HISTORICAL VIGNETTE J Neurosurg 127:927–940, 2017

Norman M. Dott, master of hypothalamic craniopharyngioma surgery: the decisive mentoring of and Percival Bailey at Peter Bent Brigham Hospital

Ruth Prieto, MD, PhD,1 and José M. Pascual, MD, PhD2

1Department of Neurosurgery, Puerta de Hierro University Hospital; and 2Department of Neurosurgery, La Princesa University Hospital, Madrid, Spain

Norman McOmish Dott (1897–1973) developed surgical neurology in , Scotland, and was a scholar of world- wide renown. One of Dott’s most notable contributions to neurosurgery was his understanding of hypothalamic physiol- ogy, mostly acquired through the comprehensive study of patients with lesions involving this region of the diencephalon, particularly craniopharyngiomas (CPs). Recognition of symptoms caused by hypothalamic disturbances allowed him to predict the accurate anatomical relationships between CPs and the hypothalamus, despite the rudimentary radiological methods available during the 1930s. His sophisticated knowledge permitted Dott to perform radical removals of CPs originating within the third ventricle floor with acceptable success. Between 1934 and 1937, he operated on 4 CP cases originating in the hypothalamus, achieving a satisfactory postoperative outcome in 3 of the 4 patients. Aware of the strong attachment of hypothalamic CPs to the infundibulo-tuberal area, Dott used a double transbasal and transventricu- lar approach to these lesions, a strategy providing an optimal view and control of the tumor boundaries. The decisive mentorship of several legendary figures of physiology and neurosurgery greatly influenced Dott’s surgical evolution. The experimental pituitary gland work he performed with Sir Edward Sharpey-Schäfer at the beginning of his career stirred Dott’s curiosity about the issue of hypothalamus-pituitary relationships. As a result, he decided to move to Peter Bent Brigham Hospital (Boston, Massachusetts) in 1923, to train in neurosurgery and neuropathology under the guidance of the leaders in these fields, Harvey Williams Cushing (1869–1939) and Percival Sylvester Bailey (1892–1973). They inspired the young Dott and shared with him their clinical and pathological expertise, in addition to their surgical strate- gies for best approaching and removing these challenging tumors. In time, Dott would come to surpass his mentors. This paper aims to credit Norman M. Dott for his decisive, modern contributions to hypothalamic CP surgery. https://thejns.org/doi/abs/10.3171/2016.9.JNS16702 KEY WORDS craniopharyngioma; Harvey W. Cushing; history; pituitary surgery; hypothalamus; Norman M. Dott; Percival Bailey; third ventricle

The most fertile source of our information regarding the tions to neurosurgery, Dott is credited as the main advo- Hypothalamus is the observation of patients with tumors of cate for the transsphenoidal approach to pituitary tumors this and related parts. in the first half of the 20th century, a technique he learned — Norman M. Dott, 193834 from Cushing.42,43,45,61 Less well known are the original, in- novative procedures Norman Dott performed in the 1930s Norman McOmish Dott (1897–1973) developed his for radical excision of hypothalamic tumors, in particular specialization in surgical neurology—the term he defi- craniopharyngiomas (CPs). These particularly challenging nitely favored—in Edinburgh (Fig. 1), a vocation undoubt- operations were described in detail in the 1938 master- edly influenced by the immense respect he held for Harvey piece, The Hypothalamus: Morphological, Functional, Williams Cushing (1869–1939), the father of modern sci- Clinical and Surgical Aspects.34 Dott devised a 2-stage entific neurosurgery.31,61 Among his well-known contribu- approach, involving first a subfrontal exposure of the ret-

ABBREVIATIONS CP = craniopharyngioma; DI = diabetes insipidus; TVF = third ventricle floor. SUBMITTED March 18, 2016. ACCEPTED September 7, 2016. INCLUDE WHEN CITING Published online January 6, 2017; DOI: 10.3171/2016.9.JNS16702.

©AANS, 2017 J Neurosurg Volume 127 • October 2017 927

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

learned from Cushing and Bailey was that the patients’ severe morbidity or death almost inevitably followed any surgical injury to the hypothalamus.15,26,27,30,34,40,53 This study reviews Dott’s innovative surgical tech- niques for the treatment of hypothalamic CPs. In partic- ular, our work analyzes the knowledge Dott acquired at Peter Bent Brigham Hospital that significantly contributed to his success with this specific topographical CP variant, judged as the most “baffling” type of brain tumor by Har- vey Cushing.14 We have systematically examined the in- formation related to the treatment of CPs at Brigham Hos- pital stored in the Manuscripts and Archives Department at Sterling Memorial Library, Yale University, New Hav- en, Connecticut, for the two periods Norman Dott spent as a visiting neurosurgical fellow at Cushing’s department: first, from November 1923 to June 1924, and later, in the summer of 1929.20 In addition, an extensive review was performed of the Cushing-Dott correspondence kept at Yale, as well as the published literature on the subjects of CPs and the hypothalamus by Harvey Cushing, Percival Bailey, and Norman M. Dott.21–23 Our major objective was to draw attention to the pathological concepts and surgi- cal lessons about CPs that Dott learned from Cushing and Bailey, which allowed him to achieve a radical removal of hypothalamic tumors. These essential lessons remain valid for neurosurgeons even today. Intellectual Background: From Engineer Apprentice to Committed Pituitary Gland Researcher Norman M. Dott was born in Colinton, on the south- ern outskirts of Edinburgh, Scotland, on August 26, 1897. Raised in a family promoting the enjoyment of culture and rational thinking, Dott aspired to become an engineer, but FIG. 1. Portrait of Professor Norman McOmish Dott (1897–1973) by on August 29, 1913, he suffered a motorcycle accident, a Sir William Oliphant Hutchinson in 1960. The original oil painting was 61 donated by Dr. Jean Hider, Dott’s daughter, in 1983 to the Royal College stroke of fate that altered the tenor of his life. He suffered of Surgeons of Edinburgh. It hangs at the Main Hall of the College. Re- a compound fracture of his left femur and tibia, requir- printed with permission of the Royal College of Surgeons of Edinburgh, ing complex surgery and from which he endured a painful owners of the portrait. Figure is available in color online only. limp for the rest of his life. His own disability along with the impression that other sick and injured patients made on him, prompted a desire to study medicine at the Uni- rochiasmatic area, followed by a second transcortical- versity of Edinburgh, from which he graduated in Decem- transventricular procedure to remove the upper portion of 61 34 ber 1919. From 1920 to 1921, Dott was trained in general the lesion within the third ventricle. Such a combination surgery under Dr. John Wheeler Dowden at the Royal In- of basal and upper approaches to complex intra-extraven- firmary (Fig. 2A). In 1923, he obtained the Fellowship of tricular CPs remains the standard method for removal of the Royal College of Surgeons of Edinburgh (FRCSE). 63,65 these lesions today. Considering Dott lacked accurate In 1908, Sir Edward Albert Sharpey-Schäfer (1850– neuroradiological methods of diagnosis, surgical micro- 1935), chair of physiology at the scopes, hormonal replacement therapies, and antibiotics, and discoverer of the active principle of the posterior pitu- his record of hypothalamic CP removal should be regard- itary gland, was invited to deliver a lecture on the physiol- ed as a remarkable accomplishment. ogy of the pituitary gland at Johns Hopkins University in During his fellowship in Boston (1923–1924), Harvey Baltimore, Maryland.38 Stunned by the lecture, a young Cushing kindled Dott’s enthusiasm for pituitary tumors Harvey Cushing immediately embarked upon his impor- and the study of pituitary and hypothalamic disturbanc- tant series of experimental hypophysectomies in dogs, and es.38,61 Dott also had the good fortune to meet Percival Syl- shortly afterward he began to treat clinical cases of pitu- vester Bailey (1892–1973), who taught him the essential itary disease.11,16,38 Nearly a decade later, in 1917, Sharpey- concepts of hypothalamic dysfunction necessary to un- Schäfer offered Dott the opportunity to join his labora- derstand the sort of symptoms observed in patients with tory of physiology as a researcher (Fig. 2B).61,62 During his CPs.2,3 Dott witnessed firsthand the disheartening results training in general surgery, Dott became actively engaged that followed Cushing’s early attempts to remove CPs in- in experiments on gastric secretions and on thyroid and pi- volving the hypothalamus. The fundamental lesson Dott tuitary physiology. Therefore, Professor Sharpey-Schäfer

928 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC Norman M. Dott, hypothalamic craniopharyngioma surgeon

FIG. 2. Dott’s research at Sharpey-Schäfer’s laboratory in the early 1920s. A: Norman Dott as part of a group of residents from the Royal Infirmary of Edinburgh in 1920–1921. Courtesy of Lothian Health Services Archive, Edinburgh University Li- brary. B: Photograph of Sir Edward Albert Sharpey-Schäfer (1850–1935), English physiologist, who is regarded as a founder of endocrinology. CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). C: Original drawings by Norman Dott of the surgical technique used in his experimental research of the pituitary function. View of the intracranial anatomy of the transorbital electro- lytic operation upon a cat (C1), and view of the field of operation in exposure of the canine pituitary (C2). Reproduced from Dott NM: Q J Exp Physiol 13: 241–282, 1923, with permission of John Wiley & Sons, Inc.33 Figure is available in color online only. should be regarded as an influential figure that helped Manuscript and Archives Department at the Sterling Me- awaken an interest in pituitary tumors in his fellows Cush- morial Library, Yale University.22,23 These letters, charac- ing and Dott.13,16,17,19,31 terized by increasing affection and familiarity, covered a Dott began his studies on the pituitary gland by assess- wide range of subjects, from technical neurosurgical top- ing the physiological effects of its ablation in dogs and cats ics to Dott’s personal life. (Fig. 2C1 and C2).33 Impressed by his talent, Sir Walter During his apprenticeship, Dott learned a vast range of Fletcher, Secretary of the Medical Research Council, ar- neurosurgical principles and techniques that would prove ranged a Rockefeller fellowship for Dott to travel to Bos- extremely valuable for his own career.24,41 Dott was im- ton for further training with Harvey Cushing.6,61 The ex- bued with Cushing’s philosophy to perform a thorough, perience he lived while working at Brigham Hospital was thoughtful study of the chronological sequence of symp- a crucial period in his life, a time that, in his own words, toms, to determine an accurate preoperative topographical “sealed [his] destiny” to devote himself to neurological diagnosis of intracranial tumors. Cushing insisted on the surgery.29,31,32,41 paramount importance of perimetry for the assessment of visual disturbances associated with pituitary tumors, in ad- Neurosurgical Instruction at Peter Bent dition to the careful interpretation of cranial radiography Brigham Hospital: Forging His Indelible studies.64 Dott also learned from his mentor the impera- tive need to perform a meticulous postmortem examina- Friendship With Harvey Cushing tion of the brain specimens, with the aim of checking for The Rockefeller fellowship gave Dott the opportunity possible diagnostic mistakes or operative errors. Finally, to become Cushing’s junior associate in surgery from No- Dott observed the enormous importance Cushing placed vember 1923 to June 1924.6,29,61 As Dott grew enthusiastic on experimental research as a fundamental tool to answer about Cushing’s activities, the latter discovered the for- clinical questions. To Dott, Harvey Cushing represented mer’s talents. Thus began an enduring personal friendship “The embodiment of an ideal, the combined experimental based on mutual respect and admiration, as evidenced by investigator and clinical surgeon” (Dott to Cushing, April the collection of 67 letters between them housed in the 27, 1924)”23

J Neurosurg Volume 127 • October 2017 929

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

Dott became fascinated by pituitary tumors, and his Sharpey-Schäfer’s and Cushing’s concepts.38 Schäfer’s interest was certainly noticed by Cushing, who assigned and Cushing’s view supported the vital role of the pitu- him the monumental task of reviewing all his pituitary ad- itary gland as the organ in control of body homeostasis enomas, a work that Dott performed in collaboration with and metabolism, a concept derived from their consistent Percival Bailey.34,35,38 Upon Dott’s return to Edinburgh, observation that hypophysectomized animals died after Cushing encouraged Dott to continue working in the field a process of progressive weakening and corporal ema- of pituitary surgery as he had full confidence in Dott’s ciation, a clinical condition Cushing defined as “cachexia abilities (Fig. 3A). Dott’s respect for Cushing’s knowledge hypophyseopriva.”11,16,55,62 Dott had interpreted the results about the pituitary gland is noticeable in the content of of his own experimental model of hypopituitarism in the their correspondence over the following years. For exam- same terms, by concluding that depression of metabolism ple, Dott wrote a letter on May 15, 1926, in which he asked was so severe after total pituitary removal that it usually Cushing for advice about what to say regarding pituitary led to the death of the animals (Fig. 2C1 and C2).33 diseases to the congress of the British Medical Associa- When Dott arrived at Brigham Hospital in 1923, Per- tion. Dott wrote, “As my experience on pituitary diseases cival Bailey was working as an assistant resident under has been acquired entirely under your [Cushing’s] direc- Cushing.7 Without even realizing it, Dott found himself tion, I shall, of course, speak from this point of view.”22 caught up in the battle between Cushing and Bailey re- He also sent Cushing reprints of the article “Diseases of garding the origin of diabetes insipidus (DI), adiposity, the pituitary body” he published in 1927 to obtain Cush- and somnolence produced by pituitary tumors. Bailey ing’s verdict on his statements about the functional role had proved that minute injuries to the hypothalamus, even played by the hypothalamus, a controversial topic at the while sparing the pituitary gland, were sufficient to cause time.22,28 Dott likewise consulted Cushing on his surgical DI, somnolence, and adiposity in dogs.4,24 Moreover, he pituitary cases. For instance, in a letter written on July 30, found that extensive lesions of the tuber cinereum were 1927, Dott reported his experience with a macroadenoma incompatible with life.4 Consequently, he defended the to Cushing:22 hypothalamic origin of both DI and the adipose-genital syndrome (Fröhlich’s). I operated on the enormous pituitary adenoma which I spoke Cushing vigorously criticized Bailey by claiming, er- to you about... The patient made an excellent primary recov- ery but suddenly developed spasmodic respiration and died roneously, that he was “unqualified” to attribute these in a few minutes, some fifteen hours later. Do you think it is symptoms to a lesion of the diencephalon. Contrary to unwise for me to attempt such cases where the risk is obvi- Bailey’s postulations, Cushing considered that the poly- ously very great at my present stage? I feel very unwilling to uria and adiposity observed in some dogs after hypophy- deny these people such chance as lies in operation and feel sectomy could be interpreted as being similar to the DI that it is humanly and scientifically the right thing to do. …I and Fröhlich’s syndrome observed in patients with large should be very glad of your advice on this subject. pituitary tumors.16–18,49 He also dismissed the results ob- Dott’s second stay in Boston, from mid-July to mid- tained by other experimental physiologists showing that August 1929, was instigated by Cushing himself, who experimental DI could be caused by a lesion limited to 1,2,8,9 thought Dott needed more time with him to polish and the hypothalamus without injuring the pituitary gland. further improve on the progress he was making in Edin- Cushing believed that these symptoms were due to the in- burgh. Dott finally agreed to come to Boston, but only for sufficient secretion of the substance produced by the pos- 1 month, apparently due to his limited finances.29,61 Three terior pituitary lobe (“pitressin”), owing to the obstruction years later, appreciative of Dott’s interest in the issue of pituitary tumors caused on its release, which he presumed occurred via an upward pathway through the pituitary pituitary-hypothalamic physiology, Cushing sent him a 17,49 copy of his recently published book chapter “The pituitary stalk into the third ventricle. body and hypothalamus” in January 1933.15 When Dott Nonetheless, Cushing confessed his puzzlement at the wrote back to thank Cushing for such a “splendid New contradictory results observed after hypophysectomy pro- Year’s gift,” he informed Cushing about his latest experi- cedures in animals and human patients, as he had never ence with CPs and how he had dealt with a recent case observed the syndrome of cachexia hypophysiopriva (Fig. 3B):22 among patients who underwent operations for pituitary tumors other than CPs.15,16,55 He missed the damage in- On the whole I have had fairly good luck with my pituitar- flicted to the tuber cinereum by the subtemporal method ies... I have been particularly fortunate with the craniopha- of hypophysectomy used in his laboratory. Such an un- ryngiomas. We did our seventh complete extirpation of a large cystic one on a child of ten a few weeks ago with good noticed injury was more easily caused in dogs due to the result... (Norman Dott to Harvey Cushing, January 5, 1933) peculiar close anatomical relationship between the gland and the third ventricle in these animals, which lack the Cushing rejoiced at Dott’s success and was proud to intervening dural barrier of the sellar diaphragm present 22 have played a part in it. in humans.49 Cushing did not accept the possible solution to the riddle, Erdheim’s suggestion that polyuria and dys- In the Midst of the Storm: The trophia adiposogenitalis (Frölich’s syndrome) observed in Bailey-Cushing Conflict on the Hierarchy of the group of hypophyseal duct tumors (CPs) could be due to the gross anatomical distortion to the tuber cinereum Hypothalamus-Hypophyseal Relationships induced by these tumors.15,36,37,49,57 The original ideas Dott had on the physiological role Working together in the analysis of symptoms present played by the pituitary gland were mostly influenced by in Cushing’s patients with pituitary adenoma, Dott and

930 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC Norman M. Dott, hypothalamic craniopharyngioma surgeon

FIG. 3. Correspondence between Norman Dott and Harvey Cushing. A: Letter written by Harvey Cushing on December 23, 1926. The red frame highlights the fragment in which Cushing expressed his interest about Dott’s cases and encouraged him to keep working. Courtesy of the Manuscript and Archives Department of the Sterling Memorial Library, Yale University. B: This letter was written by Dott on January 5, 1933. Within the red box Dott informs Cushing about his progression with pituitary tumors as well as his experience with a CP he had recently operated upon.22 Reproduced from the Manuscript and Archives Department of the Sterling Memorial Library, with permission from Susan Fraser Hider, Dott’s granddaughter. Figure is available in color online only.

Bailey confirmed Erdheim’s observations and found that disavowed it—but these are trifles as compared with his DI and somnolence only occurred in those lesions that had contributions to medical knowledge.” grown beyond the sella turcica and encroached upon the region of the hypothalamus.35 Accordingly, in their co- authored manuscript on Cushing’s series of pituitary ad- Bailey’s Categorization of “Hypothalamic enomas, they related the DI observed in some patients to Craniopharyngiomas”: Awakening Dott’s a hypothalamic lesion. When Cushing reviewed the paper, Awareness of a Forbidding Type of Lesion he disagreed with such a concept and sent a letter to Dott on May 13, 1925, in which he requested that he remove Percival Bailey presented Dott with critical informa- any assumption against his theory supporting the pituitary tion regarding the topography and pathology of CPs (Fig. origin of DI, with the following words:23 “The discussion 4). Prior to Dott’s arrival at Brigham Hospital, Bailey had of diabetes insipidus and the possible lesions of the hypo- examined the brain specimens from Cushing’s patients with CP who had died either from complications of the thalamus have so far as I can see, very little to do with the 2,4,7 subject with which you are dealing.” procedure or from tumor progression. From this valu- In spite of the admiration Dott felt for Cushing, he even- able material, Bailey learned that CPs occupying the re- tually sided with Bailey. In the speech he delivered to the gion of the third ventricle usually showed histological British Medical Association on July 23, 1926, in Notting- evidence of tumor invasion to the hypothalamic “centers” ham, he recognized the uncertainty about the origin of DI, that formed the diencephalon. As a general rule, in these but at the same time expressed, “Personally I find myself CP cases, a sharp anatomical discrimination of the tumor in discord with [hypopituitarism as the origin of diabetes boundaries from the adjacent brain tissue forming the in- insipidus and adiposity] both on experimental and clini- fundibulum and the tuber cinereum could not be made. cal grounds.”27 The great respect Dott held for Cushing Bailey categorized this type of CP as true “tumors of the probably led him to downplay his mentor’s error, as one hypothalamus.”2,3 He acknowledged that such an intimate can deduce from his apologetic words expressed on the relation between the tumor and the surrounding hypothal- thirtieth anniversary of Cushing’s death:29 “He [Cushing] amus was the critical factor that explained the high mor- persisted in an erroneous belief that “pitressin” is secreted tality and morbidity observed following surgical attempts into the cerebrospinal fluid of the third ventricle—he never to radically remove these lesions.47,48,50,51

J Neurosurg Volume 127 • October 2017 931

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

FIG. 4. Autopsied brain specimens showing the major topographical categories of CPs involving the third ventricle. A: Suprasel- lar-pseudointraventricular topography. Note the tumor is pushing and displacing upward an intact TVF (arrows), masquerading a true intraventricular position. This brain specimen corresponds to a boy aged 11 treated by Dott (surgery no. 293) who died following an attempt to remove the tumor that was found to be tightly attached to the outer surface of the TVF. Mammillary body (asterisk). Reproduced from Dott 1938,34 with permission from Susan Fraser Hider. B: Infundibulo-tuberal, or not strictly intraven- tricular, CP with a mixed consistency. The TVF between the optic chiasm and the mammillary body (the infundibulo-tuberal area) has been replaced by the basal area of the tumor. This topographical category corresponds to the concept of hypothalamic CP by Dott. C: Strictly intraventricular CP wholly located within the third ventricle cavity. The intact TVF (arrows) is identifiable below the inferior surface of the tumor. Panels B and C are reproduced from Walker and Cushing 1916, in the public domain.64 Figure is available in color online only.

Bailey’s topographical concepts about CPs convinced lesions lodged beneath the optic apparatus, which could be Dott that an accurate preoperative diagnosis of CP exten- pricked to evacuate the cyst content and achieve an ade- sion for each case was essential, to plan the optimal surgi- quate decompression of the optic chiasm.14,53 Nevertheless, cal approach for maximizing the likelihood of a radical once the drained cyst collapsed, the retrochiasmatic posi- excision while minimizing the risks of hypothalamic inju- tion of the solid, calcified portion of the lesion represented ry. For a correct diagnosis of CP topography, Dott learned an insurmountable obstacle for Cushing, due to the fact from Bailey the importance of a thorough assessment of that the optic apparatus itself hindered a proper view of the symptom chronology. For example, the development of tumor and its attachments.17 Strong adherence of the tumor adipose-genital dystrophy, followed by hypersomnia, hy- capsule to the hypothalamus precluded the use of “blind,” per/hypothermia, and/or emotional disturbances, usually forceful surgical maneuvers to dislodge the tumor, as these occurred when the tumor gradually encroached upon the were invariably followed by severe symptoms of hypotha- base of the brain.2,3 Topographical diagnosis of CPs should lamic failure, including malignant hyperthermia, leading include a campimetric examination of visual defects and to death in a few days. Discouraging experiences of cata- the identification of abnormal dense shadows found on strophic hypothalamic failure after apparently straightfor- skull radiographs, present in approximately 80% of tu- ward procedures compelled Cushing to express his belief mors of this kind.46,64 that CPs represented “the most forbidding of the intracra- nial tumors.”10,14 Novel surgical strategies to achieve a safe dissection of the cleavage plane between the tumor and the Immersion in the “Baffling Problem of hypothalamus were needed. Neurosurgery”: Cushing’s Strategies for Dott had the privilege of witnessing Cushing’s original strategies to overcome the huge difficulties posed by CPs Removal of “Hidden” Interpeduncular CPs involving the hypothalamus. According to our extensive Harvey Cushing started pituitary surgery circa 1910 at review of the Brain Tumor Registry, a total of 11 patients John Hopkins Hospital by attempting the removal of pitu- with CPs were admitted to Brigham Hospital during the itary tumors using the sublabial transsphenoidal approach, periods that Dott spent there.20 Some of these cases cor- a route that proved inadequate to safely remove tumors responded to intraventricular CPs hidden from surgical extending above the sella turcica.10,19,53 More challenging view beneath the optic chiasm. The methods devised by for Cushing was the approach to the group of “interpe- Cushing to manage these cases provided Dott with use- duncular” cystic lesions, also known at first as “suprasel- ful lessons and insights for coping with his own hypotha- lar cysts,” which did not originate within the sella and lamic CPs. could therefore not be identified preoperatively on skull On January 7, 1924, Cushing operated on a blind radiographs.53 Most of these lesions corresponded to solid- 19-year-old girl who presented with a large calcified su- cystic CPs developed at the base of the brain, within the prasellar cyst, as evidenced by the radiography studies infundibulo-tuberal region.48,50 (Patient M.P., surgery no. 20411). A right-side subfrontal Cushing taught Dott the subfrontal method to approach approach to the optic chiasm region revealed a mass bulg- the optic chiasm, his preferred route for the excision of ing beneath the lamina terminalis. Given the impossibil- CPs.28 This method allowed an easy identification of cystic ity of accessing the tumor through the interoptic space,

932 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC Norman M. Dott, hypothalamic craniopharyngioma surgeon

FIG. 5. Chiasm splitting technique by Harvey Cushing. Left: Case K.K.S., Peter Bent Brigham Hospital. A: Summary operative note on November 5, 1928. B: Original sketch by Harvey Cushing showing the anteroposterior split of the chiasm. Right: Case B.L.E., Peter Bent Brigham Hospital. Summary operative note on July 6, 1929. C: Original sketch of the surgery and discharge note written on August 17, 1929, by Harvey Cushing. D: Pictures of the patient taken on July 26, 1929, coinciding with Dott’s second visit to Boston.20 Courtesy of the Manuscript and Archives Department of the Sterling Memorial Library, Yale University. he decided to open the lamina terminalis with the aim of sion from the third ventricle, but because of the tumor’s emptying the cyst. Cushing’s own words regarding the profuse bleeding, he was able to remove only a small por- case were, “It is the first time that I have ever carried out tion of it (Fig. 5A and B).20 Although Dott did not attend this measure… the fluid from the dilated ventricles may… this procedure, he met the patient during the summer of escape by normal channels.”20 Dott witnessed how the pa- 1929 when he was readmitted for clinical assessment. At tient improved after surgery and was discharged in good that time Cushing was writing his work about “The chias- condition 3 weeks after the operation. mal syndrome,”12 which included this case. Certainly, he A similar infeasibility to remove a tumor hidden be- must have talked with Dott about the strategy he followed hind the optic chiasm occurred in another case (A.M., to approach this lesion. After the patient’s death 13 months surgery no. 20814) assessed by Dott in February 1924. later, the brain autopsy proved the presence of a CP occu- Cushing employed a subfrontal approach to the lesion, but pying the third ventricle.20 no trace of the tumor could be found, and he envisioned Cushing would soon rebound from the previous disap- for the first time splitting the optic chiasm as a potential pointment. On June 25, 1929, he decided to transect the solution. In his own words, “The only thing that could optic chiasm in a 15-year-old girl with a recurrent CP, to have been done in the way of improving the field of opera- attempt a radical removal of the tumor (patient B.L.E., sur- tion in this case would have been to split the chiasm in an gery no. 34286; Fig. 5C). On this occasion, the CP was antero-posterior direction.”20 However, he restrained him- removed successfully. Dott met the patient during her re- self from splitting the chiasm because campimetry studies covery and witnessed how she was discharged in excellent had not shown visual deficits, and eventually he used a condition (Fig. 5D). transcallosal route. Through Cushing’s experiences, Dott learned the valu- Another case of a CP hidden behind the optic chiasm able technique of chiasm splitting to reach the intra–third occurred in a 46-year-old man treated by Cushing in No- ventricle extension of CPs hidden behind the optic chiasm. vember 1928 (Patient K.K.S., surgery no. 32358). In this The transection of the chiasm could counteract the lack of patient, a ventriculography examination showed the pres- proper illumination, and it was particularly advantageous ence of a mass in the third ventricle region. After exposing to identify, under direct view, the cleavage plane of the the optic chiasm through the standard subfrontal approach, mass and its degree of adhesion to the adjacent hypothala- Cushing presumed the presence of a craniopharyngeal mus. The most valuable lesson Norman Dott took from pouch cyst hidden behind a chiasm of normal appearance. Harvey Cushing was the need to preserve hypothalamus Then he reasoned to himself, “There was nothing to be integrity at all costs. This conviction gave Dott the con- seen to the outer side of the optic nerves… Realizing that fidence to establish his own method of staged subfrontal this man’s vision was practically gone in one eye, I thought and transventricular techniques for a safer excision of the that it was advisable to split the chiasm....” By working lower infundibulo-tuberal and upper intraventricular cys- through the chiasm, Cushing attempted to separate the le- tic components of hypothalamic CPs.

J Neurosurg Volume 127 • October 2017 933

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

FIG. 6. Dott’s topographical classification of hypophyseal epidermoid tumors (CPs). A: According to Dott, hypophyseal epi- dermoid tumors (CPs) could originate in 3 points along the hypothalamic-pituitary axis: the anterior lobe of the hypophysis, the pars tuberalis wrapping the pituitary stalk, and the infundibulo-tuberal area of the TVF. M = mammillary bodies; O.C. = optic chiasm. B1–2: Progressive enlargement of CPs originated in the substance of the TVF in an upward direction inside the third ventricle cavity. C1–C2: Diagrams of sagittal and coronal sections of a CP originating in the TVF intimately related to the hypothalamus. Note the basal attachment between the basal nodule to the tuber cinereum and the forward compression of the chiasm. C3: Diagram of the same tumor as it presents on the base of the brain between the optic chiasm and the infundibulum. Images reproduced from Dott 1938,34 with permission from Susan Fraser Hider.

Growth Pattern Classification of Hypophyseal itself, within the area of the infundibulum and tuber ci- Epidermoid Tumors (CPs) nereum (Fig. 6B1 and B2). These lesions usually expand within the third ventricle. Consequently, they cause early It is remarkable that Norman Dott decided to use the symptoms of hypothalamic derangement in addition to word “craniopharyngioma” only in the letters he sent to acute hydrocephalus, due to the obstruction of the foram- Cushing, the author who precisely introduced this term ina of Monro (Fig. 6C1–C3).3,5 in the late 1920s.12 Even so, Dott did choose to refer to Although simple, this topographical classification was CPs in his scientific publications using the terms “cystic useful to preoperatively predict a rather accurate location pituitary epidermoid tumor”5,33 or “hypophyseal epider- of CPs and to plan the surgical approach accordingly. Dott moid tumor.”34 By using such terminology, Dott assumed claimed that a correct preoperative distinction between Erdheim’s embryological theory for the origin of CPs: tumors originating below or above the diaphragma sellae from cell remnants of the squamous epithelium that forms was possible with the clinical and radiological informa- the hypophyseal duct, the embryological epithelial chan- tion available at the time.26,28 He warned that the differ- nel through which Rathke’s pouch migrates to join the ent relationship between the tumor and the leptomeninges diencephalic vesicle.25,33,57 In accordance with Erdheim’s observed for the intrasellar and suprasellar CP categories theory and Bailey’s pathological findings, Dott classi- would lead to a different sequence of anatomical distor- fied hypophyseal epidermoid tumors (CPs) into 3 major tions around the tumor, which, in turn, would result in a groups, depending on their original development site along different cluster of symptoms.28 Fröhlich’s syndrome, DI, the hypophyseal-hypothalamic axis: the sellar, suprasellar, and somnolence were all symptoms occurring early in and hypothalamic topographical categories, each one as- patients with hypothalamic tumors developing within the sociated with a characteristic growth pattern (Fig. 6A). TVF as well as for suprasellar lesions extending into the Sellar CPs originate in the substance of the anterior third ventricle, whereas they did not occur in patients with lobe of the hypophysis, within the boundaries of the sella intrasellar tumors until the lesion had invaded the hypo- turcica, causing a syndrome of pituitary insufficiency. Su- thalamic region.5,28 Such a significant correlation between prasellar CPs develop from the pars tuberalis, the tongue the type of syndrome (pituitary, infundibulo-tuberal, or of adenohypophyseal glandular tissue that envelops the hypothalamic) observed in the patient and the anatomical pituitary stalk and infundibulum. These lesions, confined structures involved by the tumor has recently been con- to a subchiasmatic-suprasellar position, usually cause vi- firmed by our group in a historical cohort of CPs.8 sual symptoms resulting from anatomical distortion of the Despite the obvious interest in CPs Dott showed neighboring optic chiasm at an early stage of tumor devel- throughout his career, he published few works focused on opment. Lastly, the category of hypothalamic CPs grow these tumors. To the best of our knowledge, his first ac- within the substance of the third ventricle floor (TVF) count consisted of a brief presentation of his CP cases in a

934 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC Norman M. Dott, hypothalamic craniopharyngioma surgeon

TABLE 1. Norman M. Dott’s surgical series of hypothalamic CPs (hypohyseal epidermoid cystic tumors)* Age Surgical Periop Hypothalamic Disturbances Patient (yrs), Sex Date Approach Surgical Findings Outcome After (case Symptoms of (degree of & Tumor During Each Surgical no.) on Admission Surgery removal) Attachment Surgery After Surgery (transitory) Procedure 24, M HA, DI, libido loss, psychic Feb 1934 Posterior No tumor found None Glycosuria Good (746) changes (childishness), (1st) fossa BP & HR decreased, explora- stunted growth tion 3 wks later FTV (PTR) IFT-3V solid-cystic BP in- Somnolence, temperature Good (returned (2nd) CP; basal part creased, disturbances (decreased), to work); attached to TVF HR de- HR decreased, DI, psychic recurrence 2 creased changes (dementia), visual yrs later hallucinations HA, visual disturbances, 2 yrs later SF+ON Solid nodule infil- BP in- Temperature disturbances Moderate (DI & Fröhlich syndrome, (3rd) sacrifice trating the tuber creased, (increased and decreased), libido loss) DI, psychic changes (GTR) cinereum HR de- psychic changes (childish- (irritable) creased ness), somnolence 37, M HA, cachexia, BP Jan 1935 Pterional No tumor found None None Good (996) decreased, libido loss, (1st) somnolence The next FTV (GTR) IFT-3V cystic CP, None Poor peripheral circulation Death 3 days day attached to after surgery (2nd) TVF-3V walls 8, F HA, visual disturbances, March SF+ON Cystic CP, attached HR in- Sleep (restless then drowsy), Good (1105) vomiting, hemiparesis, 1936 sacrifice to chiasm- creased psychic changes (aggres- growth acceleration (1st) (PTR) infundibulum sive), visual hallucinations 2 mos later FTV (GTR) IFT-3V cystic CP; None Somnolence, temperature Moderate (obe- (2nd) lower pole ad- increase, oliguria, psychic sity & return herent to TVF changes (sexual excitation to school) & negativism) 37, F HS, Fröhlich syndrome, Aug 1937 SF (PTR) Basal portion None Somnolence Good (waiting (1395) somnolence, psychic (1st) infiltrating the for 2nd changes (disorientation) IFT area approach through FTV) BP = blood pressure; FTV = frontal transventricular approach; GTR = gross-total resection; HA = headache; HR = heart rate; IFT = infundibulo-tuberal; ON = optic nerve; PTR = partial tumor removal; SF = subfrontal approach; 3V = third ventricle. * As reported in the book: The Hypothalamus: Morphological, Functional, Clinical and Surgical Aspects.34 meeting of the Medico-Chirurgical Society of Edinburgh tricular route.”5 This was the first time that the intraven- in 1932 (Session CXII).25 On this occasion, he reported tricular position of CPs was acknowledged in the medi- that his surgical experience was limited to 14 CP cases out cal literature. The third and last work on CPs published of 300 intracranial tumors he had treated up to that time. by Dott was his masterwork chapter “Surgical aspects For the treatment of these cases, Dott employed the trans- of the hypothalamus,” in which he addressed in detail 4 cranial subfrontal approach he had learned from Cushing. cases he considered pure hypothalamic tumors, out of a He claimed that, contrary to the disheartening results of total series of 28 CPs he had operated on up to that time CP surgery reported by other colleagues, he had been able (about 15% of Dott’s total CP cases)34 (Table 1, Fig. 7). to achieve the successful complete removal of the tumor Actually, it has been demonstrated that this category of in 8 (57%) of these 14 cases. The remaining 6 cases cor- hypothalamic CPs, also known as infundibulo-tuberal or responded to 2 patients whose tumors were considered too not strictly intraventricular CPs, represents almost half of advanced for surgery, and 4 patients who died after incom- all cases.47,48,50,51,56,58,59,60 Therefore, Dott’s contribution to plete removal.25 the surgery of hypothalamic CPs is worth mentioning. His following article on pituitary tumors, written in col- laboration with the pathologist J. H. Biggart, defended the Clinical Impairment by CPs: Surgical Insights thesis that, contrary to other suprasellar lesions such as ad- enomas or meningiomas, the “epidermoid tumors” (CPs) into the Workings of the Hypothalamus could occupy the third ventricle and that tumors of this Dott has bequeathed to us a comprehensive knowledge this subgroup “have to be approached through a transven- of the hypothalamus through the avenue of brain surgery.

J Neurosurg Volume 127 • October 2017 935

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

learned about this project, he expressed his great enthusi- asm to Dott in a letter, sent on April 18, 1938:22 I shall look forward to your book on the hypothalamus with great interest… anything you have to say I am sure will be received with great respect. People over here are all getting hypothalamic-minded… I saw a long column in the [New York] Times a day or two ago on the thermoregulatory prov- ince of the hypothalamus which seems to act as a sort of ther- mostat to control body temperature by sweating and so on. Immediately upon reading the book, Cushing wrote to Dott on August 8, 1938, to congratulate his Scottish pupil for the “thoroughly comprehensive study [he] had made of the whole hypothalamic question… I shall, I am sure, learn much from it…”22 Published in the late 1930s, Dott’s monograph remains a classic work about hypothalamic surgery even today. However, it has been quoted only a few times in the medical literature since its publication.44,56 FIG. 7. Norman Dott in 1938, the year the book The Hypothalamus was Dott concluded his work by stating that, despite the published. A: Photograph of Norman M. Dott taken by one of his pa- hypothalamus representing a brain region not well under- tients in 1938. In October of that year the first patients enter Scotland’s stood at the time, “The observations and reflections which first dedicated neurosurgical ward, the Department of Surgical Neurol- I have recounted picture the hypothalamus as an organ of ogy in Ward 20 of the Royal Infirmary of Edinburgh. Courtesy of Lothian control and co-ordination of the more primitive bodily and Health Services Archive, Edinburgh University Library. B: Front page 34 of the book The Hypothalamus: Morphological, Functional, Clinical and psychic functions.” Following the pathway initiated by Surgical Aspects, the founding work on the clinical and surgical science Harvey Cushing, Percival Bailey, and John Farquhar Ful- on the hypothalamus.34 Reproduced from Dott 1938,34 with permission ton, Dott provided unambiguous evidence regarding the from Susan Fraser Hider. hypothalamic origin of some disturbances of water and fat metabolism, such as DI and adipose-genital dystrophy (Fröhlich’s syndrome), both once considered the conse- It was in 1927 that Dott first claimed that a number of quence of pituitary gland insufficiency (Table 1, Cases 746, symptoms originally attributed to the pituitary gland—in- 1105, and 1395).4,14,34,39 In addition, he confirmed the asso- cluding adiposity, DI, and somnolence—were actually due ciation of sleep disturbances with lesions developing at the to disturbances of the hypothalamic region.28,35 He also lo- level of the hypothalamus, even in the absence of signs of calized the heat- and water-regulating centers in the tuber intracranial hypertension. Visual hallucinations occurring cinereum.28 For that reason, he warned that the involve- after surgery in Cases 746 and 996 were interpreted by ment of the hypothalamus should be included in any con- Dott as waking dreams, a type of sleep disturbance (Table sideration of pituitary tumors, particularly in patients with 1). Finally, he emphasized the characteristic psychic dis- hyperthermia, rapidly developing adiposity or unnatural turbances observed in patients with CPs encroaching upon emaciation, vasomotor disturbances, psychological chang- the hypothalamus. These included personality changes, es, DI, or glycosuria.28 emotional volatility, with either euphoric state or apathy, Dott’s work culminated with the publication of his and impairment of memory retention (alterations present chapter on hypothalamic surgery included in the master- in Cases 746, 1105, and 1395; Table 1). The hypothalamus piece The Hypothalamus: Morphological, Functional, was now identified as a brain center which orchestrated Clinical and Surgical Aspects, at the age of 41 (Fig. 7).34 critical functions, not only for the proper homeostasis of This volume assembles an extensive and superbly illus- the inner body, but also for the stability of the psychic sta- trated account of the William Ramsay Henderson Trust tus of the individual. Lectures on the hypothalamus delivered at the Anatomy Theater of Edinburgh in October 1936 by 4 outstanding Surgery on Hypothalamic CPs neuroscientists: Sir Wilfred Edward Le Gros Clark, Pro- fessor of Anatomy at Oxford; John Beattie, Director of Re- Dott’s successful removal of hypothalamic CPs was a search at the Royal College of Surgeons, London; George product of his thoughtful understanding of the CP-brain Riddoch, an eminent neurologist from the National Square relationships, and, of no less importance, from his care- Hospital in London; and Norman Dott. This book can be ful surgical handling of brain tissue. It can be said that considered the founding work on the neuroscience of the Dott not only fulfilled but also exceeded the expectations hypothalamus in its own right. Cushing had of him. In a letter Cushing sent to Bailey on Dott judged that patients with CPs involving the hypo- August 15, 1929, he expressed the pride and high esteem thalamic area represented the most fertile source of infor- he felt for Dott with the following words: “He is a fine lad mation to understand the hypothalamus.34 Accordingly, a and has matured in just the way I hoped he would. I shall considerable length of his chapter focused on the analysis expect great things of him. It’s a poor pupil that does not of hypothalamic functions before, during, and after sur- surpass his master, as Leonardo wisely said.”21 gery of 4 hypothalamic CPs, as well as the possibility Certainly, witnessing the numerous troublesome expe- for their radical treatment (Table 1). As soon as Cushing riences that Cushing endured during his attempts of CP

936 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC Norman M. Dott, hypothalamic craniopharyngioma surgeon removal indelibly influenced Dott’s own surgical proce- Table 1; Fig. 8B2–B5). Certainly such a technical nuance dures. Training with Cushing taught Dott that CPs involv- contributed to Dott’s accurate judgment as to the degree ing the hypothalamus were not easily reachable from un- of tumor adherence to the TVF and the chances for a safe der the frontal lobe. Instead, he argued that these lesions CP radical removal while avoiding any undue injury to should be approached in the same way as true intraven- the hypothalamus.34,60 All the concepts upheld by Norman tricular tumors, a notion that represented progress over Dott’s work regarding the optimal surgical strategies for Cushing’s less precise concept of a general suprasellar the removal of hypothalamic or infundibulo-tuberal CPs topography for CPs.5,34,56 Indeed, in the revision of third remain useful and valid today.54,63,65 ventricle tumors operated on by Cushing that Fulton and Bailey coauthored, they deliberately excluded CPs, despite Conclusions their awareness that these lesions represented, “possibly the best examples of the hypothalamic syndrome.”39 Norman M. Dott should be credited for the surgical Norman Dott definitely advanced hypothalamic tumor methods he employed to safely and efficiently remove hy- surgery by realizing that any undue surgical manipulations pothalamic CPs. Between 1934 and 1937 he operated on of the CP attachment to the infundibulo-tuberal region of 4 cases of third ventricle CPs developed from the infun- the hypothalamus had devastating effects on patient out- dibulo-tuberal area of the hypothalamus, with a satisfac- come.52–54,56 Therefore, he warned against radical dissec- tory postoperative outcome in 3 out of the 4 patients. This tion of the basal portion of the tumor, the area usually series of procedures represents a notable accomplishment, showing the strongest adherence to the hypothalamus.60 especially when considering the enormous limitations of Acute hemorrhage or edema in the hypothalamus, un- the available diagnostic methods at the time, as well as the doubtedly the result of operative trauma, led to the death crudeness of the existing surgical techniques. Dott’s accept- of his patient no. 996 (Table 1).34 Dott reasoned that had he able success with hypothalamic CPs was directly related just removed the free upper half of the tumor and left in to his thorough scientific background and the vast surgical place the lower adherent portion, “…doubtless the fatality training he received at Peter Bent Brigham Hospital, under would have been avoided and the patient might have done the tutelage of Harvey Cushing and Percival Bailey. From well enough for many years.”34 the observations of the cases treated by Cushing during Such a tragic experience made Dott think that the prop- his two stays at the Brigham, Dott realized that the group er way to deal with CPs involving the hypothalamus was of CPs originating in the TVF had an intimate relationship with a double-staged procedure: one to explore and bulk with the hypothalamus. He devised a 2-stage surgical ap- out the lower portion of the lesion attached to the hypo- proach for removing hypothalamic CPs: first a basal, sub- thalamus, and a second to remove its upper portion lodged frontal, or pterional approach to attack the basal portion of within the third ventricle (Table 1).34 In his chapter, “Surgi- the tumor attached to the infundibulo-tuberal area; then a cal aspects of the hypothalamus,” Dott recommended us- subsequent transventricular approach to remove the upper ing the subfrontal route to attack the basal portion of the cystic component inside the third ventricle. He was aware CP adhered to the infundibulo-tuberal area, while leaving of the high risk of hypothalamic trauma during surgical the upper, intraventricular cystic dome of the tumor for a maneuvers for CP dissection and recommended leaving second round through a frontal-transventricular approach behind the portion of the tumor strongly attached to the (Fig. 8). TVF to avoid fatality. Dott’s surgical methods addressing To avoid the injury associated with a forced lifting of the hypothalamic CPs represent not only a notable progress in frontal lobe in patients with hydrocephalus, Dott employed the battle against one of the most serious pathologies fac- the same method used by Cushing, consisting of tapping ing contemporary neurosurgeons but also one of his major the anterior horn of the right lateral ventricle and aspirat- legacies to the field of pituitary surgery. ing the cystic content of the tumor to release tension and collapse the lobe. Then, if a flattened, compressed-forward Acknowledgments optic chiasm was found, which prevented a direct view of The authors wish to acknowledge Bill Landis and all the staff the tumor, Dott’s choice was to sacrifice and lift one of the of the Manuscript and Archives Department of the Sterling Memo- optic nerves, usually the one most impaired, to widen the rial Library, Yale University (New Haven, Connecticut), for their view and provide an expanded space for a safe dissection kind assistance in accessing both the correspondence of Harvey of the cleavage plane between the CP and the hypothala- Cushing with Norman Dott and Percival Bailey and the Cush- ing’s Brain Tumor Registry. We are grateful to Crystal Smith and mus (Fig. 8B2). This technique clearly represented a modi- Liliya Gusakova, Reference Librarians of the National Library of fication of Cushing’s midline division of the optic chiasm, Medicine, NIH (Bethesda, Maryland), Melissa Grafe, Librarian for the method he envisaged for removing inaccessible “in- the Medical History Library, Yale University (New Haven, Con- terpeduncular cysts” (intraventricular CPs).12,20 Even so, necticut), and Jack Eckert and the staff of the Francis Countway Cushing was the first surgeon who, to improve the access Medical Library at Harvard Medical School (Boston, Massachu- to a retrochiasmatic CP, proceeded to divide the right optic setts), for their kind assistance during the process of searching and nerve of the patient, on December 12, 1913 (Case “Laven- retrieving some of the original research material used in this study. stein,” surgical no. 663), and he might have informed Dott We are also indebted to Louise Williams, Archivist of the Lothian 20 Health Services Archive, and to the Royal College of Surgeons about this alternative method. Dott proceeded to sever of Edinburgh for the original pictures of Norman Dott provided one of the optic nerves in 2 of the 4 hypothalamic CP cases for this study. The authors are especially grateful to Christopher he operated on, both patients already presenting with very Rush, author of Dott’s biography With Sharp Compassion. Nor- poor vision before the procedure (Cases 746 and 1105, man Dott: Freeman Surgeon of Edinburgh for his invaluable help

J Neurosurg Volume 127 • October 2017 937

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

FIG. 8. Dott’s 2-stage approach to hypothalamic CPs. A1: Diagram of a sagittal section of surgical case no. 1105 (Table 1), showing the tumor before surgery. Note this large solid-cystic lesion grows from the tuberal area and occupies the third ventricle, causing obstructive hydrocephalus. A2: Midsagittal illustrative scheme showing the upper cystic remnant after the first procedure of CP removal through a subfrontal (SF) approach, in which the lower pole of the tumor attached to the tuber cinereum has been excised. A3: Diagram after the second operation through a frontal-transventricular (FTV) approach showing the third ventricle free of tumor. B1–B5: Surgical steps for removal of the infundibulo-tuberal portion of the lesion. B1: Exposure of the optic chiasm. Note the chiasm is pushed forward and the optic nerves are shortened. B2: The right optic nerve has been severed to give access to the lesion hidden from view behind the chiasm. B3: Dissection of the tumor from the optic chiasm and TVF. B4: The chiasm is retracted backward and the tumor is pulled out with forceps. B5: The tuberal part of the cyst has been cut away from the upper cystic component. C1–C5: Surgical steps for removal of the intraventricular cystic component of the lesion through a transfrontal-transventricular route. C1: The right lateral ventricle is approached by excising a conical section of the frontal lobe. The sketch of the surgical avenue is shown in the inset. C2–4: After sectioning both columns of the fornix, the third ventricle cav- ity is widely exposed, and the cyst wall is grasped and pulled out with forceps. C5: The white shining walls of the ventricle can be seen at the end of the procedure. Reproduced from Dott 1938,34 with permission from Susan Fraser Hider.

938 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC Norman M. Dott, hypothalamic craniopharyngioma surgeon in contacting the Dott family. We would like to particularly thank and Percival Bailey. Series I, Box 8, Folder 134. Harvey Susan Fraser Hider, Jackeline Tidder, and Katherine Mcquade, Williams Cushing Papers in the Yale University Library Dott’s grandchildren, for their kind permission to reproduce the (MS 160). (http://hdl.handle.net/10079/fa/mssa.ms.0160) letter written by Norman M. Dott on January 5, 1933, as well as [Accessed October 20, 2016] the images from his surgical procedures displayed in the book The 22. Cushing HW: Correspondence between Harvey Cushing Hypothalamus: Morphological, Functional, Clinical and Surgical and Norman Dott. Series I, Box 24, Folder 448. Harvey Aspects. Finally, we wish to express our gratitude to George Ham- Williams Cushing Papers in the Yale University Library ilton for his critical review of the language and style of the paper. (MS 160). (http://hdl.handle.net/10079/fa/mssa.ms.0160) [Accessed October 20, 2016] 23. Cushing HW: Correspondence between Harvey Cushing References and Norman Dott. Series II, Box 157, Folder 755. Harvey Williams Cushing Papers in the Yale University Library 1. Aschner B: Über die Function der Hypophyse. Pflugers (MS 160). (http://hdl.handle.net/10079/fa/mssa.ms.0160) Arch 146:1–146, 1912 [Accessed October 20, 2016] 2. Bailey P: Concerning the cerebellar symptoms produced by 24. Dott N: The history of surgical neurology in the twentieth suprasellar tumours. Arch Neurol Psychiatry 11:137–150, century. Proc R Soc Med 64:1051–1055, 1971 1924 25. Dott NM: Case of cystic pituitary epidermoid tumor. Clinical 3. Bailey P: Craniopharyngiomas. Syndrome of the hypothala- Meeting. The transactions of the Medico-Chirurgical Society mus, in Intracranial Tumors. Springfield, IL: Charles C. of Edinburgh Session CXII-1932–1933. Edinburg Med J 40: Thomas, 1933, pp 113–137 173–174, 1933 4. Bailey P, Bremer F: Experimental diabetes insipidus. Arch 26. Dott NM: Discussion on diseases of the pituitary body. Proc Intern Med (Chic) 28:773–803, 1921 R Soc Med 1:205–206, 1929 5. Biggart JH, Dott NM: Pituitary tumors: Their classification 27. Dott NM: Discussion on pituitary disorders. II. BMJ 4:1040– and treatment. Brit Med J 2:1153–1155, 1206–1208, 1936 1046, 1926 6. British Medical Journal: Rockefeller Medical Fellowships. 28. Dott NM: Diseases of the pituitary body. Med Annu 45:374– BMJ 1923(2):198, 1923 387, 1927 7. Bucy PC: Percival Bailey, 1892–1973. J Neurosurg 40:281– 29. Dott NM: Dr. Harvey Cushing, M.D. Memoir for the cente- 288, 1974 nary year of his birth. Scott Med J 14:381–386, 1969 8. Castro-Dufourny I, Carrasco R, Prieto R, Barrios L, Pascual 30. Dott NM: The early diagnosis of intracranial tumor. BMJ JM: The infundibulo-tuberal syndrome caused by craniopha- 2:891–895, 1937 ryngiomas: clinicopathological evidence from an historical 31. Dott NM: Further reflections on reintegration in specialist French cohort (1705–1973). Pituitary 18:642–657, 2015 medicine. Address to the World Congresses of Neurological 9. Castro-Dufourny I, Carrasco R, Prieto R, Pascual JM: Infun- Sciences, 1969. J Neurosurg 33:117–126, 1970 dibulo-tuberal syndrome: the origins of clinical neuroendo- 32. Dott NM: Introductory remarks. Clin Neurosurg 16:xxv– crinology in France. Pituitary 18:838–843, 2015 xxvi, 1969 10. Cohen-Gadol AA, Laws ER, Spencer DD, De Salles AAF: 33. Dott NM: An investigation into the functions of the pituitary The evolution of Harvey Cushing’s surgical approach to pitu- and thyroid glands. Q J Exp Physiol 13:241–282, 1923 itary tumors from transsphenoidal to transfrontal. J Neuro- 34. Dott NM: Surgical aspects of the hypothalamus, in Le Gros surg 103:372–377, 2005 Clark WE, Beattie J, Riddoch G, et al (eds): The Hypothala- 11. Crowe SJ, Cushing H, Homans J: Experimental hypophysec- mus: Morphological, Functional, Clinical and Surgical tomy. Bull Johns Hopkins Hosp 21:127–169, 1910 Aspects. Edinburgh: Oliver and Boyd, 1938, pp 131–185 12. Cushing H: The chiasmal syndrome of primary optic atrophy 35. Dott NM, Bailey P: A consideration of the hypophysial ad- and bitemporal field defects in adults with normal sella tur- enomata. Br J Surg 13:314–366, 1925 cica. Arch Ophtalmol (Paris) 3:505–551, 1930 36. Erdheim J: Über Hypophysenganggeschwulste und Hirm- 13. Cushing H: Concerning diabetes insipidus and the polyurias cholesteatome. Sitzungsb Kais Akad Wissen Math Naturw of hypophysial origin. Boston Med Surg J 168:901–911, Klin 113:537–726, 1904 1913 37. Fröhlich A: Ein Fall von Tumor der Hypophysis cerebri 14. Cushing H: Intracranial Tumors. Notes upon a series ohne Akromegalie. Wien Klin Rundschau 15: 883–886, of two thousand verified cases with surgical mortality 906–908, 1901 percentages pertaining thereto. Springfield, IL: Charles C. 38. Fulton JF: Harvey Cushing. A Biography. Springfield, IL: Thomas, 1932, pp 93–98 Charles C. Thomas, 1946 15. Cushing H: Papers Relating to the Pituitary Body, Hypo- 39. Fulton JF, Bailey P: Tumors in the region of the third ventri- thalamus and Parasympathetic Nervous System. Spring- cle: their diagnosis and relation to pathological sleep. J Nerv field, IL: Charles C. Thomas, 1932 Ment Dis 69: 1–25, 145–164, 261–277, 1929 16. Cushing H: The Pituitary Body and its Disorders: Clinical 40. Fulton JF, Ranson SW, Frantz AM: The Hypothalamus and States Produced by Disorders of the Hypophysis Cerebri. Central Levels of Autonomic Function. Proceedings of the Philadelphia: JB Lippincott, 1912 Association for Research in Nervous and Mental Disease, 17. Cushing H: The pituitary gland as now known, in Studies in December 20 and 21, 1939, New York. Baltimore: Williams Intracranial Physiology & Surgery. London: Oxford Uni- & Wilkins, 1940 versity Press, 1926, pp 52–103 41. Gillingham FJ: The influence of Harvey Cushing on British 18. Cushing H: Sexual infantilism with optic atrophy in cases and European neurosurgery. Surg Neurol 17:344–349, 1982 of tumor affecting the hypophysis cerebri. J Nerv Ment Dis 42. Harris P: Norman M. Dott: a biographical sketch. Clin Neu- 33:704–716, 1906 rosurg 16:xv–xxiv, 1969 19. Cushing H: The Weir Mitchell Lecture. Surgical experiences 43. Harris P: Norman McOmish Dott, 1897–1973. J Neurosurg with pituitary disorders. JAMA 63:1515–1525, 1914 40:415–417, 1974 20. Cushing HW: Brain Tumor Registry. Series I, Boxes 89–107. 44. Horwitz NH: Library: historical perspective. Norman M. Harvey Williams Cushing Papers in the Yale University Dott (1897–1973). Neurosurgery 45:944–948, 1999 Library (MS 160). (http://hdl.handle.net/10079/fa/mssa. 45. Lanzino G, Laws ER Jr: Pioneers in the development of ms.0160) [Accessed October 20, 2016] transsphenoidal surgery: Theodor Kocher, Oskar Hirsch, and 21. Cushing HW: Correspondence between Harvey Cushing Norman Dott. J Neurosurg 95:1097–1103, 2001

J Neurosurg Volume 127 • October 2017 939

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC R. Prieto and J. M. Pascual

46. McKenzie KG, Sosman MC: The roentgenological diagnosis 59. Prieto R, Pascual JM, Barrios L: Optic chiasm distortions of craniopharyngeal pouch tumors. Am J Roentg 11:171– caused by craniopharyngiomas: clinical and magnetic reso- 176, 1924 nance imaging correlations and influence on visual outcome. 47. Pascual JM, Carrasco R, Prieto R, Gonzalez-Llanos F, Alva- World Neurosurg 83:500–529, 2015 rez F, Roda JM: Craniopharyngioma classification. J Neuro- 60. Prieto R, Pascual JM, Rosdolsky M, Castro-Dufourny I, surg 109:1180–1183, 2008 (Letter) Carrasco R, Strauss S, et al: Craniopharyngioma adherence: 48. Pascual JM, González-Llanos F, Barrios L, Roda JM: Intra- a comprehensive topographical categorization and outcome- ventricular craniopharyngiomas: topographical classification related risk stratification model based on the methodical ex- and surgical approach selection based on an extensive over- amination of 500 tumors. Neurosurg Focus 41(6): E13, 2016 view. Acta Neurochir (Wien) 146:785–802, 2004 61. Rush C, Shaw JF (eds): With Sharp Compassion. Norman 49. Pascual JM, Prieto R: Harvey Cushing and pituitary Case Dott: Freeman Surgeon of Edinburgh. Edinburgh: Aber- Number 3 (Mary D.): the origin of this most baffling problem deen University Press, 1990 in neurosurgery. Neurosurg Focus 41(1):E6, 2016 62. Sharpey-Schäfer EA: An Introduction to the Study of the 50. Pascual JM, Prieto R, Carrasco R: Infundibulo-tuberal or Endocrine Glands and Internal Secretions. Stanford, CA: not strictly intraventricular craniopharyngioma: evidence Stanford University, 1914, pp 53–78 for a major topographical category. Acta Neurochir (Wien) 63. Steno J, Malácek M, Bízik I: Tumor-third ventricular rela- 153:2403–2426, 2011 tionships in supradiaphragmatic craniopharyngiomas: cor- 51. Pascual JM, Prieto R, Carrasco R, Barrios L: Displacement relation of morphological, magnetic resonance imaging, and of mammillary bodies by craniopharyngiomas involving the operative findings. Neurosurgery 54:1051–1060, 2004 third ventricle: surgical-MRI correlation and use in topo- 64. Walker CB, Cushing HC: Studies of optic-nerve atrophy graphical diagnosis. J Neurosurg 119:381–405, 2013 in association with chiasmal lesions. Arch Ophthalmol 52. Pascual JM, Prieto R, Carrasco R, Castro-Dufourny I, Bar- 45:407–437, 1916 rios L: Craniopharyngioma adherence to the hypothalamus. 65. Yaşargil MG: Craniopharyngiomas, in Yaşargil MG (ed): Neurosurg Focus 37(2):1–7, 2014 (Letter) Microneurosurgery of CNS Tumors. New York: Thieme, 53. Pascual JM, Prieto R, Castro-Dufourny I, Carrasco R, 1996, Vol IVB, pp 205–223 Strauss S, Barrios L: Development of intracranial approaches for craniopharyngiomas: an analysis of the first 160 historical procedures. Neurosurg Focus 36(4):E13, 2014 54. Pascual JM, Prieto R, Dufourny IC, Simoes RG, Carrasco Disclosures R: Hypothalamus-referenced classification for craniopharyn- The authors report no conflict of interest concerning the materi- giomas: evidence provided by the endoscopic endonasal ap- als or methods used in this study or the findings specified in this Neurosurg Rev 36: proach. 337–339, 2013 paper. 55. Pascual JM, Prieto R, Mazzarello P: Sir Victor Horsley: pio- neer craniopharyngioma surgeon. J Neurosurg 123:39–51, Author Contributions 2015 56. Pascual JM, Prieto R, Navas M, Carrasco R: Conquest of Conception and design: Prieto. Acquisition of data: both authors. third ventricle craniopharyngiomas. J Neurosurg 112:1156– Analysis and interpretation of data: both authors. Drafting 1161, 2010 (Letter) the article: Prieto. Critically revising the article: both authors. 57. Pascual JM, Rosdolsky M, Prieto R, Straub S, Winter E, Reviewed submitted version of manuscript: both authors. Ulrich W: Jakob Erdheim (1874­–1937): father of hypoph- Approved the final version of the manuscript on behalf of both yseal-duct tumors (craniopharyngiomas). Virchows Arch authors: Prieto. 467:459–469, 2015 58. Prieto R, Pascual JM: Craniopharyngiomas with a mixed Correspondence histological pattern: the missing link to the intriguing patho- Ruth Prieto, Department of Neurosurgery, Puerta de Hierro Uni- genesis of adamantinomatous and squamous-papillary variet- versity Hospital, C/Joaquín Rodrigo 2, Majadahonda, Madrid ies? Neuropathology 33:682–686, 2013 28222, Spain. email: [email protected].

940 J Neurosurg Volume 127 • October 2017

Unauthenticated | Downloaded 10/06/21 02:54 PM UTC