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Home , Ancient Egypt, Menes, Rufus of Ephesus

Neurosurg Focus 33 (2):E2, 2012

The journey of discovering skull base in ancient and the special influence of

Ali M. Elhadi, M.D., Samuel Kalb, M.D., Luis Perez-Orribo, M.D., Andrew S. Little, M.D., Robert F. Spetzler, M.D., and Mark C. Preul, M.D. Division of Neurological , Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, , Arizona

The field of anatomy, one of the most ancient , first evolved in Egypt. From the Early Dynastic Period (3100 bc) until the time of at the end of the 2nd century ad, Egypt was the center of anatomical knowledge, in- cluding neuroanatomy. Knowledge of neuroanatomy first became important so that sacred rituals could be performed by ancient Egyptian embalmers during mummification procedures. Later, neuroanatomy became a tobe studied by wise men at the ancient of Memphis. As religious conflicts developed, the study of the body became restricted. started to replace scientific research, squelching further exploration of the human body until founded the city of Alexandria. This period witnessed a revolution in the study of anatomy and functional anatomy. Herophilus of Chalcedon, of Chios, Rufus of Ephesus, and Galen of Pergamon were prominent physicians who studied at the medical school of Alexandria and contributed greatly to knowledge about the anatomy of the skull base. After the Royal was burned and were passed prohibiting human dissections based on religious and cultural factors, knowledge of human skull base anatomy plateaued for almost 1500 years. In this the authors consider the beginning of this journey, from the earliest descriptions of skull base anatomy to the establishment of basic skull base anatomy in . (http://thejns.org/doi/abs/10.3171/2012.6.FOCUS12128)

Key Words • Egypt • skull base anatomy • dissection • • Alexandria • brain extraction • Herophilus • neurosurgical history

he earliest descriptions of the anatomy of the skull the earth, the giver of grain, bears the greatest source of base date to the ancient and . It drugs, many that are healing when mixed, and many are has been claimed that anatomy was born in ancient baneful, there every man is a physician wise above - TEgypt or at least was practiced there somewhat systemati- man kind.”36 Many kings of other surrounding ancient cally, perhaps because of religious rituals involving prep- cultures sought medical advice from Egyptian physi- aration of the body and its organs for the next realm of life cians, often traveling far distances for personal attention. after death.12 Focusing on the earliest descriptions to the For example, Niqmaddu II, the king of , asked the establishment of basic cranial, including the skull base, (1375–1334 bc) for an Egyptian phy- anatomy in ancient Egypt, this historical review tracks sician.21 King Hattusili III of the asked Ramses the very beginning of the anatomical journey that eventu- II to provide him a physician to cure his sister, and even ally formed the knowledge base underlying the success of , the ruler who united the and the the neurosurgical specialty of skull base surgery. Persians, requested an Egyptian ophthalmologist to treat an eye injury.19 It appears that even though there might Ancient Egyptian Medicine have been ongoing international or cultural conflicts, such requests for services from an Egyptian physician Among the most ancient , the Egyptians were usually met with neutrality or immunity, even when became renowned for the practice of medicine combined a ruler would travel to Egypt or an Egyptian physician with what seems to be a lively inquiry into what might be would travel to another country. considered the science or of the day. The cali- According to Breasted,8 the ancient Egyptians estab- ber of Egyptian medicine is broadly recognized in nu- lished categories for their physicians. Some of these ranks merous references in both modern and ancient . are recorded in the Edwin Smith . The swnw were In The Odyssey Homer wrote that “for there [in Egypt] the “doctors of the people,” while the wabw were “cer-

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Unauthenticated | Downloaded 10/03/21 08:34 PM UTC A. M. Elhadi et al. emonially pure.” The saw were guardians who obtained their education and training in the temple palace schools, some of whom reached the position that has been trans- lated as “great palace doctors.” A junior doctor was con- sidered a swnw. A senior doctor was called imy-r-swnw. The registrar was referred to as smsw-swnw. Consultants were called shd-swnw. Furthermore, each specialist had his own title. Importantly, a physician might reach a high rank or be highly regarded, but he was still expected to be available to the common people. The chief physician of the pharaoh was expected, more or less, to the medical policy for the country.

Head Anatomy in Ancient Egypt Preserved papyri include information that provides glimpses into Egyptian medicine. Egyptian physicians, at least those in roles of royal or ritual responsibility, seem to have been careful to record information on the diag- nosis and treatment of various conditions, including head injuries. Other information (for example, methods of ex- tracting the brain through the nose or mouth) appears to relate to the rituals of , supporting a key part of view of the . Of the known pa- pyri, about 30 relate to medical and magical health. Other sources about such Egyptian information include ostraca, shards or tablets with inscriptions, on the walls of tombs (Fig. 1), analysis of , and writings from Fig. 1. Upper: Photograph of ancient Egyptian drawings on the the Greek, Roman, and Arab civilizations.15 wall of the temple showing surgical instruments: bifurcated probe, hooks, knife, knife blade, scoop probes, tooth forceps, flasks, Among the earliest Egyptian records are those from cupping vessel, sponge, double-ended probes, shears, male catheter, early 3100 bc, when , an ancient Egyptian his- saw blades, scalpels, and trivalve specula. Image available at http:// torian is said to have written, “Athothis [or ], his en.wikipedia.org/wiki/File:Kom_Ombo_Temple_Surgical_instruments. [that is, ’] son, for fifty-seven years built a palace JPG. ©Ad Meskens/Wikimedia Commons. Lower: Photograph of at Memphis and his anatomical works are extant, for he ancient surgical instruments found in the tomb of an Egyptian physician. was a physician.”32 According to Manetho, between 3100 Photograph provided by A. M. Elhadi, taken at and with the permission and 2890 bc, Djer (or Athothis) wrote some of the earli- of the Egyptian , , Egypt, 2012. est records on medicine, for example, two works called Practical Medicine and Anatomical , which may be body, and a met to the left ear, where it was believed the the first practical and systematic studies of human anat- breath of death entered the body. omy. Although Manetho is consistently cited and what Compared with many cultures, ancient Egyptians he recorded is reputable, none of his works, like Djer’s, placed a high value on preserving the condition of the hu- has survived.32 Consequently, our knowledge of what the man body after death because they believed that the same Egyptians understood about anatomy is mostly drawn body would accompany them in the afterlife. However, this from surviving papyri and ostraca. For example, the Eb- belief created a barrier when it came to dissecting human ers papyrus, which includes paragraphs on anatomical bodies for study. Although their mission was purely ritual, structures referred to as metu (plural of met, which has no embalmers, apart from physicians, possessed knowledge equivalent in English but can mean arteries, veins, ducts, of human anatomy so they could remove the internal or- tendons, or even nerves), states that there are metu to the gans of the dead and preserve them for further use in the back of the head, to the forehead, to the neck, to the eyes, afterlife. Embalmers were trained to approach the human to the eyebrow, to the nose, to the , and to the head. organs with procedures that avoided disfigurement. In fact, Altogether, about 52 metu are described in this papyrus.32 Egyptian embalmers were the first individuals in history The also describes human anatomy to purposefully encounter and evaluate the brain through with more emphasis on the head (paragraph 854g). In this the nasal cavity without having to break through the hard section, 2 metu that supply the nostrils and 4 metu from bone of the skull and disfigure it (Fig. 2).19,35 This proce- the temples that supply the eye are well described. An- dure should not be interpreted as transsphenoidal surgery. other paragraph (856g) from the same papyrus mentions Rather, it was simply a transnasal or transbasal extraction that 2 additional metu independently supply the eyes, 1 of brain tissue. While some extractions of brain tissue ap- met for each eye. This statement could refer to the optic pear to have been accomplished through relatively small nerves because the small ocular vessels could easily have and refined approaches, such as through one nasal cavity, escaped notice. According to Egyptian beliefs, there was or off to the side of the maxillary region, others produced a met to the right ear, where the breath of life entered the large, more destructive holes at the skull base.

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because it was not part of their practice needs. The oldest available document describing the procedure belongs to . He reported that the brain was removed via an approach similar to the transnasal approach,27 leaving the falx cerebrum and tentorium in place. Apparently, the bone at the superior aspect of the nose was perforated, and a curved hook (Fig. 3) was inserted into the nasal cavity to create a defect about 2 cm in diameter. This technique easily allowed extraction of the contents of the anterior and middle cranial fossae. The contents of the posterior cranial fossa were extracted by enlarging the foramen magnum. The ancient Egyptians also practiced variations in their technique of brain extraction. After a few days of death, the brain would likely have begun to deteriorate and liquefy, unlike other solid organs that were extracted, preserved, and placed in containers. Perhaps the brain was the first organ to be removed. Some mummies that have been analyzed using modern imaging techniques show evidence that the brain was sometimes removed from the left side of the face and sometimes from the right, sometimes via a transnasal approach, and some- Fig. 2. A: Photograph of a wall painting from the tomb of Senned- times via a more transethmoidal approach. The jem, who was a famous Egyptian artisan, showing attending of Djehutynakht represents an example of the latter ap- the mummy of . The embalming technique in ancient Egypt proach. This mummy shows evidence that the ethmoid air involved brain extraction through the nasal cavity. Image available at cells were completely destroyed. Several other mummies http://en.wikipedia.org/wiki/File:Anubis_attending_the_mummy_of_ show similar variations19 with defects in the ethmoidal si- Sennedjem.jpg. : Photograph of headrest used during the embalm- nus while the sphenoid sinus remains intact. ing process. C: Photograph of powder materials (in dishes) for These extractions should not be assumed to be surgi- dissolving in solution that were used by embalmers during the mummi- fication process. Photographs in panels B and C provided by A. M. El- cal, precisely targeted to preserve the sinuses, or resem- hadi, taken at and with the permission of the , Cairo, bling modern minimally invasive approaches; they were Egypt, 2012. utilitarian anatomical procedures. It is generally believed that hook-like instruments were used to pierce bone and Extraction of the brain was a method practiced not pull out brain tissue, dura mater, and other tissues. Scoop by physicians but by embalmers for a practical means of instruments were probably also used to extract the brain. removing the brain. In addition, in some crania it can be There are those who believe that stirring the brain with observed that there was preservation of the falx or ten- torium, while in others these structures were completely destroyed. In some cases, radiographic scans of cranial vaults appear to show dependent material. It is unknown whether this material is incompletely extracted brain tis- sue or perhaps other liquid material such as that used for embalming. The brain extraction procedure had no therapeutic implications in life, and there was no aim to preserve brain tissue after death. However, it seems that fine-tuning the approach to remove the brain had exqui- site utilitarian purposes in the afterlife, that is, the pres- ervation of skull and facial features to make it easy for the of the deceased person to recognize its body by being able to view its face in the afterlife.27 Postmortem procedures to extract the brain via a transnasal route date to the Old Kingdom (2686–2181 bc). The practice became more popular during the Middle Kingdom (2080–1773 bc) and the New Kingdom (1550– 1070 bc). Unfortunately, the primary written accounts of this practice did not survive. These procedures would not have been performed by physicians but by embalmers or participants in ritual preparation of the dead body. Thus, Fig. 3. Instruments used by embalmers to extract organs from the although the papyri describe ailments and diagnoses for deceased. The third tool from the top is a brain hook that was used for physicians, these sources would not have included this brain extraction. Photograph provided by A. M. Elhadi, taken at and with procedural information for ancient Egyptian physicians the permission of the Egyptian Museum, Cairo, Egypt, 2012.

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Unauthenticated | Downloaded 10/03/21 08:34 PM UTC A. M. Elhadi et al. a hook would allow the brain tissue to run out, but those brain. It appears that the approach depended on the pref- familiar with anatomical preservation methods know that erence of the embalmer, who would have gained much brain tissue rarely runs out and certainly does not do so working familiarity with such anatomical regions, just as through relatively small or restricted approaches. More the embalmer knew about the removal of other solid or- likely it was scooped or even washed out with the aid of gans. How the embalmers conceptualized the skull base special caustic or dissolving fluids through catheters or anatomy is unknown, but they must have had terminology even specula. for the structures relevant to the procedures so that they New radiological studies of mummies have improved could teach the procedures to new or apprentice embalm- our understanding of this procedure (Fig. 4). For exam- ers. The approach and its extent may also have depended ple, the mummy Djedmaatesankh had the brain removed on the social, ceremonial, or religious status of the de- transnasally from the right side through a defect in the ceased. Using lateral ethmoidal approaches, approaching anterior right ethmoid air cell, while the nasal septum, through the foramen magnum, or performing a unilateral conchae, and left and posterior right ethmoidal air cell nasal-sphenoid approach appears to have been known to walls were left intact. The Lady Hudson mummy had the preserve the face and structure of the nose and thus prob- brain removed through defects in the left ethmoid sinus ably had aesthetic implications for the deceased, both in and the paries medialis orbitae. Damage to the sphenoid this world and in the next. sinus wall is also visible. The Pa-Ib mummy had defects It is thought that the ancient Egyptians believed that in the right ethmoid sinus, the paries medialis orbitae, the , rather than the brain, was the organ respon- and the upper part of the sphenoid. These defects were sible for emotions and intelligence.11 The brain was not believed to be the approach used to remove the brain.42 regarded as the seat of the soul. Rarely was the brain Interestingly, the mummy Hatep- had intact sphe- even observed except in cases of severe open head injury. noid and ethmoid sinuses, conchae, and nasal septum, al- Even then it would not have been seen in its more normal though the brain appears to have been removed. In this solid ; rather, it would have been in a state similar case, it is thought that a transforaminal approach through to the unformed semisolid piecemeal contents extracted the foramen magnum was used. through the nose. Furthermore, The Papyrus of Ani (The These variations are evidence that Egyptian embalm- ), an ancient name for a funeral text, ers had reasonable knowledge of skull base anatomy so recounts that the dead pharaoh will be assisted by Osiris that they could use different approaches for extracting the (the of resurrection)2,7 to replace his head with the

Fig. 4. Full-body CT scout image (A) showing the mummy of an unknown male (still wrapped and in its wooden coffin). The mummy, found in , Egypt, and dating from the New Kingdom, is likely that of a member of the royal family by virtue of the crossed-arm position. Note the destroyed nasal contents between the orbits. Axial CT cuts (B and C) showing the destroyed nasal bones reaching superiorly as a defect in the cribriform plate. Note the dependent dried contents in the posterior cranium, which are the remnants of either brain tissue or embalming . Three-dimensional CT reconstruction (D) showing the crib- riform plate and nasal bone destruction (black circle). Axial CT images (E and F) of the mummy of an unknown male (Middle Kingdom, nonroyal) showing the absence of the posterior aspect of the left nasal region and sphenoid bone, extending superiorly into the cribriform plate. Many brain extractions appear to have been accomplished through approaches in line with the trajectory of the nose, that is, extending superiorly rather than directly posteriorly into the sellar region. Images in panels C–F printed with the permission of the Egyptian Museum, Cairo, Egypt, 2012.

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Unauthenticated | Downloaded 10/03/21 08:34 PM UTC Skull base anatomy in ancient Egypt head of (a god that symbolizes completion). By the end of the journey, the head is to be filled with the brain ( ). Therefore, the embalmers did not attempt to preserve the brain because they believed it would be replaced with a new one: “Menu is Horis, the Advocate of his father [Osiris], and his coming forth means his birth. The two plumes on his head are and Nephthys, when these goddesses go forth and set themselves thereon, and when they act as his protectors, and when they provide that which his head lacketh.”9 Another passage states, “I have come into thee, to the wherein is brought unto me. O Smam, I have come into thee. My heart watch- eth, my head is equipped with the White Crown. I act as the guide of the celestial beings.” The well-known is considered the oldest surgical text.26 It describes 48 surgical cases, 27 of which are related to head injuries. It is believed that this papyrus was found in the tomb of a physician and that it was written by Imhotep (2655–2600 bc), who served under the King . Imhotep was an architect, king’s advisor, and one of the earliest recorded physicians (Fig. 5). He founded a medical school in Memphis,15 where he treated patients. The papyrus includes considerable anatomical knowledge and nomenclature, importantly including descriptions of hard cranial anatomical contents and bone structures, such as a name for the occiput (). Another region called the gema is mentioned in Case 18 of the papyrus: “His gema’ (temple),: the region thereof between the corner of his eye and the orifice of his ear, at the end of his eye and the ori- fice of his ear, at the end of his mandible,”32 appears to describe the zygomatic bone. Another interesting struc- ture was described in Case 7: “As for perforating the te- pau [of his skull], it is what is in between shell and shell (papyt) of his skull. The tepau are of leather (or hide).”32 Tepau could have several interpretations. In 1992 Westen- dorf suggested that it referred to the falx cerebri. In 1930, however, the American Egyptologist James H. Breasted8 favored the cranial sutures as the proper interpretation. In Case 6 of the papyrus the dura mater was described as the membrane enclosing the head, and the cerebrospinal fluid was named as “the fluid of the interior of the head.” The papyrus also named the nasal cavity (shetyt) and described it as the chamber of the nose. Despite the medical papyri and other sources that give us a glimpse of what the Egyp- Fig. 5. Photograph of a of Imhotep (the name means tians achieved in the field of anatomy, no doubt countless “the one who comes in peace”), who served under the 3rd King other papyri and sources of information have been lost or Djoser. Imhotep was considered the first architect, engineer, and physi- destroyed or remain buried. cian in history. He was also considered the of the god Ra. This statue is from the late Ptolemaic period (30th dynasty or later). Image available at http://en.wikipedia.org/wiki/File:Imhotep.JPG. Rise of the Greek in Ancient Egypt Egyptian began to weaken by the end of through the middle.”24 Another example states that “the the 26th dynasty (685–) as the Egyptians struggled same thing applies to the membrane which surrounds the with the Persians. Finally, in Alexander the Great brain: for when, by sawing the bone, and removing it from conquered Egypt as part of his conquest of the Persian the meninx, you lay the latter bare, you must make it clean Empire. During this period, the father of medicine, Hip- and dry as quickly as possible, lest being in a moist state pocrates (460–370 bc), accumulated considerable ana- for a considerable time, it become soaked therewith and tomical knowledge of the brain as mentioned in his col- swelled; for when these things occur, there is danger of lections Corpus Hippocraticum, which includes about 70 its mortifying.”23 Whether himself wrote the medical works. For example, one description of the brain corpus remains a mystery. The volumes may have been from the corpus is as follows: “The brain of man, as in all produced by his students and followers who practiced other , is double, and a thin membrane divides it medicine and dissections in Egypt.

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Compared with the earlier papyri, the Hippocratic tigations and active education. They were supported with writings exhibit an improved understanding of brain meals, rooms, and servants, and the facility was overseen function and anatomy.30,34 The corpus attributed primary by an administrative priest of the pharaoh.6 control of the body’s function to the brain, which was Mouseion facilities were located in several parts of likely based on direct observations of injuries or mala- Alexandria, including theaters, lecture halls, gardens, dies affecting the head: “For this reason I consider the roofed walkways, residential quarters, a communal din- brain to be the most powerful organ of the man’s body for ing room, and several private study rooms where scholars when it is healthy it is our interpreter of the impressions shared ideas, studied, conducted research, and were sup- produced by the air; now, the air gives intelligence. The ported by servants, staff, and scholars (perhaps as many eyes, the ears, the tongue, the the feet, act accord- as 1000 lived in the campus-like facility), as noted by ing to the brain’s understanding; in fact, the whole body Bagnall (Fig. 6).3,6 We can infer that there was at least participates in the intelligence in proportion to its partici- some space specifically devoted to the study of anatomy, pation in the air; now, the brain is the messenger for the where the first documented and detailed human and ani- intelligence.”23 The Hippocratic writings also tracked the mal dissections, including those of the brain and skull arterial supply of the brain to the carotids arteries: “The base, were performed.22 “Doubtless the Egyptian of the remaining part of it rises upward across the clavicle to the period considered the work of the Ptolemaic anatomists right side of the neck, and is superficial so as to be seen; an unspeakable profanation, and, indeed, it was nothing near the ear it is concealed, and there it divides its thick- less than revolutionary—so revolutionary that it could not est, largest, and most hollow part ends in the brain.”23 be sustained in subsequent generations. . . . [T]he great In 332 bc, Alexander the Great conquered Egypt as Galen, at , five centuries after the time of Herophi- part of his conquest of the Persian Empire. Including the lus, was prohibited from dissecting the human subject.”22 entire Persian Empire, Alexander’s dominion was com- The Mouseion and Library flourished until about the posed of , , , Judea, Gaza, Egypt, time of the Roman conquest of Egypt in or perhaps Bactria, and and extended as far as Pun- later in ad 272, when, under the orders of Aurelian, a sec- jab and India. His conquests opened tion of Alexandria (the Bruchion, or palace quarter, along and the exchange of culture and knowledge over a vast the beautiful coastline) was burned.18 Destruction of the region previously composed of largely hostile neighbors. Mouseion and library appears to have occurred over cen- The Egyptians welcomed Alexander as a man who would turies and at the impetus of various people or groups.18 free them from Persian rule. Once he entered the As with most ancient locations in cities, stones and blocks Memphis, he declared himself as the legitimate successor of the destroyed Mouseion and library were used to con- of the . Nonetheless, he seemed to have allowed struct other buildings that now reside over the ancient the resident cultures to flourish.13 structures. Today, it is difficult if not impossible to ex- Alexander stayed in Egypt for about a year and actly locate the original structures. Visiting the beautiful founded the city that bears his name, Alexandria. For a coastline of Alexandria today, one can only imagine the time, because of its library and museum, this city har- grandeur and revolutionary exploratory spirit that must bored the greatest concentration of the world’s recorded have pervaded the area. knowledge, not only in holdings of writings, but also in Of significant impetus to the study of anatomy was the attracting philosophers, teachers, and those who can be establishment of a medical school in Alexandria around called early scientists. Alexander founded this city on a the end of the 3rd century bc.37 The medical school was site that was well known to the Greeks, as described by probably integrated into studies at the Mouseion and may Homer in The Odyssey: “There is an island called Pharos have even been part of it. It is in Alexandria that Aristot- in the rolling off the mouth of the , a day’s le’s notions on were first challenged. We can trace out for a well-found vessel with a roaring wind astern. In systematic anatomical studies of the cranium, even of the this island is a sheltered cove where sailors come to draw skull base, and the beginnings of definitions of the origins their water from a well and can launch their on an of cerebral arteries and nerves to several key figures who even keel into the deep .”25 performed their work in Alexandria at the medical school Alexandria is where the systematic study of anato- and the Mouseion. my appears to have begun, and in those efforts we find The next sections of this article review the work of evidence of investigation of the cranium. The Musaeum, Herophilus, Erasistratus, Rufus, and Galen with regard to or Mouseion at Alexandria, which included the Royal cranial anatomy and their significant tenures in Alexan- Library of Alexandria, was founded by dria. No other ancient center had as much influence on (323–) or by Ptolemy II Philadelphus (283–246 the knowledge of medicine and anatomy as Alexandria. bc)13 and was continuously supported by the Ptolemaic royal family (Ptolemy III is credited with founding a Herophilus of Chalcedon: 335–280 bc smaller library nearby).3 The Library, at one time hold- ing perhaps as many as 700,000 texts, was a part of the Herophilus was born in Chalcedon, a settlement on Mouseion. Rather than being simply a museum, it was an the Bosporus, directly across from ancient Byzantium. As institution for the best scholars of the Hellenistic world. a teenager, he moved to Cos where the medical faculty Archimedes, Aristarchus of Samos, Callimachus, Euclid, formed by Hippocrates was located. At this time, Hip- Herophilus, Erasistratus, Pappus, Hero, and others per- pocrates had been dead for more than 60 years. Nonethe- formed what appear to be well-organized scientific inves- less, he greatly influenced Herophilus’ work.1

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Fig. 6. Left: A map of Alexandria by M. Bonamy, which is the oldest known reconstruction of the city, originally from a presen- tation of August 31, 1731. Note the Bruchion area and the designation of the Museum, which is probably accurate, although other sites, such as the Serapaeum, are not. Image available in Bonamy M: Description de la Ville d’Alexandrie, telle qu’elle estoit du temps de Strabon, in Histoire de l’Académie Royale des Inscriptions et Belles Lettres 9:416–432, 1736. Right: Artist’s concep- tion of the Royal Library of Alexandria. Image available in Castaigne JA: In the time of the Ptolemies: The Alexandrian Library, in Harper’s Weekly. New York: Harper Brothers, 1908.

After completing his medical education, Herophilus Celsus and later Tertullian remarked that Herophilus traveled to Alexandria in 300 bc at about the same time vivisected at least 600 live prisoners. that the city had become fully equipped to support medi- Herophilus contributed to the knowledge of brain cal education. It was there that Herophilus, along with his anatomy as he dissected the ventricles, choroid plexus, contemporary Erasistratus, was able to perform systemic venous sinuses, arachnoid, cranial nerves and their fo- dissections and vivisections4,28 on and animals, ramina, and many other neuroanatomical structures. because Ptolemy I and Ptolemy II17 had authorized vivi- He named certain structures of the brain based on their sections of criminals sentenced to death. In fact, Herophi- shape, for example, the cerebrum (encephalon), cerebel- lus often performed such vivisections publicly so that he lum (parencephalon), torcular herophili, calamus scripto- could better demonstrate the effects of his methods. This rius, and choroid plexus.14 He described the bones forming practice on live humans was occasionally opposed by re- the skull, the intervening sutures, and the membranous ligious and moral beliefs. Cornelius Celsus wrote as fol- coverings of the brain. He described the lower brainstem 40 and spinal cord as one structure he referred to as “spinal lows: 41 Moreover, since both pains and various types of diseases arise marrow.” Herophilus and Erasistratus established the importance of the brain and the sensory and motor func- in the internal parts, they [scil. the “Rationalists”] think that 31 no one who is ignorant of these parts can apply remedies to tions of the nerves. them. It therefore is necessary to dissect the bodies of the dead According to Galen, Herophilus was the first to de- and to examine their viscera and intestines. Herophilus and scribe the connection between the cerebrum and cerebel- Erasistratus, they say, did this in the best way by far when lum through the ventricular system and the structural they cut open people who were alive, criminals out of prison, distinction between the cerebrum and cerebellum. He- received from kings. And while breath still remained in these rophilus extensively studied the lateral, third, and fourth criminals, they inspected those parts which nature previously ventricles because he thought they were part of the seat had concealed, also their position, color, shape, size, arrange- of the soul. He also described the inner lining of the ven- ment, hardness, softness, smoothness, connection, and the 41 projections and depressions of each, and whether anything is tricles as “choroid meninx or choroid twisted clusters.” inserted into another thing or receives a part of another into Galen writes about Herophilus’ description of the venous itself. For, they say, when pain occurs internally, it is impos- sinuses: “At the crown of the head the folds of the mem- sible for one who has not learned in which part each internal brane [sinus transversus] that conduct the blood come to- organ or intestine lies, to know what hurts the patient. Nor can gether into a common space like a cistern, and for this that part which is ill be treated by one who does not know what very reason it was Herophilus’ custom to call it “ it is. And when a person’s viscera are exposed by a wound, vat” [torcular herophili]. From this point, as from some one who does not know the color of an [internal] part in its acropolis, they [sinuses] send forth canals to all the parts healthy state, cannot recognize which part is intact and which lying below them.”41 Herophilus not only named the con- damaged; thus he cannot even come to the aid of the damaged parts. External remedies also can be applied more suitably by fluence of sinuses (torcular herophili), but he also com- people acquainted with the positions, shapes, and size of the pared it to the confluence in the ox, noting that it divides internal parts. . . . Nor is it cruel, as most people maintain, that evenly in the ox but unevenly in humans. remedies for innocent people of all times should be sought in When describing the human cranial nerves, Herophi- the of people guilty of crimes, and of only a few such lus and Marinus (a contemporary who lived ad 70–130) people at that. debated the of cranial nerves, especially the low-

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Unauthenticated | Downloaded 10/03/21 08:34 PM UTC A. M. Elhadi et al. er ones, that originate from the lower pons and medulla Athens. It is believed that he came from a family of doc- and the spinal roots of the accessory nerves.41 Herophi- tors, although Pliny records that he was a grandson of lus suggested that the facial nerve did not exit the cranial Aristotle through his daughter Pythias. fossa but ended as it enters the internal auditory meatus, Erasistratus became famous when he cured the dis- which he called the “blind foramen.” He described the ease of Antiochus, the son of King Seleucus, Nicator I of cavity in the floor of the fourth ventricle as the calamus Syria, to whom he had served as a . Erasistratus scriptorius (calamus means “reed ”) because this cav- is famed for his interaction with the aged King Seleu- ity resembled the groove of a pen.14,17 A conflu- cus, who married a young (Stratonice). She was ence of sinuses in the skull was originally named torcular so beautiful that Antiochus fell ardently in love with her. herophili after him. Because Stratonice was his mother-in-, however, An- Herophilus differentiated between nerves and blood tiochus hid his passion and pined away in silence. Physi- vessels and discovered the differences between motor and cians were unable to determine the cause of Antiochus’ sensory nerves. He believed that the sensory and motor disease. Even Erasistratus himself found nothing wrong nerves exited the brain and that neural transmission oc- with Antiochus’ body until he noticed that whenever Stra- curred by means of the pneuma, which was thought to be tonice entered the room, Antiochus’ skin would become a substance that flowed through the arteries along with hotter, his color would heighten, and his pulse would in- the blood. Although Herophilus stated that diseases oc- crease (Fig. 8). curred when an excess of one of the four humors impeded Erasistratus began to think that Antiochus’ disease the pneuma from reaching the brain, it is clear that he was in his mind and suspected that he might be in love. studied the base of the brain and the cranium in detailed Erasistratus told the king that his son’s malady was incur- fashion to make such observations. able because he was in love and that it was impossible for Herophilus pioneered the physiology of nerves, con- his passion to be gratified. The king asked Erasistratus sidering them responsible for voluntary movement. He with whom his son was in love, to which Erasistratus (un- possessed a considerable amount of knowledge on at least truthfully) replied, “My wife.” Erasistratus then inquired seven cranial nerves: the optic, oculomotor, trigeminal, whether the king would be willing to give up his own wife motor root of the trigeminal, facial, auditory, and hypo- if the object of his son’s affection was Stratonice. The King glossal nerves.14 According to Galen, Herophilus called was willing to do so to cure his son. Erasistratus then told the optic nerve “conduits” because it displays visible the king that his son was indeed in love with Stratonice. channels for the passage of spirits. Herophilus The king not only gave up Stratonice, but he gave his son also mentioned a single nerve that has three roots coming several provinces of his empire to rule. Erasistratus re- from the brain. This nerve was further explained by Ga- ceived 100 talents for restoring the prince’s health, which len as the glossopharyngeal, accessory, and vagus nerves could be a record for the largest sum ever received for a “wrapped” together in one sheet. Herophilus described medical fee.29 the structures entering the eye as two large nerves (V1 Erasistratus moved to Alexandria and worked with and optic) and a smaller one (oculomotor). He also first his contemporary Herophilus in medical teaching and described the styloid process, naming it after styloi, a pen anatomy. Erasistratus wrote extensively on anatomy, prac- used in Alexandria to write on wax . He also com- tical medicine, and pharmacy, although we know only the pared it to the famous lighthouse on the Island of Pharos titles of his works. Galen, Caelius Aurelianus, and oth- (Fig. 7). Herophilus also studied the blood vessels at the 41 ers record many of the shorter fragments of Erasistratus’ base of the brain, which were named rete mirabile. Un- writings. In fact, Erasistratus may be called the father of fortunately, none of the detailed writings of Herophilus ancient anatomy because of the celebrated systematic ob- survive, although many of his contributions were men- servations that he recorded. For example, he appears to tioned and confirmed by later or physicians. have been very close to discovering the circulation of the Herophilus also introduced many of the scientific blood: “The vein arises from the part where the arteries, terms used to this day to describe anatomical phenomena. that are distributed to the whole body, have their origin, He was among the first to introduce the notion of con- and penetrates to the sanguineous [or right] ventricle [of ventional terminology, as opposed to the use of “natural the heart]; and the artery [or pulmonary vein] arises from names.” He created terms to systematically describe the the part where the veins have their origin, and penetrates objects of study, named them for the first time, and estab- to the pneumatic [or left] ventricle of the heart.”39 lished nomenclature so that there was some uniformity Erasistratus’ observations were only surpassed much for study and description. later in the 17th century by William Harvey. Erasistra- tus was a talented observer. He noticed that all veins and Erasistratus of Chios: 304–250 bc arteries arise from the heart but believed that they car- Erasistratus was a well-known physician born on the ried air. He described the ventricular system of the brain island of Chios. He worked with Herophilus, and some much as it is known today: “I investigated the nature of believe that he continued Herophilus’ work after his the brain. . . . And it had a ventricle placed longitudinally death.16 Together, they contributed considerably to medi- on each side, and these were pierced through into another cal investigations and teaching in Alexandria.5 While He- one at the junction of the two parts. This one extended to rophilus was very talented in describing human anatomy, the so-called cerebellum, where there was another, small- Erasistratus contributed to physiology and functional er ventricle, each side walled off by membranes; for the anatomy. Erasistratus received his medical education in cerebellum was set off by itself.”14

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Fig. 7. A: Photograph of a replica of the famous at the Window of the World cultural park in Chang- sha, China. Image available at http://commons.wikimedia.org/wiki/File:Lighthouse_of_Alexandria_in_Changsha.jpg. B: Draw- ing of Alexandria’s lighthouse by archaeologist Hermann Thiersch (1909) considered to be an excellent rendering of the original structure. Image available at http://en.wikipedia.org/wiki/File:Lighthouse_-_Thiersch.gif. C: Comparative image from an original drawing by Austrian architect Johann Bernhard Fischer von Erlach, who illustrated the Alexandrian Pharos from travelers’ de- scriptions. The Pharos, the most recognized landmark of Alexandria, was one of the Seven Wonders of the Ancient World and one of the tallest structures of the ancient world. Built in 283 bc, it was about 140 m high, and for many years it guided for miles in the . This well-known served as a lighthouse to the bay of Alexandria in ancient Egypt and was a beacon of science, hope, and light in the Dark Ages. The lighthouse underwent various renovations and embellishments but was badly damaged in the earthquakes of ad 956, 1320, and 1323. In 1480 the rampart had disappeared and a fort was built upon it. A major archaeological expedition discovered remains of the Pharos in 1994. Image available in Bergk JA: Museum des Wundervollen, oder Magazin des Ausserordentlichen in der Natur, der Kunst und im Menschenleben. Leipzig: Baumgärtner, 1803–1805.

Erasistratus differentiated between motor and senso- renkephalis]. According to Herophilus on the other hand, ry nerves, although he thought that they were hollow and the neura that make voluntary motion possible have their carried a kind of animal spirit. When carried to the mus- origin in the cerebrum [enkephalos] and spinal marrow, cle (through motor nerves), this animal spirit caused the and some grow from bone to bone, others from muscle to muscle to balloon and shorten. So Erasistratus explained muscle, and some also bind joints together.”20 muscle contraction. He thought that the sensory nerves Erasistratus followed certain nerves from their origin arose from the membranes covering the brain and that the to their target organs: “All the processes of the nerves motor nerves arose from the brain matter itself. Rufus of were from the cerebrum; and, in brief, the brain appeared Ephesus wrote, “According to Erasistratus there are two to be the origin of the nerves of the body; for the sensa- kinds of nerves, sensory and motor nerves; the beginning tion which comes from the nostrils reaches this opening of the sensory nerves which are hollow, you could find in [olfactory plate?], likewise coming from the ears. Pro- the meninges of the brain, and those of the motor nerves cesses were also carried from the brain to the tongue and in the cerebrum [enkephalos] and in the cerebellum [pa- eyes.”14 With these words, Erasistratus corrects his previ- ous thoughts about the sensory nerves originating from the meninges. Rather, he states that all nerves originate from the brain matter. From his studies we can be certain that Erasistratus was a careful observer and dissector of the skull base and base of the brain. At the time, this was a remarkable ac- complishment given that the brain tissue or crania were probably not preserved in any manner. These investiga- tions must have resulted from vivisections or dissections performed soon after the death of his subjects. One can only imagine the team of Herophilus and Erasistratus in what must have been a filthy, bloody, fly-ridden scene probably performing demonstrations in an outdoor por- tico or courtyard for light. We would regard such demon- strations as nothing short of horrid. However, for the an- cient Alexandrians, death, perhaps even gruesome death, was a familiar part of everyday life. Such events would have been regarded as the most progressive education of the period to which students flocked from all over the Fig. 8. Painting by Jacques-Louis illustrating the tale of Era- Mediterranean world. sistratus discovering the love of Antiochus for Stratonice. This painting won David the Académie des Beaux-’ first prize in 1774. On the left Erasistratus provided a clear distinction between the Erasistratus is seated while Antiochus lies in . On the right Stra- cerebrum and cerebellum and viewed the brain as the tonice is standing and Seleucus leans forward. Image available at http:// source of intelligence. He compared the en.wikipedia.org/wiki/File:David-Antiochus_et_Stratonice.jpg. with the brains of other animals and concluded that the

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Unauthenticated | Downloaded 10/03/21 08:34 PM UTC A. M. Elhadi et al. greater the number of convolutions, the greater the intel- cited Rufus at length. For the Byzantines, Rufus was one ligence: “the Cerebrum was constructed from even more of the four great names in their medical literature. In me- and differing foldings. From this the observer may learn dieval literature, Rufus was subsumed under the reputa- that as in those animals that surpass the others in speed of tion of Galen, even to the extent that his philosophy, stud- running such as the stag and hare, well constructed with ies, and writings were credited to Galen. Recent interest muscles and nerves also for this, so also, since the man in the Arabic sources has vindicated and reinvigorated greatly surpasses other beings in intelligence, his brain knowledge of his contributions. was greatly convoluted.”14 Interestingly, Erasistratus was Rufus contributed greatly to the anatomical - interested in knowing the blood supply of the nerves, in- clature, especially in his book On Naming of the Parts troducing the idea that the nerves had small veins that of the Body. During his life, unlike those of Herophilus supplied them with nourishment and that these veins var- and Erasistratus,33 dissecting the human body was no ied according to the size and territory of the nerve. If a longer permitted in Alexandria. It is rumored that Ru- nerve had a rich supply around it, it did not need an inde- fus was disappointed with the prohibition on dissecting pendent supply. human bodies. He therefore dissected monkeys and pigs Together, Herophilus of Chalcedon and Erasistratus instead. Alexandria must still have been a center of medi- of Chios defined considerable skull base anatomy, which cal and anatomical education during his lifetime. He was opened the to future discoveries. Because they were a contemporary of Statilius Criton, who was chief physi- contemporaries, one cannot be mentioned without the cian and procurator to the emperor Trajan (ad 98–117). In other. Despite the reputation and outstanding medical his prologue to the Canterbury Tales, Geoffrey Chaucer education offered by the medical school in Alexandria, (1342–1400) named Rufus among the great physicians. most of their work and that of the ancient Egyptians were Although Rufus explained the brain much like his stored in the Royal Library of Alexandria. In 48 bc, how- predecessors Herophilus and Erasistratus, he was the ever, Julius Caesar burned this library,13 perhaps acciden- first to introduce the fact that the brain, spinal cord, and tally, during his war on Alexandria. The fire that Caesar nerves are composed of the same substance, while simul- had set to destroy the Egyptian fleet extended from the taneously distinguishing them as separate anatomical en- dockyards to the library, which at that time housed almost tities. Previously, it was thought that they were connected 500,000 scientific and historical scrolls among others. together:14 This loss may account for the subsequent fragmentation The marrow [spinal cord] arises from the brain and escapes of medical knowledge and explain why most of the in- through the hole of the cranium at the occiput [foramen mag- formation that is now known dates from later historians. num] and descends as far as the base of the spine through all After Herophilus and Erasistratus, no one contributed as vertebrae; it is not a special substance but an extension from much to the field of neuroanatomy for nearly 3 centuries the brain; it is called the marrow of the back. Nervous channels 12 [nerves] which are distributed to sense arise and emerge from until Rufus of Ephesus came to Alexandria. the brain: for example, to the ear, to the nose, and to other sen- sory parts. One of these processes comes off in front from the base of the brain, is divided into two branches [optic nerves], ad Rufus of Ephesus: 80–150 and inclines towards each of the eyes in the part called the Rufus of Ephesus, a Greek physician, was thought to basin or cavity of vision, in the form of a fossa, and which is have been born in Ephesus, on the west coast of Mi- found on each side of the nose. nor. In his later years he returned to Ephesus, from which To permit such comparisons, the tissue he studied must he takes his moniker. However, the young Rufus studied have been relatively fresh. Rufus described the optic and practiced medicine in Alexandria (http://www.faqs. nerve in more detail than previous anatomists. He was a org).10 Unlike his contemporary Soranus or later Galen, very well-respected physician and anatomist who named Rufus never lived in Rome. Instead, he spent a consid- many body parts. In terms of skull base anatomy, he de- erable amount of time in Egypt, where he continuously scribed the color of the brain and mentioned that two lay- wrote about life there. He described several of its en- ers covered the brain: a freely mobile outer layer and an demic diseases such as filariasis and other worm infes- inner layer fixed to the brain. His writings mention the tations and commented on the general state of health of carotid vessels and explain that the name, carotid, was the Alexandrian citizenry. According to historians, Ru- bestowed by a previous anatomist and signified karoein: fus wrote most of his anatomical while in Egypt, “when it is compressed the individual goes to sleep.”38 where he received anatomical training. He was convinced that studying anatomy was crucial to understanding dis- Galen of Pergamon: ad 129–199 eases. More than 90 medical works are attributed to him. A few of his works were preserved in Latin. However, Galen, a Greek physician, surgeon, and philosopher, the legacy of his studies originates from the of has garnered the greatest reputation of all physicians of most of his books into Arabic. The fate of his works and ancient times. He came from a wealthy family. His father, reputation is bound up with that of Galen and Galenism. an architect, died when Galen was 19 years old, leaving In typical fashion, although praising him, Galen does not his fortune to his young son. Following the Hippocratic refer to Rufus directly and took direct issue with him only teachings, Galen traveled to Smyrna, Corinth, Crete, Cili- rarely. To gauge the contribution of Rufus, one must ac- cia, , and finally to the great medical school of Al- cess the compilers of later Greek medical encyclopedias, exandria to learn medicine.14,15,32 He stayed in Alexandria , Aetius, and Paul of Aegina, all of whom often until he was 28 years old.

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He returned to Pergamon as physician to the gladiators all the viscera and all the intestines, and go to all the parts of of the High Priest of Asia, who was the wealthiest man in the face? Aristotle did not attempt to explain the use of any of Asia at that time. Galen is said to have acquired this posi- these parts . . . but the brain is the source of all the nerves. tion after he eviscerated an ape in front of the priest and Since the Alexandrian anatomists had first mentioned challenged other physicians to repair the damage. The phy- the name rete mirabile (attributed to Herophilus), no de- sicians refused. Galen performed the surgery by himself scription of the blood vessels of the brain was known un- and in so doing won the favor of the High Priest of Asia. til the time of Galen. He described the blood supply of the Galen learned most of his anatomical knowledge brain as follows:14 through dissections of apes and pigs because he studied That plexus called reticular by anatomists, the plexus that in Alexandria during the period when human dissections embraces the [pituitary] gland itself and extends for a great were no longer allowed.14 This is considered to be one of distance posteriorly, is the most remarkable of the bodies found the reasons why distortions of anatomy are apparent in in this region. Indeed, it extends over almost the whole base his writings. Based on the content of his writings, how- of the brain. This network is not simple; one might say [it is] like the many threads of fishermen’s nets placed one upon the ever, it is strongly believed that he participated in human other. But this naturally occurring net has the special quality dissections while living in Egypt. His knowledge of hu- that the meshes are so attached to one another that one would man anatomy was probably reinforced through trauma find it impossible to remove one of the threads without the cases he attended to as physician to the gladiators. The other. If one of them is lifted up they are all lifted at the same basis of the anatomical education that he received in Al- time because they are all held together and attached to each exandria certainly served him well in subsequent years. other. No threads produced by the hand of man can compare Galen is responsible for some of the most volumi- with them in delicacy of composition or density of network. Moreover, its formation is no ordinary matter; the largest part nous medical writings of ancient times. In his work, he of the arteries ascending from the heart to the head [carotid] presented extensive arguments directed against Aristotle, has been employed by nature for this admirable network. Little who claimed that the brain came second to the heart. Ar- branches are given off from these [carotid] arteries to the neck, istotle thought that the brain’s main function was to cool face, and external parts of the head; all the rest, ascending in a the heart through phlegm produced by the brain. Galen straight line from their source, and mounting towards the head opposed this concept. He clearly explains that the brain though the thorax and neck, are favorably gathered in that part is the primary organ in the body that controls all vital ac- of the cranium which, pierced with holes [carotid canal], allows tivities,33 and when it is injured or compressed, individu- them to pass without danger into the interior of the head. als lose sensation and movements: “If you press so much It is impossible for Galen to have described the rete mira- upon a cerebral ventricle that you wound it, immediately bile in such detail without his having repeatedly dissected the living being will be without movement and sensation, the base of the brain and floor of the cranium to become without spirit and voice.”14 intimately familiar with this cranial anatomy. Galen’s work showcases the extent of neuroanatomi- Galen detailed the course of the carotid artery as it is cal knowledge at that time. He understood that it is im- pierced and divided by the dura mater. He never provided possible to ignore the function of the brain because it names for these branches but stated the following:14 had connections to all parts of the body, especially to the They are first divided into a great number of very small - sense organs near the brain. Like his contemporaries, he es in the region between the skull and dura matter then travel- described the meninges and mentions that the inner mem- ling, some to the anterior part of the head, some to the poste- brane enclosed many arteries and veins as it followed the rior, some to the left side, some to the right, and interweaving, sulci of the brain (arachnoid). they give the impression that they have forgotten their route in 14 the brain. But that is not all the case. In fact, all these numerous Galen also tracked most of the cranial nerves. arteries come together again and unite like the roots of a trunk But, said Aristotle, all the organs of the senses do not abut on and form another pair of arteries like those that have already the brain. What is this language? I blush even today to cite this given birth to the network these latter arteries then penetrate statement. Does not a considerable nerve enter into one and into the brain by holes in the dura matter. the other ear with the membranes? Does not a part of the brain descend to each side of the nose [olfactory nerves], even more Galen also explained the venous system in great de- important than that which goes to the ears? Does not each of tail. He mentioned the different sinuses and their anatom- the eyes receive a soft [sensory] and a hard [motor] nerves, ical distributions; the great cerebral vein; and the dural the one inserting at its root, the other on the moving muscles? folds, including the falx cerebrum, falx cerebellum, and Do not four of them go to the tongue, two soft ones penetrat- tentorium. That he used fresh brains or even vivisected ing by the palate [hypoglossal?, lingual?], two other hard ones brains is obvious given that he also described how to dis- descending through the ear [chorda tympani?]? Thus, if one sect the human brain.14 must put faith in one’s eyes and touch, all the senses are in relationship with the brain. Shall I announce the other parts It is then desirable to dissect the brain itself, beginning with the that enter into the structure of the brain? Shall I say what use is membranes dividing the anterior part [falx cerebrum]. When provided by the meninges, the reticular plexus [rete mirabile], you have dissected or torn away from this the origins of the the pineal gland, the pituitary body, the infundibulum, the veins that extend laterally, beginning with the forward termina- [fornix], the vermiform eminence [vermis], the multiplicity of tion, raise it up with your fingers until you reach that large vein the ventricles, the openings by which they communicate with [great cerebral?] which extends from it and which we have said one another and the variety of configurations, the two menin- is carried deeply downwards. Again raising this upwards, give ges, the processes that go to the spinal marrow, the roots of the it to someone to hold, and then you yourself loosen it along its nerves that abut not only on the organs of the senses but also on length and gently separate it with your fingers. the pharynx, on the larynx, the oesophagus, the stomach, and Galen extensively described the relationships among

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Unauthenticated | Downloaded 10/03/21 08:34 PM UTC A. M. Elhadi et al. the brain, spinal cord, and cranial nerves. He believed Hassan, Director of the Egyptian Museum, for providing access to that there were three kinds of nerves: sensory, motor, and ; Fatma Al-Zahraa Ahmed Ragi for assistance in obtain- hard nerves (tendons), which travel from bone to bone. He ing illustrations; Dr. Yasmin El-Shazly, Head of Documentation, for providing information on illustrated antiquities; and Mr. Tarek Adb also described the spinal cord and numerous different lev- Al Aala for providing diagnostic images. els of spinal cord injuries: “After the incision, in all the nerves which lie below the place where transaction has References been made, both the two potentialities are lost, I mean the capacity of sensation and the capacity of movements. . . . 1. Acar F, Naderi S, Guvencer M, Türe U, Arda MN: Herophilus Hence from the anatomy of nerves, you can easily infer the of Chalcedon: a pioneer in . Neurosurgery 56: derangement.”14 The Alexandrian anatomists regarded the 861–867, 2005 human cerebellum and the fourth ventricle as very impor- 2. Babbitt FC: : Isis and Osiris. (http://penelope. uchicago.edu/Thayer/E/Roman/Texts/Plutarch/Moralia/Isis_ tant structures, and Galen agreed. He even considered the and_Osiris*/home.html) [Accessed June 28, 2012] cerebellum as the source of motor function in association 3. Bagnall RS: Alexandria: Library of . Proc Am Philos with the spinal cord. He claimed that the vermis acts as a Soc 146:348–362, 2002 valve to regulate the flow of the animal spirit through the 4. Bay NS, Bay BH: Greek anatomist herophilus: the father of ventricular system. Galen’s extensive contributions provide anatomy. Anat Cell Biol 43:280–283, 2010 a solid basis for understanding the extent to which skull 5. Berche P, Lefrère JJ: [Herophilus and Erasistratus: The first ex- base anatomy had been investigated in Egypt by the begin- ploration of the human body.] Presse Med 40:535–539, 2011 (Fr) ning of the 3rd century ad. 6. Blakey H: Mouseion. House of the Muse. (http://www.daily writing.net/Mouseion.htm) [Accessed June 28, 2012] Conclusions 7. Borghouts JF: Ancient Egyptian Magical Texts. Boston: Brill Academic Publishers, 1978 Knowledge about the anatomy of the human cranium 8. Breasted JH: The Edwin Smith Surgical Papyrus: Hiero- and brain began in Egypt 5 millennia ago. The process glyphic Transliteration, Translation, and Commentary. : University of Chicago Press, 1930 began with the ancient Egyptians, whose embalmers, ei- 9. Budge EAW: The Papyrus of Ani; The Egyptian Book of ther accidentally or because of their profession, acquired the Dead. (http://www.africa.upenn.edu/Books/Papyrus_Ani. anatomical knowledge to perform mummification ritu- html) [Accessed June 28, 2012] als. By the time of Galen, anatomical knowledge had ad- 10. Bujalkova M: Rufus of Ephesus and his contribution to the de- vanced considerably through human dissection and often velopment of anatomical nomenclature. Acta Med Hist Adriat by vivisection. By the end of the 4th century bc, the great 9:89–100, 2011 city of Alexandria was founded. The establishment of 11. Calkins CM, Franciosi JP, Kolesari GL: Human anatomical sci- the medical school and the library in Alexandria, cou- ence and illustration: the origin of two inseparable disciplines. Clin Anat 12:120–129, 1999 pled with the feasibility of human and animal dissection 12. Cave AJ: Ancient Egypt and the origin of anatomical science. at the Mouseion, created an incredible atmosphere for Proc R Soc Med 43:568–571, 1950 developing knowledge about one of the most concealed 13. Chapman PH: The Alexandrian Library: crucible of a renais- anatomical structures of the human body: the skull base. sance. Neurosurgery 49:1–14, 2001 This understanding influenced Arabic anatomists (for ex- 14. Clarke E, O’Malley CD: The Human Brain and Spinal ample, Rhaza and Ibn Sina) and numerous contemporary Cord: A Historical Study Illustrated by Writings From Western anatomists, including Vesalius, Piccolomini, Antiquity to the Twentieth Century, ed 2. San Francisco: Norman Publishing, 1996 Willis, Tiedemann, Owen, Leuret, and others who con- 15. da Silva Veiga PA: Health and Medicine in Ancient Egypt: tinued their work based on the foundation provided by Magic and Science. Oxford: British Archeological Reports, those who came to Alexandria. 2009, p 11 16. Dobson JF: Erasistratus. Proc R Soc Med 20:825–832, 1927 Disclosure 17. Dobson JF: Herophilus of Alexandria. Proc R Soc Med 18 (Sect Hist Med):19–32, 1925 This project was supported by funds from the Newsome Chair 18. El-Abbadi M, Fathallah OM (eds): What Happened to the in Neurosurgery Research held by Dr. Preul and from the Women’s Ancient Library of Alexandria? (Library of the Written Board of the Barrow Neurological Institute. The authors report no Word). Boston: Brill Academic Publishers, 2008 conflict of interest concerning the materials or methods used in this 19. AA, Couldwell WT: Transnasal excerebration surgery study or the findings specified in this paper. in ancient Egypt. Historical vignette. J Neurosurg 116:743– Author contributions to the study and manuscript preparation 748, 2012 include the following. Conception and design: Elhadi, Kalb, Preul. 20. Galen of Pergamon (Kühn CG, Cnoblock C, editorium cura- Acquisition of data: Kalb, Perez-Orribo. Analysis and interpreta- vit): Opera Omnia. Lipsiae. 1821-1833, 22 volumes [Transla- tion of data: Kalb, Perez-Orribo. Drafting the article: Elhadi, Preul. tion excerpts found in Clarke E, O’Malley CD: The Human Critically revising the article: Preul, Elhadi, Kalb. Reviewed submit- Brain and Spinal Cord. Berkeley, CA: University of Califor- ted version of manuscript: all authors. Approved the final version nia Press, 1968] of the manuscript on behalf of all authors: Preul. Administrative/ 21. Ghalioungui P: The Physicians of Pharaonic Egypt. Cairo: technical/material support: Spetzler, Little. Study supervision: Preul. Al-Ahram Center for Scientific, 1983 22. Gomperz T: Greek Thinkers: A History of Ancient Phi- Acknowledgments losophy. London: J. Murray, 1901, pp 220–221 23. Hippocrates, Adams F: On Injuries of the Head (author’s The authors thank the following personnel from the Egyptian transl). (http://classics.mit.edu/Hippocrates/headinjur.html) Museum, Cairo, Egypt, for wonderful expert assistance: Mr. Sayed [Accessed June 28, 2012]

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24. Hippocrates, Fischer C: The Corpus: The Hippocratic Writ- of ancient Egyptian osteotomies of the facial skeleton: insights ings. New York: Kaplan Publishing, 2008 into the mummification process. Int J Oral Maxillofac Surg 25. Homer, EV Rieu, DCH Rieu: The Odyssey (author’s transl). 40:1301–1306, 2011 New York: Penguin Books, 2003, pp 315–586 36. Prioreschi P: A . Omaha, NE: Horatius 26. Kamp MA, Tahsim-Oglou Y, Steiger HJ, Hanggi D: Trau- Press, 1995 matic brain injuries in the Ancient Egypt: insights from the 37. Sallam HN: [The ancient Alexandria school of medicine.] Gy- Edwin Smith Papyrus. J Neurol Surg Cen Eur Neurosurg necol Obstet Fertil 30:3–10, 2002 (Fr) [epub ahead of print], 2012 38. Singer C: The strange of some anatomical terms. 27. Loukas M, Hanna M, Alsaiegh N, Shoja MM, Tubbs RS: Clini- Med Hist 3:1–7, 1959 cal anatomy as practiced by ancient Egyptians. Clin Anat 24: 39. Smith W: A Dictionary of Greek and Roman Biography 409–415, 2011 and Mythology. London: John Murray, 1880, Vol 2, p 43 28. Martín-Araguz A, Bustamante-Martínez C, Emam-Mansour 40. von Staden H: The discovery of the body: human dissection MT, Moreno-Martínez JM: [Neuroscience in ancient Egypt and its cultural contexts in . Yale J Biol Med and in the school of Alexandria.] Rev Neurol 34:1183–1194, 65:223–241, 1992 2002 (Span) 41. von Staden H: Herophilus: The of Medicine in Early 29. Miller FP, Vandome AF, McBrewster J: Erasistratus. Mauri- Alexandria. Cambridge: Cambridge University Press, 1989 tius: International Book Marketing Service, 2011 42. Wade AD, Nelson AJ, Garvin GJ: A synthetic radiological 30. Missios S: Hippocrates, Galen, and the uses of trepanation in study of brain treatment in ancient Egyptian mummies. Homo the ancient classical world. Neurosurg Focus 23(1):E11, 2007 62:248–269, 2011 31. Moon K, Filis AK, Cohen AR: The birth and evolution of neu- roscience through cadaveric dissection. Neurosurgery 67: 799–810, 2010 Manuscript submitted April 13, 2012. 32. Nunn JF: Ancient Egyptian Medicine. Norman, OK: Univer- Accepted June 26, 2012. sity of Oklahoma Press, 2002, p 42 Please include this information when citing this paper: DOI: 33. Nutton V: Ancient Medicine. New York: Routledge, 2005 10.3171/2012.6.FOCUS12128. 34. Panourias IG, Skiadas PK, Sakas DE, Marketos SG: Hip- Address correspondence to: Mark C. Preul, M.D., c/o Neurosci- pocrates: a pioneer in the treatment of head injuries. Neurosur- ence Publications, Barrow Neurological Institute, St. Joseph’s Hos- gery 57:181–189, 2005 pital and Medical Center, 350 West Thomas Road, Phoenix, Arizona 35. Peacock ZS, Chapman PH, Gupta R, Kaban LB: Replication 85013. email: [email protected].

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