(The first use of induced seizures to treat a mental disorder was 70 years ago. In a series of columns, the implications of this anniversary will be explored--Ed.)
On Jan. 23, 1934, the Hungarian neuropathologist Ladislas Meduna, M.D., injected camphor-in-oil in a catatonic patient, seeking to relieve schizophrenia. The patient seized and survived. Following the model of fever therapy for neurosyphilis--a treatment that was then in high regard and wide demand--Meduna repeated the injections at three- to four-day intervals. After the fifth injection, the patient became alert and talkative, and, after two additional seizures, he was no longer psychotic or catatonic. Despite an illness of four years duration, he returned to his home and to work; at five-year follow-up he remained well. Meduna repeated the experiment in nine additional patients, reporting success in seven in his first report in 1935.
Convulsive therapy for schizophrenia was rapidly adopted throughout the world. Its benefits in depression and mania were quickly recognized as it became the main treatment of the severe psychiatrically ill. For a while it was replaced by medications that were deemed as effective, less expensive and more easily prescribed, but when the limits of the medications were realized, interest in convulsive therapy re-awakened.
The bizarre nature of inducing a seizure encouraged its stigmatization. Electroconvulsive therapy became the target of a vocal antipsychiatry movement that obtained legislative restrictions to its use. Our lack of understanding of a mechanism by which grand mal epileptic seizures could improve disordered behavior led to the belief that convulsive therapy had no scientific basis, justifying its disregard.
How did Meduna develop the notion that seizures might relieve a lifelong mental illness? How did he overcome the widespread fear of epileptic seizures so as to induce them in a human being?
Meduna was born in 1896 and, after a rigorous Catholic education, began his medical studies in Budapest, Hungary, in 1914. Anticipating a call to military service, he volunteered for the artillery, serving in the Italian front from 1915 until the war's end. After delays occasioned by postwar Communist insurrections, Meduna completed his medical studies in 1921. A year later, he was appointed to the research faculty at the Hungarian Interacademic Institute for Brain Research in Budapest.
His first report describing the structure and development of the pineal gland was followed by reports on the neuropathology of avitaminosis, lead poisoning, and the structure and concentration of microglia. In 1927, he moved to the Psychiatric Institute where he cared for hospitalized psychotic patients and learned a new language of psychopathology. Meduna described a heartbreaking work schedule with little possibility to offer relief for his patients.
Meduna had reported that an increased glial reaction followed head trauma. An effusive glial increase was also seen in patients with epilepsy, but no such reaction was measured in those with schizophrenia. Was the glial increase a response to the seizure or secondary to aging and systemic illness? Meduna identified six patients with focal seizures in whom the brain focus was surgically excised. These tissues showed an increased proliferation of glia. Meduna hypothesized, "There was almost complete abolition of the function of the glia cells in schizophrenia and an increased proliferation in epilepsy."
He screened the literature for evidence of similar antagonism. When schizophrenia was complicated by epilepsy, the epileptic attacks either became infrequent or disappeared. While 1% of patients with epilepsy admitted to the state hospital improved, 16.5% of those who developed acute psychoses remitted. Seeking to test whether the disorders could influence one another, Professor Nyir", a fellow Hungarian, had injected the blood of patients with schizophrenia into those with epilepsy, to no avail. In another report of 6,000 patients with schizophrenia, only 20 had epileptic attacks before or during their illness. In two clinical reports, the psychosis of patients with schizophrenia cleared when they developed epileptic attacks.