King Charles VIII of France's Death: From an Unsubstantiated Traumatic Brain Injury to More Realistic Hypotheses.

On April 7, 1498, Charles VIII, King of France, attended a game of palm in the ditches of the Château d'Amboise. The 27-year-old King suddenly collapsed and became comatose. He laid down, almost on his own, on a straw mat that was hastily arranged, and he died 9 hours later. His contemporaries perceived his death as a perfect reminder of fatality: a king could die alone in a miserable gallery. All who looked into this curious death had dwelled on the frontal blow to head that the king had sustained right before his demise and had not considered alternative scenarios. The present study, still with limited available evidence, aimed to reexamine the historical account of his death in light of modern medical knowledge. It is virtually impossible that a minor bump with low kinetic energy could kill a 27-year-old man. Many historical accounts of Charles VIII's life and death, including Italian ambassadors' letters, led us to reconsider the commonly held version and to propose an alternative hypothesis. We have concluded that Charles VIII had experienced an acute consciousness disorder with language impairment that could have been related to an epileptic condition secondary to neurosyphilis. We have discussed whether a more accurate diagnosis for the cause of death could be obtained by a pathological analysis of the King's remains.

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.

Neurosyphilis and classical music: the great composers and "The Great Imitator".

OBJECTIVE: Throughout history, neurosyphilis has victimized many people, including classical composers, with a wide range of clinical presentations. Six articles with descriptions of composers with possible neurosyphilis were reviewed. METHODS: Neurosyphilis is a possible diagnosis for composers like Beethoven, whose progressive hearing loss influenced his career, culminating in complete deafness. In his autopsy, cochlear nerve atrophy and cochlear inflammation were described. Donizetti developed behavioral changes, as well as headaches, general paresis and seizures. RESULTS: Both Schumann and Wolf suffered from personality changes, persecutory delusions and general paresis. Joplin and Delius also had symptoms attributed to syphilis. Autopsy findings confirmed the diagnosis of Smetana, who developed dementia, deafness and auditory hallucinations with rapid progression. His tinnitus was musically represented in his first String Quartet. CONCLUSION: Neurosyphilis victimized several notorious composers. It can be argued that neurosyphilis was a major source of inspiration as well, being responsible for the genesis of musical masterpieces.

Neurosyphilis and classical music: the great composers and "The Great Imitator" / Neurossífilis e música clássica: os grandes compositores e "A Grande Imitadora"

ABSTRACT Throughout history, neurosyphilis has victimized many people, including classical composers, with a wide range of clinical presentations. Methods: Six articles with descriptions of composers with possible neurosyphilis were reviewed. Results: Neurosyphilis is a possible diagnosis for composers like Beethoven, whose progressive hearing loss influenced his career, culminating in complete deafness. In his autopsy, cochlear nerve atrophy and cochlear inflammation were described. Donizetti developed behavioral changes, as well as headaches, general paresis and seizures. Both Schumann and Wolf suffered from personality changes, persecutory delusions and general paresis. Joplin and Delius also had symptoms attributed to syphilis. Autopsy findings confirmed the diagnosis of Smetana, who developed dementia, deafness and auditory hallucinations with rapid progression. His tinnitus was musically represented in his first String Quartet. Conclusion: Neurosyphilis victimized several notorious composers. It can be argued that neurosyphilis was a major source of inspiration as well, being responsible for the genesis of musical masterpieces.

RESUMO Através da história, a neurossífilis vitimou milhares de pessoas, incluindo compositores clássicos, com uma grande gama de manifestações. Métodos: Seis artigos com descrições de compositores com possível neurossífilis foram revisados. Resultados: Neurossífilis é um diagnóstico possível para compositores como Beethoven, cuja perda auditiva progressiva influenciou sua carreira, culminando com surdez completa. Em sua autópsia foram descritas inflamação e atrofia dos nervos cocleares. Donizetti desenvolveu alterações comportamentais, bem como cefaleias, paresia e convulsões. Tanto Schumann quanto Wolf sofreram com alterações comportamentais, delírios persecutórios e paresia. Joplin e Delius também tiveram sintomas relacionados a sífilis. Achados de autópsia confirmaram o diagnóstico de Smetana, que desenvolveu demência, surdez e alucinações auditivas rapidamente progressivas. Seu tinito foi musicalmente representados em seu Quarteto de Cordas No. 1. Conclusão: Neurossífilis vitimou diversos compositores de destaque. Pode-se argumentar que a doença chegou a ser grande fonte de inspiração e mesmo responsável pela gênese de diversas obras-primas.

Turin's breakdown: Nietzsche's pathographies and medical rationalities. / O colapso de Turim: patografias de Nietzsche e racionalidades médicas.

At age 44, after suffering a breakdown in Turin, philosopher Friedrich Nietzsche was diagnosed with neurosyphilis. There was no necropsy on his body, so this medical diagnosis has been questioned over the time. We conducted a literature review on the medical diagnosis of Nietzsche, which emphasizes three genres of pathographies that emerged successively as alternatives explanations for Nietzsche's breakdown in Turin: (1) narratives about syphilis ("demoniac-pathological"); (2) narratives about functional psychosis ("heroic-prophetic"); (3) other narratives about organic diseases, other than syphilis ("scientific-realistic"). The latter - which correspond to our study object in this work - undertake retrospective diagnostics, attempting to retrieve the "truth" underlying the disease and elucidate "Nietzsche's affair". We inquire this detective-like impetus, currently taken to the extreme by "evidence-based medicine", and we denounce its anachronism. Syphilis has become a scientific fact only after the death of Nietzsche. We conclude that the diagnosis he received is shown to be consistent with the nineteenth-century medical rationality and the syphilis status as a cultural fact at that time.

Aos 44 anos, após sofrer um colapso em Turim, o filósofo Friedrich Nietzsche recebeu o diagnóstico médico de neurossífilis. Devido à ausência de autópsia em seu corpo, tal diagnóstico médico vem sendo questionado historicamente. Realizou-se a revisão da literatura disponível sobre o diagnóstico médico de Nietzsche. Destacam-se três gêneros patográficos que emergiram sucessivamente como explicações para o colapso de Turim: (1) narrativas sobre a sífilis ("demoníaco-patológicas"); (2) narrativas sobre as psicoses funcionais ("heroico-proféticas"); (3) narrativas sobre outras doenças orgânicas, distintas da sífilis ("científico-realistas"). Estas últimas ­ que correspondem ao nosso objeto de estudo propriamente dito neste trabalho ­ empreendem diagnósticos retrospectivos, buscando extrair a "verdade" subjacente à doença e elucidar o "caso Nietzsche". Questionamos tal ímpeto detetivesco, exponenciado atualmente pela "medicina baseada em evidência", e denunciamos seu anacronismo. A sífilis tornou-se um fato científico somente após a morte de Nietzsche. Conclui-se que o diagnóstico por ele recebido mostra-se consistente com a racionalidade médica oitocentista e com o estatuto da sífilis como um fato cultural naquela época.

Thomas Mann's depiction of neurosyphilis and other diseases.

Thomas Mann (1875-1955), a Nobel Prize recipient rightly considered one of the great novelists of the twentieth century, was one of the most medically perceptive writers of recent times. His novels take place against the background of the different plagues (tuberculosis, cholera) that characterized the eighteenth and nineteenth centuries. One of Mann's later novels, Doctor Faustus, is set against a background of syphilis. In the 500-page book, which is subtitled The Life of the German Composer Adrian Leverkühn as told by a Friend, we see the theologian turned composer make a pact with the devil. He "voluntarily" contracts syphilis and, as a result of the pact and despite (or because of) the disease, Leverkühn starts a brilliant 24-year career, becoming the greatest German composer of his time. While it is widely thought that Arnold Schoenberg (1874-1951) is the model for Leverkühn, we will show that other composers of the time also inspired the fictitious musician's life and works. We will also illustrate the parallel between Leverkühn's disease progression and political events in Germany in the 1930s and 1940s and their similarity with current political events.

Historical reflections on neurosyphilis based on the 1826 treatise on general paralysis in demented patients by Louis Florentin Calmeil (1798-1895).

General paralysis is a neurological symptom of tertiary syphilis that was first identified in asylums as paralytic madness. The enlightened discussion of 60 clinicopathological cases provided by Louis Florentin Calmeil in his 1826 treatise greatly improved our knowledge of general paralysis. However, Calmeil was unable to relate this symptom to syphilis, although the latter was quite widespread at that time. Following a detailed reanalysis of Calmeil's observations with special attention to his clinical and demographic data, we conclude that this eminent clinician was unable to define the cause of general paralysis because his early 19th century mind was still under the influence of traditional knowledge and moral prejudices. For Calmeil, general paralysis belonged entirely to the realm of psychiatry.

O colapso de Turim: patografias de Nietzsche e racionalidades médicas / Turin's breakdown: Nietzsche's pathographies and medical rationalities

Resumo Aos 44 anos, após sofrer um colapso em Turim, o filósofo Friedrich Nietzsche recebeu o diagnóstico médico de neurossífilis. Devido à ausência de autópsia em seu corpo, tal diagnóstico médico vem sendo questionado historicamente. Realizou-se a revisão da literatura disponível sobre o diagnóstico médico de Nietzsche. Destacam-se três gêneros patográficos que emergiram sucessivamente como explicações para o colapso de Turim: (1) narrativas sobre a sífilis ("demoníaco-patológicas"); (2) narrativas sobre as psicoses funcionais ("heroico-proféticas"); (3) narrativas sobre outras doenças orgânicas, distintas da sífilis ("científico-realistas"). Estas últimas - que correspondem ao nosso objeto de estudo propriamente dito neste trabalho - empreendem diagnósticos retrospectivos, buscando extrair a "verdade" subjacente à doença e elucidar o "caso Nietzsche". Questionamos tal ímpeto detetivesco, exponenciado atualmente pela "medicina baseada em evidência", e denunciamos seu anacronismo. A sífilis tornou-se um fato científico somente após a morte de Nietzsche. Conclui-se que o diagnóstico por ele recebido mostra-se consistente com a racionalidade médica oitocentista e com o estatuto da sífilis como um fato cultural naquela época.

Abstract At age 44, after suffering a breakdown in Turin, philosopher Friedrich Nietzsche was diagnosed with neurosyphilis. There was no necropsy on his body, so this medical diagnosis has been questioned over the time. We conducted a literature review on the medical diagnosis of Nietzsche, which emphasizes three genres of pathographies that emerged successively as alternatives explanations for Nietzsche's breakdown in Turin: (1) narratives about syphilis ("demoniac-pathological"); (2) narratives about functional psychosis ("heroic-prophetic"); (3) other narratives about organic diseases, other than syphilis ("scientific-realistic"). The latter - which correspond to our study object in this work - undertake retrospective diagnostics, attempting to retrieve the "truth" underlying the disease and elucidate "Nietzsche's affair". We inquire this detective-like impetus, currently taken to the extreme by "evidence-based medicine", and we denounce its anachronism. Syphilis has become a scientific fact only after the death of Nietzsche. We conclude that the diagnosis he received is shown to be consistent with the nineteenth-century medical rationality and the syphilis status as a cultural fact at that time.

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.

'Shrouded in a dark fog': comparison of the diagnosis of pellagra in Venice and general paralysis of the insane in the United Kingdom, 1840-1900.

The debate on the causes and the nature of pellagra in Italy during the nineteenth century resembles and evokes the similar debate on General Paralysis of the Insane (GPI) that was growing at the same time in the United Kingdom. Pellagra and GPI had a massive and virulent impact on the populations of Italy and the UK, respectively, and contributed to a great extent to the increase and overcrowding of the asylum populations in these countries. This article compares the two illnesses by examining the features of their nosographic positioning, aetiology and pathogenesis. It also documents how doctors arrived at the diagnoses of the two diseases and how this affected their treatment.

[Robert Schumann in the psychiatric hospital in Endenich near Bonn]. / Robert Schumann in der Heil- und Pflegeanstalt Endenich bei Bonn.

BACKGROUND: The composer Robert Schumann (1810-1856) spent the last two-and-a-half years of his life in the private psychiatric hospital in Endenich. His medical records emerged in 1991 and were published by Appel in 2006. METHODS: Daily entries by the physicians were analyzed concerning psychopathology and organic signs as well as the illness-related correspondence of the people closest to Schumann. RESULTS: The numerous entries reveal the treatment typical at that time for what was at first considered to be "melancholy with delusions": shielding from stimuli, physical procedures, and a dietary regimen. The feared, actual diagnosis, a "general (incomplete) paralysis," becomes a certainty in the course of the paranoid-hallucinatory symptoms with cerebro-organic characteristics and agitated states, differences in pupil size, and increasing speech disturbances. CONCLUSION: In the medicine of the time, syphilis is just emerging as the suspected cause, and the term "progressive paralysis" is coined as typical for the course. Proof of Treponema pallidum infection was not available until 1905. Nevertheless, the clinical signs strongly refer to the course of neurosyphilis. People close to Robert, in particular his wife Clara and the circle of friends around Brahms and Joachim, cared intensively for him and suffered under the therapeutic isolation. The medical records and disease-related letters contradict the theory that Schumann was disposed of by being put into the psychiatric hospital; they show the concern of all during the unfavorable illness course.

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.

Furious Frederich: Nietzsche’s neurosyphilis diagnosis and new hypotheses / Frederico Furioso: O diagnóstico de neurossífilis de Nietzsche e novas hipóteses

The causes of Friedrich Nietzsche’s mental breakdown in early 1889 and of the subsequent slow decay to end-stage dementia along ten years will possibly remain open to debate. The diagnosis of syphilitic dementia paralytica, based only on medical anamnesis and physical examination, was considered indisputable by Otto Binswanger. On the other hand, taking into account recently described diseases, selectively collected evidence lend some support to alternative hypotheses: basal forebrain meningioma, CADASIL, MELAS and frontotemporal dementia.

As causas da crise neuropsiquiátrica de Friedrich Nietzsche no início de 1889 e de sua lenta deterioração em demência avançada ao longo de 10 anos provavelmente permanecerão uma questão em aberto. O diagnóstico da época, demência paralítica sifilítica, foi considerado por Otto Binswanger como indiscutível. Por outro lado, em vista de novas doenças descritas, evidências seletivamente ordenadas sugerem diversas hipóteses alternativas propostas ao longo das últimas décadas, como meningioma frontal, CADASIL, MELAS e demência frontotemporal.

Furious Frederich: Nietzsche's neurosyphilis diagnosis and new hypotheses.

The causes of Friedrich Nietzsche's mental breakdown in early 1889 and of the subsequent slow decay to end-stage dementia along ten years will possibly remain open to debate. The diagnosis of syphilitic dementia paralytica, based only on medical anamnesis and physical examination, was considered indisputable by Otto Binswanger. On the other hand, taking into account recently described diseases, selectively collected evidence lend some support to alternative hypotheses: basal forebrain meningioma, CADASIL, MELAS and frontotemporal dementia.

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.