Multi-modal investigations of patients with epilepsy

The current thesis begins with the exploration of the epidemiology of suspected seizure patients in a hospital setting where patients with first seizure, epilepsy and non-epileptic events may present at the same point-of-care entry. We designed a longitudinal, prospective study examining patients presenting with “seizure-specific” and “non-specific” labels. Components of evaluation contributing to revision of diagnosis included retrieval of witness accounts, epileptiform discharges on electroencephalogram (EEG), short-term monitoring of patients with acute symptomatic seizures and panel discussion of cases. These may represent the first step towards a multimodal investigation of patients with epilepsy.;In the next part of the current thesis, focus was placed on the refractory epilepsy patients. A formal treatise on a specific modality of investigation, namely video electroencephalogram (VEEG) was presented. The clinical appearance of patients at the time of seizure was known as semiology, and this was systematically explored in a cohort of patients undergoing VEEG3. By carefully examining the localizing value (which cerebral lobe) and the lateralizing value (which side) of the semiology, we discovered a new set of semiology which might point towards an epileptic focus in the medial aspect of the frontal lobe..;Electroencephalography (EEG) forms an essential part of the multi-modal investigation of epilepsy. Modern-day EEGs are performed with surface electrodes attached to the scalp to capture the electrographic information at the time of seizure but this can be hindered by muscle artifacts which decrease the localizing power of the EEG. We began with the exploration of the “hypersynchronous states” of intracranial EEG in which no muscle artifact would be present. A total of 100 focal onset seizure episodes were analyzed from 60 patients undergoing intracranial implantation4. A multivariate method was used computing the eigenvalue spectrum of the zero-lag correlation matrix of a short sliding window. We showed that there were clearly observable and statistically significant changes of the correlation structure of focal onset seizures. These changes indicated that the zero-lag correlation of multi-channel EEG either remained approximately unchanged, or especially in the case of secondary generalization, decreased during the first half of seizures. The correlation then gradually increased again before the seizures terminated. This development was qualitatively independent of the anatomical location of the seizure onset zone and it appeared to be a generic property of focal onset seizures. We concluded that the de-correlation of EEG activity was due to the different propagation times of locally synchronous ictal discharges from the seizure onset zone to other brain areas and the increase of correlation during the second half of the seizures may be causally related to seizure termination.;In the next part of our multimodal investigations, focus was made on how to use applied mathematics in procuring an accurate EEG interpretation from surface EEG. A mathematical model known as discrete wavelet transform (DWT) is a powerful tool which may help denoise the ictal EEG. It can be coupled with an absolute slope method as described in the last part of the thesis which enhances the determination of ictal foci. (Abstract shortened by UMI.).;In the second part of the current thesis, we examined the prognosis of first acute symptomatic seizures (ASS), an important component of the seizure diagnosis under the hospital setting. We challenged the traditional school of thought that “ASS are not necessarily considered epilepsy as their potential to generate unprovoked seizure is low”. By following 105 patients with ASS, we found that first ASS was associated with status epilepticus (29.5%), multiple-onset (>1 seizure within 24h on day of presentation, 35.2%) and multiple aetiologies (22.9%) with a mortality of 30% at 2 years by the Kaplan-Meier method. By using seizure recurrences in the setting of a persisting or re-emerging acute symptomatic cause, we were able to demonstrate a risk of recurrence following an ASS of 32% at 2 years with epileptiform EEG being an independent predictor2. This information sheds light onto the fact that even ASS can be “refractory” insofar as the acute symptomatic cause takes a long time to treat, is prone to re-emergence, or is irreversible. This may be seen as the second step towards a multimodal investigation of patients with epilepsy.