Eastern Europe, Romania, 1870-1970
An ongoing FENS History of European Neuroscience project by Octavian Buda, Ana-Maria Zagrean and Leon Zagrean
Last updated 20 Oct 2013
Neurology and related sciences influenced the development of both clinical and neurosciences research in modern Romania between c. 1870 and 1970. To date, the history of Romanian neurology and psychiatry in Romania has been neglected although it has much to offer in terms of understanding the connection between science, political ideals and national contexts, both at a regional and international level.
As most Romanian neuroscientists studied abroad they followed institutional models developed in Western Europe – particularly France, Germany and Britain – and were seriously influenced by debates on the relationship between neuropathology, clinical research and disease characterising the growth of British, German or French neurologists. It is important to establish the depth and quality of international collaborations in the field of neurology, and the degree of transfer of medical knowledge and research between Romania and centres of learning in Western Europe.
Particular attention is given here to the prominent Romanian neuroscientist Georges Marinesco (1863-1938).
We try to lend new insights into the study of how scholarly paradigms and institutional interactions, in general, do occur in different historical periods, and which are the agents of medical entanglements. Thus through approach of a particular national context as well as through engaging with new methodologies, we try as well to offer a glimpse of the stimulating recent inquiries on history of East European Neurosciences.
For those who already have an interest in the history of medicine, and particularly neurosciences in Central and Eastern Europe these short biopics hopefully will add to their knowledge; for those who do not read French or Romanian, it offers a possibility that some one of them will soon be available in English translation. As such, it is important for all those concerned with thinking more broadly about the history of neurosciences as a whole.
Georges Marinesco (1863-1938)
A short biography
Marinesco was Romanian and a pupil of Charcot, who became professor of neurology in Bucharest. He contributed knowledge to the anatomy and pathology of the nervous system. He coined the term chromatolysis and studied the effects of hypophysectomy, and observed the fatal effects of removal of the pituitary gland in animals. Alzheimer described neurofibrillary tangles and sclerotic plaques found in Alzheimer’s disease in 1906 and 1907. Earlier in 1892, Georges Marinesco with Paul Blocq had modified the staining techniques for glia (previously developed by Santiago Ramon y Cajal) and observed plaques in the cortices of two senile individuals with gross memory defects, mental confusion, aphasia, and apraxia [3,17]. With I.Th. Nicolesco he reported on the clinical aspects of thalamic lesions, and elaborated further on what was already known about the thalamic syndrome. With Blocq, in 1893 he reported a case of Parkinson’s disease associated with a tuberculoma in the substantia nigra. These observations were the basis of Edouard Brissaud’s suggestion in 1894 of the nigral origin of this disorder. Eponymically Marinesco is remembered for the Marinesco-Sjogren syndrome (cataracts, mental retardation, short stature delayed sexual development, and ataxia).
Later Marinesco worked with Carl Weigert in Frankfurt and then with Emil Du Bois-Raymond in Berlin. In 1890, in collaboration with the French pathologist Paul Blocq, he wrote a study of the pathologic findings discovered in Friedreich disease. In 1891, Marinesco lectured on changes in the spinal marrow in cases of amputation at the French Society of Psychiatrists.
In Berlin in 1892, Marinesco – together with the French pathologist Paul Oscar Blocq (1860-1896) and the Romanian pathologist and bacteriologist Victor Babès (1854-1926) – published an atlas of the pathologic histology of the nervous system. [4,6]
After nine years abroad Marinesco in 1897 returned to Bucharest where he received his doctorate. At Bucharest a new professorial department of neurology had been created for him at the Bucharest Pantelimon hospital. Shortly thereafter, in 1897, a chair of clinical neurology was created for him in the University of Bucharest, and he also worked in the Colentina Hospital. He remained in this post for the next 41 years and is regarded as the founder of Romanian neurology .
Marinesco maintained close academic with his Parisian colleagues and many of his articles (over 250), were published in the French language. He had a wide range of research interests, including pathological anatomy and experimental neuropathology . Daily contact with scores of the infirm and his astuteness made him put to use every one of the latest methods as they became available: the Roentgen ray, with which he investigated bone changes in acromegaly, the film camera, for the study of body movements in health and disease.
His description with Blocq of a case of parkinsonian tremor due to tumour in the substantia nigra, in 1893, was the basis for Edouard Brissaud’s (1852-1909) theory, announced the next year, that parkinsonism occurs as a consequence of damage to the substantia nigra. With the Romanian neurologist Ion Minea, confirmed Hideyo Noguchi (1876-1928) discovery of treponema in the brain in general paresis in 1913.
Marinesco died in Bucharest on 15 May 1938 at the age of 75 years.
A letter from Pavolv
Marinesco’s early research in neuropathology – the senile plaques, 1892
During the 1890s, Marinesco also became interested in the mechanisms of neurodegeneration. His findings were one of the main elements later used by Alzheimer (together with his own painstaking clinical and pathologic observations) to create a cohesive description of senile dementia. In 1892, Blocq and Marinesco described a lesion in the postmortem brains of chronic epileptic patients which represented the now familiar senile plaques found in patients with dementia. The original French article, entitled “On the lesions
and pathogeny of the so-called essential epilepsy,” was published in the Parisian medical journal La Semaine Medicale, unfortunately without illustrations [3,6].
The study was conducted between 1890 and 1892 at the Salpetriere Hospital (courtesy of Charcot), on eight deceased epileptic patients aged 50 to 68, and a ninth aged 29 at the time of death. Blocq and Marinesco performed their examinations using stains common to that period, such as hematoxylin and eosin, acidic fuchsin, and carmine, as well as Marchi’s impregnation, a technique used for demonstrating degenerate myelin with osmium tetroxide.
They also modified the staining techniques for glia, previously developed by Santiago Ramon y Cajal. In their study, only one case received special attention because they found round, small aggregates, about 60 microns in diameter, disseminated in various layers of the cortex. These were contrasted with the background tissue by an intense stain and well defined contour. They considered these structures, which had a dot-like appearance, to be “nodules of nevroglial sclerosis.”
This is the English translation by Andre Delacourte of Blocq and Marinesco’s paper published in 1892 (http://www.alzforum.org/res/for/journal/detail.asp?liveID=129):
Paul Blocq and G. Marinesco
Sur les lésions et la pathogénie de l’épilepsie dite essentielle
LA SEMAINE MEDICALE, 1892, p 445 et 446
Although both anatomy and physiopathology of epilepsy said “essential” or “idiopathic” had led to numerous publications, and very recently had the benefit of numerous works, we are still far away from a satisfactory knowledge related to this subject.
Therefore, due to the open-minded kindness of Mr Pr Charcot, we have been able to collect in his department several cases that we have investigated.
Starting from March 1890, we have been able to perform at Salpetriere hospital 9 autopsies of epileptic patients, chosen in that they had presented in their life defined criteria.
These 9 cases were true epileptics, with a clinical presentation and evolution fitting with the classical idiopathic form and moreover that died following an epilepticus status “ de morbus comitialis” and not from an intercurrent affection. Moreover, from these samples, some of them came from aged people (50 to 68 years) but others came from younger patients (29 years in one case).
Using such cases, we meticulously analyzed the central nervous system at the histological level, taking the advantage of different techniques, especially one of them never used, at least on such cases.
For all these autopsies, we have examined the brain stem and different neocortical areas. Results obtained varied according to the method employed. Indeed, while we observed abnormal features, other procedures (eosin, hematoxylin, fushin acid, carmin, etc) gave different patterns according to the method used.
Therfore results will be exposed according to each technique.
1° Marchi method:
This technique is not well known , and it is important to know that all affected structures are stained in black. Among these structures, we have recognized three catagories: fragments of degenerating myelin , cells with myelinic granulations and cells with blood granulations.
All preparations from our epileptic paptients showed constantly two types of lesions: a) perivascular alterations ; b) cellular lesions
A) Vascular alterations are characterized by the infiltration of the walls by granulous bodies. They are found all around the periphery, like a sleeve, sometimes not complete with streakson longitudinal sections.
B) Cellular lesions are found on the superficial nevroglia layer of the cortex (zone limitans) and consist of infiltration of these cells by a black granular material. It is known that for Metchnikoff, the spider -cells would play a phagocytic role in the cortex.
2° Other staining methods. – Results were, as mentioned, variable and the 9 cases can be ranked in the following categories :
* In four cases, there is no abnormalityto report, neither in cells nor in the supporting tissue
* In 4 cases, there are diffuse lesions less and more pronounced of nevroglia, at different degrees, and vascular alterations
* In one case, there are disseminated lesions of nevroglia, and alteration of blood vessels.
1. There is nothing to deal with, since nothing abnormal was found
2. We will describe the diffuse lesions of neuroglia as observed in the two cases, despite small differences, but in the same category
In on case, regarding a young patient, lesions were essentially beneath the surface. Meningeal vessels, veins, arteries are swollen, filled with blood cells, and in their surrounding we observe infiltrates of blood diffusing. Pia-mater, thicken at different places, is infiltrated by free blood cells. In the upper limitans neuroglia layer, apart from swollen vessels, we note a small hyperplasia of glial cells. The vascular hypertrophy continues in the third and fourth Meynert layers: vessel walls contain blood granular bodies ; small capillaries are coming out of the back, as if they were artificially injected.
Nerve cells, and especially pyramidal cells, and fusiform cells of the fifth Meynert layer are normal. Centrum semi- oval is also affected and contains perivascular granular lesions.
For the other case, related to an older patient, lesions hardly defined on previous preparations were more accentuated. Superficial limitans layer shows a thickness due to the formation of bands of neuroglia fibrils. Deiters layers are dramatically increased in numbers and volume, and present themselves under the very characteristic aspect described by M. Chaslin (1), in similar cases, that islarger and spiked with fine extensions, sometimes linked to vessels.
As previously described are observed swollen vessels from the pia-mater and cerebral cortex.
C. Lesions that we described as scattered in neuroglia are observed in only one case, and here again with two aspects, one of which being similar to our previous description, and the other, very peculiar, with the form of small nodules.
Limitans layer presents hyperplasia of neuroglial cells. One could observe in addition, non only in this layer, but in deeper layers, focal sclerotic lesions around vessels, with fibrillar tufts as described by M. Chaslin. Moreover, there are scattered in the different layers of the cortex, small round clusters with an approximate diameter of 60 microns, different from the tissue by a more intense staining, with regular shapes. They appear as such, with a regular distribution on preparations, with a moderately dotted structure, suggesting that some of them are authentic nodules of neuroglia sclerosis.
Similar to other cases, we note hyperplasia in neuroglia cells of the superficial layers, less pronounced than in the previous observation, despite a more pronounced fibrillar sclerosis. Pyramidal cells seem normal. Vascular alterations are very pronounced ; not only in the cortex but also in semi-oval centrum, swollen vessels are observed, sometimes with small punctiform hemorrhagia , whose focal center is surrounded by blood granular bodies. Around older foci of this type are found altered cells; they are small, without nucleus, similar to granular aggregates, strongly stained by eosin and acidic fushin.
We do notice that, in the last case, vessels from the base were very atheromatous.
Brainstem is normal in all cases, apart from the case previously described, which was presenting small scattered hemorrhages. We did not find, in any case in particular, sclerosis of olives described by some authors. If we want to compare our results to those obtained by authors that preceded us, it is important to take into consideration only similar cases, that is with essential epilepsia and not associated with idiocy, porencephalia or infantile hemiplegia.
Most frequent and constant lesions are sclerotic alterations. Indurated plaques multiple and scattered have been described by Féré. Kingsburg observed a proliferation of neuroglia cells which were, simultaneously swollen. Allen J. Smith observed a fatty degeneration of cells.
The most careful study done so far on this subject is the work of M. Chaslin. This author has observed, in five brains, examined more specifically at the level of motor regions, a sclerosis named, wrongly to our opinion, pure neuroglia sclerosis, whose main features are the following: superficial layer is composed of fibrils bundles parallel to the surface taking birth in numerous cells with hypertrophic extensions. These fibrils constitute, by places, large and compact tracts. Vessels do not present inflammation. There is only, at some points, a hyaline transformation of the wall of capillaries.
These alterations, as observed, are similar on several points to those that we observed in several cases; in the same was as M. Chaslin, we have observed fibrillar sclerosis with compact tracts and hyperplasia of spider-cells in the superficial layer. We will see, at the opposite, that our opinion is different on the interpretation of such lesions.
To summarize, and strictly from an anatomic point of view, we give from our observations the following conclusions:
1° In a certain number of idiopathic epilepsy cases, there is no detectable lesions of nervous centers ;
2° When lesions are detected, they are very variable
3° Most constant lesions, when they exist, are found in psycho-motor regions and are characterized : a) by vascular alterations and b) by hyperplasia of neuroglia, either at the surface of the cortex, or in its depth.
What lessons are we authorized to draw from these findings ? First, two aspects seem obvious: 1° Lesions can be absent ; 2° they are variable. Therefore they do not represent specific alterations, the anatomic substratum of essential epilepsy. However, their location shows that epilepsy results from, as mentioned by most authors, a cortical process, and their nature clearly indicates that the process is vascular in nature.
Therefore we are allowed to think, that far from primitive, as mentioned after M. Chaslin by several observators (Feré, Marie), these lesions are, on the contrary, secondary or, simultaneous to attacks. Indeed, first of all, they do not explain the genesis of paroxysms and even less the different somatic signs that usually coexist, in the epilepsy class that we consider. Second, we can observe, in other circumstances, vascular alterations more of less similar to the very lesions that we met systematically in our cases.
For us, these alterations only testify for a functional hyperactivity of the cortical region where there are dominant, the role of granular bodies, which where the most characteristic, being to transport remnants of tissues that are in excess due to their degradation following a transitory excess of activity. This is the repetition more or less frequent of this condition of congestion and hyperactivity that at the end will provoke, to our opinion, neuroglia sclerosis, which, indeed, is maximum in the superficial layer. One can note, from the point of view of the relationship of sclerosis with blood vessels, an accentuation in older subjects, at the very place where vessels tend to be altered in senility.
If lesions that we described are secondary to paroxysm, what can we say about the pathogenesis of the disease?
It is known , following observations from clinicians and the experiments of physiologists, that epileptic convulsions more or less similar to those of essential epilepsy can be provoked either by gross cortical lesions of psycho-motor regions, as observed for tumors, or under the influence of certain intoxications (especially on predisposed persons). But, for essential epilepsy, there is no gross lesions of the brain nor intoxication, at least well visible and defined. However, we have to take into account that, on one hand, this type of epilepsy presents a certain number of permanent character (nervous heredity, presence of degeneration, peculiar state of mind) and on the other hand the disease is observed in paroxysmic bursts, he is logical to conclude that, on one hand, the clinical feature of the epileptic is related to a specific predisposition and that on the other hand there is likely a periodic production of an agent that provoke the paroxysms.
Moreover, experimentation in the hand of M. Brown-Sequard has reproduced the two basic components: the epileptic status and the epileptic agent, generating the disease, namely epilepsy. This author has found that irritation of a specific part of spinal cord is followed, in the guinea pig, by two effects: on consisting of an epileptic state, that is the morbid state that renders possible convulsion attacks with loss of conscience, the other which is the possibility to provoke the attack. There is in the nervous system of the injured animal, a morbid effect strictly limited to the apparition of epileptic attacks, under the influence of agents that would not provoke convulsions on non-operated animals. Therefore, in some guinea pigs with a lesion of spinal cord, and that had no convulsive attack, asphyxia undertaken after provoked a frank and complete epileptic attack , instead of the ordinary convulsions of asphyxia.
By admitting that in epilepsy there is an abnormal excitability of psycho-motor regions, what could be these agents that provoke paroxysms.
The influence of a great number of those agents, most of them accidental, is already known: traumatism, fatigue, coitus, strong emotions, are susceptible in a few patients to provoke an attack.
There is an influence which, these days, seems to play a more and more important role for its involvement in paroxyms: intoxications, and in particular auto-intoxications. M. Pierre Marie, with whom we do not share its point of view related to the accidental origine and infection nature of epilepsy, has the merit to bring attention on the possible influence of infectious intoxications. Recently, M. Féré demonstrated, based upon his research on urotoxia of epileptics, that the toxicity of urines increase in the preparoxystic phase to diminish considerable after the crisis.
More recent studies are in favor of this aspect. M. Herter and Smith in 30 cas of essential epilepsy have examined the urines, not only for the levels of urea and uric acid, but also the indican and substances resulted from the presence and activity of intestinal putrefactions. But they believed from their research that intestinal putrefaction processes (on which bromure, to their opinion, has no effect) play an obvious role on essential epilepsy, in that there is a constant relationship between the intensity of these putrefactions and the frequency and feature of the crises. This excess of putrefaction processes would be a characteristic sign of the epileptic grand mal.
M.J. Cagney noticed, about two cases with peripheral neuritis that occurred in epilepsia, that the epileptic attack is probably determined, on predisposed cases, by a toxic influence more or less obscure, and he allocated this intoxication to the production of the observed neuritis.
For us due to 1° clinical facts showing that essential epilepsy is characterized by permanent manifestations and episodic paroxysms ; 2° experimental facts showing that that is is possible to determine a permanent epileptic state with episodic paroxysms ; 3° and our anatomical observations that establish that the origin of the morbid phenomenon is located in the psycho-motor region, despite the fact that this region does not present anatomical lesions that are possibly epileptogenic, we are in favor of essential epilepsy has the result of an abnormal excitability of cortico-motor regions whose anatomical origin is unknown, and with an excitability that provokes epileptic convulsions, whose production results sometimes and in specific conditions (including the integrity of the blood vessels) of substantial lesions, and for origin specific agents and at least in a few cases that are likely toxic.
Drs. PAUL BLOCQ and G.MARINESCO
Plate from Marinesco G, Étude anatomique et clinique des plaques dites séniles,
Encéphale (Paris), 1er semestre, 1912, 105–132.
Georges Marinesco: a pioneer of cinematography in neurology
In 1896, the Lumière brothers sent out crews, projectors, and cameras to various European cities including Bucharest to show moving pictures to the public and to record new material locally. The first Romanian documentary was presented to the general public in 1897.
The camera used to film that documentary was advertised in the Dreptatea newspaper, and subsequently Marinescu purchased his own model. Applying the apparatus to the study of neurologic subjects as early as November 1897, Marinescu compared cinematography with his former experiences with chronophotography or time-lapse methods .
In 1898, the Georges Marinesco began to film neurologic patients with one of his assistants, Constantin Popesco who also worked as a cameraman. Marinesco’s team was composed of other two interns, I.C. Parhon and S. Goldstein, and the French painter Jean Neyliès, a full-time collaborator of the neurology clinic. They set up a large dark screen in the yard of Pantelimon Hospital and used Marey’s methodology.
Between 1899 and 1902, Marinesco published eight papers on cinematography focusing on normal and pathologic gait. He successively studied hemiparesis, paraparesis, hysteria, ataxia, and muscle disorders. The sequences of stills were decoded abstractly in a physiopathologic approach, which was strongly influenced by the chronophotographic studies of Marey and Richer [1, 7].
Marinesco must be credited with the first medical thesis documented by motion pictures. The goal of illustration was also pursued in follow-up records. He suspended this cinematographic activity in 1902, linked with the departure of Popesco, his assistent and cameraman.
In 1973, Ion Cantacuzino, Alexandru Gaspar, and Corneliu Rusu began to make a documentary about Marinesco’s laboratory at Colentina Hospital. For this occasion, they invited Marinescu’s 81-year-old laboratory assistant, Maria Stoica.
During the filming, she remembered the location of 14 small Lumière film boxes with Marinescu’s signature on the lid. These were the original films forgotten in a small closet. The Romanian Sahia film studio in collaboration with the Romanian National Film Archive reprocessed the films. Currently, the original films are catalogued in the Romanian National Film Archive in Bucharest together with their reprocessed versions [1,6].
Only a few segments have been screened, although Ion Cantacuzino speaks of more than 70 patients. No catalog is available.
Already in 1899, Georges Marinesco summarized his views in a research and educational context: Cinematography allows us to discover phenomena that usually escape our gaze but also allows us to re-evoke them with ease. It is enough then to have good projections in order to show to our students various anomalies of gait, mimic and gesture even after we have lost sight of the patients. It allows us to follow the progression of the illness and its response to medical therapy or kinesitherapy. In this manner we have in our hands irrefutable documents to show the efficacy of treatment and at the same time reconstitute different phases of the illness. [1,15]
By comparaison, the first published mention of moving pictures in the United States dates to 1905 and came from Boston. After reporting the prior attempts of Alex McLane Hamilton, who reproduced pathologic gaits with a Lumière camera, Walter Greenough Chase expounded on the interest of the new medium in medicine. In a paper illustrated with single-frame excerpts, he presented a study of epileptic seizures performed with the assistance of Dr. Spratling and his assistants Collier, Shanahan, and Ross of the Craig Colony for Epileptics. Today, a short sequence of this study is conserved at the Huntley Film Archives, UK .
G. Marinesco’s followers
Nicolae Ionescu-Sisesti (1888-1954)
was first student in psychology at Wilhelm Wundt in Lepzig. He went eventually to Bucharest and Paris for medical studies. In Paris at the Salpêtrière Hospital in Paris, he became “interne” and “chef de clinique” under the guidance of Georges Guillain.
After his return to Bucharest in 1932 Sisesti worked closely with Marinesco. After Marinesco’s death, in 1938 Sisesti became Marinesco’ follower while he was leading the neurology clinic at Colentina Hospital and the Chair of Neurology at the Medical Faculty in Bucharest. He died suddenly in 1954 after an infection apparently occurred in his laboratory.
His contributions lie in studies on tumors of the medulla, psycho-galvanic reflexes, antigens and neuro-inflammatory processes. Sisesti published mainly in French. Two important contributions are linked to his clinical research, the formation pathologic cavities in nervous structures: syringomielia – cavities in medulla – Tumeurs médullaires associées à un processus syringomyélique, 1929 and syringobulbia – cavities in rachidian bulb, formation of cysts on the brainstem – La Syringobulbie – contribution à la physiopathologie du tronc cerebral, 1932. The importance of La Syringobulbie was highlighted by Joseph Godwin Greenfield (1884-1958) from the National Hospital for Paralysis and Epilepsy, London, in his major textbook – Neuropathology, which appeared in 1958.
Arthur Kreindler (1900–1988)
worked under the supervision of Marinesco at the Colentina Hospital. Together with Marinesco published in 1935, in France at Alcan Eds. a book on Pavlovian reflexes Des Reflexes Conditionnels, followed by Le Tonus des Muscles Striés, co-authored with Marinesco, Nicolae Ionescu-Sisesti and Oscar Sager, at Moniteur Officiel et Imprimeries de l’État, în 1937 with a foreword by the Nobel Prize winner Charles Sherrington .
Since 1948, he led the Neurology Institute of the Romanian Academy at the G. Marinesco hospital, setting up the postwar neuroscience research in Romania.
One of the highest cited works in electrophysiology is Kreindler’ Electroclinical features of convulsions induced by stimulation of brain stem, published în Journal of Neurophysiology in 1957. In 1965 Arthur Kreindler published Experimental Epilepsy, in the series Progress in Brain Research (vol. 19) by Elsevier, considered also as a standard in experimental neurology .
Oscar Sager (1894–1981)
Both collegue with Nicolae Ionescu-Sisesti and Arthur Kreindler, Sager was Marinesco’s pupil at the Colentina Hospital. Lecturer in 1940 in neurology, he was expelled at the pressure of the far right policy, during the 40’s in Romania, but returned in 1945 as Professor of neurology in Timisoara. Since 1955, Sager was leading the neurology clinic at Colentina after the death of Ionescu-Sisesti. With Marinesco’s help, Sager was visiting fellow in Holland at J.G. Duser de Barenne. With Barenne he focused on primate brain research and published 1937, the Sensory findings of the optic thalamus of the monkey, in Archives of Neurology and Psychiatry, widely cited as well. Another standard work by Sager is The Diencephalon (Romanian Academy of Sciences Press, Bucharest, 1962).
Ion T. Niculescu (1895-1957)
Worked before the second World War at Marinesco’s neurology clinic at the Colentina Hospital. He met also Dumitru Noica, another Romanian neurologist who made his studies in Paris with Joseph Babinski and Jules-Joseph Déjerine at the Salpêtrière Hospital
Since 1920, Niculescu was at the Chair of Histology at the Medical Faculty in Bucharest and became there Professor in 1936 until his death in 1957. Between 1922-24, Niculescu went to Paris to work at Salpêtrière and Ivry with Pierre Marie and Charles Foix (1882-1927). Together with Foix, Niculescu made contributions on the microscopy of thalamus, diencephalon nuclei, and neuropathology of contagious encephalitis, and published on the anatomy and blood supply of the midbrain and interbrain : Les noyaux gris centraux et la région mésencéphalo-sousoptique (1925). His late works were a treatise on neuropathology, Tratatul de Morfopatologie a Sistemului Nervos (1957) and morphology of nervous visceral terminal endings. Posthumously in 1959 the Romanian Academy edited with the French publishing label Masson a collected works of Niculescu.
Nicolas Paulesco and the transcranial hypophysectomy
Georges Marinesco was one of the first to report in 1892 the results of experimental hypophysectomy in eight cats and concluded that this procedure was compatible with survival for just few weeks .
Nicolas Paulesco described later a reliable technique for transcranial hypophysectomy in 1907, and came to a more nuanced conclusion. Paulesco and his collegue, the surgeon Balacesco, 1907, used a technique of “cerebral dislocation” to expose parts that would otherwise be inaccessible. His technique was a transtemporal approach which necessitated lifting the temporal lobe to gain access to the pituitary. In his series all the dogs from which the pituitary had been completely removed died within 24 hours following operation – after total transcranial hypophysectomy; two of the seven that had been partially hypophysectomized lived for 5 months; another lived for a year. Separation of the hypophysis from the base of the brain and total selective adenohypophysectomy were equivalent to a complete hypophysectomy. Therefore, Paulesco described a new procedure for the surgical removal of the pituitary gland that favored improved patient survival [11, 19-22].
Nicolas C. Paulesco, in full Nicolae Constantin Paulescu, (1869-1931, Bucharest), was the Romanian physiologist who conducted groundbreaking research on the antidiabetic hormone insulin. In 1888 he went to Paris to study medicine, and three years later he took a post as a nonresident medical student at the Hôtel-Dieu de Paris. There he worked with French physician Étienne Lancereaux, who was the first to suggest that diabetes mellitus originated in the pancreas, and with French scientist Albert Dastre, who had studied with Claude Bernard, the renowned physiologist who discovered the role of the pancreas in digestion. In 1901, after having received a degree in medicine (1897) and doctorates in physiology (1898) and the natural sciences (1899) from the University of Paris, Paulesco returned to Romania, where he joined the faculty of medicine at the University of Bucharest.
Paulescu’s research inspired subsequent work by American neurosurgeon Harvey Cushing, who later gained international acclaim for his research on the pituitary.
Cushing (1909), together with Crowe and Homans (1910), Lewis Reford (1909), and the rest of his team of surgical residents, followed up Paulesco’s work by using the latter’s technique in performing a large series of hypophysectomies in dogs. Their conclusions were similar to Paulesco’s: the pituitary was essential to life.
Cushing himself took a personal interest in Reford’s project. They found that the best work was being done in Romania by the physiologist Nicolas Paulesco, who had developed what seemed to be an ideal surgical approach to the pituitary of dogs. Using and refining Paulesco’s technique, and applying the extreme antisepsis and care that Cushing required for surgery on dogs and humans alike, Reford, soon joined by Samuel J. Crowe and John Homans, removed pituitaries from dozens of dogs. They mastered the operation and could do it in less than an hour; their speed and their unlimited supply of dogs – they eventually depituitarized more than a hundred – generated more experimental results than anyone else had the luxury of studying. Most of the dogs died, confirming Paulesco’s findings and the view that pituitary secretions are essential to maintaining life [8,9].
Cushing found, “in agreement with Paulesco, that a state of apituitarism due to total removal of the hypophysis leads invariably to death of the animal, with a peculiar and characteristic train of symptoms (cachexia hvpophyseopriva)”. Manifestations of hypopituitarism were also adiposity, secondary hypoplasia of the sexual organs, persisting sexual infantilism, polyuria, glucosuria, skin alterations (edemas and hypotrichosis), and lethargy, a clinical state corresponding to nowadays Fröhlich syndrome – adiposogenital dystrophy.
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10. Foix C, Nicolesco J. Anatomie cérébrale: les noyaux gris centraux et la région mésencéphalo-sous-optique; suivie d’un appendice sur l’anatomie pathologique de la maladie de Parkinson. Paris: Masson; 1925.
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