Super-Refractory Status Epilepticus Linked With Unknown Etiologies, High Mortality Rates
Patients treated for more than 28 days had a higher chance of status epilepticus cessation, but also a high risk of moderate to severe disability at discharge, according to one study.
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In a meta-analysis understanding the differences of
This systemic review and meta-analysis study is published in
To assess clinical characteristics, causes, outcomes, prognostic factors, and treatment approaches for patients with SRSE, investigators pulled 95 articles and 30 conference abstracts that included 1200 patients with nonanoxic SRSE. The researchers included all studies of patients with confirmed SRSE, which was defined as SE that continues or recurs 24 hours or more after the onset of anesthetic therapy, including cases where SE recurs on reduction or after withdrawal of anesthesia.
"Patients with reported SRSE differed significantly from unselected patients with first-time overall SE," wrote the researchers of the study. "The treating physicians may have prioritized patients with an expected more favorable overall prognosis and unknown diagnoses and avoided treatment with poorer prospects, eg, patients with brain tumors or more fragile, older patients. This may explain why established prognostic factors for in-hospital mortality, such as age and etiology, did not apply for SRSE."
Aside from the high in-hospital mortality, 81.3% of all patients saw their SRSE successfully cease with treatment. Of all patients analyzed in the meta-analysis, 26.8% were discharged from the hospital with no or minor to moderate disability. The remainder were either dead or severely disabled at discharge. Notably, the rate of successful seizure termination continued to rise with increasing duration; however, the proportion of patients with substantial disability, defined as a modified Rankin Scale score of 3 to 5, also increased substantially with longer duration of SRSE.
"The plateau in mortality after 28 days of treatment might be due to a combination of survival of the most robust patients and the reluctance of the treating physicians to terminate treatment once they had decided to continue treatment for more than 1 month (effort justification bias)," wrote the researchers. "The continuously increasing rate of seizure cessation after 28 days of treatment probably results from a combination of genuine treatment successes, reporting bias, and, conceivably, substantial brain damage destroying the epileptic focus after many weeks of continuous seizures."
Patients with SRSE had a distinct pattern of etiologies, where acute cerebral events and unknown etiologies accounted for 41.6% and 22.3% of all etiologies, respectively. Although there were only slight differences between patients with SRSE in the meta-analysis and those in larger cohort studies, investigators observed substantial differences between patients in the meta-analysis and those with first-time overall SE from a historical, retrospective, unselected cohort.
In an analysis of clinical characteristics of patients with SRSE according to their outcome (n = 266), findings showed that a favorable functional outcome was associated with younger age and lower number of antiseizure medications (ASMs) tried but not duration of SE. In addition, the SE severity score was not consistently associated with in-hospital mortality (nonsignificant for a cutoff of 3; P = .02), and there were insufficient data for the analysis of other prognostic scores.
Additional findings from the meta-analysis revealed that 50% of the cohort tried 3 to 6 ASMs, with levetiracetam, valproic acid, phenytoin, and lacosamide being used most often. The number of ASMs reported was associated with higher disability at discharge but not with reduced in-hospital mortality or higher rates of treatment success. The investigators also found no data indicating altered outcomes after treatment with barbiturates, ketamine, vagus nerve stimulator, or ketogenic diet.
Reference
Cornwall CD, Kroigard T, Kristensen JSS, et al. Outcomes and treatment approaches for super-refractory status epilepticus. JAMA Neurol. 2023;80(9):959-968. doi:10.1001/jamaneurol.2023.2407
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