"The art is long and the life short": the letters of Wilder Penfield and Harvey Cushing.

Wilder Penfield and Harvey Cushing created legacies to neurosurgery, both in terms of those they trained and in their philosophical approach to the field. Their biographies provide only brief comments on their relationship without any thorough examination of their personal correspondence. In this article the Penfield-Cushing relationship is examined through an analysis of their unpublished personal letters. The Penfield-Cushing correspondence is a treasure for neurosurgery: it provides remarkable insight into the embryonic period of the discipline and into the relationship of two of the most influential figures in modern neurosurgery.

A history of brain imaging technology in neurosurgery.

In the closing decades of the nineteenth century, diagnosis of cerebral lesions was based on the clinical examination, and often the localization and operative approaches were based on observation of seizures. The attribution of certain symptoms and signs to dysfunction arising at an identifiable focal point in the brain was the basis for clinicopathologic correlation and rational treatment. As beautiful as brain anatomy was and as skillful as clinical examination could be, there was no means to produce images of a living patient that could be used to diagnose and treat that same patient. On November 8, 1895, all of this changed with Wilhelm Röntgen's discovery of X-rays. This article aims to elucidate seminal points in the history of medical imaging as applied to the brain that have had a major impact on neurosurgery.

Herbert Henri Jasper (1906-1999): an appreciation.

Herbert Henri Jasper dedicated his life to studies of the brain in relation to the mind and behavior. He pioneered the application of the electroencephalogram (EEG) for the study of the electrical activity of the brain and used this technique in studies of consciousness, learning and particularly the examination of epileptic discharge. He utilized microelectrode recordings from single brain cells and combined this technique with microchemical analyses to study cortical and sub-cortical activity. He added substantially to our understanding of brainstem and thalamic reticular formations in conditions of consciousness and in relation to petit-mal epilepsy. His work with Wilder Penfield and associates over a quarter century elucidated the mechanisms of epilepsy and added to our understanding of the functional anatomy of the human brain. An enthusiastic and able organizer, Herbert Jasper was responsible for many international conferences on brain science and worked tirelessly to develop international collaboration among investigators of the nervous system, being one of the founders of the International Brain Research Organization and the Society for Neuroscience. His prodigious contributions in basic and clinical research will be recognized by the world community of brain science for years to come.

Entorhinal cortex in temporal lobe epilepsy: a quantitative MRI study.

BACKGROUND: The entorhinal cortex (EC) is a distinct anatomic and functional region of the anterior parahippocampal gyrus, which plays a role in seizure generation and propagation in temporal lobe epilepsy (TLE). In tissue resected from TLE patients, cell loss in the EC has been described. OBJECTIVES: To develop a standardized protocol for identifying the anatomic boundaries of the EC using high-resolution MRI and to examine morphologic changes of the EC in TLE. METHODS: We performed T1-weighted MRIs in 20 patients (7 males) with TLE (mean age 34 years) and 18 normal controls (mean age 26 years). Eleven patients had a left and 9 a right epileptic focus as defined by history, video-EEG, and surgical outcome. The volumes of the EC, the hippocampus, and the amygdala were measured using a standardized MRI protocol. Analysis of variance (ANOVA) was used to examine the effect of seizure focus lateralization and hemisphere on these volumes. An asymmetry ratio [A (%) = 100 x (R-L)/(R+L)/2] was also compared between groups using ANOVA. RESULTS: In normal controls the volume of the right EC was 1,247 +/- 127 mm3 (mean +/- standard deviation), and that of the left EC was 1,215 +/- 135 mm3 (p > 0.05). We found a bilateral reduction in the volume of the EC in TLE patients compared with controls (p < 0.05). Examination of the asymmetry ratios showed that the reduction in volume of the EC was greater ipsilateral to the epileptic focus (p < 0.05). The volumes of the hippocampus and the amygdala were smaller on the side of the focus in TLE patients compared with controls (p < 0.05). CONCLUSIONS: With a standardized protocol for the quantitative assessment of the EC, patients with unilateral TLE show bilateral reduction in the volume of the EC. However, this reduction is more severe ipsilateral to the epileptic focus.

Clinical patterns of patients with temporal lobe epilepsy and pure amygdalar atrophy.

PURPOSE: MRI volumetric measurements (MRIvol) have been proven reliable in determining mesial temporal atrophy in patients with TLE. We attempted to correlate the clinical features with different patterns of hippocampal formation (HF) and amygdala (AM) atrophy in patients with TLE without foreign tissue lesion. METHODS: We studied 65 patients with refractory TLE. They were divided into five groups according to MRIvol results: pure AM atrophy (n = 11, 10 unilateral and one bilateral), unilateral HF atrophy (n = 16), bilateral HF atrophy (n = 12), unilateral AM + HF atrophy (n = 13), and patients with normal volumes of AM and HF (n = 13). MRIvol of AM and HF were performed by using a protocol previously described by Watson et al. (Neurology 1992;42:1743-50). RESULTS: Patients with AM atrophy had later onset of seizures compared with those with unilateral HF atrophy (p < 0.01). History of febrile convulsions (p < 0.0001) and frequent secondarily generalized tonic-clonic seizures (GTCSs) were more often found in patients with HF atrophy compared with those with pure AM atrophy and those with normal volumes (p = 0.04). Prolonged postictal confusion was more often found with AM atrophy (p = 0.05). Memory impairment was more severe in patients with HF atrophy than in those with AM atrophy only or in those with normal volumes (p = 0.03). There were no significant differences among the five groups in the following parameters: age, duration of epilepsy, seizure frequency, and presence and type of aura. CONCLUSIONS: Prolonged postictal confusion appeared to be related to AM atrophy, in keeping with previous clinical observations. These patients also had a lower incidence of early febrile convulsions, older age at epilepsy onset, lower frequency of secondary GTCS, and lesser memory dysfunction compared with patients with hippocampal atrophy.

The role of auditory cortex in retention of rhythmic patterns as studied in patients with temporal lobe removals including Heschl's gyrus.

This experiment examined the participation of the auditory cortex of the temporal lobe in the perception and retention of rhythmic patterns. Four patient groups were tested on a paradigm contrasting reproduction of auditory and visual rhythms: those with right or left anterior temporal lobe removals which included Heschl's gyrus (HG), the region of primary auditory cortex (RT-A and LT-A); and patients with right or left anterior temporal lobe removals which did not include HG (RT-a and LT-a). Estimation of lesion extent in HG using an MRI-based probabilistic map indicated that, in the majority of subjects, the lesion was confined to the anterior secondary auditory cortex located on the anterior-lateral extent of HG. On the rhythm reproduction task, RT-A patients were impaired in retention of auditory but not visual rhythms, particularly when accurate reproduction of stimulus durations was required. In contrast, LT-A patients as well as both RT-a and LT-a patients were relatively unimpaired on this task. None of the patient groups was impaired in the ability to make an adequate motor response. Further, they were unimpaired when using a dichotomous response mode, indicating that they were able to adequately differentiate the stimulus durations and, when given an alternative method of encoding, to retain them. Taken together, these results point to a specific role for the right anterior secondary auditory cortex in the retention of a precise analogue representation of auditory tonal patterns.

Arthur Roland Elvidge (1899-1985): contributions to the diagnosis of brain tumors and cerebrovascular disease.

The contributions of Arthur Elvidge (1899-1985), Wilder Penfield's first neurosurgical recruit, to the development of neurosurgery have been relatively neglected, although his work in brain tumors extended the previous work of Percival Bailey and Harvey Cushing. He published rigorous correlations of clinical and histological information and formulated a revised, modern nosology for neuroepithelial tumors, including a modern histological definition of glioblastoma multiforme. Well ahead of his time, he believed that glioblastoma was not strictly localized and was the first to comment that the tumor frequently showed "satellitosis." He was the first neurosurgeon in North America to use angiography as a radiographic aid in the diagnosis of cerebrovascular disease. Having studied with Egas Moniz, he was the first to detail the use of angiographic examinations specifically for demonstrating cerebrovascular disorders, believing that it would make possible routine surgery of the intracranial blood vessels. Seeking to visualize all phases of angiography, he was the impetus behind the design of one of the first semi-automatic film changers. Elvidge and Egas Moniz made the first observations on thrombosis of the carotid vessels independently of each other. Elvidge elucidated the significance of embolic stroke and commented on the ischemic sequelae of subarachnoid hemorrhage. Besides his contributions to neurosurgery, he codiscovered the mode of transmission of poliomyelitis. Elvidge's soft-spoken manner, his dry wit and candor, mastery of the understatement, love of exotic travel, and consummate dedication to neurosurgery made him a favorite of patients, neurosurgery residents, nurses, and other hospital staff. His accomplishments and example as teacher and physician have become part of neurosurgery's growing legacy.

Neurosurgery at the Montreal Neurological Institute and McGill University Hospitals.

For the past 60 years, the Montreal Neurological Institute and Hospital and three associated McGill University teaching hospitals have provided a broad course of instruction in neurosurgery and the related neurosciences. This integrated program offers a wealth of experience in adult and pediatric neurosurgery, based on a total of 140 beds, covering a full range of general and subspecialty neurosurgery. The institute, recognized for many years as a world center for epilepsy surgery, has traditional strengths in the treatment of brain tumors and cerebrovascular and spinal disorders; it has been at the cutting edge of brain imaging in all modalities applied to neurosurgical diagnosis and cerebral localization, including three-dimensional monitoring in the operating room. New approaches to stereotactic procedures have been developed in conjunction with imaging technology, including functional neurosurgery and the versatile McGill double rotation method for radiosurgery with a linear accelerator. Experience in managing trauma, pediatric cases, and general neurosurgical problems is gained at the Montreal General Hospital, the Montreal Children's Hospital, and the Jewish General Hospital. Well-established research units, including burgeoning groups in neurogenetics, molecular neurobiology, and neural regeneration, provide a wide variety of academic opportunities to provide trainees with a sound basis for coping with the rapidly advancing field of neurosurgery.

Domus Willisi: a neuro-architectural tour.

Fifteen sites in England today can be identified with Dr. Thomas Willis, the Oxford physician and anatomist, who was the founder of neurology. Four of these were domiciles; Beam Hall, where Willis and his colleagues met to study the brain and nerves, can be claimed as the first Neurological Institute. The last dwelling place of Willis is Westminster Abbey, where in 1961 his memorial stone was renewed by neurologists and neurosurgeons. Part of this original stone marks the new Brain Imaging Centre at the Montreal Neurological Institute, where the name of Thomas Willis shares a place in the Hall of Neurological Fame.

George A. Savoy, visionary benefactor of Canadians with epilepsy, and the history of the Savoy Foundation for Epilepsy.

George A. Savoy was born in Cohoes, New York, in 1873. He left the U.S.A. in 1921 to manage the Canadian branch of a large manufacturer of ledgers and looseleaf registers. This company was asked to supply Professor Jasper's laboratory with rolls of plain unlined paper and it was George Savoy who later developed fanfolded and lined EEG paper, which was first used at the Montreal Neurological Institute. He also had personal contacts with Wilder Penfield concerning their mutual interest in the needs of patients with epilepsy. He was a successful industrialist involved with several charitable organizations funding programmes for people with epilepsy. He was opposed to the sectarianism then prevalent in Quebec, which was unfamiliar to him, and in reaction built his own institution, Dieppe House, a home for people with epilepsy, later renamed <>. It was to operate without regard to race, language or religion. In 1971, his son Harold and other generous donors decided to create a foundation to support research in epilepsy. The Foyer Savoy was sold in 1988 and the proceeds used to increase the endowment of the foundation. His grandson George M. Savoy is the current president. The fourth generation is also represented by Caroline Savoy, daughter of the president, who joined the board of directors in 1992. The foundation will distribute from $300,000 to $400,000 yearly to researchers from many different countries working in the field of epilepsy in universities and hospitals throughout Canada.

Neurosurgeon as innovator: William V. Cone (1897-1959).

Neurosurgeons are well known for being productive researchers and innovators. Few, however, have possessed the prolific ingenuity of William Cone. In 1934, he and William Penfield were cofounders of the Montreal Neurological Institute where, until 1959, he filled the twin roles of neurosurgeon-in-chief and neuropathologist. Because he did not find writing easy, many of his technical inventions and refinements remained unpublished. His numerous innovations included the extensive use of twist-drill technique for biopsy, drainage for subdural hematoma and cerebral abscess, and ventriculography. In the mid-1940's, he developed power tools driven by nitrogen that led to the modern, universally used air-driven tool systems. He had a special interest in the treatment of spinal dysfunction, for which he invented the Cone-Barton skull-traction tongs along with the Cone spinal operating table. He also devised operative procedures for vertebral fracture-dislocation and craniospinal anomalies. For the maintenance of muscle tone in the paralyzed bladder, he constructed a tidal drainage system. He introduced and popularized ventriculoperitoneal shunting techniques and carried out some of the earliest experimental trails to treat brain infections with sulphonamide and antibiotic drugs. He designed his own set of surgical suction devices, bone rongeurs, and a personal suction "air-conditioning" system for each surgeon. He had a keen early interest in intracranial tumors, and also demonstrated on monkeys how subdural mass lesions caused pupillary dilation and mesial temporal lobe damage due to cerebral compression. His work for the military during World War II on effects of altitude on brain pressure remained classified for many years. The first clipping and excision of an intracranial aneurysm is attributed to Cone. Although Penfield was known as "the Chief," Cone was referred to as "the Boss." His fervent dedication to provide total care to his patients was expressed in round-the-clock vigils; he did not separate "nursing" from "surgical" care. Ultimately, Cone's driving passion for perfection led in part to his tragic death. His accomplishments, inventions, and his example as teacher and physician have become part of neurosurgery's collective legacy.

Gelastic seizures and hypothalamic hamartomas: evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment.

We retrospectively studied 12 consecutive patients with gelastic seizures and hypothalamic hamartomas who, because of intractable epilepsy, underwent chronic intracranial EEG monitoring or epilepsy surgery. All patients had medically refractory seizures that included laughter as an ictal behavior (gelastic seizures). The hypothalamic hamartomas were identified with neuroimaging studies (12 of 12) and by pathologic verification (four of 12). Associated clinical features included behavioral disorders (n = 5), developmental delay (n = 4), and precocious puberty (n = 2). Interictal extracranial EEG predominantly showed bi-hemispheric epileptiform changes suggesting a secondary generalized epileptic disorder. Intracranial EEG recordings, performed in eight patients, indicated the apparent focal onset of seizure activity (anterior temporal lobe [n = 7] and frontal lobe [n = 1]). None of the seven patients who underwent a focal cortical resection, however, experienced a significant reduction in seizure tendency. An anterior corpus callosotomy, performed in two patients with symptomatic generalized epilepsy, resulted in a worthwhile reduction in drop attacks. Results of this study may modify the surgical strategies in patients with gelastic seizures and hypothalamic hamartomas.

Psychosocial consequences of postoperative seizure relief.

To address the question of whether complete seizure relief has a positive effect on psychosocial functioning in patients with temporal lobe epilepsy, a follow-up study was conducted at the Montreal Neurological Institute. The approach was one of "before-after" study, with focus on the successfully operated patients, those in whom complete seizure relief was obtained. The Washington Psychosocial Seizure Inventory, specifically developed and validated for use with epilepsy patients, was used for psychosocial assessments. Of 30 surgically treated patients screened for the study, 15 gained complete relief from seizures. At 1-year postoperative follow-up, they showed reductions in their problems scores on all but one of eight psychosocial scales; the average reduction ranged from 24% in Vocational Adjustment to 60% in Adjustment to Seizures. In the areas of Emotional Adjustment and Interpersonal Adjustment reductions were 37 and 48%, respectively. Among the component items, improvement was greatest in ability to concentrate and make decisions, confidence in interpersonal skills, ability to express personal opinions, and perception by others. No appreciable changes occurred in the 15 patients who did not gain complete relief of seizures; indeed, on six of the eight scales they showed a modest increase in their problem scores. This study provides evidence that complete relief from seizures leads to appreciable improvements in psychosocial well-being, manifest as early as 1-year postoperatively, in young adult patients.

Alkalosis monitored by 31P NMR in a human glioma cell line exposed to the anti-tumor drug 1,3-bis(2-chloroethyl)-1-nitrosourea.

A transient alkalosis of similar magnitude to that observed in vivo has been observed using 31P NMR and 2-deoxy-D-glucose-6-phosphate as a pH marker in a human glioma cell line, SKI-1, with demonstrated sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea. At an effective dose of 5 +/- 1 x 10 micrograms/ml, an increase of 0.13 +/- 0.05 pH units was observed within 4 +/- 1 x 10 min of introducing the drug into the perfusion chamber. Although the in vitro response is of a time course much faster than that in vivo, these results suggest that this immediate pH change could be an indicator of the cytotoxic action of the drug.

Origins of Wilder Penfield's surgical technique. The role of the "Cushing ritual" and influences from the European experience.

Wilder Penfield left two great legacies: the development of successful surgical treatment of epilepsy and the establishment with his colleagues of the Montreal Neurological Institute as a world-renowned medical center, "dedicated to relief of pain and suffering and to the study of neurology." That Harvey Cushing's surgical ritual (which stemmed from the painstaking operative methods of Halsted) played a paramount role in the origins of Penfield's surgical technique is revealed by a set of notes and drawings by Penfield during repeated visits in the 1920's to Cushing's clinic at the Peter Bent Brigham Hospital. Penfield's intellectual approach to the nervous system was derived from his studies with Sherrington. Holmes, Cajal, and Hortega. His eclectic surgical style emerged from his familiarity with the operating techniques of Halsted, Dandy, Horsely, Sargent, Cushing, Frazier, Whipple, Leriche, and Foerster. Penfield's debt to these teachers is documented in his memoirs and in an unpublished report on European neurosurgery which he sent ot the Rockefeller Foundation in 1928.

The Montreal Neurological Institute.

In this centenary year of Wilder Penfield, his contribution to the creation of the Montreal Neurological Institute is reviewed. In the early 1930's, a confluence of favorable circumstances at McGill University and the Royal Victoria Hospital, Montreal, made it possible for Wilder Penfield, with his partner William Cone, to realize his dream of a combined neurological hospital and research institute. Endowed by the Rockefeller Foundation and with initial and ongoing support from community and governments, the Montreal Neurological Institute has continued its exponential growth over the past half-century as a world center for the study and treatment of disorders of the brain and nerves.

Development of surgical therapy of epilepsy at the Montreal Neurological Institute.

Wilder Penfield's development of surgical methods for treating focal cerebral seizures, beginning with his early work in Montreal in 1928, is reviewed. The reliance on seizure pattern and focal brain pathology was enormously enhanced by the advent of EEG and direct electrical recording from the cortex during surgery. The recognition in the early 1950's of mesial temporal structures in the pathogenesis of temporal lobe epilepsy with automatism lead to more rational and successful surgical treatment. Positron emission tomography and especially magnetic resonance imaging have recently added to the essential diagnostic information of focal epilepsy provided by EEG.