The Borderland of Epilepsy: Clinical and Molecular Features of Phenomena That Mimic Epileptic Seizures

Paroxysmal losses of consciousness and other episodic neurological symptoms have many causes. Distinguishing epileptic from non-epileptic disorders is fundamental to diagnosis, but even this basic dichotomy is often challenging and is certainly not new. In 1907, the British neurologist William Richard Gowers published his book The Border-land of Epilepsy in which he discussed paroxysmal conditions "in the border-land of epilepsy-near it, but not of it" and their clinical differentiation from epilepsy itself. Now, a century later, we revisit the epilepsy borderland, focusing on syncope, migraine, vertigo, parasomnias, and some rarer paroxysmal disorders. For each condition, we review the clinical distinction from epileptic seizures. We then integrate current understanding of the molecular pathophysiology of these disorders into this clinical framework. This analysis shows that, although the clinical manifestations of paroxysmal disorders are highly heterogeneous, striking similarities in molecular pathophysiology are seen among many epileptic and non-epileptic paroxysmal phenomena.