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Youthful Season Revisited
33, 7–10 (1997) BR970879
BRAIN AND COGNITION ARTICLE NO.
Youthful Season Revisited JUHN A. WADA Divisions of Neuroscience and Neurology, University of British Columbia Hospital, Vancouver, Canada
In March of 1993, a letter from Dr. Marilyn Jones-Gotman informed me that my paper published in January 1949 had been translated years ago into English. In late September, a copy of that translation reached me from Dr. R. A. Novelly and long past memories of nearly 50 years ago flooded back to my mind. It was the immediate postwar time; my motherland was still in the ashes of extensive destruction and under the governance of American occupational forces. The old order had crumbled, and signs of inflation, poverty, and undernutrition were everywhere. My dinner as a young duty doctor at our University Hospital was a lone piece of unskinned potato and on the rare occasion a bowl of rice glue. Thin biomedical periodicals just began to appear. Neurology and neurosurgery were in an embryonic stage with no department for these specialties at any of the universities. At Hokkaido University Hospital, within the Department of Psychiatry, a 20-bed neurology ward accommodated all of the patients with neurological disorders. Care for these neurological patients was as important as that for the psychiatric patients. Physiological, pathological, and chemical investigations were very active with a large animal colony attached to the Department. As a medical student during the war years, I recall assisting with experimental brain surgery, building amplifiers, making electrodes and paste, and developing a mile-long film on which a 2-channel EEG was recorded through a magnetic oscillograph. My fingernails were stained dark brown because of the latter. Those brain tumor patients who were recommended to the few centers where some surgeons performed brain surgery were not able to seek this relief because of horrendous traveling conditions. Therefore, diagnostic
Juhn Wada initiated the use of the intracarotid amobarbital procedure in North America. This invited essay recounts the events leading to his first use of the procedure. Address reprint requests to Juhn A. Wada, Divisions of Neuroscience and Neurology, University of British Columbia Hospital, Vancouver, British Columbia V6T 2B5, Canada. 7 0278-2626/97 $25.00 Copyright 1997 by Academic Press All rights of reproduction in any form reserved.
8
YOUTHFUL SEASON REVISITED
work-up with pneumogram, ventriculogram, and angiogram was undertaken and surgery began within the Department. The observation of dysphasia following left-sided surgery during that era was not uncommon and it was an unforgettable experience to witness a righthanded patient develop dysphasia following right-sided surgery. The fact that the first monograph on angiography of the brain in Japan, published from our Department (Kakegawa, 1943), made one very much aware that the carotid and the vertebral arteries, along with a cerebrospinal fluid pathway, are vital routes through which structure and function of the brain can be assessed. Thus, we were all exposed to a chaotic but wide spectrum of brain science. From this humble beginning, neurosurgery (1966) and then neurology (1986) evolved and attained independent departmental status. For the treatment of psychiatric illnesses, insulin shock (for schizophrenia), continuous sleep (for agitated patients), and malaria fever treatment (for general paresis) were the mainstay in addition to a relatively new convulsive treatment by either electric shock or intravenous injection of pentylenetetrazol. For the latter, a muscle relaxant was not used so that generalized convulsion was a daily scene in the treatment room. It was natural that convulsive phenomenon became the subject of our intense interest with monitoring of carotid arterial (Wada, 1948) and cerebrospinal fluid pressure (Wada, 1949) as well as EEG (Wada, 1948; Wada & Kirikae, 1949). Clinically, the beneficial effect of convulsive treatment for acute schizophrenic psychosis and manic depressive illness was well acknowledged at that time. However, severe memory loss with reduced speech output as a consequence of repeated bifrontal convulsive treatment was a topic of debate as to whether it was a necessary correlate. This was particlarly intriguing to me since biauricular (instead of bifrontal) electric shock treatment did not cause convulsion but an amnestic state without too much effect on speech output (Tominaga, 1943). Brain areas affected by maximal current passage is obviously different between bifrontal and biauricular approaches: frontal lobes in the former and basal temporal areas and the brain stem in the latter. A naive question regarding mechanisms underlying amnestic state shared by either approaches in contrast to a reduced speech output only with bifrontal approach lead me to explore a means of a lateralized shock, which might minimize the severe cognitive side effect while retaining the therapeutic effectiveness. Unitemporal approach was impractical due to discomfort and pain. However, I was surprised to realize that both unilateral (frontal–parietal) electric shock and carotid pentylenetetrazol always resulted in a generalized convulsion. This caused me to wonder about the underlying mechanism. Is it due to a transcallosal spread or bilateralization through a brain stem mechanism? This question lead me to the thought of a transient hemispheric anesthetization through a carotid route to prevent seizure bilateralization, and I obtained a supply of sodium amytal from my personal contact at the U.S. Army Station Hospital in Sapporo.
JUHN A. WADA
9
As I was planning to perform carotid amytal injection, a young Japanese boy with a partial onset seizure as a consequence of a head injury came to my attention. About 2 years earlier he had been working as a cook at a nearby U.S. Army camp. A drunken G.I. claimed to be able to shoot off the cook’s hat, and the boy ended up with a penetrating wound, scraping off the skull, dura, and underlying cortical tissue anteroposteriorly to the left of the midline and with right foot monoparesis. Soon, partial seizures began originating in the paretic leg, at times becoming secondarily generalized. He was admitted to our neurology ward with status epilepticus. Rectal chloral hydrate, a routine treatment then, had little effect. Resection of his scarred brain area was obviously an option but status had to be aborted. It was under these trying circumstances that the patient and his family agreed to my suggestion of a trial carotid amytal injection to disrupt the ongoing vicious circle. A left carotid amytal injection immediately arrested his seizure while making the patient hemiplegic and mute. These conditions dissipated after an extended period of dysphasia and the patient subsequently underwent excisional surgery. This observation not only encouraged my plan of unilateral convulsive treatment—the 1949 paper was the result of my initial work on this project during 1948—but also prompted me to consider the procedure for all brain surgery candidates. With increasing demand I became formally responsible for the brain surgical program. When I look back, it was an extraordinary undertaking since I had no formal neurological or neurosurgical training. The only practical guide was a beautiful Dandy’s illustrated book on brain surgery which my brother (Juro Wada, the heart surgeon who performed the first and the last heart transplant in Japan 25 years ago) sent me from Boston upon my request. There was little time left for me except to sleep which was often interrupted. Although I became progressively more adept in the technical aspects of brain surgery, I was not advancing my learning. After 5 years in this effort, the surgical program was well established and I asked for and was granted a sabbatical leave, hoping to bring new knowledge in neurology back to my alma mater. This was in 1954. The first year was spent at the University of Minnesota Hospital and then I moved to the Montreal Neurological Institute. During 1955 I introduced carotid amytal injection to the Institute. Despite my original intention, I ended up at the University of British Columbia in Vancouver in 1956 and Canada became my adopted country. With this the opportunity to properly document my undertakings at my alma mater was lost. Retrospectively, it was an exciting era in which to live. Brain science was not yet divided into numerous specialities and there was so much to explore and learn. I realize that the work I conducted then was in some ways heroic but also reckless. It was the youthful season of my life. Over the past decades, I believe that I have been fortunate since none of my patients had unfortunate sequela from this test. However, I have come to know of a few patients whose cerebral function has become permanently
10
YOUTHFUL SEASON REVISITED
compromised as a consequence of this test elsewhere. Certainly, development of femoral catheterization made this procedure more tolerable but nonetheless it remains invasive with definite risk. As many invasive neurodiagnostic approaches have now been replaced by innocuous neuroimaging during recent years, it is no longer unrealistic to expect noninvasive assessment of language and memory processes. Indeed, there are now many indications that this is the trend of the future. Our past efforts in this regard have been worthwhile but the degree of reliability for predicting lateralization of cerebral speech function, though statistically significant, has no place in the individual decision making process (Davis & Wada, 1974, 1977; Strauss, Wada, & Kosaka, 1985; Strauss, Gaddes, & Wada, 1987; Strauss & Wada, 1988; Kosaka, 1989). While waiting for the arrival of a noninvasive alternative, I trust that judicious and innovative use of this test will not only continue to help patients but also create new information and hypotheses on the mechanism of brain function in behavioral state as reflected in this issue. REFERENCES Davis, A. E., & Wada, J. A. 1974. Hemispheric asymmetry: Frequency analysis of visual and auditory evoked responses to non-verbal stimuli. EEG & Clinical Neurophysiology, 37, 1–9. Davis, A. E., & Wada, J. A. 1977. Lateralization of speech dominance by spectral analysis of evoked potentials. Journal of Neurology, Neurosurgery & Psychiatry, 40(1), 1–4. Kakegawa, K. 1943. Angiography of the brain. [in Japanese]. Tokyo: Nanko-Do Ltd. Kosaka, B. 1989. Non-invasive predictors of cerebral dominance. Unpublished doctoral dissertation, University of Victoria, Canada. Strauss, E., Wada, J., & Kosaka, B. 1985. Visual laterality effects and cerebral speech dominance determined by the carotid amytal test. Neuropsychologia, 23(4), 567–570. Strauss, E., Gaddes, W. H., & Wada, J. 1987. Performance on a free recall verbal dichotic listening task and cerebral dominance determined by the carotid amytal test. Neuropsychologia, 25(5), 747–753. Strauss, E., & Wada, J. 1988. Hand preference and proficiency and cerebral speech dominance determined by the carotid amytal test. Journal of Clinical and Experimental Neuropsychology, 10(2), 169–174. Tominaga, H. 1943. Non-convulsve auricular electric shock treatment [in Japanese]. SeishinShinkei-Gaku-Zasshi, 47, 473–503. Wada, J. 1949. Carotid arterial pressure during epileptic seizure [in Japanese]. Igaku to Seibutsugaku, 13, 4–7. Wada, J. 1949. Pathophysiological study of convulsive phenomena: Experimental study by simultaneos measurement of carotid arterial pressure and cerebrospinal fluid pressure in man. Folia Psychiatrica Neurologica Japonica, 4, 302–342. Wada, T. 1948. Electroencephalographic studies of changes induced by electric shock in man, Folia Psychiatrica Neurologica Japonica, 3, 1–14. Wada, J., & Kirikae, T. 1949. Interictal and ictal depth electroencephalogram in epilepsy [in Japanese]. Hokkaido Igaku Zasshi, 24, 7–13.
BRAIN AND COGNITION ARTICLE NO.
Youthful Season Revisited JUHN A. WADA Divisions of Neuroscience and Neurology, University of British Columbia Hospital, Vancouver, Canada
In March of 1993, a letter from Dr. Marilyn Jones-Gotman informed me that my paper published in January 1949 had been translated years ago into English. In late September, a copy of that translation reached me from Dr. R. A. Novelly and long past memories of nearly 50 years ago flooded back to my mind. It was the immediate postwar time; my motherland was still in the ashes of extensive destruction and under the governance of American occupational forces. The old order had crumbled, and signs of inflation, poverty, and undernutrition were everywhere. My dinner as a young duty doctor at our University Hospital was a lone piece of unskinned potato and on the rare occasion a bowl of rice glue. Thin biomedical periodicals just began to appear. Neurology and neurosurgery were in an embryonic stage with no department for these specialties at any of the universities. At Hokkaido University Hospital, within the Department of Psychiatry, a 20-bed neurology ward accommodated all of the patients with neurological disorders. Care for these neurological patients was as important as that for the psychiatric patients. Physiological, pathological, and chemical investigations were very active with a large animal colony attached to the Department. As a medical student during the war years, I recall assisting with experimental brain surgery, building amplifiers, making electrodes and paste, and developing a mile-long film on which a 2-channel EEG was recorded through a magnetic oscillograph. My fingernails were stained dark brown because of the latter. Those brain tumor patients who were recommended to the few centers where some surgeons performed brain surgery were not able to seek this relief because of horrendous traveling conditions. Therefore, diagnostic
Juhn Wada initiated the use of the intracarotid amobarbital procedure in North America. This invited essay recounts the events leading to his first use of the procedure. Address reprint requests to Juhn A. Wada, Divisions of Neuroscience and Neurology, University of British Columbia Hospital, Vancouver, British Columbia V6T 2B5, Canada. 7 0278-2626/97 $25.00 Copyright 1997 by Academic Press All rights of reproduction in any form reserved.
8
YOUTHFUL SEASON REVISITED
work-up with pneumogram, ventriculogram, and angiogram was undertaken and surgery began within the Department. The observation of dysphasia following left-sided surgery during that era was not uncommon and it was an unforgettable experience to witness a righthanded patient develop dysphasia following right-sided surgery. The fact that the first monograph on angiography of the brain in Japan, published from our Department (Kakegawa, 1943), made one very much aware that the carotid and the vertebral arteries, along with a cerebrospinal fluid pathway, are vital routes through which structure and function of the brain can be assessed. Thus, we were all exposed to a chaotic but wide spectrum of brain science. From this humble beginning, neurosurgery (1966) and then neurology (1986) evolved and attained independent departmental status. For the treatment of psychiatric illnesses, insulin shock (for schizophrenia), continuous sleep (for agitated patients), and malaria fever treatment (for general paresis) were the mainstay in addition to a relatively new convulsive treatment by either electric shock or intravenous injection of pentylenetetrazol. For the latter, a muscle relaxant was not used so that generalized convulsion was a daily scene in the treatment room. It was natural that convulsive phenomenon became the subject of our intense interest with monitoring of carotid arterial (Wada, 1948) and cerebrospinal fluid pressure (Wada, 1949) as well as EEG (Wada, 1948; Wada & Kirikae, 1949). Clinically, the beneficial effect of convulsive treatment for acute schizophrenic psychosis and manic depressive illness was well acknowledged at that time. However, severe memory loss with reduced speech output as a consequence of repeated bifrontal convulsive treatment was a topic of debate as to whether it was a necessary correlate. This was particlarly intriguing to me since biauricular (instead of bifrontal) electric shock treatment did not cause convulsion but an amnestic state without too much effect on speech output (Tominaga, 1943). Brain areas affected by maximal current passage is obviously different between bifrontal and biauricular approaches: frontal lobes in the former and basal temporal areas and the brain stem in the latter. A naive question regarding mechanisms underlying amnestic state shared by either approaches in contrast to a reduced speech output only with bifrontal approach lead me to explore a means of a lateralized shock, which might minimize the severe cognitive side effect while retaining the therapeutic effectiveness. Unitemporal approach was impractical due to discomfort and pain. However, I was surprised to realize that both unilateral (frontal–parietal) electric shock and carotid pentylenetetrazol always resulted in a generalized convulsion. This caused me to wonder about the underlying mechanism. Is it due to a transcallosal spread or bilateralization through a brain stem mechanism? This question lead me to the thought of a transient hemispheric anesthetization through a carotid route to prevent seizure bilateralization, and I obtained a supply of sodium amytal from my personal contact at the U.S. Army Station Hospital in Sapporo.
JUHN A. WADA
9
As I was planning to perform carotid amytal injection, a young Japanese boy with a partial onset seizure as a consequence of a head injury came to my attention. About 2 years earlier he had been working as a cook at a nearby U.S. Army camp. A drunken G.I. claimed to be able to shoot off the cook’s hat, and the boy ended up with a penetrating wound, scraping off the skull, dura, and underlying cortical tissue anteroposteriorly to the left of the midline and with right foot monoparesis. Soon, partial seizures began originating in the paretic leg, at times becoming secondarily generalized. He was admitted to our neurology ward with status epilepticus. Rectal chloral hydrate, a routine treatment then, had little effect. Resection of his scarred brain area was obviously an option but status had to be aborted. It was under these trying circumstances that the patient and his family agreed to my suggestion of a trial carotid amytal injection to disrupt the ongoing vicious circle. A left carotid amytal injection immediately arrested his seizure while making the patient hemiplegic and mute. These conditions dissipated after an extended period of dysphasia and the patient subsequently underwent excisional surgery. This observation not only encouraged my plan of unilateral convulsive treatment—the 1949 paper was the result of my initial work on this project during 1948—but also prompted me to consider the procedure for all brain surgery candidates. With increasing demand I became formally responsible for the brain surgical program. When I look back, it was an extraordinary undertaking since I had no formal neurological or neurosurgical training. The only practical guide was a beautiful Dandy’s illustrated book on brain surgery which my brother (Juro Wada, the heart surgeon who performed the first and the last heart transplant in Japan 25 years ago) sent me from Boston upon my request. There was little time left for me except to sleep which was often interrupted. Although I became progressively more adept in the technical aspects of brain surgery, I was not advancing my learning. After 5 years in this effort, the surgical program was well established and I asked for and was granted a sabbatical leave, hoping to bring new knowledge in neurology back to my alma mater. This was in 1954. The first year was spent at the University of Minnesota Hospital and then I moved to the Montreal Neurological Institute. During 1955 I introduced carotid amytal injection to the Institute. Despite my original intention, I ended up at the University of British Columbia in Vancouver in 1956 and Canada became my adopted country. With this the opportunity to properly document my undertakings at my alma mater was lost. Retrospectively, it was an exciting era in which to live. Brain science was not yet divided into numerous specialities and there was so much to explore and learn. I realize that the work I conducted then was in some ways heroic but also reckless. It was the youthful season of my life. Over the past decades, I believe that I have been fortunate since none of my patients had unfortunate sequela from this test. However, I have come to know of a few patients whose cerebral function has become permanently
10
YOUTHFUL SEASON REVISITED
compromised as a consequence of this test elsewhere. Certainly, development of femoral catheterization made this procedure more tolerable but nonetheless it remains invasive with definite risk. As many invasive neurodiagnostic approaches have now been replaced by innocuous neuroimaging during recent years, it is no longer unrealistic to expect noninvasive assessment of language and memory processes. Indeed, there are now many indications that this is the trend of the future. Our past efforts in this regard have been worthwhile but the degree of reliability for predicting lateralization of cerebral speech function, though statistically significant, has no place in the individual decision making process (Davis & Wada, 1974, 1977; Strauss, Wada, & Kosaka, 1985; Strauss, Gaddes, & Wada, 1987; Strauss & Wada, 1988; Kosaka, 1989). While waiting for the arrival of a noninvasive alternative, I trust that judicious and innovative use of this test will not only continue to help patients but also create new information and hypotheses on the mechanism of brain function in behavioral state as reflected in this issue. REFERENCES Davis, A. E., & Wada, J. A. 1974. Hemispheric asymmetry: Frequency analysis of visual and auditory evoked responses to non-verbal stimuli. EEG & Clinical Neurophysiology, 37, 1–9. Davis, A. E., & Wada, J. A. 1977. Lateralization of speech dominance by spectral analysis of evoked potentials. Journal of Neurology, Neurosurgery & Psychiatry, 40(1), 1–4. Kakegawa, K. 1943. Angiography of the brain. [in Japanese]. Tokyo: Nanko-Do Ltd. Kosaka, B. 1989. Non-invasive predictors of cerebral dominance. Unpublished doctoral dissertation, University of Victoria, Canada. Strauss, E., Wada, J., & Kosaka, B. 1985. Visual laterality effects and cerebral speech dominance determined by the carotid amytal test. Neuropsychologia, 23(4), 567–570. Strauss, E., Gaddes, W. H., & Wada, J. 1987. Performance on a free recall verbal dichotic listening task and cerebral dominance determined by the carotid amytal test. Neuropsychologia, 25(5), 747–753. Strauss, E., & Wada, J. 1988. Hand preference and proficiency and cerebral speech dominance determined by the carotid amytal test. Journal of Clinical and Experimental Neuropsychology, 10(2), 169–174. Tominaga, H. 1943. Non-convulsve auricular electric shock treatment [in Japanese]. SeishinShinkei-Gaku-Zasshi, 47, 473–503. Wada, J. 1949. Carotid arterial pressure during epileptic seizure [in Japanese]. Igaku to Seibutsugaku, 13, 4–7. Wada, J. 1949. Pathophysiological study of convulsive phenomena: Experimental study by simultaneos measurement of carotid arterial pressure and cerebrospinal fluid pressure in man. Folia Psychiatrica Neurologica Japonica, 4, 302–342. Wada, T. 1948. Electroencephalographic studies of changes induced by electric shock in man, Folia Psychiatrica Neurologica Japonica, 3, 1–14. Wada, J., & Kirikae, T. 1949. Interictal and ictal depth electroencephalogram in epilepsy [in Japanese]. Hokkaido Igaku Zasshi, 24, 7–13.