PhD Defence Julia Pottkämper | The end is just the beginning: Unraveling the postictal state

The end is just the beginning: Unraveling the postictal state

Julia Christine Marianne Pottkamper is a PhD student in the department Clinical Neurophysiology. (Co)promotors are prof.dr.ir. M.J.A.M. van Putten and prof.dr. J. Hofmeijer from the faculty of Science and Technology and dr. J.A. van Waarde from Rijnstate Arnhem.

Epilepsy is one of the most common neurological disorders worldwide. Postictal symptoms, occurring after seizures, often form a great burden for patients and their caregivers. Approximately one-third of patients do not achieve seizure freedom with proper treatment (i.e., antiepileptic medication or surgical removal of epileptic tissue). These patients suffer from the seizure aftermath each time they have a seizure. Until today, it is unclear how we can treat the postictal state. Promising findings from animal studies showed that acetaminophen (in The Netherlands better known as ‘paracetamol’) or nimodipine (vasodilator) could improve postictal symptoms in rats.

In this dissertation, we show that the postictal state can be studied in a well-controlled environment with patients receiving electroconvulsive therapy (ECT). In ECT, a generalized seizure is evoked by electrical stimuli on the head of patients, mostly for treating severe depression. It appears that there are sufficient similarities between seizures and postictal states of ECT and epilepsy patients in order for ECT to be used as a human epilepsy model. We describe that the postictal EEG shows a clear pattern of frequencies that returns to baseline levels at approximately 1h after the seizure, which depends on seizure duration. Postictal cerebral blood flow changes depend on seizure duration, with shorter seizures leading to increased postictal perfusion and longer seizures leading to decreased perfusion. Using functional MRI, we show that postictal mean network connectivity strength decreases in the left central executive network and in the auditory network compared to baseline, which is controlled for network connectivity changes in healthy controls. Finally, with our prospective clinical trial with randomized three-condition cross-over design, we fail to replicate findings from animal models, possibly because our chosen doses of pre-ECT administered acetaminophen or nimodipine (much lower than in the animal studies) do not improve postictal EEG recovery, clinical reorientation time and postictal ASL-MRI perfusion.

With these results, we contribute to the growing body of postictal research and provide evidence that a clinical trial to investigate postictal treatment is feasible.