Background/Aims: This year marks the 100th anniversary of the first malaria fever treatment (MFT) given to patients with general paralysis of the insane (GPI) by the Austrian psychiatrist and later Nobel laureate, Julius Wagner-Jauregg. In 1921 Wagner-Jauregg reported an impressive therapeutic success of MFT and it became the standard treatment for GPI worldwide. In this study, MFT practice in the Dutch Vincent van Gogh psychiatric hospital in GPI patients who had been admitted in the period 1924-1954 is explored. Methods: To identify patients with GPI, cause-of-death statistics was used. Data on MFT were retrieved from annual hospital reports and individual patient records. Results: Data on MFT were mentioned in the records of 43 out of 105 GPI patients. MFT was practiced in a wide range of patients with GPI, including those with disease duration of more than 1 year, up to 70 years of age, and those with a broad array of symptoms and comorbidities, such as (syphilitic) cardiac disease. Inoculation with malaria was done by patient-to-patient transmission of infected blood. Conclusions: MFT practice and mortality rates in MFT-treated patients correspond to similar findings worldwide. MFT was well tolerated and MFT-treated patients had a significantly longer survival.

General paralysis of the insane (GPI) or dementia paralytica was once a fatal complication of syphilitic infection and a major reason for psychiatric hospitalization. Nowadays, physicians consider GPI to be exceptional. It should be noted, however, that syphilis re-emerged worldwide at the turn of the 20th to 21st century and a revival of GPI can, therefore, be expected. Advanced diagnosis is crucial in that treatment in the early, inflammatory phase is warranted before irreversible tissue damage occurs. Therefore, a renewed clinical awareness of the broad spectrum of psychiatric and neurologic signs and symptoms of GPI is needed. In this historical cohort study, comprising 105 patients with GPI admitted to the Dutch Vincent van Gogh Psychiatric Hospital in the period 1924-1954, the clinical presentation of this invalidating disorder is investigated and described in detail.

Objectives: General Paralysis of the Insane (GPI), or Dementia Paralytica, was once a fatal complication of syphilitic infection and a major reason for psychiatric hospitalisation. Syphilis re-emerged worldwide at the turn of the 20th to 21st century, and, considering the incubation period of 10-30 years, a revival of GPI may be expected within the next one or two decades. Early diagnosis and treatment improve prognosis and, therefore, a renewed clinical awareness of signs and symptoms of GPI is needed. Aims: This historical cohort study aims to investigate the clinical presentation of GPI in patients deceased at the Vincent van Gogh psychiatric hospital in Venray, the Netherlands, in the period 1924-1954. Methods: Annual hospital reports and individual patient's records were used for identification of patients with an established diagnosis of GPI, usually based on a combination of clinical data and positive syphilis serology. Results: Individual clinical records of 105 patients (91 men; 14 women) with GPI were available for evaluation. Median age for men (50.4 years; range 31.5 to 82.1 years) was higher than for women (43.1 years; range 34.4 to 58.4 years): p = 0.01. Most patients completed elementary school only and belonged to the lower working class. Lack of judgement and insight, hyperactivity, and confusion were the most frequently documented psychiatric symptoms, whereas speech disorders, pupillary abnormalities, micturition disorders, dementia, and cranial nerve involvement were the most frequently reported neurological symptoms. Conclusions: The clinical presentation of GPI displays a wide range of cognitive, affective, psychotic and focal neurological symptoms.