The end is just the beginning: Unraveling the postictal state

Julia C.M. Pottkämper

Research output: ThesisPhD Thesis - Research UT, graduation UT

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Abstract

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 effectively. Promising findings from animal studies showed that acetaminophen (in The Netherlands better known as ‘paracetamol’) or nimodipine (vasodilator) could improve postictal symptoms in rats.

We highlight that a clear definition for the postictal state was still lacking, which is why we provided a new definition that includes its manifestation (i.e., clinical and electroencephalography [EEG]) as well as temporal variability.

ECT appears to be a useful human model to investigate seizures and postictal states because clinical and EEG characteristics (i.e., spatiotemporal dynamics) show sufficient similarities between both epilepsy and ECT patients. With ECT, ictal and postictal phenomena can be studied in a well-controlled environment, increasing practical feasibility of clinical studies.

We describe that the postictal EEG shows a clear pattern of frequencies that return to baseline levels at approximately 1h after the seizure, which depends on seizure duration. Longer clinical reorientation time and repeated exposure to seizures are associated with longer postictal EEG recovery.

We examined postictal cerebral blood flow, measured with arterial spin labeling magnetic resonance imaging (ASL-MRI), and show clear patterns of hypoperfusion in some patients, while in others, discrete local hyperperfusion is seen. These opposite patterns depend on seizure duration.

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 and 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.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Twente
Supervisors/Advisors
  • van Putten, Michel J.A.M., Supervisor
  • Hofmeijer, Jeannette, Supervisor
  • van Waarde, Jeroen A., Co-Supervisor, External person
Award date16 Feb 2024
Place of PublicationEnschede
Publisher
Print ISBNs978-90-365-5959-1
Electronic ISBNs978-90-365-5960-7
DOIs
Publication statusPublished - 16 Feb 2024

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