Sirolimus for epileptic seizures associated with focal cortical dysplasia type II

Mitsuhiro Kato, Akiko Kada, Hideaki Shiraishi, Jun Tohyama, Eiji Nakagawa, Yukitoshi Takahashi, Tomoyuki Akiyama, Akiyoshi Kakita, Noriko Miyake, Atsushi Fujita, Akiko M. Saito, Yushi Inoue

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Objective: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II. Methods: Sixteen patients (aged 6–57 years) with FCD type II received sirolimus at an initial dose of 1 or 2 mg/day based on body weight (FCDS-01). In 15 patients, the dose was adjusted to achieve target trough ranges of 5–15 ng/mL, followed by a 12-week maintenance therapy period. The primary endpoint was a lower focal seizure frequency during the maintenance therapy period. Further, we also conducted a prospective cohort study (RES-FCD) in which 60 patients with FCD type II were included as an external control group. Results: The focal seizure frequency reduced by 25% in all patients during the maintenance therapy period and by a median value of 17%, 28%, and 23% during the 1–4-, 5–8-, and 9–12-week periods. The response rate was 33%. The focal seizure frequency in the external control group reduced by 0.5%. However, the background characteristics of external and sirolimus-treated groups differed. Adverse events were consistent with those of mTOR inhibitors reported previously. The blood KL-6 level was elevated over time. Interpretation: The reduction of focal seizures did not meet the predetermined level of statistical significance. The safety profile of the drug was tolerable. The potential for a reduction of focal seizures over time merit further investigations.

Original languageEnglish
Pages (from-to)181-192
Number of pages12
JournalAnnals of Clinical and Translational Neurology
Issue number2
Publication statusPublished - Feb 2022

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology


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