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Common characteristics of epilepsy and schizophrenia: clinical observation and depth electrode studies
Epilepsy & Behavior 6 (2005) 633–645 www.elsevier.com/locate/yebeh
Classics in Epilepsy and Behavior: 1961
Common characteristics of epilepsy and schizophrenia: clinical observation and depth electrode studies q,qq,qqq Robert G. Heath, M.D., D.M.Sc Department of Psychiatry and Neurology, Tulane University, New Orleans, LA, USA
The syndrome of epilepsy is so varied that it cannot be adequately defined. By current usage, epilepsy is actually a symptom, or group of symptoms, rather than a disease. The cause has been established for the epilepsy in many instances. There are, however, a great number of patients with epilepsy for which there is no established etiology. These patients are often referred to as the idiopathic group. Despite the apparent confusion, epilepsy is a term extensively used in clinical medicine, and clinicians understand its meaning. The group of epileptics referred to in this study have no established etiology. (Such patients, as a result of advances in medical research, ultimately may prove to have some obscure metabolic or other abnormality.) This possibility will be discussed. The most consistent symptom of epilepsy is an alteration of consciousness. Reports on epilepsy appearing in the literature since 1888 [1] describe psychological symptoms, in association with the altered consciousness, as a predominant feature in some patients. The psychological symptoms are many and diverse. They can closely resemble the picture seen in the functional psychoses [2,3]; at other times, alterations of the sensorium can predominate [4]. Gibbs, Gibbs, and Lennox in 1937 [5] proposed the diagnostic category of ‘‘psychomotor epilepsy’’ for the patient group presenting a clinical picture in which psychic symptoms were prominent. This terminology has been quite universally accepted.
q
Reproduced by permission of APA, from Am. J. Psych. 1962; 11, 1013–26. qq Read at the 117th annual meeting of The American Psychiatric Association, Chicago, Ill., May 8–12, 1961. qqq Supported by a grant-in-aid from The Commonwealth Fund. The author wishes to acknowledge the technical assistance of Charles Fontana and Owen Foss. 1525-5050/$ - see front matter Ó 2005 Published by Elsevier Inc. doi:10.1016/j.yebeh.2005.03.009
A high incidence of abnormal behavior between the seizures is frequent in the ‘‘psychomotor epileptic’’ group. The symptoms presented by many patients in this group may be the same as those presented by patients diagnosed as schizophrenic. Gibbs, Gibbs, and Lennox [5] described the electroencephalographic patterns associated with these clinical symptoms, noting that abnormal electrical activity is characteristically recorded from the temporal leads. For this reason, the terminology ‘‘temporal lobe epilepsy’’ is used interchangeably with ‘‘psychomotor epilepsy.’’ Even though some of the symptoms presented by the epileptic patients are the same as those seen in schizophrenic patients, schizophrenia has its own characteristic syndrome. The constellation of symptoms in schizophrenia is such that trained psychiatrists agree on diagnosis in the majority of cases. The EEG of the schizophrenic subject is characteristically normal. Some electroencephalographers [6–10], however, have noted that there is a slightly increased incidence of electroencephalographic abnormality in the schizophrenic group, as compared to the non-schizophrenic group. This is not a feature unique to the disease, schizophrenia, however; it occurs with similar incidence in some other disease states [6]. In a small minority of patients, the trained clinician encounters problems in differential diagnosis between the syndromes of schizophrenia and psychomotor epilepsy. This confusion usually occurs when the interictal behavioral abnormalities of the epileptic are more prolonged, i.e., less circumscribed or episodic, and when EEG abnormalities are present. Some authors [11,12] have suggested that this group of patients be considered a separate diagnostic entity. With the advent in 1950 [13] of depth recording from precise regions of the brain of man over prolonged time periods, recording abnormalities were obtained from
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specific deep nuclear masses, but not from the conventional scalp EEG recordings, in schizophrenic patients during periods of psychotic behavior. This evidence suggested to some that schizophrenia and epilepsy might be manifestations of one disease; other investigators postulated that this is evidence of a continuum between the two diseases. We have carried out depth recording studies in epileptics, schizophrenics, and control subjects (falling into neither diagnostic category) since 1950. Pertinent data from these studies, basic for this discussion as to whether or not the syndromes are related, will be presented.
Fig. 1. Anatomical structures from which recordings were studied. Note: In many subjects, multiple electrodes have been implanted in a given subcortical region.
1. Material and method Forty-eight patients have been included in the Tulane study (a total of 57 operative procedures were performed since some patients were reoperated).1 Forty of the 48 patients were psychotic with 36 of the 40 being undeniably schizophrenic by all accepted criteria. Six were epileptic: 2 of the 6 were afflicted with seizures only; 4 displayed marked behavioral symptoms in addition to seizures. Of the total 48 patients, 6 did not fall into either diagnostic category and, therefore, served as control subjects. These control subjects had other diseases; for example, intractable pain, parkinsonism, narcolepsy. They did not show recording abnormalities and, therefore, will not be considered in this presentation. Our stereotaxic method for implantation of electrodes in the brain of man has been described [13–15]. Electrodes are implanted with precision (within 2 millimeters of target point) into predetermined brain regions. The electrodes are of a design which we have demonstrated to be the most effective in recording potential changes with alterations of behavior.2 To determine the most effective electrode, we implanted electrodes of one design into one-half of a catÕs brain and electrodes of another type, to be compared, into the exact sites in the other hemisphere. The animal was given chemical compounds, including sedatives, Metrazol, and psychotomimetic drugs, which markedly altered levels of psychological awareness. Recording changes in association with the altered behavior were much more clearly revealed in the recordings obtained with the silver ball electrode. With our stereotaxic method, the electrodes remain accurately in place for periods up to two years. They are affixed by means of special plugs in the tre1
Total number of patients and operative procedures as of 4/30/61. The electrode consists of 4 strands of #40 gauge silver-plated copper wire with a one millimeter silver ball fused to the terminal end. The insulation, poly-vinyl-chloride, completely encompasses the copper wire and is affixed to the wire and silver ball with ‘‘General Cement’’ (coil coating cement). 2
phine holes, brought under the scalp for some distance, thence through the skin, and soldered to 15- or 25-place plugs. Recordings obtained in the first two weeks after implantation are difficult to interpret; they are contaminated with artifacts resulting from trauma of operation and the residual effects of anesthesia. After the initial two-week period, however, when electrodes do not move, the recordings correlate with the fluctuating clinical state of the patient. The specific brain regions from which we have recorded in our various patient groups are listed in Fig. 1. The maximal number of electrodes we have implanted in one patient is 39: 25 in the deep regions and 14 over the cortex (Fig. 2). In our earlier studies, the Grass electroencephalographic 8-channel machine (Model III-D) was used; recordings were later made by synchronizing two 8channel machines. Recently, as we have implanted more electrodes, one 16-channel (Model IV-B) and two 8-channel (Model III-D) Grass machines have been synchronized so as to record simultaneously from 32 channels. In all 36 schizophrenic patients recordings were obtained during psychotic episodes; in the last 14 of the schizophrenic patients, recordings were obtained during periods of complete remission of psychotic symptoms and during periods of severely disturbed behavior. In 4 patients with seizures and psychotic behavior, recordings were obtained both during clinical states (i.e., seizures and episodes of psychotic behavior) and during asymptomatic periods. In 6 of the epileptic patients, recordings were obtained throughout spontaneous clinical seizures; four spontaneous classical psychomotor seizures were recorded in one patient. Recordings were obtained during two spontaneous grand mal seizures in another patient. Abstracted histories of four patients whose sample recordings are included in this presentation to illustrate the data follow.3 3 Detailed histories of patients are available upon request. Space limitation prevents elaboration here.
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Fig. 2. X-ray of Patient B-5.
Patient B-5 (A.V.), white female. Diagnosis: Psychomotor and grand mal epilepsy. Date of birth: 9/26/27. Date of operation: 12/21/60. Onset of present illness at 11 with 10–15-minute black-out spells consisting of hyperactivity and beating head against wall; preoperative spells: ‘‘a scream, a fall, then running,’’—usual duration 5 minutes, but infrequently lasting up to 112 hours; sometimes exhibitionistic in spells. Three turbulent marriages with two pregnancies and one child. PhysicianÕs description of spells: adversive seizures with initial loss of consciousness followed by drawing of head to right, vocalization, clonic convulsions followed by confused, fighting state. Nov. 1960 mental status: chronic brain syndrome of unknown cause in individual of borderline defective intelligence; April 1960 right angiogram ‘‘normal’’; October 1960 EEG (and on repeated studies)—‘‘nearly continuously discharging center in right anterior temporal lobe with some overactivity in the left anterior temporal lobe.’’ All physical and laboratory examinations have otherwise consistently been within normal limits. Patient B-4 (A.D.), white male. Diagnosis: paranoid schizophrenia. Date of birth: 7/25/30. Dates of operations: 11/10/60, 5/17/61. Family history—psychosis in mother and possibly in father. Education—3 years college; hospitalizations: 1951–53 and from late 1954 to present; previous treat-
ments included a variety of chemical compounds and extensive courses of EST; EEG 9/30/60: ‘‘borderline with mild inconsistent asymmetries and a tendency for increased activity in the left temporal and anterior temporal areas,’’ although many other EEGs have been reported as ‘‘normal.’’ All other physical, x-ray, and laboratory work-ups have been within normal limits; mental status examination 9/26/60: schizophrenic reaction, paranoid type with deterioration. Patient A-26 (A.G.), colored male. Diagnosis: epilepsy. Date of birth: May, 1927 (day of month unknown). Date of operation: 10/31/57. Family history—mother psychotic. Convulsions and enuresis as a child. Delayed puberty to 19 at which time he graduated from high school high in the class of which he was president. One year Navy service with constant trouble, but honorable discharge, following which he held a job for 7 years in the Post Office Department. First seizure 1951 with ‘‘spasm, stiffness, crying, and confusion followed by depression.’’ Committed 1952–57 in mental hospital. All laboratory, x-ray, and physical examinations were within normal limits except the EEG of 5/16/57 which showed paroxysmal mixed delta–theta activity to which 500 mg Chloralose added nothing but sleep pattern. Mental status 10/29/57: ‘‘episodic periods of gross dyscontrol, occasional grand mal seizures, and episodes of confused behavior.’’
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Patient A-24 (H.G.), colored male. Diagnosis: seizures and psychotic behavior. Date of birth: 1/18/27. Date of operation: 11/29/56. Family history—brother paranoid schizophrenic. Treatment for lues 1943 with consistently negative spinal fluid examinations and no evidence at any time of neurosyphilis; otherwise, P.M.H. negative. Eleven months (1944–45) in U.S. Air Force. First ‘‘spell’’ and hospital admission in 1944; grand mal seizures have been described on numerous occasions since then up to 15 in a single day; also, a variety of psychomotor seizures beginning 1954 with subsequent amnesia. Seizure incidence significantly reduced with dilantin–phenobarbital treatment. Prolonged episodes of bizarre behavior since late 1955, leading to second mental hospital admission in 1956 at which time work-up, including a P.E.G., was within normal limits. Two weeks after discharge, he was readmitted with frequent seizures and interictal behavior described as hallucinatory and virtually unmanageable. Discharged after 5 weeks with diagnosis of psychosis with psychomotor and grand mal epilepsy; again readmitted 1956 after a series of seizures. Physical examination revealed otosclerosis and a minor stammer in speaking, but otherwise ‘‘normal.’’ Routine laboratory and x-ray studies were within normal limits. Conclusion of mental status examination in October 1956: epilepsy with episodic psychotic behavior.
2. Results The principal features of our recordings from each of the groups studied (schizophrenic, epileptic, psychotic– epileptic, and control subjects without brain disease) will be presented. Schizophrenic Group. The recordings during remission were essentially the same as those obtained from the control group. When the schizophrenic patients were in periods of active psychosis, recordings were characterized by the appearance of spiking and slow wave activity, primarily in the septal region and, to a lesser extent, in the hippocampus and amygdala. The spiking and slow wave activity spread to appear in other structures only when it was of very high amplitude in the recordings from the septal region and hippocampus (Figs. 3, 4). In schizophrenic patients displaying symptoms of retardation, i.e., catatonia and hebephrenia, there was more slow wave activity and the spiking was less sharp, better described as ‘‘sharp waves.’’ The spike was much sharper in schizophrenic patients displaying predominantly paranoid symptomatology. These recordings have been described in detail [13,15,16]. Epileptic Group. Recordings were obtained during spontaneous seizures from onset through the post-ictal phase on numerous occasions from 6 patients; psychomotor seizures were recorded in all 6 patients; record-
Fig. 3. EEG recording (cortical and subcortical) from patient B-4 during period of remission.
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Fig. 4. EEG recording (cortical and subcortical) from patient B-4 during period of psychosis.
ings were obtained during grand mal seizures in 1 patient. Recordings during Metrazol-induced seizures were obtained in 2 subjects and, on several occasions, recordings during seizures induced with electrical stimulation to deep regions (in most instances, the rostral hippocampus) were obtained. Only data from the spontaneous psychomotor and grand mal seizures will be presented. The most striking feature of the recordings from epileptic patients between seizures was their variability. This variability can be demonstrated adequately only by reviewing entire records. Cut-outs of recordings from Patient B-5 only partially demonstrate the important features (Figs. 5–9). During interictal periods, most of the epileptic subjects presented paroxysms of abnormal activity which appeared in one area and then another, but which always began in parts of the olfactory brain (hippocampus, amygdala, and septal region). During the recording in Fig. 5, no gross behavioral abnormalities were apparent. Patient B-5 was showing poor contact with reality during the time that the recording in Fig. 6 was made. She expressed the idea that she was communicating with her long deceased father and asked if her thoughts were being recorded by the ‘‘machine.’’ A focal spike appeared in the septal region. Leads only one millimeter removed did not reflect this. The abnormal activity occasionally was reflected in recordings from the cortex and less frequently in the conventional scalp leads. When the recordings in Fig. 7 were obtained Patient B-5 did not present the gross clinical manifesta-
tion of a clinical seizure despite the paroxysmal burst of seizure-like activity. Recordings, however, were obtained during spontaneous psychomotor seizures on four occasions in this patient; on three occasions, the paroxysmal seizural activity began in the left posterior hippocampus, spread to the left anterior hippocampus, amygdala, and septal region, and then to all parts of the brain; on one occasion, the seizure began in the right hippocampus, spread to the septal region, and then took over in all leads. Figs. 8 and 9 are cut-outs from the recordings of Patient B-5 during one of her psychomotor seizures. This seizure had a duration of approximately 2 to 3 minutes, during which time there was a loss of contact; the patient had a fixed, staring gaze and did not reply to questions nor respond to sensory stimulation. She appeared not to recognize persons or surroundings. There were rhythmical movements of her hands, maximal on the left. This activity was characterized by forced grasping of the right hand by the left. Simultaneously, a slight turning of the head to the left occurred. The seizure disappeared gradually after 3 to 5 minutes. Fig. 8 shows the development of the seizure originating in the left posterior hippocampus. The seizural discharges spread to the amygdala and the lowest left anterior hippocampal lead, then to the middle left anterior hippocampal lead, and finally to the uppermost of the three left anterior hippocampal leads. At approximately the same time, a series of monophasic spike discharges occurred in the middle left
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Fig. 5. EEG recordings (cortical and subcortical) from patient B-5 demonstrating characteristic activity between seizures (inter-ictal).
Fig. 6. EEG recordings (cortical and subcortical) from patient B-5 showing focal spike in septal region.
anterior septal lead. This was followed in 10 seconds by seizural-type activity consisting principally of monophasic and diaphasic spike discharges and delta activity into the right hippocampal lead and the cortex. Fig. 9 is a cut-out of the recording at the time the clinical seizure was most evident. As the generalized seizure began to
diminish, 14- to 15-second spindling-type activity appeared in the upper two electrodes of the right amygdala with the uppermost electrode showing the highest amplitude wave. Some seizural activity persisted in the left amygdala and left anterior and posterior hippocampal leads for 20 more seconds. For some time post-
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Fig. 7. EEG recordings (cortical, subcortical, and scalp) from patient B-5.
Fig. 8. EEG recording (cortical and subcortical) from patient B-5 showing development of seizure originating in left posterior hippocampus.
ictally, there was high amplitude delta activity. Following this seizure, the delta activity remained focal and confined to the uppermost anterior septal lead.
Figs. 10 and 11 are sample recordings obtained from a patient (A-24) with grand mal epilepsy. This patient, in contrast to Patient B-5, entered into phases of complete
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Fig. 9. EEG recordings (cortical and subcortical) from patient B-5 at time the clinical seizure was most evident.
remission with recordings being normal for days or weeks. A recording obtained during a period of remission is shown in Fig. 10; a recording obtained at the onset of a seizure is shown in Fig. 11. The paroxysmal seizural activity began in the amygdala and hippocampus. The patient, during this period, was disturbed, out of contact with reality, and displayed characteristic psychotic symptoms. The paroxysmal activity next spread to include the septal region. This activity remained limited to the amygdala, hippocampus, and septal region for a matter of 50 to 80 seconds, and then appeared also in all other deep and cortical structures. When the activity became generalized, the patient displayed the typical clonic and tonic movements characteristic of the grand mal seizure. The post-ictal recordings showed generalized slow wave activity in association with the clinical picture of stupor.4 Essentially, these same principal features were seen in recordings from other patients during grand mal seizures. Epileptic–Psychotic Group. Four patients with grand mal epilepsy who, in addition, suffered interictal periods of severely disorganized psychotic behavior with delusions, hallucinations, and agitation as principal symptoms, were included in this study. The periods of decompensated, psychotic behavior of these patients lasted from several days to 3 months. In two patients, A-24 and A-26, presenting similar behavior during these 4 At the time of presentation, a 16 mm. film of the EEG recording was shown. The film is available for loan.
periods, we obtained similar recordings characterized by sharp spiking with slow wave activity which was striking in the degree of its abnormality. During such periods when the behavior of the patients was psychotic, these abnormalities only occasionally appeared on the cortical leads and less often on the scalp leads (when employed). Several patients in the series had electrodes implanted into the reticular activating system. In no instance were we able to correlate electrical changes from these leads with behavior (see Figs. 12 and 13). A significant observation, in our opinion, was the striking difference in recordings of this patient group during interictal psychosis compared to those of the severely decompensated psychotic schizophrenic group, even though the clinical picture during these periods was nearly indistinguishable. In contrast to the relatively infrequent spiking (appearing every 5 to 20 seconds, or less often), often associated with some slow activity in the septal region, hippocampus, and amygdala in the schizophrenic patients, the epileptic–psychotic patients showed dramatic spiking of higher amplitude appearing more frequently along with much more pronounced slow wave activity. The principal feature these two patient groups had in common was the appearance of the primary recording abnormality in the same anatomical regions. The abnormality, however, appeared more frequently in other structures as well in the epileptic– psychotic group; i.e., it was recorded from the cortical leads and, less often, from the scalp leads, usually in the temporal region. It is important to emphasize, how-
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Fig. 10. EEG recording (cortical and subcortical) from patient A-24 during period of remission.
Fig. 11. EEG recordings (cortical and subcortical) from patient A-24 at time of onset of seizure.
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Fig. 12. EEG recordings (cortical and subcortical) from patient A-26 during period of remission.
ever, that cortical and scalp recordings never appropriately reflect the storm of abnormal activity present in the specific subcortical structures. Similar findings in the epileptic–psychotic group have recently been reported by Sherwood [17].
Several authors have suggested the possibility of demonstrating the abnormal subcortical electrical activity on routine scalp recordings by administering chemical compounds that, seemingly, activate electroencephalographic abnormalities [18–23]. In our studies, this
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Fig. 13. EEG recordings (cortical and subcortical) from patient A-26 during period of psychosis.
promising lead has not been substantiated. We have employed alpha chloralose, 6, 7, 8, 9-tetrahydro-5-azeptetrazole (Metrazol), and thiopental sodium (Pentothal) as activators, but have not been able to demonstrate that the specific abnormalities appearing on the subcortical recordings are demonstrable on scalp recordings. These activating drugs do induce a higher incidence of abnormalities on scalp recordings, but this occurs in the nonpsychotic, non-epileptic control group in essentially the
same incidence as in the schizophrenic group. The details of this rather extensive study are being prepared for publication (27).5 5
The three compounds were administered on two separate occasions to each of 77 patients of a carefully screened population of schizophrenics on the Tulane Research Unit of the East Louisiana State Hospital, Jackson, and to each of 25 prisoner volunteers of the Louisiana State Penitentiary at Angola who had been carefully screened.
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3. Discussion The principal issues with which we are concerned are first, does the utilization of the special techniques described contribute to our understanding of the nature of the two disorders, schizophrenia and epilepsy, and, secondly, is there a relationship between the two disorders? It is worth restating that epilepsy is a symptom, not a separate disease entity. Within the epilepsies, however, there is a syndrome with relatively well demarcated symptoms and a brain dysrhythmia for which no definite etiology or consistent pathology has been established. It is this syndrome, sometimes called ‘‘idiopathic epilepsy,’’ with which we are concerned here. The diagnosis of schizophrenia is dependent upon clinical symptoms and the course of the disease. Symptoms of psychosis can result from a wide variety of pathological processes. In schizophrenia, however, no definite etiology and pathology have been established; patients analogously could be characterized as ‘‘idiopathic psychotic.’’ The absence of a definite etiology and pathology are the principal bases for confusion in boundaries between these processes. The reasons advanced for relating these two diseases, namely the presence of psychotic symptoms in association with seizures in the epileptics and the occasional appearance of temporal lobe spikes6 in patients diagnosed as schizophrenics, are not valid since these criteria are not specific. The depth recordings of the seizural group are quite different from those of the schizophrenic group. This is so even during periods when the epileptic is displaying clinical features indistinguishable from the schizophrenic. The anatomical regions from which the abnormal recordings are obtained are the same for the two groups. In the seizural group, however, the abnormalities are more pronounced in the hippocampus and amygdala and less pronounced in the septal region. Recording abnormalities in the schizophrenic patients are predominantly in the septal region. There is no reason, in the authorÕs opinion, for concluding that the two processes, schizophrenia and epilepsy, represent a single disease because of involvement of the same anatomical structures. It is our experience that similar symptoms appear whenever these anatomical structures are implicated, regardless of the nature of the pathological process; for example, psychotic behavioral symptoms and altered electrical activity also are present with tumors,
6 Although it is necessary to refer to the sites of abnormal electrical discharge, the author wishes to caution against considering any part of the brain as an isolated center. This would be a gross, unjustified oversimplification. At this stage, it is of some value to relate, where possible, clinical phenomena with electrical activity in specific sites. We, however, must remain cognizant that the brain is so richly interconnected that unusual activity in any one part affects all other parts.
degenerative processes, infections, and toxic agents affecting these structures [25,26]. We have conducted studies with chemical compounds which affect the septal region, hippocampus, and amygdala in profound and differing ways. These studies have contributed to our understanding of the schizophrenia– epilepsy relationship. The effects of Metrazol on the brain are widespread. When Metrazol induces seizures, however, a rhythmical discharge of the type recorded spontaneously in the epileptics is recorded first from these same olfactory structures. When the administration of d-LSD produces psychotic symptoms, the clinical symptoms are associated with abnormal electrical discharges which are most marked in recordings from these same anatomical structures. The recording abnormalities resemble those seen in schizophrenic patients (with some distinguishing differences—15). The administration of Metrazol is not associated with the appearance of psychotic symptoms. The administration of d-LSD does not induce seizures. Thus, although these two compounds affect the same anatomical structures, they apparently do so differently and different symptoms result. Studies designed to clarify the nature of the biochemical lesion in these two endogenous processes, schizophrenia and epilepsy, have progressed. Evidence is accumulating to suggest a rather precise and specific biochemical abnormality basic to the processes. The administration of taraxein, a product obtained from the serum of schizophrenic patients, produced recording abnormalities and psychotic behavior resembling that seen in schizophrenic patients. Increasing the dosage of taraxein does not induce seizures; this suggests that the cells of the brain are affected in a specific manner by these chemical compounds. Our depth recording and biochemical studies suggest that there may be an independent disease, schizophrenia, and an independent disease, epilepsy, and that there may be a highly specific biochemical lesion present for each disease. It seems, on the basis of studies conducted thus far, that the chemical lesions affect cells of a common anatomical locale, but affect them in different ways.
4. Summary Data presented, gathered by special techniques, add some clarification to the nature of the seemingly similar and related disease processes of schizophrenia and epilepsy. These data indicate that schizophrenia and epilepsy probably are different entities.
References [1] Jackson, J. H.: Brain, 11: 179, 1888–1889. [2] Gibbs, F. A.: J. Nerv. Ment. Dis., 113: 522, 1951.
Classics in Epilepsy and Behavior / Epilepsy & Behavior 6 (2005) 633–645 [3] Ervin, F., Epstein, A. W., and King, H. E.: A.M.A. Arch. Neurol. Psychiat., 74: 488, 1955. [4] Magnus, O.: Folia Psychiat. Neerl., 57: 264, 1954. [5] Gibbs, F. A., Gibbs, E. L., and Lennox, W. G.: Brain, 60: 377, 1937. [6] Hill, D.: Folia Psychiat. Neerl., 51: 95, 1948. [7] Pond, D. A., Rey, J. H., and Hill, D.: Electroenceph. Clin. Neurophysiol., 2: 111, 1950. [8] Rodin, E. A., DeJong, R. M., Waggoner, R. W., and Bagchi, B. K.: A.M.A. Arch. Neurol. Psychiat., 77: 449, 1957. [9] Ostow, M.: Trans. Amer. Neurol. Ass., 79: 81, May 1952. [10] Heath, R. G.: Studies in Schizophrenia. Cambridge: Harvard University Press, 1954. [11] Hoch, P. H.: Am. J. Psychiat., 99: 507, 1943. [12] Monroe, R. R.: A.M.A. Arch. Gen. Psychiat., 1: 205, 1959. [13] Heath, R. G., et al.: Studies in Schizophrenia. Cambridge: Harvard University Press, 1954. [14] Becker, H. C., Founds, W. L., Peacock, S., Heath, R. G., Llewellyn, R. C., and Mickle, W. A.: Electroenceph. Clin. Neurophysiol., 9: 533, 1957.
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[15] Heath, R. G., and Mickle, W. A.: Electrical Studies on the Unanesthetized Brain. New York: Paul B. Hoeber, 1960. [16] Heath, R. G.: Confin. Neurol., 18: 305, 1958. [17] Sherwood, S. L.: Electrographic Depth Recordings from the Brains of Psychotics. Presented at New York Academy of Sciences meeting, New York City, April 1961. [18] Monroe, R. R., Jacobson, G., and Ervin, F.: A.M.A. Arch. Neurol. Psychiat., 76: 536, 1956. [19] Bickford, R. G.: Electroenceph. Neurophysiol., 3: 378, 1951. [20] Leiberman, D. M.: J. Neurol. Neurosurg. Psychiat., 16: 30, 1953. [21] Smith, K., Ulett, G. A., and Johnson, L. C.: A.M.A. Arch. Neurol. Psychiat., 77: 528, 1957. [22] Bickford, R. G., Sem-Jacobsen, C. W., White, P. T., and Daly, D.: Electroenceph. Neurophysiol., 4: 275, 1952. [23] Goldman, D.: Ann. N.Y. Acad. Sci., 80: 687, 1959. [24] Heath, R. G.: In preparation. [25] Heath, R. G.: Studies in Schizophrenia. Cambridge: Harvard University Press, 1954. [26] Lennox, M., and Brody, B. S.: J. Nerv. Ment. Dis., 104: 237, 1946.
Classics in Epilepsy and Behavior: 1961
Common characteristics of epilepsy and schizophrenia: clinical observation and depth electrode studies q,qq,qqq Robert G. Heath, M.D., D.M.Sc Department of Psychiatry and Neurology, Tulane University, New Orleans, LA, USA
The syndrome of epilepsy is so varied that it cannot be adequately defined. By current usage, epilepsy is actually a symptom, or group of symptoms, rather than a disease. The cause has been established for the epilepsy in many instances. There are, however, a great number of patients with epilepsy for which there is no established etiology. These patients are often referred to as the idiopathic group. Despite the apparent confusion, epilepsy is a term extensively used in clinical medicine, and clinicians understand its meaning. The group of epileptics referred to in this study have no established etiology. (Such patients, as a result of advances in medical research, ultimately may prove to have some obscure metabolic or other abnormality.) This possibility will be discussed. The most consistent symptom of epilepsy is an alteration of consciousness. Reports on epilepsy appearing in the literature since 1888 [1] describe psychological symptoms, in association with the altered consciousness, as a predominant feature in some patients. The psychological symptoms are many and diverse. They can closely resemble the picture seen in the functional psychoses [2,3]; at other times, alterations of the sensorium can predominate [4]. Gibbs, Gibbs, and Lennox in 1937 [5] proposed the diagnostic category of ‘‘psychomotor epilepsy’’ for the patient group presenting a clinical picture in which psychic symptoms were prominent. This terminology has been quite universally accepted.
q
Reproduced by permission of APA, from Am. J. Psych. 1962; 11, 1013–26. qq Read at the 117th annual meeting of The American Psychiatric Association, Chicago, Ill., May 8–12, 1961. qqq Supported by a grant-in-aid from The Commonwealth Fund. The author wishes to acknowledge the technical assistance of Charles Fontana and Owen Foss. 1525-5050/$ - see front matter Ó 2005 Published by Elsevier Inc. doi:10.1016/j.yebeh.2005.03.009
A high incidence of abnormal behavior between the seizures is frequent in the ‘‘psychomotor epileptic’’ group. The symptoms presented by many patients in this group may be the same as those presented by patients diagnosed as schizophrenic. Gibbs, Gibbs, and Lennox [5] described the electroencephalographic patterns associated with these clinical symptoms, noting that abnormal electrical activity is characteristically recorded from the temporal leads. For this reason, the terminology ‘‘temporal lobe epilepsy’’ is used interchangeably with ‘‘psychomotor epilepsy.’’ Even though some of the symptoms presented by the epileptic patients are the same as those seen in schizophrenic patients, schizophrenia has its own characteristic syndrome. The constellation of symptoms in schizophrenia is such that trained psychiatrists agree on diagnosis in the majority of cases. The EEG of the schizophrenic subject is characteristically normal. Some electroencephalographers [6–10], however, have noted that there is a slightly increased incidence of electroencephalographic abnormality in the schizophrenic group, as compared to the non-schizophrenic group. This is not a feature unique to the disease, schizophrenia, however; it occurs with similar incidence in some other disease states [6]. In a small minority of patients, the trained clinician encounters problems in differential diagnosis between the syndromes of schizophrenia and psychomotor epilepsy. This confusion usually occurs when the interictal behavioral abnormalities of the epileptic are more prolonged, i.e., less circumscribed or episodic, and when EEG abnormalities are present. Some authors [11,12] have suggested that this group of patients be considered a separate diagnostic entity. With the advent in 1950 [13] of depth recording from precise regions of the brain of man over prolonged time periods, recording abnormalities were obtained from
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specific deep nuclear masses, but not from the conventional scalp EEG recordings, in schizophrenic patients during periods of psychotic behavior. This evidence suggested to some that schizophrenia and epilepsy might be manifestations of one disease; other investigators postulated that this is evidence of a continuum between the two diseases. We have carried out depth recording studies in epileptics, schizophrenics, and control subjects (falling into neither diagnostic category) since 1950. Pertinent data from these studies, basic for this discussion as to whether or not the syndromes are related, will be presented.
Fig. 1. Anatomical structures from which recordings were studied. Note: In many subjects, multiple electrodes have been implanted in a given subcortical region.
1. Material and method Forty-eight patients have been included in the Tulane study (a total of 57 operative procedures were performed since some patients were reoperated).1 Forty of the 48 patients were psychotic with 36 of the 40 being undeniably schizophrenic by all accepted criteria. Six were epileptic: 2 of the 6 were afflicted with seizures only; 4 displayed marked behavioral symptoms in addition to seizures. Of the total 48 patients, 6 did not fall into either diagnostic category and, therefore, served as control subjects. These control subjects had other diseases; for example, intractable pain, parkinsonism, narcolepsy. They did not show recording abnormalities and, therefore, will not be considered in this presentation. Our stereotaxic method for implantation of electrodes in the brain of man has been described [13–15]. Electrodes are implanted with precision (within 2 millimeters of target point) into predetermined brain regions. The electrodes are of a design which we have demonstrated to be the most effective in recording potential changes with alterations of behavior.2 To determine the most effective electrode, we implanted electrodes of one design into one-half of a catÕs brain and electrodes of another type, to be compared, into the exact sites in the other hemisphere. The animal was given chemical compounds, including sedatives, Metrazol, and psychotomimetic drugs, which markedly altered levels of psychological awareness. Recording changes in association with the altered behavior were much more clearly revealed in the recordings obtained with the silver ball electrode. With our stereotaxic method, the electrodes remain accurately in place for periods up to two years. They are affixed by means of special plugs in the tre1
Total number of patients and operative procedures as of 4/30/61. The electrode consists of 4 strands of #40 gauge silver-plated copper wire with a one millimeter silver ball fused to the terminal end. The insulation, poly-vinyl-chloride, completely encompasses the copper wire and is affixed to the wire and silver ball with ‘‘General Cement’’ (coil coating cement). 2
phine holes, brought under the scalp for some distance, thence through the skin, and soldered to 15- or 25-place plugs. Recordings obtained in the first two weeks after implantation are difficult to interpret; they are contaminated with artifacts resulting from trauma of operation and the residual effects of anesthesia. After the initial two-week period, however, when electrodes do not move, the recordings correlate with the fluctuating clinical state of the patient. The specific brain regions from which we have recorded in our various patient groups are listed in Fig. 1. The maximal number of electrodes we have implanted in one patient is 39: 25 in the deep regions and 14 over the cortex (Fig. 2). In our earlier studies, the Grass electroencephalographic 8-channel machine (Model III-D) was used; recordings were later made by synchronizing two 8channel machines. Recently, as we have implanted more electrodes, one 16-channel (Model IV-B) and two 8-channel (Model III-D) Grass machines have been synchronized so as to record simultaneously from 32 channels. In all 36 schizophrenic patients recordings were obtained during psychotic episodes; in the last 14 of the schizophrenic patients, recordings were obtained during periods of complete remission of psychotic symptoms and during periods of severely disturbed behavior. In 4 patients with seizures and psychotic behavior, recordings were obtained both during clinical states (i.e., seizures and episodes of psychotic behavior) and during asymptomatic periods. In 6 of the epileptic patients, recordings were obtained throughout spontaneous clinical seizures; four spontaneous classical psychomotor seizures were recorded in one patient. Recordings were obtained during two spontaneous grand mal seizures in another patient. Abstracted histories of four patients whose sample recordings are included in this presentation to illustrate the data follow.3 3 Detailed histories of patients are available upon request. Space limitation prevents elaboration here.
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Fig. 2. X-ray of Patient B-5.
Patient B-5 (A.V.), white female. Diagnosis: Psychomotor and grand mal epilepsy. Date of birth: 9/26/27. Date of operation: 12/21/60. Onset of present illness at 11 with 10–15-minute black-out spells consisting of hyperactivity and beating head against wall; preoperative spells: ‘‘a scream, a fall, then running,’’—usual duration 5 minutes, but infrequently lasting up to 112 hours; sometimes exhibitionistic in spells. Three turbulent marriages with two pregnancies and one child. PhysicianÕs description of spells: adversive seizures with initial loss of consciousness followed by drawing of head to right, vocalization, clonic convulsions followed by confused, fighting state. Nov. 1960 mental status: chronic brain syndrome of unknown cause in individual of borderline defective intelligence; April 1960 right angiogram ‘‘normal’’; October 1960 EEG (and on repeated studies)—‘‘nearly continuously discharging center in right anterior temporal lobe with some overactivity in the left anterior temporal lobe.’’ All physical and laboratory examinations have otherwise consistently been within normal limits. Patient B-4 (A.D.), white male. Diagnosis: paranoid schizophrenia. Date of birth: 7/25/30. Dates of operations: 11/10/60, 5/17/61. Family history—psychosis in mother and possibly in father. Education—3 years college; hospitalizations: 1951–53 and from late 1954 to present; previous treat-
ments included a variety of chemical compounds and extensive courses of EST; EEG 9/30/60: ‘‘borderline with mild inconsistent asymmetries and a tendency for increased activity in the left temporal and anterior temporal areas,’’ although many other EEGs have been reported as ‘‘normal.’’ All other physical, x-ray, and laboratory work-ups have been within normal limits; mental status examination 9/26/60: schizophrenic reaction, paranoid type with deterioration. Patient A-26 (A.G.), colored male. Diagnosis: epilepsy. Date of birth: May, 1927 (day of month unknown). Date of operation: 10/31/57. Family history—mother psychotic. Convulsions and enuresis as a child. Delayed puberty to 19 at which time he graduated from high school high in the class of which he was president. One year Navy service with constant trouble, but honorable discharge, following which he held a job for 7 years in the Post Office Department. First seizure 1951 with ‘‘spasm, stiffness, crying, and confusion followed by depression.’’ Committed 1952–57 in mental hospital. All laboratory, x-ray, and physical examinations were within normal limits except the EEG of 5/16/57 which showed paroxysmal mixed delta–theta activity to which 500 mg Chloralose added nothing but sleep pattern. Mental status 10/29/57: ‘‘episodic periods of gross dyscontrol, occasional grand mal seizures, and episodes of confused behavior.’’
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Patient A-24 (H.G.), colored male. Diagnosis: seizures and psychotic behavior. Date of birth: 1/18/27. Date of operation: 11/29/56. Family history—brother paranoid schizophrenic. Treatment for lues 1943 with consistently negative spinal fluid examinations and no evidence at any time of neurosyphilis; otherwise, P.M.H. negative. Eleven months (1944–45) in U.S. Air Force. First ‘‘spell’’ and hospital admission in 1944; grand mal seizures have been described on numerous occasions since then up to 15 in a single day; also, a variety of psychomotor seizures beginning 1954 with subsequent amnesia. Seizure incidence significantly reduced with dilantin–phenobarbital treatment. Prolonged episodes of bizarre behavior since late 1955, leading to second mental hospital admission in 1956 at which time work-up, including a P.E.G., was within normal limits. Two weeks after discharge, he was readmitted with frequent seizures and interictal behavior described as hallucinatory and virtually unmanageable. Discharged after 5 weeks with diagnosis of psychosis with psychomotor and grand mal epilepsy; again readmitted 1956 after a series of seizures. Physical examination revealed otosclerosis and a minor stammer in speaking, but otherwise ‘‘normal.’’ Routine laboratory and x-ray studies were within normal limits. Conclusion of mental status examination in October 1956: epilepsy with episodic psychotic behavior.
2. Results The principal features of our recordings from each of the groups studied (schizophrenic, epileptic, psychotic– epileptic, and control subjects without brain disease) will be presented. Schizophrenic Group. The recordings during remission were essentially the same as those obtained from the control group. When the schizophrenic patients were in periods of active psychosis, recordings were characterized by the appearance of spiking and slow wave activity, primarily in the septal region and, to a lesser extent, in the hippocampus and amygdala. The spiking and slow wave activity spread to appear in other structures only when it was of very high amplitude in the recordings from the septal region and hippocampus (Figs. 3, 4). In schizophrenic patients displaying symptoms of retardation, i.e., catatonia and hebephrenia, there was more slow wave activity and the spiking was less sharp, better described as ‘‘sharp waves.’’ The spike was much sharper in schizophrenic patients displaying predominantly paranoid symptomatology. These recordings have been described in detail [13,15,16]. Epileptic Group. Recordings were obtained during spontaneous seizures from onset through the post-ictal phase on numerous occasions from 6 patients; psychomotor seizures were recorded in all 6 patients; record-
Fig. 3. EEG recording (cortical and subcortical) from patient B-4 during period of remission.
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Fig. 4. EEG recording (cortical and subcortical) from patient B-4 during period of psychosis.
ings were obtained during grand mal seizures in 1 patient. Recordings during Metrazol-induced seizures were obtained in 2 subjects and, on several occasions, recordings during seizures induced with electrical stimulation to deep regions (in most instances, the rostral hippocampus) were obtained. Only data from the spontaneous psychomotor and grand mal seizures will be presented. The most striking feature of the recordings from epileptic patients between seizures was their variability. This variability can be demonstrated adequately only by reviewing entire records. Cut-outs of recordings from Patient B-5 only partially demonstrate the important features (Figs. 5–9). During interictal periods, most of the epileptic subjects presented paroxysms of abnormal activity which appeared in one area and then another, but which always began in parts of the olfactory brain (hippocampus, amygdala, and septal region). During the recording in Fig. 5, no gross behavioral abnormalities were apparent. Patient B-5 was showing poor contact with reality during the time that the recording in Fig. 6 was made. She expressed the idea that she was communicating with her long deceased father and asked if her thoughts were being recorded by the ‘‘machine.’’ A focal spike appeared in the septal region. Leads only one millimeter removed did not reflect this. The abnormal activity occasionally was reflected in recordings from the cortex and less frequently in the conventional scalp leads. When the recordings in Fig. 7 were obtained Patient B-5 did not present the gross clinical manifesta-
tion of a clinical seizure despite the paroxysmal burst of seizure-like activity. Recordings, however, were obtained during spontaneous psychomotor seizures on four occasions in this patient; on three occasions, the paroxysmal seizural activity began in the left posterior hippocampus, spread to the left anterior hippocampus, amygdala, and septal region, and then to all parts of the brain; on one occasion, the seizure began in the right hippocampus, spread to the septal region, and then took over in all leads. Figs. 8 and 9 are cut-outs from the recordings of Patient B-5 during one of her psychomotor seizures. This seizure had a duration of approximately 2 to 3 minutes, during which time there was a loss of contact; the patient had a fixed, staring gaze and did not reply to questions nor respond to sensory stimulation. She appeared not to recognize persons or surroundings. There were rhythmical movements of her hands, maximal on the left. This activity was characterized by forced grasping of the right hand by the left. Simultaneously, a slight turning of the head to the left occurred. The seizure disappeared gradually after 3 to 5 minutes. Fig. 8 shows the development of the seizure originating in the left posterior hippocampus. The seizural discharges spread to the amygdala and the lowest left anterior hippocampal lead, then to the middle left anterior hippocampal lead, and finally to the uppermost of the three left anterior hippocampal leads. At approximately the same time, a series of monophasic spike discharges occurred in the middle left
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Fig. 5. EEG recordings (cortical and subcortical) from patient B-5 demonstrating characteristic activity between seizures (inter-ictal).
Fig. 6. EEG recordings (cortical and subcortical) from patient B-5 showing focal spike in septal region.
anterior septal lead. This was followed in 10 seconds by seizural-type activity consisting principally of monophasic and diaphasic spike discharges and delta activity into the right hippocampal lead and the cortex. Fig. 9 is a cut-out of the recording at the time the clinical seizure was most evident. As the generalized seizure began to
diminish, 14- to 15-second spindling-type activity appeared in the upper two electrodes of the right amygdala with the uppermost electrode showing the highest amplitude wave. Some seizural activity persisted in the left amygdala and left anterior and posterior hippocampal leads for 20 more seconds. For some time post-
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Fig. 7. EEG recordings (cortical, subcortical, and scalp) from patient B-5.
Fig. 8. EEG recording (cortical and subcortical) from patient B-5 showing development of seizure originating in left posterior hippocampus.
ictally, there was high amplitude delta activity. Following this seizure, the delta activity remained focal and confined to the uppermost anterior septal lead.
Figs. 10 and 11 are sample recordings obtained from a patient (A-24) with grand mal epilepsy. This patient, in contrast to Patient B-5, entered into phases of complete
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Fig. 9. EEG recordings (cortical and subcortical) from patient B-5 at time the clinical seizure was most evident.
remission with recordings being normal for days or weeks. A recording obtained during a period of remission is shown in Fig. 10; a recording obtained at the onset of a seizure is shown in Fig. 11. The paroxysmal seizural activity began in the amygdala and hippocampus. The patient, during this period, was disturbed, out of contact with reality, and displayed characteristic psychotic symptoms. The paroxysmal activity next spread to include the septal region. This activity remained limited to the amygdala, hippocampus, and septal region for a matter of 50 to 80 seconds, and then appeared also in all other deep and cortical structures. When the activity became generalized, the patient displayed the typical clonic and tonic movements characteristic of the grand mal seizure. The post-ictal recordings showed generalized slow wave activity in association with the clinical picture of stupor.4 Essentially, these same principal features were seen in recordings from other patients during grand mal seizures. Epileptic–Psychotic Group. Four patients with grand mal epilepsy who, in addition, suffered interictal periods of severely disorganized psychotic behavior with delusions, hallucinations, and agitation as principal symptoms, were included in this study. The periods of decompensated, psychotic behavior of these patients lasted from several days to 3 months. In two patients, A-24 and A-26, presenting similar behavior during these 4 At the time of presentation, a 16 mm. film of the EEG recording was shown. The film is available for loan.
periods, we obtained similar recordings characterized by sharp spiking with slow wave activity which was striking in the degree of its abnormality. During such periods when the behavior of the patients was psychotic, these abnormalities only occasionally appeared on the cortical leads and less often on the scalp leads (when employed). Several patients in the series had electrodes implanted into the reticular activating system. In no instance were we able to correlate electrical changes from these leads with behavior (see Figs. 12 and 13). A significant observation, in our opinion, was the striking difference in recordings of this patient group during interictal psychosis compared to those of the severely decompensated psychotic schizophrenic group, even though the clinical picture during these periods was nearly indistinguishable. In contrast to the relatively infrequent spiking (appearing every 5 to 20 seconds, or less often), often associated with some slow activity in the septal region, hippocampus, and amygdala in the schizophrenic patients, the epileptic–psychotic patients showed dramatic spiking of higher amplitude appearing more frequently along with much more pronounced slow wave activity. The principal feature these two patient groups had in common was the appearance of the primary recording abnormality in the same anatomical regions. The abnormality, however, appeared more frequently in other structures as well in the epileptic– psychotic group; i.e., it was recorded from the cortical leads and, less often, from the scalp leads, usually in the temporal region. It is important to emphasize, how-
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Fig. 10. EEG recording (cortical and subcortical) from patient A-24 during period of remission.
Fig. 11. EEG recordings (cortical and subcortical) from patient A-24 at time of onset of seizure.
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Fig. 12. EEG recordings (cortical and subcortical) from patient A-26 during period of remission.
ever, that cortical and scalp recordings never appropriately reflect the storm of abnormal activity present in the specific subcortical structures. Similar findings in the epileptic–psychotic group have recently been reported by Sherwood [17].
Several authors have suggested the possibility of demonstrating the abnormal subcortical electrical activity on routine scalp recordings by administering chemical compounds that, seemingly, activate electroencephalographic abnormalities [18–23]. In our studies, this
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Fig. 13. EEG recordings (cortical and subcortical) from patient A-26 during period of psychosis.
promising lead has not been substantiated. We have employed alpha chloralose, 6, 7, 8, 9-tetrahydro-5-azeptetrazole (Metrazol), and thiopental sodium (Pentothal) as activators, but have not been able to demonstrate that the specific abnormalities appearing on the subcortical recordings are demonstrable on scalp recordings. These activating drugs do induce a higher incidence of abnormalities on scalp recordings, but this occurs in the nonpsychotic, non-epileptic control group in essentially the
same incidence as in the schizophrenic group. The details of this rather extensive study are being prepared for publication (27).5 5
The three compounds were administered on two separate occasions to each of 77 patients of a carefully screened population of schizophrenics on the Tulane Research Unit of the East Louisiana State Hospital, Jackson, and to each of 25 prisoner volunteers of the Louisiana State Penitentiary at Angola who had been carefully screened.
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3. Discussion The principal issues with which we are concerned are first, does the utilization of the special techniques described contribute to our understanding of the nature of the two disorders, schizophrenia and epilepsy, and, secondly, is there a relationship between the two disorders? It is worth restating that epilepsy is a symptom, not a separate disease entity. Within the epilepsies, however, there is a syndrome with relatively well demarcated symptoms and a brain dysrhythmia for which no definite etiology or consistent pathology has been established. It is this syndrome, sometimes called ‘‘idiopathic epilepsy,’’ with which we are concerned here. The diagnosis of schizophrenia is dependent upon clinical symptoms and the course of the disease. Symptoms of psychosis can result from a wide variety of pathological processes. In schizophrenia, however, no definite etiology and pathology have been established; patients analogously could be characterized as ‘‘idiopathic psychotic.’’ The absence of a definite etiology and pathology are the principal bases for confusion in boundaries between these processes. The reasons advanced for relating these two diseases, namely the presence of psychotic symptoms in association with seizures in the epileptics and the occasional appearance of temporal lobe spikes6 in patients diagnosed as schizophrenics, are not valid since these criteria are not specific. The depth recordings of the seizural group are quite different from those of the schizophrenic group. This is so even during periods when the epileptic is displaying clinical features indistinguishable from the schizophrenic. The anatomical regions from which the abnormal recordings are obtained are the same for the two groups. In the seizural group, however, the abnormalities are more pronounced in the hippocampus and amygdala and less pronounced in the septal region. Recording abnormalities in the schizophrenic patients are predominantly in the septal region. There is no reason, in the authorÕs opinion, for concluding that the two processes, schizophrenia and epilepsy, represent a single disease because of involvement of the same anatomical structures. It is our experience that similar symptoms appear whenever these anatomical structures are implicated, regardless of the nature of the pathological process; for example, psychotic behavioral symptoms and altered electrical activity also are present with tumors,
6 Although it is necessary to refer to the sites of abnormal electrical discharge, the author wishes to caution against considering any part of the brain as an isolated center. This would be a gross, unjustified oversimplification. At this stage, it is of some value to relate, where possible, clinical phenomena with electrical activity in specific sites. We, however, must remain cognizant that the brain is so richly interconnected that unusual activity in any one part affects all other parts.
degenerative processes, infections, and toxic agents affecting these structures [25,26]. We have conducted studies with chemical compounds which affect the septal region, hippocampus, and amygdala in profound and differing ways. These studies have contributed to our understanding of the schizophrenia– epilepsy relationship. The effects of Metrazol on the brain are widespread. When Metrazol induces seizures, however, a rhythmical discharge of the type recorded spontaneously in the epileptics is recorded first from these same olfactory structures. When the administration of d-LSD produces psychotic symptoms, the clinical symptoms are associated with abnormal electrical discharges which are most marked in recordings from these same anatomical structures. The recording abnormalities resemble those seen in schizophrenic patients (with some distinguishing differences—15). The administration of Metrazol is not associated with the appearance of psychotic symptoms. The administration of d-LSD does not induce seizures. Thus, although these two compounds affect the same anatomical structures, they apparently do so differently and different symptoms result. Studies designed to clarify the nature of the biochemical lesion in these two endogenous processes, schizophrenia and epilepsy, have progressed. Evidence is accumulating to suggest a rather precise and specific biochemical abnormality basic to the processes. The administration of taraxein, a product obtained from the serum of schizophrenic patients, produced recording abnormalities and psychotic behavior resembling that seen in schizophrenic patients. Increasing the dosage of taraxein does not induce seizures; this suggests that the cells of the brain are affected in a specific manner by these chemical compounds. Our depth recording and biochemical studies suggest that there may be an independent disease, schizophrenia, and an independent disease, epilepsy, and that there may be a highly specific biochemical lesion present for each disease. It seems, on the basis of studies conducted thus far, that the chemical lesions affect cells of a common anatomical locale, but affect them in different ways.
4. Summary Data presented, gathered by special techniques, add some clarification to the nature of the seemingly similar and related disease processes of schizophrenia and epilepsy. These data indicate that schizophrenia and epilepsy probably are different entities.
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[15] Heath, R. G., and Mickle, W. A.: Electrical Studies on the Unanesthetized Brain. New York: Paul B. Hoeber, 1960. [16] Heath, R. G.: Confin. Neurol., 18: 305, 1958. [17] Sherwood, S. L.: Electrographic Depth Recordings from the Brains of Psychotics. Presented at New York Academy of Sciences meeting, New York City, April 1961. [18] Monroe, R. R., Jacobson, G., and Ervin, F.: A.M.A. Arch. Neurol. Psychiat., 76: 536, 1956. [19] Bickford, R. G.: Electroenceph. Neurophysiol., 3: 378, 1951. [20] Leiberman, D. M.: J. Neurol. Neurosurg. Psychiat., 16: 30, 1953. [21] Smith, K., Ulett, G. A., and Johnson, L. C.: A.M.A. Arch. Neurol. Psychiat., 77: 528, 1957. [22] Bickford, R. G., Sem-Jacobsen, C. W., White, P. T., and Daly, D.: Electroenceph. Neurophysiol., 4: 275, 1952. [23] Goldman, D.: Ann. N.Y. Acad. Sci., 80: 687, 1959. [24] Heath, R. G.: In preparation. [25] Heath, R. G.: Studies in Schizophrenia. Cambridge: Harvard University Press, 1954. [26] Lennox, M., and Brody, B. S.: J. Nerv. Ment. Dis., 104: 237, 1946.