Case Study Middle Childhood Onset of Interictal Psychosis ROCHELLE CAPLAN, M.D., W. DONALD SHIELDS, M.D., LISA MORI, PH.D., AND SUE YUDOVIN, R.N., M.N., C.N.S.
Abstract. The authors describe three children (mean age = 7.8 years) with complex partial epilepsy, left temporal lobe involvement, and interictal schizophrenia-like psychosis. As described in adults with complex partial epilepsy, these children met DSM-III criteria for schizophrenia, their affect was intact, and they demonstrated no negative signs of schizophrenia. Unlike adult epileptic patients, these children demonstrated psychotic symptomatology despite inadequate seizure control and after a short latency period. The possible role of early onset seizures, temporal lobe lesions, and kindling on the developing brain are discussed. J. Am. Acad. Child Adolesc. Psychiatry, 1991,30,6:893-896. Key Words: complex partial epilepsy, schizophrenia, temporal lobe, middle childhood. Lindsay et al. (1979) reported that 10% of children with temporal lobe epilepsy developed psychosis by adulthood, in particular, if they had experienced cataclysmic rage attacks and hyperkinetic reactions in childhood. To the best of the authors' knowledge, there have been no reports of middle childhood or prepubertal onset of interictal psychosis. The temporal lobe, in particular the left temporal lobe, is thought to playa role in the schizophrenia-like psychosis associated with epilepsy (Flor-Henry, 1983; Perez et al., 1985; Slater and Beard, 1963) and schizophrenia (Brown et al., 1986; Gur et al., 1985). Although schizophrenia and epilepsy appear to occur together (See review in McKenna et al., 1985), Landolt (1958) and, more recently, Wolf and Trimble (1985) have hypothesized that there is an antagonism between the symptoms of epilepsy and the adult onset of interictal schizophrenia-like psychosis. Two main findings support this hypothesis. First, adults with interictal psychosis become psychotic when their seizure frequency decreases (Dongier, 1958; Kristensen and Sindrup, 1978; Slater and Beard, 1963). Second, electroencephalogram EEG) evidence of seizure discharges undergo forced normalization when the patient becomes psychotic (Landolt, 1958; Pakalnis et al., 1987). In adults, the average length of time from the onset of the seizure disorder to the onset of psychosis, the latency period, is 14 years (Slater and Beard, 1963). One of the Accepted May 23, 1991. Dr. Caplan, Assistant Professor, is with the Division of Child Psychiatry, Pediatric Epilepsy Research Group, University of California, Los Angeles. Dr. Shields, Associate Professor, and Ms. Yudovin are with the Departments ofNeurology and Pediatrics, Pediatric Epilepsy Research Group, University of California, Los Angeles. Dr. Mori, Assistant Clinical Professor, is currently affiliated with the Department of Psychiatry, University of California at Irvine. Supported by the National Institute of Mental Health Research Scientist Development Award K01-MH00538. Reprint requests to Dr. Caplan, Neuropsychiatric Institute, Rm. 48253A, University of Los Angeles of California, 760 Westwood Plaza, Los Angeles, CA 90024. 0890-8567/9113006-0893$03.0010© 1991by the American Academy of Child and Adolescent Psychiatry. l.Am.Acad. Child Adolesc.Psychiatry, 30:6, November 1991
proposed mechanisms of interictal psychosis is that repetitive seizures kindle the limbic system during the latency period (Stevens and Livermore, 1978). The limbic system then independently produces the psychotic symptoms. Several researchers, however, have reported that the psychosis associated with epilepsy begins after a relatively short latency period or after the surgical removal of the limbic lobe (Jensen et al., 1979; Koch-Weser et al., 1988; Sherwin, 1981). The authors present this report on three children with seizure disorder and interictal schizophrenia-like symptoms to alert clinicians to the following: First, despite the infrequency of middle childhood onset schizophrenia (Tanguay and Asarnow, 1985), young children can develop interictal schizophrenia-like symptoms; second, the onset of schizophrenia-like psychosis can occur in the absence of a history of aggressive acting out behavior; and third, antagonism between epilepsy and interictal schizophrenia-like symptoms may not occur in middle childhood.
Case Reports Case 1 An 8-year-old Caucasian girl with complex partial seizures was referred for a psychiatric evaluation because of expressed death wishes. Her early medical history is remarkable for a single, left-sided tonic seizure at the age of 8 months and staring spells from the age of 2 years 3 months. Over the years, the child's seizure pattern included an aura, followed by deviation of the head and eyes to the right, cursive seizures in which she walked to the right, and occasional grand mal attacks. The patient's seizures were variably controlled with different combinations of anticonvulsants. Other than the presence of premature pubic hair, the child's medical and neurological examination were normal. The EEG demonstrated left-sided slowing primarily over the left temporal region, asymmetry of beta and sleep spindles, and interictalleft midtemporal to anterior temporal spikes. The magnetic resonance imaging (MRI) scan revealed a lesion of the left posterior mesotemporal lobe.
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The child's developmental history included an uncomplicated pregnancy, a Cesarian section for prolonged labor, a normal birth weight, and normal developmental milestones. The patient was placed in a special class because of poor learning and socialization skills. At the age of 7 years 6 months, she expressed the wish to die, and this was attributed by the mother to difficulties the child had in adjusting to a new school teacher. After expressing death wishes again at the age of 8 years, the child's neurologist (W.D.S.) referred her for a psychiatric examination. There is no family history of epilepsy and psychiatric disorders. At psychiatric examination, the child reported auditory hallucinations in which she heard her left "bad" brain talking to her right "good" brain about her. She also reported olfactory hallucinations in which she perceived a bad smell that emanated from her teacher. She was fearful and anxious as she reported visual illusions and hallucinations. She perceived the senior author to be a witch and saw monsters in her office. Kiddie Formal Thought Disorder Ratings (Caplan et aI., 1989) demonstrated severe illogical thinking. The child denied active suicidal ideation. Her affect was neither blunted nor inappropriate. She had a full scale IQ of 80, with verbal and performance scores of 78 and 85, respectively. The child's seizure control and psychiatric condition gradually deteriorated, with increased pervasiveness of hallucinations, illusions, and thought disorder. Telemetry demonstrated that the psychotic symptoms were interictal. After stereotactic surgical removal of a left posterior temporal and posterior hippocampal ganglioglioma, her seizures and her psychiatric symptoms subsided.
Case 2 An ll-year 5-month-old Caucasian boy with complex partial seizures was referred for psychiatric evaluation because of oppositional behavior. He had two generalized seizures at the age of 13 months and began to have myoclonus drop attacks and tonic clonic seizures from the age of 2 years 6 months. At the time of his psychiatric examination, he was having two seizures a day and had therapeutic levels of nitrazepam and valproic acid. The child's family history was unremarkable for psychiatric and neurological disorders. His physical and neurological examinations were normal. The EEG demonstrated intermittent slowing over the left frontal region and two independent spike foci in the left frontal and posterior temporal regions. No abnormalities were found on the MRI. This child was born after an uncomplicated pregnancy and delivery with a birth weight of 6 lbs. 4 oz. His motor milestones were normal. Language development, however, was slow. He was placed in a special school because of poor academic performance. During the 6 months that preceded his psychiatric evaluation, he was preoccupied with fires and with sibling rivalry toward his older brother. A psychiatric consult was requested by the patient's neurologist (W.D.S.) because the parents were having difficulty dealing with the child's preoccupations. During the psychiatric examination, the patient reported delusions of persecution and auditory hallucinations. A group 894
of strangers was planning to kill him. The patient heard these people talking about him and saying that he should die. The child denied preoccupation with fires. He was, however, preoccupied with aggressive measures he would use to take revenge on his brother. Kiddie Formal Thought Disorder Ratings (Caplan et aI., 1989) demonstrated severe illogical thinking and poverty of content of speech. His affect was appropriate. He denied suicidal ideation. On the WISC-R (Wechsler, 1974), this child had a full-scale, verbal, and performance IQs of 71,69, and 75, respectively. The parents refused psychiatric treatment for the patient. When seen 3 and 6 months after the initial psychiatric assessment, there was no change from the child's initial psychiatric status. His seizures continued to be uncontrolled.
Case 3 This 6-year-old Caucasian boy with complex partial seizures was referred for psychiatric examination because of school difficulties. From age 9 months, he experienced biannual clusters that lasted 1 to 2 months. Between these periods, the patient was seizure free. During a seizure, the child first reported a strange sensation. He then became flushed and would curl up into a fetal position. Although able to follow simple commands, the child was unable to recall what happened to him during a seizure. Treatment with a variety of anticonvulsant drugs has not controlled the seizures or prevented the biannual clusters. The patient's physical and neurological examinations were unremarkable. During seizures, his EEG demonstrated a normal background with left inferolateral frontal slowing followed by rhythmical theta activity. There were no abnormal MRI findings. His developmental history was also unremarkable, and he currently attends a regular school. The family history is positive for epilepsy and for collagen disease but not for psychiatric disorders. During his psychiatric examination, this patient reported that he heard a boy's voice in his head. This voice was responsible for the bad and good things that happened to him. Kiddie Formal Thought Disorder Ratings (Caplan et aI., 1989) demonstrated moderate illogical thinking. The child's affect was euthymic and appropriate. Hyperactivity, distractibility, and poor impulse control were observed and validated from the Conners Teacher and Parent Questionnaires (Goyette et aI., 1978). There had been no deterioration in the child's overall functioning. On the WISC-R, this child had a full-scale IQ of 123, a verbal IQ of 119, and a performance IQ of 121. During his last seizure cluster, this child continued to hear the voice inside him. He also reported that the senior author and his parents looked like ghosts during that period. He is currently undergoing psychiatric follow-up. Discussion As a result of the internalizing nature of these children's behavior problem, the children's parents, teachers, and neurologists had not considered the possibility of severe psychopathology, such as psychosis in these children. Cases 1 and 2 met DSM-III-R criteria for schizophrenia. These two children had hallucinations, formal thought disorder, del.Am.Acad. Child Adolesc. Psychiatry, 30:6, November 1991
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lusions or bizarre fantasies, social and academic dysfunction, and a progressive downhill dysfunctional course in the 6 months that preceded their psychiatric interview. Case 3 also had hallucinations, formal thought disorder, bizarre fantasies, and mild school difficulties. However, there was no history of a downhill course, and his social functioning was adequate. Despite the clinical similarity to schizophrenia, these children were not diagnosed as schizophrenic because an organic factor initiated and maintained their schizophrenia-like interictal psychosis . Three features of the clinical presentation of these children resemble those of adult patients with interictal psychosis. First, the clinical manifestations of two of the three children were similar to those of schizophrenic children (Perez et aI., 1985; Slater and Beard, 1963). Second , they demonstrated no negative symptoms (Slater and Beard, 1963; Toone et aI., 1982). Third , two of the three children had predominantly left temporal involvement (Flor-Henry, 1983; Perez et aI. , 1985; Sherwin, 1981; Toone et aI., 1982). The positive symptoms of schizophrenia-hallucinations, delusions , and formal thought disorder (Crow, 1980)-and the symptoms of interictal psychosis (Trimble, 1977) could reflect increased dopamine activity and temporal lobe involvement. There are several possible mechanisms for psychosis in temporal lobe epilepsy. First, Davison (1983) has suggested that the psychosis of patients with temporal lobe tumors is etiologically related to the underlying cerebral damage and not to the seizures . Roberts et al., (1990) recently reported that young adult patients with medial temporal gangliogliomas were at risk for developing a preoperative or postoperative schizophrenia-like psychosis. The patient in case 1 had a temporal lobe ganglioglioma. It is, therefore, possible that direct involvement of limbic structures by the ganglioglioma impaired limbic structures involved in the schizophrenic process. Alternatively, there is evidence that the developing animal brain is more susceptible to seizures than the adult brain (Moshe, 1981; Swann et aI., 1988). Early onset of seizures could, therefore, damage limbic areas involved in schizophrenia. Perinatal limbic and prefrontal lesions have been found in postmortem studies of adult schizophrenic patients (Bogerts , 1989). Weinberger (1987) has hypothesized that early neurodevelopmental lesions could disrupt dopamine tracts to the mesolimbic area and lead to positive and negative symptoms of schizophrenia. Finally, the developing brain is also more sensitive to kindling than the adult brain (Moshe , 1981). Kindling of the limbic system through repeated seizures might play a role in activating the symptomatology of interictal psychosis (Stevens and Livermore , 1978). Recent evidence indicates that amygdala kindling in the rat is associated with reduced presynaptic (Mintz et al., 1987) and increased postsynaptic rat limbic dopaminergic function (Csernansky et aI., 1988). Unlike adult epilepsy patients with interictal psychosis (Dongier, 1958; Kristensen and Sindrup, 1978; Slater and Beard, 1963), however, all three children had frequent seizures while they were actively psychotic . Trimble (1977) has hypothesized that there is decreased dopaminergic function during seizures but increased dopamine function during l.Am.Acad . Child Adolesc .Psychiatry, 30 :6, November 1991
interictal psychosis . In rats, Sato (1983) demonstrated that . a hyperdopaminergic state resulting from chronic amphetamine treatment is associated with an increased seizure threshold. The mechanism for transition between the hypothesized hypodopaminergic and hyperdopaminergic states in patients with epilepsy and interictal psychosis, however, is not clear . In contrast to the 14-year long latency period described in adults (Slater and Beard, 1963), these children demonstrated schizophrenia-like symptoms after a relatively brief latency period of 5.4 years, 9 years, and 5.3 years . The early onset of psychosis in the cases presented in this paper could, therefore, reflect the increased vulnerability of the developing limbic system to tumors , seizures, and kindling. In conclusion, this case report suggests that some children with complex partial seizures develop a schizophrenia-like psychosis in association with an uncontrolled seizure disorder , a relatively short latency period, and an absence of significant " externalizing" behaviors .
References Bogerts , B. (1989 ) , The role of limbic and paralimbic pathology in the etiology of schizophrenia. Psychiatry Res., 29:255-256 . Brown, R., Colter, N. , Corsellis, A. N. et al (1986) , Postmortem evidence of structural brain changes in schizophrenia. Arch . Gen.
Psychiatry, 43:36--42. Caplan, R., Guthrie, D . , Fish , B., Tanguay , P. E. & David-Lando, G. (1989), The Kidd ie Formal Thought Disorder Rat ing Scale (KFTDS ). Clinical assess ment, reliability, and validity. J . Am. Acad.
Child Adolesc. Psychiatry, 28:208-216. Crow , T . J. (1980) , Molecular pathology of schizophrenia: more than one disease proce ss . Br, Med . J . [Clin. Res.] , 280:1-9 . Csernansky, J. G., Mellentin, J., Beauclair, L. & Lombrozo, L. (1988) , Mesolimbic dopaminerg ic supersensitivity following electrical kindling of the amygdala. Biol. Psychiatry. 23:285-294 . Davison , K. (1983) , Sch izophrenia-like psychoses associated with organic cerebral disorders: a review. Psychiatr. Dev .• 1:1-34. Dongier, S . (1958), Statistical study of clinical and electroencephalographic manifestations of 536 psychotic episodes occurring in 516 epileptics between clinic al seizures. Epilepsia, I: 117-142. Flor-Henry, P. (1983) , Determinants of psychosis in epilepsy. Latera lity and forced normalization. Bioi . Psychiatry. 18:1045-1057 . Goyette, C. M. , Conners, C. K. & Ulrich , R. F. (1978 ), Normative data on revised Conners Parent and Teachers Rating Scales. J.
Abnorm. Child Psychol.• 6:221-236. Gur, R . E. , Gur , R. C . , Skolnick, B . E. et al. (1985) , Brain function in psychiatric disorders. III . Regional cerebral blood flow in unmedicated schizophrenic s. Arch. Gen. Psychiatry. 42:329-334 . Jensen , I. & Larson , J . K. (1979), Ment al aspects of temporal lobe epilepsy, follow-up of 74 patients after resection of a temporal lobe . J . Neural. Neurosurg. Psychiatry. 42:256-265. Koch-Weser, M., Garron, D. C., Gilley , D . W. et al (1988 ), Prevalence of psychologic disorders after surgical treatment of seizures. Arch. Neural.. 45: 1308-1311. Kristensen , O. & Sindrup , E. H. (1978) , Psychomotor epilepsy and psycho sis I. Physical aspe cts. Acta Neural. Scand.. 57:361-377 . Landolt, H . (1958) , Seri al electroencephalographic investigations during psychotic episodes in epileptic patients and durin g schizophrenic attacks. In: Lectures on Epilepsy, ed. L. De Haas . New York: Elsevier Science Publishing Company, Inc. , pp. 91-133 . Lindsay, J . , Ounsted, C. & Richards , P . (1979) , Long-term outcome in children with temporal lobe seizures . III. Psychiatric aspects in childho od and adult life . Dev. Med. Child Neurol., 21:630-636. McKenna, P. J., Kane , J. M. & Parri sh, K . (1985) , Psychotic syndromes in epilepsy . Am . J . Psychiatry, 142:895-904. Mintz, M., Tomer, S ., Houpt, S. & Herberg, L. 1. (1987), Amygdala
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kindling modifies interhemispheric dopaminergic asymmetry. Exp.
Neurol., 96:137-144. Moshe, S. L. (1981), The effects of age on the kindling phenomenon. Dev. Psychobiol., 14:75-81. Pakalnis, A., Drake, M. E., Kuruvilla, J. & Kellum, J. B. (1987), Forced normalization: acute psychosis after seizure control in seven patients. Arch. Neurol., 44:289-292. Perez, M., Trimble, M. R., Murray, N. M. K. & Reider, I. (1985), Epileptic psychoses: an evaluation of PSE profiles. Br. J. Psychia-
try, 146:155-163. Roberts, G. W., Done, D. J., Bruton, C. & Crow, T. J. (1990), A "mock up" of schizophrenia: temporal lobe epilepsy and schizophrenia-like-psychosis. Bioi. Psychiatry, 28: 127-143. Sato, M. (1983), Long-lasting hypersensitivity to methamphetamine following amygdaloid kindling in cats: the relationship between limbic epilepsy and the psychotic state. Bioi. Psychiatry, 18:525536. Sherwin, A. (1981), Psychosis associated with epilepsy: significance of the laterality of the epileptogenic lesion. J. Neurol. Neurosurg.
Psychiatry, 44:83-85. Slater, E. & Beard, A. W. (1963), The schizophrenia-like psychoses of epilepsy. Br. J. Psychiatry, 109:95-150. Stevens, J. R. & Livermore, A. (1978), Kindling of the mesolimbic
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dopamine system: an animal model of psychosis. Neurology, 28:3646. Swann, J. W., Brady, R. J., Smith, K. L. & Pierson, M. G. (1988), Synaptic mechanisms of focal epileptogenesis in the immature nervous system. In: Disorders of the Developing Nervous System: Changing Views on Their Origins, Diagnoses, and Treatments . Alan R. Liss, Inc., pp. 19-49. Tanguay, P. E. & Asanow, R. (1985), Schizophrenia in children. In: Psychiatry, eds. R. Michels & J. O. Cavenar. Philadelphia: J. B. Lippincott, Co., pp. 1-9. Toone, B. K., Garralda, M. E. & Ron, M. A. (1982), The psychoses of epilepsy and the functional psychoses. A clinical and phenomenological comparison. Br. J. Psychiatry, 141:256-261. Trimble, M. R. (1977), The relationship between epilepsy and schizophrenia: a biochemical hypothesis. Bioi. Psychiatry, 12:299-304. Wechsler, D. (1974), Manual for the Wechsler Intelligence Scale for Children - Revised. New York: The Psychological Corporation. Weinberger, D. R. (1987), Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry, 44:660669. Wolf, P. & Trimble, M. R. (1985), Biological antagonism and epileptic psychosis. Br. J. Psychiatry, 146:272-276.
J.Am.Acad. Child Adolesc.Psychiatry, 30:6, November 1991
Abstract. The authors describe three children (mean age = 7.8 years) with complex partial epilepsy, left temporal lobe involvement, and interictal schizophrenia-like psychosis. As described in adults with complex partial epilepsy, these children met DSM-III criteria for schizophrenia, their affect was intact, and they demonstrated no negative signs of schizophrenia. Unlike adult epileptic patients, these children demonstrated psychotic symptomatology despite inadequate seizure control and after a short latency period. The possible role of early onset seizures, temporal lobe lesions, and kindling on the developing brain are discussed. J. Am. Acad. Child Adolesc. Psychiatry, 1991,30,6:893-896. Key Words: complex partial epilepsy, schizophrenia, temporal lobe, middle childhood. Lindsay et al. (1979) reported that 10% of children with temporal lobe epilepsy developed psychosis by adulthood, in particular, if they had experienced cataclysmic rage attacks and hyperkinetic reactions in childhood. To the best of the authors' knowledge, there have been no reports of middle childhood or prepubertal onset of interictal psychosis. The temporal lobe, in particular the left temporal lobe, is thought to playa role in the schizophrenia-like psychosis associated with epilepsy (Flor-Henry, 1983; Perez et al., 1985; Slater and Beard, 1963) and schizophrenia (Brown et al., 1986; Gur et al., 1985). Although schizophrenia and epilepsy appear to occur together (See review in McKenna et al., 1985), Landolt (1958) and, more recently, Wolf and Trimble (1985) have hypothesized that there is an antagonism between the symptoms of epilepsy and the adult onset of interictal schizophrenia-like psychosis. Two main findings support this hypothesis. First, adults with interictal psychosis become psychotic when their seizure frequency decreases (Dongier, 1958; Kristensen and Sindrup, 1978; Slater and Beard, 1963). Second, electroencephalogram EEG) evidence of seizure discharges undergo forced normalization when the patient becomes psychotic (Landolt, 1958; Pakalnis et al., 1987). In adults, the average length of time from the onset of the seizure disorder to the onset of psychosis, the latency period, is 14 years (Slater and Beard, 1963). One of the Accepted May 23, 1991. Dr. Caplan, Assistant Professor, is with the Division of Child Psychiatry, Pediatric Epilepsy Research Group, University of California, Los Angeles. Dr. Shields, Associate Professor, and Ms. Yudovin are with the Departments ofNeurology and Pediatrics, Pediatric Epilepsy Research Group, University of California, Los Angeles. Dr. Mori, Assistant Clinical Professor, is currently affiliated with the Department of Psychiatry, University of California at Irvine. Supported by the National Institute of Mental Health Research Scientist Development Award K01-MH00538. Reprint requests to Dr. Caplan, Neuropsychiatric Institute, Rm. 48253A, University of Los Angeles of California, 760 Westwood Plaza, Los Angeles, CA 90024. 0890-8567/9113006-0893$03.0010© 1991by the American Academy of Child and Adolescent Psychiatry. l.Am.Acad. Child Adolesc.Psychiatry, 30:6, November 1991
proposed mechanisms of interictal psychosis is that repetitive seizures kindle the limbic system during the latency period (Stevens and Livermore, 1978). The limbic system then independently produces the psychotic symptoms. Several researchers, however, have reported that the psychosis associated with epilepsy begins after a relatively short latency period or after the surgical removal of the limbic lobe (Jensen et al., 1979; Koch-Weser et al., 1988; Sherwin, 1981). The authors present this report on three children with seizure disorder and interictal schizophrenia-like symptoms to alert clinicians to the following: First, despite the infrequency of middle childhood onset schizophrenia (Tanguay and Asarnow, 1985), young children can develop interictal schizophrenia-like symptoms; second, the onset of schizophrenia-like psychosis can occur in the absence of a history of aggressive acting out behavior; and third, antagonism between epilepsy and interictal schizophrenia-like symptoms may not occur in middle childhood.
Case Reports Case 1 An 8-year-old Caucasian girl with complex partial seizures was referred for a psychiatric evaluation because of expressed death wishes. Her early medical history is remarkable for a single, left-sided tonic seizure at the age of 8 months and staring spells from the age of 2 years 3 months. Over the years, the child's seizure pattern included an aura, followed by deviation of the head and eyes to the right, cursive seizures in which she walked to the right, and occasional grand mal attacks. The patient's seizures were variably controlled with different combinations of anticonvulsants. Other than the presence of premature pubic hair, the child's medical and neurological examination were normal. The EEG demonstrated left-sided slowing primarily over the left temporal region, asymmetry of beta and sleep spindles, and interictalleft midtemporal to anterior temporal spikes. The magnetic resonance imaging (MRI) scan revealed a lesion of the left posterior mesotemporal lobe.
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The child's developmental history included an uncomplicated pregnancy, a Cesarian section for prolonged labor, a normal birth weight, and normal developmental milestones. The patient was placed in a special class because of poor learning and socialization skills. At the age of 7 years 6 months, she expressed the wish to die, and this was attributed by the mother to difficulties the child had in adjusting to a new school teacher. After expressing death wishes again at the age of 8 years, the child's neurologist (W.D.S.) referred her for a psychiatric examination. There is no family history of epilepsy and psychiatric disorders. At psychiatric examination, the child reported auditory hallucinations in which she heard her left "bad" brain talking to her right "good" brain about her. She also reported olfactory hallucinations in which she perceived a bad smell that emanated from her teacher. She was fearful and anxious as she reported visual illusions and hallucinations. She perceived the senior author to be a witch and saw monsters in her office. Kiddie Formal Thought Disorder Ratings (Caplan et aI., 1989) demonstrated severe illogical thinking. The child denied active suicidal ideation. Her affect was neither blunted nor inappropriate. She had a full scale IQ of 80, with verbal and performance scores of 78 and 85, respectively. The child's seizure control and psychiatric condition gradually deteriorated, with increased pervasiveness of hallucinations, illusions, and thought disorder. Telemetry demonstrated that the psychotic symptoms were interictal. After stereotactic surgical removal of a left posterior temporal and posterior hippocampal ganglioglioma, her seizures and her psychiatric symptoms subsided.
Case 2 An ll-year 5-month-old Caucasian boy with complex partial seizures was referred for psychiatric evaluation because of oppositional behavior. He had two generalized seizures at the age of 13 months and began to have myoclonus drop attacks and tonic clonic seizures from the age of 2 years 6 months. At the time of his psychiatric examination, he was having two seizures a day and had therapeutic levels of nitrazepam and valproic acid. The child's family history was unremarkable for psychiatric and neurological disorders. His physical and neurological examinations were normal. The EEG demonstrated intermittent slowing over the left frontal region and two independent spike foci in the left frontal and posterior temporal regions. No abnormalities were found on the MRI. This child was born after an uncomplicated pregnancy and delivery with a birth weight of 6 lbs. 4 oz. His motor milestones were normal. Language development, however, was slow. He was placed in a special school because of poor academic performance. During the 6 months that preceded his psychiatric evaluation, he was preoccupied with fires and with sibling rivalry toward his older brother. A psychiatric consult was requested by the patient's neurologist (W.D.S.) because the parents were having difficulty dealing with the child's preoccupations. During the psychiatric examination, the patient reported delusions of persecution and auditory hallucinations. A group 894
of strangers was planning to kill him. The patient heard these people talking about him and saying that he should die. The child denied preoccupation with fires. He was, however, preoccupied with aggressive measures he would use to take revenge on his brother. Kiddie Formal Thought Disorder Ratings (Caplan et aI., 1989) demonstrated severe illogical thinking and poverty of content of speech. His affect was appropriate. He denied suicidal ideation. On the WISC-R (Wechsler, 1974), this child had a full-scale, verbal, and performance IQs of 71,69, and 75, respectively. The parents refused psychiatric treatment for the patient. When seen 3 and 6 months after the initial psychiatric assessment, there was no change from the child's initial psychiatric status. His seizures continued to be uncontrolled.
Case 3 This 6-year-old Caucasian boy with complex partial seizures was referred for psychiatric examination because of school difficulties. From age 9 months, he experienced biannual clusters that lasted 1 to 2 months. Between these periods, the patient was seizure free. During a seizure, the child first reported a strange sensation. He then became flushed and would curl up into a fetal position. Although able to follow simple commands, the child was unable to recall what happened to him during a seizure. Treatment with a variety of anticonvulsant drugs has not controlled the seizures or prevented the biannual clusters. The patient's physical and neurological examinations were unremarkable. During seizures, his EEG demonstrated a normal background with left inferolateral frontal slowing followed by rhythmical theta activity. There were no abnormal MRI findings. His developmental history was also unremarkable, and he currently attends a regular school. The family history is positive for epilepsy and for collagen disease but not for psychiatric disorders. During his psychiatric examination, this patient reported that he heard a boy's voice in his head. This voice was responsible for the bad and good things that happened to him. Kiddie Formal Thought Disorder Ratings (Caplan et aI., 1989) demonstrated moderate illogical thinking. The child's affect was euthymic and appropriate. Hyperactivity, distractibility, and poor impulse control were observed and validated from the Conners Teacher and Parent Questionnaires (Goyette et aI., 1978). There had been no deterioration in the child's overall functioning. On the WISC-R, this child had a full-scale IQ of 123, a verbal IQ of 119, and a performance IQ of 121. During his last seizure cluster, this child continued to hear the voice inside him. He also reported that the senior author and his parents looked like ghosts during that period. He is currently undergoing psychiatric follow-up. Discussion As a result of the internalizing nature of these children's behavior problem, the children's parents, teachers, and neurologists had not considered the possibility of severe psychopathology, such as psychosis in these children. Cases 1 and 2 met DSM-III-R criteria for schizophrenia. These two children had hallucinations, formal thought disorder, del.Am.Acad. Child Adolesc. Psychiatry, 30:6, November 1991
CHILDHOOD INTERICTAL PSYCHOSIS
lusions or bizarre fantasies, social and academic dysfunction, and a progressive downhill dysfunctional course in the 6 months that preceded their psychiatric interview. Case 3 also had hallucinations, formal thought disorder, bizarre fantasies, and mild school difficulties. However, there was no history of a downhill course, and his social functioning was adequate. Despite the clinical similarity to schizophrenia, these children were not diagnosed as schizophrenic because an organic factor initiated and maintained their schizophrenia-like interictal psychosis . Three features of the clinical presentation of these children resemble those of adult patients with interictal psychosis. First, the clinical manifestations of two of the three children were similar to those of schizophrenic children (Perez et aI., 1985; Slater and Beard, 1963). Second , they demonstrated no negative symptoms (Slater and Beard, 1963; Toone et aI., 1982). Third , two of the three children had predominantly left temporal involvement (Flor-Henry, 1983; Perez et aI. , 1985; Sherwin, 1981; Toone et aI., 1982). The positive symptoms of schizophrenia-hallucinations, delusions , and formal thought disorder (Crow, 1980)-and the symptoms of interictal psychosis (Trimble, 1977) could reflect increased dopamine activity and temporal lobe involvement. There are several possible mechanisms for psychosis in temporal lobe epilepsy. First, Davison (1983) has suggested that the psychosis of patients with temporal lobe tumors is etiologically related to the underlying cerebral damage and not to the seizures . Roberts et al., (1990) recently reported that young adult patients with medial temporal gangliogliomas were at risk for developing a preoperative or postoperative schizophrenia-like psychosis. The patient in case 1 had a temporal lobe ganglioglioma. It is, therefore, possible that direct involvement of limbic structures by the ganglioglioma impaired limbic structures involved in the schizophrenic process. Alternatively, there is evidence that the developing animal brain is more susceptible to seizures than the adult brain (Moshe, 1981; Swann et aI., 1988). Early onset of seizures could, therefore, damage limbic areas involved in schizophrenia. Perinatal limbic and prefrontal lesions have been found in postmortem studies of adult schizophrenic patients (Bogerts , 1989). Weinberger (1987) has hypothesized that early neurodevelopmental lesions could disrupt dopamine tracts to the mesolimbic area and lead to positive and negative symptoms of schizophrenia. Finally, the developing brain is also more sensitive to kindling than the adult brain (Moshe , 1981). Kindling of the limbic system through repeated seizures might play a role in activating the symptomatology of interictal psychosis (Stevens and Livermore , 1978). Recent evidence indicates that amygdala kindling in the rat is associated with reduced presynaptic (Mintz et al., 1987) and increased postsynaptic rat limbic dopaminergic function (Csernansky et aI., 1988). Unlike adult epilepsy patients with interictal psychosis (Dongier, 1958; Kristensen and Sindrup, 1978; Slater and Beard, 1963), however, all three children had frequent seizures while they were actively psychotic . Trimble (1977) has hypothesized that there is decreased dopaminergic function during seizures but increased dopamine function during l.Am.Acad . Child Adolesc .Psychiatry, 30 :6, November 1991
interictal psychosis . In rats, Sato (1983) demonstrated that . a hyperdopaminergic state resulting from chronic amphetamine treatment is associated with an increased seizure threshold. The mechanism for transition between the hypothesized hypodopaminergic and hyperdopaminergic states in patients with epilepsy and interictal psychosis, however, is not clear . In contrast to the 14-year long latency period described in adults (Slater and Beard, 1963), these children demonstrated schizophrenia-like symptoms after a relatively brief latency period of 5.4 years, 9 years, and 5.3 years . The early onset of psychosis in the cases presented in this paper could, therefore, reflect the increased vulnerability of the developing limbic system to tumors , seizures, and kindling. In conclusion, this case report suggests that some children with complex partial seizures develop a schizophrenia-like psychosis in association with an uncontrolled seizure disorder , a relatively short latency period, and an absence of significant " externalizing" behaviors .
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