Psychosis in epilepsy patients

Summary   Epileptic psychoses reflect a fundamental disruption in the fidelity of mind and occur during seizure freedom or during or after seizures. The psychotic symptoms in epilepsy share some qualities with schizophrenic psychosis, such as positive symptoms of paranoid delusions and hallucinations. Psychotic syndromes in epilepsy are most common but not exclusively associated with temporal lobe epilepsy. De Novo psychosis following epilepsy surgery is rare. Forced normalization—psychosis associated with dramatic reduction of epileptiform activity or seizures is described in small series only. Ictal and postictal psychosis can be prevented with seizure control, but postictal and chronic interictal psychoses require multidisciplinary and psychopharmacologic management.     

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.     

Postictal psychosis in temporal lobe epilepsy

PURPOSE: Postictal psychosis is a well-known complication, occurring especially in patients with temporal lobe epilepsy. It usually runs a benign course. The literature on this topic is sparse, and the underlying pathogenic mechanisms are not known. METHODS: We report five patients with temporal lobe epilepsy in whom postictal psychosis developed during the course of video-EEG monitoring; they were studied with hexamethyl-propyleneamine-oxime single-photon emission computed tomography (HMPAO-SPECT) during and after the psychotic event. RESULTS: In comparison to the interictal state, all SPECT scans obtained during postictal psychosis were remarkable for bifrontal and bitemporal hyperperfusion patterns. Some studies also demonstrated unilateral left lateral frontal hyperperfusion. These cortical blood-flow patterns appeared to be distinct from those obtained during complex partial seizures. CONCLUSIONS: Our data suggest that postictal psychoses in patients with temporal lobe epilepsy are associated with hyperactivation of both temporal and frontal lobe structures. This hyperperfusion may reflect ongoing (subcortical) discharges, active inhibitory mechanisms that terminate the seizure, or simply a dysregulation of cerebral blood flow.     

Postictal Psychosis: A Comparison with Acute Interictal and Chronic Psychoses

Summary: We studied 30 patients with postictal psychosis and compared them with 33 patients with acute interictal psychosis and 25 patients with chronic psychosis. All patients had either complex partial seizures (CPS) or EEG temporal epileptogenic foci. Patients with postictal psychosis had a high incidence of psychic auras and nocturnal secondarily generalized seizures. The most striking feature that distinguished postictal psychosis from both acute interictal and chronic psychoses was phenomenological: the relatively frequent occurrence of grandiose delusions as well as religious delusions in the setting of markedly elevated moods and feeling of mystic fusion of the body with the universe. In addition, postictal psychosis exhibited few schizophreniform psychotic traits such as perceptual delusions or voices commenting. Reminiscence, mental diplopia, and a feeling of impending death were also fairly frequent complaints of patients with postictal psychosis. Interictal acute psychosis and chronic epileptic psychosis were psychopathologically similar. Although acute interictal and chronic epileptic psychoses could simulate schizophrenia, postictal psychosis results in a mental state quite different from that of schizophrenic psychosis.     

Characteristics of postictal psychosis in a psychiatric center

The clinical characteristics of 12 cases of postictal psychosis treated at Taipei City Psychiatric Center, Taipei, Taiwan, were retrospectively reviewed. Increased seizure frequency, especially with generalized tonic-clonic seizures, was the major risk factor predisposing to postictal psychosis. The psychotic symptoms were variable with delusions and/or hallucinations. These patients showed a much longer history of epilepsy (21.9 +/- 10.7 years) prior to the development of postictal psychosis than has been previously reported. The possible mechanisms in the pathophysiology of psychosis in epileptics were discussed.     

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.     

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.     

Violence and Epilepsy: A Close Relation Between Violence and Postictal Psychosis

Summary: Purpose: We investigated the incidence of well-directed violent behavior and suicide attempts in patients with temporal lobe epilepsy, with special attention to postictal psychosis.
Methods: We compared 57 episodes of postictal psychosis with 62 episodes of acute interictal (or alternative) psychosis and with 134 complex partial seizures. All patients were matched for age and for age at onset of seizures.
Results: The incidence of well-directed violent behavior against human beings was significantly higher (23%) during postictal psychotic episodes than during acute interictal episodes (5%) and postictal confusion (1%). Suicide attempts were also more frequent during postictal psychosis (7%) than during either acute interictal psychosis (2%) or postictal confusion (0%).
Conclusions: Our study showed that well-directed violent and self-destructive behavior was not a feature of epileptic psychosis in general but a specific hallmark of postictal psychosis.     

Epileptic psychosis

A relationship between serious psychiatric disorders and epilepsy has been observed since antiquity. An association between schizophrenia and epilepsy has been noted since the turn of century, but this relationship appeared to be uncertain. From the 1950s on, a number of studies were devoted to this subject. Epileptic patients are more risk for psychosis than the general population. Others psychiatric syndromes, some of which have been individualized recently, can occur in patients with epilepsy: alternative psychosis, affective states, postictal psychoses, postoperative psychoses. In this article we present the different aspects of the psychoses of epilepsy. Their knowledge allows in most cases a precise diagnosis and an appropriate treatment.     

Postoperative psychoses in epileptic patients after temporal lobectomy

Introduction – Psychosis is the most severe psychiatric complication after epilepsy surgery. Patients and methods – We evaluated postoperatively at 1 year the psychoses of a series of 57 adult patients with intractable epilepsy who underwent temporal lobe surgery. Results – Five patients (8.8%) developed postoperative psychosis. Two (3.5%) of these 5 revealed postictal psychotic episodes in connection with persisting seizures, both of them had had similar episodes even preoperatively. Two patients (3.5%) exhibited a definite and one patient (1.8%) a probable de novo schizophrenia. Conclusion – Our findings clearly emphasize the need for careful postoperative psychiatric follow-up for patients with temporal lobectomy.     

Analogy between psychosis antedating epilepsy and epilepsy antedating psychosis

Purpose: Patients with recurrent epileptic seizures after the development of psychosis (Psychosis‐Epilepsy) have been regarded as belonging to a different clinical entity from those with epilepsy antedating the development of psychosis (Epilepsy‐Psychosis). However, clinical characteristics of patients with Psychosis‐Epilepsy have not been well described, except for early German studies. We aimed to estimate the reliability of distinction between Psychosis‐Epilepsy and Epilepsy‐Psychosis by comparing their clinical characteristics. Methods: Among 312 patients with epilepsy and psychosis enrolled in this multicenter study, 23 patients had Psychosis‐Epilepsy and 289 patients had Epilepsy‐Psychosis (i.e., interictal psychosis). Demographic (i.e., sex, age at time of evaluation, and intellectual functioning), psychiatric (i.e., age at onset of psychosis, subtype of psychosis, duration of psychotic episode, and a family history of psychosis), and epileptic (i.e., age at onset of epilepsy, subtype of epilepsy, seizure type, and a family history of epilepsy) characteristics of both groups were compared. Key Findings: Clinical characteristics, either in their psychoses or epilepsies, except for age‐related variables, were equivalent between patients with Psychosis‐Epilepsy and those with Epilepsy‐Psychosis. Time intervals between onset of psychosis and that of epilepsy in the two groups showed a normal distribution curve. Significance: The presence of many common features and the linear distribution of the time intervals did not fully support that Psychosis‐Epilepsy and Epilepsy‐Psychosis were two distinctly different entities. Among certain patients who have genetic vulnerabilities to both psychoses and seizures, psychosis may develop either antedating or postdating the development of epilepsy. These findings may suggest a necessary reconceptualization of psychoses in epilepsy.     

Psychosis and epilepsy: a neurologist's perspective.

Epilepsy and psychosis are diseases of the brain which cause considerable impact on quality of life particularly when they occur in the same individual. This review comments on postictal psychosis, chronic schizophrenia like psychosis in epilepsy, and the psychoses related to the treatment of epilepsy with antiepileptic drugs and surgery. Possible mechanisms of psychosis including the concept of forced normalization and dopaminergic overactivity in the mesolimbic system are discussed.     

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.     

Psicosis epiléptica periictal,una causa de psicosis reversible

Introduction

Epileptic psychoses are categorised as peri-ictal and interictal according to their relationship with the occurrence of seizures. There is a close temporal relationship between peri-ictal psychosis and seizures, and psychosis may present before (preictal), during (ictal) or after seizures (postictal). Epileptic psychoses usually have acute initial and final phases, with a short symptom duration and complete remission with a risk of recurrence. There is no temporal relationship between interictal or chronic psychosis and epileptic seizures. Another type of epileptic psychosis is related to the response to epilepsy treatment: epileptic psychosis caused by the phenomenon of forced normalisation (alternative psychosis), which includes epileptic psychosis secondary to epilepsy surgery. Although combination treatment with antiepileptic and neuroleptic drugs is now widely used to manage this condition, there are no standard treatment guidelines for epileptic psychosis.

Clinical cases

We present 5 cases of peri-ictal epileptic psychosis in which we observed an excellent response to treatment with levetiracetam. Good control was achieved over both seizures and psychotic episodes. Levetiracetam was used in association with neuroleptic drugs with no adverse effects, and our patients did not require high doses of the latter.

Conclusions

Categorising psychotic states associated with epilepsy according to their temporal relationship with seizures is clinically and prognostically useful because it provides important information regarding disease treatment and progression. The treatment of peri-ictal or acute mental disorders is based on epileptic seizure control, while the treatment of interictal or chronic disorders has more in common with managing disorders which are purely psychiatric in origin. In addition to improving the patient's quality of life and reducing disability, achieving strict control over seizures may also prevent the development of interictal psychosis. For this reason, we believe that establishing a treatment protocol for such cases is necessary.     

Temporal lobe epilepsy masquerading as psychosis - a case report and literature review

The psychoses of epilepsy are well recognized complications of seizure disorders, diagnosed easily from the history. However, in the absence of recognized seizures, the diagnosis can be challenging. We present a 27-year-old female, who suffered a treatment refractory psychosis for 6 years. She did not report, or display, any seizure activity, and extensive investigation was unremarkable. The onset of new symptoms prompted a repeat work-up which clinched the diagnosis of psychosis of epilepsy. Treatment with Lamotrigine and Amisulpiride achieved an excellent response, and she has remained symptom free for 7 months. We conclude with a brief literature review.     

Difference in age of onset of psychosis between epilepsy and schizophrenia

To clarify the nature of psychosis development in epilepsy patients, we studied differences in age of onset of psychosis between epilepsy patients with psychosis (epilepsy-psychosis) and schizophrenia patients. Subjects were 282 patients with epilepsy-psychosis (36 postictal, 224 interictal, and 22 bimodal psychoses) and 612 schizophrenia patients. Age of onset was compared between the schizophrenia group and the whole epilepsy-psychosis group as well as its subgroups. Effects of sex and family history of psychosis on age of onset were also evaluated. Epilepsy patients developed psychosis later (mean age 30.1) than schizophrenia patients (mean age 26.6). Among epilepsy-psychosis subgroups, postictal psychosis and interictal psychosis showed a later onset than schizophrenia. In interictal psychosis, while chronic schizophrenia-like psychosis occurred at similar age compared to schizophrenia, brief episodic psychosis occurred at later age. Epilepsy-psychosis patients showed no sex difference in age of onset, whereas female schizophrenia patients showed a later onset than male schizophrenia patients. Both the epilepsy and schizophrenia patients with family history of psychosis tended to develop psychosis at an earlier age, although this did not reach statistically significant level. The findings of the study suggest that the nature of epilepsy-psychosis is not fully equivalent to that of schizophrenia.     

Pathophysiology of epilepsy

This work reviews the current knowledge on epileptogenesis and pathophysiology of epilepsy. Recently, gene defects underlying four monogenic epilepsies (generalized epilepsy with febrile seizures, autosomal dominant nocturnal frontal lobe epilepsy, benign familial neonatal convulsions and episodic ataxia type 1 with partial seizures) have been identified, shedding new light on the pathophysiology of epilepsy as these diseases are caused by ion channel mutations. Although epileptic syndromes differ pathophysiologically, common ictogenesis-related characteristics as increased neuronal excitability and synchronicity are shared as well as mechanisms involved in interictal-ictal transition. Emerging insights point to alterations of synaptic functions and intrinsic properties of neurons as common mechanisms underlying hyperexcitability. This work also reviews the neurochemical mechanisms of epilepsy. An imbalance between glutamate and gamma-aminobutyric acid neurotransmitter systems can lead to hyperexcitability but catecholaminergic neurotransmitter systems and opioid peptides were shown to play a role in epileptogenesis as well. An overview of currently available anti-epileptic drugs and their presumed mechanisms of action is given as an illustration of the neurochemistry of epileptogenesis. Most anti-epileptic drugs exert their anti-epileptic properties through only a few neurochemical mechanisms that are meanwhile basic pathophysiological mechanisms thought to cause seizures.     

Psychological factors in retrograde amnesia: Self-deception and a broken heart

The psychoses of epilepsy are well recognized complications of seizure disorders, diagnosed easily from the history. However, in the absence of recognized seizures, the diagnosis can be challenging.

We present a 27-year-old female, who suffered a treatment refractory psychosis for 6 years. She did not report, or display, any seizure activity, and extensive investigation was unremarkable. The onset of new symptoms prompted a repeat work-up which clinched the diagnosis of psychosis of epilepsy.

Treatment with Lamotrigine and Amisulpiride achieved an excellent response, and she has remained symptom free for 7 months.

We conclude with a brief literature review.     

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.