Introduction: The causes of epilepsy

Epilepsy is a symptom of cerebral irritability, with a huge variety of possible underlying causes. Epilepsy with onset in children and adolescents is predominantly genetically determined, whereas onset of epilepsy in adults results mainly from acquired structural causes. Yet even in patients for whom there is a clear structural cause—traumatic brain injury being the obvious example—there is clear evidence of genetic influence on their predisposition to epilepsy. This supplement reports on ‘‘The Causes of Epilepsy’’ Teaching Course at the 10th European Congress on Epileptology, London, United Kingdom, October 2012. The course provided a unique opportunity for an audience primarily of epileptologists to hear world authorities present and discuss their understanding of the causes of epilepsy in adults and children. The priority in assessing a patient with a suspicion or label of epilepsy is to establish that indeed it is epilepsy. Even in 2012, this is not straightforward and relies heavily upon the clinical history and witness account. Investigations, such as interictal electroencephalography (EEG) and brain magnetic resonance imaging (MRI), although important, are often inadequate alone to establish a clear diagnosis. Having established epilepsy, the clinician must try to identify its cause, since this informs both the treatment and prognosis. The causes of epilepsy differ between children and adults, and between the intellectually normal and the learning disabled. The most common epilepsy in childhood has the best prognosis—the benign childhood focal epilepsies (Guerrini & Pellacani, 2012)—although even here there are overlaps with developmental dyslexia and subtle indications of structural changes on detailed imaging. The reflex epilepsies (Kasteleijn-Nolst Trenit , 2012) are a genetically determined group of epilepsies for which neurophysiologic investigations are unusually valuable and treatment responsiveness is the rule. Children presenting first with simple febrile seizures (Cross, 2012) have a mostly benign condition, with little increased risk of subsequent epilepsy. However, infants carrying the SCN1A gene may present first with a febrile seizure but may rapidly progress to a treatment-resistant epilepsy syndrome with learning disability—the Dravet syndrome. The full phenotype of the SCN1A disorders continues to broaden. Children with so-called ‘‘catastrophic’’ epilepsies (Covanis, 2012) present a major challenge to the pediatric epileptologist, given the treatment-resistant nature of their seizures and the overall poor prognosis. Too often still, seizures progress to life-threatening status epilepticus, the need for intensive care treatments, and the major challenge of pharmacologically resistant continuous epilepsy (Trinka et al., 2012). The most important structural explanation for adultonset epilepsy is, of course, hippocampal sclerosis (Malmgren & Thom, 2012), forming the basis of the syndrome of medial temporal lobe epilepsy. Increasingly sophisticated and powerful MRI enables hippocampal sclerosis to be identified—and potentially cured with surgery—in an increasing number of patients worldwide. Other structural causes offering potential surgical cure are cortical dysplasia (Hauptman & Mathern, 2012), although the surgical outcomes are consistently less impressive than for hippocampal sclerosis or arteriovenous malformations (Al-Shahi Salman, 2012), where the surgical intervention is aimed as much at preventing bleeding or rebleeding as it is to treat the epilepsy. Head injury is a common and preventable cause of epilepsy (Christensen, 2012), although the holy grail of a formula that predicts the precise likelihood of epilepsy following an injury using various characteristics continues to elude us (mainly because of variations in genetic susceptibility). The close link of alcohol and drugs to head injury forms another strand to this story. Alcohol itself may provoke seizures, particularly through its abrupt withdrawal (Leach et al., 2012). Illicit drugs—notwithstanding that illegal substances are not subjected to rigorous clinical trial—must also play a role in epilepsy. There are many important medical causes of seizures, with an increasing focus currently on the immunologic causes of epilepsy (Nabbout, 2012). The identification of a new treatable and preventable group of epilepsies is remarkable, and has changed the diagnostic landscape. How Address correspondence to Professor Phil E. M. Smith, The Alan Richens Epilepsy Unit, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, U.K. E-mail: smithpe@cf.ac. uk