thiopental and Encephalitis

We report on three acute encephalitis patients with refractory, repetitive partial seizures (AERRPS). All three suffered acute febrile episodes associated with status epilepticus, which necessitated high-dose barbiturate therapy under artificial ventilation for several weeks. Electroencephalography (EEG) revealed a predominance of diffuse epileptiform discharges initially, subsequently developing into periodic bursts of these discharges. Reduction of the barbiturate dosage resulted in clinical and subclinical partial seizures appearing repetitively in clusters. Prolonged fever persisted for 2-3 months, even several weeks after normalization of cell counts in the cerebrospinal fluid. The EEG showed an improvement after resolution of this fever, and seizures became less frequent, although still intractable. Oral administration of high-dose barbiturate and benzodiazepines were partially effective during the acute phase, and a barbiturate dependency, lasting for years, was noted in one patient. Steroid administration was effective in stopping the febrile episodes in one patient, with concurrent improvement in seizure control. Magnetic resonance imaging showed enhancement of bitemporal cortical areas in one patient, and high signal intensity on T2 weighted image in the bilateral claustrum in another patient. Diffuse cortical atrophy appeared within two months after the onset of encephalitis in all patients. The evolution of the seizures and EEG findings suggested a high degree of cortical excitability in AERRPS. In this report, we propose a tentative therapeutic regimen for seizure control in this condition. We also hypothesize that a prolonged inflammatory process exists in the cerebral cortex with AERRPS, and may be pivotal in the epileptogenesis.

Topics: Acute Disease; Anti-Inflammatory Agents; Anticonvulsants; Brain; Cell Count; Cerebrospinal Fluid; Child; Delirium; Drug Resistance; Electroencephalography; Encephalitis; Epilepsies, Partial; Female; Fever; Humans; Magnetic Resonance Imaging; Male; Midazolam; Pneumonia; Status Epilepticus; Thiopental; Tomography, X-Ray Computed; Treatment Outcome; Unconsciousness

Thiopental is one of the intravenous anesthetics used widely. Several reports have demonstrated that thiopental inhibits the immune responses. We investigated whether or not thiopental inhibits the production of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS) in human glioma cells (A-172). Moreover, we determined whether or not thiopental modulates activation of the transcription factor NF-kappaB, a factor that regulates expression of the genes that code for proinflammatory cytokines in A-172 cells and in experimental murine brain inflammation. Thiopental inhibited TNF-alpha production induced by LPS in A-172 cells. Electrophoretic mobility shift assays demonstrated that thiopental inhibited NF-kappaB activation induced by LPS in A-172 cells. In experimental murine brain inflammation induced by intracerebroventricular injection of LPS, intraperitoneal injection of thiopental inhibited NF-kappaB activation. Western blot analysis indicated that this inhibition was linked to preservation of IkappaBalpha protein expression in A-172 cells. The chloramphenicol acetyltransferase assay revealed that NF-kappaB-dependent reporter gene expression was suppressed in A-172 cells exposed to thiopental. These findings are consistent with the idea that thiopental exerts antiinflammatory effects in cultured cells and experimental murine brain inflammation, through suppression of TNF-alpha production via inhibition of NF-kappaB activation.

Topics: Anesthetics, Intravenous; Animals; Brain; Brain Neoplasms; DNA-Binding Proteins; Encephalitis; Gene Expression Regulation; Genes, Reporter; Glioma; Humans; I-kappa B Proteins; Immune System; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Thiopental; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Topics: Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Coma; Dexamethasone; Encephalitis; Female; Humans; Infant; Male; Phenobarbital; Positive-Pressure Respiration; Seizures; Thiopental