Status epilepticus and multiple organ system dysfunction

Recent reports have suggested the possible association of status epilepticus and multiple organ system failure. The purpose of this case control study was to investigate this association and to identify factors that predispose individuals with status epilepticus (SE) or aborted status epilepticus (ASE) to develop multiple organ system failure (MOSF) or multiple organ system dysfunction (MODS).^ For the purpose of the study, definitions of SE, ASE, MOSF, and MODS were operationalized as follows: SE was defined as any seizure lasting for a duration of $\ge$30 minutes or intermittent seizures lasting for $\ge$30 minutes from which the patient does not regain consciousness. ASE was defined as any seizure lasting for a duration of $\ge$10 minutes but $<$30 minutes and which was aborted as a result of a medical intervention. MOSF was defined as the failure of $\ge$2 organ systems in the same patient; organ system failure was said to be present whenever standard MOSF criteria were met. MODS was defined as the dysfunction of $\ge$2 organ systems in the same patient; organ system dysfunction was said to be present, whenever the monitor(s) of that organ's function exceeded the normal range for the physiological or laboratory parameters.^ Medical records of 686 individuals between the age of 5 and 44 years, with history of seizures needing hospitalization at the Texas Children's Hospital or Methodist Hospital, Houston, Texas, between 1991-95 were reviewed and 100 individuals with SE/ASE were identified. Of these 100 individuals with SE/ASE, 45 developed MOSF/MODS during their hospitalization and 9 of these individuals died. Using multivariate analyses, it was found that adult individuals who had an "acute" etiology of their seizure disorder (OR = 5.23; 95%CI: 0.41, 66.24) and children who had a "remote" etiology of their seizure disorder (OR = 3.92; 95%CI: 0.53, 29.22), were more likely to develop MOSF/MODS compared with those who had other etiologies of the seizure disorder. Individuals with SE lasting more than one hour were more likely to develop MOSF/MODS compared with individuals with SE lasting less than 1 hour (OR = 6.51; 95%CI: 1.63, 25.92). Individuals who presented with the SE/ASE episode as their first seizure episode were more likely to develop MOSF/MODS compared to those with a previous history of seizure episodes (OR = 1.78; 95%CI: 0.36, 8.82).^ The major limitations of this study includes the relatively small sample size and the study being performed in only two institutions. However, this is the first study of this kind and should therefore be viewed as largely exploratory in nature. Future studies should investigate the relationship of the risk factors identified in this study using a larger number of institutions and patients. ^

POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders.

PURPOSE: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. METHODS: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. RESULTS: Four patients of multiple different ethnicities, age 3-18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher syndrome. CONCLUSION: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.