Epilepsy

   Called "the falling sickness," epilepsy was once seen primarily as a psychiatric illness, one of William Cullen’s "neuroses." Seizure patients who also had psychiatric symptoms often landed in asylums and were included in psychiatric textbooks. Epilepsy as a so-called neuropsychiatric condition thus has a place in the history of psychiatry, even though in a strict sense epilepsy is defined as seizures associated with sudden electrical discharges of the brain (thus implicitly placing it in the province of neurology because neurology has inherited all behavioral disorders—such as Parkinson’s disease—associated with specific brain lesions). Interestingly, virtually all antiepileptic medications turn out to have significant uses in psychiatry. Although many of the symptoms of epilepsy had been well characterized since the Ancients, only in the nineteenth century did the current classification evolve that distinguishes between primary generalized (often idiopathic) seizures and partial seizures (often associated with a specific lesion).

   In his 1815 article "On Epilepsy" ("De l’épilepsie"), Étienne Esquirol said that in the hospitals they were now differentiating between "le grand et le petit mal," in other words, in today’s parlance, between tonic-clonic convulsions (grand mal seizures) and absence seizures (petit mal seizures) (Esquirol, I, p. 281). Then, in 1824, Esquirol’s student Louis-Florentin Calmeil (1798–1895), in his doctoral dissertation On Epilepsy (De l’épilepsie), supplied "absence" seizures as a synonym for petit mal. Calmeil also introduced into medicine the term "état de mal," translated into English as "status epilepticus," a series of uninterrupted seizures having a poor outcome. During the years, grand and petit mal have both been considered "true" epilepsy because the cause was unknown and at autopsy the brain seemed to be normal.

   A major concept to emerge in the nineteenth century was "focal" seizures: symptoms beginning on one side of the body caused by a specific brain lesion. Codifying focal into a larger theory of epilepsy was the work of English neurologist John Hughlings Jackson (1835–1911), who from 1862 to 1906 studied convulsive phenomena at the National Hospital for the Relief and Cure of the Paralysed and the Epileptic in Queen Square in London (later called the National Hospital for Nervous Diseases). In the 1860s, Jackson worked out the notion of unilateral epilepsy: partial, or focal, fits originating from a lesion in the basal ganglia or cerebral cortex and then tracking to other muscle groups. This later became known as "Jacksonian" epilepsy. In Jackson’s concept of the hierarchy of layers in the central nervous system, fits associated with the brainstem ("pontobulbar") originated at the lowest level; "epileptiform" fits, later called Jacksonian, originated from the middle level; and "epilepsy" as such came from the highest level, or cerebral cortex. In an article in 1875, reprinted in his Selected Writings, Jackson revived previous medical thinking about sensory "dreamy" state seizures, later called temporal lobe epilepsy, or psychomotor epilepsy. Jackson’s work was spread through a myriad of dispersed articles, and an excellent guide to it is the magisterial study of medical historian Owsei Temkin, The Falling Sickness (1945; second enlarged edition, 1971). (See also Positive vs. Negative Symptoms.) The investigation of epilepsy was placed on a modern footing with the development of electroencephalography by Hans Berger in the 1920s.

   As for the treatment of epilepsy, London physician Charles Locock (1799–1875) proposed the use of bromide salts at a meeting in 1857 of the Royal Medical and Chirurgical Society. Of note as well, the bromide salts also had some efficacy as sedatives in the treatment of what was then called "hysteria." The landmark drug for the treatment of convulsions was the barbiturate phenobarbital (Luminal), which was patented by the Bayer company in 1911 and launched the following year. (See BARBITURATES.) Phenobarbital was also the classic long-acting sedative drug of the prebenzodiazepine period. In 1938, at the instigation of Boston neurologist and neurosurgeon Tracy Jackson Putnam (1894–1975), the Parke-Davis company launched the nonsedating anticonvulsant phenytoin (Dilantin), which later showed efficacy in the treatment of mania.

   In the 1990s and after, a number of anticonvulsant drugs started to be indicated as "mood stabilizers" in mania, notably valproic acid, first synthesized in 1882. Valproic acid’s antiepileptic properties were discovered serendipitously in 1963, and shortly thereafter the sodium salt of the drug, called sodium valproate (Depakine) was marketed as an anticonvulsant and antimanic; another formulation, semi-sodium valproate, called sodium divalproex (Depakote), was introduced to the United States in 1983 as effective in epilepsy; it was later indicated for mania, and in 1997 was approved by the U.S. Food and Drug Administration for migraine headache. Epilepsy thus remains integrated with psychiatry at the level of pharmacotherapy. It has never been convincingly demonstrated that epilepsy itself is a source of psychiatric symptoms or represents a distinctive kind of personality, contrary to the conventional wisdom of the nineteenth century.