Malaria therapy in Spain: 100 years after its introduction as a treatment for the general paralysis of the insane.

This article addresses the implementation of malaria fever therapy in Spain. Neuropsychiatrist Rodríguez-Lafora first used it in 1924, but Vallejo-Nágera was the main advocate for the technique. He had learned the method from Wagner von Jauregg himself, and he worked in the Military Psychiatric Clinic and the San José Mental Hospital, both in Ciempozuelos (Madrid). Vallejo-Nágera worked with the parasitologist Zozaya, who had travelled to England with a Rockefeller Foundation grant in order to learn from British malariologist, Sydney Price James. This article details the results of the uneven implementation of this treatment in Spanish psychiatric institutions. Although syphilologists and internists used fever therapy for the treatment of general paralysis of the insane, they were much less enthusiastic than psychiatrists.

Multiple cerebral syphilitic gummas mimicking brain tumor in a non-HIV-infected patient: A case report.

We present a unique case of symptomatic early neurosyphilis in a non-HIV-infected patient. A 47-year-old man with a history of diabetes mellitus presented with generalized seizures. He did not manifest any neurological deficits. At first, multiple brain tumors were suspected based on findings from magnetic resonance imaging of the brain. However, serological and cerebrospinal fluid tests for syphilis yielded positive results, and the masses were reduced using amoxicillin. Multiple cerebral syphilitic gummas were therefore diagnosed. High-dose penicillin therapy was initiated and syphilitic gummas disappeared after five months. Treponema pallidum could invade the central nervous system at an early phase, and sometimes may be difficult to distinguish from malignant brain tumor. If intracranial lesions are identified in a syphilis-infected patient, cerebral syphilitic gumma should be considered as a differential diagnosis.

Síndrome extrapiramidal con corea generalizada como forma de presentación atípica de leucoencefalopatía multifocal progresiva / Extrapyramidal syndrome with generalized chorea as an atypical presentation of progressive multifocal leukoencephalopathy

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Malaria Fever Therapy for General Paralysis of the Insane: A Historical Cohort Study.

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.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

BACKGROUND: Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. METHODOLOGY/PRINCIPAL FINDINGS: Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. CONCLUSIONS/SIGNIFICANCE: Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in good physical condition after withdrawing anti-neurosyphilis regimen. We did not see an exacerbation of neutropenia in patients with the readministration of benzylpenicillin.

Pyrotherapy for the Treatment of Psychosis in the 21st Century: A Case Report and Literature Review.

The concept that fevers can improve the condition of patients with certain medical and psychiatric diseases dates back to Hippocrates. Over the centuries, it has been observed that fevers and infectious agents have been beneficial for a broad spectrum of diseases, including neurologic conditions such as epilepsy and psychiatric illnesses including melancholy and psychosis. Interest in the concept of fever as a treatment for disease, termed pyrotherapy or pyretotherapy, peaked in the late 1800s and early 1900s thanks to the Nobel Prize winning work of Julius Wagner-Jauregg for his studies with malaria therapy for general paralysis of the insane, now more commonly referred to as neurosyphilis. The use of inoculations of infectious agents for their fever-inducing effects in the treatment of neurosyphilis quickly spread throughout the world, and, by the 1920s, it was considered by many to be the treatment of choice for neurosyphilis as well as other psychotic disorders. However, with the discovery of penicillin for the treatment of syphilis, which coincided with the advent of convulsion-oriented practices including electroconvulsive therapy and insulin coma for the treatment of psychotic disorders, pyrotherapy soon lost favor among psychiatrists and, since the 1950s, it has largely been overlooked by the scientific community. In this article, the authors provide a brief literature review of the history of pyrotherapy and present a case report of a woman with schizoaffective disorder and severe psychotic symptoms who experienced a remarkable resolution of psychotic symptoms following an episode of bacteremia with high fever.

Penicillin Encephalopathy: An Unlikely Adversary in the Treatment of Neurosyphilis--Case Report and Review of the Literature.

UNLABELLED: Penicillin encephalopathy is a rare, potentially reversible phenomenon of drug-induced neurotoxicity. CASE: A 65-year-old female with a history of HIV was admitted with a three-day history of worsening headache, confusion, and lethargy. On examination she was awake but confused. Cerebrospinal fluid (CSF) and serum venereal disease research laboratory (VDRL) test returned positive and the patient was started on intravenous penicillin G with probenecid. On the second day of therapy, she developed myoclonic jerking, consistent with penicillin neurotoxicity. Repeat labs also showed new onset renal failure. Penicillin and probenecid therapy were stopped with a resolution of symptoms. Subsequently, therapy without probenecid was reinstituted uneventfully. DISCUSSION: Herein, we describe a female who developed penicillin neurotoxicity after initiation of intravenous penicillin therapy with probenecid for neurosyphilis. It is important that penicillin-induced toxicity be considered if characteristic myoclonic movements accompany encephalopathy. The presence of coexistent renal compromise should heighten the vigilance of clinicians.

[Treatment of syphilis with malaria or heat]. / Behandeling van syfilis met malaria of warmte.

Until the end of the Second World War, syphilis was a common sexually transmitted infection. This stigmatising infectious disease caused mental decline, paralysis and eventually death. The history of syphilis was given public attention because of 'malaria therapy', which had been applied from the First World War onwards in patients with paralytic dementia. In 1917, the Austrian physician Julius Wagner-Jauregg (1857-1940) induced fever in these patients by infecting them with malaria parasites; in 1927, he received the Nobel Prize for his discovery of the healing properties of malarial fever. One source, not cited anywhere, is an interview that the American bacteriologist and science writer/medical journalist Paul de Kruif conducted with Wagner-Jauregg in 1930. The reporting of this meeting, and De Kruif's later involvement in the mechanical heat treatment of patients with syphilis, form the inspiration for this article. When penicillin became available, both treatments became obsolete.

Laryngotracheal mucormycosis: Report of a case.

Airway mucormycosis is a deadly opportunistic infection that affects immunocompromised persons, particularly diabetics and those undergoing chemotherapy. Although it is typically a pulmonary or sinonasal infection, mucormycosis can affect the larynx and trachea, with devastating results. We report the case of a 46-year-old man with human immunodeficiency virus infection, hepatitis C infection, neurosyphilis, and recently diagnosed Burkitt lymphoma who presented with dysphonia and stridor after receiving one dose of intrathecal chemotherapy. Flexible laryngoscopy detected the presence of fibrinous material that was obstructing nearly the entire glottis. Surgical debridement revealed a firm mucosal attachment; there was little bleeding when it was removed. After debridement, the patient's dyspnea improved only to recur 2 days later. After an awake tracheotomy, laryngoscopy and bronchoscopy identified necrosis extending from the supraglottic area to the carina tracheae. Biopsies demonstrated hyphal architecture consistent with mucormycosis. Despite continued debridements, the fibrinous material reaccumulated. The patient was placed in hospice care; his airway remained patent, but he died from other causes several weeks after presentation. The management of airway mucormycosis is challenging and complex. Fungal airway infections should be considered in the differential diagnosis of an immunosuppressed patient who presents with dyspnea, dysphonia, and vocal fold immobility. Timely diagnosis and management are critical for a successful outcome, although the prognosis is poor if the infection is widespread, even with the best of efforts.

Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953.

Physicians deliberately inoculated marginalized patients with malaria, using them as reservoirs to facilitate malarial fever therapy for syphilitic patients. The history presents ethical questions in an evolving historical context.

Research by Psychiatrists of Chosun Chongdokbu Hospital and Keijo Imperial University in Korea during Japanese Colonial Rule / 신경정신의학

Eighty-three of 114 original articles and abstracts of research published by neuropsychiatrists of Chosun Chongdokbu Hospital (the Japanese colonial government hospital in Korea) and Keijo (Seoul) Imperial University Hospital during the Japanese colonial period (1910-1945) in journals including Shinkeigaku-zassi (Neurologia), Seishin-shinkei-gaku zassi (Psychiatria Et Neurologia Japonica), and The Journal of Chosun (Korea) Medical Association were reviewed. Most articles were on clinical research based on descriptive and biological psychiatry while only 4 articles were on dynamic psychiatry, probably because Japanese pioneers in psychiatry had introduced German psychiatry into Japan during the 1880s. The first paper was written by Dr. Shim Ho-sub. Professor Kubo of Keijo (Seoul) Imperial University published most articles, followed by Dr. Hikari, Dr. Hattori, and Dr. Sugihara. There were more articles on symptomatic psychosis and morphine addiction, followed by general paralysis, schizophrenia, neurological diseases, narcolepsy, epilepsy, and neurasthenia. The meaningful articles even for today were comparative studies between Japanese and Koreans and articles on opioid use disorder in Korea. Authors reported a markedly lower rate of psychotic inpatients in the population of Koreans compared with Japanese. Japanese researchers argued that, because of simpleness in social life in Korea and less violence or excitement in symptoms, Korean mental patients could be cared for by family or members of the community, or be treated by shamanism rather than bringing them to a public mental hospital, and poverty also prohibited hospital care. Finding of higher ratio of schizophrenia to manic-depressive psychosis among Koreans than Japanese was discussed in relation to delayed cultural development of Korea compared to Japan. In addition, traditional customs prohibiting marriage between relatives in Korea was related to low prevalence of manic-depressive psychosis, local endemic malaria was related to low prevalence of general paresis, and poor general hygiene was related to high prevalence of epilepsy. Unclear (undifferentiated) form of psychotic symptoms including hallucination and delusion was reported in more Koreans than Japanese. Also Korean patients showed a more atypical form in diagnosis. Authors added that they had found no culture-specific mental illness in Korea. However, no Korean psychiatrists were included as author in such comparative studies. Comparative studies on constitution between Koreans and Japanese mental patients and prisoners were also unique. However, no Korean psychiatrists participated in such comparative studies. In studies on morphine addiction in Koreans, Japanese researchers argued that such studies were necessary to prevent introduction of morphine-related criminal phenomena to Japan. Meanwhile, Dr. Kubo had left a notion on adaptation problems of Japanese living in the foreign country, Korea. Nevertheless he reported nothing about psychosocial aspects of mental illness in relation to political, cultural, and economic difficulties Koreans were experiencing under the colonial rule of Japan. These general trends of studies based on German biological and descriptive psychiatry and policies of colonial government to isolate "dangerous" mental patients in hospital appeared to reflect colonial or ethnopsychiatry of those days. These policy and research trends seem to have worsened stigma attached to mental disorders. Japanese tradition of psychiatric research was discontinued by return home of Japanese scholars with the end of WWII and colonial rule.

Profile of patients treated with malariotherapy in a psychiatric hospital in Porto Alegre, Brazil: a historical note / Perfil dos pacientes tratados com malarioterapia em hospital psiquiátrico de Porto Alegre: nota histórica

Introduction: Malariotherapy was a treatment to cure neurosyphilis developed in 1917 by Wagner-Jauregg, by inoculating blood infected with malaria in patients with neurosyphilis. The patient had febrile episodes that often cured him of the syphilitic infection. This treatment won the Nobel Prize in Medicine in 1927 and it was introduced in Hospital Psiquiátrico São Pedro (HPSP) in 1929. Methods: This is a descriptive retrospective cross-sectional study with collection of historical secondary data. Data were collected from a sample of 19 medical records of patients treated with malariotherapy in HPSP, in 1929 and 1930. Results: Most patients were white men aged from 25 to 40 years. The mean length of hospital stay was 1.4 year and the outcomes at this early application of malariotherapy were mostly negative (63.2% died). Discussion: The 19 cases evaluated in this study refer to the first year of application of malariotherapy in HPSP. The statistics available on the total number of dead and cured people over the 10 years this therapy was deployed suggest that the outcomes were better in the subsequent years, possibly due to improvement of technique. As a consequence of this innovative research, which had as its principle reorganizing the central nervous system by using the seizure triggered by malaria fever, other forms of shock therapies were developed, such as insulin therapy, cardiazol shock therapy, and electroconvulsive therapy (AU)

Introdução: A malarioterapia foi um tratamento para a cura da neurossífilis desenvolvido em 1917 por Wagner-Jauregg, através da inoculação de sangue contaminado pela malária em pacientes com neurossífilis. O paciente apresentava episódios febris que, muitas vezes, curavam-no da infecção sifilítica. Esse tratamento recebeu o Prêmio Nobel de Medicina em 1927 e foi introduzido no Hospital Psiquiátrico São Pedro (HPSP) em 1929. Métodos: Este é um estudo transversal retrospectivo descritivo com coleta de dados secundários históricos. Foram coletados dados de uma amostra de 19 prontuários médicos de pacientes tratados com malarioterapia no HPSP, em 1929 e 1930. Resultados: A maioria dos pacientes eram homens brancos com idades entre 25 e 40 anos. O tempo médio de internação foi de 1,4 ano e os desfechos nesse início de aplicação da malarioterapia foram majoritariamente negativos (63,2% foram a óbito). Discussão: Os 19 casos avaliados neste estudo referem-se ao primeiro ano de aplicação da malarioterapia no HPSP. As estatísticas existentes sobre o total de curados e mortos ao longo dos 10 anos de implantação dessa terapêutica sugerem que os desfechos dos anos seguintes foram melhores, possivelmente pelo aprimoramento da técnica. Como consequência dessa pesquisa inovadora, que tinha como princípio reorganizar o sistema nervoso central por meio da convulsão desencadeada pela febre da malária, outras formas de terapias de choque foram desenvolvidas, tais como a insulinoterapia, o choque por cardiazol e a eletroconvulsoterapia (AU)

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.