Sirolimus improves seizure control in pediatric patients with tuberous sclerosis: A prospective cohort study

Seizure. 2020 Jul:79:20-26. doi: 10.1016/j.seizure.2020.03.018. Epub 2020 Apr 26.

Abstract

Purpose: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis.

Methods: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs.

Results: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up.

Conclusions: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy.

Keywords: Epilepsy; Pediatric; Sirolimus; Tuberous sclerosis; mTOR inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacology*
  • Child
  • Child, Preschool
  • Epilepsy / drug therapy*
  • Epilepsy / etiology
  • Female
  • Humans
  • Infant
  • Male
  • Outcome Assessment, Health Care*
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Sirolimus / administration & dosage
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Tuberous Sclerosis / complications
  • Tuberous Sclerosis / drug therapy*

Substances

  • Anticonvulsants
  • Protein Kinase Inhibitors
  • TOR Serine-Threonine Kinases
  • Sirolimus