RESUMO
Refractory status epilepticus (RSE) occurs in patients with SE when they fail to respond to traditional medical therapy. Because there are very few case reports of topiramate (TPM) treatment of RSE in adult patients, we examined our experience with TPM with regard to its safety and efficacy in seizure termination in RSE in an adult patient population. We report a retrospective review of 35 adult patients with RSE who were treated with TPM in addition to other antiepileptic drugs (AEDs) between 2003 and 2010. After failure of initial treatments of benzodiazepines and weight-based intravenous loading doses of standard AEDs, TPM tablets were crushed and administered via nasogastric tube. Data were collected on age, gender, history of epilepsy, etiology of RSE, daily dose of TPM, co-therapeutic agents, treatment response, and disposition. Following initiation of TPM use and discontinuation of continuous intravenous anesthetics with no additional AEDs administered, cumulative cessation of RSE in patients was 4/35 (11%) at one day, 10/35 (29%) at two days, and 14/35 (40%) at three days. However, when including all patients and comparing the two patient groups in which RSE was or was not terminated within three days of initiating TPM as the last or not last AED given, there was no significant difference. Time to TPM response was not associated with the type of seizures, etiology of SE, or whether there was a history of epilepsy. There were no documented side effects or complications of therapy with TPM. This study provides support for the use of TPM as an adjunctive agent in the treatment of RSE.
Assuntos
Anticonvulsivantes/uso terapêutico , Frutose/análogos & derivados , Estado Epiléptico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Frutose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Convulsões/induzido quimicamente , Fatores de Tempo , Topiramato , Adulto JovemRESUMO
OBJECTIVE: To further characterize the Th1 (proinflammatory) vs. the Th2 (antiinflammatory) cytokine profile after severe traumatic brain injury (TBI) by quantifying the ventricular cerebrospinal fluid concentrations of Th1 cytokines (interleukin [IL]-2 and IL-12) and Th2 cytokines (IL-6 and IL-12) in infants and children. DESIGN: Retrospective study. SETTING: University children's hospital. PATIENTS: Twenty-four children hospitalized with severe TBI (admission Glasgow Coma Scale score, <13) and 12 controls with negative diagnostic lumbar punctures. INTERVENTIONS: All TBI patients received standard neurointensive care, including the placement of an intraventricular catheter for continuous drainage of cerebrospinal fluid. MEASUREMENTS AND MAIN RESULTS: Ventricular cerebrospinal fluid samples (n = 105) were collected for as long as the catheters were in place (between 4 hrs and 222 hrs after TBI). Cerebrospinal fluid samples were analyzed for IL-2, IL-4, IL-6, and IL-12 concentrations by enzyme-linked immunoassay. Peak and mean IL-6 (335.7 +/- 41.4 pg/mL and 259.5 +/- 37.6 pg/mL, respectively) and IL-12 (11.4 +/- 2.2 pg/mL and 4.3 +/- 0.8 pg/mL, respectively) concentrations were increased (p <.05) in children after TBI vs. controls (2.3 +/- 0.7 pg/mL and 1.0 +/- 0.5 pg/mL) for IL-6 and IL-12, respectively. In contrast, peak and mean IL-2 and IL-4 concentrations were not increased in TBI children vs. controls. Increases in the cerebrospinal fluid concentration of IL-6 were significantly associated with admission Glasgow Coma Scale score of =4 and age of =4 yrs. Increases in cerebrospinal fluid IL-4 and IL-12 were associated with child abuse as an injury mechanism (both p =.05 vs. accidental TBI). CONCLUSIONS: This study confirms that IL-6 levels are increased in cerebrospinal fluid after TBI in infants and children. It is the first report of increased IL-12 levels in cerebrospinal fluid after TBI in infants and children. Further, it is the first to report on IL-2 and IL-4 levels in pediatric or adult TBI. These data suggest that selected members of both the Th1 and Th2 cytokine families are increased as part of the endogenous inflammatory response to TBI. Finally, in that both IL-6 and IL-12 (but neither IL-2 nor IL-4) can be produced by astrocytes and/or neurons, a parenchymal source for cytokines in the brain after TBI may be critical to their production in the acute phase after TBI.