Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy-A Preliminary Study in a Brazilian Cohort Sample.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

Diagnóstico de encefalite límbica não paraneoplásica de etiologia imunomediada: estudo de caso e revisão de literatura / Diagnosis of immune-mediated non-paraneoplastic limbic encephalitis: case report and literature review

A encefalite límbica vem sendo descrita como um distúrbio neurológico raro, que afeta seletivamente as estruturas do sistema límbico. Clinicamente, é caracterizada como uma desordem neurológica debilitante, que se desenvolve como encefalopatia rapidamente progressiva, causada por inflamação encefálica. Objetivamos aqui relatar um caso de encefalite do sistema límbico de provável etiologia autoimune para melhor conhecimento da comunidade médica, bem como averiguar métodos diagnósticos deste quadro. Paciente do sexo masculino, 59 anos, admitido em nosso serviço com queixa de confusão mental. O exame clínico evidenciou desorientação, disartria, paresia e parestesia no hemicorpo esquerdo, dificuldade de marcha, desvio de rima e histórico de epilepsia há 2 anos. No estudo por ressonância magnética do crânio, foram observadas extensas lesões que acometiam a região mesial do lobo temporal direito, todo o hipocampo e giro para-hipocampal direito, estendendo-se pelo fórnix até a porção posterior do hipocampo esquerdo, substância branca do lobo frontal bilateral. Mediante os resultados da investigação complementar, o paciente foi tratado com pulsoterapia de metilpredinisolona por 5 dias, resultando na regressão parcial dos sintomas. Atualmente, o paciente se encontra em seguimento ambulatorial para acompanhamento. A encefalite límbica é uma doença rara, porém muito importante de ser investigada e diagnosticada precocemente, uma vez que a progressão da doença pode causar incapacidade e sequelas irreversíveis.

Limbic encephalitis has been described as a rare neurological disorder affecting the limbic system structures selectively. Clinically, it is characterized as a debilitating neurological syndrome that develops as a quickly progressive encephalopathy caused by brain inflammation. This paper reports a case of limbic encephalitis, probably of autoimmune etiology, aiming to improve the knowledge of the medical community, and to promote a debate on diagnosis methods for this pathology. The patient is male, 59 years old, and was admitted at our service complaining of mental confusion. The clinical examination showed disorientation, dysarthria, left hemiparesis and paresthesia, gait difficulties, light asymmetrical smile, and history of epilepsy 2 years ago. The magnetic resonance imaging of skull showed extensive lesions affecting the mesial region of the right temporal lobe, the entire hippocampus, and right parahippocampal gyrus, extending through the fornix to the posterior portion of the left hippocampus, white matter of bilateral frontal lobe. Based on the complementary investigation results, the patient was treated with intravenous methylprednisolone for five days. Currently, he is being followed in the outpatient's department. Although being rare, limbic encephalitis shall be investigated and diagnosed early because its progression can lead to disability and irreversible sequelae

Autonomic dysfunction is frequent and disabling in non-paraneoplastic sensory neuronopathies.

INTRODUCTION: Sensory neuronopathies (SN) are characterized by asymmetric non-length dependent sensory deficits and sensory ataxia. Autonomic dysfunction in SN was not yet evaluated regarding its frequency, characteristics and relationship to sensory deficits. To address these issues, we performed a comprehensive clinical and neurophysiological evaluation of a large cohort of patients with non-paraneoplastic SN (np-SN). METHODS: We enrolled 50 consecutive patients with npSN and 32 age/sex-matched healthy controls. They were clinically evaluated (SCOPA-Aut scale) and underwent neurophysiological autonomic assessment (quantitative sudomotor axon reflex test, heart rate variability and sympathetic skin response). RESULTS: Mean age of patients was 50.9 ±â€¯10.3 years and there were 18 men. npSN patients had higher SCOPA-Aut scores than controls (26.63 ±â€¯12.72 vs. 12.66 ±â€¯9.11, p < .001). QSART was abnormal in 92% of the patients - sweat volumes in all examined sites were smaller among patients (p < .001). Cardiovascular autonomic neuropathy was more frequent in these patients as well (p < .001). CONCLUSION: Altogether our results suggest that autonomic dysfunction in distinct domains is frequent in npSN patients. These findings suggest that the clinical picture of npSN is related to a double neuronopathy: sensory and autonomic.