Rationale:
Guidelines for treatment of focal seizures describe simply packed as focal seizures but this often fails good seizure control. Among them, most frequent and harmful refractory seizures were focal onset tonic seizures (FTS) and focal to bilateral tonic-clonic seizures (FBTCS). This study aimed to clarify effective antiseizure medications (ASMs) for these two seizure types in patients with non-lesional focal refractory epilepsy (NLRFE).
Methods:
Patients with NLRFE and FTS and/or FBTCS which had not responded to
>2 AMSs, and directly treated by the author for
>one year were recruited from retrospective review of medical records. The patients were aged 2-50 years, mostly under 20 years. FTS and FBTCS were diagnosed by the description or videos of seizures by witnessed persons and interictal EEG findings in many cases, and by video-EEG monitoring in some cases. A particular ASM was added on or switched from previous ASMs, with dosing-up to maximum tolerated dose, if needed. The efficacy was evaluated at the best seizure reduction after the change of the particular ASM, which lasted
> 3 months. When the ASM was discontinued earlier because of adverse events, it was evaluated as ineffective. Seizure frequency was obtained from medical records and seizure diary of the caregivers.
>50% responder rate (RR) was obtained in ASMs given to
> 10 cases. The previous efficacy of the ASMs was included in the present results.
Results:
FTS were identified in 266 cases and FBTCS in 117 cases. Some patients had both seizure types. For FTS, the number of
>50% seizure reduction cases/total administered cases for each AED were: LTG 117/128, KBr 60/68, PER 46/54, ZNS 163/199, PB 98/154, PHT 39/82, CZP 38/95, CLB 33/101, TPM 12/46, VPA 35/184, CBZ 13/145, GBP 2/17, and LEV 2/47 in high RR order. For FBTCS, the same ratios were: LTG 22/23, PER9/10, ZNS 45/51, PHT 23/30, PB 25/35, CLB 20/33, CZP 19/31, CBZ 35/66, TPM 8/15, and VPA 15/64 in high RR order. Other ASMs were not reached to 10 cases.
CBZ as the first line drug for focal seizures in general, but FTS poorly responded to CBZ different from an ordinary recommendation in the present study. CBZ was more effective for FBTCS than for FTS, but far effective ASMs for FBTCS were similar to FTS. The present study had limitations: many subjects resistant to > two ASMs had already been treated with CBZ and/or VPA, and good responders to CBZ and/or VPA were not included in the present study. This might lead to extremely low RR of CBZ and VPA in the present study. Treatment and evaluation of efficacy were done by single person (KS) which causes two risks: previously effective ASMs were apt to be used and the evaluation might be subjective, although it is based on the same standard.
Conclusions: Though the present study was retrospective with some biases, efficacy of ASMs for refractory non-lesional FTS and FBTCS was clearly different among AMSs. Effective ASMs included LTG, KBr, PER and ZNS, followed by PB and PHT.
Funding: None