Epilepsy is a neurological disorder that affects 1-2% of the population, and is characterized by recurrent spontaneous seizures and corresponding abnormalities in the electroencephalogram (EEG). The nature of the seizures may vary greatly, from short spells of freezing and staring in childhood absence epilepsy, to dramatic tonic-clonic seizures in adults, involving falling to the ground and jerking of the limbs. Not only the type of seizures differs greatly between subjects, but also the seizure frequency (from several seizures per day to e.g. one per year).

Cortical hyperexcitability

Epileptic seizures are caused by a problem in the regulation of brain activity; more specifically, an imbalance between brain excitation and inhibition. During a seizure, the brain cortex becomes hyperactive in such a way that normal information processing is temporally disrupted. The nature of the seizure depends on what part of the brain is involved (which area of the brain, and how big it is).

Treatments and risks

Epilepsy may be treated using anti-epileptic drugs (AEDs), which restore the balance between brain excitation and inhibition (i.e. away from hyperexcitability). In doing so, they may suppress overall brain activity and thus in turn actually cause cognitive problems. Similarly, epileptic seizures (and ongoing abnormal brain activity in between seizures) may compromise brain function as well. This means that in treating epilepsy using AEDs, in close consultation between doctor and patient, a careful trade-off should be made between sufficient seizure suppression on the one hand, and preservation of brain function and cognition on the other hand.

Not every patient achieves sufficient seizure freedom on AEDs. Chances for treatment success actually drop with every next AED that is tried, and are virtually zero already for the 4th drug. Patients for whom drug treatment is unsuccessful may be eligible for epilepsy surgery, in which the part of the brain that triggers the seizures (the so-called epileptic focus) is removed. This procedure is only possible if the epileptic focus can be well identified (e.g. well visible on MR scans), and always holds a risk for damaging surrounding brain tissue, thus compromising brain function.

Cognitive comorbidity

Taken together, although maybe not broadly known, cognitive problems are an important aspect of epilepsy and concern both the disease itself, as well as its treatment. It is estimated that about half the epilepsy patients suffer from cognitive problems to a certain extent, and this accounts for about half the disease burden. A specific form of cognitive impairment which receives special attention within the Neu3CA program, is accelerated cognitive aging.

The Neu3ca brain research program aims to better understand how the cognitive problems of epilepsy are caused and how they may be treated or prevented. We think it is important to gain awareness of this less well known aspect of epilepsy, since cognitive well-being is essential for societal and job participation as well as for quality-of-life.