Julius Wagner-Jauregg (1857-1940): Introducing fever therapy in the treatment of neurosyphilis.

For centuries, heat has been used in various ways for the cure of mental diseases. Hippocrates noted that malarial fever could have a calming effect in epileptics. Centuries later, Galen described a case of melancholy cured as a result of an attack of quartan fever. In 19th century, the eminent French psychiatrist Philippe Pinel, in his treatise on insanity referred to the beneficial effect of fever. An opinion expressed few years later by his pupil Jean-Étienne Dominique Esquirol in his treatise entitled Des maladies mentales considérées sous les rapports médical, hygiénique et médico-légal. However, in 1917, the Austrian neuro-psychiatrist Julius Wagner Jauregg pointed out the therapeutic value of malaria inoculation in the treatment of dementia paralytica. In 1927, Wagner Jauregg received for this work the Nobel Prize in Medicine, being actually the first psychiatrist to win the Nobel Prize. He studied medicine at the University of Vienna and received his doctorate in 1880. In 1889, he was appointed Professor of Psychiatry and Director of the Graz's Psychiatric Clinic, a position that he held until 1928. Working in the asylum, Wagner Jauregg noted that insane patients with general paralysis occasionally became sane after some febrile episode. After experimenting with several artificial methods (streptococci, tuberculin) to induce fever, he concluded that malaria was the most satisfactory. Actually, malaria infection was an acceptable risk for the patients, as quinine would be administered as soon as syphilis was cured. In 1917, he reported the first favorable results of his study. Patients were inoculated via intravenous injections with malaria. Some physicians were starting the administration of anti-syphilitic treatment (bismuth, salvarsan and later penicillin) after 10-12 febrile paroxysms, while others initiated the regimen the first febrile-free day after 8 malarial paroxysms. The therapeutic regimen was completed with the administration of quinine sulfate to terminate the malaria infection. It is worth mentioning that the above treatment was followed in hospital under strict monitoring of patients' vital signs and regular laboratory tests. In the following years of his discovery, artificial fever was induced by any one of the following methods: the introduction into the patient of a parasitic disease; the injection of a foreign protein; injections of chemical substances such as sulphur; electrical means such as the administration of diathermy or radiotherapy, or placing the patient in an electromagnetic field; and simple immersion of the individual in a hot bath, or placing him in a heat cabinet. Wagner Jauregg's therapy was highly admired and was used on neurosyphilis cases well onto the 1950's. However, with the introduction of penicillin in syphilis' treatment, fever therapy effectively ended. Wagner Jauregg's study led to all the methods of stress therapy used in psychiatry, as electric shock, and insulin.