Ongoing work continues to focus on comparative effectiveness analyses, long term follow up, biomarker identification, as well as interventions, that may improve outcome.

​references

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Genetic biomarkers

​Assessment of Time to Treatment

We identified a case series on a KCNA2 mutation found in one of our patients and collaborated with another pSERG center that had 2 patients with this mutation (Sachdev et al., 2017). These are the first reported patients with this mutation and refractory status epilepticus. With the collaboration of the Institute for Genomic Medicine at Columbia University, we have found that pediatric patients with refractory status epilepticus have a high frequency of genetic encephalopathies, including some of the more severe genetic epilepsy diagnoses (Heinzen Cox et al., 2018). Of the 80 samples sequenced, 16 (20%) had a pathogenic or likely pathogenic variant in a known gene: 10 were new diagnoses, 4 had known diagnoses, and 2 had missing information on genetic testing (Heinzen Cox et al., 2018).

In addition to timing analyses, , we analyzed several aspects of variability of care to identify ways to improve care pathways. We explored additional aspects that could contribute to these patients’ comorbidities, such as administration of low BZD doses (Tchapyjnikov et al., 2016; Vasquez et al., 2018a), inadequate escalation between the BZDs and non-BZD antiseizure medications (ASMs) (Sheehan et al., 2018), and the use of continuous infusions (CIs) (Arya et al., 2018a; Vasquez et al., 2018b; Gaínza-Lein et al., 2017). Almost half of the refractory SE patients received lower than recommended doses within the 10 minute recommended timeframe, which is independently associated with prolonged seizure duration and length of ICU stay (Vasquez et al., 2018a). We also identified variability in escalation between BZD and non-BZD ASMs indicating that delays to BZD and non-BZD treatment are common and occur mainly outside of the hospital (Sheehan et al., 2018). Furthermore seizure termination occurs in approximately 94% of patients by the second cycle of therapy, although, a minority often requires more than three cycles of CIs. Midazolam remains the most frequently administered first-line CI agent, followed by pentobarbital (Tasker et al., 2016). After these agents, there is high variability in the drug of choice among centers which has been evident studying their hospitals’ SE treatment pathways (Vasquez et al., 2018c). In the pSERG cohort, approximately 50% of patients received CIs as part of SE treatment. After using propensity score matching, the treatment of rSE with continuous infusions was independently associated with increased in-hospital mortality, longer ICU duration and failure to return to baseline function at discharge (Gaínza-Lein et al., 2017).

Previous Study Results

Future studies

Variability in Care​

Last updated April 2020

​Status epilepticus (SE) is defined as prolonged or recurrent seizures without return to conscious baseline in between. It is one of the most common neurological emergencies that affects children, with an incidence of 17-23/100,000 per year. The short-term mortality of pediatric SE is 0-3%, but can be as high as 20-40% in refractory SE (rSE). Other complications from SE can include cognitive and neurodevelopmental decline, epilepsy and recurrent SE.


Many facets of pediatric refractory status epilepticus care continue to be based on expert opinion and case report or case series data. To improve this knowledge gap, we initiated a collaboration across several North American centers to collect clinical data and biological specimens in pediatric patients with refractory status epilepticus and convulsive seizures at onset, utilizing variability in care as natural trial. To date, work focused on time to treatment and types of treatment applied, variability in care, as well as genetic biomarkers.

As an initial step, and potentially modifiable treatment variable, we evaluated the timing of treatment in pediatric patients with refractory status epilepticus and (Sánchez Fernández et al., 2015) . Follow up analyses focused on the differences of patients with an epilepsy diagnosis before the status epilepticus event, versus patients with no prior epilepsy (Sánchez Fernández et al., 2017). We found that patients with a prior epilepsy diagnosis did not receive faster treatment, but patients with prior status epilepticus events did. We also found that treatment was significantly delayed in the pre-hospital setting. These results provide an opportunity for improvement in the time to treatment in patients with prior epilepsy, as families could administer rescue medications.

Subsequently, we identified a relationship between time to treatment and outcome, specifically demonstrating that the patients who receive the first line treatment after 10 minutes of convulsive seizure onset are more likely to require continuous infusions and patients in the late treatment group have an increase in mortality (Gaínza-Lein et al., 2018). This data may impact the treatment of status epilepticus by changing the perception of acute seizure and status epilepticus treatment, tentatively converting it into an extremely time sensitive emergency, similar to stroke, or other cardiovascular emergencies.

We were able to establish that there are delays in treatment of pediatric convulsive status epilepticus, and have shown that those delays contribute to poorer outcomes. Furthermore, we analyzed factors associated with delays to treatment. Seizures that begin outside of the hospital and intermittent seizures were associated with longer delays to treatment. These factors highlight potential areas of interventions to improve time to treatment (Sánchez Fernández et al., 2018).