Abstracts

Rationale: Animal studies suggest that prolonged and recurrent seizures cause increased excitability associated with synaptic reorganization, neuronal damage and neurogenesis. We used transcranial magnetic stimulation (TMS) to prospectively study the in vivo effect of recurrent seizures on cortical excitability during the evolution of chronic epilepsy. Methods: Fifty-seven drug naïve patients with newly diagnosed epilepsy (29 idiopathic generalised epilepsy [IGE], 28 focal epilepsy) were prospectively evaluated over 3 years. Motor threshold (MT) and cortical excitability on recovery curve analysis using paired pulse stimulation at short ( 2- 15 ms) and long (50 - 300 ms) interstimulus intervals (ISIs) were measured three times; before, 8 - 12 weeks and 24 - 30 months after starting medication. The patients were divided at the end of a three year follow-up period into refractory (14/29 IGE, 16/28 focal epilepsy) and well controlled (seizure free) groups. Results: The main changes were seen at the longer ISIs. At onset and at 12 weeks after medication, all groups (well controlled and refractory) had increased cortical excitability maximum at the 250 and 300 ms ISIs. At 30 months the patients with refractory seizures had extension of the hyperexcitability to the 100 and 200 ms ISIs (p < 0.01, effect sizes ranging from 0.5 - 0.6). This was seen in both IGE and the ipsilateral hemisphere in focal epilepsy. The contralateral hemisphere was not hyperexcitable compared to controls at onset but progressively became so starting at 12 weeks with refractory seizures. Conversely, cortical excitability decreased in the well controlled groups after medication. Conclusions: Refractory epilepsy is associated with changes in cortical excitability, evident within 3 months of onset, with subsequent progression, These changes may be the direct result of recurrent seizures possibly reflecting synaptic plasticity evident in animal models of chronic epilepsy.