Epilepsy is a condition that affects 0.6-0.8% of the world population, rendering it the most common neurological disorder after stroke. It is characterized by recurrent unprovoked seizures, due to abnormal, excessive or synchronous neuronal activity in the brain and by a vast range of causes, triggering events, symptoms and brain locations where the seizures originate. In 25% of the affected population, seizures cannot be controlled by antiepileptic drugs or surgery. However, it has been suggested, that at least some types of seizures are predictable.

Seizures compromise the quality of life of patients with epilepsy to a great extent and may result in serious self-injuries from various causes. Epilepsy has been also associated with a sudden death rate that is at least 10 times of the same rate for the general population (sudden unexplained death in epilepsy - SUDEP). Therefore, the importance and usefulness of seizure prediction cannot be overstated, as it would increase epileptic patients’ autonomy, drastically reduce accidents and self-injuries related to epileptic seizures and, as a whole, improve the patients’ quality of life dramatically. Upon successful completion, we envision using these algorithms in compact, wearable predictor systems that will take full advantage of the state-of-the-art in personalized monitoring systems, further improving the quality of life of people with epilepsy.

General Objectives

The general objectives of the present project are in accordance with the objectives of the program and the specific action (ΥΓΕΙΑ/ΔΥΓΕΙΑ), as it concerns a neurological disorder - epilepsy - that affects millions of people worldwide (second only to stroke). Epilepsy greatly compromises quality of life, both physically and psychologically, and it increases mortality rate. Βy developing novel, improved strategies for predicting epileptic seizures, the proposed approach has the potential of elucidating some of the implicated mechanisms and dramatically improving the quality of life of patients with epilepsy. The results could be also used in personalized monitoring systems, which are becoming more portable and discreet, improving quality of life and self-autonomy further. State-of-the art signal processing techniques will be used in order to achieve the stated goals, and as a result the researchers to be employed will acquire skills that will enable them to compete in research on an international level. The acquired expertise and results will be also important for the research and technological development of Cyprus, as Bioengineering is a key priority area. Finally, the acquisition of a wealth of data from PA1 will lead to the availability of a large database of epilepsy data in Cyprus, which will be very important in driving relevant future studies. Other objectives include the publication of the research results in high-impact refereed journals.

Scientific and Technological Objectives

In the context of the present project we aim to: (i) collect long-term video-EEG and ECG data simultaneously in patients with epilepsy (the anticipated number is around 50 for the project duration) (ii) record the occurrence of subjective prodromal symptoms and identify their neural/cardiac correlates (iii) evaluate the performance of different EEG prediction algorithms, placing emphasis on multivariate, patient-specific approaches. We will also consider novel and emerging concepts in EEG signal analysis, such as the assessment of Granger causality with multivariate autoregressive linear and nonlinear models, mutual information and nonlinear “black-box” models, in order to identify changes in functional connectivity during the pre-ictal phase (4) extract complementary information from simultaneous ECG measurements (5) design appropriate data fusion schemes that will utilize the aforementioned multimodal information efficiently and (6) extensively evaluate the performance of the multimodalalgorithms in a rigorous statistical manner, by assessing both their specificity and sensitivity. In this context, we will place emphasis on using well-suited methods for assessing statistical significance, such as surrogate data. The availability of long recordings of experimental data for each subject is particularly important to this end.

Added Value and Benefit

Epilepsy is a widespread disease - up to 5% of people in the world may have at least one seizure in their lives ( - that has significant personal, social and economic consequences. These include profound physical and psychological impact on the patients, which in turn have a profound social and economical impact, affecting a significant portion of the population and especially sensitive population age groups, the young and the aged. Based on the age-specific incidence rates in European studies, the estimated number of new cases per year amongst European children and adolescents is 130 000 (incidence rate 70 per 100 000), 96 000 in adults 20–64 years (30 per 100 000) and 85 000 in the elderly 65 years and older (100 per 100 000). It is estimated that around 7,000-8,000 people with epilepsy exist in Cyprus, of which about 30% are drug-resistant.

Epilepsy is also associated with an increased risk of mortality. Death may be related to an underlying brain disease, such as a tumour or infection, seizures in dangerous circumstances, leading to life-threatening injuries. Epilepsy-related deaths in young adults in the UK, for example, are 3 times higher than standard age-related mortality rates. Very importantly, people with epilepsy are at least 10 times more probable to suffer sudden death (sudden unexplained death in epilepsy – SUDEP) compared to the general population,with probable causes including cardiac or respiratory arrest. Controlling seizures is considered to be the most important preventive measure against SUDEP; hence, seizure prediction would contribute in this direction. From the social point of view, people with epilepsy experience problems in the areas of personal relationships and even sometimes legislation. For example, people with epilepsy were prevented from marrying in the United Kingdom or the U until recently, while they can only drive if they have been free of seizures for a year. In the 25 European Union member countries, Iceland, Norway, and Switzerland the estimated total cost of the disease in Europe was €15.5 billion in 2004, indirect costs being the single most dominant cost category (€8.6 billion).

The socioeconomic burdens of epilepsy are obviousfrom the abovementioned facts. Therefore, successful completion of the proposed project will not only lead to the production of new scientific knowledge, but also to a vast improvement in the quality of life of the patients as well as a decrease in the related social and economic costs.Furthermore, the scientific outcomes of the project could be further used in portable, personalized monitoring systems, i.e., portable EEG and ECG, which will take advantage of the recent advances in body sensor network and mobile communications technology. This would further improve the quality of life by decreasing the frequency of hospital admissions (by self-managing the seizures where possible and avoiding accidents and self injuries).