William P. van Wagenen and the first corpus callosotomies for epilepsy

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✓ As a trainee of Dr. Harvey Cushing, cofounder and first president of the American Association of Neurological Surgeons, and founder of a prestigious international academic fellowship, Dr. William P. van Wagenen is an important figure in the history of neurological surgery. Perhaps less well known or appreciated is his seminal role as the first neurosurgeon to attempt, study, and publish results of the corpus callosotomy procedure for patients with epilepsy, and his collaboration with Andrew J. Akelaitis, which led to the description of some features of “split-brain” patients 2 decades before similar work in the 1960s eventually resulted in a Nobel Prize for Roger W. Sperry in 1981. These contributions firmly establish William P. van Wagenen as one of the founding pioneers in the surgical treatment of patients with epilepsy.

Abbreviations used in this paper: AANS = American Association of Neurological Surgeons; SSS = superior sagittal sinus.

Abstract

✓ As a trainee of Dr. Harvey Cushing, cofounder and first president of the American Association of Neurological Surgeons, and founder of a prestigious international academic fellowship, Dr. William P. van Wagenen is an important figure in the history of neurological surgery. Perhaps less well known or appreciated is his seminal role as the first neurosurgeon to attempt, study, and publish results of the corpus callosotomy procedure for patients with epilepsy, and his collaboration with Andrew J. Akelaitis, which led to the description of some features of “split-brain” patients 2 decades before similar work in the 1960s eventually resulted in a Nobel Prize for Roger W. Sperry in 1981. These contributions firmly establish William P. van Wagenen as one of the founding pioneers in the surgical treatment of patients with epilepsy.

As the AANS celebrates its 75th anniversary, it is appropriate to reexamine the contributions of one its founders, Dr. William P. van Wagenen. Dr. van Wagenen (Fig. 1) was born on May 24, 1897, in Nunda, New York. He moved at an early age with his parents to a farm in Worcester, New York. Stimulated by the study of science in high school, he successfully competed for a New York state college scholarship that allowed him to study at Cornell University (Table 1). His medical education and surgical internship ultimately led to subspecialty training in neurological surgery with Dr. Harvey Cushing, and a prominent place in the world of academic neurosurgery.

Fig. 1.
Fig. 1.

Photograph of Dr. William P. van Wagenen (1897–1961). Reprinted with permission from the Society of Neurological Surgeons.

TABLE 1

Milestones in the life of Dr. William P. van Wagenen

Born May 24, 1897, in Nunda, New York
Spent childhood in Worcester, New York
Completed undergraduate study at Cornell University in 1918 after receiving a New York state college scholarship
Completed medical education at Harvard University in 1922
Internship at Memorial Hospital, New York City and Peter Bent Brigham Hospital, Boston
Surgical residency at Memorial Hospital, New York City
Began neurosurgical residency training under Dr. Harvey Cushing in 1925
Subsequent training at Rochester General Hospital, New York (residency) and Munich, Germany (fellowship)
Assistant professor and Chief of Neurosurgery, University of Rochester Medical Center, New York (1928 onward)
During World War II was appointed to Lawson General Hospital, Atlanta as a Major in 1942; and was appointed Chief of Neurosurgery, Cushing General Hospital, as a Lieutenant Colonel in 1944
After the war served as Chief of Neurosurgery, University of Rochester Medical Center, New York
Retired in 1954 from active neurosurgical service
Died in 1961 from acute hemorrhagic pancreatitis

Dr. van Wagenen was a major early organizer of the Harvey Cushing Society, and the idea for this new neurosurgical society grew through his correspondence with R. Glenwood Spurling.14 Together with Eustace Semmes and Temple Fay, these individuals held an organizational meeting on October 10, 1931, at the Raleigh Hotel in Washington, DC, to lay the groundwork for the founding of the new society.14 The first meeting of the Harvey Cushing Society took place the following year on May 6, 1932, with Dr. van Wagenen installed as its first president. Only in the 1960s was the name of the Harvey Cushing Society changed to the AANS.

Not as well known as his role in the founding of the Harvey Cushing Society is his introduction of the technique of corpus callosotomy for the treatment of medically refractory epilepsy. In this report, we trace this particular seminal contribution of Dr. van Wagenen and how it subsequently became important in the epilepsy surgery armamentarium, and also how the study of such “split-brain” patients led to enormous insight into the understanding of the differentiated functions of the 2 halves of the brain.

In their landmark 1940 paper, van Wagenen and Herren17 reported an important observation in a series of gliomas of the corpus callosum:

In the early part of the life history of the tumors in this series, convulsions were common. In late stages, convulsions were much rarer; if they did occur they were unilateral and usually were not accompanied by loss of consciousness. In other words, as the corpus callosum was destroyed generalized convulsive seizures became less frequent.

They adduced other supportive observations. For example, in a patient with multiple meningiomas, including a 4-cm parasagittal meningioma progressively projecting into the substance of the corpus callosum, they observed many convulsive seizures early in the course of the disease but few in the late stages. They also reported on 2 patients with a long history of epilepsy who showed decreased seizure frequency following intracranial hemorrhages—from the anterior cerebral artery in the first patient and from a sylvian branch of the middle cerebral artery in the second. From these cases, they inferred that convulsions become less frequent as association pathways are destroyed. These clinical observations set the stage for a surgical approach, that is, surgical division of the corpus callosum “in an effort to limit the spread of a convulsive wave to one half of the cerebrum.”17

Van Wagenen's Operative Technique for Corpus Callosotomy

In the procedure he developed, van Wagenen used tribromoethanol with amylene hydrate, procaine, and ether for induction of anesthesia. The patient was positioned supine with a 35° head elevation. Cutaneous incisions were made for exposure of the right frontal region and for 1 in of the left parasagittal region lateral to the SSS. Bur holes were made (Fig. 2), and the bone flap was raised. The bone flap was cut using a Gigli saw, except for cutting across the SSS posteriorly where a DeVilbiss rongeur was used. The SSS was exposed for the medial limit of the craniotomy. The dura mater was then opened widely with the pedicle along the sinus. In some cases, van Wagenen found it advantageous to ligate the anterior one third of the SSS (Fig. 3).

Fig. 2.
Fig. 2.

Illustration of the corpus callosotomy procedure showing the typical incision in the bone in relation to the coronal suture and the midline. Reprinted with permission from van Wagenen and Herren: Arch Neurol Psychiatry 44:740–759, 1940. Copyright (c) 2008, American Medical Association. All rights reserved.

Fig. 3.
Fig. 3.

Illustration of the corpus callosotomy procedure showing the brain after exposure, in which the dura is reflected across the longitudinal (superior sagittal) sinus, where it is left at closure. The dura is also brought out of the bone incision elsewhere. The longitudinal sinus has been ligated. Reprinted with permission from van Wagenen and Herren: Arch Neurol Psychiatry 44:740–759, 1940. Copyright (c) 2008, American Medical Association. All rights reserved.

The right frontal lobe was retracted away from the falx until the anterior cerebral arteries were exposed above the anterior part of the body of the corpus callosum (Fig. 3). The corpus callosum was then divided, and the lateral ventricle (usually the left) was entered. The patient's head position was elevated and then lowered to facilitate division of the genu and splenium of the corpus callosum, respectively (Fig. 4). In this way even the posterior body and splenium of the corpus callosum could be approached through a predominantly precoronal craniotomy. During this division, the third ventricle was opened. In some cases, the limb of the fornix was divided on 1 side just anterior to the foramen of Monro or bilaterally where it joins the body of the corpus callosum. Interestingly, division of the fornix was conducted in 4 of the 10 patients originally described (Table 2) without any adverse neuropsychological sequelae reported. None of the patients underwent an anterior commissurotomy. After achieving adequate hemostasis, the dura was not closed, but rather brought out of the edge of the wound at all points and sutured to the pericranium to prevent extradural fluid accumulation. The bone flap was then tied in position using silk sutures.17

Fig. 4.
Fig. 4.

Illustration of the corpus callosotomy procedure showing exposure of the corpus callosum and sagittal section of the brain, demonstrating the area of the corpus callosum cut, as well as the site of division of the fornix. Reprinted with permission from van Wagenen and Herren: Arch Neurol Psychiatry 44:740–759, 1940. Copyright (c) 2008, American Medical Association. All rights reserved.

TABLE 2

Summary characteristics of the first 10 patients of Dr. van Wagenen who underwent corpus callosotomies*

Case No.Age (yrs), SexInitial Seizure TypeOperative ProcedurePostoperative Seizure StatusOutcome
133, MGTCdivision of the CC from the genu to the anterior third of the splenium.rt-sided Jacksonian seizures w/ no LOCsatisfactory
226, MGTCstage 1: division of 5 cm of the midportion of the CC2 seizures with LOC, then seizure-freesatisfactory
stage 2: division of another 1.5 cm of the CC rostrally
stage 3: division of the CC from the rostrum to the tip of the splenium, division of the fornix
326, FGTCstage 1: division of the body & upper half of the CCseizure-freesatisfactory
stage 2: division of the entire CC & left fornix
410, MGTCdivision of the body of the CC3 episodes of “blank stares” & occasional bed wetting, no seizuresreported significant improvement in intellectual function
524, FGTCstage 1: division of the rostral half of the genu & the body of the CCgeneralized seizures related to menses, w/ & w/o LOCsatisfactory
stage 2: division of CC from genu to splenium
616, FGTCdivision of the rostral half of the genu & the body of the CCdecrease in frequency of GTC seizuresimprovement in seizure status reported by patient's mother
736, FGTC & absence seizuresdivision of the genu & body of the CC2 episodes of confusion, then rt-sided Jacksonian seizures w/o LOCsatisfactory
843, FGTC & absence seizuresdivision of rostral part of the genu & the body of the CCepisodes of absence seizures, no reported convulsionssatisfactory
925, MGTCcomplete section of the CC & division of the lt limb of the fornixGTC & a few unilateral Jacksonian seizures in the immediate postop periodunexplained post-op fever for 4 weeks, temporary hemiparesis
1014, MGTC & absence seizuresdivision of the entire CC & lt limb of the fornixJacksonian seizures without LOCsatisfactory

* CC = corpus callosum; GTC = generalized tonic-clonic; LOC = loss of consciousness.

Fluids were administered up to 4000 ml per day, and all medication (including bromides, phenobarbital, and phenytoin) was withdrawn at admission, so that the effect of the surgical intervention on seizures could be observed. If seizures were observed, phenobarbital was reinstituted and fluids were limited to 1500–2000 ml per day.

The First 10 Corpus Callosotomies

In their first 10 cases (Table 2), van Wagenen and Herren reported that the preoperative workup consisted of the usual general, neurological, and laboratory examinations to rule out brain tumors, hypoglycemia, syphilis, and other conditions as potential causes for seizures. Plain roent-genograms of the skull and electroencephalograms were routinely obtained. Photographs and motion pictures were obtained for abnormalities of gait, posture, and palsy of extremities. Gait was recorded on an electrobasogram, a device that produced gait records on film.16 In some patients, studies of gastric motility were performed. Detailed studies were performed by both a psychiatrist and a psychologist. Postoperatively, particular attention was paid to the psychiatric and psychological examinations in all patients. Attempts were also made to obtain monthly records of the patients' activity, general condition, and freedom from seizures.

The first 10 patients included 5 males and 5 females (Table 2). The median age of the patients was 25.5 years (mean 25.3 years, range 10–43 years). All patients had generalized tonic-clonic seizures, and 3 had absence seizures as well. The operations were conducted in a single stage in 7 patients, in 2 stages in 2 patients, and in 3 stages in 1 patient (Table 2). Three patients (Cases 2, 3, and 5) underwent > 1-stage surgery due to inadequate seizure control from the previous surgery (Table 2). Most patients underwent only partial division of the corpus callosum (genu or genu and body). Apparently the genu and body were empirically targeted, because the conclusion of therapeutic adequacy according to the extent of division versus safety was not clear. Outcome was described as satisfactory in 7 patients, and all patients showed some improvement in seizure control postoperatively. Postoperative neuropsychological analyses in these patients were performed by van Wagenen's colleague Andrew J. Akelaitis, a psychiatrist who studied pre- and postoperative gnosis, praxis, language, and visual functions.1–3

Subsequent Patient Series and the “Splitting” of the Brain

After van Wagenen and Herren's description of the first series of corpus callosotomies for epilepsy, more than 20 years elapsed before the next case series describing corpus callosotomies in humans was published.5,10,11 Bogen and colleagues5 described the results of a corpus callosotomy and anterior commissure division performed on February 6, 1962, for a patient with 1 to 3 generalized convulsions per week despite best medical therapy. In 1965, they reported the patient to be completely free from generalized seizures and stated that although the patient had deficits in interhemispheric integration (demonstrated under specialized testing conditions), the patient's general well-being and behavior were improved.5 In 1970, Luessenhop10 described surgical division of the corpus callosum, anterior commissure, and 1 fornix in a 32-month-old boy and in a 3-year-old boy, both with medically refractory epilepsy. Both patients showed significantly improved seizure control postoperatively. Following these results, a corpus callosotomy for epilepsy was championed during the 1970s by Donald H. Wilson, Alexander Reeves, and coworkers at Dartmouth Medical School. By 1982, at the Dartmouth conference organized by Wilson and Reeves, the use of callosotomy for epilepsy was reported from 6 more clinical centers4 and subsequently became commonplace.12,13

The exact reason or reasons for the gap in time between van Wagenen and Herren's initial description of corpus callosotomy for epilepsy and the next reported series are unclear and probably multifactorial. We contacted the AANS historian and conducted a detailed review of the transactions of the American Neurological Association (1941–1970) and did not find obvious opposition to his article. Joseph Bogen's commentary4 is particularly useful in this regard:

Although Van Wagenen and Herren seemed pleased with their results, no one else took up the operation. This may have been in part because of the onset and continuation for 5 years of World War II, or longer term outcomes may have been unfavorable and generally known although unpublished…. An important factor was the growing conviction, reaching a peak in the 1950s, that the reticular formation and its rostral targets in the thalami are of particular importance for seizure spread. As Penfield and Jasper stated in one of the great classics of epileptology: it seems reasonable to assume, therefore, that generalization of the motor seizure does not take place by spread of excitation through cortical circuits. It must spread through the more closely interrelated neuronal network of the higher brain stem, in a centrencephalic system with symmetrical functional relationships to both sides of the body.

Another important factor could have been remorse on the part of van Wagenen himself. Although this is not clearly documented, when Bogen4 contacted Frank Smith, former Chief of Neurosurgery at the University of Rochester,

asking for as much information as he could provide, his reply was quite short, including that, “Dr. Van Wagenen always was sorry about what he did to those patients”… For over a decade there were persons in Boston who referred to us as “the West Coast butchers.” Without the excellent work of Wilson and Reeves, it is quite likely that our efforts (as well as of others, like Wada) would not have been widely accepted.

Concurrent studies of animals that had undergone corpus callosotomies had demonstrated no marked changes in normal behavior, but when each hemisphere was tested separately, it was clear that the animal responded as if with 2 autonomous brains, each with separate skills.15 In the 1960s and 1970s, Roger W. Sperry, Michael S. Gazzaniga, and colleagues conducted extensive neuropsychological investigations of split-brain epileptic patients.6–9 Most patients initially seemed quite normal, but specialized tests (largely using tachistoscopic presentation of visual stimuli to 1 visual field only) showed hemispheric specialization for certain tasks such as object naming or visuospatial tasks. These studies provided evidence that the left hemisphere specializes in language processes and the right is dominant in visuospatial tasks, and that the left and right brains could function independently of each other despite a deficiency in interhemispheric integration. “Split-brain” patients thus contributed dramatically to our understanding of the functional specialization of the cerebral hemispheres, and for this work Sperry was awarded the Nobel Prize in 1981. In his Nobel lecture, Sperry did briefly cite Akelaitis' work but not that of van Wagenen. The “right brain–left brain” concept directly arising from these studies subsequently permeated popular culture beginning in the 1980s.

How do Gazzaniga and Sperry's discoveries compare with the original observations of Akelaitis? Akelaitis concluded that patients who underwent callosotomy did not have deficits of right–left integration of cerebral function and postulated that subforniceal commissural pathways must exist to explain this. Bogen4 commented that this finding may in retrospect be related to the incompleteness of most of the corpus callosotomies that van Wagenen performed. Sperry, in comparison with Akelaitis, also had the distinct advantage of employing the more sophisticated stimulus presentation method of the tachistoscope to reach the conclusion that the 2 cerebral hemispheres are specialized for certain functions. Norman Geschwind, in a comment in the 1968 transactions of the American Neurological Association,9 also speculated that neuropsychological outcome following a corpus callosotomy may be related to age of seizure onset; that is, that patients presenting with early brain damage and seizures may have bilateral cerebral dominance or alternatively are able to use ipsilateral pathways, whereas patients with later seizure onset cannot.

Conclusions

Van Wagenen's contribution, as with Wilder Penfield and others, is yet another example of how developments in neurosurgery led directly to developments in neuroscience. Though rarely recognized, primacy in performing corpus callosotomy for epilepsy should be ascribed to van Wagenen and primacy in describing the associated neuropsychological sequelae should go to Akelaitis, even if superseded by the later results of Gazzaniga and Sperry.

Van Wagenen's academic contributions continue to serve the field of neurosurgery (Table 3). He cofounded the Harvey Cushing Society; established the most prestigious academic neurosurgical fellowship for study abroad; outlined the origin of meningiomas from arachnoid cells; conceived of the idea of a brain tumor registry; introduced corpus callosotomy for epilepsy; and indirectly enabled the later study of split-brain patients. On the 75th anniversary of the founding of the Harvey Cushing Society, van Wagenen's legacy lives on in the success of his society and his fellowship, and corpus callosotomy still plays an important role in the treatment of selected patients with medically refractory generalized epilepsy.13,16

TABLE 3

Some significant contributions of Dr. William P. van Wagenen

Outlined the origin of meningiomas from arachnoidal cells (with John Rhodes)
Reported the accuracy of air studies in localizing brain lesions
Devised surgical approaches to the choroid plexus, 3rd ventricle, and corpus callosum
Conceived of the idea of a brain tumor registry
Reported on the association of Pantopaque myelography with chemical meningitis
Introduced corpus callosotomy for the treatment of medically refractory epilepsy
Cofounded the Harvey Cushing Society (later renamed the AANS)
Founded a fellowship for neurosurgical graduates to study abroad (van Wagenen Fellowship)

References

Article Information

Address correspondence to: Devin K. Binder, M.D., Ph.D., Department of Neurological Surgery, University of California, Irvine, 101 The City Drive South, Building 56, Suite 400, ZOT 5397, Orange, California 92868. email: dbinder@uci.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photograph of Dr. William P. van Wagenen (1897–1961). Reprinted with permission from the Society of Neurological Surgeons.

  • View in gallery

    Illustration of the corpus callosotomy procedure showing the typical incision in the bone in relation to the coronal suture and the midline. Reprinted with permission from van Wagenen and Herren: Arch Neurol Psychiatry 44:740–759, 1940. Copyright (c) 2008, American Medical Association. All rights reserved.

  • View in gallery

    Illustration of the corpus callosotomy procedure showing the brain after exposure, in which the dura is reflected across the longitudinal (superior sagittal) sinus, where it is left at closure. The dura is also brought out of the bone incision elsewhere. The longitudinal sinus has been ligated. Reprinted with permission from van Wagenen and Herren: Arch Neurol Psychiatry 44:740–759, 1940. Copyright (c) 2008, American Medical Association. All rights reserved.

  • View in gallery

    Illustration of the corpus callosotomy procedure showing exposure of the corpus callosum and sagittal section of the brain, demonstrating the area of the corpus callosum cut, as well as the site of division of the fornix. Reprinted with permission from van Wagenen and Herren: Arch Neurol Psychiatry 44:740–759, 1940. Copyright (c) 2008, American Medical Association. All rights reserved.

References

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2

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Akelaitis AJ: A study of gnosis, praxis, and language following section of the corpus callosum and anterior commissure. J Neurosurg 1:941021944

4

Bogen JEThe neurosurgeon's interest in the corpus callosum. Greenblatt SHDagi TFEpstein JH: A History of Neurosurgery Park Ridge, ILAmerican Association of Neurological Surgeons1997. 489498

5

Bogen JEFisher EDVogel PJ: Cerebral commissurotomy: a second case report. JAMA 194:132813291965

6

Gazzaniga MSBogen JESperry RW: Dyspraxia following division of the cerebral commissures. Arch Neurol 16:6066121967

7

Gazzaniga MSBogen JESperry RW: Observations on visual perception after disconnexion of the cerebral hemispheres in man. Brain 88:2212361965

8

Gazzaniga MSBogen JESperry RW: Some functional effects of sectioning the cerebral commissures in man. Proc Natl Acad Sci U S A 48:176517691962

9

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10

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12

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13

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16

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17

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