Major Psychiatric Disorders Subsequent to Treating Epilepsy by Vagus Nerve Stimulation

Purpose. The goal of this work was documentation of incidence, phenomenology, pathogenesis, and treatment of psychiatric disorders occurring subsequent to treating epilepsy by vagus nerve stimulation (VNS).Methods. In a series of 81 patients treated by VNS, all patients who developed major psychiatric complications underwent systematic psychiatric evaluation and treatment with psychotropic medication; VNS was modified if necessary.Results. After the seizure frequency was reduced by at least 75%, 7 of 81 patients (9%) developed major psychiatric disorders: Six became severely dysphoric (5 with catastrophic rage and 4 with psychotic symptoms), and one became psychotic. All 7 patients had experienced dysphoric disorders and 2 had experienced psychotic episodes prior to the VNS treatment. Five patients had frequent daily seizures prior to treatment. Remission or satisfactory improvement was achieved with psychotropic medication in 6 patients, aided by decreasing or interrupting VNS in two patients. One patient was noncompliant and suffered a fatal outcome.Conclusion. Severe interictal dysphoric disorders associated with catastrophic rage and psychotic episodes may develop on suppressing seizures by VNS in patients with previous epilepsy-related psychiatric disorders. Patients with multiple daily seizures may be more vulnerable to this occurrence. The phenomenon corresponds to the common finding of interictal dysphoric and psychotic symptoms emerging when inhibitory mechanisms predominate (alternative psychiatric disorders in the absence of seizures, or forced normalization of the EEG). The dysphoric symptom of catastrophic rage appears to occur more often on seizure suppression by VNS than by antiepileptic drugs. Psychiatric intervention, primarily with antidepressant medication, must be available to secure a good outcome; decrease of VNS may occasionally be required.     

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.     

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.     

The interictal dysphoric disorder: recognition, pathogenesis, and treatment of the major psychiatric disorder of epilepsy

The unawareness of psychiatrists about the importance of epilepsy dates back half a century, when epilepsy became considered an ordinary neurologic disorder. Epileptic seizures, however, can be provoked in every human being. Epilepsy is an extraordinary disorder that, beyond its well-known neurologic complexities, tends to become complicated with a wide range of specific psychiatric changes; they occur on the establishment of a temporal-limbic focus of intermittent excessive neuronal excitatory activity that produces increasingly inhibitory responses. These changes are distinct from those related to the two major psychiatric spheres for which a genetic basis is established, i.e., the manic-depressive and schizophrenic disorders, and represent a genetic sphere of its own. Apart from more subtle personality changes and the serious late complications of interictal psychoses and suicidal episodes, the key psychiatric syndrome associated with epilepsy consists of the interictal dysphoric disorder, with its characteristic intermittent and pleomorphic symptomatology. This disorder was clearly identified about a century ago by Kraepelin, when he established a comprehensive basis for the modern classification of the psychiatric disorders, at a time when epilepsy represented an area of major interest to psychiatrists. A practical method of recognizing the dysphoric disorder is reported. The disorder tends to be very treatable by combining psychotropic (chiefly antidepressant) with antiepileptic medication. The variations in treatment approach required are discussed and illustrated by representative case studies. Psychiatrists must become familiar with the psychiatric aspects of epilepsy to be able to assist the neurologists who focus on the neural complexities of the illness. They also must become able to recognize, among their own patients, the presence of a subictal dysphoric disorder that requires the same treatment as the interictal dysphoric disorder; combined treatment with antidepressant and antiepileptic medication is likewise indicated for the premenstrual dysphoric disorder, a condition that appears to belong to the spectrum of epilepsy-related psychiatric disorders. Furthermore, they must learn how an ignored population in their care, epilepsy patients confined to state hospitals, can be properly treated. Of particular importance is the need for psychiatrists to become familiar with the role of the paroxysmal affects in the general human condition, with their basic conflict to be intermittently angry and irascible yet otherwise good-natured, helpful, and religious--a conflict that tends to be particularly accentuated among patients with the "Sacred Disease."     

Psychiatric Outcome of Temporal Lobectomy for Epilepsy: Incidence and Treatment of Psychiatric Complications

Summary: Purpose: To determine the incidence of psychiatric disorders before and after surgical treatment for partial epilepsy and to document the effectiveness of their treatment.
Methods: Fifty consecutive patients treated surgically for focal epilepsy (44 temporal and six frontal) were evaluated by established neuropsychiatric methods before surgery and over a mean period of 2 years after surgery. The patients with interictal dysphoric disorders, with or without psychotic episodes, were treated with tricyclic antidepressant medication alone or combined with serotonin selective reuptake inhibitors and, if necessary, with the addition of risperidone.
Results: Before surgery, 25 (57%) of the 44 patients with temporal lobe epilepsy had dysphoric disorders. After surgery, 17 (39%) of the 44 patients experienced either de novo psychiatric complications (six psychotic episodes, six dysphoric disorders, and two depressive episodes) or exacerbation of preoperative dysphoric disorder (three patients). Eight previously intact patients of the 19 (42%) developed dysphoric disorders after surgery that were significantly related to recurrence of seizures. All psychiatric complications occurred in the first 2 months after surgery, except for the six patients intact before surgery, who had a recurrence of seizures. A significant predictor of ultimate excellent psychiatric outcome was complete absence of seizures after surgery. All postoperative psychiatric complications remitted on treatment with psychotropic medication in the compliant patients.
Conclusions: An exceptional psychiatric morbidity is associated with the months after temporal lobectomy. Possible pathogenetic mechanisms are discussed. Antidepressant drugs are very effective in treating the psychiatric disorders of chronic epilepsy; their use in conjunction with the surgical treatment of epilepsy appears to be crucial for the overall positive outcome of a significant number of patients.     

Clinical features, diagnosis, and treatment of dysphoric states and psychoses associated with epilepsy

Although dysphoric states and psychoses represent clinically relevant psychiatric complications in patients with epilepsy, their symptomatologies are complex and therefore frequently underrecognized and undertreated in daily psychiatric routine. Detecting dysphoric states and psychoses secondary to the psychotropic effects of various antiepileptic drugs is often challenging, even for the most experienced psychiatrists. This article gives an overview of epidemiology, clinical features, diagnosis, and therapy of interictal, peri-ictal, and alternative dysphoric states and psychoses in patients with epilepsy. Further, potential drug interactions between antiepileptic and psychiatric medications are discussed.     

Single photon emission computed tomography (SPECT) brain imaging using N,N,N'-trimethyl-N'-(2 hydroxy-3-methyl-5-123I-iodobenzyl)-1,3-propanediamine 2 HCl (HIPDM): intractable complex partial seizures

HIPDM-SPECT brain imaging was performed in four patients with intractable complex partial seizures (CPS). Three patients had an epileptogenic focus in one temporal lobe and underwent anterior temporal lobectomy. Interictal HIPDM-SPECT demonstrated decreased regional cerebral perfusion (rCP) in the epileptogenic area in only one patient, but ictal studies showed increased rCP in the epileptic foci of all three patients. In the fourth patient, interictal HIPDM-SPECT showed increased rCP in the area of epileptogenic focus; when antiepileptic medication was taken, rCP decreased. HIPDM-SPECT brain imaging is useful for localizing epileptogenic foci in CPS.     

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.     

Therapy for Neurobehavioral Disorders in Epilepsy

Summary:  Neurobehavioral disorders commonly affect patients with epilepsy. In addition to the behavioral changes during and immediately after seizures, the epileptogenic disorder of function often extends further into the postictal and interictal period. Cognitive impairments commonly affect attention, memory, mental speed, and language, as well as executive and social functions. Reducing seizure frequency and the antiepileptic drug burden can reduce these problems. Attentional deficits may respond to therapies for attention-deficit/hyperactivity disorder, but apart from patients with this comorbid disorder, their efficacy is unproven in other epilepsy patients. No effective therapies are established for other cognitive problems, but pragmatic, compensatory strategies can be helpful. Behavioral disorders include fatigue, depression, anxiety, and psychosis. Many of these disorders usually respond well to pharmacotherapy, which can be supplemented by psychotherapy. Cognitive and behavioral disorders can be the greatest cause of morbidity and impaired quality of life, often overshadowing seizures. Yet these problems often go unrecognized and, even when identified, are often undertreated or untreated.     

Therapy for neurobehavioral disorders in epilepsy

Neurobehavioral disorders commonly affect patients with epilepsy. In addition to the behavioral changes during and immediately after seizures, the epileptogenic disorder of function often extends further into the postictal and interictal period. Cognitive impairments commonly affect attention, memory, mental speed, and language, as well as executive and social functions. Reducing seizure frequency and the antiepileptic drug burden can reduce these problems. Attentional deficits may respond to therapies for attention-deficit/hyperactivity disorder, but apart from patients with this comorbid disorder, their efficacy is unproven in other epilepsy patients. No effective therapies are established for other cognitive problems, but pragmatic, compensatory strategies can be helpful. Behavioral disorders include fatigue, depression, anxiety, and psychosis. Many of these disorders usually respond well to pharmacotherapy, which can be supplemented by psychotherapy. Cognitive and behavioral disorders can be the greatest cause of morbidity and impaired quality of life, often overshadowing seizures. Yet these problems often go unrecognized and, even when identified, are often undertreated or untreated.     

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.     

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.     

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.     

Epileptic psychoses and anticonvulsant drug treatment

Forty four consecutive patients with epilepsy and psychoses were studied retrospectively for psychotic episodes associated with changes in antiepileptic drug therapy. Twenty seven patients (61%) developed their first episode of psychosis unrelated to changes in their antiepileptic drug regimen. Twenty three of these patients developed psychoses with temporally unrelated changes in seizure frequency. Many patients had chronic schizophrenia-like psychotic symptoms. Seventeen patients (39%) developed their first episode of psychosis in association with changes in their antiepileptic drug regimen. Twelve patients developed psychoses temporally related to seizure attenuation or aggravation. Many of their psychotic symptoms were polymorphic with a single episode or recurrent episodes. No marked differences were found in the various clinical backgrounds between the two groups. In the drug-related group, seven patients developed psychoses after starting add-on therapy with a new antiepileptic drug, six after abruptly discontinuing their drugs, and four after taking an overdose of antiepileptic drugs. Based on the present findings, drug regimens should be changed gradually and compliance should be maintained to prevent epileptic psychoses.     

Running down phenomenon and acute interictal psychosis in medial temporal lobe epilepsy

PURPOSE: To examine the relationship between presurgical acute interictal psychosis and postsurgical running down phenomenon in a strictly homogeneous group with medial temporal lobe epilepsy. METHODS: Forty patients with mesial temporal sclerosis and an ultimate excellent surgical outcome, were divided into running down positive and negative groups. Various clinical and laboratory data, including presurgical psychotic episodes, were analyzed in the two groups. RESULTS: Patients in the running down positive group exhibited a significantly high incidence of presurgical history of acute interictal psychosis. CONCLUSION: We hypothesize that areas of secondary epileptogenesis beyond the scope of the primary epileptogenic zone, suggested by postsurgical running down phenomenon, may play an important role in the blockage and shift of the habitual propagation of seizure activity from the primary epileptogenic zone, to which Wolf attributed acute interictal psychosis.     

Postictal psychosis syndrome: a clinical entity to be recognized

INTRODUCTION: Post-ictal psychosis syndrome (PIP) belongs to the group of epileptic psychoses which, according to the most commonly used classification, is to be distinguished from ictal psychoses, on one hand, and from inter-ictal psychoses, on the other. OBJECTIVES: The present paper aims to review recent data concerning the clinical, therapeutic and pathophysiological aspects of PIP. METHODS: We report four cases of PPI, which involved four patients hospitalized at the Salpêtrière hospital between 2001 and 2005, and discuss these cases in light of the relevant literature. RESULTS: The PIP fit generally occurs in patients suffering from intractable temporal lobe epilepsy which started several years before. The psychiatric disorders suddenly take hold after a series of complex partial seizures with frequent secondarily generalized tonic clonic seizures. During the episode, EEG recordings do not show any epileptic activity. Psychiatric symptoms consist of persecutory delusive ideas, verbal and visual hallucinations, agitation, and aggressiveness. Mood disorders are variable from one patient to another and exhibit intraindividual fluctuation. In most patients given antipsychotic drugs, the short-term outcome of PIP is favorable . In the long-term, even if recurrence is the main long-term risk, progression to severe mood disorders or to poor prognosis inter-ictal psychosis is possible. Accordingly, the clinician must be aware of this syndrome in order to correctly diagnose PIP since effective treatment with antipsychotic drugs is available. CONCLUSION: The short-term prognosis of PPI is usually favorable but this syndrome can potentially develop in the long-term to more severe psychiatric disorders. It is, therefore, important to recognize PIP syndromes which respond more readily to pharmacological treatments than other types of psychoses.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and psychosis in children and teenagers

Psychosis related to epilepsy or antiepileptic treatment can occur in teenagers and very rarely in children. Postictal, interictal and antiepileptic‐drug‐induced psychosis have all been reported in young people. Whether ictal psychosis occurs in this age group remains open to debate. Neuronal antibody encephalitis such as anti‐NMDA receptor encephalitis can present with seizures and psychosis, both of which can resolve with prompt, appropriate immunotherapy. In addition, there have been several reports in which the terms psychosis or psychotic features have been used loosely to describe behavioural disturbance in children with epilepsy; in these cases there have apparently been no diagnostic features of psychosis, implying that these terms should not have been used. The management of epilepsy‐related psychosis in young people is similar to that in adults. Antipsychotic medication should not be withheld if it is needed on clinical grounds. If the psychosis has been induced by antiepileptic medication then a medication review is necessary.     

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.     

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.