Proposal for a New Five-Axis Classification Scheme for Psychoses of Epilepsy

Epilepsy & Behavior 1, 343–352 (2000) doi:10.1006/ebeh.2000.0113, available online at http://www.idealibrary.com on

Proposal for a New Five-Axis Classification Scheme for Psychoses of Epilepsy Masato Matsuura,* ,1 Naoto Adachi, † Yasunori Oana, ‡ Yoshiro Okubo, § Tsunekatsu Hara, ¶ and Teiichi Onuma 㛳 *Nihon University School of Medicine, †Adachi Clinic, ‡Saint Paul Hospital, § Tokyo Medical and Dental University, ¶Komagino Hospital, and National Saikata Hospital, Tokyo, Japan Received June 13, 2000; revised September 21, 2000; accepted for publication September 23, 2000

Based on an overview of the literature and a multicenter study in Japan, we propose a new five-axis classification scheme for psychoses of epilepsy: (1) epilepsy variables, (2) psychopathology variables, (3) ictus/EEG variables, (4) precipitating factors of psychoses, (5) organic background. A total of 128 patients, 63 males and 65 females, with epilepsy and psychoses were recruited from five treatment centers. A wide heterogeneity of psychoses of epilepsy was demonstrated and categorization by a single axis was shown to be inadequate. Cluster analysis revealed four subgroups characterized by their psychopathology, temporal relationship to seizure occurrence, and EEG changes during psychoses. By comparing with the control epileptic group without psychoses, higher rates of mild intelligence disturbance and abnormal findings by brain imaging were proven among the psychotic group. The scheme involves a dimensional representation of individual patients to capture the complexity of their clinical background and to relay clinical information accurately and systematically. It is believed to hold direct therapeutic implications and to contribute to promoting research by enabling accumulation of a large number of patients on a multicenter basis. © 2000 Academic Press Key Words: psychoses of epilepsy; heterogeneity; multiaxis classification; multicenter study.

INTRODUCTION

ner, DSM-IV criteria of the American Psychiatric Association APA (4) use two subcategories, psychotic disorder due to epilepsy (two subtypes, with hallucination and with delusion) and catatonic disorder due to epilepsy. Both classifications were designed to apply psychopathology due to general medical condition and neither categorization addresses the psychoses of epilepsy directly. Classification of psychoses of epilepsy based on etiology is the preferred method. From this standpoint, Pond (5) stated that psychoses of epilepsy were caused either by epilepsy-causing brain damage, seizure-related phenomena, or non-seizure-related psychopathology. However, in clinical settings, psychoses of epilepsy stem from a complex of these factors, and it is difficult for individual patients to be placed into only one of these categories. When psychoses of epilepsy are categorized by a single criterion, different pathophysiologies may be included within the same cate-

The clinical phenomenology of psychosis developing after the onset of epilepsy shows widespread heterogeneity and many classification schemes have been reported for psychoses of epilepsy. According to the WHO dictionary of epilepsy (1), psychoses of epilepsy are classified by their clinical course, acute or chronic. However, the distinction between acute and chronic is not always clear (2). According to Chapter 5 of the ICD-10 guidelines of WHO (3), psychoses of epilepsy are categorized into three subgroups: organic hallucinosis, organic catatonic disorder, and organic delusional (schizophrenia-like) disorder. In a similar man1

To whom correspondence should be addressed at Department of Neuropsychiatry, Surugadai Nihon University Hospital, 1-8-13 Surugadai, Kanda, Chiyoda-ku, Tokyo 101-0062. Fax: ⫹3-3293-1733. E-mail: [email protected]. 1525-5050/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

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344 gory. Moreover, classification schemes based on uncertain etiological hypotheses may have little support. In such circumstances, the usefulness of any diagnostic classification is thought to be directly related to its ability to provide clinically useful information for therapeutic action. A categorical approach to psychoses has been demonstrated to have limitations in terms of therapeutic applicability compared with dimensional representation (6). Development of psychoses in patients with epilepsy is thought to stem from a combination of biological and psychosocial interactions. A multiaxis classification involves a dimensional representation and has the advantage of capturing the complexity of these clinical situations, and of describing the heterogeneity of individuals presenting with the same categorical diagnosis. In the present study, we performed an overview of the published literature on classification of psychoses of epilepsy and proposed a new multiaxis classification scheme that enables accurate and systematic communication of clinical information. Based on clinical trial results obtained using this scheme by a multicenter study in Japan, some risk factors for the development of psychoses in epileptic patients are discussed.

SUBJECTS AND METHOD We conducted an overview of the literature related to classification of psychoses of epilepsy and analyzed the various criteria used for classification. Based on these findings, we propose a novel five-axis classification scheme. This scheme was applied to patients with epilepsy and psychoses who were currently being treated at five centers in Japan (the psychotic group). Age- and sex-matched epileptic patients with the same epilepsy type, who had no history of psychoses, were also evaluated at each center (the control group). The centers included three university hospitals, one national hospital, and one private hospital, and all had an epilepsy clinic as well as a general psychiatric clinic. The doctors in charge of patient care, all of whom were qualified neuropsychiatrists, completed the scheme. The definition of psychosis was in accordance with the ICD-10 guideline (3), which is identical to the broader definition of DSM-IV (4). Psychosis was thus defined as the presence of hallucinations (insight is not maintained by DSM-IV criteria), delusions, or a limited number of several behavior abnormalities, such as gross excitement and overactivity, marked psychomotor retardation, and catatonic behavior. The Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

Matsuura et al. TABLE 1 Criteria for Classification of Psychoses of Epilepsy Reference

Main criterion

Farlet, 1860 cited in (3) Samt, 1875 cited in (7) Landolt, 1958 (8) Donigier, 1959/1960 (9) Serafetinides and Falconer, 1962 (10) Gastaut, 1973 (1) Bruens, 1974 (2) Ko¨hler, 1975 (11) Toone, 1981 (12) Wolf et al. 1986 (13) World Health Organization, 1992 (3) American Psychiatric Association, 1993 (4) Mendez, 1995 (14) Onuma, 1997 (15) Sachdev, 1998 (16)

Seizure relation Clinical course Clinical course Psychopathology Psychopathology Clinical course Clinical course Clinical course Seizure relation Multidimension Psychopathology

Subcriterion

EEG changes EEG changes

Psychopathology Psychopathology

Psychopathology Seizure relation Multidimension Seizure relation

Clinical course

inclusion criterion was the development of a psychosis after the onset of epilepsy. The exclusion criterion was the presence of consciousness disturbance during psychosis. Patients with senile dementia, personal history of alcohol abuse, or severe head trauma after the onset of epilepsy were also excluded. Cluster analysis was conducted using the hierarchical and nearest-neighbor methods. All patients in the psychotic group were included as variables and the validator for the clusters of patients was an association with clinical variables coded in each axis. ␹ 2 tests were applied to the frequency data for comparison between the psychotic and control groups.

RESULTS Overview of the Literature An overview of the literature revealed that psychopathological symptomatology, clinical course, and a temporal relationship between the development of psychosis and seizure occurrence have been the dominant criteria for classification of psychoses of epilepsy (1– 4, 7–16) as shown in Table 1. One group of researchers used a subcriterion that included the relationship to seizure activity or EEG changes (8), while another group used multidimensional criteria (13, 15). Although psychopathology has frequently been used as the main or subcriterion, various subcategories have been reported (2– 4, 8 –12, 14), as shown in Table

New Classification for Psychoses of Epilepsy TABLE 2 Classification of Psychopathology of Psychoses of Epilepsy Reference Landolt, 1958 (8)

Donigier, 1959/1960 (9)

Serefatinides and Falconer, 1962 (10)

Bruens, 1974 (2)

Ko¨hler, 1975 (11)

Toone, 1981 (12) WHO, 1992 (3)

American Psychiatric Association, 1993 (4)

Mendez, 1995 (14)

Classification of Psychopathology Twilight psychotic state with productive symptomatology Secondary induced syndrome Secondary reactive syndrome Hebephrenic episode Paranoid episode Catatonic episode Pure hallucinosis Systematized delusion Acute confusional psychotic episode Paranoid with affective symptomatology Schizophrenia-like psychosis Alternating psychoses with productive symptomatology Paranoid syndromes Schizophrenia-like syndrome Episodic schizophrenia-like psychoses Affective psychoses Atypical (or mixed) psychoses Chronic schizophrenia-like psychoses Schizophrenia-like/Paranoid psychosis Affective psychosis Delusional (schizophrenia-like) disorder Hallucinosis Catatonic disorder Psychotic disorder (delusion dominant) Psychotic disorder (hallucination dominant) Catatonic disorder Schizophrenia-like/delusional psychosis Affective psychosis

2. Many precipitating factors of psychoses, such as co-morbidity of other psychiatric disorders, specific personality traits, changes in antiepileptic drug regimen, and psychosocial factors, have been reported. Organic background including intelligence disturbance, past history of brain damage, and abnormal findings on brain imaging techniques have also been shown to correlate with the development of psychoses of epilepsy. Proposal for a Five-Axis Classification Scheme Based on an overview of the literature, we proposed an original five-axis classification scheme (Table 3). 1. Axis 1 (epilepsy variables) A. Type of epilepsy was classified according to the International Classification of Epilepsies and Epileptic Syndromes (17).

345 B. Laterality of focus was assessed based on clinical EEG findings. Ictal EEG was assigned a higher priority in determining the focus than interictal epileptic discharges. When ictal EEG could not be recorded and interictal discharges appeared bilaterally, its dominance over 75% on one side was defined as a unilateral focus, while all other cases were defined as bilateral foci (18). 2. Axis 2 (psychopathology variables) A. Type of psychoses was coded according to the F2 category of ICD-10, Chapter 5 (3). B. Clinical course of psychoses was divided into four categories. A single episode implied a duration of psychosis longer than 1 day and remission within 1 year. Recurrent episodes indicated a relapse of psychotic episode(s) with a period of remittance of longer than 2 months. Chronic course was defined as a duration of psychotic state over 1 year without remittance for more than 2 months. The fourth category was that of chronic course after recurrent psychotic episodes. 3. Axis 3 (ictus/EEG variables) A. The temporal relationship between onset of psychosis and seizure occurrence was categorized into four groups. Interictal onset implied development of psychosis during a seizure-free period or a period in which seizure frequency remained unchanged. Postictal onset was defined as development of psychosis within 1 week of the previous seizure(s). Parictal onset was defined as development of psychosis when seizure frequency had increased twofold higher than usual. Alternative onset implied that the patient had became completely seizure free or the frequency had dramatically decreased during a 1-month period prior to the onset of psychosis. B. EEG changes were categorized into four groups. No changes in EEG implied that the frequency of epileptic discharges during psychosis was within twice the usual frequency during the nonpsychotic state, and aggravation EEG meant that the frequency was twofold higher than usual. Improvement in EEG was said to have occurred when epileptic discharge had diminished completely or decreased dramatically. The fourth category was that of unknown causes for EEG changes during psychosis. Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

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TABLE 3 Five-Axis Classification Scheme of Epileptic Psychoses Axis 1: Epilepsy variables A. Type of Epilepsy 1. Idiopathic generalized 2. Idiopathic localization-related 3. Symptomatic/cryptogenic generalized 4. Frontal lobe 5. Temporal lobe 6. Parietal lobe 7. Occipital lobe 9. Others B. Laterality of focus 1. Left 2. Right 3. Bilateral 4. Diffuse 9. Others Axis 2: Psychopathology variables A. Type of psychoses 1. Hallucinosis 2. Delusional disorder 3. Paranoid schizophrenia-like disorder 4. Hebephrenic schizophrenia-like disorder 5. Acute transient psychotic disorder 6. Catatonic disorder 9. Others B. Clinical course of psychosis 1. Single episode 2. Recurrent episodes 3. Chronic course 4. Chronic after recurrent episodes 9. Others Axis 3: Ictus/EEG variables A. Psychosis onset and temporal relationship with seizures 1. Interictal 2. Postictal 3. Parictal 4. Alternative 9. Others B. EEG changes during psychosis 1. Not changed 2. Aggravated 3. Normalized 4. Unknown 9. Others

4. Axis 4 (precipitating factors) A. Comorbidity of other psychiatric disorders was coded according to the F06 category of ICD-10, Chapter 5, which includes mood disorders, dissociative disorder, emotionally labile disorder, and anxiety disorder (3). B. Specific personality traits were coded according to ICD-10 RDC F07, option 1 (19). Apathetic personality trait implied consistent impairment of ability to continue purpose-directed activity. Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

Axis 4: Precipitating factors A. Comorbidity of psychiatric disorders 0. None 1. Mood disorder 2. Anxiety disorder 3. Dissociative disorder 4. Emotionally labile disorder 9. Others (Provoke psychosis: definitely/probably/unlikely) B. Specific personality traits 0. None 1. Apathetic 2. Pseudo-psychopathic 3. Limbic-epileptic 9. Others (Provoke psychosis: definitely/probably/unlikely) C. Changes in antiepileptic drug regimen 0. None 1. Add-on 2. Discontinuation 3. Overdoses 9. Others (Provoke psychosis: definitely/probably/unlikely) D. Psychosocial factors 0. None 1. Specify (Provoke psychosis: definitely/probably/unlikely) Axis 5: Organic background A. Intelligence disturbance 0. None 1. Mild 2. Moderate 3. Severe 9. Others B. Past histories of brain damages 0. None 1. Specify C. Abnormalities by brain imaging techniques 0. None 1. Specify

Pseudo-psychopathic personality trait, characterized by irritability and outbursts of anger, was defined as disinhibition of impulse or demand without consideration of social custom. Limbepileptic personality traits included excessive suspiciousness, ethical adherence, circumstantiality, viscosity, hypergraphia, and changes in sexual behavior. C. Changes in antiepileptic drug regimen were categorized into three groups; psychoses that

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developed after add-on therapy, after discontinuation, and after an overdose. D. Psychosocial factors were coded psychosocial and environment problems according to the fourth axis of DSM-IV (4). The assessment as to whether the doctor in charge thought each factor had provoked the psychosis definitely, probably, or unlikely was also coded. 5. Axis 5 (organic background) A. Intelligence disturbance was assessed by clinical findings with reference to the results of psychometric intelligence tests according to the ICD-10 guideline (3). B. Past history of brain damage was specified. C. Abnormalities in brain CT and/or MRI were specified. Clinical Trial on a Multicenter Basis A total of 128 cases (male 63, female 65) in the psychotic group, as well as the control group, were recruited across five centers. The average age of the psychotic group was 39.9 ⫾ 12.8 years and the average age at onset of epilepsy was 13.5 ⫾ 9.8 years. These were similar to those of the control groups (38.1 ⫾ 12.8 years and 14.9 ⫾ 11.0 years, respectively). Among the psychotic group, the average age at onset of psychosis was 27.9 ⫾ 9.5 years and average period from onset of epilepsy to that of psychosis was 14.3 ⫾ 10.0 years. The results of each axis of the psychotic and control groups are summarized in Table 4. Type of Epilepsy and Laterality of Focus (Axis 1) Patients with temporal lobe epilepsy were the most prevalent (n ⫽ 61), followed by those with other types of symptomatic localization-related epilepsies (frontal 22, parietal 6, occipital 3, other than temporal but undetermined 14). Idiopathic generalized epilepsy (n ⫽ 9) and symptomatic generalized epilepsy (n ⫽ 7) were relatively rare. The frequency of the laterality of epileptic focus among the psychotic group was equally distributed: left-sided focus was seen in 37 cases and right-sided focus in 35 cases. There were 18 cases with bilateral foci and 26 cases with diffuse epileptic discharges. The distribution of focus laterality was similar in the control group (left-sided focus in 36 cases, right-sided focus in 27 cases, bilateral foci in 10 cases, and diffuse epileptic discharges in 15 cases).

In patients with temporal lobe epilepsy among the psychotic group, the side difference of the focus was also equally distributed: left-sided focus was seen in 22 cases, right-sided focus in 22 cases, and bilateral foci in 13 cases. The distribution of focus laterality among the control group was also similar (left-sided focus in 21 cases, right-sided focus in 15 cases, bilateral foci in 6 cases).

Type of Psychosis and its Clinical Course (Axis 2) Among the psychotic group, patients with a paranoid schizophrenia-like disorder (n ⫽ 52) were the most prevalent, followed by those with a delusional disorder (n ⫽ 24), and acute transient psychotic disorder (n ⫽ 22). Patients with hebephrenic schizophrenia-like disorder (n ⫽ 13) were also seen, while cases of catatonic disorder (n ⫽ 9) and hallucinosis (n ⫽ 7) were relatively rare. Single-episode (n ⫽ 31), recurrent-episode (n ⫽ 44), and chronic course (n ⫽ 43) psychoses were equally distributed. There were eight patients who showed recurrent episodes at an earlier stage and then a chronic course at a later stage. Clinical course and the type of psychosis were correlated. Acute transient psychotic disorder and catatonic disorder frequently showed a single episode or recurrent episodes. In contrast, paranoid schizophrenia-like disorder, delusional disorder, and hebephrenic schizophrenia-like disorder frequently showed recurrent episodes or a chronic course.

Temporal Relationship between Onset of Psychosis and Seizure Occurrence and EEG Changes during Psychosis (Axis 3) Among the psychotic group, patients with interictal psychosis (n ⫽ 88) were the most prevalent, followed by those with postictal psychosis (n ⫽ 21), while cases of alternative (n ⫽ 8) and parictal (n ⫽ 4) psychosis were rare. Two patients showed characteristics of both alternative and postictal psychosis. They developed psychoses after diminution of complex partial seizures and just after relapse of secondarily generalized seizure. Cases showing no changes in EEG (n ⫽ 49) during psychosis were prevalent, while cases showing normalization (n ⫽ 8) and aggravation (n ⫽ 4) of EEG were rare. However, cases in which the EEG could not be recorded during psychosis (n ⫽ 67) were the most prevalent. Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

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TABLE 4 Multiaxis Classification Scheme of 128 Epileptic Patients with Psychoses across Multicenters Psychotic Axis 1: Epilepsy variables A. Type of epilepsy Temporal lobe epilepsy Frontal lobe epilepsy Symptomatic localization-related epilepsy (unknown focus) Idiopathic generalized epilepsy Symptomatic/cryptogenic generalized epilepsy Parietal lobe epilepsy Occipital lobe epilepsy B. Laterality of epileptic focus Left-sided Right-sided Bilateral Diffuse Axis 2: Psychopathology variables A. Type of psychosis Paranoid schizophrenia-like disorder Delusional disorder Acute transient psychotic disorder Hebephrenic schizophrenia-like disorder Catatonic disorder Hallucinosis B. Type of clinical course Recurrent episodes Chronic course Single episode Chronic after recurrent episodes Axis 3: Ictus/EEG variables A. Temporal relationship with seizure occurrence Interictal Postictal Alternative Parictal

Control

48% 17

48% 17

11 7

11 7

6 5 2

6 5 2

29% 27 14 6

28% 21 8 11

41% 19 17 10 7 6

— — — — — —

34% 34 24 6

— — — —

69% 16 6 3

— — — —

B. EEG changes Unchanged Normalized Aggravated Unknown Axis 4: Precipitating factors A. Comorbidity of psychiatric disorders Mood disorders Dissociative disorder Emotionally labile disorder Anxiety disorder B. Specific personality traits Pseudo-psychopathic Limbic-epileptic Apathetic C. Changes in antiepileptic drug regimen Add-on Discontinuation Overdoses D. Psychosocial factors present Axis 5: Organic background A. Intelligence disturbance* Present mildly Present moderately B. CNS lesion in premorbid history present C. CNS lesion by neuroimaging present**

Psychotic

Control

38% 6 3 52

— — — —

4% 3 2 2

2% 9 2 2

9% 9 2

5% 13 2

6% 4 2 9%

— — — —

39% 9

16% 5

27%

24%

38%

25%

* P ⬍ 0.05. ** P ⬍ 0.01.

Precipitating Factors of Psychoses (Axis 4) A comorbidity of psychiatric disorders among the psychotic group was found in 26 patients. These cases included affective disorder (n ⫽ 9), dissociative disorder (n ⫽ 6), emotionally labile disorder (n ⫽ 5), and anxiety disorder (n ⫽ 4). Among these cases, those in which the disorder was found to have provoked the psychosis definitely or probably included 16 patients (13%). The incidence and distribution of comorbidity among the control group were similar (affective disorder in 2 cases, dissociative disorder in 11 cases, emotionally labile disorder in 2 cases, and anxiety disorder in 3 cases). Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

Specific personality traits were found in 26 patients among the psychotic group. These included limbepileptic personality (n ⫽ 12), pseudo-psychopathic personality (n ⫽ 11), and apathetic personality (n ⫽ 3). Among these cases, those in which the trait was thought to have provoked the psychosis included 20 patients (16%). The incidence and distribution of specific personality traits among the control group were also similar (limbepileptic personality in 16 cases, pseudo-psychopathic personality in 11 cases, emotionally labile disorder in 6 cases, and apathetic personality in 2 cases).

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New Classification for Psychoses of Epilepsy

Changes in antiepileptic drug regimen prior to the onset of psychosis were found in 23 patients among the psychotic group. These included add-on of a new antiepileptic drug (n ⫽ 11), abrupt discontinuation (n ⫽ 7), overdose (n ⫽ 3), and a combination of these three. Among these cases, those in which the change was thought to have provoked the psychosis included 15 patients (12%). A prominent psychosocial event(s) prior to the development of psychosis was noted in 38 patients. Among these cases, those in which the event was thought to have provoked the psychosis included 12 patients (6%). Organic Background (Axis 5) Sixty-two patients among the psychotic group had some intelligence disturbance (mild disturbance in 50 patients and moderate in 12 patients). The frequency was significantly (␹ 2 ⫽ 22.4, P ⬍ 0.01) higher than that among the control group (mild disturbance in 20 patients and moderate in 6 patients), especially for that of the mild type. Past history of brain damage was noted in 34 patients among the psychotic group. These cases included, in order of frequency, encephalitis, perinatal disturbance, brain contusion, status of febrile convulsions, postoperative state of brain tumor, and cerebrovascular accident. The frequency and distribution were similar among the control group (31 cases). Abnormal findings by brain CT and/or MRI were noted in 49 patients among the psychotic group. These cases included, in order of frequency, diffuse brain atrophy, unilateral hippocampal atrophy, focal brain atrophy, and small tumorous lesion. The frequency was significantly (␹ 2 ⫽ 5.2, P ⬍ 0.05) higher than that among the control group (32 cases) but the distribution was similar. Cluster Analysis Among the psychotic group, four clusters were discriminated: (I) 35 patients, (II) 12 patients, (III) 39 patients, (IV) 42 patients. Clinical variables showing a significant association with these four clusters of type of psychosis, temporal relationship with seizure occurrence, and EEG changes during psychosis. Cluster I was characterized by interictal onset of psychosis (94%) and by chronic types of psychopathology, such as delusional disorder (26%) and hebephrenic schizophrenia-like disorder (17%). Cluster II was clearly discriminated from other clusters, characterized by post-

ictal onset (83%) and by acute transient psychotic disorder (100%). Clusters III and IV were characterized by interictal onset (79 and 55%, respectively) and by paranoid schizophrenia-like disorder (54 and 38%, respectively). Cluster III was also characterized by no changes in EEG during psychosis (92%), while EEG normalization during psychotic state was observed among some cases in cluster IV (12%).

DISCUSSION The definition of psychosis, as well as the categorization of each axis of the present classification scheme, is based largely on ICD-10 (3) criteria. Although the use of ICD-10 or DSM-IV (5) restricts the potential for understanding of the psychoses of epilepsy, it appears reasonable to follow these criteria given that their categorization has been validated by a large number of international clinical trials and is widely employed in psychiatry at present. Moreover, it makes it possible to compare the psychoses of epilepsy with functional psychoses or other organic psychoses. One of the reasons for the lack of a standardized classification scheme for psychoses of epilepsy stems from the different definitions of psychosis used by different researchers. Both ICD-10 and DSM-IV define psychosis not as a disease but as a state characterized by the presence of hallucinations (without insight), delusions, or several behavioral abnormalities. Although disturbance of consciousness may be difficult to test, its existence justifies the diagnosis of delirium even when psychotic symptoms are present. Because ictal psychoses are accompanied by consciousness disturbance to varying degrees, we excluded them from the definition of psychosis in epilepsy, as some researchers have already done (20, 21). Whether ictal psychosis should be included or not in the classification scheme requires further examination. A problem might be the possible underreporting of ictal psychosis in the sense that it is likely to occur in the community and not come to the attention of neuropsychiatrists. Simple partial status may be misinterpreted as psychosis because it may include hallucinations and thought disorders under clear consciousness (22). However, as this insight into hallucinations indicates, its manifestation does not represent a real psychosis. Another issue to be discussed is the duration of psychotic symptoms accepted as psychosis. Dongier (9) accepted duration of a few hours to define psychosis. However, her definition included ictal psychoses, Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

350 especially those of nonconvulsive status epilepticus. More than 70% of non-convulsive status epilepticus resolve within 24 hours (7); adoption of a minimum duration of 24 hours for the definition of psychosis may serve to exclude ictal psychoses. Although limitations may exist in the present study because of its very clinical nature, the present results of a relatively large sample across multiple centers make it possible to discuss some risk factors for development of psychosis in patients with epilepsy. Patients with temporal lobe epilepsy were prevalent in the present study, as shown in axis 1A, but no conclusion on the rate of psychosis in different types of epilepsy could be drawn due to the lack of community-based data. Our previous hospital-based study showed that temporal lobe epilepsy was the most frequent type of epilepsy in unselected series of adult epilepsies (25). Many previous studies have reported a high prevalence of psychoses in temporal lobe epilepsy (2, 5, 8, 9, 21, 23, 24), while a review of the literature of controlled studies reveals that the prevalence of psychoses in temporal lobe epilepsy was similar to that of other types of epilepsies (7). Because most patients with epilepsy and psychosis had multiple seizure types, we did not include seizure types in axis 1 to avoid complexity. Although the present study had a limitation in that laterality of focus was determined by scalp EEG findings, the data revealed no side difference in epileptic focus, as shown in axis 1B, and this was true in the case of temporal lobe epilepsy. A lack of a lateralization difference and a relatively high rate of bilateral foci in psychotic patients, as in the present study, have been reported previously (20, 23, 26). The type of psychosis was highly heterogenous, as shown in axis 2A, and among them, pure hallucinosis and catatonic disorder were relatively rare, findings that are similar to those of previous studies (9, 12, 23). For coding axis 2B, the definition of chronicity required further examination. There have been reported durations of at least 6 months (7) or 1 year (27) for the definition of chronicity. This study noted that several patients remitted over 6 months and within 1 year, and thus a 1-year duration for the definition of chronicity is thought to be valid. Eight cases showed recurrent episodes at an earlier stage and chronic course at a later stage. Previous descriptions of such patients can be found in the literature (2, 11, 12, 23, 26). Categorization of psychoses of epilepsy according to the temporal relationship between development of psychosis and seizure occurrence has not been clearly defined, given that very subtle clinical seizures could Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.

Matsuura et al.

mistakenly be considered absent. Despite this limitation, it has been widely used traditionally from the interest of pathophysiology of developing psychoses in epilepsy. In the present results of axis 3A, interictal onset was most prevalent, while postictal onset amounted to 16%, a finding that was similar to reported rates (7, 9). Parictal onset, which occurs in cases in which increased seizure frequency is accompanied by a gradual development of psychosis, was only 4%. This category will likely be missed if seizure frequency over prolonged periods is not documented in detail (7). Landolt (8) described the phenomenon of forced normalization and used EEG changes as a dominant criterion for classification of psychoses of epilepsy. Given that in many patients the EEG could not be recorded during psychosis, as shown in axis 3B, a limitation might exist in its use as a main criterion for classification. In this regard, the concept of alternative psychosis introduced by Tellenbach (28), which focused on the clinical absence of seizures, is thought to be useful. Although Dongier (9) described the phenomenon of forced normalization or alternative psychosis in 24% of her 516 cases, most studies (7, 16) reported smaller rates similar to the 6% found in the present study. Precipitating factors were coded in axis 4 and the judgment of their influence on development of psychoses was based on clinical impression by the doctor in charge. The frequency and distribution of comorbidity and specific personality traits did not differ between the psychotic and control groups. Some researchers have reported on the contribution of personality deviations to developing psychosis (29), whereas others have found no contribution (23). The specific personality traits of the ICD-10 RDC F07 category (19) are those of descriptive guidelines and operational criteria for them are needed for further clarification. Twelve percent of the psychoses were thought to have been provoked by changes in antiepileptic drug regimen. We have already stressed that maintenance of compliance and slow changes in drug regimen are crucial for preventing development of psychosis (30, 31). Nine percent of the subjects were evaluated as having developed their psychosis by stressful psychosocial events. The possible influence of psychosocial factors like stigmatization, discrimination, and deprivation on the development of psychosis in epilepsy has been reported (28). The proportion of intelligence disturbance, especially that of mild type, was significantly higher in the psychotic group than in the control group. Ferguson et

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New Classification for Psychoses of Epilepsy

al. (32) postulated that a cognitive deficit following a brain lesion predisposes patients to psychosis. Although the rate of past history of brain damage did not differ between the two groups, various abnormal CT/MRI findings were significantly higher in the psychotic group than in the control group. Slater et al. (23) reported on the contribution of nonspecific brain damage to development of schizophrenia-like psychoses (20, 23), especially those with cortical atrophy and ventricular enlargement. Toone et al. (33) could not replicate the findings. Involvement of hippocampal atrophy in the development of psychosis is also still a controversial issue. Some studies reported its contribution (34) while others did not (10, 35). Cluster analysis of the present results showed the validity of classifying psychoses of epilepsy into interictal and postictal onset. However, there might be a parictal onset between these two extremes and alternative onset might constitute a part of the interictal psychosis subgroup. The psychopathology of interictal onset was characterized by paranoid schizophrenia-like disorder, delusional disorder, hebephrenic schizophrenia-like disorder, and hallucinosis, while that of postictal onset was characterized by acute transient psychotic disorder. Because there is an overlap between them, classification of psychoses of epilepsy according to a single criterion is not justified. The present results revealed a wide variety of psychoses of epilepsy. Some previous studies classified psychoses of epilepsy from a multidimensional standpoint. Wolf et al. (13) categorized them by their temporal relationship with seizure occurrence, changes in antiepileptic drug regimen, psychological precipitant, and chance coincidence. Onuma (15) categorized them by their temporal relationship with seizure occurrence, clinical course, and EEG changes. However, as they placed these categories at the same axis, there may be patients who belong to more than one category at the same time. The present five-axis classification scheme describes a dimensional representation of individual patients accurately and systematically and is thought to carry direct therapeutic implications. By further accumulation of clinical findings of a large sample on a multicenter basis, we were able to understand the pathogenesis, establish the treatment, estimate the prognosis, and ultimately apply appropriate measures for preventing psychoses of epilepsy. Establishment of a new multiaxis classification scheme is thought to contribute not only to therapeutic activity but also to research promotion.

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