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.     

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.     

Is interictal EEG activity a biomarker for mood disorders in temporal lobe epilepsy?

Objective

Psychiatric comorbidities are frequent in temporal lobe epilepsy (TLE), and symptoms of these comorbidities may be related to epilepsy activity. Here we evaluated interictal EEG activity in TLE patients with or without psychiatric comorbidities.

Methods

A cohort study of 78 patients with TLE, with evaluation of wake/sleep interictal scalp EEG. All subjects were submitted to a psychiatric structured clinical interview (SCID) for the diagnosis of lifetime psychiatric comorbidities. Three major diagnostic categories were studied: mood disorders, anxiety disorders, and psychosis. We then evaluated differences in interictal EEG activity between patients with and without these psychiatric comorbidities.

Results

Infrequent EEG interictal spikes, defined as less than one event per minute, were significantly associated with mood disorders in TLE (p = 0.02).

Conclusions

Low intensity seizure disorder has been associated with a decrease in interictal EEG discharges and with an increase in psychiatric symptoms in TLE, a phenomenon known as forced normalization. In our study, we observed a low interictal spike frequency on EEG in TLE patients with mood disorders.

Significance

A low spike index might be a neurophysiological marker for depression in temporal lobe epilepsy.     

A study of epilepsy-related psychosis

The association of epilepsy and psychosis is studied. Among the 500 patients of epilepsy evaluated, there were 12 patients, 8 males and 4 females with epilepsy-related psychosis. Their average age was 38 years. The interval between the age of onset of epilepsy and psychotic features was 9 years. Complex partial seizures were present in 7 patients and primary generalized tonic-clonic seizure was present in 1 patient. Four patients had post-ictal psychosis, 7 had acute interictal psychosis and 1 patient had chronic psychosis. The inter-ictal and chronic psychoses were schizophreniform whereas the post-ictal psychoses were not. EEG showed a temporal focus in 7 patients with complex partial seizures and an extra-temporal focus was identified in 4 out of the other 5 patients. Imaging (CT scan/MRI) revealed abnormalities in 10 patients. This study attempts to define the characteristics of psychoses occurring in epileptics.     

Psychotic disorders in Argentine patients with refractory temporal lobe epilepsy: A case–control study

The issue of psychotic disorders in epilepsy has given rise to great controversy among professionals; however, there are not many studies in this area and the physiopathological mechanisms remain unknown. The aim of this study was to describe the spectrum of psychotic disorders in an Argentine population with refractory temporal lobe epilepsy (RTLE) and to determine the risk factors associated with psychotic disorders. Clinical variables of the epileptic syndrome were compared among a selected population with RTLE with and without psychotic disorders (DSM-IV/Ictal Classification of psychoses). Logistic regression was performed. Sixty-three patients with psychotic disorders (Psychotic Group, PG) and 60 controls (Control Group, CG) were included. The most frequent psychotic disorders were brief psychotic episodes (35%) (DSM-IV) and interictal psychosis (50%) (Ictal Classification). Risk factors for psychotic disorders were bilateral hippocampal sclerosis, history of status epilepticus, and duration of epilepsy greater than 20 years.     

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.     

Surgical treatment of temporal lobe epilepsy with interictal psychosis: results of six cases

We describe the postsurgical outcome of six patients with medically intractable temporal lobe epilepsy and interictal psychosis who underwent temporal lobe resection. All patients were submitted to a comprehensive presurgical investigation, including prolonged video-EEG monitoring. Despite their psychotic disorders, all patients were able to provide informed consent and we were able to complete the investigation of all cases. Surgical complications occurred in two cases. Seizure outcome was Engel class I (free from incapacitating seizures) in all except one patient. There was no worsening of their psychoses. Until now, there has been relative improvement in the mental conditions of five patients. Although psychosis has been considered by some authors as a contraindication to epilepsy surgery, with appropriate psychiatric intervention, patients with refractory epilepsy and chronic interictal psychosis may be submitted to prolonged presurgical investigation and undergo surgery successfully.     

Psychomotor epilepsy and psychosis. II PHYSICAL ASPECTS

In a controlled investigation the clinical findings in 96 patients with paranoid/hallucinatory psychosis and partial epileptic seizures with complex symptoms, were compared with the findings in 96 control patients with the same type of epilepsy without psychosis of median 24 years' duration. The median age at onset of psychosis was 34 years, after epilepsy of median 21 years' duration. The seizure frequency of complex, partial seizures was significantly lower in the psychotic group, while the frequency of generalized seizures did not differ. A significant preponderance in the psychotic group of left-handed patients, etiological factors and neurological signs reflecting organic damage, and seizures of automatic behaviour indicates that epileptic psychoses are caused by structural lesions affecting the deep parts of the temporal lobe.     

Interictal psychoses in comparison with schizophrenia--a prospective study

PURPOSE: To prospectively investigate the incidence of interictal psychoses of epilepsy patients, and make a comparison between those with interictal psychoses and patients with schizophrenia in respect to their responses to antipsychotic drugs, as well as psychotic states. METHODS: We undertook a two-part prospective investigation. In Part I, the psychotic episodes of 619 epilepsy patients were investigated, while 182 patients with psychotic syndromes were followed in Part II, of whom 59 were diagnosed with schizophrenia and 13 with epilepsy with interictal psychoses. The Positive and Negative Syndrome Scale was used for efficacy assessment. RESULTS: The average annual incidence of interictal psychosis was 0.42% during the 56-month study period. A significant difference was found between patients with schizophrenia and epilepsy patients with interictal psychoses in respect to results on the negative subscale of the PANSS at the initial examination (mean scores of 18.1 and 13.2, respectively, p = 0.004). The response rates one year later for these groups were 27.1% and 53.8%, respectively, which showed a trend of better response to the antipsychotic medication by the epilepsy group (p = 0.098). Initial and maximum doses of antipsychotic drugs used for epilepsy patients with interictal psychoses were significantly lower than those used for patients with schizophrenia (p = 0.008 and p = 0.006, respectively). CONCLUSIONS: Schizophrenia and epileptic psychosis showed different symptom profiles. On average, epilepsy patients with interictal psychoses achieved higher remission rates with lower doses of antipsychotic drugs as compared to patients with schizophrenia in the present 1-year follow-up study.     

Les psychoses postictales

In epilepsy patients, psychotic states are related to a group of psychotic disorders with a specific phenomenology in which potential pathophysiological mechanisms are believed to be closely related to the epileptic disorder itself. Postictal psychosis is a very specific syndrome in relation to seizure activity: a clear temporal relationship exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures, with a characteristic lucid interval which lasts from two to 120 h. The psychotic state may be related to the withdrawal of anticonvulsants, often in connection with video-EEG monitoring. The phenomenology of the psychotic state is often pleomorphic, with abnormal mood, paranoid delusions and hallucinations, with some clouding of consciousness or no evidence of impaired consciousness. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without neuroleptic treatment. The majority of the patients suffer from complex partial seizures with frequent psychic auras that secondarily become generalized. In the majority of cases, prepsychotic EEG abnormalities persist during the psychosis. Frequent bitemporal foci are recorded on the EEG and MRI abnormalities (including mesial temporal sclerosis) are seen in more than half of the cases. The results of clinical, morphologic and metabolic available studies will be briefly discussed.     

Mitochondrial disorders and epilepsy

Introduction

Mitochondrial respiratory chain defects (RCD) often exhibit multiorgan involvement, affecting mainly tissues with high-energy requirements such as the brain. Epilepsy is frequent during the evolution of mitochondrial disorders (30%) with different presentation in childhood and adulthood in term of type of epilepsy, of efficacy of treatment and also in term of prognosis.

State of art

Mitochondrial disorders can begin at any age but the diseases with early onset during childhood have generally severe or fatal outcome in few years. Four age-related epileptic phenotypes could be identified in infancy: infantile spasms, refractory or recurrent status epilepticus, epilepsia partialis continua and myoclonic epilepsy. Except for infantile spasms, epilepsy is difficult to control in most cases (95%). In pediatric patients, mitochondrial epilepsy is more frequent due to mutations in nDNA-located than mtDNA-located genes and vice versa in adults. Ketogenic diet could be an interesting alternative treatment in case of recurrent status epilepticus or pharmacoresistant epilepsy.

Conclusion

Epileptic seizures increase the energy requirements of the metabolically already compromised neurons establishing a vicious cycle resulting in worsening energy failure and neuronal death.     

Complete remission of epileptic psychosis after temporal lobectomy: case report

We report a case of a female patient with refractory complex partial seizures since 15 years of age, recurrent postictal psychotic episodes since 35 which evolved to a chronic refractory interictal psychosis and MRI with right mesial temporal sclerosis (MTS). After a comprehensive investigation (video-EEG intensive monitoring, interictal and ictal SPECT, and a neuropsychological evaluation including WADA test) she was submitted to a right temporal lobectomy. Since then, she has been seizure-free with remission of psychosis, although with some persistence of personality traits (hiperreligiosity, viscosity) which had been present before surgery. This case supports the idea that temporal lobectomy can be a safe and effective therapeutic measure for patients with MTS, refractory epilepsy and recurrent postictal epileptic psychosis or interictal epileptic psychosis with postictal exacerbation.     

Clinical management of recurrent postictal psychosis

Although there are numerous reports of interictal psychosis in epileptic patients, there are few studies describing the longitudinal course and treatment of postictal psychosis. The goal of this study was to define the clinical features, natural history, and possible interventional methods in a group of patients with complex partial seizures and postictal psychosis. We studied seven patients who manifested psychotic behavior following an increase in their seizure frequency. Mean follow-up was 83 months. Patients underwent neuropsychiatric testing, cranial magnetic resonance imaging, and extensive EEG evaluation. All but one patient had severe epilepsy. An increased number of seizures was followed by a brief period of lucidity and then psychosis, which lasted between 2 and 14 days and tended to recur (mean, one episode every 4 months). EEGs done during the psychotic episodes generally demonstrated a mild diffuse background slowing without evidence of ictal epileptiform discharges. Evaluation between episodes revealed no persistent psychiatric features. The patients rarely required hospitalization or neuroleptic medications. Patients usually responded to mild sedation, close observation, and a supportive environment.     

Categorical vs dimensional classifications of psychotic disorders

Objective

Both categorical and dimensional methods appear relevant to classifying psychotic disorders; however, there is no clear consensus on the most appropriate categories and dimensions or on the best approach for constructing nosologic criteria that integrate these 2 methods. This review examines the evidence on specific dimensions and categories that would best characterize psychoses.

Method

Entries in the MEDLINE database between 1980 and 2011 were searched for studies of the dimensional and/or categorical structure of psychosis. Studies were included if samples represented a spectrum of psychotic disorders and dimensions/categories were empirically derived using principal components analysis, factor analysis, or latent class analysis.

Results

Most dimensional studies observed 4 or 5 dimensions within psychosis, with positive, negative, disorganization, and affective symptom domains most frequently reported. Substance abuse, anxiety, early onset/developmental, insight, cognition, hostility, and behavioral/social disturbance dimensions appeared in some studies. Categorical studies suggested 3 to 7 major classes within psychosis, including a class similar to Kraepelin's dementia praecox and one or more classes with significant mood components. Only 2 studies compared the relative fit of empirically derived dimensions and categories within the same data set, and each had significant limitations.

Conclusion

There is relatively consistent evidence on appropriate categories and dimensions for characterizing psychoses. However, the lack of studies directly comparing or combining these approaches provides insufficient evidence for definitive conclusions about their relative merits and integration. The authors provide specific recommendations for designing future studies to identify valid dimensions and/or categories of the psychoses and investigate hybrid approaches to model the structure of the underlying illnesses.     

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.     

Psychosis of Epilepsy: A Neurologist's Perspective

Psychosis of epilepsy (POE) comprises a group of disorders that are closely associated with epileptic seizures. These include interictal POE, postictal psychosis, and alternative psychosis (also known as "forced normalization"). Neurologists have, in general, played a limited role in the evaluation and management of patients with POE. Yet, as reviewed in this paper, a good understanding of electrophysiologic, neuroradiologic, and neuropathologic variables associated with POE can yield valuable data in the evaluation of the seizure disorder of these patients. The purpose of this review article is to highlight the clinical, neuroradiologic, neurophysiologic, and neuropathologic aspects of POE that can assist in the evaluation and management of the associated seizure disorder and to identify the circumstances in which a timely therapeutic intervention by neurologists can avert or minimize the occurrence of a psychotic episode. Specifically, the clinical characteristics of interictal POE and ictal, postictal, and alternative psychotic episodes are highlighted together with their potential pathogenic mechanisms and the associated treatment issues. Finally, discussions of psychotic disorders following epilepsy surgery and the pharmacotherapy of psychotic disorders in patients with epilepsy are presented.     

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.