Eponims in Neuroanatomy

Herein it is reviewed several contributions to neuroanatomy in the period extending from the renaissance, when interest in the old Greek medicine revived, to the end of the 18 th century. I will concentrate on three eponyms: 1) the circle of Willis; 2) the Sylvian fissure; 3) the foramen of Monro. The work of these three eponymists will be put into the context of the evolution in neuroanatomy of the period in which they worked. Contributions to neuroanatomy have been added over the centuries, although to a lesser degree in the period between Galen (130-200) and the renaissance. Galen’s work had been authoritative for over twelve centuries. Medieval physicians kept to his anatomy unquestioning. It had about the same status in medicine as the bible in religion. Important renovations started in the renaissance period.

It became possible to dissect human beings, in some cases only once a year (14 th century), at first mainly to confirm Galen’s findings. Although Mondino de Luzzi (1275-1326) had dissected thirteen bodies himself, his successors again climbed the cathedra to leave the handwork to their assistants. 1,p.125 Among the first persons in this period to work on neuroanatomy was Leonardo da Vinci (1452-1519), one of the great artists of Italian renaissance. He is known to have produced beautiful neuroanatomical work, but he is not considered important with this respect as his work did not contribute to progress during his period. Much of his work was kept in sketchbooks to be discovered more than two centuries later. With respect to general anatomy, Vesalius (1514-1564) is considered one of the most important anatomists, as he discovered many errors in Galen’s teachings. He did not neglect the nervous system. His Fabrica (1543) shows several neuroanatomical figures. In the seventh book e.g., fifteen diagrams of the brain are depicted. With respect to neuroanatomy Giacomo Berengario da Carpi (c.1460-c.1530, also known as Berengarius), who was born near Modena and taught in Pavia and Bologna, handed the knife himself, like Da Vinci, and opened many bodies. He discovered an error in Galen’s neuroanatomy prior to Vesalius: he found that there is no rete mirabile, a plexus of anastomising vessels at the base of the brain in human being (1523). 2,p.38 Other persons who made contributions to neuroanatomy during this period were the German Lorenz Fries (Laurentius Phryesen 1489-1550), the French Charles Estienne (1503-1564, also called Stephanus), the German Johann Eichmann (Dryander 1500-1560) and the Italian Bartolomeo Eustachi (1520-1574, also called Eustachius, well-known for the tube he described, but that was known previously to Alcmaeon of Croton as was mentioned by Aristotle). Although Eustachius produced good pictures of the base of the brain, including cranial nerves and pons, the latter structure is associated with Varolio. Vesalius (1514-1564) From Fabrica (1543) book VII fig. 7A new method in brain anatomy - The pons Varolii Costanzo Varolio, also called Varolius (1543-1575) was professor of anatomy at Bologna university, the oldest university in the world, founded in 1088. He became physician to pope Gregory XIII. His method for dissection of the brain was new. Whereas his predecessors dissected the brain from top down, he made sections from base to top. He wrote about his new method in a letter addressed to Gerolamo Mercurale (1530-1606; Padova, 1572). By applying this method, it was easier to observe structures at the base of the brain. In his 1573 De nervis opticis nonnullisque aliis praetor communem opinionem in Humano capite observatis. (Patavii, apud Paulum et Antonium Meiettos fratres), he was able to observe several structures, including the hippocampus, the cerebral peduncles, and the pons. The latter structure had been omitted by Vesalius (Fabrica, 4 th book). Furthermore, he was able to describe the course and termination of the cranial nerves. 2,p.49 Moreover, he followed the course of the optic nerve. 3,p.216 Varolius (1543-1575) ‘Processus transversalis cerebri, qui dicitur Pons’ Dye injections in neuroanatomy - The circle of Willis 2,p.55-61,4 Entering the 17 th century, several important contributions to neuroanatomy were made. Probably the most important person was Thomas Willis (1621-1675). He studied at Oxford University, after which he became one of the most important physicians there and a member of the Virtuosi, an informal group of experimental scientists. He described his method of medical research, based on careful notes taken on individual patients, as what might be called inductive generalization. He compared the notes of his observations and adapted general notions from particular events. 5 This method became the common denominator of his clinical writings (1659 to 1675). He developed his own chemical, neuroanatomical, and neuropathological research and lectured about the results and their interpretation. At the time, he was still aware of Aristotle, but even more of the "moderns", including Pierre Gassendi (1592-1655), the Epicurean antagonist of René Descartes. The philosopher John Locke (1632-1704), a medical student, took notes of Willis' lectures. Willis’ books were printed in Latin, but they are now usually quoted from the 1681 English translation by the Restoration playwright, Samuel Pordage (1633-1691), which is far from accurate. 6 This is a serious source of misunderstandings, since researchers of our time regularly mistake Pordage's translation for Willis' original. Willis' The anatomy of the brain (1664), probably his best known work, is the source for the eponym, the Circle of Willis. 7 The book was the result of a first attempt to use what would now be called an interdisciplinary approach to unravel the secrets of the nervous system. Willis had previous experience of working in teams with William Petty (1623-1687), other Oxford Virtuosi, but also with practicing physicians. He and his collaborators, Richard Lower (1631-1691), Thomas Millington (1628-1704), and Christopher Wren (1632- 1723, architect of St. Paul's cathedral in London), used neuroanatomy, comparative neuroanatomy, animal experiments, pathological neuroanatomy, intravenous dye injections, and several new ways of preparing human and animal brains. The intravenous dye injections were only second to work of the Dutch anatomist Frederik Ruysch (1638-1731). Willis’ descriptions and illustrations of the brain and its vessels and nerves were more accurate and complete than what had been presented before. ...we have already shewn, that these Vessels are variously and very much ingrafted or inoculated among themselves, not only the Arteries with the Veins, but what is more rare and singular, Arteries with Arteries; to wit, the Carotidick Arteries of one side, in many places, are united with the Carotides of the other side; besides the Vertebrals of either side among themselves, and are also inoculated into the posterior branches of the Carotides before united. The joynings together of the Carotides, in most living Creatures, are made about the Basis of the Skull under the Dura Mater... 8, p.82Thomas Willis (1621-1675) The Circle of Willis The system of anastomoses at the base of the brain had been partly described previously by Gabriele Fallopio (1523-1562), a pupil of Vesalius, Guilio Casserio (1545-1605), teacher of William Harvey (1578- 1657), Johann Vesling (1595-1649), both teaching at Padua, and others. The Swiss physician Johann Jakob Wepfer (1620-1695) is said to have priority over Willis for the complete description of the Circle in his book on stroke of 1658. 9,p.65 However, the arguments in favor of Willis are stronger. He published the first complete illustration of the Circle, probably drawn by Wren, with the help of the new method of taking the brain out of the skull developed by Willis' team. His case of a man who died of a mesenteric tumor, having lived without any neurological deficit despite a nearly obliterated right carotid artery, probably with the help of the right vertebral artery, which was three times its normal size, shows that Willis was aware of the physiological importance of the Circle. In his work, the original anatomical preparation, its correct illustration, and the interpretation within a coherent clinical, neuroanatomical, and neurophysiological context provide the background and adequate setting for the eponym. Willis reclassified the cranial nerves into nine pairs, moving the trochlear nerve to the fourth position (from the original eighth). Terms introduced by him were thalamus opticus, lentiform bodies, and corpus striatum. He also described the spinal accessory nerve. He attributed vital functions to the cerebellum due to imprecise experiments, probably also damaging the lower brainstem. He localized perception in the corpora striata, memory to the gyri, instinct to the midbrain, and imagination to the corpus callosum, moving away from the ancient ventricular localization. 2,p.55-61 He wrote on several ‘diseases of the brain’, including convulsive diseases, seizures, hysteria, hypochondria, and extrapyramidal disorders. In his London Practice of Physick (1685), he described myasthenia gravis, but also cases of migraine. He described what would come to be known as Jacksonian epilepsy, explaining the gradual progress of the convulsions as the result of accumulation of exploding animal spirits in the nerves originating in the brain, a typical iatrochemical explanation of the period (vide infra). In a treatise on hysteria and hypochondria, he appended a discourse on the warming of the blood, introducing the theory of internal combustion within the blood, with the help of oxygen absorbed from the lung. Another appended treatise, "of muscular motion", explained muscle contraction as an effect of explosions with the muscle, increasing its volume, and shortening its length. In his De anima brutorum (1672), he wrote two chapters on headache. He classified different types of headache according to the time pattern (continuous, intermittent and intermittent with vague and uncertain attacks). This division shows similarities to the one used in the classification of fevers. Interesting is the following part from these chapters: he mentioned that headache may appear in seasonal clusters of daily attacks at fixed hours. He observed polyuria as a symptom of migraine attacks, slowly ascending aura symptoms, as well as premonitory symptoms, such as hunger. He described symptoms that may be interpreted as a slowly spreading spasm and presumed that headache is caused by increased supply of blood, moving more rapidly "and, boiling up towards the head, is constricted, or stopped, in its passage at predisposed sites; then it soon gathers there in greater abundance and distends the vessels, strongly inflating the membranes, tearing the nerve fibres apart from each other, and thus inducing painful corrugations in them". 10 In April 1657, Willis married Mary Fell and they had nine children. He was elected Fellow of the Royal Society in 1663, and in 1666, he moved to London, where he lived as a practicing physician. After the death of his wife in 1670, he married Elizabeth Calley in 1672. Willis died from pneumonia in 1675 and was buried in Westminster Abbey. Another method of brain sectioning - The Sylvian Aqueduct and Fissure 11,12 The name Sylvius is associated with various structures within the nervous system, including the fissure and aqueduct between the third and fourth ventricle. The latter structure has been associated with Jacobus Sylvius (1478-1555), the Paris professor of anatomy, who was one of the teachers of Vesalius The aqueduct,however, had already been mentioned in De usum partium, where Galen pointed to a canal that provided a communication between the cerebrum and cerebellum. However, he may have meant the extension of the third ventricle into the subarachnoid space (recessus pinealis). In his Fabrica (1543), Vesalius mentioned an ‘anuslike orifice of the meatus which extends from the third to the fourth ventricle’ below the quadrigeminal bodies. Jacobus Sylvius probably used the description of his pupil Vesalius. However, this was not the source of the ascription of the aqueduct to Sylvius. The source is found in chapter 21 of Sylvius’ Disputationem medicarum decas (1663), where he described a canalis vel aquae-ductus between the conjoined roots of the spinal cord and under "our bridge" [pons Varoli] and the corpora quadrigemina. The aqueduct was certainly known before Sylvius, and in that respect Haller 13 and Morgagni 14 were correct when they called attention to the impropriety of naming the aqueduct after Franciscus Sylvius. It seems that the attribution followed Thomas Bartholinus' words, a homage to his contribution to the anatomy of the cerebrum. Franciscus dele Boë (1614-1672), called Sylvius, descendant from a protestant family from Cambrai, France, whose family had moved to Germany for religious reasons, was born in Hanau. Following his medical studies at the universities of Sedan, France and Leiden, The Netherlands, where he held a disputation entitled Positiones variae medicae (1634), he made a study-tour to Southern German universities. He became doctor of medicine at the university of Basel (1637), defending a thesis entitled De animali motu ejusque laesionibus. Following a short period of practicing medicine in his birthplace, he graduated again at Leiden University in 1638. During the second period there, he became famous for his anatomy courses. In the funeral oration, it was said that “many students, and certainly not the worst ones, attended his courses, so that it seemed as if only he could understand and explain anatomy”. 15 One of these students was Thomas Bartholinus (1616- 1680), son of the famous Danish anatomist Caspar Bartholinus (‘the elder’, 1585-1629). Thomas' notes of the course of 1640-1641 were included in the 1641 edition of his father's well-known textbook Institutiones anatomicae. They were later published separately as Dictata ad C. Bartholini Institutiones Anatomicas in Sylvius's Opera. Franciscus dele Boe, Sylvius (1614-1672) Thomas Bartholinus (1616-1680) Physiology at the time was an integral part of anatomy. It was not unusual that Sylvius demonstrated the circulation of the blood. He convinced the professors of the medical faculty of the truth of William Harvey's theory. In fact, Harvey’s 1628 publication (De motu cordis) had caused a scientific storm, leading to a flood of publications pro and contra. The reaction was similar to the one caused by Vesalius’ 1543 publication, also considered by some to be a form of impetuous modernism against the authority of Galen. Several physicians and philosophers working in the Netherlands, defended the theory, including the physician Johan van Beverwijck (1594-1647) and René Descartes (1595-1650; see his Discours de la méthode, although he misinterpreted the diastole), who both corresponded with Harvey. The circulation-concept was not new to Sylvius; he had already defended the lung circulation in his thesis of 1634, i.e. six years after Harvey's De motu cordis. Since there was no prospect of a professorship in Leiden, Sylvius moved to Amsterdam (1641), where he practiced for seventeen years, spending his leisure hours in anatomy and chemistry. In 1658, he returned to Leiden, where he became professor of medicine, officially accepting the chair with an inaugural address De Hominis Cognitione. He often taught at the bedside during daily visits to patients in the local Caecilia Hospital, usually about frequently occurring diseases. Applying the Socratic method, he guided his students to the correct diagnosis, prognosis, and therapy. He demonstrated the nature of the pathological changes by post-mortem examination. His clinical teaching method attracted many students even from abroad. Little is known of Sylvius's family life. He married Anna de Lingne in 1649, when he was still living in Amsterdam. They had two children that died early. His wife died in 1657, the year before Sylvius moved to Leiden. In December 1666, he married Magdalena L. Schletzer. One daughter was born from this marriage, but both, mother and daughter died during the plague of 1669, Magdalena at the age of 21. Sylvius suffered seriously from the plague but survived.Anatomy was one of the pillars of Sylvius's medical system. His contributions to the anatomy of the brain were recognized by Thomas Bartholinus, who wrote in the revised edition of his father, Caspar's anatomy textbook (1641, translated and published several times) that ‘we can not pass over in silence the very accurate anatomist D. Franciscus Sylvius [since] we borrow from his noble brain and ingenuity the admirable new structure of the brain’. 16 Sylvius' "notae de cerebro" are clearly indicated by "F.S." in the textbook. According to his pupil Niels Stensen (1638-1686), he developed his own method of dissecting the brain. It may be considered a combination of the traditional approach of Galen and that of Varolius, whose method was described above. The discoveries in neuroanatomy were published in the disputation De spirituum animalium in cerebro, cerebelloque confectione, per nervos distributione, atque usu vario, defended by the student Gabriel Ypelaer under Sylvius' supervision in 1660. It was included as fourth disputation in Sylvius' Disputationem medicarum decas (1663). The fissura cerebri lateralis Sylvii is described in paragraph nine of the thesis. ...the surface of the cerebrum is very deeply marked by twistings (gyri) which are somewhat similar to convolutions of the small intestine. Particularly noticeable is the deep fissure or hiatus which begins at the roots of the eyes (oculorum radices)... it runs posteriorly above the temples as far as the origin of the brain stem (medullae radices). It divides the cerebrum into an upper, larger part and a lower, smaller part. Twistings occur along the fissure's length and depth even with the origins of smaller convolutions at the most superior part of it. 17 The Sylvian fissure This is no doubt the first description of this structure, as is testified by Albrecht von Haller (1708-1777). 18 It derives from Sylvius' accurate study of the outer surface of the brain carried out as a consequence of his interest in the distribution of the vascular system on the brain surface and from his interest in the gray matter as far it was related to the production of the animal spirits. Iatrochemistry in Sylvius’ and Willis’ work 1,pp.148-54,11 Following the discussion of Willis and Sylvius, a few words should be dedicated to important physiological ideas of the period. As written above, physiology at the time was naturally included in the subject of anatomy. The discovery of the circulation endorsed the iatrophysical school of thought, in which physicians tried to explain physiology and pathophysiology by physical ways. Another school of thought at the time was iatrochemistry, a system in which physiology, pathology, and therapy were described in chemical terms. The latter system is considered to have been prepared by Paracelsus (1493-1541) and Van Helmont (1577-1644). The Scientific Revolution led to new ideas about the processes of food assimilation, excretion, and breathing. Moreover it furthered new practices in drug therapy. 19 Sylvius may be considered one of the proponents of iatrochemistry. In fact, his iatrochemistry was a chemical humoral pathology. Fundamental to his system was the effervescence, i.e. the vehement reaction between acid and alkaline secretions thought to occur, for instance, in the duodenum or the right ventricle of the heart. Sylvius rejected the classical qualities and humors. From classical physiology, he only retained the concept of animal spirits. These spirits were believed to be isolated from blood and transported by the carotid and cervical arteries in the capillaries of the brain surface in a process analogous to distillation. The most spiritual part of the blood passed the pores of capillaries, first in the gray matter and then in the white matter. During this process, the aqueous parts were eliminated and "coagulated" to a fluid which moved through the ventricles. The animal spirit was the finest and purest body fluid. It resembled wine spirit, easily evaporating and expanding. It was partly used in the brain itself and partly transported through the nerves to the muscles. There, the unused animal spirit was reabsorbed by lymphatics and returned to the blood for re-use. Sylvius published his pathophysiology under the title Praxeos medica idea nova. Unfortunately, he could only complete the first volume (1671). The other volumes were published posthumously by a former pupil.Generally speaking, diseases were caused by abnormal effervescences due to abnormal secretions that could be either sharp alkaline or sharp acidic. A defective animal spirit resulting from accumulation of a volatile acid spirit, for instance, was thought to cause epilepsy. For treatment the physicians prescribed alkaline salts, opposing the action of the excess of acid. Although Sylvius had many pupils who became famous (Bartholinus, Stensen, De Graaf, Swammerdam), iatrochemistry in the Netherlands was not endorsed by influential naturalists. However, this was different abroad, for instance in Germany, France, and England. In the latter country, Willis was considered an important advocate of iatrochemical physiology, applying the method in practice in a more scientific way than Sylvius. Spirits, salt, sulfur, water, and earth were considered the elements causing fermentation in the body. He attached importance to the animal spirits, pushing Sylvius’ role of alkali and acid to the background. Finally, however, the iatrochemical school was defeated by the iatrophysical school. The iatrophysical school 1,p.153-4, 2, p.71-9 Although Isaac Newton (1642-1727) is considered one of the most important scientists of the so-called Scientific Revolution of the 16 th and 17 th centuries, one of the founders of mechanics in Italy was the Galileo Galileï (1564-1642), who opined that measuring and weighing should be among the principles of physics. This country would be the first where naturalists tried to explain biological functions in this way. Sanctorius (1561- 1636), professor in Padua and Venice, tried to introduce several instruments for measuring physiological and pathological processes. Other important naturalists to apply iatrophysics were Giovanni Alfonso Borelli (1608- 1679), who, like Descartes, stayed at queen Christina’s court in Sweden, Lorenzo Bellini (1643-1704), and Giorgi Baglivi (1668-1707). Borelli believed that muscles contracted by discharge of a fluid from the hollow nerve into the muscle. Using a nerve-muscle preparation, the Dutch naturalist Jan Swammerdam (1637-1680) demonstrated that the nerve did not inflate any substance into the muscle. The volume of the muscle did not change during contraction. Typical iatrophysical pictures from Giovanni Alfonso Borelli (1608-1679) Borelli’s De motu animalium (1680) One of the most influential proponents of the iatrophysical school was René Descartes (1596-1650), who lived at several places in The Netherlands for a large part of his life, where most of his books were published. He became one of the proponents of the iatrophysical school, which may be demonstrated in several of his books, including Des passions de l’âme (1649) and De Homine (1662), in which he demonstrated reflex action. The Danish Niels Stensen (1643-1686) may also be considered an important iatrophysicist. He was very critical about Willis’ De cerebri anatome, demanding a more scientific approach, reproaching him too many speculations. During a presentation in Paris (at Thévenot’s home, 1665), he said: ‘Messieurs, au lieu de vous promettre de contenter vostre curiosité touchant l’anatomie du cerveau, je vous fais icy une confession sincère et publique, que je n’y connois rien [sic]’. [Gentlemen, instead of promising to satisfy your curiosity with regard to cerebral anatomy, I confess sincerely and publicly, I don’t know anything about it]. 20 Though living a few decades later, another important proponent of iatrophysics was Herman Boerhaave (1668-1738), who is best characterized as a systematist. ‘He taught a body of doctrines whose parts integrated one with the other to form a well-organized whole’. 21 Almost every phenomenon dealing with health or disease could be explained in this system. The systems originated from observation complemented by reasoning. In fact, his system had three major sources, a) the laws of mechanics (iatrophysics); b) findings from microscopy; and c) knowledge resulting from vascular injections. 22Interestingly, some critics considered the iatrochemical and iatrophysical schools phenomena of decay, returning to pre-renaissance deduction instead of modern induction, in which observation and experiment played an important role. Bedside observation gradually became more important than theorizing. The most important medical school, applying bedside teaching, in the first part of the 18 th century was Leiden University, where Boerhaave was teaching. With respect to (patho)physiology, he applied humoral as well as solid theories. He considered nerves to be hollow, arising from the medulla of the brain and spinal cord. Spirits still formed the basis of his explanation of the function. He localized the sensorium commune at the transition of white and gray matter. His teachings belong to the most influential of the 18 th century. After his death in 1738, the centre of medical teaching gradually moved to Edinburgh, where the following eponymist would teach. The foramen of Monro 23 Alexander Monro "Secundus" (1733-1817) was born in a family of medical tradition. His grandfather John Monro (1670-1740) had studied medicine at Leiden under his compatriot Archibald Pitcairne (1652-1713), and became one of the protagonists of the foundation of a medical school at Edinburgh. John Monro trained his son Alexander Monro "Primus" (1697-1767) to become the first professor of anatomy at Edinburgh (1719), after studying with Boerhaave in Leiden, and with William Cheselden (1688-1752) in London. Monro “Secundus” began his medical studies at Edinburgh in 1752. He also became a pupil of William Hunter (1718- 1783) in London. He began to give evening lectures in anatomy for his father in his second year as a medical student (1753). He took his MD degree and became assistant professor of anatomy and surgery two years later. He stayed in Berlin with Johann Friedrich Meckel (1714-1774) for a short period, and when his father became ill, he took over the Edinburgh anatomy chair from him (1758). In addition to teaching students anatomy, medicine, and surgery for over fifty years, increasing from about sixty to over 400 students a year by 1800, Monro "Secundus" was considered one of the leading Edinburgh practicing physicians. "Secundus" later also occupied chairs in medicine and surgery, and passed on his chair of anatomy in 1798 to his son Alexander Monro "Tertius" (1773-1859), who occupied the chair till 1846, keeping it a "family chair" for 126 years. Despite the fact that he held three chairs, including that of surgery, Monro "Secundus" practiced little surgery. Moreover, he failed to teach surgery and surgical anatomy adequately, which led the Edinburgh surgeons to ask for a separate chair of clinical surgery; but Monro succeeded in blocking the proposal. Another black mark against "Secundus" was his manipulation of the succession of his son Alexander "Tertius" to his chair of anatomy. Charles Darwin (1809-1882), who came to Edinburgh to study medicine in 1825, wrote that the lectures of Monro "Tertius" on human anatomy were as dull as he was himself. 24 "Secundus'" first original book was: Observations on the Structure and Functions of the Nervous System (1783), 25 containing his unpublished much earlier work on the anatomy of the cerebral ventricles. The clinical content was clearly influenced by his senior colleague Robert Whytt (1714-1766), who had been professor of both the practice of medicine, and of the institutes of medicine (physiology). Whytt was one of the originators of the pre-eminence of the Edinburgh school later in that century (after Boerhaave’s death in Leiden, 1738); it attracted students from afar, including the future leaders of American medicine, by the quality of the teaching of Joseph Black (1728-1799) in chemistry, William Cullen (1710-1790) and John Gregory (1725-1773) in medicine, and of Monro "Secundus" in anatomy, as well as in medicine. Monro "Secundus’ " studies included the anatomy of the eye and ear, and the nature of the nerve impulse. He was acquainted with the leaders of the "Scottish Enlightenment", the historian William Robertson, the philosopher David Hume, the economist Adam Smith, the chemist Joseph Black, the mathematician John Playfair, as well as his medical colleagues. He was married to Katherine Inglis by whom he had seven children. He continued to teach till 1807 and died in his 85th year in 1817. In his classical Observations on the Structure and Functions of the Nervous System (1783) Monro “Secundus” stated that he had first demonstrated the foramen (or, more correctly, the two foramina) thirty years earlier at the age of 20 years. So far back as the year 1753, soon after I began the study of anatomy, I discovered that the lateral ventricles of the human brain communicated with each other, and at the same place, with the Middle or Third ventricle ... the four ventricles are in reality different parts of one cavity. 25 In this book he also quoted a letter written in 1762 in Latin by John Morgan (1735-1789) to Sir John Pringle (1707-1782) about Monro's demonstration of the foramen to himself and other Edinburgh students; Morgan was to be the founder of the first American medical school in Philadephia. In 1764 Monro “Secundus”, with Whytt and his own elder brother Donald Monro (1728-1802), consulted on a three year old boy with hydrocephalus, which was followed by autopsy. In December of the same year, he read a paper to the Edinburgh Philosophical Society, the forerunner of the Royal Society of Edinburgh, on the communications of the ventricles. Although he was the Secretary of the Society, he did not publish it in the Society'sTransactions. The book contains drawings of the normal third ventricle, marking the site of the foramen, the anatomical relations, the vein from the lateral ventricle passing through the foramen into the third ventricle, to form posteriorly the vein of Galen. Monro gave due credit to earlier anatomical descriptions of the cerebral ventricles which had indicated continuity of the four ventricles, particularly by Galen. Monro also referred to observations by Vieussens, Winslow, and Lieutaud, but was critical of their lack of anatomical detail. A major, and wrong, criticism by Albrecht von Haller's (1708-1777), was Monro's denial of connection between the fourth ventricle and the spinal canal: the correct detailed description of the fourth ventricle foramina came from François Magendie (1825) and Hubert von Luschka (1859), whose names are still associated with the medial and lateral foramina respectively. Monro would not have known Leonardo da Vinci's drawings of wax casts of a continuous ventricular system. 26 Monro's other book (1797), 27 entitled Three Treatises of the Brain, the Eye and the Ear, of which the first is Observations on the Communications of the Ventricles of the Brain with each other and on the Internal Hydrocephalus, repeats the 1783 descriptions, with further drawings of normal anatomy by Andrew Fyfe. In the 1797 text Monro discusses the symptoms and signs of both chronic and acute hydrocephalus, following Whytt's earlier teaching, and properly dismisses both medical and surgical treatment of hydrocephalus. As recently as 1925 Harvey Cushing 28 had to agree with this negative attitude: ... infants with hydrocephalus - for which a greater number of treatments have as yet been advocated (I have been guilty of advocating one or two myself) than successes recorded - if indeed there are any clear-cut successes recorded. They have come since, with the advent of tolerable plastic shunt tubing. Also, structural abnormalities at the foramen of Monro are often amenable to direct neurosurgical treatment. Alexander Monro "Secundus" (1733-1817) F: a natural passage by which the lateral ventricles communicate with each other and with the third ventricle (1783) The clinical significance of the interventricular foramen of Monro is based on disorders of the "third" circulation, that is, the circulation of the cerebro-spinal fluid (CSF), as described by Retzius, Key, Weed, Cushing, and others. The CSF stems mainly from the choroid plexus in the lateral ventricles, passes through the foramen of Monro into the third, and thence through the aqueduct of Sylvius into the fourth ventricle, and on into the subarachnoid space via the foramina of Magendie and Luschka. The foramen of Monro is one of the narrows, liable to obstruction by any pathological process in, or near, the third ventricle. Such an obstruction will lead to dilatation of one, or more likely both, lateral ventricles, with symptoms of raised intracranial pressure: headache and vomiting, disorders of consciousness, eye movement and pupillary disorders, as described two and a half centuries ago by Whytt and Monro.Expanding lesions at this site are the various gliomas of the third ventricle; more chronic processes are upward extensions or pituitary tumors and craniopharyngiomas, which may cause pituitary of hypothalamic disorders en route, and rarely akinetic mutism, before leading to symptoms and signs of raised intracranial pressure. The most benign lesions are colloid cysts. It is ironic that one such cyst was found post mortem in the third ventricle of Cushing, one of the pioneers of surgery in this territory. 29 A heavy smoker, Cushing died of vascular disease before the cyst had become large enough to obstruct his foramen of Monro. References 1 Lindeboom GA. Inleiding tot de geschiedenis der geneeskunde (7e editie, bewerkt door MJ van Lieburg). Rotterdam, Erasmus Publishing, 1993 2 McHenry LC. Garrison’s History of Neurology. Springfield (IS): Thomas; 1969. 3 Norman JM. Morton’s Medical bibliography. 5th edition. Aldershot (Hants): Scolar Press; 1991. 4 Isler H. The circle of Willis. In: Koehler PJ, Bruyn GW, Pearce JMS. Neurological eponyms. New York, Oxford University Press, pp. 56-62. 5 Isler H. Thomas Willis 1652-1675, Doctor and Scientist. New York, Hafner Publishing Company, 1968. 6 Dewhurst K. Willis' Oxford Casebook. Oxford, Sandford Publications, 1981. 7 Willis T. Cerebri Anatome: Cui accessit Nervorum Descriptio et Usus. Londini 1664, types Jac. Flesher, Impensis Jo. Martyn & Ja Allestry. Oxoniae, e theatro Sheldoniano, 1672. 8 Willis T. The anatomy of the brain and the nerves. Feindel W. (Ed.). 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