Gaetano Perusini
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Gaetano Perusini (24 February 1879 – 8 December 1915) was an Italian physician. He was the pupil and colleague of
Alois Alzheimer Alois Alzheimer ( , , ; 14 June 1864 – 19 December 1915) was a German psychiatrist and neuropathologist and a colleague of Emil Kraepelin. Alzheimer is credited with identifying the first published case of "presenile dementia", which Kraepel ...
and contributed to the definition of
Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
.


Education and early family life

Gaetano Perusini was born in
Udine Udine ( , ; fur, Udin; la, Utinum) is a city and ''comune'' in north-eastern Italy, in the middle of the Friuli Venezia Giulia region, between the Adriatic Sea and the Alps (''Alpi Carniche''). Its population was 100,514 in 2012, 176,000 with t ...
on February 24, 1879 to a successful family of physicians. Perusini’s father, Andrea, was the Chief Physician of the Civil Hospital of Udine and his mother, Paolina Cumano, was the daughter of two prominent surgeons from
Trieste Trieste ( , ; sl, Trst ; german: Triest ) is a city and seaport in northeastern Italy. It is the capital city, and largest city, of the autonomous region of Friuli Venezia Giulia, one of two autonomous regions which are not subdivided into provi ...
. Perusini lost his father when he was only seven years old. This lack of a paternal force in the family enabled his growth and upbringing to be influenced mainly by his mother, a strong maternal personality, who guided his studies and encouraged his interest in medicine. Perusini began studying medicine at the
University of Pisa The University of Pisa ( it, Università di Pisa, UniPi), officially founded in 1343, is one of the oldest universities in Europe. History The Origins The University of Pisa was officially founded in 1343, although various scholars place ...
and then went on to finish his training at the University of
Rome , established_title = Founded , established_date = 753 BC , founder = King Romulus (legendary) , image_map = Map of comune of Rome (metropolitan city of Capital Rome, region Lazio, Italy).svg , map_caption ...
. In Rome, he often visited the local psychiatric clinic, the Lungara Mental hospital. After graduating, Perusini decided to specialize in
psychiatry Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry. Initial psych ...
, spending time at the psychiatric clinic of Augusto Giannelli and the neuropathology laboratory of Giovanni Mingazzini. Thanks to his time at professor Giovanni Mingazzini’s laboratory, Perusini gained a deep passion for mental illnesses and an interest in pathological anatomy, which led to his enthusiasm to discover the organic basis of mental illnesses. Perusini graduated with a degree in
Medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
at the age of 22, defending a thesis on
Criminal Anthropology Anthropological criminology (sometimes referred to as criminal anthropology, literally a combination of the study of the human species and the study of criminals) is a field of offender profiling, based on perceived links between the nature of a ...
written under the guidance of prof. Giannelli.


The Augusta D. case

In November 1906, during a meeting of the psychiatry society in Tübinge,
Alzheimer Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As t ...
presented a case of premature
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
: Augusta D., a 51 years old woman, who died only four years after she was diagnosed.The anatomical findings highlighted cortical
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
, and diagnostic methods revealed accumulations of
neurofibrils Neurofilaments (NF) are classed as type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with microtubules (~25 nm) and ...
within neurons and "miliary foci" (rounded foci) deposit of "an abnormal substance" outside of them. The presentation of the case was received coldly and no questions were asked for clarification from the speaker, much less from the moderator of the debate, the psychiatrist
Alfred Hoche Alfred Erich Hoche (; 1 August 1865 – 16 May 1943) was a German psychiatrist known for his writings about eugenics and euthanasia. Life Hoche studied in Berlin and Heidelberg and became a psychiatrist in 1890. He moved to Strasbourg in 1891. F ...
, of
Freudian Sigmund Freud ( , ; born Sigismund Schlomo Freud; 6 May 1856 – 23 September 1939) was an Austrian neurologist and the founder of psychoanalysis, a clinical method for evaluating and treating pathologies explained as originating in conflicts i ...
origin and therefore an opponent of Kraepelin, who made Alzheimer’s report seem clinically and scientifically irrelevant. Only the following year, after having changed the title, will Alzheimer be able to publish it in a brief report, without iconographic material. Alzheimer was convinced that he was facing a rare
brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
pathology and therefore decided to entrust the case to Perusini for a more in-depth and detailed evaluation of both the clinical aspects and the
histopathological Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
findings. Perusini re-examined the case of Augusta D. and collected three other cases (47, 63 and 67 years old) of severe and rapid dementia in a 59 pages treatment accompanied by 79 drawings depicting the neuronal alterations, made by Perusini and collected in four tables. Perusini believed that the neuro-pathological findings of the early onset cases did not differ from the
senile Dementia is a disorder which manifests as a Syndrome, set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negativ ...
ones, in fact in his discussion, he deliberately included the two senile cases (63 and 67 years old). By doing this, Perusini would have predicted the modern conception of this disease according to which presenile and senile dementia are not two isolated entities and, at the same time, disproved the position of Kraepelin that rejected this possibility.


Perusini’s contribution to the definition of Alzheimer's disease

In his mesmerising work “On the nosographic value of some typically senile histological findings” Perusini defines the history of
neuropathology Neuropathology is the study of disease of nervous system tissue, usually in the form of either small surgical biopsies or whole-body autopsies. Neuropathologists usually work in a department of anatomic pathology, but work closely with the clinic ...
of senile dementia. According to his findings, the first ever mention of senile plaques was by Blocq and Marinesco, in 1892, regarding an elderly patient suffering of
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
. Unfortunately, the description for miliary scleroses was attributed to Redlich in 1898 and Perusini’s work was overlooked at the time. Perusini’s dissertation on senile plagues convey the following topics: nomenclature, history, staining techniques results of microhistochemical research, differential diagnosis, origin and nature of senile plaques and their meaning in various human conditions. The second part of his work contained an examination of the neurofibrillary alterations described by Alzheimer in 1908, Perusini reported that: "The altered neurofibrils in Bielschowsky solution have the most unusual aspects: wound in complex tangles which scarcely maintain the structure of nervous cells, they appear, within the tissue, almost as "skeletons'' of nervous cells …" In addition to the previously mentioned skeletons, other elements ought to be mentioned in which neurofibrils appear to be much thinner but arranged in complex convergent and divergent whirls' ' , p. 194 Unfortunately, due to technical limitations on staining, Perusini was unable to draw precise conclusions regarding the correlation between senile plagues and neurofribillar alterations, and on the structure of
neuroglia Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form mye ...
. Nonetheless, it is important to emphasize the up-to-dateness and the accuracy of Perusini’s statements and work on staining. However, he was able to affirm that "the presence of neurofibrillar alterations can only be considered as one of the
histopathological Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...
findings within senile cerebral involution" 0, p. 196 additionally he encouraged the facilitation of further studies to take place regarding this topic. In 1909, Perusini’s work "Histologische und Histopathologische Arbeiten" (printed in 1910) was published, in which he examined four cases and provided a detailed description on both
histology Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
and clinical cases. In one of the cases, with the collaboration of Sioli and Alzheimer, there was an identification of the presence of neurofibrillary alterations and military foci in the
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
, he concluded that  "we are surely in the presence of a peculiar and relatively unknown disease … which cannot be included into any group of known diseases.” Perusini’s work in 1911 provided abundant information regarding histological iconography, he described that it is "centered upon the diagnostic value of anatomopathological findings within plaques and neurofibrillar alterations as described by Alzheimer.” Perusini’s brilliant work attributed the identification of the atypical forms of senile dementia to Alzheimer’s disease, his extremely brilliant work provided a detailed description. It is worth mentioning his very modern conclusions: “senile plaques are among the characteristic findings within cerebral involution. In this sense they can be said to be characteristic of senile dementia: they are present in every senile patient's brain; moreover, their number, diffusion and dimensions indicate somehow the seriousness of the involutive process.”


The Return to Italy and World War I

Perusini eventually returned to
Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
in 1911, and although his work was known all over
Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
he was unable to find a suitable and stable academic position. It was not until 1913 that he was able to find a professional post as an assistant in the
Mombello Psychiatric Hospital The Mombello Psychiatric Hospital, also known as the Giuseppe Antonini of Limbiate Psychiatric Hospital, was the largest asylum in Italy, covering with multiple buildings located as to form a small village. It is located in the Italian commune of ...
in
Milan Milan ( , , Lombard: ; it, Milano ) is a city in northern Italy, capital of Lombardy, and the second-most populous city proper in Italy after Rome. The city proper has a population of about 1.4 million, while its metropolitan city h ...
. Perusini was raised in a patriotic family which likely influenced his decision to enlist, albeit hiding his professional identity, into the army as a volunteer at the outbreak of the
First World War World War I (28 July 1914 11 November 1918), often abbreviated as WWI, was one of the deadliest global conflicts in history. Belligerents included much of Europe, the Russian Empire, the United States, and the Ottoman Empire, with fightin ...
. Eventually, the military discovered his medical professional background and was assigned to the first aid post in
San Floriano del Collio San Floriano del Collio ( sl, Števerjan; fur, San Florean dal Cuei) is a ''comune'' (municipality) in the Province of Gorizia in the Italian region Friuli-Venezia Giulia, located about northwest of Trieste and about northwest of Gorizia, on the ...
, where on November 28, 1915 he was hit by shrapnel while assisting the wounded.


Death and legacy

Gaetano Perusini died on December 8, 1915  in the Red Cross hospital in
Cormons Cormons or Cormòns ( sl, Krmin, german: Kremaun) is a ''comune'' (municipality) in the Italian region Friuli-Venezia Giulia, located about northwest of Trieste and about west of Gorizia, on the border with Slovenia. Cormons borders the f ...
, in one of the houses his family owned, and received the silver medal for valor. Although Peursini died at a young age of 36 and was thus unable to continue his research, his scientific contribution to the definition of the clinical and neuropathological aspects of
neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
dementia, must be remembered. It is widely believed that his name has the right to be joined to that of Alzheimer's in the more correctly defined disease of Alzheimer-Perusini.


Main works

* On the clinical and histological aspects of a particular mental illness of advanced age. Histological and Histopathological Works, Volume III. H.2 (''Über klinische und histologische eigenartige psychische Erkrankung das späteren Lebensalters , Nissl-Alzheimer)'', published in 1909 * Pathological anatomy in psychiatry (''L'anatomia patologica in psichiatria (suoi fini, suoi mezzi)'') written in 1909, published by Rivista Sperimentale di Freniatria. * On the nosographic value of some histopathological findings characteristic for senility ''(Sul valore nosografico di alcuni reperti istopatologici caratteristici per la senilità. Rivista di Neuropatologia, Psichiatria ed Elettroterapia 4)'', published by Journal of Neuropathology, Psychiatry and Electrotherapy 4 (IV) in two parts in 1911.


Notes


Bibliography

* Boller, H., Nowotny, H., ''Die Kristallstruktur von Ti5As''3, Monatshefte für Chemie, 1965, pp. 565–569 * Carelli, Laura, Pezzati, Rita, Poletti, Barbara, Zago, Stefano, ''La comunicazione della diagnosi di malattia di Alzheimer: aspetti clinici ed etico-giuridici'', Ricerche di Psicologia (2), May 2013, pp. 501–523 * ''ERT and Alzheimer's disease'', Inpharma Wkly, 8 April 1998 * Lucci, B., ''The contribution of Gaetano Perusini to the definition of Alzheimer's disease'', The Italian Journal of Neurological Sciences, February 1998, pp. 49–52 * McMenemey, W. H., ''Alois Alzheimer and his disease'', Ciba Foundation Symposium - Alzheimer's Disease and Related Conditions, Chichester, UK, John Wiley & Sons, 1970, pp. 5–9 * Nissl, F, Alzheimer, A, ''Histologische und Histopathologische Arbeiten über die Grosshirnrinde'', The Journal of Nervous and Mental Disease, January 1922, pp. 75 * Rosso, Mattia, Chu, Duong, ''Gaetano Perusini (1879-1915)'', Journal of Neurology, 2021, pp. 4400–4401 * Smith, Theodore L., ''Rivista Italiana di Neuropatologia'', Psichiatria ed Elettroterapia, The American Journal of Psychology, July 1908, pp. 425 {{DEFAULTSORT:Perusini, Perusini 1879 births 1915 deaths 20th-century Italian physicians Italian military personnel killed in World War I Alzheimer's disease researchers Deaths by hand grenade