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.     

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.     

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.     

Recognition of the Various Expressions of Anxiety, Psychosis, and Aggression in Epilepsy

Summary:  Anxiety, psychosis, and aggressive behavior are among the frequent comorbid psychiatric disorders identified in patients with epilepsy. Often the clinical manifestations of these disorders vary according to their temporal relation relative to seizure occurrence. Thus, postictal symptoms of anxiety or psychosis differ in severity, duration, and response to treatment with interictal symptomatology. Psychiatric symptomatology in epilepsy can appear concurrently with the seizure disorder and improve or remit on the abolition of epileptic activity. We refer to these as paraictal psychiatric phenomena. Such is the case of aggressive disturbances associated with gelastic seizures caused by hypothalamic hamartomas. In this article, three case studies are presented to illustrate the importance of distinguishing psychiatric symptoms of anxiety, psychosis, and aggression, with respect to their temporal relation with seizure occurrence.     

Clinique et neurobiologie des psychoses post-ictales

Psychosis in epilepsy can be categorized in relation to seizures in two main categories: interictal psychosis and postictal psychosis. Postictal psychosis (PIP) is a specific syndrome in relation to seizure activity: a clear temporal relation exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures. However, this very specific syndrome is not included as such within the DSM-5, and PIP belongs to the category “Psychotic disorder due to another medical condition”. Diagnostic criteria are: (1) episode of psychosis within 1 week after a seizure(s); (2) psychosis lasts more than 15 hours and less than 2 months; (3) delusions, hallucinations in clear consciousness, bizarre, or disorganized behavior, formal thought disorder, or affective changes; and (4) no evidence AED toxicity, non-convulsive status epilepticus, recent head trauma, alcohol, or drug intoxication or withdrawal, prior chronic psychotic disorder. The presence of a lucid interval between the last seizure and start of changes rules out a simple postictal delirium. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without any treatment. Prepsychotic EEG abnormalities persist during the psychosis. Risk factors for PIP include: long standing localization-related epilepsy, extratemporal onset, bilateral epileptiform activity, secondary generalization, slowing of the EEG background activity and personal or family history of psychiatric disorders. Brain MRI frequently shows structural abnormalities. Several functional neuroimaging studies have shown hyperperfusion in various cerebral regions during PIP, suggesting an excessive activation of particular structures of the brain rather than a postictal depression of cerebral activity. Implanted electrode studies have shown that the EEG correlate of psychotic symptoms differs from the ictal EEG correlate of epileptic seizures. The value of antipsychotic treatment in PIP requires further studies. Despite their role in symptomatic relief, there is no clear effect of neuroleptics on duration or prognosis of PIP. Different combinations of pharmaceutical interventions can be tried on a case by case basis: (1) oral administration of benzodiazepine; (2) combined oral administration of benzodiazepine and atypical neuroleptics; (3) intramuscular administration of dopamine-blockers for rapid tranquilization of violent or agitated patients. The notion that neuroleptic drugs lower the seizure threshold has no clinical significance: there is no evidence that antipsychotic drugs increase seizure frequency in epileptic patients treated with antiepileptic drugs.     

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.     

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.     

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.     

Acute Psychosis During Intracranial EEG Monitoring: Close Relationship Between Psychotic Symptoms and Discharges in Amygdala

PURPOSE: This report examined the underlying mechanism of psychosis associated with epilepsy. METHODS: An adult patient with epilepsy manifesting acute psychosis during long-term EEG monitoring is presented, together with a literature review on this subject. RESULTS: A 25-year-old woman with intractable temporal lobe epilepsy developed acute psychosis while she underwent long-term intracranial EEG monitoring. After a clustering of seizures, she manifested psychotic symptoms including hallucination, stupor, and repeated fear. The transition of psychotic symptoms corresponded to the changes in frequency and morphology of seizure discharges restricted to the left amygdala. Improvement of psychosis coincided with disappearance of seizure discharges. CONCLUSIONS: This case confirmed a close relationship between psychotic symptoms and seizure discharges in the left amygdala. It is suggested that paroxysmal bombardment of the medial temporal lobe structure may be a pathogenetic factor of acute psychosis associated with epilepsy.     

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.     

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.     

Diagnosis and management of depression and psychosis in children and adolescents with epilepsy

The neurologic dysfunction underlying epilepsy can predispose patients to psychiatric disorders, and the incidence of both depression and psychosis is increased in people with epilepsy. Depressive disorders are the most frequently recognized psychiatric comorbidities in people with epilepsy, but depression in children can be particularly difficult to recognize. Clinicians need to inquire about not only classic symptoms of depression such as anhedonia but also less obvious symptoms such as unprovoked irritability, unsubstantiated complaints of lack of love from family members, somatic complaints, and problems with concentration and poor school performance. The diagnosis of depressive disorders in children with epilepsy and mental retardation is even more difficult. Physicians need to be alert for the presence of iatrogenic depression, which may result from antiepileptic drugs or epilepsy surgery. People with epilepsy are also at increased risk for psychosis, which can be interictal, postictal, or (rarely) an expression of ictal activity. This psychosis can be related to seizure remission (ie, alternative psychosis) or iatrogenic (eg, related to antiepileptic drugs or following temporal lobectomy). Although both antidepressants and antipsychotic drugs have the potential to lower the seizure threshold and increase seizures, careful drug selection, dosing, and slow titration can minimize this risk, allowing treatment to proceed.     

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.     

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.     

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.     

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.