ABSTRACT
BACKGROUND: Tuberculosis is prevalent in China, which is the second greatest contributor to the global tuberculosis burden. Tuberculosis meningitis (TBM) is the most severe disease form but few reports describe long-term clinical outcomes and prognostic factors. Thus, we studied these features in Chinese TBM patients. METHODS: A retrospective follow-up study was used to collect clinical features and outcomes of adult TB meningitis at the First Affiliated Hospital of Chongqing Medical University from June 2012 to August 2015. Univariate analysis and multivariate analysis were used to identify predictive factors associated with outcomes at discharge and follow-up. RESULTS: TBM patients (N = 154) were a median age of 41 years (range: 16-82 years). Median time to follow-up was 26.4 months (range: 9.3-46.5 months) and 31% had poor outcomes at follow-up and limb weakness (p = 0.016), lower GCS scores (p < 0.001), cranial-nerve palsy (p = 0.024), and hydrocephalus (p = 0.009) were closely associated with these poor outcomes. Furthermore, a high neutrophil to lymphocytes ratio, high D-dimer, a low albumin to globulin ratio and slow background of EEG associated with poor outcomes as well. CONCLUSIONS: Mortality and disability associated with TBM are high in China. Limb weakness, GCS scores, cranial-nerve palsy and hydrocephalus were independent predictors of poor outcomes, and AGR, NLR, D-dimer, and EEG abnormalities may be prognostic factors of TBM.
Subject(s)
Antitubercular Agents/therapeutic use , Hydrocephalus/diagnosis , Mycobacterium tuberculosis/drug effects , Trochlear Nerve Diseases/diagnosis , Tuberculosis, Meningeal/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , China , Electrocorticography , Female , Fibrin Fibrinogen Degradation Products/metabolism , Follow-Up Studies , Humans , Hydrocephalus/drug therapy , Hydrocephalus/microbiology , Hydrocephalus/pathology , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/microbiology , Male , Middle Aged , Multivariate Analysis , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/pathogenicity , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/microbiology , Prognosis , Retrospective Studies , Risk Factors , Serum Albumin/metabolism , Serum Globulins/metabolism , Trochlear Nerve Diseases/blood , Trochlear Nerve Diseases/drug therapy , Trochlear Nerve Diseases/pathology , Tuberculosis, Meningeal/drug therapy , Tuberculosis, Meningeal/microbiology , Tuberculosis, Meningeal/pathologyABSTRACT
Studies have shown that neurofibromin (NF1) restricts GABA release at inhibitory synapses and regulates dendritic spine formation, which may play an important role in temporal lobe epilepsy (TLE). NF1 expression was detected by double-label immunofluorescence, immunohistochemistry, and western blot analysis in the brains of pilocarpine-induced epilepsy model rats at 6 h, 24 h, 72 h, 7 days, 14 days, 30 days, and 60 days after kindling. NF1 was localized primarily in the nucleus and cytoplasm of neurons. NF1 protein levels significantly increased in the chronic phase (from 7 days until 60 days) in this epileptic rat model. After NF1 expression was knocked down by specific siRNA, the effects of kindling with pilocarpine were evaluated on the 7th day after kindling. The onset latencies of pilocarpine-induced seizures were elevated, and the seizure frequency and duration were reduced in these rats. Our study demonstrates that NF1 promoted seizure attacks in rats with pilocarpine-induced epilepsy.
Subject(s)
Epilepsy/metabolism , Neurofibromin 1/metabolism , Seizures/metabolism , Animals , Disease Models, Animal , Down-Regulation , Epilepsy/pathology , Hippocampus/metabolism , Lentivirus/metabolism , Male , Pilocarpine , Rats, Sprague-Dawley , Recombination, Genetic/genetics , Seizures/pathologyABSTRACT
To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats.
