Hypothalamic hamartoma and epilepsy: the pathway of discovery.

Pathological laughter has been recognized as an epileptic manifestation since the dawn of modern neurology, and is attributed to Trousseau. The association of laughing (gelastic) seizures with hypothalamic hamartoma was clearly described nearly 50 years ago [1], although the probable first case, described as an ‘astrocytoma’ was published in 1938 [1, 2]. In 1967, Gascon and Lombroso analyzed the issue of gelastic seizures in more detail, and suggested the importance of diencephalic lesions in many cases [3]. The lesions were often not identified on pneumoencephalography and CT scanning, in part because previously there was no high index of suspicion for the presence of such lesions in patients with laughing attacks. However, an important French series documented laughing attacks, with hypothalamic hamartomas, recognized largely by CT scan [4, 5], beginning the more detailed epileptological description of the syndrome. The advent of magnetic resonance imaging greatly facilitated identification of the lesions and resulted in more widespread recognition, clinical characterization and scientific enquiry [6]. Many patients did not have precocious puberty, considered a hallmark of these lesions, but presented with intractable epilepsy. The early onset of gelastic seizures, often in the neonatal period, was then recognized and the appearance, later in the first decade, of generalized spike and wave, tonic attacks, and drop attacks, suggested the presence of a secondary, generalized epileptic process. This emerged as a major feature associated with, and probably responsible for the cognitive and behavioural deterioration, important in the catastrophic epilepsy which some of the children developed [6].