Outcome and antiepileptic drug policies after childhood epilepsy surgery in children

Abstract

Epilepsy is defined as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. Of patients with newly diagnosed epilepsy, 70–80% respond well to medical treatment, while 20–30% develop intractable epilepsy. For intractable epilepsy patients with a clearly localized, or at least lateralized epileptic focus, epilepsy surgery is a valuable treatment option. The aims of epilepsy surgery are to achieve postoperative seizure freedom, stop the developmental regression caused by intractable seizures, and to decrease the adverse effects of antiepileptic drugs (AEDs) on cognition through withdrawal of AEDs. This thesis focusses on functional outcome, seizure outcome and antiepileptic drug policies after childhood epilepsy surgery. We first studied if indications for epilepsy surgery changed over the years and if indications for surgery had broadened. We found that although more complex cases were operated on over time and medication was withdrawn earlier after surgery, success rates at two years remained stable. Secondly, we assessed integrity of the brain by studying underlying etiology, MR imaging and EEG recordings that were part of clinical investigations in children, in relation to their motor, cognitive and seizure outcome. We found etiology to be an important predictor for functional outcome. Children with developmental etiology more often lost hand function postoperatively and showed less improvement in gross motor function compared to others. Loss of hand function could be predicted based on corticospinal tract damage on preoperative MRI. Furthermore, unambiguous contralateral MRI abnormalities were associated with seizure recurrence, severe mental delay, and lack of cognitive improvement after hemispherectomy, while contralateral EEG abnormalities did not negatively influence postsurgical outcome. Nevertheless, contralateral MRI abnormalities should not be a contra-indication for surgery, as even the ‘failures’ do better than they would have done without surgery.Thirdly, we studied if early discontinuation of AEDs after surgery would be safe, and whether it would improve functional recovery in terms of cognition. In our large European TimeToStop (TTS) cohort of 766 children, we studied AED withdrawal policies and found that, although shorter time intervals to both start and completion of AED withdrawal slightly increased the risk for seizure recurrences, early AED withdrawal did not affect long-term seizure outcome. It might unmask incomplete surgical success sooner, identifying children who need continuous drug treatment and preventing unnecessary continuation of AEDs in others. Furthermore we found that complete AED withdrawal improved psychomotor speed 24 months after surgery in 57 Dutch children, and that start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were all associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome in a subgroup of the TTS cohort of 301 patients. To confirm our non-experimental findings prospectively, we are close to starting the randomized TimeToStop trial, in which we will investigate whether early AED withdrawal improves cognitive function in terms of attention and intelligence, quality of life and behaviour, and aim to confirm safety of early reduction, in terms of seizure recurrences, eventual seizure freedom and “seizure and AED freedom”