Historical vignette J Neurosurg 125:1301–1314, 2016

Sir Hugh Cairns and World War II British advances in head injury management, diffuse brain injury, and concussion: an tale

James L. Stone, MD, Vimal Patel, PhD, and Julian E. Bailes, MD

Department of , NorthShore Neurological Institute, NorthShore University HealthSystem, Evanston, Illinois

The authors trace the Oxford, , roots of World War II (WWII)–related advances in head injury management, the biomechanics of concussion and brain injury, and postwar delineation of pathological findings in severe concussion and diffuse brain injury in man. The prominent figure in these developments was the charismatic and innovative –trained neurosurgeon Sir Hugh Cairns. Cairns, who was to closely emulate Cushing’s surgical and scholarly approach, is credited with saving thousands of lives during WWII by introducing and implementing innovative programs such as helmets for motorcyclists, mobile neurosurgical units near battle zones, and the military usage of penicillin. In addition, he inspired and taught a generation of neurosurgeons, neurologists, and neurological nurses in the care of brain and spinal cord injuries at Oxford’s Military Hospital for Head Injuries. During this time Cairns also trained the first full-time female neurosurgeon. Pivotal in supporting animal research demonstrating the critical role of acceleration in the causation of concussion, Cairns recruited the physicist Hylas Holbourn, whose research implicated rotary acceleration and shear strains as particularly damaging. Cairns’ work in military medicine and head injury remain highly influential in efforts to mitigate and manage brain injury. http://thejns.org/doi/abs/10.3171/2015.8.JNS142613 Key Words Hugh Cairns; biomechanics; head injury; diffuse brain injury; concussion; helmets; Harvey Cushing; British neurosurgery; history

n 1934, Winston Churchill (1874–1965), the future The British military’s neurosurgical and neurological British prime minister, informed Parliament of the response to the challenges of World War II (WWII) result- threat of German hostility leading to a European war ed in significant progress in the organizational structure, thatI could include massive aerial bombing of London. By management, and resultant outcome from head injuries, autumn of 1938 war seemed inevitable, and it was feared which was of much relevance to future military and ci- that Germany could begin bombardment at any time. A vilian trauma management. Head injury research in pri- trial nighttime blackout in London was held in August of mates and in vitro modeling of human head injury led to 1939, and after Germany invaded Poland in early Septem- biomechanical theories of brain injury that continue to be ber of that year, blackouts at sunset were mandated with no influential today. These theories include the critical roles lights allowed after dark for one-half of a decade. A month of acceleration/deceleration forces in the production of later Germany invaded and occupied multiple neighbor- concussion, and of rotary or angular forces in shear force ing countries, prompting the United Kingdom (UK) and injuries of the brain. France to declare war on Germany. In June of 1940, Ger- The dynamic and pioneering Oxford-based British neu- many invaded and began the occupation of France, and rosurgeon Sir High Cairns (1896–1952) was personally by September of that year London was bombarded by the involved in the conduct of all phases of these uniquely in- Germans for 57 consecutive nights. More than 1 million fluential neurological and neurosurgical initiatives during London homes were damaged or destroyed and more than WWII. He had the foresight, gained the necessary high- 40,000 civilians were killed, approximately one-half in level political and military trust and financial support, and London, and the remainder in other industrial UK cities carried out the critical organizational planning and imple- and ports.15,43,89 mentation. In the fashion of his neurosurgical mentor Har-

Abbreviations EMS = Emergency Medical Services; MNSU = Mobile Neurosurgical Unit; MRC = British Medical Research Council; RAMC = Royal Army Medical Corps; UK = United Kingdom; WWI = World War I; WWII = World War II. SUBMITTED November 14, 2014. ACCEPTED August 13, 2015. include when citing Published online February 19, 2016; DOI: 10.3171/2015.8.JNS142613.

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Unauthenticated | Downloaded 09/29/21 01:22 AM UTC J. L. Stone, V. Patel, and J. E. Bailes vey Cushing (1869–1939), Cairns insisted upon extensive clinical documentation and outcome analyses, and person- ally oversaw a multitude of in-depth, well-written publica- tions resulting from these WWII experiences. Hugh Cairns Early Career and Neurosurgical Training With Cushing Hugh William Bell Cairns was born and raised in South Australia, where he finished secondary and medi- cal school at , served as a World War I (WWI) physician in the Middle East and France, and came as a Rhodes Scholar to Oxford’s Balliol College in early 1919 (Fig. 1). 89 Handsome, athletic, bright, and outgoing, with a captivating personality, Cairns caught the attention and was an invited guest to the home of his physiology teacher, Sir Charles Sherrington (1857–1952), and the internist Sir William Osler (1849–1919), with whom he had rounded at the .43 Lady Osler first introduced Cairns to the well-known American neurosurgeon Harvey Cushing (1869–1939).43 At Oxford, Cairns did a surgical residency and spent a period as anatomy demonstrator at the Radcliffe Infirmary. He married a gifted daughter of A. L. Smith, a well-respected teacher and the Headmaster of Balliol College.72 In 1921 Cairns became a fellow of the Royal College of Surgeons, went to the London Hos- pital as house surgeon, and later was appointed as first as- sistant to the notable general surgeon Sir Henry Souttar (1875–1964). Souttar, who performed some neurosurgical procedures and described the bicoronal incision, was also a founder of the Society of British Neurological Surgeons in 1926.22 Sherrington, and especially London neurologist Fig. 1. Hugh Cairns (1896–1952). Papers of Hugh Cairns, Bodleian Library, Oxford; scanned with permission of his daughter, Elizabeth George Riddoch (1888–1947), saw distinctive potential in Nussbaum. Cairns, who exhibited boundless energy and determina- tion, “qualities necessary to develop modern neurosur- gery” in London.11,70,72 Sir Walter Morley Fletcher (1873– 1933) of the British Medical Research Council (MRC) and who pointed the path to the advancement of this newest a close friend of Cushing also came to know Cairns.44 branch of surgery by physiological experimentation in ad- The above individuals helped Cairns obtain a Rock- dition to clinical and pathological contributions…he was efeller traveling fellowship to spend a full year of neuro- the first surgeon to devote the bulk of his time to neu- surgical training under Harvey Cushing in Boston (1926– rological surgery…about 60%, 40% general surgery.”55 1927). Soon after Cairns’ arrival, Cushing’s astute sec- Cairns, however, is considered the first surgeon in Great retary Ms. Stanton noted, “Cairns here for a year…Runs Britain to devote himself exclusively to neurosurgery. around everywhere so as to waste no time…Going to be (1886–1961) of Manchester, England, a great success.”8 In the fall of 1927 Cairns returned to had briefly visited Cushing and is credited with initiating London as one of the first neurosurgeons in that city to be neurological surgery as an actual surgical “specialty” in trained in modern methods. In a lengthy letter to Cairns Great Britain after WWI but performed general surgery immediately after his training, Cushing emphasized the as well.58,82 Norman M. Dott (1897–1973), of Edinburgh, critical need for neurosurgical specialization to properly Scotland, who trained with Cushing several years before advance this demanding field.44 It was clear that Cairns’ Cairns, continued pediatric general surgery in addition to goal in London was to develop a dedicated neurosurgical neurosurgery.82 These modern neurosurgical pioneers and service emulating the meticulous and painstaking opera- friends shared the same struggles, ideals, and goal of “a tive techniques, clinic organization, and system of record self-contained unit with the ambition to raise [neurosurgi- collection he learned from Cushing.43,89 cal] work…to the top level of international ranking.”59,89 Sir William Macewen (1848–1924) of Glasgow, Scot- Cairns developed a fine reputation at the London Hos- land, and Sir Victor Horsley (1857–1916) of London, pital with its first neurological surgery service. This was England, pioneered neurosurgery in the late 19th and due to his diligence, perseverance, engaging personality, early 20th centuries.39 Although Macewen antedated and surgical results. Cairns was a particular favorite of 43 Horsley by 6–7 years in performing successful antisep- Cushing, who wrote to the Rockefeller Foundation: tic brain operations based on cerebral localization, Hors- …young Cairns…with all the necessary qualifications for ley is often labeled the “father of neurological surgery… success – ambition, vigorous health, enthusiasm, good train-

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ing, breeding, and most winning personal qualities…wants ing. Cairns was believed to have been significantly moved to devote his entire time to the furtherance of neurosurgical by the tragedy, as it was apparent that a helmet might have work in London which since Horsley’s death is practically avoided serious brain injury and saved Lawrence’s life.64,80 non-existent….” As early as 1934, Cairns began to think about transfer- Cairns subsequently obtained financial support from ring his growing neurosurgical service to Oxford, where the Rockefeller Foundation to include surgical equipment there was room for expansion and where he had friends and subsidize neurosurgical assistants and trainees. At the and influence.43,65 In addition to having a beguiling charm London Hospital, Cairns met a young, talented research and manner, Cairns was politically astute and could be pathologist named Dorothy Russell (1895–1983), whom relentless to serve his needs. By the summer of 1935 he encouraged to study neuropathology. With Cairns’ sup- Cairns had broadened his ideas to include the formation port she obtained a Rockefeller fellowship to study for of a high-quality research and clinical medical school and several years in Boston and Montreal (1928–1929) and be- shared these ideas with neurologist and supportive friend came a leading world authority in neuropathology.5,6 In the Sir E. Farquhar Buzzard (1871–1945), an eminent London next few years Cairns was appointed surgeon to the two neurologist and physician to King George V, who held Os- principal London neurological hospitals at Maida Vale ler’s previously held chair as Regius Professor of Medicine (1931–1934) and the National Hospital of Nervous Disease at Oxford.28,43 Buzzard had witnessed the failure of simi- at Queen Square, London (1934–1937). lar plans for Oxford by the Rockefeller Foundation in the However, the London Hospital and its senior surgeons late 1920s and was determined that this should not happen would not commit adequate space or facilities to the again.28,44 dedicated and independent neurosurgical department that By 1936 Cairns shared his more extensive written Cairns believed was necessary. At Queen Square, where proposals with Buzzard, and a scheme was developed Cairns performed only 1 operation, the senior neurolo- to gather support for the plan at the highest levels. Buz- gists believed in a “dominance” of neurology over neuro- zard arranged meetings between Cairns and other influ- surgery and resisted changes such as granting admission ential Oxford University officials who recalled the earlier privileges and beds to the surgeons and providing facili- failed effort.28,43 In 1936 Buzzard was also president of ties attractive to private patients in the style that Cushing the British Medical Association and the Oxford host of had developed in Boston.43,44,65,82 The Rockefeller Founda- its annual meeting. At the formal British Medical Asso- tion, although well disposed to providing financial support ciation reception, it was arranged for Cairns to be intro- to neurological centers in North America and Europe, re- duced by his wife’s mother, a “grande dame of Oxford” alized Cairns’ potential but believed the well-known neu- to the billionaire automotive manufacturer Lord Nuffield rological center at Queen Square held a better chance for (1877–1963). 59 Nuffield, a native of the Oxford area with a success.44 particular interest in medical philanthropy, took a special During this period, most of England’s established se- liking to the energetic and highly convincing Australian. nior general surgeons remained unconvinced that Cush- In short order, Nuffield endowed benefactions (including ing’s delicate, overly slow, and plodding techniques with a foundation) amounting to approximately 12.5 million gentle handling of all tissues, and meticulous control of pounds (27 million by 1955) to significantly reorganize bleeding, resulted in a better outcome.39 Many elder sur- and bolster Oxford’s medical school as a center for re- geons also believed that the speed of surgery was of prime search, teaching, and clinical expertise.59 Cairns became importance, as anesthetics were more unpredictable and a key figure in the planning, building, and organization dangerous with prolonged operations. In addition, Cush- of the new medical school. He was appointed the Nuffield ing had worked with British surgeons during WWI and Professor of Surgery at Oxford (1937) and founded the was known to be a difficult individual at times.24 Finally, neurosurgical unit at the Radcliffe Infirmary (Fig. 2). The few if any English surgeons believed it possible to make enthusiasm engendered by Cairns was quite remarkable. an adequate living by specializing in neurological surgery He had unparalleled ability to assemble the new surgery alone. Thus, dabbling as a “dilettante” in some neurosur- department, including new wards and offices, and to at- gical procedures was considered adequate.59 tract new heads of other departments. Not surprisingly, in In May of 1935, T. E. Lawrence (1888–1935)—better addition to neurosurgery, Cairns “was an excellent teacher 28 known as “Lawrence of Arabia,” the celebrated British of general medical principles.” However, in early 1938, WWI hero, Oxford scholar, author, and authority on Ara- within several months of Cairns moving from London to bia—was fatally injured in a motorcycle accident. Law- Oxford, unrest was escalating in Europe. Oxford was to become the leading neurosurgical center in Great Britain rence swerved to avoid an oncoming vehicle, lost control, 43,58 and pitched forward over the handlebars. Cairns drove just before, during, and for 5 or 6 years after WWII. about 100 miles to consult on Lawrence, who suffered a severe head injury with skull fracture and survived in a World War II Contributions coma for 5–6 days until he died from chest complications. In 1938 Cairns was appointed advisor to the War Of- The family allowed Cairns to perform the autopsy and fice on the care of head injuries in the armed forces.81 This take the brain.43,58,80 The brain, likely in poor condition, was not surprising, because since the early 1930s, Cairns was presumed to have been given to Dorothy Russell for had been a civilian consultant neurosurgeon to Queen Al- study, but no autopsy report is available. Lawrence was exandra’s Military Hospital at Millbank, a Royal Army not wearing a helmet, as “crash helmets” at that time were Medical Corps (RAMC) facility. Senior military person- predominately worn by those involved in motorcycle rac- nel knew Cairns well, liked and respected him, and ap-

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Fig. 3. Brigadier Cairns in uniform during WWII. Reproduced from Jef- ferson G: Memories of Hugh Cairns. J Neurol Neurosurg Psychiatry 22:155–166, 1959, with permission of BMJ Publishing Group Ltd. Fig. 2. Hugh Cairns (right) with Harvey Cushing (left) in front of the Nuffield Institute, July 1938. From Fraenkel GJ: Hugh Cairns: The First Nuffield Professor, Oxford, Oxford University Press, 1991. Charles P. Symonds (1890–1978; pronounced “Simonds”), who was consultant neurologist to the Royal Air Force, and neurologist George Riddoch, a pioneer in the treat- ment of WWI brain and spinal cord injuries, to assist him preciated his work. About this time, the British Ministry in the planning and operation of a military hospital for of Health began serious organization of their Emergency head injuries at Oxford.72 Before the end of 1938 Cairns Medical Services (EMS) primarily to provide for possible had decided upon the use of St. Hugh’s College for Wom- air-raid casualties.43,88 Neurosurgeons and neurologists, en near the Radcliffe Infirmary to be the site of Oxford’s some of whom had been involved in WWI, were mobilized Military Hospital for Head Injuries, serving the army and for military and civilian designation and assignments. Un- air force. The hospital opened in February 1940 with 50 der the Ministry of Health in 1938, Cairns together with beds, and that month Cairns, who had been an acting colo- Jefferson divided England between them for civilian EMS nel, was appointed as brigadier and the neurosurgical head neurosurgical organization.43 In July or August of 1938, in of the RAMC (Fig. 3).43 This was a major step in estab- anticipation of a projected steel shortage, Cairns wisely lishing concrete recognition by the British Army Medi- convinced the War Office to procure “all surgical instru- cal Service of neurosurgery as a surgical specialty distinct ments which would be required by army neurosurgical from general surgery. units during the impending war. Consequently, neurosur- The St. Hugh’s Military Hospital for Head Injuries—af- gical instruments were never in short supply.”80 “This was fectionately nicknamed “the Nutcracker Suite”—had a cen- in sharp contrast to the situation in other specialties…”80 sus that grew to 300, rising to 430 at the height of the battle By the fall of 1938, with war seemingly inevitable, it of Normandy in June of 1944. During WWII, St. Hugh’s was decided that Oxford was an ideal location for a neu- treated approximately 13,000 head injuries and became a rological and neurosurgical military hospital as Cairns training ground for a generation of neurosurgeons and neu- and his team were already there. Without significant war- rologists, anesthetists, medical students, neurological nurs- related heavy industry, Oxford was unlikely to be bombed es, orderlies, and other medical personnel, many of whom (and never was), yet it was in reasonable proximity to Lon- had fled the Nazis.15,43 Cairns, in the tradition of Cushing, don where many casualties were expected. Cairns asked realized much would be learned from this wartime experi-

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Unauthenticated | Downloaded 09/29/21 01:22 AM UTC Hugh Cairns: an Oxford tale ence, and insisted that meticulous clinical records be kept, anticipating the necessity of accuracy in forthcoming pub- lications.15,76–78,85 St. Hugh’s was also the base station for the Mobile Neurosurgical Units (MNSUs; see below). Cairns created two convalescent homes for neurologi- cal rehabilitation, a recently introduced and much valued field.19,48 Brigadier George Riddoch, recalling the particu- lar displeasure and hopeless outlook for young soldiers with spinal cord injuries in WWI, induced the British gov- ernment to establish a special center for these individuals and convinced neurologist/neurosurgeon Ludwig Gutt- mann (1899–1980) to take charge of this service. Due to Riddoch’s vision, the world’s first “Spinal Injuries Centre” was established at Stoke Mandeville Hospital in Ayles- bury, England.11,27,49,55,68 During this period Cairns was also responsible for training the first full-time female neurosurgeon, Diana K. Beck (1902–1956).46 Dr. Beck was highly qualified, having been a fellow of the Royal College of Surgeons of Edinburgh, fellow of the Royal College of Surgeons of England, Surgical Registrar, Demonstrator and Lecturer in Anatomy and Surgical Anatomy at London’s Royal Free Hospital, and Clinical Clerk at Queen Square.43 At age 37 she was appointed House Surgeon to Cairns in January 1939, and completed her neurosurgical training at St. Hugh’s in 1943. A favorite of Cairns, she was a highly motivated, able, and experienced surgeon. Cairns placed her in charge of the introductory course in clinical sur- gery, and she was also very productive in Dorothy Rus- sell’s laboratory.43,46 Upon leaving Oxford in 1943, Beck was assigned by EMS Director Jefferson in the north of London, and then at Bristol. She was given a senior ap- pointment at London’s Middlesex Hospital (1947), where she was the first woman to head a neurosurgical service, and completed a fine career in neurosurgery until her un- expected death in 1956.46

Motorcycle Crash Helmets The subsequent bombing of London (1940) brought forth an abundance of severe head injuries in both civil- Fig. 4. A. H. S. “Hylas” Holbourn (1907–1962), Oxford physicist. Photo- ians and the military, especially military dispatch motor- graph courtesy of Ms. Sheila C. Gear. cycle riders and pillion passengers.43,64,72,74,88 Cairns had been tracking accidents in military dispatch motorcy- clists,14 and he stated,12 In 1939 Cairns elicited the help of Oxford physicist My interest in crash helmets arises solely from the fact that and motorcycle enthusiast A. H. S. “Hylas” Holbourn during the War, I spent a considerable part of my time treat- (M.A., Edinburgh; D.Phil., Oxford; 1907–1962; Fig. 4), on ing injured motor-cyclists at the Military Hospital for Head the study of crash helmets especially as applied to mo- Injuries at Oxford. In other words, it was the segregation of torcycle accidents.14,20,72 MRC grants helped support this the Army’s head-injury patients in special centres which made work. Motorcycle helmets were carefully studied after ac- possible the prompt recognition of the importance of crash cidents and correlated with radiological and clinical find- helmets. ings as well as outcomes in head-injured patients. This Cairns reported that 2279 motorcyclists and associated work proved the importance of helmet usage and led to passengers were killed within the first 21 months of the improved helmet design (Figs. 5 and 6).12,14,20 war (more than 3 per day), and two-thirds of these deaths Cairns and Holbourn were influenced by MRC-sup- were army members.12,14 A head injury was present in 92% ported experimental work begun in early 1940 on acceler- of motorcycle-related injuries, and although not the sole ation concussion by neurologists Denny-Brown and Rus- cause of death, it was clearly a major factor in the major- sell (1941, see below).68 It is likely that Holbourn’s training ity.15,19 The situation was compounded by blackouts from in physics and earlier research convinced him that angular nightly air-raid bombings and the recklessness of youth. acceleration from sudden head rotation was most injuri- However, Cairns found 7 cases of motorcyclists who were ous to the brain: “This is the cause of all gross bruises or wearing crash helmets and none were fatally injured.14,20 lacerations of the cortex remote from the site of the blow.

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Fig. 5. WWII British military motorcycle crash helmets. A: Vulcanized rubber helmet with an inner suspension system connected by a com- mon cord at the helmet’s base. Any break in the cord can result in the rider’s head contacting the hard crown of the inner shell. B: Wood pulp helmet whose inner suspension slings are stitched separately through the substance of the outer shell, and the cords at the base merely retain the hatband in place. Reproduced from Cairns H, Holbourn H: Head injuries in motor-cyclists: with special reference to crash helmets. BMJ 1:591–598, 1943, with permission from BMJ Publishing Group Ltd.

» Fig. 6. Motorcycle helmet images. A: Helmet from a 23-year-old soldier who struck a stationary vehicle at 30 miles per hour and was rendered unconscious. Right frontal damage and detachment of the outer shell and inner sling of the vulcanized helmet (arrows) is shown. A scalp laceration and slightly depressed nonsurgical frontal skull fracture was present. In a few days he was alert with return to full duty. B: Helmet from a 23-year-old soldier who was passing a van at 40–50 miles per hour and crashed into it as it swerved. He was briefly unconscious with several days of headache. The vulcanized helmet had fractured in the right temporal and parietal region and projected anteriorly (arrows), and a loop of the sling tore off. The patient recovered fully despite a right frontal scalp laceration and linear skull fracture. Reprinted (A and B) from Cairns H: Head injuries in motor-cyclists. The importance of the crash helmet. BMJ 2:465–471, 1941, with permission from BMJ Pub- lishing Group Ltd. C: Drawing of a helmet from a 27-year-old soldier who was speeding with his head down, struck the back of a stationary vehicle, and was rendered comatose. He showed signs of asphyxia without external signs of head injury and died several days later. Multiple thoracic vertebral fractures were present. His pulp-type crash helmet showed a large, deep dent in the frontal region (arrow). The autopsy, performed by Dorothy Russell, showed bronchopneumonia, a small amount of bilateral subpial hemorrhage, numerous symmetrically scat- tered hemispheric petechial hemorrhages, and diffuse white matter softening. There was no spinal cord injury. Death was likely related to a severe, diffuse concussional head injury as no spinal cord injury was evident. Reproduced from Cairns H, Holbourn H: Head injuries in motor- cyclists: with special reference to crash helmets. BMJ 1:591–598, 1943, with permission from BMJ Publishing Group Ltd.

All the available evidence points to its being also the cause of concussion.”20 Holbourn, whose help was acknowledged in Cairns’ 1941 paper on motorcycle crash helmets, apparently shared the above opinion with Cairns, as this paper mentions two received any severe blow…and this suggests a fairly se- helmeted patients: Case V suffered a concussion and post- vere head injury from violent rotation of the head, [and]… concussion syndrome, which “crash helmets cannot be helmets have the theoretical disadvantages that they in- expected to prevent”; and for Case VI, unconscious for crease the diameter of the head and so leverage [the head, several days, his helmet showed “marks of violence which increasing]…the likelihood of broken neck and rotational were slight, and it is therefore doubtful whether his head acceleration within the cranium.”14,29 In their joint paper

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Unauthenticated | Downloaded 09/29/21 01:22 AM UTC Hugh Cairns: an Oxford tale of 106 head injuries in those wearing helmets, Cairns and Holbourn (1943) concluded that hospitalized, injured mo- torcyclists who were wearing helmets, as compared with hospitalized motorcyclists who were not, had a signifi- cantly reduced percentage of skull fractures, neurological damage, concussion, and prolonged amnesia associated with concussion, and inability to return to duty. They also believed that helmets likely kept a number of motorcyclists from even coming to the hospital after an accident.20 They believed helmets decreased local damage to the scalp and skull, especially from pointed objects, and less- ened the numbers of depressed and penetrating skull frac- tures with associated brain injury: “The so called coup lesion is, in our view, due to the bending of the skull un- der the blow.”20 The shell of the helmet also functions by “lengthening the blow, that is by spreading it out over a longer interval of time, so that it is not so intense at any particular instant…lengthening reduces not only the local Fig. 7. The first MNSU parked outside of the Nuffield Institute of Medi- injury but all other effects of the blow.”20 The helmet shell cal Research, 1940. The vehicle housed all necessary equipment to can slide over objects perform emergency neurosurgical operations. From Cairns H: The orga- nization for treatment of head wounds in the British Army. Br Med Bull …instead of stopping more abruptly, as the unprotected head 3:9–14, 1945, by permission of Oxford University Press. would do owing to its greater coefficient of friction…The blow is also lengthened to some extent by the rotation of the helmet relative to the head…But the main way in which the blow is spread over a longer time is by means of the buffer- (1906–1997) at the Canadian Neurosurgical Center in Bas- ing action of the slings [being stretched] and hatband [com- ingstoke, England (personal communication to J. L. Stone pressed]. (bracketed material added by authors) by E. Alexander Jr., May 1996; personal communication to The effect of the blow lasts all this time, instead of only J. L. Stone by E. H. Botterell, May 1996).10,15 during the time taken to deform the scalp and skull. They believed the suspension (sling) components on helmets Mobile Neurosurgical Units could and should be significantly improved.20 In WWI, Cushing (1918) demonstrated improved re- Cairns and Holbourn (1943) concluded that the hard, sults with an early, definitive operation; debridement of vulcanized rubber outer shell helmets tended to fracture, devitalized brain tissue, in-driven bone fragments, and resulting in underlying skull fractures being twice as com- foreign bodies; dural closure; and primary 2-layer closure mon and an increased incidence of concussion and con- of the scalp. Other WWI European surgeons likewise ad- cussion related amnesia, as compared with those wearing vocated aggressive approaches that led to a lessening of wood pulp outer shell helmets. The wood pulp helmets had fatal infection and the dreaded complication of fungating an outer shell consisting of compressed wood pulp cov- herniation of injured brain tissue through a defect in the ered by a thin film of cloth, which tended to crush more skull and scalp.23,32,56,57 The postoperative mortality rate in on impact. The pulp helmet also had a more secure inter- penetrating injuries not receiving adequate early surgical nal headband liner and suspension system to prevent the treatment was approximately 50%, and many died before rider’s head from coming into contact with the crown of they could be treated.29,31 the outer shell (Figs. 5 and 6).12,20 To enable neurosurgical teams to definitively treat In 1941 Cairns was responsible for making helmets head injuries within 24–48 hours after injury, as Cush- compulsory for army motorcyclists, and by the end of 1942 ing advocated,30,31 Cairns came up with the idea of us- he clearly had demonstrated a significant decrease in mo- ing MNSUs.15,16 The MSNU vehicles had the appearance torcycle deaths.12,68 “This is an example,” he wrote, “of the of a large ambulance or modified truck (Fig. 7), and the impelling need for hasty decision in wartime on questions first MNSU was assembled in May of 1940. Almost all which really should have been worked at thoroughly be- of the MNSU staff had been trained at St. Hugh’s, and tween the wars.”12 Although foolishly resisted for decades “the (Cushing) standard of documentation and neurologi- by civilian motorcyclists, in 1973 helmet usage became cal examination never slipped, despite the circumstances law in the UK.64,88 Motorcycle helmets have been shown in which they worked.”80 The MNSUs generally worked to reduce the risk of head injury by almost 70%, and death in conjunction with a host hospital or temporary casualty by more than 40%.62 clearing station close enough to the front lines for timely Interestingly, the abundance of head injuries in WWII general triage and neurosurgical evaluation. The host unit British and Canadian military dispatch motorcyclists also would provide postoperative beds, extra staff, catering, led to the recognition of the necessity to evacuate sizable laundry, pathology, radiology, etc.15,16 The MSNU had 1 hemorrhagic coup or contrecoup frontal and temporal neurosurgeon, 1 triage neurologist, 1 anesthetist, 2 gen- cerebral contusions by craniotomy. Associated acute or eral RAMC officers, 2 nurse sisters, 4 RAMC orderlies, subacute subdural hematomas may be present as well. and 2 RAMC drivers. Each MNSU had its own electrical These WWII investigations were led by E. Harry Botterell generator, water supply, tents, 2 heated operating tables,

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Unauthenticated | Downloaded 09/29/21 01:22 AM UTC J. L. Stone, V. Patel, and J. E. Bailes and operative illumination. There were 2 neurosurgical instrument sets and 1 general use set. The equipment was sufficient to carry out at least 200 cranial operations with- out replacements.15,81 Of critical importance, Cairns convinced the military authorities that each unit must have its own power suc- tion, electrocautery (diathermy), and lighted brain retrac- tors:16,59,73 “Such luxury army surgeons had never had before…it speaks volumes for the respect and regard in which Cairns was held by the War Office…that he was able to get these things…[and thus] the units were able to obtain hitherto unheard of results in penetrating head wounds.”59 It took only a brief period for the army medical and surgical units to learn how the MNSUs could be opti- mally interfaced with the existing services. This allowed definitive neurosurgical operation upon brain injuries, usually within about 24 hours of injury (Fig. 8).1,3,15,79 Six active MNSUs were used in France, North Africa, Italy, Northern Europe, India, and Asia, and more than 20,000 patients (80% of soldiers and airmen with head injuries) were treated.15 In Italy 1 unit performed 334 operations in 16 days and another 208 in 15 days.80 About 90% of those with scalp wounds and simple skull fractures returned to their units, and 70% of the brain injured were employable, although few returned to full duty. It was clear that this early deployment of neurosurgical skills resulted in prima- ry healing in 85%, a considerable reduction in infection, morbidity, and mortality rates, and improved the quality of survival.3,15,38,80,81 Of much importance in the final years of the war, the MNSUs were also used in the introduction and critical evaluation of the use of penicillin in injured neurosur­gi­ cal patients (see below).15,41 MNSU 6 took part in the inva- sion of Normandy in 1944, and later in WWII the British M­NSUs were coordinated with air evacuation of neurosur- gical patients.15 The MNSUs are considered the precursor of the mobile army surgical hospital, or MASH, units, and the concept was so successful that it was later used by the US Army in conjunction with helicopter evacuation in Korea, Vietnam, and Desert Storm, decreasing the elapsed time to several hours between injury and definitive debridement.1,81

Howard Florey, Cairns, and Penicillin Trials in the Military In 1928, the Scottish bacteriologist and physician Al- exander Fleming (1881–1955), while examining a Staph- ylococcus culture plate, noted a halo of inhibited bacte- rial growth around a contaminant blue-green mold.33,40,50 Fleming concluded the mold (Penicillium notatum) re- leased a substance that inhibited bacterial growth, which he later termed “penicillin.”42 Fleming cultured the origi- nal mold but was limited in his ability to purify, concen- Fig. 8. A: Young man with through-and-through transfrontal gunshot trate, and produce substantial stable amounts of penicillin wound upon arrival 16 hours after injury to MNSU 5, Naples, Italy, May to perform adequate clinical trials.42,60 1944. B: Scalp shaved, entry and exit wounds shown. C: Diagrams The key physician investigator who would lead this im- showing the line of the skin incision and area of brain damage. D: The patient, 10 days after surgery, was still confused with slight right-sided portant task was Howard Florey (1898–1968), a meticulous weakness. His bone defect was subsequently repaired and he returned and skilled research professor of pathology at Oxford and to duty. From Schorstein J: An atlas of head wounds illustrating standard an Australian colleague of Cairns. After reading Flem- operative technique. Br J Surg 55 (Suppl 1):27–61, 1947. ©British Jour- ing’s work, in 1938 Florey and coworker Ernst B. Chain nal of Surgery Society Ltd. Reproduced with permission of John Wiley & (1906–1979) began to investigate the chemical, pharma- Sons Ltd. on behalf of the BJSS Ltd.

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Unauthenticated | Downloaded 09/29/21 01:22 AM UTC Hugh Cairns: an Oxford tale cological, and chemotherapeutic properties of penicillin.25 They devised methods to increase the yield of penicillin, demonstrated slight if any toxicity in mice, and reported a 90% and 100% success rate in curing mice infected with Staphylococci or Streptococci, respectively, compared with death in all controls.25 While this research was under way, Florey wrote to the MRC for support in September of 1939, “I can get clinical co-operation from Cairns for any products we produce and I have tested on animals.”43,65 In January 1941 Florey approached Cairns with a view to clinical trials in patients with infections at the Radcliffe Infirmary. Cairns quickly directed him to the Nuffield Professor of Medicine, Leslie J. Witts (1898–1982).28,43,65 Thus, in February 1941, the first ever systemic usage and clinical trials of penicillin were performed on Professor Witts’ Radcliffe Infirmary patients.42 Penicillin was given intravenously in 5 patients with Staphylococci and Strepto- cocci infections and was also applied locally to 4 cases of eye infection. In all these cases a favorable therapeutic re- sponse was obtained, although intravenous administration not uncommonly gave immediate rigors and occasionally fever due to pyrogenic impurities in the penicillin.2 Florey saw the possibilities of the use of penicillin in war surgery, and in 1942 limited amounts of penicillin were sent to the Middle East forces in Cairo, where the results at first were encouraging, and later impressive. In April 1943, penicillin also became available at St. Hugh’s for the treatment of meningitis and the results were strik- ing.43 In late May 1943, the War Office sent Cairns and Florey to go together to North Africa and Sicily for 3 months to study potential field usage and penicillin dosage in the treatment of brain injuries, and set up clinical trials (Fig. 9).27,65 These trials were largely coordinated with the MNSUs and results sent back to Oxford.17,41 Penicillin was Fig. 9. Cairns (left) and Howard Florey (right) in North Africa conducting used locally (topically) in 23 penetrating brain wounds clinical trials with penicillin, 1943. From Fraenkel GJ: Hugh Cairns: The 3–12 days after injury at the time of postdebridement clo- First Nuffield Professor, Oxford, Oxford University Press, 1991. sure. Almost all wounds were infected with gram-positive organisms and 13 showed purulence. Three patients died, 2 of them from intracranial infection (< 10% infection mortality rate). The remainder made a satisfactory recov- to initiate a timely program of research on brain injury. ery. Bacteriological results showed that after 2 days of Several additional members were added in 1941.27 The treatment with penicillin, gram-positive cocci were usu- committee chairman was noted neurophysiolosist Ed- ally no longer found, whereas coliform organisms were gar D. Adrian (1889–1977), who in 1932 shared the No- invariably present. In several cases S. aureus was found bel Prize in Medicine or Physiology with Charles Sher- to be penicillin resistant, and there was no indication that rington. Other committee members included neurologists local installation of penicillin was toxic or caused damage George Riddoch, Charles P. Symonds, Macdonald Critch- in the low concentrations then available. ley (1900–1997), neuropathologist J. G. Greenfield (1884– Further experiences with penicillin in the treatment 1958), and neurological surgeons Geoffrey Jefferson, of brain abscess, paranasal sinus infection, and meningi- Hugh Cairns, and Norman Dott.27 Both Jefferson and Rid- tis in both military and civilian populations were highly doch had significant WWI experience with neurological successful.3,15,18,26,27 By the time of the Normandy invasion injuries. In 1941 the Brain Injuries Committee introduced in June of 1944, mass-produced supplies of penicillin had “A Glossary of Psychological Terms Commonly Used in become available, bolstered by American production of Cases of Head Injury”67 in an early but unsuccessful at- 43,60 penicillin. Florey was honored for his work on penicil- tempt to standardize the usage of descriptive terms related lin, knighted in 1944, and shared the Nobel Prize in Physi- to head injury. 63 ology or Medicine in 1945 with Fleming and Chain. The Brain Injuries Committee supported landmark research by Symonds-trained neurologists Derek Denny- Brain Injuries Committee and Experimental Brown (1901–1981) and W. Ritchie Russell (1903–1980) Acceleration-Induced Concussion on acceleration-induced concussion in cats and mon- In early 1940, the MRC established a Brain Injuries keys.34,36,37 These studies concluded that after sufficient Committee of prominent neurologists and neurosurgeons impact, the forces of acceleration or deceleration caused

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Unauthenticated | Downloaded 09/29/21 01:22 AM UTC J. L. Stone, V. Patel, and J. E. Bailes concussion (loss of consciousness) or subconcussion (a stunned or dazed condition), each without apparent acute macroscopic or microscopic lesions. However, concussion or subconcussion did not occur if the head was rigidly held when the blow was delivered.37,36 By using a brass pendulum with a broad leading end, the head (usually the occipitoparietal region) was struck and set into motion from the resting position. The forces of deceleration were largely eliminated by the head com- ing to rest against a soft wool cushion (Fig. 10).36 In all but 1 case, anesthetized animals or decerebrate prepara- tions were used. In these animals a certain degree of in- tensity of the blow (adequate stimulus) was required with dependence on the rate of increase in velocity (concussion threshold 0–28.4 feet/second in the monkey, 23 feet/sec- ond in the cat) before appreciable reversible changes were realized, such as bradycardia; blood pressure drop and then elevation; respiratory cessation, slowing, or irregular- ity; absent or depressed corneal and pinna reflexes; and unresponsiveness. A brief rise of intracranial pressure did occur when the head was struck, but was not believed high enough or of sufficient duration to account for functional Fig. 10. Denny-Brown and Russell’s (1941) experimental method of changes. producing concussion by the forces of acceleration. After impaction and Denny-Brown and Russell (1941) also found that blows several centimeters of motion, the primate head gradually comes to rest not sufficient to cause concussion still may affect the “va- against a soft cushion. From Greenblatt HS (ed): A History of Neuro- surgery in Its Scientific and Professional Contexts, Park Ridge, Illinois, go-glossopharyngeal system,” producing bradycardia, va- AANS, 1997. Reproduced with permission from the American Associa- somotor, and respiratory changes, along with incomplete tion of Neurological Surgeons. loss of consciousness (subconcussion). Transient abolish- ment of the corneal reflex and total loss of reaction (para- lytic signs of concussion) were noted in an unanesthetized monkey inadvertently impacted.35,37 Hylas Holbourn and the Physics of Brain Injury Pendulum blows above the concussion threshold were Hylas Holbourn (see above), as a Research Physicist in generally necessary to cause focal skull fractures, micro- Cairns’ Department of Surgery, also performed important scopic or macroscopic injury, cerebral contusions, and investigative work in the Oxford University Laboratory brain lacerations. This implied that upon the general back- of Physiology in the early 1940s.51 His objective was the ground of concussion more severe injuries sequentially understanding of blunt brain injury as determined by the developed. They found subpial petechial hemorrhages to physical properties of the skull and brain, utilizing the occur in the upper segments of the cervical spinal cord primary Newtonian laws of physics and motion. In these and brainstem with increasing forces, which they believed studies he acknowledged the help of Cairns, Dorothy Rus- were due to direct rupture of small vessels from localized sell, neurosurgeon George F. Rowbotham (1899–1975), stress and strain (distortion). and neurologist W. Ritchie Russell. Holbourn constructed The mode of injury in these experiments was consid- 2D gelatin models in the shape of a cross-section of the ered akin to that commonly termed “blunt head injury” human brain, which he subjected to sudden rotations or by clinicians, in that the striking object is so much heavier impacts, as might be caused by blows to the head. Utiliz- than the head that “within a few milliseconds…the latter ing polarized light, he detected the resulting shear strains takes up at least the full velocity of the striker on impact.”36 in the gelatin. He also performed theoretical calculations Denny-Brown and Russell believed that cushioning to study cerebral torque and induced shear strains under methods used to decrease the blow delay “the transfer of various forces (Fig. 11).7,53 velocity”—that is, “the rate of increase (or decrease) in Holbourn assumed that a substance with the physical velocity [acceleration or deceleration]…without dimin- properties of brain tissue (similar to highly incompressible ishing the amount of change.”37 In other words, although but easily deformed clay-like substances studied in engi- the “final velocity and momentum may be the same,” the neering) is more likely to be damaged by rotational “shear “slight delay introduced by a helmet” must greatly lessen strains” during the blow than the linear or translational ten- the damaging velocity change. A monkey fitted with an sile strains of compression and rarefaction (pulling apart). internally padded, small metal (tobacco can) helmet was Shear strain is the sliding of one part of tissue across anoth- subjected to typical concussive and fracture level blows, er, as in the wobbling of jelly or a “deck of cards when de- but neither was observed as in unprotected animals with formed from a neat rectangular pile into an oblique-angled identical blows. They conjectured that the use of a hel- pile.”51 He believed rotational forces were the most prob- met damped down the blow and protected the brain by able cause of both superficial laceration and general dam- decreasing the “fling of the brain” they envisioned with age to the brain structure, including nerve fibers, neurons “acceleration concussion.”37 and their dendrites, and vascular structures.51–54

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mental workers had in producing brain damage (or con- cussion) in small animals, which often develop permanent neurological signs or death after blows to the head.47,84 Holbourn was perhaps the first to provide factual knowl- edge of physical properties of the brain, surface mem- branes, and skull, which conformed to the known facts of brain injury and afforded a plain explanation by the laws of physics.51 He believed that if the precise details of how the head was struck were known, brain damage could be predict- ed with reasonable accuracy.51,53 Finally, as the hemispheres are not exact replicas but mirror images of each other, under certain conditions such as rotation in multiple planes, dam- age would be asymmetrical in the 2 hemispheres.51,84

Hugh Cairns After WWII Following the war Cairns returned to surgical practice, teaching, and research, and published on a wide range of neurosurgical topics. Cairns and Symonds were knighted Fig. 11. Gelatin-filled, 2D model of the human skull and brain depicting in 1946 for their military contributions. In that year Cairns the intensity of shear strains resulting from forward rotation caused by was also called to attend to the American general George an occipital blow. Darker regions indicate sites of maximum shear strain S. Patton, who subsequently died of a fracture/dislocation distortion. Reproduced from Blackwood W, Dodds TC, Sommerville JC: of the cervical spine. Much of the neurosurgical load at Atlas of Neuropathology, Edinburgh, E. & S. Livingston, ©1949. Oxford was taken by his associate Joe Pennybacker (1907– 1983), as Cairns traveled widely to lecture and assumed more administrative activities. Projects included distur- Focal skull distortion from impact certainly altered the bances of consciousness with diencephalic injury, the use shape of the brain, but Holbourn believed this was rarely of streptomycin in tuberculosis, treatment of meningitis, sufficient to cause serious widespread brain damage. He and studies of cingulate gyrus excision in the monkey. believed that elasticity and distortions (bending) of the Cairns subsequently performed cingulate gyrus excision in select psychiatric patients with mixed results. He also skull tend to cause merely local indentations and focal 72 contusional types of injuries and not the diffuse neuronal became interested in hemispherectomy. insult that gives rise to concussion. The uncommon, slow- Cairns smoked about 15 cigarettes per day and had er crushing types of injuries to the immobile skull were been in robust health until late December of 1951, when known to produce generalized distortions and fractures, he had an attack of abdominal pain and vomiting. He saw typically without loss of consciousness unless very exten- his friend, the Oxford internist Leslie Witts, who found an sive.61,68,75,78,87 abdominal mass on examination. He was operated on the Other than localized brain injuries due to skull impact next day, and a large lymphosarcoma was resected from and distortion with or without fracture, Holbourn further his right colon. Despite radiation therapy and reoperation considered the injurious physical forces or strains delivered he stoically died of disease progression about 6 months later at age 56. He had a very happy marriage, leaving a to the brain to be mainly those that arose by the change 43 in the velocity of the head caused by a blow. He divided widow and 4 children. W. R. Russell, who collaborated with Cairns during and these into velocity changes in a straight line, i.e., “linear 70 (or translational) acceleration,” and an infinite number of after the war years, stated, rotary axis velocity changes, i.e., “rotary or angular accel- He was amazingly easy to work with…Always appreciative eration.” The linear forces he felt produced small compres- of the work of his colleagues and provided every facility sion or rarefaction strains with minimal or no injurious ef- to further their researches. He formed the most important fect, while rotational acceleration forces he believed to be training-ground for neurosurgeons in this country, and there many times greater, and a significant cause of severe shear must be over a score of his trainees…who have formed simi- lar neurosurgical clinics in many parts of the world. He played strains such as in the temporofrontal and high convexity 51 the game of life with enthusiasm and an insistence on highest surface areas. Holbourn’s work showed that almost every possible standards which were an inspiration. His work was injury to the mobile head results in acceleration and de- his life, and holidays were short intervals during which vigor- celeration, plus rotational strains. The momentum must be ous physical activity strengthened him for the next session. sufficient and the rate of change sufficiently rapid to result He was always convinced that things could be improved, and in brain damage. Similarly, if the movement of the head his insistent pressure for changes naturally provoked opposi- is suddenly arrested by impact against a solid object, the tion at times; but his motives were so transparently honest and sincere that he usually gained much support. We had looked momentum or inertia of the brain mass causes continued forward to many more years of happy collaboration, but as movement. Thus, acceleration or deceleration of the head this cannot now be, we must maintain what he has built. is essentially similar. Holbourn also believed “that the shearing strains Lord W. R. Brain, a personal friend, wrote,70 set up during rotation are less the smaller the [animal’s] In Cairns’ success there were many ingredients…athletic brain,”51,66 and accounted for the difficulties that experi- physique, untiring capacity for work, manipulative skill and

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high intelligence…(but) Cairns added an imaginative vision, ested in the treatment of head injury as well as the bio- which served him alike in his everyday activities and in larger mechanics and neuropathology of concussion and diffuse affairs. He had an unusual insight…which contributed to his brain injury. Present goals include mitigation or elimina- minute attention to detail. His approach to larger questions was empirical, and guided by an intuition which led him suc- tion of injury, helmet design in relation to linear and rota- cessfully to explore possibilities in research and treatment… tional tolerance thresholds, the cumulative effects of even He lived with a humorous zest, which sprang from some very mild concussions, the possible role of accumulated perennial youthfulness. One could not picture Hugh Cairns as impacts without concussion (subconcussion), and the iden- an old man…. tification of injury biomarkers.4,9,45,66,71,86 Although much Three decades later, Leslie Witts stated, “There was work remains to be done, recent neuropsychological and especially advanced MRI studies are suggestive of such always an aura and magnetism about Cairns which was damage, as our Oxford pioneers predicted. very difficult to define, but which attracted people to him and made them work with him along the lines that he wanted….setting them to work quite happily, and they Acknowledgments would stay with him. Very few…had this manifest aura of We thank Dr. Sabina Strich for her assistance in the early greatness that surrounded Cairns.”43 Cairns was unique in preparation of this paper. Her important work on the neuropathol- his “personal confidence, integrity and a capacity to brush ogy of severe, diffuse head injury remains remarkably pertinent aside obstacles. His plans were far-sighted, yet simple and to the present time. We are particularly grateful to Sir Graham direct, and people found themselves co-operating because Teasdale, FRCP, FRCS, honored guest of the 2014 annual meeting 69 of the AANS, for his insightful comments and suggestions after of his unique resolution, charm and utter dependability.” reviewing earlier drafts of the paper. Ms. Sheila C. Gear kindly Similarly, in the manner of his mentor Harvey Cushing, and graciously supplied us with a photograph of her father, Hylas Cairns could not neglect detail in his projects, publica- Holbourn. Elizabeth Nussbaum, the youngest daughter of Hugh tions, or the treatment of patients. Consequently, his legacy Cairns, provided permission to use an early photograph of her has been lasting. father. Finally we thank Ruth Humphrey, medical librarian, for assistance with background research. Conclusions References Cairns, like his mentor Harvey Cushing, believed it im- 1. Aarabi B: History of the management of craniocerebral portant to definitively treat and debride head injuries as wounds, in Aarabi B, Kaufman HH, Dagi TF, et al (eds): soon as possible after injury. Early in WWII he formed Missile Wounds of the Head and Neck. Park Ridge, IL: well-equipped MNSUs near the front lines for this pur- American Association of Neurological Surgeons, 1999, pp pose. Cairns also mandated crash helmets for motorcycle 3–16 riders and enlisted the help of Oxford physicist A. H. S. 2. Abraham EP, Chain E, Fletcher CM, Florey HW, Gardner Holbourn to improve upon helmet design and to study the AD, Heatley NG, et al: Further observations on penicillin. biomechanics of brain injury. Cairns saw to it that care- Lancet 238:177–189, 1941 ful records of the injured were kept for later analysis and 3. Ascroft PB: Control of sepsis in a hospital in North Africa. Lancet 243:594–595, 1944 publication. His Oxford team established the first hospi- 4. Bailes JE, Petraglia AL, Omalu BI, Nauman E, Talavage T: tal and rehabilitation centers for brain-injured patients, Role of subconcussion in repetitive mild traumatic brain in- as well as the first spinal cord injury center. During this jury. J Neurosurg 119:1235–1245, 2013 period Cairns, in conjunction with colleague Howard Flo- 5. Bailey OT: Dorothy S. Russell. Surg Neurol 5:267–268, rey, facilitated the earliest clinical trials of penicillin usage 1976 in hospitalized civilians and WWII military injuries, and 6. Bailey OT: In memoriam: Dorothy S. Russell, Sc.D., M.A., demonstrated dramatic results despite the small amounts M.D., F.R.C.P. (1895–1983). J Neuropathol Exp Neurol 43:546–548, 1984 of the drug then available. 7. Blackwood W, Dodds TC, Sommerville JC: Atlas of Neuro- At the London Hospital and the Radcliffe Infirmary in pathology. Edinburgh: E. & S. Livingston, 1949 Oxford, Cairns trained or influenced a number of neuro- 8. Bliss M: Harvey Cushing: A Life in Surgery. New York: surgeons from Europe and abroad with particular interest Oxford University Press, 2005, p 416 in head injury including Douglas Northfield, Joseph Pen- 9. Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson nybacker, George F. Rowbotham, Reginald S. Hooper, J. DA, McLean AJ: Staining of amyloid precursor protein to M. Small, Murray Falconer, Walpole Lewin, John M. Pot- study axonal damage in mild head injury. Lancet 344:1055– 1056, 1994 ter, Bryan Jennett, Peter H. Schurr, and many more from 10. Botterell EH: Brain-injuries and complications, in Carling the WWII era who became academic leaders in neurosur- ER, Ross JP (eds): British Surgical Practice. London: But- gery. Cairns’ team at Oxford, in addition to Pennybacker terworth, 1948, pp 349–384 and Holbourn, included neuropathologists Dorothy Rus- 11. Bucy PC: George Riddoch. Surg Neurol 4:351, 1975 sell and, near the end of WWII, Sabina Strich (born 1925). 12. Cairns H: Crash helmets. 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17. Cairns H: Penicillin in head and spinal wounds. Br J Surg 44. Fulton JF: Harvey Cushing: A Biography. Springfield, IL: 32:199–207, 1944 Charles C. Thomas, 1946, pp 539–540 18. Cairns H: Penicillin in suppurative lesions of the brain and 45. Gennarelli TA: Future directions in brain injury research. meninges. Brain 70:251–261, 1947 Prog Neurol Surg 28:243–250, 2014 19. Cairns H: Rehabilitation after injuries to the central nervous 46. Gilkes CE: An account of the life and achievements of Miss system. Proc R Soc Med 35:295–308, 1942 Diana Beck, neurosurgeon (1902–1956). Neurosurgery 20. Cairns H, Holbourn H: Head injuries in motor-cyclists: with 62:738–742, 2008 special reference to crash helmets. BMJ 1:591–598, 1943 47. Gurdjian ES: Impact Head Injury: Mechanistic, Clinical 21. Cairns H, Oldfield RC, Pennybacker JB: Akinetic mutism and Preventive Correlations. Springfield: Charles C. Thom- with an epidermoid cyst of the 3rd ventricle. Brain 64:273– as, 1975 290, 1941 48. 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Chalif JI, Gillies MJ, Magdum SA, Aziz TZ, Pereira EA: Bull 3:147–149, 1945 Everything to gain: Sir Hugh Cairns’ treatment of central 54. Holbourn AHS: The mechanics of trauma with special refer- nervous system infection at Oxford and abroad. Neurosur- ence to herniation of cerebral tissue. J Neurosurg 1:190– gery 72:135–142, 2013 200, 1944 27. Committee of Privy Council for Medical Research: Medical 55. Horrax G: The era of neurosurgery as a surgical specialty, Research in War: Report of the Medical Research Coun- in Neurosurgery: An Historical Sketch. Springfield, IL: cil for the Years 1939–45. London: H. M. Stationary Office, Charles C. Thomas, 1952 1947 56. Horsley V: An address on gunshot wounds of the head. Lan- 28. Cooke AM: My First 75 Years of Medicine. London: Royal cet 185:359–362, 1915 College of Physicians of London, 1994 57. Horsley V: Discussion of gunshot wounds of the head. Trans 29. Curnow WJ: Bicycle helmets: a scientific evaluation, in de Med Soc Lond 38:112–128, 1915 Smet A (ed): Transportation Accident Analysis and Pre- 58. Hughes JT: Lawrence of Arabia and Hugh Cairns: crash hel- vention. Hauppauge, NY: Nova Science Publishers, 2008, pp mets for motorcyclists. J Med Biogr 9:236–240, 2001 141­–177 59. Jefferson G: Memories of Hugh Cairns. J Neurol Neurosurg 30. Cushing H: Concerning operations for the craniocerebral Psychiatry 22: 155–166, 1959 wound of modern warfare. Mil Surg 38:601–615, 1916 60. Lax E: The Mold in Dr. Florey’s Coat: The Story of the 31. Cushing H: A study of a series of wounds involving the brain Penicillin Miracle. New York: Henry Holt and Company, and its enveloping structures. Br J Surg 5:558–684, 1918 2004 32. Cybulski GR, Stone JL, Patel KJ: Sir Victor Horsley’s contri- 61. LeCount ER, Apfelbach CW: Pathologic anatomy of traumat- butions to the study and treatment of gunshot wounds of the ic fractures of cranial bones and concomitant brain injuries. head. Neurosurgery 63:808–812, 2008 JAMA 74:501–511, 1920 33. Debus AG: World’s Who’s Who in Science: A Biographi- 62. Liu BC, Ivers R, Norton R, Boufous S, Blows S, Lo SK: Hel- cal Dictionary of Notable Scientists from Antiquity to the mets for preventing injury in motorcycle riders. Cochrane Present. Chicago: Marquis-Who’s Who, 1968 Database Syst Rev (1):CD004333, 2008 34. Denny-Brown D: Brain trauma and concussion. Arch Neurol 63. Ludovici LJ: Fleming: Discover of Penicillin. Bloomington, 5:13–15, 1961 IN: Indiana University Press, 1952 35. Denny-Brown D: Cerebral concussion. Physiol Rev 25:296– 64. Maartens NF, Wills AD, Adams CB: Lawrence of Arabia, Sir 325, 1945 Hugh Cairns, and the origin of motorcycle helmets. Neuro- 36. Denny-Brown D, Russell WR: Experimental cerebral concus- surgery 50:176–180, 2002 sion. J Physiol 99:153, 1940 65. Macfarlane G: Howard Florey, the Making of a Great Sci- 37. Denny-Brown D, Russell WR: Experimental cerebral concus- entist. Oxford: Oxford University Press, 1979 sion. Brain 64:93–164, 1941 66. Margulies SS, Thibault LE: An analytical model of traumatic 38. Ecker AD: A bacteriologic study of penetrating wounds diffuse brain injury. J Biomech Eng 111:241–249, 1989 of the brain, from the surgical point of view. J Neurosurg 67. Medical Research Council: A Glossary of Psychological 3:1–6, 1946 Terms Commonly Used in Cases of Head Injury. MRC 39. Finger S, Stone JL: Landmarks of surgical neurology and the War Memorandum No. 4. London: H.M. Stationery Office, interplay of disciplines. Handb Clin Neurol 95:189–202, 2010 1941 40. Fleming A: On the antibacterial action of cultures of a peni- 68. Northfield DWC: Head injury, in: The Surgery of the Cen- cillium, with special reference to their use in the isolation of tral Nervous System: A Textbook for Postgraduate Stu- B. influenzæ. Br J Exp Pathol 10:226–236, 1929 dents. Oxford: Blackwell Scientific, 1973, pp 753–763, 839 41. Florey HW, Cairns H: A review of the Florey and Cairns 69. Nuffield Department of Surgical Sciences: Sir Hugh Cairns. report on the use of penicillin in war wounds. J Neurosurg (http://www.nds.ox.ac.uk/about-us/our-history/sir-hugh- 1:201–210, 1944 cairns) [Accessed November 17, 2015] 42. Florey HW, Chain E: The development of penicillin in medi- 70. Obituary: Hugh, William Bell Cairns. Lancet 2:202–203, cine. Hygeia 22:300–302, 1944 1952 43. Fraenkel GJ: Hugh Cairns: First Nuffield Professor of 71. Ommaya AK: Head injury mechanisms and the concept of Surgery, Oxford University. Oxford: Oxford University preventive management: a review and critical synthesis. J Press, 1991 Neurotrauma 12:527–546, 1995

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72. Pennybacker J: Sir Hugh William Bell Cairns. 1896–1952. 86. Teasdale G, Zitnay G: History of acute care and rehabilitation Surg Neurol 4:347–350, 1975 of head injury, in Zasler ND, Katz DI, Zafonte RD, Zafonte 73. Rowbotham GF: A historical survey of the treatment of inju- RD (eds): Brain Injury Medicine: Principles and Practice. ries to the head. Neurol Neurocir Psiquiatr 11:19–29, 1970 New York: Demos Medical Publishing, 2012, pp 13–25 74. Rowbotham GF: Mechanisms of injuries of the head, in 87. Vance BM: Fractures of the skull: Complications and causes Acute Injuries of the Head: Their Diagnosis, Treatment, of death: a review of 512 necropsies and of 61 cases studied Complications and Sequels. Edinburgh: E. & S. Living- clinically. Arch Surg 14:1023–1092, 1927 stone, 1964, pp 56–92 88. Walker NM: Hugh Cairns—neurosurgical innovator. J R 75. Russell WR: Cerebral involvement in head injury. Brain Army Med Corps 154:146–148, 2008 55:549–603, 1932 89. Williams ET: Cairns, Sir Hugh William Bell (1896–1952). 76. Russell WR: Disability caused by brain wounds; a review of Australian Dictionary of Biography. (http://adb.anu.edu. 1,166 cases. J Neurol Neurosurg Psychiatry 14:35–39, 1951 au/biography/cairns-sir-hugh-william-bell-5464) [Accessed 77. Russell WR, Espir MLE: Traumatic Aphasia: A Study of November 17, 2015] Aphasia in War Wounds of the Brain. Oxford, UK: Oxford University Press, 1961 78. Russell WR, Schiller F: Crushing injuries to the skull; clini- cal and experimental observations. J Neurol Neurosurg Disclosures Psychiatry 12:52–60, 1949 The authors report no conflict of interest concerning the materi- 79. Schorstein J: An atlas of head wounds illustrating standard als or methods used in this study or the findings specified in this operative technique. Br J Surg 55 (Suppl 1):27–61, 1947 paper. 80. Schurr PH: The Cairns memorial lecture: the Cairns tradi- tion. J Neurol Neurosurg Psychiatry 53:188–193, 1990 Author Contributions 81. Schurr PH: The evolution of field neurosurgery in the British Army. J R Soc Med 98:423–427, 2005 Conception and design: Stone. Acquisition of data: Stone, Patel. 82. Schurr PH: So That Was Life: A Biography of Sir Geof- Analysis and interpretation of data: Stone. Drafting the article: frey Jefferson: Master of the Neurosciences and Man of Stone. Critically revising the article: Patel. Reviewed submitted Letters. London: Royal Society of Medicine Press, 1997 version of manuscript: all authors. Approved the final version of 83. Strich SJ: Diffuse degeneration of the cerebral white matter the manuscript on behalf of all authors: Stone. Administrative/ in severe dementia following head injury. J Neurol Neuro- technical/material support: Patel, Bailes. surg Psychiatry 19:163–185, 1956 84. Strich SJ: Shearing of nerve fibres as a cause of brain dam- Correspondence age due to head injury: a pathological study of twenty cases. James L. Stone, Department of Neurosurgery, NorthShore Neu- Lancet 278:443–448, 1961 rological Institute, NorthShore University HealthSystem, 2650 85. Symonds CP, Ritchie Russell W: Accidental head injuries: Ridge Ave., 3rd Fl., Kellogg Bldg., Evanston, IL 60201. email: Prognosis in service patients. Lancet 241:7–10, 1943 [email protected].

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