Before the Twentieth Century

The intracranial tumors we now call meningiomas existed before the start of recorded history, which we know because of the unique changes they sometimes induce in the adjacent skull. The oldest paleopathological evidence of a hyperostosing meningioma is a skull excavated in southwestern Germany estimated to be 365,000 years old,2 and many additional specimens have been preserved from North and South America, Europe, and Africa.3 There is no written record of a tumor that can be recognized as a meningioma until the seventeenth century, when a patient who died with progressive dementia was found at autopsy to have a hard, rounded extraaxial mass adjacent to the falx that had not infiltrated the brain.4,5 However, before the advent of modern imaging, the presentation of meningiomas, as with other intracranial lesions, was an impenetrable mystery unless the tumor caused some external sign such as a hyperostotic mass. Clinical signs such as headaches, vomiting, visual changes, hemiparesis, and seizures certainly could have been observed but would not have been well enough understood to support a specific diagnosis. Indeed, many meningiomas are clinically silent, and only symptomatic cases would have come to medical attention before modern imaging.

The first documented attempts at surgical removal of extraaxial convexity lesions, some of which were probably meningiomas, took place in the eighteenth century. One French series of some 20 patients having hyperostotic skull lesions likely included osteomyelitis and skull metastases as well as meningiomas.6 Early attempts at resection were severely hindered by the lack of anesthesia, antisepsis, and appropriate surgical tools. Some surgeons merely exposed the tumor surface and applied a caustic solution to it, allowing the wound to heal by granulation—if it healed at all. Other surgeons performed a craniotomy around the mass by drilling holes and connecting them with a saw, then cauterizing or ligating the tumor. The French master surgeon Antoine Louis used this method to perform a complete resection of a parietal meningioma in at least one patient, treating the open tumor with “Malmsey wine mixed with herbs and rose honey” until the underlying tissue became necrotic and was able to be removed in several stages.7 The patient apparently survived.

Obviously, these treatments were fraught with danger and only the most courageous or desperate patients would have submitted to such an ordeal. Several documented operations in the eighteenth and nineteenth centuries ended in the patient’s death within minutes or hours.6,8 Inadequate exposure ( Fig. 2.1 ) was common because the externally apparent, hyperostotic portion of the tumor might not reflect the full extent of the underlying intracranial mass. Lack of modern histological examination makes it impossible to be sure what types of tumors these early surgeons actually took in hand, and many of these masses were probably syphilitic gummas, skull metastases, plasmacytomas, and other types of pathology rather than meningiomas as we know them today.

Advances in pathology and physical diagnosis during the eighteenth and nineteenth centuries, especially in France, made it possible to correlate histories, symptoms, and physical examination findings during life with autopsy findings. Jean Cruveilhier’s Anatomie pathologique du corps humain (published 1829–1842) included detailed illustrations of meningiomas, accurately describing their typical locations as the convexities, petrous bone, olfactory groove, middle fossa, tentorium, and falx, and correlating them with symptoms and physical findings.9 At least in theory, these advances laid the groundwork for diagnosing such a tumor by neurological examination alone. It would be several decades before this was actually achieved, but during the nineteenth century several successful operations for dural-based tumors with overlying hyperostoses or palpable masses were performed, by Pecchioli in 1835,10 by Macewen in 1881 (perhaps a syphilitic gumma),11 and most famously in 1885 by Francesco Durante, a professor of surgery in Rome who successfully diagnosed and removed a left olfactory groove meningioma in a 35-year-old woman with anosmia, a left third nerve palsy, downward displacement of the left eye by the tumor, and cognitive and mood changes.12,13 This operation, which lasted 1 hour, resulted in the complete resection of a 70 g tumor. The surgical cavity was drained through the left nasal cavity via an opening in the ethmoid sinus, which had been eroded by the tumor. The patient made a good recovery, even after undergoing a second operation for recurrence 11 years later, and was still alive and in good health 20 years after her initial operation.12 The case gained renown for its satisfying surgical result and favorable neurological outcome, and was published in the Lancet 13 and presented at the International Medical Congress in Washington, D.C., in 1887. At least another two dozen operations on hyperostotic tumors that were probably meningiomas were recorded in the last decades of the nineteenth century.6

The Early Twentieth Century: Before Cushing

By the beginning of the twentieth century, the three necessary ingredients for minimally successful brain surgery were firmly in hand. Anesthesia had been available since the late 1840s, Lister’s antiseptic methods since the 1860s, and Ferrier’s advances in cerebral localization since 1876. But not until ~1910 would the next important technical advances in brain surgery become available—Cushing’s hemostatic methods and his understanding and early control of intracranial pressure. During this interval it became increasingly possible to localize many enlarging intracranial mass lesions, particularly those located near the primary motor cortex, by means of Jacksonian seizures, localized weakness, and the ophthalmoscopic diagnosis of elevated intracranial pressure. Surgeons were willing to operate despite the dangers, because of the known dismal natural history under medical treatment alone. But early mortality rates were very high. Of 38 brain tumor cases collected in an 1894 review, 20 (53%) had ended in early postoperative deaths.14 In reaction to this situation some neurologists and surgeons attempted to specify “requisites for operability” for brain tumors, and then to use autopsy data to define the percentage of brain tumor patients who might conceivably benefit from operation. Ernst von Bergmann specified that a truly operable tumor must be not too large, not metastatic, not multiple, encapsulated, and exposed on the surface of the convexity.15 Using similar criteria, Starr estimated in 1893 that ~7% of brain tumors were operable.16 In 1905 Walton and Paul classified only 3.3% of 424 tumor cases as definitely operable—“primary, accessible, well defined tumors which may be removed without cutting into brain tissue… [with] distinctive symptoms.”

From our present perspective, these criteria essentially limit the field of “operable tumors” to convexity meningiomas, but this diagnostic entity had not yet been defined. Still, in retrospect, we can identify two operations undertaken in the United States in the late-nineteenth century for meningiomas based on cerebral localization, rather than using an external bony swelling as a landmark.17 Robert Weir’s patient presented in 1887 with homonymous hemianopsia and papilledema, and an occipital tumor was diagnosed. Through an occipital craniotomy, a large fleshy mass (~9 by 7 cm) that presented on the convexity was enucleated with a spoon, and the shell was fractured off its attachment to the falx using finger dissection. The patient died that night from postoperative hemorrhage.18 W.W. Keen’s patient, also in 1887, presented with headaches, papilledema, progressive aphasia, and right hemiplegia beginning in the arm; Keen diagnosed a left frontal tumor. In a 2-hour operation, he completely removed an 88 g left frontal convexity meningioma by dissecting around it with his little finger. After a lengthy convalescence, marked by poor wound healing, the patient recovered and lived for 30 years without recurrence ( Fig. 2.2 ).19,20 For Keen, at age 50 one of America’s leading surgeons, it had been his “very first modern brain operation… my heart ‘sank down into my boots.’ But dangerous as the procedure might be I had to go ahead.” Harvey Cushing, at the end of his own career, wrote that Keen’s “vivid account” should be read “by every beginner who may… feel trepidation at the task ahead of him.”21

Cushing’s Contributions

Today, successful surgical treatment of most meningiomas is a standard expectation of medical care, but a century ago, the favorability of these tumors to surgical management was at best a theoretical extrapolation from what was then known about their pathology, etiology, and location. At that time, only a handful of surgical cases had been described in the literature, most with daunting mortality rates (46.6% in Victor Horsley’s series of 1913).22 It was known, principally from Horsley’s relatively few survivors, that the long-term recurrence rate of completely excised meningiomas (generally called “meningeal endotheliomas” or “sarcomas” during this period) was very low.22 By 1906, Horsley considered that “all tumors which, growing from the meninges, penetrate the brain, or which are encapsulated… can all be excised with a good permanent result.”23 Cushing, before having a single personal case of meningioma, wrote in 1908 that they “offer[ed] the most favorable type of tumor for operation.”24 The challenge was clearly framed: successful complete excision might represent a cure, if the patient could only survive the surgery.

The cumulative contributions of one neurosurgeon, Harvey Cushing, over his career stand alone in their significance for the safe and successful surgical management of meningiomas. Cushing’s 1938 monograph Meningiomas: Their Classification, Regional Behavior, Life History, and Surgical End Results describes in great detail 313 patients who underwent surgical treatment of their meningiomas between 1903 and 1932.21

Just as successful diagnosis and appropriate surgical exposure were crucial obstacles to successful surgical re-section of meningiomas before the twentieth century, the next great hurdle to be overcome was achieving adequate hemostasis. Due to the possibility of severe and often fatal blood loss, as well as the inadequacy of anesthesia, most cranial operations before the twentieth century were shockingly brief by today’s standards—less than an hour in many cases. Cushing demonstrated an acute recognition of the importance of hemostasis and was a careful, meticulous, even slow surgeon by the standards of the time.25,26 In his words, “More operative fatalities have been due to exsanguination and its consequences than all other causes combined.” This was especially true of meningiomas, due to their frequent vascularity and proximity to the dural venous sinuses. Dandy, a fearless surgeon who was technically without peer, felt that meningiomas “offer[ed] the most difficult battles in cranial surgery.”27

Cushing observed his first meningioma resection as a medical student. The procedure was performed by John Elliot at the Massachusetts General Hospital on a 31-year-old man with a growing vertex skull lesion and vision and gait problems. The operation was conduced in two stages. During the first stage, a portion of the bony mass was removed, but blood loss was so significant that the second stage had to be delayed by 3 weeks. Cushing served as the anesthetist for the second stage, using chloroform as recommended by Horsley. The operation, which lasted 90 minutes, involved removal of the residual tumor with “hammer, chisel, scissors, and fingers.”28 The patient died half an hour later, presumably from massive blood loss and shock. Autopsy confirmed tumor infiltration of the sagittal sinus.8

Perhaps impelled by this early experience, Cushing helped popularize the use of intraoperative cardiorespiratory monitoring and fluid resuscitation, frequently arranging for a typed blood donor to be available in case a transfusion was needed, and experimenting with auto-transfusion of blood recovered from suction in the operating room.28 Many operations were conducted under local anesthesia to avoid the hypotensive effects of general anesthesia. Early in his career, Cushing discarded chloroform as a general anesthetic in favor of ether, which did not have as severe a hypotensive effect.

Technical innovations specifically addressed hemostasis, as with his use of silver clips to ligate cortical vessels from 1910 onward.29 Raw muscle (from another operating room—usually pectoralis muscle from a radical mastectomy for cancer—or from the patient’s own leg)30 was used as a topical hemostatic agent due to its high concentration of fibrin. The introduction of Bovie’s electrocautery in 1926 made possible the surgical management of tumors previously considered unresectable, enabling the control of excessive bleeding and the removal of tumor core with wire loops.26,31,32 Cushing felt the device was such an important advance that he brought back several patients whose first attempted resections had been limited by uncontrollable bleeding, attempting to complete resections he had previously considered impossible. The difficult cases increased his operative mortality for a period while he learned the limits of the new technique.28

Cushing initially attempted en bloc resections of meningiomas by preference, sometimes also removing adjacent involved bone, leaving significant dural defects, which he closed with fascial grafts. However, he eventually adopted a strategy of debulking the center of the tumor, often with electrocautery, before removing its capsule, a technique still commonly used today.21,33

Many of these innovations are illustrated in Cushing’s final meningioma case, from 1938, which involved a very large (9 cm) tumor in a 45-year-old woman. The procedure was performed under local anesthesia. Although systolic blood pressure at one point dropped to 40 mm Hg, the tumor’s arterial supply was successfully defined and severed, and a complete resection was achieved by debulking the core and stripping away the capsule. The patient was kept on the operating table for several hours for close blood pressure monitoring, and thereafter made a complete recovery, returning to her job as a decorator. Routine skull x-rays showed no signs of recurrence up to 5 years after surgery.28

Cushing’s contributions are notable not only for innovations in surgical technique but also for exhaustive attention to detail, particularly with respect to the clinical examination. Like his mentors William Osler and Henry Thomas, he ascribed great importance to accurate and complete description of the neurological examination. He was thus able to define coherent clinical syndromes relatable to meningiomas of the convexities, suprasellar region, olfactory groove, sphenoid wing, falx, and parasagittal region as well as the cerebellopontine angle, thus aiding in informed, intelligent surgical exposure of these tumors. In collaboration with his assistant Louise Eisenhardt, he conducted detailed follow-up on his patients, slowly amassing invaluable data on the long-term outcomes of his cases. Eisenhardt began collecting survival data prospectively on all of Cushing’s tumor patients beginning in 1922, with enough accuracy to enable retrospective calculation of Kaplan-Meier curves.28 In anticipation of the contemporary standards of brain tumor treatment, these data included information on quality of life as measured by a return to “useful work” or the patient’s previous occupation: “the mere lengthening of a patient’s months or years without making them more livable is… no justification whatsoever of an operative procedure.”34

This attention to long-term follow-up is apparent in the story of Cushing’s most famous meningioma patient, General Leonard Wood. Wood was a military surgeon, originally one of Theodore Roosevelt’s Rough Riders and renowned for his courage in battle. He had a long history of a right frontoparietal skull-based mass, for which he underwent an extracranial procedure with a diagnosis of “fibrosarcoma.” Intractable left-sided motor seizures led him to seek a second opinion from Cushing in 1910, thereby making him the third patient in Cushing’s series. In two operations, performed 4 days apart, Cushing successfully removed a right parasagittal meningioma.21,35 Wood was discharged from the hospital a month later and went on to make a full recovery, later becoming governor of Cuba, serving as President Taft’s chief of staff, and running for president in 1920 as the original Republican favorite to succeed Woodrow Wilson. Eventually, he experienced renewed left-sided seizures and underwent a second resection of his tumor in 1927. Unfortunately, he experienced an intraventricular hemorrhage and died a few hours after the operation, a tragedy that greatly distressed Cushing.25 Wood’s brain is preserved at the Yale University School of Medicine.