ABBREVIATIONS: CT, computed tomography; EMI, Electric and Musical Industries
Pigmaei gigantum humeris impositi plusquam ipsi gigantes vident
[If I have seen further it is by standing on the shoulders of giants] - —Sir Isaac Newton (136)
In debates over the paternity of the discipline of neurosurgery, Sir Victor Horsley frequently vies with Harvey Cushing and notable others, including the Englishman Sir Rickman Godlee and the Scot Sir William MacEwen (19,87,89,95,120,137,167). Yet, it is a truth universally acknowledged, even west of the Atlantic, that stereotaxis (as he named it back then) was invented in London by the Englishman. Although Dittmar, in Germany, had used a guided probe to transect the rodent medulla in 1873 (33) and the Russian Zernov had described an encephalometer enabling brain surface localization in 1889 (181), neither technique enabled targeting with respect to a fixed three-dimensional Cartesian coordinate system.
Sir Victor Alexander Haden Horsley (1857– 1916) (Fig. 1A) studied medicine in University College London before training surgically there. He was the first neurophysiologist who was also a neurosurgeon, pioneering a Great British tradition of such hybrid scholars that were particularly prevalent in the stereotactic community (137). His uniquely deft approach to neurosurgery, derived from experiments on more than 100 primates, made a reputation such that when tenure became available at the National Hospital for the Paralyzed and Epileptic in Queen Square in 1886, “the Staff intended to have Horsley and nobody else” (140, p 27).
Like Sir Isaac Newton two centuries before him, Robert Henry Clarke (1850–1926) (Fig. 1B) read mathematics at Cambridge University. He then undertook medicine at St. George's Hospital in London before surgical training in Glasgow. He returned to London to work with Horsley in the late 1880s (30). Throughout the following decades, Horsley became intellectually consumed by the experimental challenges of cerebral localization of motor function, following the seminal work of Hughlings Jackson and others.
After Clarke developed aspiration pneumonia after aspirin inhalation in the early 1890s, he traveled to Egypt to convalesce. While there, legend has it that while gazing up at the stars and contemplating his place in them, he conceived an apparatus through which probing intracranial instruments could be inserted; the apparatus could be clamped to an animal's head by laterally placed skull pins, bars attached to plugs inserted into the external auditory meatus, and further bars resting upon the nose and orbital margins, which would fix the device to a Cartesian coordinate system. He presented his idea to Horsley on his return to England soon afterward (155). A decade later, in 1905, they commissioned James Swift, a machinist at Palmer & Company in London, to construct the first machine from brass, “Clarke's stereoscopic instrument employed for excitation and electrolysis,” comprising frame, carrier, and needle holder and costing £300 (Fig. 2) (159). Results from experimental use of the first instrument for targeting electrolytic lesions in the deep cerebellar nuclei of rhesus macaques were published in 1906 (26). In 1908, Horsley and Clarke described the apparatus and its use in greater depth, coining the term “stereotaxic” from the Greek words stereos (meaning “solid”) and taxis (meaning “arrangement”) (82). “By this means any cubic millimetre in the brain can easily be identified, recorded, and referred to” (26, p 1799).
Although Clarke suggested that the apparatus might be useful in humans, neither he nor Horsley pursued the idea, and they acrimoniously ceased collaboration shortly afterward. Nevertheless, the apparatus, including its proposed use in humans, was patented by Clarke in 1914, and he devoted much time to improving it. A rectilinear modification enabling needle inclination at different angles in an equatorial frame enabling 360 degrees of movement was described by 1920 (Fig. 2) (23). Three others used the original apparatus in London for experimental work: first, the visiting American surgeon Ernest Sachs, who studied the optic thalamus (154), and then the neurologist S.A. Kinnier Wilson, who studied the basal ganglia of 25 monkeys using the “Clarke-Horsley machine” (179).
Clarke's original instrument was last applied by F.J.F. Barrington, a London urologist who used it to study the effect of brain lesions upon feline micturition (12). Barrington died suddenly in 1956. Among the contents of his laboratory, “in true British fashion, was a biscuit tin” (120a, p 33). It contained a number of pieces first thought to be the original apparatus but later found to be only parts. After many inquiries, a technician in the Royal Veterinary College where Barrington had once worked produced a mahogany box containing the original model, and it was returned to University College London in 1970. It now resides in the Science Museum in London, having been promoted from closed storage to prominent display by the senior author (TZA) in 2000 (Fig. 3). Two further apparatus designs were made for Clarke by machinists Goodwin and Velacott, also of Palmer & Company in London, and exported to the United States for animal research soon after the First World War; one of them was sent to Johns Hopkins with the proviso that the Baltimore institution would publish Clarke's stereotactic atlas (39).
Translation of Horsley-Clarke stereotaxy to humans was considered not only by Clarke, but also by one of Horsley's students, the Canadian Aubrey Mussen. Mussen purchased one of the original Horsley-Clarke contraptions secondhand for £100 while working at the National Hospital in London from 1905 to 1906, returning to McGill University with it and subsequently publishing results from studies of the hypoglossal nuclei that Horsley traversed with his deep cerebellar lesions (130). Mussen designed further stereotactic instruments with Clarke, including a “cyclotome,” a probe used to make disk-shaped incisions along its axis, and a “spherotome,” used to cut spherical volumes, to which the leukotome of António Egas Moniz bears much resemblance (23).
Having returned to London in 1914, Mussen designed and had commissioned a modification of the Horsley-Clarke apparatus for use in humans, completed around 1918, again in brass, and most likely again manufactured by Palmer & Company (Fig. 4). In the frame, electrode holders slid along horizontal graduated bars or vertical corner posts, enabling orthogonal approaches to intracranial structures in anteroposterior and lateral directions. The apparatus required a human brain atlas, and Mussen envisaged its use to thermocoagulate tumors using “Galvanic current … through a 5 mm trephine in the skull and puncturing the dura without exposing the brain at all” (17, p 1245). In the 2 decades that followed, Mussen neither completed the human atlas nor convinced neurosurgical colleagues to take up use of his frame (90). He wrapped the unused British-made apparatus in newspaper dating from the 1940s and placed it in his attic (43).
Sachs, Wilson, and Barrington all had loan of the original Horsley-Clarke frame after Horsley's original experiments. Sachs and Mussen used Clarke's second and third frames, respectively, for animal experiments in North America throughout the 1920s, (131,156), as did others during the following decade. However, the key challenges in translating experimental animal stereotaxy into a clinical tool were twofold. First, there was great variability between human cranial landmarks and cerebral structures and, second, humans could not be killed like animals to enable confirmatory histology to determine accurate targeting and, thus, experimental validity.
Three decades after Horsley and Clarke's work, Spiegel and Wycis devised an apparatus for stereotactic neurosurgery in humans, publishing their achievement in 1947 (164). The North Americans established “stereotactic” as the preferred term, fusing the Greek stereos with the Latin word tactis, the pluperfect passive form of the verb tangere (meaning “to touch”). Their major advances were, first, to create a frame tailored to the individual cranium by means of a plaster cranial cap and, second, to align their frame not just to the cranium but also to brain landmarks such as the calcified pineal gland and the foramen of Monroe by means of intraoperative pneumoencephalography, hence their naming their device a “stereoencephalotome.”
Should you scratch deeply enough a man of pioneering spirit, the chances are that you will draw Scottish blood. - —Harvey Cushing (153, p 423)
British stereotactic surgery remained quiescent for half a century after Horsley, spanning the two World Wars, the discipline only reaching the clinic after word spread of Spiegel and Wycis' invention. At first, primary applications were for treating psychiatric disorders, and, later, clinical usage diffused to movement disorders in the 1950s and chronic pain in the 1960s.
Ahead of the rest, two Scottish pioneers and an English crusader emerged, each a clinical polymath but with a discrete focus to their research endeavors. In London, Geoffrey Knight developed stereotactic subcaudate tractotomy for psychiatric disorders, treating hundreds of patients, while the doyen of the London establishment, Sir Wylie McKissock, used a freehand approach. In Edinburgh, John Gillingham embraced stereotactic surgery for multiple clinical indications, designing his own stereotactic frame. In turn, he inspired his associate Ted Hitchcock, first at Edinburgh and then in Birmingham, to pioneer stereotactic approaches to the brainstem and high cervical spinal cord.
Francis John Gillingham (1916–) (Fig. 5) trained in St. Bartholomew's Hospital in London before entering the neurosurgical faculty at Edinburgh in 1950. Gillingham spent 12 years as first assistant to Norman McOmish Dott, one of the great triumvirate alongside Sir Hugh Cairns in Oxford and Sir Geoffrey Jefferson in Manchester, the apostles of Cushing who definitively established neurosurgery as a specialty in Great Britain (40,153,160). Like his mentor, Dott, Gillingham was a brilliant and pioneering aneurysm surgeon (48,171). He was also a passionate educator who introduced the concept of subspecialty fellowships to British neurosurgical training (49), but his greatest contribution was to stereotactic surgery.
Gillingham's introduction to stereotactic surgery came from the Parisian neurosurgeon Gerard Guiot. Guiot had recently visited Edinburgh to learn aneurysmal surgery from Dott and Gillingham, and they had become friends. Guiot's 1953 telegram to Gillingham read “I have something interesting to show you—come over,” (50, p 139). Gillingham obeyed, and 4 days were then spent performing freehand pallidotomies to treat parkinsonism by means of a subfrontal approach to the anterior perforated substance, with interruption of the ansa lenticularis and with the patient under local anesthesia, as described by Fenelon and Thiebaut after the seminal discoveries of Cooper (27,38,58).
Gillingham returned convinced, treating two patients in Edinburgh in 1955 and 1957, respectively, and reporting long-term improvements in tremor, rigidity, and quality of life. However, wishing to avoid the demanding subfrontal approach, if possible, he adapted Guiot's stereotactic method (57). In 1960, he published results from stereotactic “thermal electrocoagulation lesions of the globus pallidus, internal capsule and thalamus either separately or in combination” (50, p 1395) in a further 58 patients who underwent operations between 1957 and 1959 (53). In addition to the globus pallidus and internal capsule, he began targeting the ventrolateral thalamus for refractory tremor on the basis of work by Hassler (61). “Of these  patients 53, or 88%, had tremor and/or rigidity abolished or significantly reduced without complications” (53, p 1402).
Gillingham drew several conclusions from his early clinical results. On targeting, he wrote that “The best type of lesion … would seem to be the double one, made at the same time in the ventro-lateral nucleus of the thalamus and in the globus pallidus 16 mm from the mid-line, both lesions bordering on the internal capsule…. Bilateral lesions in the treatment of bilateral Parkinsonism, provided they are small and strategically placed, would seem to be eminently practicable … usually with an interval of three to six months between the two operations” (50, p 1401). On his modification of Guiot's stereotactic apparatus, he felt “that the merits of this method lie in the relatively short operative procedure and in its accuracy and simplicity. Its principles are based on the fact that the globus pallidus and thalamus bear a reasonably constant anatomic relationship to the anterior and posterior commissures, the intercommissural line, and the mid-sagittal plane of the head …” (50, p 1396) “The method used has evolved progressively, and is unique, in allowing the creation of lesions in the globus pallidus, internal capsule, or thalamus with one electrode track at different depths” (53, p 1402).
In their stereotactic apparatus design, Guiot and Gillingham favored operative principles to prioritize patient comfort, not restricting the patient's movements by clamping the head and attempting to obviate the need for multifarious calculations. Guiot planned a parasagittal approach in which he used intraoperative encephalography to delineate the midline and intercommissural point. Gillingham favored an occipitoparietal entry to avoid the striate arteries and horizontal patient positioning to reduce putative brain shift. Thus, the Guiot-Gillingham stereotactic apparatus was devised (Fig. 6). Radiopaque midline markers were used for the procedure, and a 1-mm steel ball was placed in each 5-mm lesion for subsequent charting. The ball was seen to fall through the necrotic lesion over a period of weeks, elegantly providing an estimate of its size. The frame's conception preceded Hassler's discovery of the thalamus as a target for tremor, and Gillingham attributed to serendipity that his posterior approach enabled multiple targets to be lesioned in a single pass (50).
Despite impressive clinical outcomes, Gillingham noted some inaccuracy to his lesions in the context of Brierley and Beck's demonstration that relationships between basal ganglia structures and commissural landmarks were highly variable (21,47). David Whitteridge, his neurophysiologist colleague at Edinburgh, had demonstrated to him in 1961 how microelectrode recordings could distinguish between gray and white matter and thus delineate the lateral geniculate nuclei in the cat (46). He immediately saw their utility for distinguishing functionally between deep brain structures, and, with his colleague Michael Gaze, he developed the technique for humans, as did Guiot (59). Fundamental physiological insights were gained in the quest to improve lesion accuracy and clinical efficacy, including spontaneous rhythmical discharge in the thalamus, which was found to be synchronous with tremor (Fig. 7) (42). With the use of microelectrode recordings, target localization could be done accurately with a margin of error of less than 1 mm.
Throughout the 1960s and 1970s, Gillingham evolved the Guiot-Gillingham apparatus. He added a phantom to allow an oblique track to more medial brain targets for epilepsy and psychiatric disorders, then an inferior extension to the posterior limb of the frame for targeting the cerebellum, brainstem, and cervical spine in chronic pain and dystonias (52). In 1977, he added a motor to automatically drive an electrode in at a slow and measured rate for microelectrode recording. Alongside the functional treatments, stereotactic surgery for deep hematomas and tumor biopsies was also performed (91). Ten-year follow-up in the post-levodopa era of a second 60-patient parkinsonian cohort of Gillingham's that underwent surgery between 1965 and 1967 showed a decline in efficacy for bradykinesia but consistent relief of tremor and rigidity (94). He remained engaged in academic neurosurgery well into his ninth decade, authoring insightful reviews of stereotactic surgery for Parkinson's disease (51).
As Gillingham became Dott's protégé, so Ted Hitchcock became Gillingham's. Edward Robert Hitchcock (1929–1993) studied medicine at Birmingham and trained in neurosurgery at Oxford before joining the Edinburgh staff at the then-recently-opened Western General Hospital in 1965. While there, he received unique exposure to Gillingham's stereotactic surgery, which attracted international visitors like Guiot and Housepian (85). In the late 1960s, Hitchcock's own interest was chronic pain and, in particular, developing his idea of percutaneous high spinal stereotactic commissural myelotomy. This procedure aimed to divide the decussating spinothalamic tracts but reduce the risks of respiratory paralysis conferred by open cordotomy through a targeted lesion, primarily aimed at chronic pain that was attributable to neoplasia. It required access below the plane of a versatile frame; thus, he invented his own target-centered arc system, which was attached to a hollow square aluminum base ring that was secured to the cranium by three-point fixation (Fig. 8). Vertical and horizontal bars determined probe length and laterality. The system was first used both for surgery and for microelectrode recording in the spinal cord by a percutaneous approach using portable x-rays (62,63,72). Hitchcock reported initial results of good or complete pain relief in 13 of 19 patients at follow-up periods ranging from 1 week to 4 years (66). A stereotactic pontine approach to spinothalamic tractotomy and to the trigeminal nucleus for anesthesia dolorosa was also applied (64,65,74,78,80), as were approaches to the thalamus and dentate nucleus to treat dystonia and, in particular, the spasticity of cerebral palsy (54). The rationale behind the stereotactic pontine spinothalamic approach was to provide good analgesia with minimal risks to respiration, micturition, and upward gaze (65). Hitchcock wrote of his apparatus in the early 1970s that “the design and construction make this one of the most accurate, adaptable and simplest of modern stereotactic instruments” (161, p 104).
Hitchcock became Professor of Neurosurgery at Birmingham in 1978, succeeding Brodie Hughes (1913–1989), who was also a stereotactic surgeon of some repute (86,119). Hitchcock put his stereotactic frame to many further clinical uses, including biopsy of supratentorial, infratentorial, and high spinal tumors and intraventricular masses (71,73,76), foreign body removal (70), real-time clipping of otherwise inoperable arteriovenous malformations (161), and image-guided craniotomies (68); in the 1980s, he also used it in the planning and treatment stages of radiosurgery (79). These many varied clinical indications in brain and spine earned him the nickname “Columbus of the brain” in the local clinical neuroscience community. At the Midland Hospital for Neurology and Neurosurgery, he used his stereotactic expertise to establish a program at first for adrenal medullary transplantation and, in the late 1980s, for fetal mesencephalic transplantation in Parkinson's disease, performing the procedure on 55 patients and gaining fundamental insights into its mechanisms (69,75,77,109).
Neurosurgery for psychiatric disorders in Great Britain mirrored treatment in the United States, its popularity following Freeman and Watts' simplification of Moniz's procedure in the 1940s (41,128). Its most assiduous British proponent was the London neurosurgeon, Sir Wylie McKissock (1906–1994), founder of the Neurosurgical Department at Atkinson Morley's Hospital in Wimbledon (150). The illustrious McKissock favored a freehand approach to the frontal lobe from above (96). He described the rostral leukotomy in 1951 as a rejoinder to Freeman and Watt's transorbital “ice-pick” leukotomy, which he considered to contravene “established aseptic surgical principles” (126,127, p 92). McKissock's immense practice, covering swathes of South England, and his reputation for extraordinary surgical speed inculcated a peripatetic service, as he visited other hospitals in his car with his surgical instrument set in the boot, drawing parallels with Freeman (13,35). It is suggested that McKissock alone may have performed one-quarter of the 10,365 procedures performed in the United Kingdom from 1942 to 1954, as reported by Tooth and Newton in 1961 (172).
Geoffrey Cureton Knight (1906–1994) of Hammersmith and Brook Hospitals in London and Woolwich saw, more readily than McKissock, the merits of stereotactic approaches over freehand techniques in reducing the morbidity and mortality of neurosurgery for psychiatric disorders, and, indeed, the two debated such issues in 1959 (100,127). After his freehand experience (106), Knight created the procedure of stereotactic subcaudate tractotomy in 1961, using a modified stereotactic device that his London colleague, the Scottish neurosurgeon Ian Reay McCaul (1916–1989), reported in 1959 (119,125). His first few hundred orbital undercuttings led him to conclude that lesions extending posteriorly under the caudate were most efficacious and that the last 2 cm were key (101,102). Knight used bony landmarks on lateral x-rays and, later, air encephalography to guide him. In addition, he used brachytherapy as an ablative tool, implanting radioactive yttrium (90Y) to create a flat lesion approximately 20 by 20 by 7 mm (Fig. 9) (103–105).
The treatment proved effective and endured 4 decades amid the demise of other psychosurgical treatments. Knight's group described the treatment of 1300 patients with “nonschizophrenic affective disorders,” 40 to 60% going on to live normal or near-normal lives with a reduction in suicide rates from 15% to 1% (20,81). Long-term outcomes were published by the psychiatrist Bridges and the London neurosurgeon John Bartlett, Knight's successor beginning in 1972. After the retirement of Knight, the unit was named the Geoffrey Knight Unit for Affective Disorders to emphasize Knight's appreciation of the fundamental importance of psychiatric evaluation, both in diagnosis and in full consideration of medical treatments before offering surgery. In 1996, the unit moved to the Maudsley Hospital, Professor Checkley succeeded Dr. Bridges as its psychiatrist, and 90Y production ceased. Bartlett adapted a Leksell frame arc (Elekta, Stockholm, Sweden) compatible with modern neuroimaging using concepts that underlay the McCaul device. Radiofrequency lesioning replaced radioisotope implantation (121,122).
It is a tribute to Knight that the Atkinson Morley Hospital's neurosurgeon Alan Richardson (1926–1998), profoundly influenced by McKissock—as all around the great man were—adapted a stereotactic approach for his psychiatric procedures (96). Together with his psychiatrist colleague Desmond Kelly, he combined Knight's subcaudate tractotomy with a cingulotomy to invent the procedure of limbic leukotomy in the early 1970s (Fig. 10) (92,93). It is interesting to note that cingulotomy for psychiatric disorders was first performed in 1948 in Oxford by Sir Hugh Cairns, albeit freehand, before the advent of stereotactic surgery (178). Both Knight's subcaudate tractotomy and Richardson's limbic leukotomy continue to be performed worldwide, including in the United Kingdom and North America, in carefully selected cases that are refractory to medical treatment (22,37,107).
Stereotactic neurosurgery was embraced by Dott's unit in Edinburgh and, after Cairns, Pennybacker appointed Sid Watkins to establish an Oxford service, but other regions also were keen to commence it. In Manchester, Jefferson's successor, Richard Johnson, appointed John Dutton to undertake a high volume of ablations for parkinsonism and other stereotactic procedures throughout the 1960s using a Leksell frame. Soon after, John Gleave (1925–2006) established a stereotactic service in Cambridge, also using a Leksell frame, treating parkinsonism with cryosurgery, and developing a side-cutting stereotactic biopsy cannula (123,177). Other British neurosurgeons, such as McCaul, made and modified stereotactic frames. Of particular note was the frame of Alfred Michael Bennett (1920–1996) and his use of a sphere inserted into a burr hole to aid targeting (15,18). Bennett's apparatus was popular locally, being used by Sid Watkins and later David Thomas in London, among others (36,144). Most designs were less radical and, therefore, perhaps less memorable than those of Gillingham and Hitchcock. However, far from echoing the designs of the English cartoonist William Heath Robinson, these innovative neurosurgeons taught and inspired experimental endeavors in the generations that followed. Several of the ventures amounted to little, but the ones that yielded fruit have changed the specialty forever, transforming many patients' lives in the process.
Of necessity to enable their targeting, Horsley and Clarke also produced the first stereotactic atlas, a monkey version appearing in their 1908 publication. Later publications were by Clarke, at first for the cat, in collaboration with the British ophthalmic surgeon E. Erskine Henderson in 1912, and later by Clarke alone for the rhesus macaque in 1920 (23–25). Both atlases comprised 2-mm-thick brain slices. The latter atlas showed sections of monkey brain at calibrated intervals with a scale giving slice thickness and height from the base of the apparatus. Sections were registered by a Cartesian coordinate system to the skull landmarks of the inferior orbital rim and both external auditory canals, to which the frame was fixed. Zero axes were the plane between these structures axially, the midsagittal plane, and the coronal plane between both external auditory meati orthogonal to both other planes.
There is no doubt that human brain atlases produced outside Great Britain, in particular by Spiegel and Wycis, Schaltenbrand and Bailey, and Talairach, transformed stereotactic functional neurosurgery. Schaltenbrand detailed anatomic nuclei with an emphasis on the thalamus and adjacent deep brain structures that is now indispensable to deep brain stimulation for movement disorders, and Talairach revealed the vasculature relevant to epilepsy surgery (157,163,166). Nevertheless, another “Columbus of the brain,” the British neurosurgeon Sid Watkins, made rigorous contributions.
Eric Sidney Watkins (1932–) was charged by Joe Pennybacker with the task of starting stereotactic neurosurgery at the Radcliffe Infirmary in Oxford in the 1950s. He was initially dissatisfied with the variability of basal ganglia structures with respect to the frequently uncalcified and, thus, radiolucent pineal gland using the Spiegel and Wycis atlases, but the Schaltenbrand and Talairach atlases appeared shortly after and were of aid to him. Initially, the globus pallidus and ansa lenticularis were targeted for parkinsonian rigidity, tremor, and dystonia, and then the lateral thalamus was targeted in the 1960s. An interest in creating his own atlas developed in the early 1960s from a desire to commence the therapy of thalamotomy for pain combined with concern about the adequacy of available atlases to accurately enable targeting based on anatomy alone in the absence of subjective or physiological guidance. Encouragement came from neurosurgical colleagues John Andrew and Valentine Logue, who were also keen to commence such treatment in London.
Another atlas that became available was that of Brierley and Beck, who sectioned 40 brains in 3- to 5-mm slices, relating them in a proportional hypothesis for thalamic nuclear determination to anterior and posterior thalamic limits and the midthalamic point and describing great individual variations (21). However, Watkins found the atlas to be limited clinically, because the use of simultaneous positive and air ventriculography using air in the ambient cisterns to outline the pulvinar nuclei and thus the thalamic limits was not consistently reproducible.
At the National Hospital for Nervous and Mental Diseases, with Sid Watkins nearby at the Royal London Hospital, John Andrew produced in 1969 a greatly enlarged atlas with drawings defining in detail deep brain nuclei, including the thalamus and its relations (5). The atlas was based upon 38 formalin-fixed brains. It measured the position of the thalamic centromedian nucleus with the use of 1-mm coronal slices with reference planes between the posteroinferior margin of the foramen of Monro and the posterior commissure and the midpoint between the ventricular surfaces of the anterior and posterior commissures. Its utility lies in the presentation of statistical data in a graphic form together with stereotactic coordinates superimposed on simple line drawings of the thalamus.
In 1978 at the London Hospital, Fari Afshar detailed brainstem and cerebellar nuclei, again under Sid Watkins' supervision (1). The impetus for the Afshar atlas came from an interest in attempting to ameliorate spasticity in cerebral palsy by ablation of the cerebellar dentate nucleus. Approximately 30 brains were prepared by the use of positive-contrast ventriculography with the skull and brain mounted in a stereotactic frame in order to accurately correlate structures with coordinates. Again, formalin fixation of 1-mm slices was performed. A modified Mulligan stain was used, and each section was magnified with drawings made by a camera lucida. Reference planes were the fourth ventricular floor and fastigium and the midsagittal plane. As before, variability profiles were quantified, and standard deviations were presented.
Both Watkins atlases are rich resources that are still used to help ratify localization and, indeed, the Afshar atlas continues to augment heated debates regarding the targeting of the novel functional neurosurgical treatment of deep brain stimulation of the pedunculopontine region for Parkinson's disease (124).
Watkins has commented on the major difficulties in measurement caused by distortion related to fixation and shrinkage, with past atlases suffering from approximately 10% shrinkage. To reduce shrinkage to 2 to 5%, he used Corsellis' technique—a 10-day formalin suspension after removing brain and skull en bloc minus the frontal and facial bones (28). To appease undertakers' disgust at the cosmetic consequences, each cadaver's scalp was replaced over a plaster of Paris prosthesis fixed to a broom handle on a nail inserted into the cervical canal. Nevertheless, cremation of the augmented cadavers remained suboptimal, precipitating a strike among undertakers serving the London Hospital by the time Afshar's posterior fossa atlas reached its completion (175).
The British Engineer
There must be a beginning of any great matter, but the continuing unto the end until it be thoroughly finished yields the true glory. - —Sir Francis Drake, [1540–1596; Drake to Walsingham, Cape Sagres, Portugal. May 17, 1587 (Letter)]
By the late 1970s, British stereotactic functional surgery was a decade on from its first successes, having declined with the advent of neuropsychopharmacology. Levodopa was introduced to relieve Parkinson's disease (29), and chlorpromazine and monoamine oxidase inhibitors were found to ameliorate schizophrenia and depression, respectively. Thus, case series showing good relief after lesional surgery for chronic pain paled against the background of new analgesics and peripheral neuromodulatory therapies. Stereotactic approaches to tumors had been established but were found challenging by many neurosurgeons who were not steeped in the subspecialty. Although Watkins lived life in the fast lane (176), becoming medical advisor to Fédération Internationale de l'Automobile Formula One racing (176), Hitchcock continued to innovate and, alongside Bartlett and Richardson, continued using psychiatric procedures for medically refractory depression, obsessive-compulsive disorders, and anxiety; however, the still-fallow field awaited advances in other domains. Enter the British engineer.
Sir Godfrey Newbold Hounsfield (1919–2004) (Fig. 11) joined Electric and Musical Industries (EMI) in Hayes, Middlesex, in 1951, having previously been a radio mechanic and then a radar mechanic in the Royal Air Force before obtaining a diploma from Faraday House Electrical Engineering College in London. At EMI, he worked first on radars and guided weapons and then on the first all-transistor computers. During a weekend ramble in 1967, he conceived what later became the first EMI scanner and the technique of computed tomography (CT), which he described humbly as “a realization that you could determine what was in a box by taking readings at all angles through it,” (176a, p 226).
By recording multiple pictures from a rotating photon source, a series of slices could be photographed, and a three-dimensional image could then be reconstructed from the slices. After initial successful experiments with a cylindrical phantom containing radiopaque objects in his Hayes laboratory using x-rays, Hounsfield forged a collaboration with James Ambrose (1923–2006), a radiologist at Atkinson Morley's Hospital, to translate the device's utility to humans. McKissock gave the endeavor his blessing (13). Hounsfield set to work on bullocks' heads obtained from a kosher slaughterhouse in East London to obviate the traumatic intracranial hemorrhage observed after conventional slaughter (147). Ambrose interpreted the early scans and suggested the use of sodium iothalamate contrast to highlight tumors (4). His early interpretations and predictions formed the basis of contemporary diagnostic neuroradiology (2,3). The scan of the first patient, in 1971, revealed a cyst in the brain (83). In 1979, Hounsfield was awarded the Nobel Prize for Physiology or Medicine together with Allan Cormack, the Cape Town physicist whose mathematical theories Hounsfield had realized (84).
The advent of CT reawakened the use of stereotactic surgery in Britain. Several neurosurgeons began to experiment with CT-compatible apparatus, both imported (usually Leksell) and that of Gillingham and Hitchcock (50,67). Magnetic resonance imaging followed shortly after, again with frames being modified as required. After a quiescent decade, the late 1980s augured a renaissance. Alongside the emerging limitations of drug therapies for movement disorders, which resurrected the clinical indications for functional neurosurgery, great advances came from increasing computer power, enabling the fusion of more spatially robust CT information with the greater soft tissue detail of magnetic resonance imaging and comparison with computed brain atlas images. In Britain, the current generation of senior stereotactic neurosurgeons was gaining their clinical training and conducting their first research, some in classical stereotactic methods abroad, some by subspecialty fellowships in Britain, thanks to Gillingham's enduring influence upon neurosurgical programs, and others by animal experiments true to the hybrid scientist-surgeon mold of Horsley. The stage was set for 2 decades of rapid advances in stereotactic neurosurgery.
Lars Leksell's genius showed not only in his frame design (111), in which he used the novel arc-quadrant principle, but also in his insight that focused radiation could be used as the tool. Many intersecting radiation beams focused toward a target would result in a high cumulative radiation dose, with radiation intensity declining rapidly with distance from the “isocenter.” Thus, a deep brain structure could be lesioned noninvasively by focused radiation. The technology could be applied to acoustic neuromas, arteriovenous malformations, and other discrete pathologies. Radiosurgery was born in 1951 (112).
Britain acquired one of the first gamma knives in 1985, as did Argentina just 3 years after the Falklands War. David Forster achieved incredible feats in leading the campaign to fund the device on the British National Health Service, building the infrastructure over 2 years to host it and ultimately purchasing the first custom-made unit in 1985. The National Center for Stereotactic Radiosurgery was refurbished in 1991, and its cobalt sources were renewed. Andras Kemeny, Matthias Radatz, and Jeremy Rowe are the neurosurgeons at the unit, receiving approximately one-half to two-thirds of all radiosurgery referrals from all over the United Kingdom. Approximately 500 cases a year are performed, a third of cases treated being arteriovenous malformations, with small- to medium-sized acoustic neuroma treatment having increased from 10% to one-third during the period 1994 to 2001. In addition, approximately 100 meningiomas and other cranial base or recurrent tumors are treated per year. Other indications for treatment include trigeminal neuralgia, pituitary tumors, and metastases, although the latter two indications are treated in smaller proportions than outside the United Kingdom, reflecting more conservative referral patterns (152). For similar reasons, few epilepsy and functional cases have been performed.
Several neurosurgical centers use linear accelerators to perform radiosurgery, each performing up to 40 cases per year. A gamma knife was also acquired in 1998 by the Cromwell Hospital in London, which is run privately by Christer Lindquist. The hospital's gamma knife has treated 1000 patients since installation and was recently upgraded.
Seminal European catalysts in the crucible of fin de siècle British stereotactic surgery were without doubt Benabid's application of thalamic deep brain stimulation to Parkinson's disease in 1987 and Laitinen's resurrection of Leksell's pallidotomy in 1992 (14,110). Functional neurosurgery was resurrected at the Radcliffe Infirmary in Oxford 4 decades after Watkins' departure under the headship of Mr. Chris Adams (7). At Oxford and Charing Cross Hospital in London, as we had already established with Alan Crossman in Manchester by the early 1990s, at the same time as DeLong's team across the Atlantic, that lesions made to the subthalamic nucleus in primates reversed the motor symptoms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism (10,11,16), we undertook stereotactic surgery of this target and others (8,9,116,141,142,146). At the same time, we continued nonhuman primate research into establishing the pedunculopontine nucleus as a potential target for gait freezing and postural instability (88,129,133,134). The subthalamic nucleus is now the target of choice for Parkinson's disease surgery, and initial clinical results of targeting the pedunculopontine nucleus show great promise (99,151,158,165).
Other translational research at the University of Oxford and Imperial College London included invasive deep brain electrophysiological insights into tremor and dystonia (115,117,174), the use of single-photon emission tomography (145), magnetoencephalography (108), and diffusion tensor imaging (6,132) to study deep brain stimulation, and research into deep brain stimulation for pain and blood pressure control and brainstem control of exercise (55,56). We have used deep brain stimulation to treat 70 patients with dystonia (180) and 60 patients with chronic pain (138), and we perform one-fifth of Britain's movement disorders surgery.
In Bristol, Professor Steven Gill has continued the Great British tradition of innovation, creating a stereotactic frame convenient for radiosurgery under Professor David Thomas' supervision in London (97,162) and performing several clinical firsts, including glial cell-derived neurotrophic factor infusion and pedunculopontine nucleus stimulation for patients with Parkinson's disease (45,118,143,149). With a current Hunterian Professor of the Royal College of Surgeons, Mr. Nik Patel, he continues to drive the field forward.
After the retirement last decade of Mr. John Miles in Liverpool, whose tremendous pain practice still left time for several innovations (31,32,139), Professor David Thomas also recently retired as the Gough-Cooper Professor of Neurosurgery at the National Hospital of Neurology and Neurosurgery at Queen Square. He had devoted 3 decades to the improvement of stereotactic surgical techniques with and without frames (34,98,168–170). Britain recently welcomed Professor Marwan Hariz at Queen Square as the first Edmond J. Safra Chair of Functional Neurosurgery, establishing a biennial international workshop that, like its host, is truly unique for its conviviality and candor (Fig. 12).
In 2008, a century on from Horsley's first experiments, almost all of the 34 hospitals conducting neurosurgery in Great Britain and Northern Ireland have consultants able to offer stereotactic surgery. One-third of these hospitals have subspecialty-trained stereotactic surgeons who offer functional procedures. Most of these surgeons are affiliated with universities and are conducting clinical or translational research, or both. From Cardiff to Cambridge to Liverpool to Newcastle and beyond, far from being the reserve of the eccentric scientist-surgeons looked upon with suspicion by the rest of the neurosurgical fraternity, stereotactic surgery has become an established clinical subspecialty and academic discipline in its own right.
The Past as Prologue
The empires of the future are the empires of the mind. - —Sir Winston Churchill (1943, speaking at Harvard)
The Society of British Neurological Surgeons, formed in 1929, has recently begun devoting specific sections to stereotactic and functional neurosurgery at its meetings. Its journal, the British Journal of Neurosurgery, is currently edited by Mr. Thelekat Varma, assisted by Mr. Paul Eldridge, both of whom are experts in stereotactic surgery. Another society with a focus on pain that welcomes stereotactic neurosurgeons, the Neuromodulation Society of the United Kingdom and Ireland, was founded in 2001. Such factors prove good indicators of the definitive establishment of the subspecialty in the United Kingdom.
The current and future status of neurosurgical training in Great Britain is uncertain, with a recent move to enable entry to a 7-year “run-through” residency in the specialty commencing with neurosciences exposure after 2 “foundation years” of internships, usually comprising less than a year of general surgical experience (60,135). A 1-year subspecialty year follows the 7-year residency; academic experience during training is potentially discouraged in all but a handful of trainees, who are appointed to “integrated academic training.” It is too early to predict whether such moves will promote or stifle the rich British tradition of surgeon-scientists. As has been observed, “one disappointing area at present is the reluctance of United Kingdom trainees to commit themselves to a career in academic neurosurgery, the majority preferring the seemingly more secure and definitely better remunerated posts in the National Health Service” (127a, p 158).
Further challenges to British neurosurgical training include a European Working Time Directive limiting doctors' hours to a 48-hour week beginning in 2009, which increases the tensions between training and service (114). Standards have remained constant during the past decade (113) and may be augmented by the structure of competence-based progression implemented by Professor Alan Crockard (60). However, we maintain that stereotactic neurosurgeons must, first and foremost, be excellent general neurosurgeons who are well versed in the anatomy of their procedures and able to deal with potential complications, and that they must be masters of the cantatas before they attempt the fugues. Seventy-seven years after Dott first clipped an aneurysm (171), few new British consultants have ever done so. Fewer still have performed functional procedures, but, perhaps they will do so within half the time since Dott, because they all may have stereotactic surgery in their repertoire by the end of their training.
Gildenberg has commented that there are several tenets of the field of stereotactic surgery (44): that there is a need to be innovative—a better way to do something may be more apparent to the most junior member of the team rather than the most senior; that stereotactic surgeons work as a community and not in isolation; that stereotactic surgery is, to a large extent, a basic science. Although not appealing to the neurosurgeon interested only in a better way to cut, it is exciting to one appreciating the associated basic science. Finally, there is awed appreciation for the insight and courage of the true pioneers in the field. The British school exemplifies such principles. It is hoped that its practitioners will continue to hold true to them in the current era of excitement and beyond.
The authors receive financial support for research from the UK Medical Research Council, Norman Collisson Foundation, Charles Wolfson Charitable Trust, and Oxford Comprehensive Biomedical Research Centre.
We thank Mr. Chris B.T. Adams, M.Chir. and John Bartlett for helpful comments; Professor David G.T. Thomas, Professor Anthony J. Strong, M.D., Professor John D. Pickard, M.Chir., Mr. Robert Macfarlane, M.D., and Mr. Colin Watts, Ph.D. for advice on historical sources; and Professor Marwan I. Hariz, Ph.D. for Figure 12.
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Pereira et al. have provided a detailed and interesting historical perspective on how stereotactic surgery advanced in Great Britain during the past century. Not only is the pertinent time line presented, but also the style provides the reader with some appreciation of the personalities and motivation of the major players. Not only is there agreement that the seeds of stereotactic concepts were planted in the laboratory of Sir Victor Horsley, but also he is also generally acknowledged to be the father of modern day functional neurosurgery. The examples of cross-fertilization of ideas freely shared and the handing of the torch to successive generations are still the patterns on which stereotactic and functional neurosurgery continue to advance.
Philip L. Gildenberg
This is an excellent historical review of stereotactic neurosurgery in the United Kingdom. I feel blessed that I was given the opportunity to live through some of the history recounted here, fortunate to have known many of the people referred to in this article, and honored to call some of them friends. And I have heard oral, admittedly anecdotal, versions of that history that render it all the more colorful. I will start with this story John Gillingham told me:
He and his good friend, Gerard Guiot, were inspired by the work of Fenelon who was placing a coagulation probe above the optic tract to lesion the ansa lenticularis in awake patients with Parkinson's disease and tremor. Fenelon had developed this technique after Russell Meyers had established that the ansa lenticularis was the key to the management of tremor. However, Meyers' transventricular approach to the ansa had a 10% mortality!
Gillingham and Guiot adopted Fenelon's technique but noted that, at the awake craniotomy, retraction of the frontal lobe to properly visualize the optic tract stretched the lenticulostriate arteries. They then discussed stereotactic lesioning of the ansa; Guiot proposed a coronal approach.
Neither Gillingham nor Guiot spoke the other's language very well. Gillingham communicated with Guiot by speaking English with a French accent; Guiot drew pictures when his English failed him. So, Guiot, a talented artist, drew anatomic cross sections of the anatomy on a blackboard for Gillingham in order to illustrate the surgical approach.
Gillingham admired the drawing and its anatomic sophistication and then said: “Gerard, my friend, you have forgotten something very important in this drawing: the blood vessels!” “Tu as raison!” Guiot answered, “You are right!”
It was at that moment that both saw the wisdom of approaching the ansa lenticularis target from the posterior. They developed the frame as described in this article. Guiot went on to target the medial pallidum, then ventrolateral (ventro-oralis posterior/ventral intermediate nucleus), and this approach was perfect for the neurophysiologic localization methods he developed with Albe Fessard. Gillingham used the approach to lesion the pallidum then the pallidothalamic fibers in the anterior portion of the internal capsule's posterior limb. The only substantive difference between Guiot's and Gillingham's frames was that Guiot's frame directed the lesioning probe at a fixed 6-degree medial trajectory (to account for the obliquity of the internal capsule); Gillingham's frame directed the probe parallel to the midline. Both understood, very early on, the importance of electrophysiological target corroboration.
As an aside: when Russell Meyers learned of the posterior approach to the ansa and pallidum he declared:” Leave it to the French and Brits to approach a problem from behind!”
Robert Henry Clarke's contribution was not necessarily the development of a stereotactic frame (as Pereira et al. note: probe positioning devices had been used for about 30 years before that). However, incorporating a navigational Cartesian coordinate system to the frame may have truly been an original concept. They suggested that Clarke received his inspiration from the start during a trip to Egypt. My understanding was that he found himself in Alexandria, the home of Claudius Ptolemy (100–178 AD), astronomy, cartography, and navigation. For centuries geographical location has been defined by a coordinate system: latitude and longitude; a concept easily abstracted to intracranial navigation.
I doubt that Horsley and Clark's falling out stemmed from a simple row over the adaptation of the stereotactic concept to humans (although I would like to believe this). Their acrimony started before this, possibly when Horsley was knighted. What started as friendship and collaboration, degenerated into jealousy, mistrust, and bickering. As Horsley's fame grew, Clarke became ever more resentful and sour with his own descent into obscurity.
Americans credit E.A. Spiegel with the first human subcortical stereotactic procedure in 1947. However, Spiegel was in communication with Clarke in the early 1920s and tried to have a stereotactic frame constructed by Palmer & Company. But the price of £300 was too steep for him at the time. Of particular interest is that each of Spiegel's versions of human stereotactic devices bore striking similarities to the devices pictured in Clark's 1920 monograph. Indeed, in 1912, Clarke submitted to the British Patent Office a patent application a device for a human stereotactic instrument.
Certainly British stereotactic neurosurgery has a rich history of innovation, and I could go on and on with stories; John Gillingham, Ted Hitchcock, David Thomas, and others were great raconteurs. But it is important for us to realize that the United Kingdom is an island only in geography. For the past 100 years British stereotactic surgeons and scientists have generously shared their techniques and innovations with the rest of the world (I recall John Gillingham, on a visit to Texas, bringing me one of his semimicroelectrodes so that I could copy it.) When the practice of stereotactic neurosurgery had virtually died in America with the advent of L-dopa, stereotactic techniques survived in England (as well as in France, Sweden, and Germany) and were passed on to young neurosurgeons from around the world.
Patrick J. Kelly
New York, New York
With his appointment in 1884 as Professor-Superintendent of the Brown Institution, a veterinary research facility, Victor Horsley embarked on a landmark series of experiments to delineate the functions of the cerebral hemispheres of primates. In collaboration with Charles Beevor and E.A. Schafer, he extended the pioneer work of David Ferrier using both ablations and electrical stimulations. The development of Robert Clarke's apparatus allowed Horsley to make lesions in the deep cerebellar nuclei without violating the overlying cerebellar cortex. He did not live to see adaptation of the frame to human subjects, nor could he have envisioned the enormous impact that this innovation would have on the field of neurological surgery in the century that followed. In this informative article, Pereira et al. mentioned Wylie McKissock's criticism of the ice-pick leucotomy procedure. This transorbital approach was adopted by Walter Freeman, a neuropsychiatrist. His early collaborator was James Watts, a neurosurgeon trained by Charles Frazier and Otfrid Foerster. Watts in essence agreed with McKissock and as a consequence severed his relationship with Freeman. He wrote the following in a second edition of their book: “It is Walter Freeman's opinion that transorbital lobotomy is a minor operation. It is my opinion that any procedure involving cutting of brain tissue is a major surgical operation, no matter how quickly or atraumatically one enters the intracranial cavity. Therefore, it follows logically, that only those who have been schooled in neurosurgical technics and can handle complications which may arise should perform the operation (1).”
Norman H. Horwitz
1. Freeman W, Watts JW: Psychosurgery.
Springfield, Charles C. Thomas, 1950, ed 2, pp 58–61.