Discovery of Malaria Inoculation to Treat Dementia Paralytica by Ruhi Sahu

Discovery of Malaria Inoculation to Treat Dementia Paralytica by Ruhi Sahu https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g en-us 2023-02-23 16:24:20 UTC 2023-02-25 01:07:37 UTC hello@padlet.com https://padlet.net/icons/png/1f4a1.png The Beginnings of Dementia Paralytica sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493396690 Dementia paralytica, also referred to as general paresis of the insane, was initially observed in mental hospitals in Paris shortly after the Napoleonic wars (1). The disease was clinically and pathologically described by Antione Laurent Bayle, who presented his findings in his doctoral thesis, "Recherches sur l'arachnitis chronique," on November 21, 1822, in Paris (2, 3). Bayle's thesis detailed six cases of dementia paralytica that exhibited autopsy results of chronic meningitis (2). The disease was regarded as its own condition, and it was thought to be a direct consequence of brain lesions or pathological changes, such as chronic arachnoiditis (2). Although cases of this disease were identified in England as early as 1672, it was generally considered a new disease with lots of room for investigation.

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]]> 2023-02-24 03:12:39 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493396690 A Cause of Dementia Paralytica sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493398581 While Bayle had previously suggested a connection between mental disorders and syphilis, it was not until 1857 that the reference became clear for progressive general paresis (PGP). Esmarch and Jessen noticed that a significant number of PGP patients had a history of syphilis, which was later corroborated by several scientists who concluded that syphilis was the root cause of PGP (1). Alfred Fournier, in particular, confirmed this hypothesis in “La syphilis du cerveau” in the Journal of Nervous and Mental Disease in Paris in 1879 (2). Many authors continued to support the pathology of syphilis playing an integral role in the pathogenesis of PGP. This discovery was critical in determining the origins of dementia paralytica, allowing scientists to continue investigating a cure or more precise treatment for the disease (1).

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]]> 2023-02-24 03:15:14 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493398581 The Turning Point for Dementia Paralytica sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493453427 On June 14th, 1917, Julius Wagner-Jauregg received a blood sample from a soldier wounded on the Balkan war front who was suffering from tertian malaria but had not yet been treated with quinine, which was a common therapy for malaria during the time (1). The artifact above is a picture of soldiers on the Balkan war front during this time (2). This blood sample was injected into nine patients with PGP, of which one passed away, two were sent to asylums, and six displayed strong improvements. Yet, of the six improving patients, four of them suffered from relapse while two patients made full recoveries. Based on these results, Wagner-Jauregg continued to inoculate patients with tertian malaria by acquiring the plasmodium from the blood of soldiers struck with malaria at a nearby hospital (3). This was the first time the therapeutic value of malaria inoculation was noted as a potential treatment for PGP.

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]]> 2023-02-24 04:32:02 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493453427 Nobel Prize! sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493454905 Julius Wager-Jauregg continued his efforts, and by 1921, Wagner-Jauregg published an article reporting that over 200 patients had been treated with malaria. Of those, 50 patients had recovered enough to be able to continue their job. In 1927, Wagner-Jauregg become the first psychiatrist to be awarded a Nobel Prize in Medicine for demonstrating malaria therapy could successfully treat patients with dementia paralytica (1). The artifact above is a photo of him from the Nobel Foundation archive (2). His discoveries were ultimately able to save hundreds of patients and provide a new avenue of treatment options.

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]]> 2023-02-24 04:34:17 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493454905 A Look into Fever Therapy sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493462557 In 1883, while working as a resident at the Vienna asylum, Wagner-Jauregg observed a woman with severe psychosis. Interestingly, after she contracted erysipelas, an acute bacterial skin infection typically accompanied by a high fever, the woman was cured of her psychosis (1). The artifact above is an image of Streptococcus pyogenes, the bacterium responsible for most cases of erysipelas and the organism that infected the woman in 1883 (2). Although Wagner-Jauregg did not formally investigate fever therapy until the 1900s, this case caught his attention and sparked his interest in understanding how such an infection could cure a mental illness (1).

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]]> 2023-02-24 04:46:56 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493462557 Impact of Feverish Diseases sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493469867 In 1887, Wagner-Jauregg conducted extensive literature searches on the relationship between feverish disease and psychoses, which resulted in the publication of an article titled "The Effect of Feverish Disease on Psychoses". His background and medical training in pathophysiology made him open to the possibility of a biological cause for certain forms of psychosis, and he believed that a therapeutic solution should also exist. After reviewing the literature and simply based on some descriptions of his personal observations, such as the woman being cured of her severe psychosis, Wagner-Jauregg was convinced that infectious diseases had the potential to cure patients with mental illnesses (1). The same year Wagner-Jauregg was doing this, patients with mental illnesses were crowded on the other side of the globe at the Blackwell’s Island asylum in New York (2). This contrast shows the importance of Wagner-Jauregg’s continued efforts in the field of psychiatry, especially as there were very few improvements and a strong stigma attached to the mentally ill.

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]]> 2023-02-24 05:00:13 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2493469867 Rosenblum's Hidden Findings sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494429392 Regardless of the circulating literature presenting the potential for fevers to treat psychosis, Alexander Rosenblum was the first to intentionally induce intermittent fevers into patients in 1876. Rosenblum induced fever using malaria, typhoid, and relapsing fever and reported that of these 22 psychiatric patients, 11 of them were cured after receiving the treatment. However, his discovery did not receive much attention due to its publication in a smaller journal. Since inducing fever in patients was controversial, Rosenblum decided to not include these findings in his article. It was much later that B. Oks decided to share these findings with the public. Wager-Jauregg acknowledged this experiment at the International Neurological Congress in London. The image above is a translated quote of commentary depicting Rosenblium’s impact by S.J. Zakon. While this finding was not highly recognized, this played an important role in the continuation of fever therapy and its potential use for treating mental illnesses (1).

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670443/

]]> 2023-02-24 23:14:31 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494429392 Koch’s Discovery of Tuberculin sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494435550 One key event that inspired Wagner-Jauregg to continue his research experiments was Robert Koch’s pertinent finding. In 1890, Koch announced his discovery of tuberculin, an extract from tubercle bacilli that was originally used to cure tuberculosis (1). The artifact above is a picture of tuberculin from the Robert Koch Institut (2). Recognizing that tuberculin could artificially induce a fever in patients, Waggner-Jauregg used tuberculin to cure two psychosis patients. However, with concerns about the use of tuberculin circulating, he decided to discontinue his experiments and focused on other possibilities (2).

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]]> 2023-02-24 23:33:36 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494435550 The Element of Fever sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494442796 Hippocrates explained fever as a part of the Humoral Theory, in which he discussed four humors, or bodily fluids: blood, phlegm, black bile, and yellow bile (1). The Humoral Theory, dating back to Ancient Greece and Rome, was a system of medicine that was accepted in the 16th-century “Hippocratic era”. As stated in On the Nature of Man in the Hippocratic Corpus, disease was considered an imbalance of the four humors as depicted in the artifact above (2). Yellow bile, associated with the element of fire as hot and dry, was associated with fever. Thus, an excess of yellow bile would cause a fever, which would be useful in removing the infection out of the patient. As other ideas arose, such as the Germ Theory, humorism diminished but remained an important step in understanding disease and fevers (1).

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]]> 2023-02-24 23:55:07 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494442796 Treating the Mentally Ill sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494450374 In early history, there was virtually no care for patients with mental illnesses. Those who were affected were often sent to prisons and almshouses or had to be watched by their family. Benjamin Rush was an individual who advocated for freeing patients with mental illnesses from the stigma by treating them with medicine, so when there was treatment, it was largely similar to other treatments available or being experimented on at the time, such as bloodletting (1). Rush also used a tranquilizing chair in 1810 to control blood flow to the brain to help with the “madness”, which is shown in the artifact above (2). He focused on seeing insanity as brain damage, progressing the field of mental health at the time (1).

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]]> 2023-02-25 00:17:16 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494450374 Docent: Julius Wagner-Jauregg sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494462393 Julius Wagner-Jauregg (1857-1940), the receiver of the Nobel Prize in Physiology or Medicine in 1927, would be the best person to take you through this museum. He studied medicine at the University of Vienna and received his doctorate, then was later appointed as a Professor of Psychiatry and Director of the Graz’s Psychiatric Clinic. While he worked in the asylum, he observed many of his patients to find that fevers helped some of them recover. He began experimenting by inducing fevers into patients to eventually find and publish his work on the therapeutic value of malaria inoculation in treating dementia paralytica (1). While not as well known as some of his counterparts, he made great strides in the progression of treating the mentally ill and opened up a new source of fever therapy.

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(1) https://pubmed.ncbi.nlm.nih.gov/24185088/#:~:text=However%2C%20in%201917%2C%20the%20Austrian,to%20win%20the%20Nobel%20Prize.

]]> 2023-02-25 00:55:46 UTC https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494462393 Neurosyphilis Today sahuruhi https://padlet.com/sahuruhi/gu7i9jsoh54wyr8g/wish/2494466269 Neurosyphilis, or the bacterial infection of the central nervous system, is now very uncommon but typically occurs in patients who have had untreated syphilis for 10-20 years. Regardless, over the years we have learned so much more about the disease, including its definitive signs and symptoms as well as how to treat it in a way that is not malaria inoculation. For instance, we now know exams and blood tests can be completed to detect certain substances that are produced by the bacteria, such as Treponema pallidum particle agglutination assay (TPPA), along with testing for spinal fluid. Because fever therapy ended with the introduction of penicillin, this antibiotic continues to treat neurosyphilis through injection and/or orally (1, 2). While a life-threatening complication of syphilis, neurosyphilis today is, fortunately, an uncommon occurrence and has a more definite and safe treatment available. It is thanks to Wagner-Jauregg’s findings that have helped pave the path in gaining knowledge about neurosyphilis, and general paresis in particular, along with a potential treatment before the invention of penicillin.

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