Seizure-related Inflammation in Refractory Epilepsy Patients

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Arvo building, Yellow Hall F025, address: Arvo Ylpön katu 34.

Tiina Alapirtti

Doctoral defence of Lic.Med. Tiina Alapirtti

Seizure-related Inflammation in Refractory Epilepsy Patients : A video-EEG study

The field of science of the dissertation is Neurology.

The opponent is professor Seppo Soinila (University of Turku). Professor Jukka Peltola acts as the custos.

The language of the dissertation defence is Finnish.

Seizure-related inflammation in refractory epilepsy patients

Epilepsy is a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures, which are transient disorders of cerebral function due to abnormal neural activity to varying extents in different brain regions. Approximately 30 % of patients suffer from refractory epilepsy with recurrent seizures, even though they use antiepileptic medication. Focal refractory epilepsy with temporal lobe origin has been widely studied. During the last two decades, increasing interest has been focused on clarifying inflammatory seizure-related factors which are related to refractory epilepsy.

Cytokines are proteins that are involved in inter-cellular communication; they are involved in immune responses as well as regulating cell growth, tissue homeostasis and repair. Analyses of cytokines in the blood can provide information about seizure-related inflammation. Cell free-DNA (cf-DNA) in plasma is released from apoptotic and necrotic cells and has displayed inflammatory properties. C-reactive protein (CRP) is an acute phase protein.

The purpose of this thesis was to investigate seizure-related inflammatory factors in refractory epilepsy patients in a well-controlled video-electroencephalographic (VEEG) environment.  The thesis is based on four scientific articles. Seventy-eight consecutive patients with refractory focal epilepsy admitted to the VEEG monitoring unit were included in the study, and of these, 51 patients experienced at least one epileptic seizure during the recording period. Plasma samples were collected for the analysis of the inflammatory markers at the beginning of the four-day recordings, and at 3, 6, 12 and 24 hours after the first verified seizure.

The present thesis provides evidence that in patients with human refractory epilepsy, immunological changes are related to the seizure. Temporal lobe epilepsy (TLE) differs from many other epilepsies in the immunological responses occurring after acute seizure. This is the first time that it has been demonstrated that only in TLE a low baseline IL-6 level and a smaller amount of seizures (≤10/month) during the last year associated with an increase in IL-6 after the single seizure. If the levels of IL-6 were elevated or there had been many more seizures (>10/month) during the last year, a single seizure exerted no effect on IL-6 levels in TLE. More severe seizure types and longer seizures evoke a greater inflammatory response with higher IL-6 and CRP levels after the seizure. Cf-DNA may be involved in refractory epilepsy; the levels after seizure are lower, if epilepsy has lasted longer. In conclusion, the immune system seems to be involved in the long-term changes such as cell loss or damage to brain networks   in patients with refractory epilepsy. Inflammatory responses may either confer protection or increase the severity of the injury.


The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2363, Tampere University Press, Tampere 2018. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1869, Tampere University Press 2018.

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