epilepsy surgery: historical highlights 1909–2009

Epilepsy Surgery: Historical Highlights 1909–2009*William Feindel, *Richard Leblanc, and yAntonio Nogueira de Almeida

*Montreal Neurological Institute & Hospital, McGill University, Montreal, Quebec, Canada; and yDepartmento de

Neurologia do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil

SUMMARY

This review focuses on some historical highlights

of the surgery of epilepsy, beginning with the

reports of Horsley, Krause, and Cushing to which

appeared in 1909, the year that The Inter-

national League Against Epilepsy (ILAE) was

inaugurated. We then outline key contributions

from Europe and North America, and examine

particularly the evolution of our understanding of

temporal lobe seizures, which have now become

the most common form of epilepsy amenable to

surgical cure.

KEY WORDS: Epilepsy surgery, Cortical map-

ping, Temporal lobe resection, Amygdala, Hippo-

campus, Mesial temporal sclerosis.

A Landmark Year for Epilepsy

The year 1909 stands out as a landmark in the annalsof the history of epilepsy and as a year of hope for themillions afflicted with epileptic seizures. In the late sum-mer of that year, the inaugural meeting of the InternationalLeague Against Epilepsy (ILAE) took place in Budapest,amid the elegant ambiance of the XVI International Medi-cal Congress. The Congress was attended by a host of dis-tinguished physicians in neurology and the emergingspecialty of neurosurgery. Scientific talks were presentedby the pioneer neurosurgeons Sir William Macewen(1848–1924) of Glasgow and Professor Fedor Krause(1857–1937) of Berlin; by Professor Emil TheodorKocher (1841–1917) of Berne, who received the NobelPrize that same year (the first surgeon laureate) for hisstudies on the thyroid gland; and by Kocher’s former stu-dent, Dr. Harvey Cushing (1869–1939), from The JohnsHopkins Hospital, a rising star in the new field of pituitarysurgery, who reported at The Congress his first case ofpartial hypophysectomy for acromegaly, with a successfuloutcome (Cushing, 1909a, 1909b). Cushing’s travel diarygives a lively account of these crowded days, with colorfuldescriptions of the titled Hungarian hosts and eminent dig-nitaries assembled from many nations (Fulton, 1946).

A few months before the founding of the ILAE, on May6, Sir Victor Horsley (1857–1916) delivered the Linacre

Lecture at Cambridge University on The Function of theSo-called Motor Area of the Brain (Horsley, 1909). Hecited his report of 1886 on his first three cases of focalJacksonian epilepsy. He had operated upon these patients,urged and abetted by John Hughlings Jackson (1835–1911) and David Ferrier (1843–1928). Although Horsleydid not stimulate the cortex in any of these three opera-tions, he was informed by his brain-mapping experimentsusing electrical stimulation of the rolandic cortex on mon-keys. In his Linacre Lecture, he also reported an operationon a boy who had developed uncontrollable, violentmovements of his left arm. Horsley used a bipolar elec-trode to obtain responses from the cortex in front of thecentral fissure; these ranged from movements of the faceat the inferior portion, then of fingers, elbow and shoulder,as he went upward on the precentral cortex (Fig. 1). Afterexcision of the mapped ‘‘motor’’ cortex, the boy devel-oped not only paresis of the arm but also demonstrablesensory loss in his face and arm, an observation that ledHorsley to conclude that the pre-rolandic cortex servedboth as a motor and sensory center. This viewpoint was atodds with the contemporary findings of Sherrington andothers, and one still under debate today (Uematsu et al.,1992; Boling et al., 2002).

Also in 1909, Fedor Krause, Germany’s leading neuro-surgeon, published a five-page article on Die operativeBehandlung der Epilepsie in a Berlin medical journal. Hefollowed this with more extensive expositions of the surgi-cal treatment of epilepsy, during the course of which heproduced detailed maps of the human motor cortex(Krause, 1912; Krause & Schurn, 1932).

Before Harvey Cushing went to Budapest to attend theInternational Medical Congress, his seminal paper in

Address correspondence to William Feindel, Montreal NeurologicalInstitute and Hospital, 3801 University Street. Suite 109, Montreal,Quebec H3A 2B4, Canada. E-mail: [email protected]

Wiley Periodicals, Inc.ª 2009 International League Against Epilepsy

Epilepsia, 50(Suppl. 3):131–151, 2009doi: 10.1111/j.1528-1167.2009.02043.x

HISTORY OF EPILEPSY 1909–2009: THE ILAE CENTURY

131

Brain (Cushing, 1909a) reported for the first time sensoryresponses and the sensory auras of focal attacks, producedby electrical stimulation of the postcentral cortex, in twopatients awake under local anesthesia during the opera-tions.

Therefore, by the time the ILAE was founded in 1909,neurosurgeons were already breaking new ground in thesurgical therapy and scientific understanding of epilepsy.

History of Epilepsy Surgery

Many scholarly accounts of the history of epilepsy haveappeared, notably the two classical editions of The FallingSickness by Temkin (1945, 1971). Reviews of the devel-opment of epilepsy surgery over the last century may beconsulted in numerous multiauthor volumes, includingthose by Penfield and Erickson (1941), Penfield and Ras-mussen (1950), Walker (1951), Penfield and Jasper(1954), Engel (1993a, 1993b, 2005), L�ders (1991), Ap-uzzo (1991), Theodore (1992), Wyllie (1993), Wyler andHermann (1994), and Greenblatt et al. (1997). The mono-graph on The Temporal Lobe and Limbic System by Gloor(1997) details historical aspects of anatomy, pathology,and physiology in relation to the clinical treatment oftemporal lobe epilepsy. The recent Textbook of EpilepsySurgery edited by Hans L�ders (2008), with 105 chapters,running to an encyclopedic 1,600 pages, contributed byhundreds of international authors, provides an indispensi-ble reference for this vast subject.

Readers are referred to these sources for definitivediscussions on important historical aspects of epilepsysurgery, such as hemispherectomy, corpus callosotomy,corticectomy for dysplasia, and stereotaxic approaches,which we have excluded from this selective review.

The Pioneer Work of Horsley

The observation by Paul Broca (1824–1880) that focalcerebral lesions can produce speech deficits (Broca, 1876)and the demonstration by Gustav Fritsch (1838–1891) andEduard Hitzig (1838–1907) that selective sites on the cere-bral cortex can be excited by electrical stimulation to pro-duce specific motor responses (Hitzig, 1900), ledHughlings Jackson to consider focal epilepsy as a mani-festation of cortical irritation. He suggested treatment byremoval of the irritating focus (Jackson, 1870, 1873), andprevailed on his neurosurgical colleague, Victor Horsley,to perform craniotomy to effect a cure of epilepsy(Horsley, 1886). It was a challenge for a young doctor juststarting surgical practice (Taylor, 1987).

The patient, James B., a 22-year-old Scotsman, hadbeen run over by a cab in Edinburgh when he was a child.He sustained a depressed comminuted skull fracture withlocal brain damage, which at age 15 led to episodes of fitsand occasional attacks of life-threatening status epilepti-cus. The focal motor seizures affected, in order, the oppo-site leg, the upper arm, the wrists and fingers, and face.Before operation the patient was given a quarter grain ofmorphine and put under chloroform anesthesia. Horsleymentions that brain operations can be performed underlocal anesthesia, using a very strong solution of cocaine toblock the pain from the dura. He enlarged the bone defectresulting from the prior injury. The scarred dura, adherentto the scalp, was raised with the skin flap to expose ahighly vascular 3 · 2 cm scar, which he excised alongwith a border of cortex. The presence of a discrete corticalvascular scar and the arrest of the focal motor seizures fol-lowing its excision provided direct support for Jackson’sconcept of the etiology of focal epilepsy.

Figure 1.

Horsley’s sketches of

stimulation points on the motor

cortex at operation (left) and

from the excised specimen of

cortex (right). (Horsley; Linacre

Lecture, 1909).

Epilepsia ILAE

132

W. Feindel et al.


Horsley presented this and two similar operative casesof focal fits to the British Medical Association (Horsley,1886). After hearing Horsley’s lecture, Professor Jean-Martin Charcot (1825–1893) remarked, ‘‘Not only hadEnglish surgeons cut out tumors of brain, but here was acase in which it was probable that epilepsy had been curedby operative measures.’’ Hughlings Jackson stated, ‘‘therewas in every case of epileptiform seizures a persisting dis-charging lesion.’’ He believed the starting point of the fitwas a sign of the seat of the ‘‘discharging lesion,’’ andadvocated cutting out that lesion, whether it was producedby tumor or not. These auspicious beginnings of epilepsysurgery broadened into a wider field of brain surgery, anarea in which Horsley made frequent reports over the nextdecade (Horsley, 1906, 1909).

Horsley’s results from epilepsy surgery were initiallyfavorable; all patients survived. Localization of the site forsurgery was obvious in the two patients with skull defectsfrom head injuries. But the focal onset of the seizure in thethird case was correctly interpreted by Jackson to point tothe motor cortex as the site of the epileptogenic lesion,which proved to be a tuberculoma. Horsley and Charles E.Beevor (1854–1908) had observed thumb and fingerresponses from cortical stimulation in their experimentson monkeys: it was the comparison of these findings withthe patient’s focal seizure onset that led Jackson to advisean exploratory operation that disclosed the lesion.

Unfortunately not all neurosurgeons had the skill ofVictor Horsley, or the benefit of Hughlings Jackson’sadroit guidance. More significantly, identification of themotor strip, in the absence of cortical electrical stimula-tion, depended on external landmarks that were notori-ously unreliable, despite studies by Broca that related thecentral fissure to the coronal suture (Broca, 1876). Furtheradvances in the surgical treatment of focal epilepsyawaited the development of local anesthetic agents withbetter asepsis and hemostasis. But the close collaborationof the neurologist–epileptologist, the epilepsy surgeon,and the experimentalist, exemplified by Jackson, Horsley,Ferrier, and Beevor would serve as a model for the surgi-cal treatment of epilepsy (Jackson, 1888; Horsley, 1892,1906).

Sir William Osler (1849–1919), the Regius Professor ofMedicine at Oxford, had been well aware of Horsley’sreport on the first three patients that he had operated uponfor Jacksonian seizures. ‘‘One of the most interestingaspects of modern surgery’’ Osler stated, ‘‘relates to thetreatment of epilepsy, Jacksonian and idiopathic’’ (Osler,1889). Osler became an early protagonist for the role ofsurgery for epilepsy and, in addition, strongly influencedthe neurosurgical careers of Cushing and Penfield(Feindel, 2003a, 2003b). In discussing the early instanceof surgery for brain tumor performed by Rickman Godlee(1849–1925) in 1884 in London, William Osler referred tohis own observation of a postmortem examination at

Montreal in 1883, which had disclosed a small frontal gli-oma in the leg center. The patient, a physician’s child, hadintermittent Jacksonian seizures for 12 years and diedeventually in status epilepticus. This was ‘‘an instance,’’Osler wrote, ‘‘in which an operation would have been jus-tifiable and possibly have been the means of saving life’’(Osler, 1885). A vindication of Osler’s positive views forepilepsy surgery is provided by a similar case report of apatient with surgical cure of focal seizures caused by asmall glioma (Feindel, 2009).

In 1907, after hearing William Macewen and DonaldArmour (1869–1933) review their experiences in brainsurgery, Osler (by then the Regius Professor of Medicineat Oxford) commented, ‘‘a great deal of skepticism inregard to the value of operation in cases of cerebral tumorwas a result of the bicipital condition of neurology.’’ Osleradded that he ‘‘would prefer to see neurology a specialdepartment so that there would not be neurological physi-cians and surgeons, but medico-chirurgical neurologists,properly trained in the anatomical, physiological, clinicaland surgical aspects of the subject’’ (Osler, 1907). Thisdictum could well serve as a directive for neurosurgeonswho take up epilepsy surgery.

Early Surgery for Epilepsy

in The United States

The patients reported by Victor Horsley were the firstexamples where the sites of the operation and corticalablation were informed by experimental cortical stimula-tion results, combined with the astute interpretation of thefocal seizure pattern to indicate the appropriate area of theepileptic focus. But as Herman Flanigin (b. 1920) and hisassociates point out (Meador et al., 1988; Flanigin et al.,1991) in their thorough review of the surgical treatment ofepilepsy, it was Benjamin W. Dudley (1785–1870) inLexington, Kentucky, who in 1828 was among the first inNorth America to report the results of trephination forposttraumatic epilepsy. He operated on five patients; threebecame seizure-free and two improved.

Flanigin et al. (1991) also refer to Stephen Smith(1823–1922), who listed 27 cases of trephination for epi-lepsy in the United States (Smith, 1852). They note that in1861, John Shaw Billings (1838–1913) credited EphraimMcDowell (1771–1830) of St. Louis for operations onmore than 100 patients for epilepsy. In these pre-Listeriantimes, sepsis presented as the major complication.

Fedor Krause and Epilepsy

Surgery

During the 19th century some surgeons suggested thatepilepsy is the result of an increased production of cere-brospinal fluid and that seizures are produced by sudden

133

Epilepsy Surgery: Historical Highlights


changes in cerebral blood flow resulting in an acute rise inintracranial pressure. Measures were devised to equili-brate the assumed elevation in intracranial pressure in epi-leptics, most notably the valve operation devised byTheodor Kocher and adopted by Fedor Krause.

After a large craniectomy, the resected dura wasreplaced by a galeal flap that partially covered the brain,thereby creating a ‘‘valve’’ through which, it was consid-ered that cerebrospinal fluid could escape (Krause, 1909).This type of operation was abandoned when laboratoryinvestigation failed to demonstrate that intracranial hyper-tension or cerebral hyperemia produce seizures, and whenthe results of surgery, analyzed by Krause and others,proved unsatisfactory. Nonetheless, a possible causal rela-tionship between circulatory factors and epileptic seizureswould remain a persistent problem for investigation byKrause (1912), Foerster and Penfield (1930a, 1930b), andPenfield (1933, 1937).

From 1893 to 1912 Fedor Krause operated on 96patients for the treatment of epilepsy (Leblanc, 1990). Inmany of these operations he used faradic stimulation tomap the motor strip and identify epileptic areas, whichwere more excitable to the electrical current. Krausethereby confirmed the demonstration of Horsley (1909)that the central dogma of discrete functional localizationapplies to man. These observations led to the productionof detailed maps of the human motor strip and establishedcortical resection as a safe and effective treatment forfocal epilepsy (Krause, 1909, 1912).

Causes of Focal Epilepsy

Krause recognized that focal epilepsy could be causedby a variety of conditions affecting the brain and its cover-ings. With regard to the surgery of focal epilepsy he recog-nized three important conditions: tumors involving andirritating the motor area, infantile cerebral palsy, and thosecases with a cortical scar. He paid special attention to post-traumatic phenomena as a cause, astutely postulating thatepilepsy could produce changes beyond the primary spas-mic center. This led him to believe that ‘‘operative inter-vention will favorably influence the atrophic and scleroticmetamorphoses known to flourish in the cortices of somany epileptics’’ (Krause, 1912). Krause believed that aposttraumatic scar could be related to epileptogenicity:‘‘the leptomeninges may be found in a condition of cicatri-cial transformation and united with the cerebral cortex; or,scars may even be discovered within the substance of thelatter’’ (Krause, 1912).

According to Krause (1912), posttraumatic scars couldproduce ‘‘adhesions with the arachnoid, pia, and the sur-face of the brain’’ and these changes ‘‘could affect thecortical blood vessels present within bands of cicatricialtissue.’’ Krause shared with Adolf Kussmaul (1822–1902)the view that anemia of the cerebral cortex bears an impor-

tant relation to the origin of epileptic spasms, and sug-gested that focal epilepsy could be produced in a reflexmanner by the traction of scars on the encased blood ves-sels. Krause thus recognized all the elements that WilderPenfield (1891–1976) would later demonstrate within aposttraumatic meningeal cerebral cicatrix, such as pro-duced by him in experimental animals, or examined in thelaboratory of P�o Del R�o Hortega (1882–1945), oras observed in Otfrid Forester’s (1878–1941) resectedspecimens.

Krause also recognized that the primary spasmic center,the epileptogenic area, may be distant from the structurallesion. He considered the operative strategy in such cases,addressing ‘‘the question whether the morbid focus onlyshould be excised, or in conjunction with it the primaryspasming field as well’’ (Krause, 1912). He stressed that‘‘in a few instances I have adopted the latter plan withexcellent result.’’ This foreshadows the current concept ofan ‘‘epileptogenic border zone,’’ Penfield’s term for cortexso severely disrupted by tumor or scar that it cannot gener-ate electrical activity itself. Krause’s advice to resect boththe structural lesion and the epileptic area is now currentlyaccepted practice.

Cortical Stimulation

and Resection

Krause operated without the aid of contrast radiology orelectroencephalography (EEG). Because the basis oflocalization was the patient’s clinical presentation, mostof his cases were of Jacksonian epilepsy. The seizurefocus could not be precisely identified preoperatively;therefore, he stressed the necessity of a wide surgicalexposure. If no etiology such as a tumor was identified,then faradic stimulation could be employed to locate theprimary spasming point.

During stimulation of the brain Krause had three physi-cians observe the patient: one to inspect the face, a secondthe upper part of the trunk and upper extremities, and athird the lower part of the trunk and the lower extremities.Observations of muscular contractions of face and extrem-ities were dictated to the recorder, while the located cen-ters were noted on a sketch of the cerebral surface by theartist (Krause, 1912). With the aid of these extensive andlabor-intensive techniques of observation and drawings ofthe operative field to record results, Krause was able toproduce one of the first detailed human brain maps local-izing the motor strip to the precentral gyrus (Fig. 2). AsHorsley (1909) and others had shown clearly in primates,Krause concluded that:

The anterior central convolution contains all the [motor]foci located. Their arrangement on the cortical surface issuch that the centres for the lower extremity occupy theuppermost portion of the convolution near the sinus

134

W. Feindel et al.


longitudinalis . . . the lower extremity engages as its locusapproximately the upper one-fourth of the central convo-lution. About one-half of the middle portion responds tostimuli with contralateral muscular contractions of theupper extremity, from the shoulders down to the fingers.The lower one-third of the convolution discloses, uponirritation, the foci of the muscles of the face and those ofmastication. Here should also be found the centres of themuscles of the larynx, the platysma myoides, and the mus-cles of the tongue (Krause & Schurn, 1931).

Although cautioning surgeons that the primary spas-ming center of the right hand should be excised with greatdelicacy and that Broca’s cortical field for speech is evenmore sensitive than the center of the arm, Krause nonethe-less recognized that preoperative pareses and paralysesfrequently improved, in some cases of perinatal injuryproducing infantile hemiplegia, after resection of the epi-leptogenic area, even if this included the central region. Inthis way Krause anticipated Penfield’s concept of nocifer-ous epileptic cortex exercising a deleterious effect on theremainder of the brain, producing neurologic symptomsthat are improved with resection of the epileptogenic area.This predates the now common observation that hemi-spherectomy in previously paralyzed patients frequentlyimproves their motor function.

Krause was aware that advocacy of cortical resectionfor epilepsy ran counter to the opinion of his contempo-raries; he, therefore, paid special attention to the follow-up of his patients to determine the results of surgery.Taking advantage of the efficient Prussian postal sys-tem, his patients were requested to answer a specificquestionnaire that addressed their general condition, andspecific features such as the presence or absence of epi-leptic seizures and, if present, their nature and fre-quency; the state of their memory and intellectualfaculties; the nature and duration, if any, of their currentmedical treatment; and the patient’s own appreciation ofhis condition (better, worse, or the same) followingsurgery.

Of 55 patients undergoing cortical resection for Jackso-nian epilepsy, 29 answered his questionnaire. Four othersdied from status epilepticus within 6 days after surgery.Of the other 29, 11 were the same as before the operation,3 became aggravated, and 8 showed a marked improve-ment and amelioration of the symptoms and seizures.Very good results were obtained in three cases; four caseswere completely cured. Aware that epilepsy can have afluctuating course, Krause did not consider patients per-manently cured until they had been seizure-free for5 years.

Figure 2.

Map of responses from electrical stimulation of the motor cortex (Krause, 1912).

Epilepsia ILAE

135



Harvey Cushing and the

Sensory Cortex

In 1901, on a visit to Charles Sherrington’s (1857–1952) physiologic laboratory in Liverpool, Harvey Cush-ing helped to map the motor cortex in three primates,including that of a gorilla. His sketches, used by A. S. F.Leyton (1869–1921) and Sherrington in a report of 1917,showed motor responses from a narrow precentral strip,rather than the wider territory described by Horsley andhis associates. Later, at the Johns Hopkins Hospital, Cush-ing (Thomas & Cushing, 1908) reported on stimulation ofmotor cortex in more than 50 operations, confirming theresults of Krause.

The next year, Cushing described operations involvingfaradic stimulation of the postcentral gyrus on two patientswith focal sensorimotor attacks. The patients were keptawake under local anesthetic during the operations, whileCushing utilized a stimulating probe created after thedesign of Sherrington (Cushing, 1909a, 1909b). The sen-sory responses in the hand and arm were likened by thepatient to the feeling of weakness or ‘‘goneness’’ that initi-ated the attacks. Lower in the postcentral gyrus a sensationof warmth in the arm, rather vague and indescribable, wasreported (Fig. 3).

In the second patient, stimulation behind the postcentralvein was described as though someone had touched orstroked the finger or the back of the hand. Incision into theupper part of the postcentral gyrus in the first patientrevealed no lesion; no resection was made. In the secondcase, further exposure disclosed a lesion of the superior

part of the postcentral convolution, which was thought tobe irremovable. In these cases, Cushing thus demon-strated, for the first time, the sensory function of this post-central area. In a footnote to his Linacre Lecture, Horsley(1909) acknowledged Cushing’s discovery of the sensorynature of the postcentral area. These studies of corticallocalization evidently influenced Cushing’s later classifi-cation of a large series of meningiomas, by relating themto cortical regions with specific functions (Cushing &Eisenhardt, 1938).

Writing in August 1932 to Wilder Penfield in Montreal,Cushing noted, ‘‘. . . I, too, just thirty years ago was extir-pating a cortex [sic] for epilepsy. If I had had the industryand ability that you and Foerster combine, I might havegone ahead with it and made something out of it. But Isoon dropped it for things I thought I could do better’’(Preul & Feindel, 2001).

Otfrid Foerster and Cerebral

Localization

After World War I many soldiers with posttraumaticepilepsy made their way to Otfrid Foerster in Breslauto seek relief of their affliction. Like Krause, Foersterinitially had few technologic means to localize the seizurefocus. He depended almost entirely on the chance obser-vation of a seizure to exhibit a focal onset. To better studythe onset and spread of seizures Foerster was the first toreport, in 1924, on the use of hyperventilation to precipi-tate an epileptic attack. He was also one of the first toapply pneumoencephalography for the preoperative

Figure 3.

Stimulation points that evoked

motor and sensory responses

and reproduction of patient’s

aura (sensation of warmth)

from the postcentral gyrus

(Cushing, 1909a).

Epilepsia ILAE

136

W. Feindel et al.


lateralization and location of the focal lesion in patientswith posttraumatic epilepsy (Foerster, 1925).

Foerster, trained in neurology with J. Jules Dejerine(1849–1917) and Carl Wernicke (1848–1905), took up thescalpel commenting, it is said, that he could do no worsethan his previous surgical colleague since, after Foersterlocalized the cerebral lesion and indicated where to oper-ate, all the patients died.

Foerster operated on patients who were under localanesthesia and, perhaps reflecting his early interest inarchaeology, he opened the cranial vault by piecemealronguering. The epileptogenic area was identified byelectrical stimulation in an attempt to reproduce thepatient’s usual seizure, by traction on the epileptogenicscar, and by intraoperative hyperventilation. Theserudimentary techniques would eventually be enhancedin 1934, by the first use, with his coworker HansAltenburger (1902–1938), of intraoperative electrocorti-cography (ECoG) (Foerster & Altenburger, 1935).They also investigated the physiologic use of ECoG,in a manner akin to evoked potentials, by recordingthe effects of visual stimulation, of stimulation of theplantar response, or of mental activity.

Foerster benefited greatly from his collaboration withOskar Vogt (1870–1959) and C�cile Vogt (1875–1962),who were investigating cortical localization in animals.This resulted in a more detailed human cortical map(Foerster, 1934). On the 100th anniversary of the birth ofHughlings Jackson in 1936, Foerster summarized hisexperience with cortical stimulation in the IXth HughlingsJackson Lecture of the Royal Society of Medicine(Foerster, 1936).

Between the wars, the clinic of Foerster was briefly vis-ited by a host of North American neurosurgeons suchAlfred Adson (1887–1951) from the Mayo Clinic, MaxMinor Peet (1885–1949) and Edgar Kahn (1900–1945)from the University of Michigan, Leo Davidoff (1898–1975) from New York, Paul Bucy (1904–1993) from Chi-cago, and the physiologists John Fulton (1899–1960) andMargaret Kennard (1891–1976) from Yale.

In 1930 Foerster was invited by Cushing to be ‘‘Sur-geon-in-chief, pro tempore’’ at the Peter Bent BrighamHospital in Boston. Foerster’s contributions to neurosur-gery would also be recognized by the British Associationof Neurological Surgeons who visited his Breslau clinic in1937, where he discoursed on brain tumors, and waselected an emeritus member of the association.

Foerster benefited from the generosity of the Rockefel-ler Foundation to establish a neurologic institute, underhis directorship, in Breslau; he continued his work throughthe Weimar years, through the rise of National Socialism(Z�lch, 1969, 1973). His death, in 1941, in the darkestdays of the war, after the blitz and the Battle of Britain,would be noted by his British colleagues Hugh Cairns(1896–1952), Lord Russell Brain (1886–1961), and Sir

Geoffrey Jefferson (1886–1961), the latter commenting‘‘It will be a grief to many to learn that they will not meetOtfrid Foerster again’’ (Jefferson, 1941).

Foerster and Penfield

One of Foerster’s earliest and most productive collabo-rations had been with the young Wilder Penfield, who hadbecome interested in cerebral scars as a factor in focal epi-lepsy. This had taken Penfield in 1924 from New York tothe laboratory in Madrid of P�o Del R�o Hortega, withwhom he studied the reaction of neuroglia and microgliato brain wounds (Del R�o Hortega & Penfield, 1927;Penfield, 1927). So it was with a prepared mind that hevisited Foerster in 1928.

During a 6-month stay in Breslau, Penfield appliedSpanish gold and silver staining techniques to study thereaction of the neuroglia to cerebral trauma (Penfield,1977). From their detailed study of 12 operative cases,came the first systematic histologic examination oflesions in posttraumatic epilepsy, the first testablehypothesis of the etiology of this phenomenon, and a ther-apeutic rationale for exchanging an epileptogenic men-ingocerebral cicatrix for a clean surgical wound (Foerster& Penfield, 1930a, 1930b) (Fig. 4). Penfield’s examina-tion of these resected posttraumatic scars revealed fibrousbands projecting inward from the meningeal surface,penetrating the cortex, and extending deep into the whitematter in more or less parallel lines. These bands of bloodvessels and collagenous fibers intermingled with neuraland glial filaments; the three components intertwined like‘‘strands in a rope.’’

Penfield (1933) noted:

An outstanding feature of all these scars is the rich plexusof newly-formed vessels in and about the cicatrix. Thisvascular plexus anastomoses very freely with the largevessels which enter the scar from without. It also anasto-moses freely with intracerebral vessels in as much as thesurface of the dura continues to bleed after it is completelyexposed and cut free from surrounding dura . . .

Foerster had observed that epileptic seizures can be ini-tiated by electric stimulation around the meningocerebralcicatrix, as well by gentle traction on the cicatrix itself. Heand Penfield proposed that the resultant traction on theencased blood vessels might set up a ‘‘vaso-motor reflexsecondary to this traction,’’ which could be ‘‘responsiblefor the initiation of the convulsive seizures’’ (Foerster &Penfield, 1930a, 1930b).

Penfield and the Montreal

School

After his return to Montreal in 1928, Penfield furtherinvestigated this vascular hypothesis in the first series of

137



epileptic patients that he operated on, thus for the first timecharacterizing the vascular physiology of the epilepticbrain (Penfield, 1933, 1937). He observed that the mostfrequent sequela of an epileptic seizure is ‘‘the appearanceof focal areas of cortical anaemia,’’ which he consideredmight be responsible for postictal paralysis.

In other operations, Penfield observed vasoconstrictionof pial arteries that was sufficiently severe to interruptblood flow. Less frequently he observed dilation of thevascular bed characterized by bright red arterial bloodshunting into veins (Penfield, 1937). However, furtherobservation of epileptic patients at the time of surgery andjudicious use of newly available technology in the form ofthe ‘‘Gibbs blood flow thermocouple, the Matthews elec-trocardiograph, operative photography and runningdescriptive dictation’’ would lead him to abandon this con-cept of reflex vasoconstriction as the cause of posttraumat-ic epilepsy (Penfield, 1937). Nonetheless the investigationof this hypothesis by his students Everett Lyle Gage(1901–1972) (1931), Jerzy Chorobski (1902–1986)(Chorobski & Penfield, 1932), and Francis McNaughton(1906–1986) (1937) led to the demonstrations of theinnervation of meningeal and cerebral blood vessels andproduced the first study of cerebral vasospasm, by FrancisEchlin (1906–1988) (1939).

Wilder Penfield’s

Early Career

Wilder Penfield had been introduced to the nervous sys-tem through his studies with Charles Sherrington atOxford in 1915–1916 and again in 1920–1921. Explaininghow he was led into neurosurgery, Penfield later wrote ‘‘Itwas the inspiration of Sherrington. He was, so it seemed tome from the first, a surgical physiologist, and I hoped thento become a physiological surgeon’’ (Penfield, 1977).

From his work at Oxford, Penfield became familiar withthe observations on cortical localization by electrical stim-ulation in animals by Ferrier (1876) and in primates byLeyton and Sherrington (1917) (Feindel, 2007). Penfieldcentered his main career on the science and surgery of epi-lepsy (Penfield, 1930, 1967; Penfield & Erickson, 1941;Penfield & Jasper, 1954; Lewis, 1981). His experiencewith Foerster came at a critical period in Penfield’s career.While in Germany, freed from his busy surgical practicein New York, Penfield also took on the substantial task oforganizing an authoritative compendium by internationalauthors that appeared in three volumes as the Cytologyand Cellular Pathology of the Nervous System (Penfield,1932), an enduring classic reprinted in 1965.

Penfield became familiar with Foerster’s use of localanesthesia and electrical stimulation to map motor andsensory areas of the human cortex exposed at operation, sothat these could be protected during surgical excision ofepileptogenic brain (Foerster & Penfield, 1930a, 1930b).But Penfield would go beyond Foerster by mapping otherareas of cortex that subserve speech, hearing, vision, and,perhaps most crucial of all, memory function. He recordedthese observations on cortical localization in a long seriesof publications with many associates (Penfield, 1975;Eccles & Feindel, 1978 [includes bibliography ofPenfield’s writings]; Feindel, 1977).

Recurrent analyses were also reported on the follow-upresults of surgical excision in controlling seizures. In 1937,Penfield and Edwin Boldrey (1906–1988) analyzed resultsfrom 163 craniotomies in which electrical stimulation ofthe exposed cerebral cortex in humans was carried outunder local anesthesia (Penfield & Boldrey, 1937). Themotor and sensory maps thus obtained provided no evi-dence for area 6a beta, the tertiary motor area, as describedin the monkey by the Vogts, or for the existence of various‘‘extrapyramidal motor areas’’ reported by Foerster.

Figure 4.

Operative diagram of a case

from a series of 12 patients

treated surgically for focal

seizures (Foerster & Penfield,

1930a).

Epilepsia ILAE

138

W. Feindel et al.


These cortical maps, like those of Horsley, Krause, andFoerster, gave the topographic localization for differentparts of the body. The Montreal results were synthesizedfor visual purposes into a ‘‘homunculus,’’ which cartoonedthe relative size and order of the cortical representation(Penfield & Boldrey, 1937). They found an overlap in thefunction of the so-called sensory and motor cortex so thatsome sensory responses were obtained from the precentralor ‘‘motor’’ gyrus whereas, conversely, a number of motorresponses were obtained from the ‘‘sensory’’ postcentralgyrus. In addition, they noted a large overlap of the corti-cal areas from which stimulation evoked responses relat-ing to different parts of the body, an important finding inconsidering the mechanisms of ‘‘plasticity’’ of the motorcortex in recovery from focal lesions (Fig. 5).

Penfield’s early operations for epilepsy were based pri-marily on an intense study of the clinical seizure patternand by cortical mapping and stimulation at operation toevoke the patient’s aura (Penfield, 1930). The focal lesion,often a meningocerebral scar from trauma or infection,could also be epileptogenic cortex bordering a brain tumoror angioma (Penfield & Erickson, 1941), as first surmisedby Krause (1912).

Penfield’s First Temporal

Lobectomy

Shortly after they arrived in Montreal, in November1928, Penfield and his surgical partner, William Cone(1897–1959), performed their first operation utilizing theFoerster method. The patient, a young man previouslytreated for a subdural hematoma and contusion, had asmany as 20 seizures each day. Three operations eventuallyled to improvement (Feindel, 1991). At the third opera-tion, the thin scarred cortex of the temporal lobe waswidely resected (Fig. 6). Afterward the patient exhibiteda greatly reduced number of seizures, which were stillfurther decreased to four in the 13 years after he began totake Dilantin.

Penfield referred to this operation as his first temporallobectomy (Feindel, 1993). Stimulation in the midfrontalcortex caused the patient’s eyes to blink; Penfield noted alocal blanching of the pial arteries at the same site. Thiswas the earliest of many observations, including arterialconstriction and arterialized blood in veins draining epi-leptic zones, which supported the concept of a cerebralvascular mechanism for epilepsy (Foerster & Penfield,

Figure 5.

Overlap of cortical zones relating to movement and sensation evoked from the rolandic region (Penfield & Boldrey,

1937).

Epilepsia ILAE

139



1930a, 1930b). Focal hyperemia, especially after focal sei-zures or in relation to vascular shunts in tumors and cysts(Penfield, 1933, 1937, 1971), eventually led to the con-cept of ‘‘red cerebral veins,’’ a feature that still demandsmore exact physiologic explanation (Feindel & Perot,1965).

The Montreal Neurological

Institute

The Montreal Neurological Institute (MNI) opened in1934, fulfilling Penfield’s dream to combine in the sameedifice a hospital for patients with neurologic disorders, aresearch center for the scientific study of the nervous sys-tem, and a teaching Department of Neurology and Neuro-surgery for McGill University. By this time Penfield hadfully prepared himself by scientific studies and by devel-oping his eclectic surgical technique derived from PercySargent (1873–1933), Harvey Cushing, Walter Dandy

(1886–1946), Charles Frazier (1870–1936), and OtfridFoerster (Feindel, 1977; Penfield, 1977; Preul & Feindel,1991). The institute provided a fertile setting for the workon epilepsy, where surgical physiology, cellular pathol-ogy, radiology, and, later, neuropsychology, EEG andneurochemistry were all applied to advance the under-standing of the pathophysiologic processes underlyingfocal seizures.

From the beginning, Penfield and his team attracteddiverse and international groups of associates. Manyreturned to lead university departments of neurosurgeryin the United States and abroad, where they set upunits for the scientific study and surgical treatment ofepilepsy (Feindel, 1977, 1993; Flanigin et al., 1991). Inthe early operative series for epilepsy, surgical expo-sure of a region suspected of causing focal seizuressometimes revealed no visible lesion, so that no surgi-cal removal could be made. However, negative explora-tions became less frequent with the advent of EEG

Figure 6.

Penfield’s drawing of operation

in 1928 to show vascular

features and double excisions,

including his first temporal

lobectomy for posttraumatic

seizures (Wilder Penfield

Archive).

Epilepsia ILAE

140

W. Feindel et al.


introduced in 1937 at the Institute by Herbert Jasper(1906–1999).

Jasper Joins Penfield

at the MNI

In 1937, a chance encounter at Brown University ledPenfield to bring Herbert Jasper and EEG to Montreal.Although Penfield was initially skeptical about this newtechnology, his opinion changed when Jasper applied thetechnique to investigate the MNI patients on whom sur-gery was being considered. EEG had been developed byHans Berger (1873–1941) in 1929, (Gloor, 1969) but wasonly acknowledged by the international community afterAdrain and Matthews (1934) confirmed Berger’s originalresults (Adrian, 1934). Jasper took a doctorate in psychol-ogy then changed to research in neurophysiology. A pio-neer in the use of EEG, he later became an outstandingleader in the neurosciences (Feindel, 1999). Jasper andCarmichael (1935) published the first report in Americaon research application of EEG, in the same year that theBoston group led by Frederic Gibbs (1903–1992) hadnoted its clinical value in epilepsy (Gibbs et al., 1935).

Surgery for Temporal

Lobe Seizures

The surgical treatment of epilepsy attracted more atten-tion in the decade from 1945 to 1955, when seizures aris-ing from the temporal lobe became a subject of increasinginterest. Until that time, surgery had been directed mainlyto the convexity of the cerebral hemispheres and mostoften for removal of traumatic scars or tumors.

In 1936, Frederic Gibbs and William Lennox (1884–1960) of the Boston school of EEG, classified psychomo-tor seizures as a separate entity from petit mal and grandmal for the first time. They considered epilepsy to be aparoxysmal ‘‘disordered functioning of the rate-regulatingmechanism of the brain’’ (Gibbs et al., 1936). Accord-ingly, the presence of a structural lesion was more oftenthe exception than the rule, and the various types ofseizures would be considered only as variations on the pat-tern of dysrhythmia (Gibbs et al., 1938). Their approachpromoted EEG into a strategic position for diagnosis ofepilepsy. Nevertheless, the authors failed to localize theorigin of the psychomotor seizure because the referenceelectrode linked to the ears distorted temporal activity(Gibbs et al., 1935). Using this method, most of their‘‘localized dysrhythmias’’ were found in the frontal andoccipital regions (Gibbs et al., 1936).

By contrast, Jasper had long suspected that the mesialtemporal structures played a role in the origin of seizures,although available technology could give only an ‘‘indica-tion, not the localization, of deep lying disturbances.’’ In

his words, although ‘‘localized potentials were obtainedfrom surface aspects of the frontal, precentral, parietal,and occipital areas . . . discharges originating subcortical-ly or from underlying distant cortical areas, e.g., the cornuammonis, might spread to the surface and give apparentlocalizing signs in these areas’’ (Jasper & Hawke, 1938).

During his early days at the MNI, Jasper commutedweekly from Brown University, Providence, Rhode Islandto Montreal in order to carry out EEG investigation onpatients on whom Penfield would then operate (Jasper,1958). Penfield’s recognition of the importance of neuro-physiology in the evaluation of epileptic patients led himto provide in 1939, through support from private citizensand the Rockefeller Foundation, a new EEG laboratory atthe institute. It was dedicated to the selection of patientsfor surgery and to provide the techniques for recordingfrom the cortex during operation (Jasper, 1941, 1991).The EEG work enhanced the neurophysiologic researchthat flourished under Herbert Jasper’s vigorous leadershipto add greatly to the recognition of the institute as an inter-national center for training in the neurosciences.

From the 1940s onward, the close integration betweenneurophysiology and neurosurgery, a mirror of the friend-ship between Penfield and Jasper, made the MNI a leadingworld center for the surgical treatment of epilepsy (Fig. 7).Other centers, such as the epilepsy surgery program at theUniversity of Illinois began later, in 1945, when FredericGibbs moved to Chicago to work with Percival Bailey(1892–1973) (Hermann & Stone, 1989).

In 1941, Jasper and John Kershman (1906–1951) pro-posed a classification for epilepsy based on forms and

Figure 7.

Wilder Penfield (sitting) and Herbert Jasper, 1954

(Wilder Penfield Archive).

Epilepsia ILAE

141



patterns of EEG waves, localization of the activity, andclinical characteristics of the fits (Jasper & Kershman,1941). The classification emphasized localization of thefocus and was particularly applicable for surgeons lookingfor cerebral lesions (Penfield & Erickson, 1941; Lennox,1949). Regarding psychomotor epilepsy, Jasper andKershman (1941) wrote:

It seems clear from the nature of these disturbances thatthe temporal lobe and subjacent structures, probably in thearchipallium, are the regions primarily involved. This is inaccord with the electrographic localization, which so fre-quently seems to be deep to the temporal lobes (e.g., thehippocampus) near the midline or to involve an area firstin one temporal lobe and then in the other.

Although by 1941 Jasper was already aware that mesialtemporal structures might play a role in the origin of psy-chomotor epilepsy, one of the major obstacles for remov-ing these structures was the lack of knowledge about theirfunction. For example, it was believed that the hippocam-pus was an area devoted to olfaction. But in his criticalanalysis, Alf Brodal (1910–1988) (1947) exonerated thehippocampus from any connection with the olfactory sys-tem; it then became a well known (and captivating) ana-tomic structure looking for a function. Furthermore,Heinrich Kl�ver (1897–1979) and Paul Bucy (1904–1992) (Kl�ver & Bucy, 1939) published results of experi-ments on monkeys in which they resected both temporallobes. The resultant syndrome, named after the authors,was characterized by psychic blindness, compulsion, lossof emotional reaction, and increase in sexual activity, asyndrome that obviously would be disastrous if producedby surgical resection in patients. The findings in monkeysled Bailey to restrict his excisions in patients to the antero-lateral cortex of the temporal lobe (Bailey & Gibbs, 1951).

Penfield considered EEG and ECoG useful if they coulddisclose pathologic areas in the brain. Focal pathology,such as uncommon calcified hemangiomas in the temporallobe, might show paroxysmal discharges on scalp EEGand abnormal waves localized to the area of the temporallesion at operation (Penfield & Ward, 1948). But if a visi-ble lesion was not found at the place indicated by therecording of epileptic activity, Penfield would usuallydecline to perform a resection. Because of this approach,in the 1930s about 20% of ‘‘exploratory craniotomies’’ forepilepsy were closed without cortical removal.

Limited Success of

Anterolateral Temporal

Corticectomy

The success rate of just over 50% in the MNI surgicalseries indicated that resection limited to the anterolateraltemporal cortex did not eliminate all the epileptogenic

tissue in many patients (Penfield & Flanigin, 1950). Per-sistent seizures in some cases led Penfield to carry out asecond operation to extend the mesial resection of the tem-poral lobe to eliminate the spike activity shown on theECoG. Penfield also noted that these mesial structures,including uncus and the hippocampus, were tough, rub-bery, slightly yellow, and often had a harder texture withresistance to removal by suction.

In 1949, Jasper presented a preliminary report at thesecond International Congress of Electroencephalographyin Paris of 24 patients with temporal lobe epilepsy oper-ated upon by Penfield in which only two had the uncusremoved (Jasper, 1949). Penfield was looking for lesions;Jasper admitted that in some cases there was no visibleabnormality in the excised material and added, ‘‘it seemsclear, therefore, that the patho-physiological state of spikefoci may not always be associated with structural altera-tions which can be seen by present methods of micro-scopic examination.’’ In light of later evidence, these‘‘cortical spike foci’’ were projected from deep mesialstructures of the temporal lobe, so that the anterolateralcortex itself might well show no pathologic changes.Moreover, the abnormal tissues of the mesial temporalregions were often removed by suction, and thus not avail-able for pathologic examination. This was later remediedby Murray Falconer (1910–1977) by providing the neuro-pathologist Alfred Meyer (1895–1990) with en blocexcisions (Meyer et al., 1954).

In 1950, Penfield and Flanigin reviewed 68 patientswho had surgery for temporal lobe seizures from 1939 to1949 at the MNI (Penfield & Flanigin, 1950). All subjectshad at least one year of follow-up. In this series, 10patients had the uncus removed; 2 also had hippocampalremoval. The seizures were controlled in half of thepatients. Electrophysiologic abnormalities, such as spikeactivity and slow waves, were often recorded from thetemporal cortex in this series (Jasper, 1949; Jasper et al.,1951), but an anatomic substrate had not yet been properlysubstantiated (Fig. 8). In one case, Penfield stimulated theuncinate region and produced an attack of automatismrecorded from electrodes he placed over the temporal cor-tex (Jasper et al., 1951) (Fig. 9).

Meanwhile, at the University of Illinois in Chicago,Frederic Gibbs et al. (1948) by EEG studies assigned theorigin of psychomotor seizures to the anterior and lateralcortex of the temporal lobe. In 1951, Percival Bailey andFrederic Gibbs reported their first 25 operations from1947 to 1950. These were guided by EEG and ECoG. Theresections were confined to gyrectomies in the lateral andanterior aspects of the temporal lobe. Like Penfield,Bailey was an expert neuropathologist and also looked forvisible lesions at the epileptogenic sites localized byECoG (Bucy, 1974). In their initial series, Bailey reportedopaqueness and thickening of the leptomeninges, atrophyof the convolutions, and scarring of old contusions in the

142

W. Feindel et al.


removed tissue. In no instance did his extirpation extendto the insula or to the upper bank of the lateral fissure; healso carefully avoided the hippocampus. Bailey was con-cerned to avoid the severe deficits demonstrated aftermesial bitemporal resections in monkeys (Kl�ver & Bucy,1939).

In regard to surgery for seizures related to the temporallobe, Penfield started the MNI series in 1939 (Penfield &Ward, 1948; Penfield & Flanigin, 1950), which was fol-lowed later by Bailey’s studies in Chicago in 1947 (Bailey& Gibbs, 1951). Arthur A. Morris (b. 1917), a neurosurgi-cal resident at the MNI from 1944 to 1946, reported fromWashington, DC, five patients that he operated upon in1948 and 1949, in ‘‘whom there was no specific alterationin gross or histologic pathology of the tissue removed’’(Morris, 1950). These first resections, as described byMorris, were based on the operating procedure he learnedat the MNI while studying with Penfield and Jasper from1945 to 1946, which did not include excision of the uncusor hippocampus (Feindel et al., 1996; Almeida et al.,

2008). Morris (1956) reported a later series with longerfollow-up, in which he carried out larger removals toinclude these mesial structures, as in the operative proce-dure published previously from the MNI by Penfield andBaldwin (1952) and taken up earlier by Falconer (1953)and his associates (Meyer et al., 1954).

The Amygdala and Hippocampus

In the early 1950s, clues from experimental animalstudies pointed to the mesial and inferior surfaces of thetemporal lobe for the origin of the epileptic attack. BirgerKaada (1951) produced attacks of arrest of movement,licking, chewing, and swallowing by stimulating theamygdala, the head of hippocampus, and the pyriformregion in animals. Henri Gastaut (1915–1995) and hiscoworkers produced experimental epileptogenic lesionsby injecting alumina into the mesial temporal structures(Gastaut & Vigouroux, 1952). In order to understand sei-zure propagation, other laboratory studies investigated the

Figure 8.

Diagram to show localization of

electrocorticographic

abnormalities and sites of lesions

in patients with temporal lobe

seizures operated upon by

Penfield from 1939 to 1949. The

darkest areas indicate maximal

abnormalities, which are

localized to lateral and anterior

temporal regions (Jasper et al.,

1951).

Epilepsia ILAE

143



connections of anterior temporal cortex with the rest of thebrain (Ajmone-Marsan & Stoll, 1950; Stoll et al., 1951;Green & Shimamoto, 1953). Feindel and Gloor (1954)produced epileptic discharge from stimulation of theamygdala and the reticular formation of the brainstem incats, which resembled the findings at operation onhumans.

Convincing physiologic evidence that the mesial tem-poral region was a crucial zone for the generation of tem-poral lobe seizures came from the systematic reproductionin 16 patients of habitual auras and other typical featuresof their attacks, by depth stimulation at operation withinand around the amygdala, involving also sometimes theventral claustrum and the anterior insula (Feindel et al.,1952). The responses were emotional (such as fear), vis-ceral (epigastric aura), impaired consciousness and con-fused memory, or brief seizures with automatism andamnesia for the ictal period. During this amnesic period,there was blockage of the input to memory but retention of

older memories, a feature well described by HughlingsJackson (Jackson & Colman, 1898) for his patient ‘‘Z.’’The resulting seizure discharges on corticography spreadrapidly, often with low-voltage fast activity, engagingmuch of the temporal cortex (Fig. 10). These findingscalled for a meticulous excision of the amygdaloid regionto ensure relief from attacks (Feindel & Penfield, 1954).The juxtaposition and overlap of the amygdala and hippo-campus, and the contiguity of the amygdala with the glo-bus pallidus, present anatomic features that make itdifficult to separate these two structures in depth recordingand stimulation and, in addition, to ensure adequate resec-tion of the amygdala, while sparing the hippocampus.These observations drew attention to the significance ofthe human claustroamygdaloid complex in short-termmemory, consciousness, and emotions (Feindel &Penfield, 1954).

Curiously, in the MNI experience, stimulation ofthe hippocampus directly exposed at operation rarely

Figure 9.

First electrocorticography (ECoG) recording of a temporal lobe seizure, after stimulation by Penfield of the uncus,

to show widespread activation of temporal cortex, associated with automatism (Jasper et al., 1951).

Epilepsia ILAE

144

W. Feindel et al.


produced such auras or ictal responses, even though epi-leptic abnormality might be recorded from the anteriorpart of the structure. Depth stimulation of the amygdala incats reproduced these electrographic features of wide-spread cortical seizure activity, similar to responses pro-duced by stimulation of the brainstem reticular formation(Feindel & Gloor, 1954). These findings demonstratedthat the epileptic activity recorded from the lateral andanterior temporal cortex might be secondary to an epilep-tic focus deep in the claustroamygdaloid complex (Feindel& Penfield, 1954).

The group from the MNI also proposed that ‘‘incisuralsclerosis,’’ the gross scarring and atrophy of the mesialtemporal structures encountered by the surgeon, couldresult from an ischemic injury caused by tentorial herni-ation, with compression of the uncinate region and hip-pocampus, or compromise of their blood supply,associated with either difficult birth or childhood braininjury (Earle et al., 1953). They based their theory onfocal pathologic abnormalities found in a series of 157patients with temporal lobe epilepsy operated upon byPenfield.

As resection of the anteromesial structures became theaccepted treatment for temporal lobe epilepsy, a functionfor the hippocampus became elucidated. A syndrome ofdefect in recent memory but preservation of intellectual

function was reported by Milner and Penfield (1955) fromthe MNI series, in two patients after unilateral temporalexcision in the presence of what later became recognizedas bilateral mesial temporal pathology, involving espe-cially the hippocampus (Penfield & Milner, 1958;Penfield & Mathieson, 1974).

William Scoville (1906–1984) and his group atHartford, based on neurophysiologic studies (Liebersonet al., 1951), carried out bilateral resections of themesial temporal regions in a few patients with epilepsy.One patient, H. M., now famous in the annals of neuro-psychology, developed a similar deficit in recent mem-ory, which confirmed the MNI report that thehippocampi were especially involved in the ‘‘retentionof new experiences’’ (Scoville & Milner, 1957). Thesefindings, together with the previous observation by Fein-del and Penfield (1954) that stimulation in the region ofthe amygdala evoked ictal amnesia with separationbetween short-term and long-term memory, directedattention to the important role of the mesial temporalstructures in memory mechanisms (Milner, 1958; Fein-del, 1964). Later studies showed that unilateral resectionof the amygdala resulted in no memory deficit, but lar-ger extent of resection of the hippocampus was associ-ated with detectable memory impairment (Leonard,1991).

Figure 10.

Stimulation points in the insula

and claustroamygdaloid complex

that provoked features of auras

or brief seizures with

automatism and amnesia in 16

patients (Feindel & Penfield,

1954).

Epilepsia ILAE

145



Anteromesial Temporal Lobe

Resection

In 1952, based on the above evidence, Penfield andMaitland Baldwin (1918–1970) published their now clas-sical report describing the technique for subtotal temporallobectomy that included the amygdala and hippocampalcomplex. They concluded that ‘‘the abnormal, scleroticarea of the cortex, which must be removed in most cases,lies in the deepest, most inferior and mesial portion of the[temporal] lobe. . .’’ (Figs. 11 and 12).

Their report laid out the resection that would serve asthe model for temporal lobe surgery, going more mesialthan the anterolateral procedure carried out by Bailey andGibbs (1951) and Morris (1950). From 1953 onward, otherneurosurgical centers, often involving surgeons and scien-tists who had studied at the MNI, took up anteromesialtemporal lobe resection for the treatment of seizures(Morris, 1956; Baldwin & Bailey, 1958; Van Buren &Ajmone-Marsan, 1960). Falconer (1953), as noted, intro-duced the important modification of en bloc resection,which allowed his pathologists to examine the hippocam-pus and amygdala in toto (Meyer et al., 1954). Falconer(1953) also emphasized that temporal lobe pathology inhis cases was sometimes associated not only with a diffi-cult birth, but also with febrile seizures of infancy(Falconer & Taylor, 1968).

The importance attained by this topic spurred severalmeetings devoted to the study of psychomotor epilepsy. In1954, Gastaut and his associates organized in Marseilles acolloquium on advances in the treatment of temporal lobe

epilepsy. This gave an opportunity for Penfield to providean overview of the early experimental and surgical resultsof his team at the MNI that established the important roleof the mesial temporal region in the pathogenesis and sur-gical treatment (Penfield, 1956).

Another colloquium sponsored by Baldwin and Bailey(1958) at the National Institutes of Health, U.S.A.,extended and confirmed the significance of subtotal tem-poral lobectomy, including particularly the mesial tempo-ral structures, for treating temporal lobe seizures.Rasmussen and Jasper (1958), using electrodes combiningstimulation and recording, confirmed and extended theearlier findings of Feindel and Penfield (1954) that clinicaland electrographic features of temporal lobe seizurescould consistently be initiated by stimulation in the amyg-daloid region. Attending this colloquium, a Brazilianneurosurgeon, Paulo Niemeyer (1914–2004) presented hisinnovative surgical approach of selective resection ofthe amygdala and hippocampus with preservation of thetemporal neocortex (Niemeyer, 1958).

The ingenious application of stereotactics for implant-ing depth electrodes used by the Paris school of Talairachand associates offered a new dimension for the preopera-tive analysis of seizure localization that became widelyadopted from the early 1960s (Talairach et al., 1958;Crandell & Babb, 1993; L�ders, 2008).

Conclusions

Over the last 50 years, in neurosurgical centersthroughout the world, thousands of patients afflicted with

Figure 11.

Drawing to show features of subtotal anterior-mesial

temporal lobectomy for temporal lobe seizures as

developed at the MNI (Penfield & Baldwin, 1952).

Epilepsia ILAE

Figure 12.

Surgeon’s view of the ‘‘Montreal Procedure’’ at the final

stage of subtotal anterior-mesial temporal lobectomy,

after excision of the amygdala and hippocampus

(Wilder Penfield Archive).

Epilepsia ILAE

146

W. Feindel et al.


temporal lobe seizures have been treated with increasingsuccess by operation (Engel, 1987; L�ders, 1991; L�derset al., 2008). The standard anteromesial resection asdetailed by Penfield and Baldwin (1952), and taken up inmost centers, was based mainly on the original procedureintroduced by the MNI group, often referred to as ‘‘TheMontreal Procedure,’’ which distinguished it from theanterior-lateral gyrectomies preformed by Bailey andassociates in Chicago (Green et al., 1951).

In 1991, a report compared two long-term follow-upseries of 100 patients each, operated upon between 1961and 1980, with anteriomesial resections. One series had alarge and the other a minimal hippocampal removal, butboth had resection of the amygdala. A 65% success ratewas achieved in both series (Feindel & Rasmussen, 1991;Rasmussen & Feindel, 1991). This evidence indicated thatthe standard subtotal lobectomy, as originally describedby Penfield and Baldwin (1952), could be more limited interms of the amount of neocortical tissue removed(Fig. 13). This study also confirmed the importance of rad-ical resection of the amygdala (Feindel & Penfield, 1954)and showed that satisfactory outcome can result withoutmajor hippocampectomy.

Selective removal of the amygdala and hippocampus,introduced by Niemeyer, 1958, was modified by Wieserand Yasergil (1982), Andr� Olivier (b. 1938) (1991) andmany others, with up to 80% successful control of seizuresin selected patients (Wieser, 1991). These results indicatethat the anterolateral temporal cortex, which first directedthe attention of Gibbs and Jasper to the temporal lobebecause of its epileptic spiking, need not be excised inmany cases (Feindel et al., 1996). The role of the amyg-dala in the generation and propagation of temporal lobeseizures was confirmed in extensive studies by Gloor andreported in his monograph on the temporal lobe and limbicsystem (Gloor, 1999).

Since the 1970s, the advent of the revolutionary tech-nology of computerized neuroimaging, particularly mag-netic resonance imaging (MRI), has resulted in thedetection of lesions in 25% of patients examined for tem-poral lobe seizures (Fig. 14). In another 30%, atrophy ofthe hippocampus, amygdala, and entorhinal cortex hasbeen well documented and correlated with the local tissuepathology (Kuzniecky et al., 1987; Feindel, 1991;Berkovic et al., 2004). The exactness of anatomic depic-tion of the temporal resection by MRI now makes it possi-ble to evaluate more precisely the postoperative results incomparison to the pathology and to the anatomic patternof the surgical excision; thus the series of cases from dif-ferent neurosurgical centers can be compared.

The widespread success of anteromesial temporal loberesection renders this one of the most effective operationsin the field of neurosurgery (Falconer, 1974; Feindel,1974; Engel, 1987; L�ders, 1991; Engel 1993a, 1993b;Feindel et al., 1996; L�ders et al., 2008). But many sub-stantial questions remain to be answered (Feindel, 2008,2009). Can the attractive hypothesis of tentorial herniationas a cause for incisural sclerosis be validated? How doinfantile generalized febrile seizures lead to focal, unilat-eral pathology? What is the specific epileptogenic role ofjuxtaposed structures such as the amygdala, entorhinalcortex, subiculum, hippocampus, insula, and claustrum inthe origin and propagation of temporal lobe seizures?What are the physiologic and cognitive deficits resultingfrom focal surgery involving these structures and their cir-cuitous connections? And how might these deficits beminimized by ‘‘tailoring’’ the pattern of resection in theindividual patient, commensurate with successful relief ofseizures? How much of the hippocampal region must beexcised to obtain a seizure-free outcome without compro-mise of memory function? An extensive review by Sch-ramm (2008) addressing patterns of resection of thetemporal lobe, reported from 53 neurosurgical centers,confirms the efficacy of surgery but offers no adequateevidence to answer these basic questions.

Epilepsy was Penfield’s great teacher, as it was for somany of the pioneer surgical figures noted in this review(Penfield, 1967). The excitation from the neuronal

Figure 13.

Hatched lines indicate anterior cortical and amygdalar

resection (large arrows) and a more posterior

resection to include 2–4 cm of the hippocampus (small

arrows). Both types of resections yielded a long-term

follow-up rate of 65% in two series of 100 patients who

were seizure free, or who had rare seizures (Feindel &

Rasmussen, 1991).

Epilepsia ILAE

147



substrate in the lateral temporal cortex of past experi-ences (‘‘flash-backs’’) during surgical treatment was analmost startling phenomenon that enthralled Penfield tothe end of his long career (Penfield, 1975). The automa-tism and amnesia characteristic of some temporal lobeseizures, noted by Jackson and Colman (1898) andevoked by stimulation in the region of the claustro-amygdaloid complex, involves a temporary but strikinginterference with memory recording and absence ofhigher mental activity or mind, that still demands furtherelucidation (Feindel & Penfield, 1954). The function ofthe nondominant parietal lobe (H�caen et al., 1956) andthe extensive findings on lateralization and localizationof speech function (Penfield & Roberts, 1959), werebuilding blocks upon which some of the modern views of

separable functions of the two halves of the human brainbecame established. The assessment of frontal lobe func-tion after large excisions by Penfield (Penfield & Evans,1935; Hebb & Penfield, 1940) presaged the clinical neu-ropsychology studies by Milner and her train of graduatestudents. Her orderly and scholarly evaluations of surgi-cal patients of Penfield and Scoville identified the criticalrole of the hippocampal region in short-memory memoryfunction (Milner & Penfield, 1955; Scoville & Milner,1957; Penfield & Milner, 1958). The temporary and par-tial paresis of one cerebral hemisphere by injection ofintracarotid sodium amytal, a technique introduced byWada, became a useful test for determining the lateralityof speech function (Wada & Rasmussen, 1960) and forevaluating memory responses in patients with bitemporalseizure activity (Milner et al., 1962). Many technicaladvances in the selection and investigation of patientswith seizures have been developed, such as the computer-ized monitoring of ictal and interictal EEG (Ives &Gloor, 1978; Gotman, 1985, 1989).

Over a period of 80 years Penfield and his associatesauthored a rich canon of literature on the surgical and sci-entific aspects of epilepsy. Many of their publicationsbecame classics in the field of neurology (for Penfield bib-liography see: Eccles & Feindel, 1978). Rasmussen’smeticulous long-term follow-up studies with his associ-ates of the surgical patients treated at Montreal since 1928now extend to more than 6,000 dossiers. These have pro-vided invaluable documentation of the expectations, suc-cess rates, pitfalls, and questions still to be answered aboutthe surgical treatment of epilepsy (Penfield & Rasmussen,1950; Penfield & Jasper, 1954; Gloor & Feindel, 1963;Feindel, 1975; Rasmussen, 1983; Anderman, 1987;Feindel & Rasmussen, 1991; Olivier, 1991; L�ders, 1991;Almeida et al., 2008; Feindel, 2008, 2009).

The surgical cure of epilepsy has offered relief forcountless patients, as confirmed from many neurosurgicalcenters world-wide (Engel, 2005; L�ders et al., 2008).Future directions of this special field of neurosurgery havebeen sagely discussed by other authors, who have offeredsensible guidelines based on historical perspectives(Rasmussen, 1983; Engel, 1993a,b, 2005; Andermann &Harkness, 2008). Three major global challenges face thefield of epilepsy surgery: the development of additionalcomprehensive epilepsy centers, the more effective use ofexisting epilepsy centers to provide surgical treatment, andintensified research into basic mechanisms of epilepsy sothat the need for surgery might ultimately be eliminated.

As Penfield optimistically pointed out in his last book,The Mystery of the Mind (1975), ‘‘Epilepsy, though shewears the frightening mask of tragedy in her approach toeach patient, takes off the mask at times before the physi-cian who has the wit to stop and ponder her riddles.’’ Hisstatement stands as a fitting comment for this centennialcelebration of the founding of the ILAE.

Figure 14.

Magnetic resonance imaging (MRI) of patient ‘‘Q’’ who

had seizures, with olfactory auras, and automatism,

showing a venous angioma in the region of the amyg-

dala (Feindel Photo Archive, 1986).

Epilepsia ILAE

148

W. Feindel et al.


Acknowledgments

This study was supported by the Medical Class of 1945 Fund ofMcGill University and the Thomas Willis Fund of the Montreal Neuro-logical Institute. The authors are grateful to Matthew Garsia for editorialassistance, to Ann Watson, Carol Weins and Claudia Ugolik for help withreferences, and to Helmut Bernhard for formatting the illustrations.

We confirm that we have read the journal’s position on issues involved inethical publication and affirm that this report is consistent with thoseguidelines.

Disclosure: The authors declare no conflict of interest.

References

Adrain ED, Matthews BHC. (1934) The Berger rhythm: potentialchanges from the occipital lobes in man. Brain 57:355–385.

Adrian ED. (1934) Electrical activity of the nervous system. Arch NeurolPsychiatry 32:1125–1136.

Ajmone-Marsan CA, Stoll J. (1950) Subcortical connections of the tem-poral pole in relation to temporal lobe seizures. Arch Neurol Psychia-try 66:669–686.

Almeida AN, Teixeira MJ, Feindel WH. (2008) From lateral to mesial:the quest for a surgical cure for temporal lobe epilepsy. Epilepsia49:98–107.

Anderman F. (1987) Identification of candidates for surgical treatment ofepilepsy. In Engel J Jr (Ed) Surgical treatment of the epilepsies.Raven Press, New York, NY, pp. 51–70.

Andermann F, Harkness W. (2008) The future of epilepsy surgery. InL�ders H (Ed) Textbook of epilepsy surgery. Informa Healthcare,London, pp. 197–199.

Apuzzo MLJ. (Ed) (1991) Neurosurgical aspects of epilepsy surgery.Amer Assoc Neurol Surg, Park Ridge, Ill.

Bailey P, Gibbs F. (1951) The surgical treatment of psychomotor epi-lepsy. JAMA 145:365–370.

Baldwin M, Bailey P. (Eds) (1958) Temporal lobe epilepsy. Charles C.Thomas, Springfield, Ill.

Berkovic S, Andermann E, Olivier A, Ethier R, Melanson D, RobitailleY, Kuzniecky R, Peters T, Feindel W. (2004) Hippocampal sclerosisin temporal lobe epilepsy demonstrated by magnetic resonance imag-ing. Ann Neurol 29:175–182.

Boling W, Olivier A, Fabinyi G. (2002) Historical contributions to themodern understanding of function in the central area. Neurosurgery50:1297–1310.

Broca P. (1876) Sur la topographie cranio- c�r�brale ou sur les rapportsanatomique du crane et du cerveau. Rev Anthropol 2e s�rie V:193–248.

Brodal A. (1947) The hippocampus and the sense of smell. A review.Brain 70:179–223.

Bucy P. (1974) Percival Bailey, 1892–1973. J Neurosurg 39:281–288.

Chorobski J, Penfield W. (1932) Cerebral vasomotor nerves and theirpathway from the medulla oblongata. With observations on the pialand intracerebral vascular plexus. Arch Neurol Psychiatry 28:1257–1289.

Crandell PH, Babb TL. (1993) The UCLA epilepsy program: historicalreview 1960–1992. J Clin Neurophysiol 10:226–238.

Cushing H. (1909a) A note upon the faradic stimulation of the postcentralgyrus in conscious patients. Brain 32:44–53.

Cushing H. (1909b) Partial hypophysectomy for acromegaly: withremarks on the function of the hypophysis. Ann Surg 50:1002–1017.

Cushing H, Eisenhardt L. (1938) Meningiomas: their classification,regional behaviour, life history, and surgical end results. Charles CThomas, Springfield, Ill.

Del R�o Hortega P, Penfield W. (1927) Cerebral cicatrix: the reaction ofneuroglia and microglia to brain wounds. Bull Johns Hopkins Hosp41:278–303.

Earle KM, Baldwin M, Penfield W. (1953) Incisural sclerosis and tempo-ral lobe seizures produced by hippocampal herniation at birth. ArchNeurol Psychiatry 69:27–42.

Eccles J, Feindel W. (1978) Wilder Graves Penfield 1891–1976. BiogrMem Fellows R Soc 24:473–513 *(Includes bibliography of Penfield,pp. 501–513).

Echlin FA. (1939) Cerebral ischaemia and its relation to epilepsy (M.Sc.Thesis). McGill University, Montreal.

Engel J Jr (Ed). (1987) Surgical treatment of the epilepsies. Raven Press,New York, NY.

Engel J Jr (Ed). (1993a) Surgical treatment of the epilepsies, 2nd ed.Raven Press, New York, NY.

Engel J Jr. (1993b) Historical perspectives and future directions.In Wyllie E (Ed) The treatment of epilepsy: principles and practice.Lea & Febiger, Philadelphia, pp. 989–998.

Engel J Jr. (2005) The emergence of neurosurgical approaches to thetreatment of epilepsy. In Waxman S (Ed) From neuroscience to neu-rology: neuroscience, molecular medicine, and the therapeutic trans-formation of neurology. Elsevier, Amsterdam, pp. 81–105.

Falconer MA. (1953) Discussion on the surgery of temporal lobeepilepsy: surgical and pathological results. Proc R Soc Med 46:971–974.

Falconer MA, Taylor DC. (1968) Surgical treatment of epilepsy due todrug-resistant mesial temporal sclerosis: etiology and significance.Arch Neurol 19:353–361.

Falconer MA. (1974) Mesial temporal (Ammon’s horn) sclerosis as acommon cause of epilepsy: etiology, treatment and prevention.Lancet 2:767–770.

Feindel W, Penfield W, Jasper MM. (1952) Localization of epilepticdischarge in temporal lobe automatism. Trans Am Neurol Assoc.77:14–17.

Feindel W, Gloor P. (1954) Comparision of electroencephalographiceffects of stimulation of amygdala and brainstem reticular formationin cats. Electroencephalogr Clin Neurophysiol 6:389–402.

Feindel W, Penfield W. (1954) Localization of discharge in temporallobe automatism. Arch Neurol Psychiatry 72:605–630.

Feindel W. (1964) Memory and speech function in the temporal lobe inman. In Brazier MA (Ed) Brain Function II: RNA and brain function;memory and learning. University of California Press, Berkeley andLos Angeles, pp. 276–298.

Feindel W, Perot P. (1965) Red cerebral veins. A report on arteriovenousshunts in tumors and cerebral scars. J Neurosurg 22:315–325.

Feindel W. (1974) Temporal lobe seizures. In Magnus O, Lorentz deHass AM (Eds) Handbook of clinical neurology. North-HollandPublishing, Amsterdam, pp. 87–106.

Feindel W. (1975) Factors contributing to the success or failure of surgi-cal intervention for epilepsy. In Purpura DP, Penry JK, Walter RD(Eds) Advances in neurology. New York, Raven Press, pp. 281–298.

Feindel W. (1977) Wilder Penfield (1891–1976): the man and his work.Neurosurgery 1:93–100.

Feindel W. (1991) Development of surgical therapy of epilepsy at theMontreal Neurological Institute. Can J Neurol Sci 18:549–553.

Feindel W, Rasmussen T. (1991) Temporal lobectomy with amygdalec-tomy and minimal hippocampal resection: review of 100 cases. Can JNeurol Sci 18:603–605.

Feindel W. (1993) Toward a surgical cure for epilepsy: the work of Wil-der Penfield and his school at the Montreal Neurological Institute. InEngel J Jr (Ed) Surgical treatment of the epilepsies, 2nd ed. RavenPress, New York, NY, pp. 54–66.

Feindel W, Leblanc R, Villemure JG. (1996) History of the surgicaltreatment of epilepsy. In Greenblatt SH, Dagi TF, Epstein NH (Eds.)A history of neurosurgery. American Association of NeurologicalSurgeons, Park Ridge, Ill, Chap. 23: pp. 465–488.

Feindel W. (1999) Herbert Henri Jasper: an appreciation. Can J NeurolSci 26(Suppl 3):224–229.

Feindel W. (2003a) Osler and the ‘‘medico-chirurgical neurologists’’:Horsley, Cushing and Penfield. J Neurosurg 99:188–193.

Feindel W. (2003b) Theodore Brown Rasmussen (1910–2002). Epilepsysurgeon, scientist and teacher. J Neurosurg 98:631–637.

Feindel W. (2007) The physiologist and the neurosurgeon: the enduringinfluence of Charles Sherrington on the career of Wilder Penfield.Brain. 130:2758–2765.

Feindel W. (2008) Epilepsy surgery in Canada. In L�ders H (Ed) Text-book of epilepsy surgery, Chapter 12. Taylor & Francis, Abingdon,Oxford, pp. 103–115.

149



Feindel W. (2009) Osler vindicated: glioma of the leg center; Jacksonianepilepsy; removal and cure; 50 year follow up. J Neurosurg 105(in press).

Ferrier D. (1876) The functions of the brain. Smith, London.Flanigin HF, Hermann BP, King DW. (1991) The history of surgical

treatment of epilepsy in North America prior to 1975. In L�ders H.(Ed) Epilepsy surgery. Raven Press, New York, NY, pp. 19–35.

Foerster O, Penfield W. (1930a) Der narbenzug am und im gehirn beitraumatischer epilepsie in seiner bedeutung f�r das zustandekommender anf�lle und f�r die therapeutische bek�mpfung derselben. Z Neu-rol Psychiatry 125:475–572.

Foerster O, Penfield W. (1930b) The structural basis of traumatic epi-lepsy and results of radical operation. Brain 53:99–119.

Foerster O. (1934) Uber die bedeutung und reichweite des lokalisation-sprinzips im nervensystem. Verh Dtsch Ges Inn Med 46:117–211.

Foerster O, Altenburger H. (1935) Elektrobiologische vorg�nge an dermenschlichen hirnrinde. Dtsch Z Nervenheilkd 135:277–288.

Foerster O. (1936) The motor cortex in man in the light of HughlingsJackson’s doctrines. Brain. 59:135–159.

Fulton JF. (1946) Harvey Cushing, a biography. Charles C. Thomas,Springfield, Ill.

Gage EL. (1931) The effects of vasomotor nerve section on experimentalepilepsy (M.Sc. Thesis). McGill University, Montreal.

Gastaut H, Vigouroux RN. (1952) L�sions �pileptog�nes amygdalo-hippocampiques provoqu�es chez le chat par injection de ‘‘cr�med’alumine’’. Rev Neurol 87:607–609.

Gibbs FA, Davis H, Lennox WG. (1935) The electro-encephalogram inepilepsy and in conditions of impaired consciousness. Arch NeurolPsychiatry 34:1133–1148.

Gibbs FA, Lennox WG, Gibbs EL. (1936) The electro-encephalogram indiagnosis and in localization of epileptic seizures. Arch Neurol Psy-chiatry 36:1225–1235.

Gibbs FA, Gibbs E, Lennox WG. (1938) Cerebral dysrhythmias ofepilepsy. Measures for their control. Arch Neurol Psychiatry 39:298–314.

Gibbs EL, Gibbs FA, Fuster B. (1948) Psychomotor epilepsy. ArchNeurol Psychiatry 60:331–339.

Gloor P, Feindel W. (1963) Affective behaviour and temporal lobe. InMonnier M (Ed) Physiologie und pathophysiologie des vegetativennervensystems. II: Pathophysiologie. Hippokrates-Verlag, Stuttgart,pp. 685–716.

Gloor P. (1969) Hans Berger on the electroencephalogram in man.Electroencephalogr Clin Neurophysiol Suppl pp. :1–350.

Gloor P. (1997) The temporal lobe and limbic system. Oxford Universitypress, New York, NY.

Gotman J. (1985) Automatic recognition of interictal spikes. Electroen-cephalogr Clin Neurophysiol 37:93–114.

Gotman J. (1989) Automatic detection of seizures and spikes. J Clin Neu-rophysiol 16:130–140.

Green JR, Duisberg REH, McGrath WB. (1951) Focal epilepsy of psy-chomotor type: a preliminary report of observations on effects of sur-gical therapy. J Neurosurg 8:157–172.

Green JD, Shimamoto T. (1953) Hippocampal seizures and their propa-gation. Arch Neurol Psychiatry 70:687–702.

Greenblatt SH, Dagi TF, Epstein MH (Eds) (1997) A history of neurosur-gery: in its scientific and professional contexts. The American Asso-ciation of Neurological Surgeons, Park Ridge, Ill.

Hebb DO, Penfield W. (1940) Human behaviour after extensive bilateralremoval of the frontal lobes. Arch Neurol Psychiatry 44:421–438.

H�caen H, Penfield W, Bertrand C, Malmo R. (1956) The syndrome ofapractognosia due to lesions of the minor cerebral hemisphere. ArchNeurol Psychiatry 75:400–434.

Hermann BP, Stone JL. (1989) A historical review of the epilepsy sur-gery program at the University of Illinois Medical Center: the contri-butions of Bailey, Gibbs and collaborators to the refinement ofanterior temporal lobectomy. J Epilepsy 2:155–163.

Hitzig E. (1900) Hughlings Jackson and the cortical motor centres in thelight of physiological research. Brain 23:544–581.

Horsley V. (1886) Brain surgery. BMJ 2:670–675.Horsley V. (1892) The structure and the functions of the brain and spinal

cord. Griffin, London.Horsley V. (1906) On the technique of operation on the central nervous

system. Lancet 2:484–490.

Horsley V. (1909) The function of the so-called motor area of the brain(Linacre Lecture). BMJ 11:125–132.

Ives JR, Gloor P. (1978) A long-term time-lapse video system to docu-ment the patient’s spontaneous clinical seizure synchronized with theEEG. Electroencephalogr Clin Neurophysiol 45:412–416.

Jackson JH. (1870) A study of convulsions. Trans St Andrews Med GradAssoc. 3:162–204.

Jackson JH. (1873) On the anatomical, physiological, and pathologicalinvestigation of epilepsies. A study of convulsions. West RidingLunatic Asylum Med Reports 3:315–319.

Jackson JH. (1888) On a particular variety of epilepsy (‘‘intellectualaura’’), one case with symptoms of organic brain disease. Brain11:179–207.

Jackson JH, Colman WS. (1898) Case of epilepsy with tasting move-ments and ‘‘dreamy state’’ – very small patch of softening in the leftuncinate gyrus. Brain 21:580–590.

Jasper HH, Carmichael L. (1935) Electrical potentials from the intacthuman brain. Science 81:51–53.

Jasper HH, Hawke WA. (1938) Electro-encephalography. IV. Localiza-tion of seizure waves in epilepsy. Arch Neurol Psychiatry 39:885–901.

Jasper HH. (1941) Electroencephalography. In Penfield W, Erickson TC(Eds) Epilepsy and cerebral localization. Charles C Thomas, Spring-field, Ill, pp. 380–454.

Jasper HH, Kershman J. (1941) Electroencephalographic classificationof the epilepsies. Arch Neurol Psychiatry 45:903–943.

Jasper HH. (1949) �tude anatomo-physiologique des �pilepsies. Electro-encephalogr Clin Neurophysiol (Suppl 2):99–111.

Jasper HH, Pertuisset B, Flanigin H. (1951) EEG and cortical electro-grams in patients with temporal lobe seizures. Arch Neurol Psychia-try 65:272–290.

Jasper HH. (1958) Functional subdivisions of the temporal region in rela-tion to seizure patterns and subcortical connections. In Baldwin M,Bailey P (Eds) Temporal lobe epilepsy. Charles C Thomas, Spring-field, Ill, pp. 40–57.

Jasper HH. (1991) History of the early development of electroencepha-lography and clinical neurophysiology at the Montreal NeurologicalInstitute: the first 25 years 1939-1964. Can J Neurol Sci 18:533–548.

Jefferson G. (1941) Otfrid Foerster. Lancet 1:503.Kaada BR. (1951) Somato-motor, autonomic and electrocorticographic

responses to electrical stimulation of ‘‘rhinencephalic’’ and otherstructures in primates, cat, and dog. Acta Physiol Scand 24(Suppl 83):1–285.

Kl�ver H, Bucy P. (1939) Preliminary analysis of functions of the tempo-ral lobes in monkeys. Arch Neurol Psychiatry 42:979–1000.

Krause F. (1909) Die operative behandlung der epilepsie. Med KlinBerlin 5:1418–1422.

Krause F (Haubold A, Thorek M, trans.). (1912) Surgery of the brain andspinal cord based on personal experience. Rebman, New York, NY.

Krause F, Schurn H. (1931, 1932) Die spezielle chirurgie der gehirnkrankheiten. 2bd. Die epileptischen erkrankungen. Enke, Stuttgart.

Kuzniecky R, de la Sayette V, Ethier R, Melanson D, Andermann F,Berkovic S, Robitaille Y, Olivier A, Peters T, Feindel W. (1987)Magnetic resonance pathology imaging in temporal lobe epilepsy:pathological correlations. Ann Neurol 22:341–347.

Leblanc R. (1990) Fedor Krause: pioneer seizure surgeon [Abstr].Epilepsia 31:616–617

Lennox WG. (1949) Discussion sur la classification des �pilepsies.Electroencephalogr Clin Neurophysiol (Suppl 2):132–136.

Leonard G. (1991) Temporal lobe surgery for epilepsy; neuropsycho-logical variables related to seizure outcome. Can J Neurol Sci18(Suppl 4):593–597.

Lewis J. (1981) Something hidden. A biography of Wilder Penfield.Doubleday, Garden City, NY.

Leyton ASF, Sherrington CS. (1917) Observations on the excitablecortex of the chimpanzee, orang-utan, and gorilla. J Exp Physiol11:135–222.

Lieberson WT, Scoville WB, Dunsmore RH. (1951) Stimulation studiesof the prefrontal lobe and uncus in man. Electroencephalogr ClinNeurophysiol 3:1–8.

L�ders H (Ed). (1991) Epilepsy surgery. Raven Press, New York, NY.L�ders H (Ed). (2008) Textbook of epilepsy surgery. Informa Healthcare,

London.

150

W. Feindel et al.


McNaughton FL. (1937) The innervation of the intracranial blood ves-sels and dural sinuses. In Penfield W (Ed) The circulation of the brainand spinal cord. Association for Research in Nervous and MentalDiseases XVIII. Williams & Wilkins, Baltimore, MD, pp. 178–200.

Meador KJ, Loring DW, Flanigin HF. (1988) History of epilepsy surgery[Abstr.]. Neurology 38 (Suppl 1, No 3): 383.

Meyer A, Falconer MA, Beck F. (1954) Pathological findings in temporallobe epilepsy. J Neurol Neurosurg Psychiatry 17:276–285.

Milner B, Penfield W. (1955) The effect of hippocampal lesions on recentmemory. Trans Am Neurol Assoc. 80:42–48.

Milner B. (1958) Psychological defects produced by temporal lobe exci-sions. Res Publ Assoc Res Nerv Ment Dis 36:244–257.

Milner B, Branch C, Rasmussen T. (1962) Study of short-term memoryafter intracarotid injection of sodium amytal. Trans Am Neurol Assoc.87:224–226.

Morris AA. (1950) The surgical treatment of psychomotor epilepsy. MedAnn Dist Columbia 19:121–131.

Morris AA. (1956) Temporal lobectomy with removal of uncus, hippo-campus, and amygdala: results for psychomotor epilepsy three to nineyears after operation. Arch Neurol Psychiatry 76:479–496.

Niemeyer P. (1958) Transventricular amygdalo-hippocampectomy intemporal lobe epilepsy. In Baldwin M, Bailey P (Eds) Temporal lobeepilepsy. Charles C Thomas, Springfield, IL, pp. 461–482.

Foerster O. (1925) Zur pathogenese und chirurgischen behandlung duepilepsie. Zentralbl Chir 52:531–549.

Olivier A. (1991) Surgery of epilepsy: overall procedure. In Apuzzo MLJ(Ed) Neurosurgical aspects of epilepsy. American Association ofNeurological Surgeons, Park Ridge, IL, pp. 117–148.

Osler W. (1885) A contribution to Jacksonian epilepsy and the situationof the leg centre. Am J Med Sci 89:31–37.

Osler W. (1889) On conditions of the brain suitable for operation. CanPract 14:165–167.

Osler W. (1907) Discussion, British Medical Association meeting. Lan-cet 2:334.

Penfield W. (1924) Meningocerebral adhesions. A histological study ofthe results of cerebral incision and cranioplasty. Surg Gynecol Obstet39:803–810.

Penfield W. (1927) The mechanism of cicatrical contraction in the brain.Brain 50:499–517.

Penfield W. (1930) The radical treatment of traumatic epilepsy and itsrationale. Can Med Assoc J 23:189–197.

Penfield W. (Ed) (1932) Cytology and cellular pathology of the nervoussystem, 3 vols. Paul B Hoeber, New York, NY.

Penfield W. (1933) The evidence for a cerebral vascular mechanism inepilepsy. Ann Intern Med Assoc. 7:303–310.

Penfield W, Evans J. (1935) The frontal lobe in man: a clinical study ofmaximum removals. Brain 58:115–133.

Penfield W. (1937) The circulation of the epileptic brain. Res Publ AssocRes Nerv Ment Dis 18:605–637.

Penfield W, Boldrey E. (1937) Somatic motor and sensory representationin the cerebral cortex of man as studied by electrical stimulation.Brain 60:389–443.

Penfield W, Erickson TC. (1941) Epilepsy and cerebral localization:a study of the mechanism, treatment and prevention of epilepticseizures. Charles C Thomas, Springfield, Ill.

Penfield W, Ward A. (1948) Calcifying epileptogenic lesions, hemangi-oma calcificans; report of a case. Arch Neurol Psychiatry 60:20–36.

Penfield W, Flanigin H. (1950) Surgical therapy of temporal lobe sei-zures. Arch Neurol Psychiatry 64:491–500.

Penfield W, Rasmussen T. (1950) The cerebral cortex of man. A clinicalstudy of localization of function. Macmillan, New York, NY.

Penfield W, Baldwin M. (1952) Temporal lobe seizures and the tech-nique of subtotal temporal lobectomy. Ann Surg 136:625–634.

Penfield W, Jasper H. (1954) Epilepsy and the functional anatomy of thehuman brain. Little, Brown & Co, Boston, Mass.

Penfield W. (1956) Epileptogenic lesions. Acta Neurol Psychiatr Belg56:75–88.

Penfield W, Milner B. (1958) Memory deficit produced by bilaterallesions in the hippocampal zone. Arch Neurol Psychiatry 79:475–497.

Penfield W, Roberts L. (1959) Speech and brain-mechanisms. PrincetonUniversity Press, Princeton, NJ.

Penfield W. (1967) Epilepsy, the great teacher. The progress of one pupil.Acta Neurol Scand 43:1–10.

Penfield W. (1971) Remarks on incomplete hypothesis for the control ofcerebral circulation. J Neurosurg 35:124–127.

Penfield W, Mathieson G. (1974) Memory – autopsy findings and com-ments on the role of hippocampus in experiential recall. Arch Neurol31:145–154.

Penfield W. (1975) The mystery of the mind. Princeton University Press,Princeton, NJ.

Penfield W. (1977) No man alone. A neurosurgeon’s life. Little, Brown& Co, Boston, Mass.

Preul MC, Feindel W. (1991) Origins of Wilder Penfield’s surgical tech-nique. The role of the ‘‘Cushing ritual’’ and influence from the Euro-pean experience. J Neurosurg 75:812–820.

Preul MC, Feindel W. (2001) ‘‘The art is long and the life is short’’: theletters of Wilder Penfield and Harvey Cushing. J Neurosurgery95:148–161.

Rasmussen T, Jasper HH. (1958) Temporal lobe epilepsy: indication foroperation and surgical technique. In Baldwin M, Bailey P (Eds) Tem-poral lobe epilepsy. Charles C Thomas, Springfield, IL, pp. 440–460.

Rasmussen T. (1983) Surgical treatment of complex partial seizures:results, lessons and problems. Epilepsia 24(Suppl 1):S65–S76.

Rasmussen T, Feindel W. (1991) Temporal lobectomy: 100 review caseswith major hippocampectomy. Can J Neurol Sci 18(Suppl 4):601–602.

Schramm J. (2008) Temporal lobe epilepsy surgery and the quest for opti-mal extent of resection: a review. Epilepsia 49:1296–1307.

Scoville WB, Milner B. (1957) Loss of recent memory after bilateral hip-pocampal lesions. J Neurol Neurosurg Psychiat. 20:11–21.

Smith S. (1852) The surgical treatment of epilepsy, with statistical tables,comprising all of the recorded cases of ligature of the carotid artery:and also of trephining the cranium by American surgeons. N Y J MedCollateral Sci 8:220–242 (table, pp. 236–241).

Stoll J Jr, Ajmone-Marsan C, Jasper HH. (1951) Electrophysiologicalstudies of the subcortical connections of the anterior temporal regionof the cat. J Neurophysiol 14:305–316.

Talairach J, David M, Tournoux P. (1958) L'exploration chirurgicalest�r�otaxique du lobe temporal dans l'�pilepsie temporale. Masson etCie, Paris.

Taylor DC. (1987) One hundred years of epilepsy surgery: Sir VictorHorsley’s contributions. In Engel J Jr (Ed) Surgical treatment of theepilepsies. Raven Press, New York, NY, pp. 7–11.

Temkin O. (1945, 1971) The falling sickness: a history of epilepsy fromthe Greeks to the beginning of modern neurology. Johns HopkinsUniversity Press, Baltimore, MD.

Theodore WH (Ed). (1992) Surgical treatment of epilepsy. Elsevier,Amsterdam.

Thomas HM, Cushing H. (1908) Removal of a subcortical cystic tumor ata second-stage operation without anesthesia. JAMA 50:847–856.

Uematsu S, Lesser RP, Gordon B. (1992) Localization of sensorimotorcortex: the influence of Sherrington and Cushing on the modern con-cept. Neurosurgery 30:904–913.

Van Buren JM, Ajmone-Marsan CA. (1960) A correlation of autonomicand EEG components in temporal lobe epilepsy. Arch Neurol 3:683–703.

Wada J, Rasmussen T. (1960) Intracarotid injection of sodium amytal forthe lateralization of cerebral speech dominance. Neurosurgery17:266–282.

Walker AE (Ed). (1951) A history of neurological surgery. Williams &Wilkins, Baltimore, Md.

Wieser HG, Yasergil NG. (1982) Selective amygdalohippocampectomyas a surgical treatment of mesiobasal limbic epilepsy. Surg Neurol17:445–447.

Wieser HG. (1991) Selective amygdalohippocampectomy: indicationsand follow up. Can J Neurol Sci 18:617–627.

Wyler AR, Hermann BP. (Eds) (1994) The surgical management of epi-lepsy. Butterworth-Heinemann, Boston.

Wyllie E (Ed). (1993) The treatment of epilepsy: principles and practice.Lea & Febiger, Philadelphia, PA.

Z�lch KJ. (1969) Otfrid Foerster — physician and naturalist, November9, 1873-June 15, 1941. Springer-Verlag, New York, NY.

Z�lch KJ. (1973) Otfrid Foerster. Surg Neurol 1:313–316.

151



epilepsy surgery: historical highlights 1909–2009

Documents