Abstracts

Rationale: JME is a common IGE but therapy is fraught with problems because optimal treatment involves VPA. Particular difficulties arise in selecting appropriate therapy for women of child bearing age because of risks of spina-bifida, other malformations and reduced IQ in their children. For many of these patients prolonged trials of therapy to prove efficacy are not a viable option. Methods to rapidly assess likely effectiveness of alternative therapies are needed. We propose that change (and suppression) of the EEG Photo-Paroxysmal-Response (PPR) would provide an early indicator of efficacy. Methods: We designed a 20 wk 1:1 randomised double blind 1-way cross-over parallel group study to compare VPA and LTG monotherapy in JME patients. At 4 weekly visits; LTG & VPA doses were adjusted blindly on clinical grounds via a double dummy, tandem, dosing technique. And trough AED concentrations, seizure frequencies & types, PPR during IPS and adverse effects were recorded. Only grade 3 or 4 PPR's were included. IPS testing was carried out and standardised to "SPR" utilising a standard protocol (Kasteleijn-Nolst Trenite et al., 2012). Results: 74 JME patients were identified. All gave informed consent. Ethics approval was obtained prospectively. 40 were taking VPA monotherapy. 17 VPA Rx'd patients agreed to enter the study (M:F=13:4), nine of whom had PPR on previous EEG. At study entry 4 exhibited a persistent PPR. At study end 2 VPA Rx'd patients still had PPR's and 4 LTG Rx'd patients had PPR's. All the LTG PPR's were higher than baseline. In the LTG group the PPR had risen and trended down again as dose was increased (Figure 1). In the LTG group myoclonic seizures had increased markedly but returned to baseline levels by study end associated with progressive LTG dose increases (Figure 2). Conclusions: LTG initially suppressed PPR less effectively than VPA but a dose-response effect of LTG on PPR was identified. Efficacy of LTG for all types of JME seizures was demonstrated, also with a dose-response relationship. Increased LTG doses appeared to overcome transient worsening of myoclonus. Change in PPR did correlate with LTG effect and may be utilised as an early indicator of efficacy. Reference Kasteleijn-Nolst Trenite D, Rubboli G, Hirsch E, Martins da Silva A, Seri S, Wilkins A, Parra J, Covanis A, Elia M, Capovilla G, Stephani U, Harding G. (2012) Methodology of photic stimulation revisited: Updated European algorithm for visual stimulation in the EEG laboratory. Epilepsia 53:16-24.