según el tipo hístico.

A descriptive, longitudinal and retrospective study of 8 patients with tumors of the central nervous system in the first year of life was carried out. They were diagnosed in the Southern Children Hospital of Santiago de Cuba from 1987 to 2008, 5 of them (62,5 per cent) had died when the present article was made. The treatments indicated in this case are the resection of the tumor mass, the most radical surgery depending on its size and localization, as well as the chemotherapy according to the tissular type.

Recurrent neuromyelitis optica with diffuse central nervous system involvement: case report

Diversas doenças desmielinizantes podem ocorrer em crianças, sendo muitas vezes o diagnóstico diferencial entre elas difícil. Critérios diagnósticos têm sido propostos para algumas destas entidades, entretanto nenhum deles pode ser considerado definitivo. O objetivo deste trabalho é apresentar o caso de um paciente de 10 anos de idade, com quadro recorrente de neurite óptica bilateral e mielopatia. Os dados clínicos e liquóricos preencheram critérios para o diagnóstico de neuromielite óptica de Devic. O diagnóstico diferencial foi especialmente difícil em relação à esclerose múltipla, pois não apenas os nervos ópticos e medula foram acometidos, visto que em um dos surtos registrou-se hemiparesia, com acometimento facial. A ressonância magnética foi também compatível com esclerose múltipla. Este caso ilustra que pacientes com doenças desmielinizantes do SNC podem preencher critérios diagnósticos para mais de uma delas, o que torna o julgamento clínico uma ferramenta ainda importante na abordagem e condução clínica destes casos.

Efecto terapéutico de las estatinas en patología degenerativa del SNC: comentario sobre una publicación experimental reciente / Therapeutic use of Statins in degenerative pathology of the CNS: a commentary of a recent experimental paper

Statins (HMG-CoA reductase inhibitors) are widely used for the treatment of hypercholesterolemia. Statins reduce the risk of coronary pathology; they are well tolerated and have few adverse effects. During the last years mounting evidence suggest that statins could be also useful for several autoimmune and neurodegenerative diseases. Proposed mechanisms include effects on plasma lipoproteins, endothelial function, atheroma reduction, thrombosis and inflammation. The realization that brain ischemia produces inflammation of the brain opens a new field for discovery of novel therapeutic agents for stroke. Here, I comment on a paper from Chen et al. ("Statins induce angiogenesis, neurogenesis, and synaptogenesis after stroke", Ann Neurol 2003; 53: 743-751) that proposed that atorvastatin and simvastatin reduced tissue damage and enhanced functional outcome when administered to rats 1 day after experimental stroke. Animals treated with statins showed increases in vascular endothelial growth factor, cyclic guanosine monophosphate, angiogenesis, cell proliferation and neurogenesis, and increase in synaptophysin. Although the authors concluded that atorvastatin induced brain plasticity and had neurorestorative activity, I think that significant additional experiments are required in order to sustain some of the mechanisms proposed by them. However, evidence on the effect of statins on experimental autoimmune encephalomyelitis and other inflammatory disease is also discussed here, because they cast light on alternative mechanisms that could be responsible for the better outcome of stroke animals treated with statins. Inflammation is attractive in therapeutic terms, considering its rapid initiation, its progression for several hours after stroke and its enormous contribution to brain damage.

Symptomatic muscle involvement in neurosarcoidosis: a clinicopathological study of 5 cases

We report on the clinical course and histopathologic muscle alterations of five patients diagnosed with neurosarcoidosis, who underwent biopsy due to their muscle manifestations. The five patients were females and only one was less than 40 years of age. Proximal muscle weakness was presented by all and only two patients complained of myalgia. Only normal values of serum muscle enzymes were detected. Electromyography revealed diverse findings such as normal, myopathic and neuropathic patterns. Granuloma was not present in one muscle biopsy. Two patients thoroughly recovered by taking only prednisone and one patient required a methotrexate addition for 3 months before becoming asymptomatic. The other two patients received azathioprine, one due to steroid side effects but without a satisfactory evolution, and the other to strengthen the prednisone régime, with excellent results

Favourable outcome in a patient with central nervous system lupus.

We report a case of paediatric lupus who during her admission developed near fatal central nervous system complication of status eilepticus with respiratory paralysis and was managed with intravenous immunoglobulins, extended course of methyl prednisolone with a favourable outcome.

Drug treatment of neurocysticercosis.

Neurocysticercosis, the most common parasitic disease of the central nervous system, was treated surgically for a long time. Praziquantel (an isoquinolone) and albendazole (an imidazole) are anticysticercal drugs that are currently being used for the treatment of neurocysticercosis. Both have been reported to eliminate or markedly reduce the number and size of cysticerci. Albendazole is less expensive than praziquantel, and is as effective when given for 8 days as compared to longer periods. In a small number of comparative trials, albendazole appeared to be slightly more effective than praziquantel for the treatment of parenchymal cysticercosis. Albendazole has also been found effective in ventricular, subarachnoidal and racemose forms of the disease. However, the response to treatment is not universal. Treatment with these drugs has been associated with a high frequency of adverse reactions, probably due to the host's inflammatory reaction to the dying parasites. Headache, nausea and seizures are common but usually transient. Steroids appear to ameliorate these effects and their concomitant administration has been advocated. However, no data are available to support this view. The rationale of medical therapy in spinal cysticercosis is presently based on the reported efficacy of anticysticercal drugs in cerebral cysticercosis. A marked improvement in an associated seizure disorder following anticysticercal therapy has been observed. Though seizure control is better, the total duration of anti-epileptic drug therapy has not been determined. Some single enhancing computed tomography lesions in patients of epilepsy may be benign forms of neurocysticercosis. The spontaneous resolution of a majority of these lesions has led to doubts of them being merely infective in aetiology. Also, a controlled trial could not demonstrate any beneficial effect of albendazole on such lesions. Hence, most authors recommend that these patients should be treated with anti-epileptic drugs only. Doubts persist about the efficacy of anticysticercal drugs in altering the natural course of the disease and the reported tendency of cysticercus lesions to resolve.

Neurotoxoplasmose em pacientes com síndrome de imunodeficiência adquirida: estudo de 33 casos / Central nervous system toxoplasmosis in patients with the acquirred immunodeficiency syndrome: study od 30 cases

Os autores estudaram, retrospectivamente, as manifestações clínicas de 33 pacientes adultos com o diagnóstico de Síndrome de Imunodeficiência Adquirida (SIDA) e neurotoxoplasmose, internados no Serviço de Doenças Infecciosas e Parasitárias do Hospital Universitário Antônio Pedro no período de abril de 1986 a dezembro de 1994, realizando uma correlação com os achados neurorradiológicos e os achados neuropatológicos de 10 pacientes. Dos 33 pacientes estudados, 27 (81,8 por cento) eram do sexo masculino, com predomínio do grupo etário compreendido entre 20 e 40 anos (72,6 por cento). Quanto ao comportamento de risco, observou-se um predomínio da transmissão por via sexual. As manifestações neurológicas mais freqüentes foram: sinais de localização (26 casos - 78,7 por cento); alterações do estado mental (24 casos - 72,7 por cento); cefaléia (20 casos - 60,6 por cento) e crise convulsiva generalizada (18 casos - 54,5 por cento). Quanto aos achados neurorradiológicos, verificou-se que a grande maioria dos pacientes apresentava lesões múltiplas (19 casos - 57,5 por cento) localizadas em hemisférios cerebrais (24 casos - 72,7 por cento) e núcleo da base (16 casos - 48,4 por cento) com captação nodular do contraste (16 casos - 48,4 por cento). Verificou-se ainda que o edema perilesional estava presente em 28 (84,8 por cento) casos e produziu efeito de massa em 16 (48,4 por cento). A instituição do tratamento para neurotoxoplasmose foi acompanhada de resposta parcial em 27 (82,0 por cento) pacientes, resposta completa em dois (6,0 por cento) e ausência de resposta em quatro (12,0 por cento). Na maioria dos casos (20 pacientes - 83,2 por cento), o tempo de sobrevida após o início da terapêutica foi inferior a 12 meses, sendo que em 15 (62,4 por cento) deles foi inferior a seis meses. O estudo histopatológico do Sistema Nervoso Central (SNC) foi realizado em 10 (41,6 por cento) dos 24 pacientes que evoluíram para o óbito. Em todos os casos observou-se alterações morfológicas do SNC. A neurotoxoplasmose ativa foi diagnosticada em cinco (50 por cento) casos, em todos havendo concordância entre o diagnóstico clínico, neurorradiológico e os achados neuropatológicos. Em quatro casos, a neurotoxoplasmose foi considerada a causa primária de morte. Nos cinco pacientes restantes foi constatada a presença de lesões cicatriciais, algumas de aspecto cístico, localizadas em hemisférios cerebrais, núcleos da base e tronco cerebral

Itraconazole and fluconazole in three neuro-paracoccidioidomycosis patients / Itraconazol e fluconazol em 3 pacientes com neuro-paracoccidioidomicose (PBM) cerebral

Three paracoccidioidomycoses (OBM) patients: Male, age 44,51 and 53 years old, form workers, heavy smokers, alcoholics were admitted in to Emílio Ribas Hospital, Såo Paulo, SP, with dyspnea, expectorative cough in all of them and evolutive cardiac edema in two C.O.P.D. inpatients. Hypertensive / nephropathy - 2, adenopathy - 2, clubbing finger, Cor pulmonale (C.O.P.D.), hepatoesplenomegaly and severe interstitial bilateral infiltrate lung lesions were related in 2 patients. Encephalopaty and cerebelar ataxia in one, focal convulsive crises, hypoastesia right arm and Mingazzini neurologic examens were observed in two patients. Paracoccidioides brasiliensis was recovered from bronchoscopy. Pulmonary function showed: bronchodilator no response and 2 mixels test, hypergamaglobulinemia, increases seric level alcaline phosphatase in 3, policytemia in 2 and complement fixation reaction rancing from 1/8 to 1/64 with negative counter immunoelectrophoresis, like laboratorial examens. Berebral C.T. -scan confirmed active nodules in three and cerebelar abscess in one. Azoles therapy revealed one early deth and after 18 months the presence of active nocules (C.T.-scan skull) in 2 of all chronic lung PBM patients

Neuroesquistossomose / Central nervous system schistosomiasis

O comprometimento neurológico é uma complicação não muito freqüente da esquistossomose. O envolvimento das porções inferiores da medula e da cauda equina é o mais comum. São relatados dois casos em que os pacientes apresentaram instalação subaguda de paraparesia com sorologia positiva para esquistossomose no líquido cefalorraqueano. Tratamento foi efetuado com corticosteróides e oxaminiquine.

Severe forms of neurocysticercosis: treatment with albendazole

Study of 22 patients with the severe form of neurocysticercosis treated with albendazole (ABZ) administered in 6 different schedules ranging from 15 to 30 mg/kg/day for 21 to 60 days. Dextrochloropheniramine and ketoprofen were the adjuvant drugs. Multiple symptoms were observed in 90.9 per cent of patients. Intracranial hypertension was manifested in 90.9 per cent. Hydrocephaly occurred in 86.4 per cent. Evolution was satisfactory in 10 patients, 8 died and 4 had sequelae. Tomographic studies showed the appearance of an isolated IVth ventricle in 9 patients, after ventriculoperitoneal shunt, before ABZ treatment in 3 of them, during in 5 and after treatment in one. Median clinical follow-up duration was 10 months for the patients who died and 3-4 years for survivors. In 3 patients there was an increase in cyst size during the administration of the 15 mg/kg/day ABZ dose, which was not observed in any patient when the 30 mg/kg/day dose was used.

Forma granulomatosa da criptococose cerebral: relato de caso / Granulomatous form of cerebral cryptococcosis: a case report

A criptococose do sistema nervoso central na sua forma granulomatosa ou criptococoma é rara, sendo mais frequente a forma meningítica ou meningoencefalítica. Apresentamos o caso de um paciente de 56 anos, nao portador da síndrome de imunodeficiência adquirida, com manifestaçao clínica inicial da síndrome de hipertensao intracraniana em decorrência de criptococoma occípito-parietal que foi removido cirurgicamente, seguido do tratamento medicamentoso com anfotericina-B e 5-fluorocitosina. A fiosiopatologia, o diagnóstico por imagem e o tratamento sao revistos.