Psychosis of epilepsy--an approach to a biological basis for postictal and interictal psychoses

Postictal and interictal changes in behavior and the corresponded neurochemical data in the kindling model of epilepsy are reviewed briefly to explore a biological base for epileptic psychosis. Kindling can be a potent animal model to study this problem. A possible participation of both TRH and opioid system in prolonged postictal behavior disorder and of TRH, mesolimbic system and/or PI response to excitatory amino acid in interictal behavior disorder are discussed. A further experimental study is required to disclose the basic mechanism of epileptic psychosis.     

Progression of postictal to interictal psychosis

PURPOSE: To describe a case series of patients with both postictal psychosis (PIP) and chronic interictal psychosis (IIP). METHODS: We retrospectively reviewed the records of 43 patients with PIP from a comprehensive epilepsy center to find evidence of both PIP and IIP in the same patient. RESULTS: Six (13.9%) of the 43 patients met all the criteria for both PIP and IIP. Five of our six patients had multiple documented PIPs before they became chronically psychotic. The range of length of time between PIP and IIP was 7 to 96 months. Postictal and interictal psychotic behavior was similar or identical in five of six cases. CONCLUSIONS: The results of this study suggest a progression from PIP to IIP: there is a similarity between the symptoms of the two psychoses, a history of multiple PIPs before the first IIP, and a period of months to years between PIP and IIP onset.     

Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a retrospective comparison with psychoses in temporal lobe epilepsy.

There have been few studies of the psychopathology of patients with frontal lobe epilepsy (FLE). The majority of studies of both inter-ictal and post-ictal psychoses have strongly suggested the influence of temporal lobe disturbance on psychoses. Patients with organic brain damage or schizophrenia, however, sometimes show frontal lobe dysfunction. The purpose of this study was to better understand the effect, if any, of frontal lobe disturbance and seizure on psychopathology. Patients were divided into four groups based on epilepsy type and preceding seizures; 8 with FLE/inter-ictal psychosis, 3 with FLE/post-ictal psychosis, 29 with temporal lobe epilepsy (TLE)/inter-ictal psychosis, and 8 with TLE/post-ictal psychosis. Psychopathologic symptoms were retrospectively reviewed based on case notes, using a modified brief psychiatric rating scale (BPRS). Psychomotor excitement, hostility, suspiciousness, and hallucinatory behaviour were prominent features in all four groups. Six orthogonal factors were derived by factor analysis from the original data based on the 18 BPRS items. FLE patients with inter-ictal psychosis showed marked hebephrenic characteristics (i.e. emotional withdrawal and blunted effect). Our findings suggest that patients with FLE can exhibit various psychiatric symptoms. However, their psychotic symptoms, hebephrenic symptoms in particular, may often be overlooked.     

Reexamination of interictal psychoses based on DSM IV psychosis classification and international epilepsy classification

We sought to examine interictal psychoses based on the international epilepsy classification and DSM IV criteria, with special attention paid to epilepsy types as well as to subcategories of psychoses. One hundred thirty-two outpatients were studied, each with definite evidence of both epilepsy and interictal psychosis clearly demarcated from postictal psychosis. We compared them with 2,773 other epilepsy outpatients as a control. Risk factors for psychosis were examined within the temporal lobe epilepsy (TLE) group and the more extended group of symptomatic localization-related epilepsy. Further, nuclear schizophrenia and other nonschizophrenic psychotic disorders were compared. We confirmed a close correlation between TLE and interictal psychoses. Within the TLE group, only early epilepsy onset and a history of prolonged febrile convulsions were revealed to be significantly associated with interictal psychosis. Within the symptomatic localization-related epilepsy group, such parameters as complex partial seizures, autonomic aura, and temporal EEG foci were closely associated with psychoses. There was also a significant difference between groups as to ictal fear and secondary generalization. Whereas patients with early psychosis onset and a low intelligence quotient were overrepresented in the nuclear schizophrenia group, drug-induced psychosis and alternative psychosis were underrepresented. TLE proved to be preferentially associated with interictal psychoses. Within the TLE group, medial TLE in particular was found to be more closely associated with psychosis. Our data support the original postulation of Landolt, stating that alternative or drug-induced psychoses constitute a definite subgroup of interictal psychoses, which are different from chronic epileptic psychoses that simulate schizophrenia.     

Treatment of the interictal psychoses

BACKGROUND: The interictal "schizophrenia-like" psychoses of epilepsy conventionally are treated with antipsychotic medication with uncertain results. In patients with these psychoses, a preceding and concomitant dysphoric disorder usually can be documented. Effectiveness of the pharmacologic treatment by the combination of drugs that is effective for severe interictal dysphoric disorders is demonstrated in a series of patients with interictal psychosis. METHOD: Patients were treated with the combination of a tricyclic antidepressant and a selective serotonin reuptake inhibitor, enhanced if necessary by a small amount of the atypical neuroleptic risperidone. The series consisted of 8 consecutive patients with interictal psychosis seen over a 20-month period. Two additional patients seen over the past 10 years who required a different therapeutic intervention were also included. RESULTS: Five of the 8 consecutive patients achieved full remission of their psychosis; 3 patients could not be reached for the full treatment effort. One patient with a malignant psychosis had been treated successfully (prior to the series reported) by surgical removal of a left frontal epileptogenic zone; a second patient (treated after the series) recovered only upon elimination of the antiepileptic drug that had suppressed clinical seizures but had resulted in an alternating psychosis. CONCLUSION: Interictal psychoses can be viewed as severe interictal dysphoric disorders with psychotic features. The same combination of psychotropic medication that is effective for severe interictal dysphoric disorders serves as the primary therapy for interictal psychoses. The interictal psychiatric disorders presumably result from seizure-suppressing mechanisms that are the targets of the proconvulsant drugs. Upon suppression of seizures, some patients with interictal psychosis may require modification of the antiepileptic medication responsible for excessive inhibition. Complete surgical removal of the epileptogenic zone can eliminate a chronic interictal psychosis upon postoperative fading of inhibitory mechanisms.     

Alternating and postictal psychoses: review and a unifying hypothesis

A comparison of the clinical and pathophysiological features of postictal psychosis and brief interictal or alternating psychosis was undertaken to examine if the underlying mechanisms are distinct in these 2 conditions. A selective review of the published literature in English on epilepsy and brief psychosis was carried out. The literature indicates that even though brief postictal and alternating psychoses are considered to be separate syndromes, they have a number of similarities. It can be argued that the underlying pathomechanisms are common, with the brain's inhibitory processes in response to seizures playing a key role in the development of the psychosis. These homeostatic mechanisms manifest as electrophysiological, cerebral blood flow, and neurotransmitter and receptor changes. Both syndromes are likely to be associated with prolonged inhibition in limbic circuits, with further seizures modifying the psychosis depending upon whether it is associated with disinhibition or hypersynchrony involving enhanced inhibition. The neurotransmitter with a key role is GABA, although ionic currents, catecholamines, opiates, adenosine, glutamate, and nitric oxide play a role. Brief postictal and alternating psychoses provide an opportunity to understand the complex relationships between epilepsy and schizophrenia-like brief psychotic episodes, and this understanding can assist in their management.     

Psychoses and epilepsy. A case study

Over the last few decades much research has been done into the raised level of psychiatric comorbidity in epilepsy. On the basis of a case study of a patient suffering from post-ictal psychoses we explain the psychiatric differential diagnosis within the framework of epilepsy and we investigate the frequent psychiatric side-effects of anticonvulsants. It is concluded that the links between epilepsy and psychiatric symptoms are complex and that the neuropsychiatry of epilepsy is concerned with syndromes that are unique and do notfit into modern psychiatric classification systems.     

The price of seizure control: dynorphins in interictal and postictal psychosis

Postictal and interictal psychoses are relatively common complicating factors in the clinical course of epilepsy, yet their neurobiological substrates are poorly understood. Recent evidence shows that kappa opioid receptor (KOR) activation elicits anticonvulsant and psychotomimetic effects. In view of this background, here we introduce the hypothesis that epilepsy-related psychoses may partially result from excessive hippocampal dynorphin release and kappa opioid receptor overstimulation aimed at seizure control.     

The expression of interictal, preictal, and postictal facial-wiping behavior in temporal lobe epilepsy: a neuro-ethological analysis and interpretation

By videotape recordings analysis we investigated the frequencies of interictal, preictal, and postictal wiping or rubbing movements targeting the face region (face wiping, FW) in 17 right and 13 left mesial temporal lobe epilepsy (MTLE) patients. Patients' data were compared with FW frequencies obtained in 22 healthy controls listening to a presentation. Results showed that: (1) FW movements were present in both controls and patients; however, the patient groups showed lower interictal and preictal FW rates relative than controls; (2) right and left temporal lobe seizures were followed by a marked increase in the expression of wiping activities directed to the nose as well as to other face regions with respect to the interictal-preictal period; (3) during the first 5min postictal FW was performed preferentially with the hand ipsilateral to the seizure focus; (4) postictal examination of the patient by an observer, especially if of the opposite sex, resulted in a higher incidence of FW acts. After temporal lobe seizures there is an exaggerated expression of movements targeting the face region, and not exclusively directed to the nose. According to an ethological interpretation of the FW behavior as a motor behavior present throughout the phylogenetic scale, from rodents to primates, we suggest the postictal emergence of an innate action pattern modulated by external emotional-cognitive stimuli.     

Autonomic nervous system functions in interictal and postictal periods of nonepileptic psychogenic seizures and its comparison with epileptic seizures

Purpose(1) To evaluate autonomic nervous system (ANS) functions during both interictal and postictal periods in a group of cases with nonepileptic psychogenic seizures (NEPS) and a group of epileptic patients to determine whether they have autonomic dysfunction. (2) If a significant difference can be established between epileptic and NEPS groups, to determine whether ANS tests can be used as a clinical helper in the differentiation between epileptic seizures (ES) and NEPS.MethodsANS functions (sympathetic skin response and R–R interval variation) were measured during both interictal and postictal periods in 25 patients who had NEPS and 30 patients who had primary generalized tonic–clonic seizures (GTCS) and partial seizures with secondary GTCS, as well as once in the healthy control group.ResultsWhen the patient group with NEPS both in the interictal and postictal period was compared with the control group, functions of both sympathetic and parasympathetic systems were found normal. This finding implies that patients with NEPS have normal ANS functions. A comparison of the epileptic patient group in the interictal and postictal periods with the control group revealed that the former had dysfunctions in both the sympathetic and parasympathetic systems. When patients with NEPS were compared with the ES, the measurements in sympathetic and parasympathetic nervous system functions during the interictal and postictal periods in the ES group were significantly different than those of the NEPS group.ConclusionThis finding indicates that measurements of ANS functions may be helpful in differentiating between ES and NEPS.     

A prospective study of postictal psychoses with emphasis on the periictal type

PURPOSE: To assess prospectively episodes of postictal psychosis. METHODS: We followed 108 consecutive patients with temporal lobe epilepsy, who were divided into three groups: those without psychotic episodes (n=87, N group), those with interictal psychosis (n=13, IIP group), and those with postictal psychosis (n=8, PIP group). The first episode of postictal psychosis, which was defined as a psychotic episode that occurred within 1 week after the end or within 3 days before the beginning of seizure clusters, was assessed with the Brief Psychiatric Rating Scale (BPRS) and Social Dysfunction and Aggression Scale (SDAS) during the observation period. RESULTS: The duration of illness was significantly different between the N and PIP groups (p=0.004) and between the N and IIP groups (p=0.039). The average initial BPRS score (obtained 3.0 days after the end of the seizure cluster) was 19.7, and then decreased to 5.8 after 1 week, and finally normalized at 1.5 after 1 month. A statistically significant decrease in BPRS scores was found between the initial assessment and those obtained after 1 week (p=0.011). Those who had psychotic episodes without a lucid interval tended to have episodes more often than monthly, and experienced additional seizure recurrence even during the psychotic episodes. Two patients exhibited a frank manic phase, and three patients showed excessively aggressive behavior, as determined by the SDAS. CONCLUSIONS: Postictal psychosis should be subdivided into the nuclear type, with an established clinical picture as an indirect aftereffect of seizure activity, and the atypical periictal type, which is a direct manifestation of limbic discharge.     

Frequency and age-related variables in interictal psychoses in localization-related epilepsies

PURPOSE: Several studies have described that patients with temporal lobe epilepsy (TLE) develop psychoses more frequently than patients with extra-temporal localization-related epilepsy (LRE). However, few controlled studies have demonstrated an increased susceptibility to psychosis in TLE patients. As one of a series of multi-center studies on psychosis in epilepsy, we investigated whether the frequency of interictal psychosis differs between types of LRE. METHODS: We reviewed some biological characteristics of 197 PE patients with interictal psychosis and of 456 LRE patients with no history of psychosis. Type of PE was determined as TLE, frontal lobe epilepsy, parietal lobe epilepsy, occipital lobe epilepsy, and multi-lobar epilepsy/undifferentiated lobar epilepsy by clinical symptoms, EEG findings, and neuroimaging. The frequency of psychosis for each type of LRE was compared. Ages at onset of epilepsy and psychosis and the time interval between onset of each were also analyzed. RESULTS: There was no significant correlation between psychosis and epilepsy type (P=0.211). Age-related variables also failed to show any significant differences between LRE types (age at onset of epilepsy, P=0.369; age at onset of psychosis, P=0.852; the time interval, P=0.893). CONCLUSIONS: Patients with LREs as well as with TLE are susceptible to interictal psychosis. The mean ages at onset of symptoms and the interval between onset of epilepsy and onset of psychosis that we observed suggest that patients with LREs, regardless of focus, may share similar processes in the development of psychiatric symptoms.     

Effects of seizure repetition on postictal and interictal neurocardiac regulation in the rat

PURPOSE: Human epilepsy is associated with abnormalities in cardiac regulation, as measured by reductions of heart rate variability (HRV) and approximate entropy (ApEn), but it is not known how these abnormalities are related to seizure experience. METHODS: Baseline electrocardiogram (ECG) was recorded from seizure-naive rats. They were subjected daily to maximal electroshock (MES), which induced tonic seizures with hindlimb extension, for a total of 10 days. ECG was obtained for 30 min before and after the first and last seizure. R-R variability, spectral variability, and ApEn were calculated to determine changes in pre- and postictal cardiac regulation. Before the last seizure, interictal parameters were compared with baseline values to determine changes in interictal HRV as a consequence of seizure repetition. Postictal values obtained after the last seizure were compared with the initial postictal data to look for changes in postictal cardiac regulation. RESULTS: During the postictal state, a mild, but significant, loss of ApEn was present after either the first or last seizure. Seizure repetition induced loss of R-R variability and high-frequency spectral band, which was present both interictally and postictally. CONCLUSIONS: The results suggest that convulsive seizures are associated with an immediate reduction of the complexity of cardiac rhythm regulation, as reflected by reductions of ApEn. Seizure repetition may induce long-term neural abnormalities in neurocardiac regulatory systems, especially parasympathetic, which limit appropriate autonomic responses. These acquired abnormalities may, in turn, predispose individuals to cardiac arrhythmia and sudden unexpected death in epilepsy.     

The postictal psychosis of epilepsy: investigation in two patients

Patients with epilepsy have a higher incidence of psychosis. Epilepsy-related psychotic behaviors include a chronic interictal schizophreniform illness, an "alternating psychosis" which remits with seizure activity, and ictal or perictal psychotic behaviors. In addition, there is an uncommon and less understood psychosis characterized by brief psychotic episodes during the postictal period. This report describes two patients with postictal psychosis and correlates their behavior with the pattern of seizures, electroencephalographic discharges, and anticonvulsant and psychotropic medications. The findings suggest that postictal psychosis results from increased epileptiform activity and continued cerebral dysrhythmia, has a latency in onset and is not due to the immediate postictal delirium, and reflects an exacerbation of underlying psychopathological tendencies. This report further discusses the potential pathophysiological mechanisms and management of this disorder.     

Subacute postictal aggression in patients with epilepsy

Three men with epilepsy (age range, 38-62) who exhibited brief episodes of violent behavior during the postictal period are described. Disease duration ranged from 27 to 44 years. Patients had both complex partial seizures and secondarily generalized tonic-clonic seizures, which were refractory to antiepileptic drugs. Postictal aggression occurred shortly after a seizure and lasted 5-30 minutes. The patients displayed physically and verbally aggressive behavior toward others, but regained consciousness promptly and showed regret afterward. Interictal EEGs revealed temporal spikes, SPECT showed hypoperfusion in the temporal and frontal areas in two patients, and neuropsychological examination revealed poor frontal lobe function in two patients. Characteristics of our cases are consistent with subacute postictal aggression (SPA) reported previously. Epilepsy of prolonged duration and brain dysfunction involving a broad area including the temporal and frontal lobes may be associated with the occurrence of subacute postictal aggression.     

Psychoses in drug-resistant temporal lobe epilepsy.

In the survey of 74 Danish patients with temporal lobe epilepsy who underwent temporal lobectomy, a total of 20 patients were psychotic. Nine of these became psychotic during the follow-up period, six of them after cessation of their epileptic seizures. There were 13 schizophrenia-like psychoses, six paranoid delusional and depressive psychoses, and one childhood psychosis. Operation was on the right side in 39 and on the left side in 35 patients. When the various psychotic groups were compared with each other or with the nonpsychotic patients, the side of operation was not found to be statistically important. The patients with psychoses were older at operation and showed a higher rate of focal lesions in the resected specimens. Although more psychotic patients were bright or normally gifted, and had achieved a higher standard of schooling than nonpsychotic patients, their social status after operation was inferior. Surgery had no effect on psychosis present preoperatively nor on its possible postoperative onset. The diagnosis of psychosis was not considered to be contraindication to temporal lobectomy.     

Recurrent postictal psychosis after remission of interictal psychosis: further evidence of bimodal psychosis

PURPOSE: To ascertain whether bimodal psychosis (i.e., independent postictal and interictal psychosis) in patients with epilepsy can be characterized by postictal psychosis that develops after interictal psychosis remits. Methods: We reviewed the records of 14 patients with bimodal psychosis treated at a national center hospital.Clinical and psychopathological characteristics of the patients were examined. RESULTS: Among the 14 patients with bimodal psychosis, four initially had interictal psychosis, and 10 initially had postictal psychosis. That is, interictal-antecedent bimodal psychosis characterized four cases, and postictal-antecedent bimodal psychosis characterized 10 cases. Patients with interictal-antecedent bimodal psychosis composed 2.2% of the total patients with epilepsy and psychosis (n = 180) and 28.5% of total patients with bimodal psychosis. All four patients with interictal-antecedent bimodal psychosis had partial epilepsy with complex partial seizures, bilateral EEG abnormalities, and borderline (or decreased) intellectual functioning. Most of these clinical features are common to both types of bimodal psychosis. Among patients with interictal-antecedent bimodal psychosis, the mean age at the onset of the initial symptoms was 10.8 years (SD, 4.3 years) for epilepsy, 24.4 (6.1) years for interictal psychosis, and 33.8 (4.5) years for postictal psychosis. CONCLUSIONS: In a few patients, postictal psychosis develops after the remission of interictal psychosis. Interictal-antecedent bimodal psychosis is not likely a discrete entity because of several characteristics common to both types of bimodal psychosis. Patients may have greater vulnerability to psychosis and develop psychotic episodes easily, regardless of the presence of preceding seizures.