Abstracts

Despite authoritative reviews in 2005 on the subject of photosensitive patients and their epileptiform EEG responses to intermittent photic stimulation (IPS)(Fisher et al. Covanis, Verrotti et al., Kasteleijn et al.), gleaning the essential components necessary to effectively study a new AED in the photosensitivity model are not readily available. This work proposes a novel rationale for the use of the photosensitivity model in the development of new AEDs and perhaps as a surrogate marker for AED efficacy in epilepsy. The amended FDA laws (1992,1997) permit approval of a new AED on the basis of a AED[apos]s effect on a surrogate marker, one that can be reasonably expected to predict the clinical outcome (Katz R. The development of AEDs: regulatory perspective. In AEDs 5^th Levy R et al.; Philadelphia 67-68, 2002)., A survey of epileptologists with extensive experience in performance of studies in the photosensitivity model, was conducted to arrive at consensus statements for the clinical utility of the model in assessing the activity of potential new AEDs in epilepsy., [italic]Advantages[/italic] include:
1.The range of photoparoxysmal EEG responses (PPRs) is a stable, repeatable and objective measure of the epileptic state of the brain
2. The procedure of IPS establishing the photosensitivity ranges has been standardised with also clear diminishment of risks to evoke seizures (EU consensus)
3. Only a limited number of patients (20)during a limited time period (number of days 3-5) are necessary to have a reliable outcome 4. AEDs limit, reduce or even abolish the PPRs 5. The results provide some guidance as to the choice to dose in further phase II and III trials 6. Comparison of strength of effect of AEDs in the photosensitive patients 7. Correlation of pharmacodynamic and pharmacokinetic data 8. A first experience of the effect of a new AED on the EEG background can be established 9. Testing in female patients in an early stage of development 10. A PPR is found in patients with generalised as well as focal epilepsy types and syndromes and reflects a general susceptibility to epilepsy 11. AEDs effective in the photosensitivity model are effective also in epilepsy patients in general 12. Compliance is secured as well as monitoring of subjective and objective side-effects13. Flexibility of design with immediate results.
[italic]Disadvantages[/italic] include:
1. Only about 5% of patients above 18 years of age show a PPR 2. Photic stimulation may provoke a seizure 3. Highly skilled centers are necessary to perform such a study., The photosensitivity model offers an excellent way of testing efficacy and tolerability of AEDs in a very standardized, controlled and safe manner in the early development.,