Study Reveals Factors Influencing Progression of Pediatric Refractory Convulsive Status Epilepticus

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Recent research indicated that obtaining specific variables early in established pediatric status epilepticus cases could lead to more personalized care and potentially predict refractory convulsive status epilepticus development in patients with convulsive seizures.

Katrina Peariso, MD, PhD, assistant professor neurology at Cincinnati Children's Hospital Medical Center

Katrina Peariso, MD, PhD

In an observational case-control study recently published in Neurology, investigators observed no association between the time to initial benzodiazepine (BZD) or second-line antiseizure medication (ASM) and progression to refractory convulsive status epilepticus (RSE) in patients with responsive established status epilepticus (rESE). In addition, a family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Overall, investigators concluded that early attainment of these variables may help care for this patient population in a more personalized way and provides evidence that specific factors may predict RSE in pediatric patients with convulsive seizures.1

The study compared pediatric patients with convulsive SE whose seizures stopped after BZD and a single second-line ASM (n = 87) with those requiring more than a BZD and a single second-line ASM to stop their seizures (RSE; n = 140). Among 595 episodes of pediatric SE collected, a univariate analysis performed showed no differences in time to the first BZD (RSE, 16 minutes [IQR, 5-45]; rESE, 18 minutes [IQR, 6-44], P = .068) and shorter time to second-line ASM in patients with RSE (RSE, 65 minutes; rESE, 70 minutes; P =0.021). In both the univariable and multivariable regression analyses, family history of seizures (OR, 0.37; 95% CI, 0.20-0.70; P = .0022) and a prescription for rectal diazepam (OR, 0.21; 95% CI, 0.078-0.53; P = .0012) was associated with decreased likelihood of progression to RSE.

Clinical Takeaways

  • The timing of initial benzodiazepine (BZD) or second-line antiseizure medication (ASM) administration may not be indicative of progression to refractory convulsive status epilepticus (RSE) in responsive established status epilepticus (rESE) cases.
  • Identifying patient-specific variables early in pediatric responsive established status epilepticus (rESE) may lead to more tailored care and could potentially serve as predictors for the development of RSE in children with convulsive seizures.
  • Notable factors associated with a decreased likelihood of progression to RSE include a family history of seizures and a prescription for rectal diazepam, providing insights into potential protective elements in pediatric seizure cases.

“In total, these data demonstrate that, while time to treatment with a first-line and second-line ASM is not associated with the development of treatment-resistant RSE, the data do not refute work showing that delays in treatment may increase the duration of SE in some patients who go onto develop RSE,” lead author Katrina Peariso, MD, PhD, assistant professor neurology at Cincinnati Children's Hospital Medical Center, and colleagues wrote.1 “Therefore, early treatment is likely critical for a subset of patients that, currently, we do not have the clinical tools to identify on presentation. Identification of patient-related variables and new technologies to obtain acute electrophysiologic data may lead to an accurate method for determining which patient’s SE will be refractory to early ASM treatment.”

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Patient data were obtained from the pediatric Status Epilepticus Research Group study cohort between June 2011 and April 2019. Investigators explored clinical variables that could be obtained early after presentation to emergency medical services using a univariate analysis of the collected data. The significant variables were then retained for the univariable and multivariable regression analyses. Additionally, multivariable logistic regression models were used to fit age-matched and sex-matched data for gathering variables associated with RSE.

The authors observed no differences of factors in the patients’ medical history associated with a risk of seizures and/or SE, including epilepsy, febrile seizures, developmental delay, and cerebral palsy. Despite this, having a family history of seizures was less frequent in patients with RSE (21%) compared with those who have rESE (31%) (P = .013). In addition, authors noted having a prescription for rectal diazepam was less frequent in patients with RSE (39%) than in patients with rESE (49%) (P = .030).

"We hypothesize that the reduced odds of developing RSE in patients having been prescribed rectal diazepam or patients with a family history of seizures may be that these variables are effective at sorting out underlying causes of SE that tend to more easily respond to current recommended interventions for SE. These may include such underlying causes as new-onset familial epilepsies, febrile seizures, and patients with epilepsy who may have missed a dose of ASM despite the cause not being readily apparent on presentation to the emergency department,” Peariso et al noted.1

Approximately 39 (45%) patients with rectal diazepam in the rESE group and 70 (50%) of the patients in the RSE group received rectal diazepam as first-line ASM treatment. Although not statistically significant, the magnitude of the difference in time to first BZD treatment between the patients with prescribed rectal diazepam compared with those who did not have one in both the RSE (47 minutes [SD 15] vs 86 minutes [SD 21]; p = 0.68) and rESE groups (59 minutes [SD 25] vs 83 minutes [SD 28]; p = 0.53) was notable, according to the study authors. However, it was also noted that the magnitude of these differences was similar between the RSE and rESE groups.

“The purpose of a home prescription for rectal diazepam is to reduce the time a patient with a tendency to prolonged or repeated seizures spends seizing by having a BZD that can be given early after seizure onset. Overall, having a prescription for rectal diazepam at home did reduce the time to initial BZD over the entire cohort; however, it did not influence the time to treatment nor the use of rectal diazepam as a first-line medication between the RSE and rESE groups. Therefore, time to treatment does not explain the association of having a prescription for rectal diazepam with the rESE group,” Peariso et al noted.1

REFERENCES
1. Peariso K, Arya R, Glauser T, et al. Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children. Neurology. 2023;101(5):e546-e557. doi:10.1212/WNL.0000000000207472
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