Psychiatric comorbidity in refractory focal epilepsy: A study of 490 patients

We studied the prevalence and associated factors of psychiatric comorbidities in 490 patients with refractory focal epilepsy. Of these, 198 (40.4%) patients had psychiatric comorbidity. An Axis I diagnosis was made in 154 patients (31.4%) and an Axis II diagnosis (personality disorder) in another 44 (8.97%) patients. After logistic regression, positive family history of psychiatric comorbidities (O.R. = 1.98; 95% CI = 1.10–3.58; p = 0.023), the presence of Axis II psychiatric comorbidities (O.R. = 3.25; 95% CI = 1.70–6.22; p < 0.0001), and the epileptogenic zone located in mesial temporal lobe structures (O.R. = 1.94; 95% CI = 1.25–3.03; p = 0.003) remained associated with Axis I psychiatric comorbidities. We concluded that a combination of clinical variables and selected structural abnormalities of the central nervous system contributes to the development of psychiatric comorbidities in patients with focal epilepsy.     

EEG-fMRI in children with pharmacoresistant focal epilepsy

PURPOSE: To evaluate the usefulness of EEG-combined functional magnetic resonance imaging (EEG-fMRI) to localize epileptogenic sources. METHODS: Six children (age 8-15 years) with lesional or nonlesional pharmacoresistant focal epilepsy were studied. RESULTS: We found significant activations in four children, activation and deactivation in one child, and widespread deactivation in another. In four children, activations colocalized with the presumed location of the epileptic focus, one of which was confirmed by intracranial EEG. CONCLUSIONS: EEG-fMRI is a promising tool to noninvasively localize epileptogenic regions in children with pharmacoresistant focal epilepsy.     

Electrocorticographic and neurochemical findings after local cortical valproate application in patients with pharmacoresistant focal epilepsy

Because oral pharmacological treatment of neocortical focal epilepsy is limited due to common systemic side effects and relatively low drug concentrations reached at the epileptic foci locally, application of antiepileptic agents directly onto the neocortical focus may enhance treatment tolerability and efficacy. We describe the effects of cortically applied sodium valproate (VPA) in two patients with pharmacoresistant neocortical focal epilepsy who were selected for epilepsy surgery after a circumscribed epileptic focus had been determined by invasive presurgical evaluation using subdural electrodes. Local VPA modified epileptic activity as electrocorticographically recorded from the chronic focus in both patients. In addition, VPA induced local increase of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in cortical tissue samples, whereas the excitatory glutamate was possibly decreased. In this clinical pilot study, we could show antiepileptic effects of cortically applied VPA in humans by electrocorticographic and neurochemical parameters.     

Psychiatric comorbidity in adult patients with idiopathic generalized epilepsy

We reviewed the medical records of 157 adult (18 years) patients with firmly diagnosed idiopathic generalized epilepsy (IGE) to investigate the extent and the type of psychiatric comorbidity and its relationship to various IGE syndromes and other epilepsy-related neurobiological factors. Forty-one patients (26.1%, 14 men and 27 women, median age: 34.0 years, range: 18-68, mean: 36.5) had comorbid mental disorders according to the 10th revision of the International Classification of Diseases (ICD-10) criteria, with four patients having a dual diagnosis. Mood disorders were the most common comorbid mental disorder (46.7%), followed by anxiety-panic disorder (26.7%). Comorbid psychiatric disorders occurred in all syndromes and in association with all seizure types, and, as in focal epilepsies, seizure control was significantly better in patients without psychiatric comorbidity (40.5% vs 19.5%, chi(2)(1)=5.873, P=0.015).     

Psychiatric comorbidity in epilepsy

Many studies on psychiatric comorbidity in epilepsy have been performed using many different patient groups and diagnostic instruments. This methodological heterogeneity complicates comparison of the findings. In this article, psychiatric disorders in epilepsy are reviewed from the perspective of the DSM classification system. The empirical findings of axis I clinical disorders and axis II personality disorders are described separately. Furthermore, the existence and specificity of conditions such as interictal dysphoric disorder, interictal behavior syndrome, and psychosis of epilepsy are discussed. From the many studies that have been performed on this topic it can be learned that there is a need for well-controlled studies using representative patient groups and valid and standardized diagnostic instruments. So far, the majority of the studies have concerned axis I disorders; relatively little research has been performed on axis II personality disorders. More research on personality disorders, as well as on the relative contributions of the different (brain- and non-brain-related) factors to the relationship between epilepsy and psychiatric disorders, is recommended.     

Juvenile myoclonic epilepsy: Psychiatric comorbidity and impact on outcome

Juvenile myoclonic epilepsy (JME) is a well-defined age-related idiopathic epilepsy syndrome. Past studies have emphasized the difficulties in the treatment of patients with JME, which have been attributed to some specific psychiatric, psychological, and psychosocial characteristics. These aspects have aroused a significant amount of interest in the last two decades. In this article, the available studies that investigated the prevalence of psychiatric disorders (PDs) in JME and its impact on seizure outcome were reviewed in order to provide an update to clinicians about these two important aspects associated with this common epilepsy syndrome. The review disclosed a high prevalence of PDs in patients with JME, particularly mood, anxiety, and personality disorders. In addition, most recent studies have also observed that overall prevalence of PDs in JME has not shown statistically significant differences when compared with TLE, an epilepsy syndrome where the psychiatric aspects are most frequently studied. Taken together, data regarding the prevalence of PDs and their possible consequences on seizure outcome on JME indicate that special attention should be directed to psychological disturbances and psychiatric symptoms in this epilepsy syndrome. The early recognition and treatment of psychiatric symptoms, as well as psychological disturbances and psychosocial difficulties, should be considered fundamental to JME prognosis.This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?     

Psychiatric comorbidity in patients with epilepsy: implications for diagnosis and treatment

Psychiatric disorders frequently occur in patients with epilepsy but the diagnosis is frequently missed and therapeutic opportunities are often lost. These comorbidities assume greater importance as epidemiological data show their frequent association with impaired function and quality of life, and advances in neurobiology better define their pathophysiological relationship and therapies. Epilepsy presents a model for understanding psychiatric illness. Deciphering the role of different biological and environmental risk factors may help identify high-risk patients and allow for early intervention. Antiepileptic drugs are frequently used to manage psychiatric syndromes although the mechanisms of their psychotropic action remain uncertain. As recognition and treatment of comorbid psychiatric disorders in epilepsy remain suboptimal, we need to increase the awareness of physicians, patients, their caregivers, and the health care system. Better recognition will help to develop and implement appropriate diagnostic and treatment programs, and improve functional outcomes and quality of life in people with epilepsy.     

Psychiatric comorbidity in children with new onset epilepsy

The aim of this study was to characterize the distribution, timing, and risk factors for psychiatric comorbidity in children with recent onset epilepsy. Children aged 8 to 18 years with recent onset epilepsy (<1 year in duration) of idiopathic etiology (n=53) and a healthy comparison group (n=50) underwent a structured psychiatric diagnostic interview to characterize the spectrum of lifetime-to-date history of comorbid psychiatric disorder. There was no significant difference between the children with recent onset epilepsy and healthy comparison children in sex (31 males, 22 females vs 23 males, 27 females) or mean age 12.7y [SD 3.3] vs 12.7y [SD 3.2]). Children with recent onset epilepsy exhibited an elevated rate of lifetime-to-date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis I disorders compared with the comparison group. They showed significantly higher rates of depressive disorders (22.6 vs. 4%, p=0.01), anxiety disorders (35.8 vs 22%, p<0.05), and attention-deficit-hyperactivity disorder (26.4 vs 10%, p=0.01) with elevated but less prevalent rates of oppositional defiant and tic disorders. A subset of children with epilepsy (45%) exhibited DSM-IV Axis I disorders before the first recognized seizure, suggesting the potential influence of antecedent neurobiological factors that remain to be identified. The increased prevalence of psychiatric comorbidity antedating epilepsy onset may be consistent with the presence of underlying neurobiological influences independent of seizures, epilepsy syndrome, and medication treatment.     

Psychiatric comorbidity in juvenile myoclonic epilepsy

OBJECTIVE: To assess the prevalence of psychiatric disturbances among patients with juvenile myoclonic epilepsy (JME). METHODS: Forty-three patients with JME (22 female, 21 male, mean age 32.4+/-13, range 15-63) were assessed by means of the Structured Clinical Interviews for DSM-IV (SCID-I and SCID-II). Current and lifetime psychiatric diagnoses were assigned. RESULTS: Thirty-five percent of the JME patients suffered from one or more psychiatric disorders (Axis I and Axis II). Personality disorders were present in 23% and Axis I disorders in 19%. Altogether, 47% had a psychiatric disorder at any time of their life. CONCLUSIONS: Psychiatric diagnoses are slightly higher than in representative community samples. The substantially increased number of personality disorders in JME patients might be attributed to frontal lobe deficits.     

Efficacy and tolerability of oral lacosamide as adjunctive therapy in pediatric patients with pharmacoresistant focal epilepsy

The results of adjunctive lacosamide treatment in 18 pediatric patients with pharmacoresistant focal epilepsy are reported. All had severe forms of focal epilepsy with or without secondary generalization and were concurrently receiving one to three other antiepileptic drugs. Lacosamide was administered orally, and final dose, after slow titration, ranged between 1.7 and 10 mg/kg. Mean treatment duration was 8 months (range=3 weeks-17 months). Treatment efficacy was assessed at two time points with a 1-year interval. The reported greater than 50% reduction in seizure frequency was 36% in the initial short-term and 20% in the following long-term assessment. Side effects, mostly somnolence and irritability, were reported by 39% of patients in both evaluations. Our data suggest that lacosamide treatment in pediatric patients is safe at doses up to 10 mg/kg/day without any major side effects, but studies in larger series are needed to validate and extend these findings.     

Epilepsy surgery outcome in coexisting symptomatic refractory focal epilepsy and benign focal epilepsy of childhood

Epilepsy surgery may successfully treat refractory symptomatic focal epilepsy in patients with coexisting benign focal epileptiform discharges. Reported here is the outcome after resective epilepsy surgery in three children with pharmacoresistant lesional focal epilepsy in whom seizures of benign focal epilepsy of childhood had been recorded. Two patients had left temporal epilepsy due to a malformation of cortical development; one of these had dual pathology, with additional ipsilateral hippocampal sclerosis. One child had catastrophic left hemispheric epilepsy due to left hemimegalencephaly. Frequent, habitual seizures of symptomatic epilepsy resolved after surgery (follow-up duration, 32-55 months); however, rare benign focal seizures of childhood have continued. These cases demonstrate that lesional pharmacoresistant focal epilepsy can be successfully treated with resective epilepsy surgery even when coexisting with benign focal epilepsy of childhood. During postoperative follow-up, careful documentation of breakthrough seizures due to benign focal epilepsy of childhood is important, so that these patients are not labeled as surgical failures.     

The psychiatric comorbidity of epilepsy

Several studies have assessed the prevalence of psychiatric disorders in epilepsy. They are characterized by considerable heterogeneity, because of differences in the population setting and type of study. A non-systematic review of the literature allows us to draw some useful, although not definite, conclusions. Six per cent of people with epilepsy in the general population appear to suffer from a psychiatric disorder, while this rises to 10-20% in populations with temporal lobe and/or refractory epilepsy. Mood disorders are the most common culprit (24-74%), particularly depression (30%), followed by anxiety disorders (10-25%), psychoses (2-7%) and personality disorders (1-2%). This comorbidity appears to be related to endogenous and exogenous (including iatrogenic) factors and to the severity and chronicity of epilepsy. Conditions such as schizophrenia-like psychosis of epilepsy and interictal dysphoric disorder are represented only in epilepsy. Adequate recognition and treatment of psychiatric conditions in epilepsy is essential for patient management because of their considerable burden in morbidity and quality of life.     

Long-term developmental outcome in patients with West syndrome after epilepsy surgery

It has been hypothesized that early seizure control may prevent children with intractable epileptic spasms (ES) from developmental regression and may contribute to better developmental outcome. The effectiveness of surgery for ES has been reported. We investigated long-term post-operative outcomes of seizure control and development in patients with symptomatic West syndrome (S-WS) who underwent epilepsy surgery. Six children who underwent surgical intervention for intractable ES were retrospectively investigated. Cortical malformations were observed on pre-operative MRI in all patients, with hemispheric or multilobar involvement in four children and focal lesions in two. Following surgery, we measured motor function, developmental age (DA), language skills, and sociopsychological function for up to 7years (mean, 4.9years). Post-operative seizure outcome was Engel Class I (n=4) or III (n=2). Motor function and DA was increased following surgery in six and five patients, respectively. Two patients started to speak in sentences following focal resection. Autistic features were noted in four of the five examined patients post-operatively. None of the patients showed developmental regression following surgery. Epilepsy surgery for S-WS with ES may result in good seizure control and improvement in motor development. Improvement in cognitive function was modest in this small cohort of children and autistic features were noted post-operatively in a substantial proportion of the children. While seizure control can be obtained by epilepsy surgery, early intervention for sociopsychological comorbidities may be warranted in children with S-WS.     

Seizure outcome after epilepsy surgery in patients with normal preoperative MRI

OBJECTIVE: To determine outcome after epilepsy surgery in patients with normal preoperative magnetic resonance imaging (MRI). METHODS: 24 adult and paediatric patients with normal preoperative MRIs were studied. They underwent epilepsy surgery between 1994 and 2001 and had at least one year of follow up. RESULTS: At the most recent follow up, nine patients (37%) were seizure-free and 18 (75%) had at least a 90% reduction in seizure frequency with weekly or monthly seizures. Seizure freedom was not significantly different after resections in frontal (5/9) or temporal regions (4/13) (p = 0.24, Fisher's exact test), or among patients with or without localising features on EEG, PET, or ictal SPECT. Subdural grids, used in 15 of 24 patients, helped tailor resections but were not associated with differences in outcome. Histopathology showed cortical dysplasia in 10 patients (42%), non-specific findings in 13 (54%), and hippocampal sclerosis in one (4%). Cortical dysplasia was seen in seven patients with frontal resection (78%) and non-specific findings in nine (69%) with temporal resection. Seizure outcome did not differ on the basis of location of resection or histopathology. CONCLUSIONS: While these results were less favourable than expected for patients with focal epileptogenic lesions seen on MRI, they represented worthwhile improvement for this patient population with high preoperative seizure burden. In this highly selected group, no single test or combination of tests further predicted postoperative seizure outcome.     

Psychiatric comorbidity in psychogenic nonepileptic seizures compared with epilepsy

ObjectivesPsychogenic nonepileptic seizures (PNESs) are closely linked with psychological distress, but their etiology is not well-understood. We reviewed psychiatric comorbidity in PNESs and epileptic seizures (ESs) with an aim to assist understanding, diagnosis, and management of PNESs.MethodsA search of Web of Science, MEDLINE (PubMed), PsycINFO, and Scopus identified 32 relevant studies on the prevalence of psychiatric comorbidity in PNESs. We used meta-analysis to compare psychiatric comorbidity between PNESs and ESs.ResultsSamples with PNESs had high rates of psychiatric comorbidity overall (53–100%), notably including posttraumatic stress disorder (PTSD), depression, and personality and anxiety disorders. Compared with ESs, samples with PNESs had more psychiatric comorbidity overall (RR: 1.30, 95% CI: 1.14–1.48, p < 0.0001) with significantly elevated risks found for PTSD, personality disorder, and anxiety but not depression.ConclusionsPsychiatric disorders are more common in PNESs than ESs. Because of methodological limitations of available studies, causality cannot be established; prospective longitudinal designs are required.     

Psychiatric outcome of epilepsy surgery in patients with psychosis and temporal lobe drug-resistant epilepsy: A prospective case series

ObjectivesTemporal lobe resistant epilepsy has been associated with a high incidence of psychotic disorders; however, there are many controversies; while some patients get better after surgery from their psychiatric condition, others develop psychosis or de novo depression. The aim of this study was to determine the psychiatric and seizure outcome after epilepsy surgery in patients with a previous history of psychoses.MethodsSurgical candidates with temporal lobe drug-resistant epilepsy and a positive history of psychosis diagnosed during the presurgical psychiatric assessment were included. A two-year prospective follow-up was determined after surgery. The DSM-IV Structural Interview, GAF (global assessment of functionality, DSM-IV), Ictal Classification for psychoses, and Engel's classification were used. The Student t test and chi-square–Fisher tests were used.ResultsDuring 2000–2010, 89 patients were admitted to the epilepsy surgery program, 14 patients (15.7%) presented psychoses and were included in this series. After surgery, six patients (43%) did not develop any psychiatric complications, three patients (21%) with chronic interictal psychosis continued with no exacerbation, three patients (21%) developed acute and transient psychotic symptoms, and two patients (14%) developed de novo depression. Seizure outcome was Engel class I-II in 10 patients (71%). Total GAF scores were higher after surgery in patients found to be in Engel class I–II (p < 0.05).ConclusionsPatients with comorbid psychosis and temporal lobe drug-resistant epilepsy may benefit from epilepsy surgery under close psychiatric supervision.     

Psychiatric comorbidity in epilepsy: a study comparing patients with mesial temporal sclerosis and juvenile myoclonic epilepsy

We evaluated the frequency of psychiatric disorders (PDs) in a homogenous series of patients with temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS), as compared with patients with juvenile myoclonic epilepsy (JME), aiming to determine possible differences in psychiatric diagnoses between these two epileptic syndromes. Data from 170 patients with refractory TLE-MTS and from 100 patients with JME were reviewed and compared. The prevalence of PDs was high in both groups of patients with epilepsy: PDs were present in 85 patients with TLE-MTS (50%) and 49 patients with JME (49%). Among the TLE-MTS group, mood (25.8%), psychotic (15.8%), and anxiety (14.1%) disorders were the most frequent diagnoses, whereas anxiety and mood disorders (23 and 19%, respectively) were the most common among patients with JME. Psychoses were significantly associated with MTS (P<0.01) and anxiety disorders with JME (P<0.05). These findings suggest the existence of an anatomic correlation between PDs and brain structures involved in both epilepsy syndromes.