Social Adjustment and Competence 35 Years After Onset of Childhood Epilepsy: A Prospective Controlled Study

Summary: Purpose: To study the effect of childhood-onset epilepsy without other neurologic deficit on adult social adjustment and competence.
Methods: Social competence was studied in a prospective, population-based cohort of childhood-onset epilepsy after a mean follow-up of 35 years. One hundred patients (60% of the total cohort) had no other neurologic problems ("epilepsy only"), and for each patient, two matched controls, a "random" control and an "employee" control were chosen.
Results: Good social outcome was significantly reduced in the "epilepsy only" cohort compared with random controls: education [cumulative odds ratio (COR), 2.4; 95% confidence interval (CI), 1.4–4.11; employability (COR, 7.3; 95% CI, 2.7–20.0); and marriage rate (COR, 3.7; 95% CI, 1.9–7.3). The patients with epilepsy rated their own ability to control their lives as "poor or missing" four times more frequently than the employee controls. Patients receiving antiepileptic polytherapy, but not monotherapy, were significantly less satisfied with their present life (OR, 6.7; 95% CI, 1.9–24.1) and felt their general health was significantly poorer (OR, 5.1; 95% CI, 1.2–21.3) than did the employee controls. Furthermore, patients with continuing seizures were significantly less satisfied with their present life (OR, 4.1; 95% CI, 1.1–15.1) than were employee controls.
Conclusions: Many patients with "epilepsy only" beginning in childhood have persistent and significant social-adjustment and competence problems in adulthood.     

Reproductive Activity and Offspring Health of Young Adults with Childhood-Onset Epilepsy: A Controlled Study

Summary: Purpose : To study reproductive activity and offspring health in a prospective follow-up setting.
Methods : After a 35-year follow-up of a population-based patient cohort with childhood-onset "epilepsy only", 100 (56.8%) of 176 surviving patients were shown to have "epilepsy only", i.e., recurrent unprovoked seizures with no associated neuroimpairment. Their reproductivity and offspring health were compared with those of matched controls.
Results : The marriage rate and fertility of patients with "epilepsy only" were significantly reduced as compared with those of matched controls. Continuation of antiepileptic drug (AED) treatment was significantly associated with reduced reproduction, whereas occurrence of seizures during the previous 5 years was not. The incidence of epilepsy was nine times greater among the children of patients than among those of controls. No higher risks were observed in pregnancy or delivery in patients, nor were increased rates of birth defects in their offspring than in those of contols. Exposure to AEDs during pregnancy did not increase these risks.
Conclusions : Patients with "epilepsy only" since childhood have fewer marriages and fewer children than expected. However, when they marry, their pregnancies and deliveries are unremarkable and their children do not have increased congenital health problems. Obviously, etiologies causative of both epilepsy and associated neurological impairments are more harmful to the course of pregnancy and delivery and offspring health than are those resulting in "epilepsy only".     

Antiepileptic drugs in the treatment of psychiatric disorders

The clinical interface between psychiatry and neurology is epilepsy; the pharmacological expression of this interface is antiepileptic drugs (AEDs), as they are used to treat both epilepsy and psychiatric disorders, especially bipolar disorders. The prevalence of psychiatric comorbidity and the risk of suicidal behavior/ideation/suicide are markedly increased in patients with epilepsy (PWE). Though AEDs receive initial indications for the treatment of epilepsy, currently the majority of AEDs are used to treat pain and psychiatric disorders. Thus in selecting the appropriate AEDs for treatment of PWE, consideration should be given to which AEDs best treat the epileptic disorder and the psychiatric comorbidity. This review is an overview of 21 AEDs in which negative psychotropic properties, approved indications in psychiatry, off-label studied uses in psychiatry, and principal uses in psychiatry are presented with literature review. A total of 40 psychiatric uses have been identified. Of the 21 AEDs reviewed, only 5 have U.S. Food and Drug Administration and/or European Medicines Agency psychiatric approval for limited uses; the majority of AEDs are used off-label. Many of these off-label uses are based on case reports, open-label studies, and poorly controlled or small-sample-size studies. In some instances, off-label use persists in the face of negative pivotal trials. Further placebo-controlled (augmentation and monotherapy) parallel-arm research with active comparators is required in the complex field of AED treatment of psychiatric disorders to minimize the treatment gap not only for PWE with psychiatric disorders, but also for psychiatric patients who would benefit from properly studied AEDs while minimizing adverse effects.     

Psychiatric Comorbidity in Chronic Epilepsy: Identification, Consequences, and Treatment of Major Depression

Summary: The purpose of this article is to review the topic of interictal psychiatric comorbidity among adult patients with chronic epilepsy, focusing specifically on those studies that have used contemporary psychiatric nosology. Five specific issues are addressed: (a) the risk and predominant type(s) of psychiatric comorbidity in chronic epilepsy, (b) adequacy of recognition and treatment of psychiatric comorbidity, (c) the additional burdens that comorbid psychiatric disorders impose upon patients with chronic epilepsy, (d) the etiology of these disorders, and (e) strategies for treatment. Current appreciation for these issues in epilepsy is contrasted to related fields (e.g., primary care, psychiatry, and epidemiology), where considerable attention has been devoted to the identification, consequences, and treatment of psychiatric comorbidity. The issue of psychiatric comorbidity in epilepsy is reviewed with the aim of identifying a clinical and research agenda that will advance understanding of at least one important psychiatric condition associated with epilepsy—namely, major depression.     

Outcomes After Seizure Recurrence in People with Well-Controlled Epilepsy and the Factors That Influence It

Summary: Purpose: To determine the risk of further seizures and probability of further remission after a first seizure recurrence in patients in remission of their epilepsy, and to examine the prognostic factors influencing this risk.
Methods: Continued follow-up of a cohort of 409 patients with a recurrence of seizures after randomization to the Medical Research Council (MRC) Antiepileptic Drug Withdrawal Study.
Results: By 3 years after a seizure, 95% of patients have experienced a further 1-year remission of their epilepsy and by 5 years 90% of patients have experienced a further 2-year remission. The most important factors contributing to the risk of further seizures after a first seizure after randomization were the previous seizure-free interval, having partial seizures at recurrence, and having previously experienced seizures while receiving treatment. There was no evidence that the group of patients who had discontinued or reduced treatment before the occurrence of their first seizure after randomization had a different outcome from those patients who continued treatment.
Conclusion: Our results provide no evidence that discontinuation of antiepileptic drugs (AEDs) modifies the long-term prognosis of a person's epilepsy, although it does increase the risk of seizures in the 1- to 2-year period after discontinuation.     

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.     

Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: a review of current clinical experience

PURPOSE: We reviewed the impact of planned discontinuation of antiepileptic drugs (AEDs) in seizure-free patients on seizure recurrence and the seizure outcome of reinstituted treatment. METHODS: A literature review was performed yielding 14 clinical observations of seizure recurrence after discontinuation and its treatment outcome. RESULTS: Seizure recurrence rate after AED discontinuation ranged between 12 and 66% (mean 34%, 95%CI: 27-43) in the 13 reviewed studies (no data in one study). Reinstitution of AEDs after recurrence was efficacious between 64-91% (mean of 14 studies, 80%, 95%CI: 75-85%) at follow-up. Mean follow-up ranged from 1-9 years. Seizure outcome of resumed treatment was not different for series in children and adolescents (84%, mean of 4 studies, 95%CI: 75-93) or in adults only (80%, mean of 9 studies, 95%CI: 74-86). Although seizure control was regained within approximately one year in half of the cases becoming seizure free, it took some patients as many as 5-12 years. In addition, in 19% (mean of 14 studies, 95%CI: 15-24%), resuming medication did not control the epilepsy as before, and chronic drug-resistant epilepsy with many seizures over as many as five years was seen in up to 23% of patients with a recurrence. Factors associated with poor treatment outcome of treating recurrences were symptomatic etiology, partial epilepsy and cognitive deficits. CONCLUSIONS: These serious and substantial risks weigh against discontinuation of AEDs in seizure-free patients, except perhaps for selected patients with idiopathic epilepsy syndromes of childhood or patients with rare seizures.     

Initiation of Treatment and Selection of Antiepileptic Drugs in Childhood Epilepsy

Summary:  Purpose: A retrospective study was carried out on 53 cases with childhood epilepsy to evaluate the validity of the initial selection of antiepileptic drug (AED).
Methods: We investigated the AEDs selected at the beginning of the treatment from the medical records of 53 untreated cases. A follow-up study was undertaken to evaluate the effects of the AEDs. In the second study, we investigated the AEDs of 10 cases with atypical benign partial epilepsy (ABPE), to clarify whether the initial AEDs selected for rolandic epilepsy were related to the appearance of ABPE.
Results: The AEDs used at the initial stage consisted of carbamazepine (CBZ), valproic acid (VPA), phenobarbital (PB), and vitamin B₆. The main AEDs were CBZ and VPA for localization-related epilepsy, and VPA for generalized epilepsy. The initial selection of AEDs in 41 (85.4%) of 48 cases treated with AEDs were considered to be correct from the results of follow-up. We could not specify any AEDs that related to the appearance of ABPE.
Conclusions: The selection of AED in this series was considered to be most appropriate. We proposed a criterion to determine whether to begin the AED treatment immediately at the initial seizure.     

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.     

Epilepsy and suicide: pathogenesis, risk factors, and prevention

Depression and suicide tendencies are common in chronic diseases, especially in epilepsy and diabetes. Suicide is one of the most important causes of death, and is usually underestimated. We have analyzed several studies that compare mortality as a result of suicide in epileptic patients and in the general population. All the studies show that epileptic patients have a stronger tendency toward suicide than healthy controls. Moreover it seems that some kinds of epilepsy have a higher risk for suicide (temporal-lobe epilepsy). Among the risk factors are surgery therapy (suicide tendency five times higher than patients in pharmacological therapy), absence of seizures for a long time, especially after being very frequent, and psychiatric comorbidity (major depression, anxiety-depression disorders, personality disorders, substance abuse, psychoses). The aim of the review was to analyze the relationship between suicide and epilepsy, to identify the major risk factors, and to analyze effective treatment options.