Behavioral aspects of pediatric epilepsy syndromes

Apart from control of the seizures, two of the most important factors in determining how well a child with epilepsy progresses toward independence are cognition and behavior. The diagnosis of the correct epilepsy syndrome often provides information with regard to probability of good seizure control and intellectual outcome. However, relatively little has been published on the behavioral aspects of the various epilepsy syndromes. In West syndrome there is emerging evidence that early effective treatment might improve outcome in terms of both cognition and behavior. The work on this syndrome in children with tuberous sclerosis has demonstrated an association between temporal lobe tubers and autism. In Dravet syndrome, a variety of psychiatric disorders have been reported, including hyperactivity and autistic features. This is another epilepsy syndrome that tends to be resistant to treatment, implying that the prognosis has to be guarded. The behavioral problems reported with Lennox-Gastaut syndrome also include autistic features, as well as generally sluggish behavior. It is very likely that these characteristics largely reflect the effect of ongoing seizure activity. Autistic features, aggression, and hyperkinesis have been described with Landau-Kleffner syndrome. The behavior may improve dramatically with appropriate medical treatment or after multiple subpial transection. Although the syndrome of benign partial seizures with centrotemporal or rolandic spikes is said to have a very good prognosis, it is becoming increasingly evident that behavioral problems such as concentration difficulties, tempers, hyperactivity, and impulsivity might occur. Juvenile myoclonic epilepsy has been associated with very variable behavioral traits, sometimes with immature personality features and poor social adjustment suggesting frontal lobe dysfunction. Because many of the reports of behavioral disturbance associated with epilepsy syndromes are anecdotal and do not include validated measures of behavior it would be unwise to draw firm conclusions from them at this stage. Carefully conducted prospective studies, paying particular attention to any behavioral improvements that occur with successful treatment of the epilepsy, are required.     

Modern perspectives on epilepsy in relation to psychiatry: behavioral disturbances of epilepsy

In this paper, the second of a two-part series on current psychiatric aspects of epilepsy, the authors consider the classification and management of the various kinds of psychoses and other behavior disturbances associated with some cases of epilepsy. After discussing the common aspects of epilepsy and schizophrenia, they describe attempts to categorize epileptic psychoses, focusing on a classification of ten kinds of psychoses that they believe has broadest application. They present guidelines for psychopharmacological management of epilepsy accompanied by behavior disturbance, with emphasis on anticonvulsant monotherapy, and they discuss possibly related seizure disorders and possible etiologies of behavioral symptoms of epilepsy.     

Psychiatric and behavioral comorbidities in epilepsy: A critical reappraisal

Psychiatric and behavioral disorders are important aspects of epilepsy and have received increasing attention in the last several years. The literature upon which most of the field relies contains some biases that must be carefully examined and resolved in future studies. First, in the pediatric epilepsy literature, many reports find that children with epilepsy have high levels of behavioral and psychiatric disorders when compared to appropriate controls. Most of these studies rely on parent‐proxy completed instruments to assess these behavioral endpoints. Parents’ reports are not objective but reflect parents’ reactions and emotions. Increasing evidence suggests inherent biases in proxy reports and highlights the need to assess children directly. Second, periictal phenomena may be mischaracterized as underlying mood disorders. Third, many studies report elevated levels of psychiatric morbidity before and after the diagnosis of epilepsy, suggesting an inherent relation between the two types of disorders. Psychogenic nonepileptic seizures, while widely recognized as posing a diagnostic dilemma in the clinic, may account for some of these research findings. Diagnostic errors between epilepsy and psychogenic nonepileptic seizures need careful consideration when evaluating studies demonstrating associations between psychiatric disorders and epilepsy or poorer seizure control in association with psychiatric disorders in people who have epilepsy. Mental health concerns are important for everyone. An accurate, undistorted understanding of the relation between mental health disorders and epilepsy is essential to ensure appropriate therapy and to avoid unnecessary and potentially harmful treatments and common misconceptions.     

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.     

Key Issues in Addressing the Comorbidity of Attention Deficit Hyperactivity Disorder and Pediatric Epilepsy

Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of epilepsy encountered by clinicians. However, relatively little information is available to guide optimal diagnostic and treatment strategies. Differentiating ADHD from effects of epilepsy requires careful history taking and emphasis upon characteristic symptoms and course of illness. Rating scales for ADHD are well validated and may aid clinical management. Use of antiepileptic drugs may cause cognitive or behavioral side effects yet may improve behavior in some cases. Historically, clinicians have been hesitant to treat ADHD comorbidity for fear of lowering the seizure threshold. However, an aggregate of recent evidence now suggests that stimulants may be well tolerated and effective for ADHD comorbid with epilepsy. Studies that further clarify pathophysiology and treatment outcomes are needed in order to enhance clinical efficacy and quality of life for this population.     

Chronobiological paradigms of mental life and clincial neurosciences]

Circadian fluctuations of normal and abnormal behavioural processes have been classically reported from statistically validated chronograms (averaged displays of data as a function of time). Going more deeply into the research with rhythmometric investigations reveals that the temporal organization of psychophysiological functions involving several oscillatory systems may compose possible circadian paradigms of brain integration and pathological chronorisk for clinical neuroscience (seizure susceptibility for epilepsy and related states, brain circulatory disturbances, stress-related events, emotional or affective manifestations, and psychosomatic disorders). Rhythmometrically analyzed, the temporal fluctuations of behavioural events tend to indicate that cerebral integrations are circadian, circaseptidian or infradian stage-dependent processes whose chronobiologic characteristics are possibly predictable on the basis of mathematical models. More generally, the present study reveals that: 1) several neurological or psychiatric disorders are directly or indirectly concerned with chronobiologic processes, and that 2) cerebral and behavioural time variations can be detected and described in neurology and psychiatry as algorithmically-formulatable recurring psychophysiological changes with a waveform validated by inferential statistical computer methods. Such rhythmometric procedures applied to neurological or psychiatric events suggest also the development of new epistemological concepts in the fields of comparative psychophysiology and theoretical neuroscience.     

Cognitive and behavioral complications of frontal lobe epilepsy in children: a review of the literature

Frontal lobe epilepsy (FLE) is considered the second most common type of the localization-related epilepsies of childhood. Still, the etiology of FLE in children, its impact on cognitive functioning and behavior, as well as the response to antiepileptic drug treatment in children has not been sufficiently studied. This review focuses on these aspects of FLE in childhood, and reveals that FLE in childhood is most often cryptogenic, and impacts on a broad range of cognitive functions. The nature and severity of cognitive deficits are highly variable, although impaired attention and executive functions are most frequent. Young age at seizure onset is the only potential risk factor for poor cognitive outcome that has been consistently reported. The behavioral disturbances associated with FLE are also highly variable, although attention deficit/hyperactivity disorder seems most frequent. In 40% of children with FLE satisfactory seizure control could not be achieved. This is a higher percentage than reported for the general population of children with epilepsy. Therefore, pediatric FLE, even if cryptogenic in nature, is frequently complicated by impairment of cognitive function, behavioral disturbances, and therapy-resistance. Given the impact of these complications, there is a need for studies of the etiology of frontal lobe epilepsy-associated cognitive and behavioral disturbances, as well as pharmacotherapy-resistance.     

The impact of epilepsy on subjective health status

Epilepsy is a chronic disorder that has complex effects on many aspects of personal health. Recent advances in the methods to reliably and validly assess subjective health status have allowed major advances in our understanding of these diverse effects, and have also provided evidence to guide treatment and future research. Studies that have included measures of quality of life, patient preferences, and disability in epilepsy have shown that the magnitude of the adverse effects of recurrent seizures on many aspects of subjective health status is as large as that seen with diabetes mellitus and active cardiovascular disease. Studies of patient-oriented, comprehensive outcomes after epilepsy surgery indicate positive treatment effects in broad areas of function and well-being. Although few trials of epilepsy drugs have included health outcome instruments, available studies suggest that greater than 50% seizure reduction is associated with improved quality of life. Adverse medication effects and depression appear to have a strong association with subjective health status in epilepsy, independent of seizure frequency.     

Diagnosis and measurement of adolescent depression: a review of commonly utilized instruments

We surveyed 160 recent studies of adolescent depression (publication dates ranged from March 1996 to August 2000) and identified 33 different diagnostic and symptom measurement instruments being used by various investigators. We also found that more than one in three of the studies measuring depressive symptom severity in adolescents relied on instruments designed for use with adults. We then reviewed in detail the design features and psychometric properties of the 12 instruments most commonly used in studies of adolescent depression and attempted to characterize their strengths and weaknesses. Our main conclusions are as follows: Too many different instruments are being used by investigators, presumably due to a lack of consensus as to which are the most valid and reliable tools. Instruments designed for use in adults and never validated in adolescent populations are frequently used with no evidence for their developmental sensitivity. Many studies are using instruments that demonstrate substantial weaknesses in validity and/or reliability. The need for a parsimonious, easily administered, valid, and reliable tool(s) to diagnose and measure symptom severity in adolescent depression has not yet been met.     

Psychiatric Disorders in Epilepsy: Clinical Aspects

Increased levels of psychiatric morbidity are associated with epilepsy in adults and children. The relationship between type of epilepsy, seizure focus, and nature of psychiatric disturbance remains controversial and varies across studies. Behavioral disturbances associated with epilepsy may be related to the seizure discharge itself, interictal discharges, adverse psychosocial consequences of chronic epilepsy, underlying CNS pathology, or antiepileptic drugs. Such symptoms could also coexist with epilepsy without there being a causal relationship between the two. The major psychiatric conditions associated with epilepsy are psychosis, personality disorders, depression, and anxiety. The clinical aspects of these disorders as they relate to epilepsy are reviewed.     

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 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.     

Psychiatric comorbidity, health, and function in epilepsy

Epilepsy is a chronic condition that has complex effects on social, vocational, and psychological function. Several psychiatric disorders have been shown to have increased prevalence in persons with epilepsy compared to the general population. Depression appears to be the most common psychiatric comorbidity, but anxiety and other diagnoses have not been extensively investigated. Several studies have found that depression or psychological distress may be the strongest predictors of health-related quality of life, even including seizure frequency and severity, employment, or driving status. Despite the high prevalence and adverse effects of comorbid psychiatric disorders in epilepsy, very little is known about optimal treatment strategies, or even the efficacy of standard treatments. Further research is needed to increase understanding of the mechanisms of psychiatric illness in epilepsy, the effects of depression and anxiety on long-term clinical outcomes, and the most effective treatments.     

Neuropsychologic effects of frontal lobe epilepsy in children

Most published neuropsychologic studies on frontal lobe epilepsy have been performed on mixed groups of adults and adolescents with epilepsies of varying etiology. The cognitive profile of frontal lobe epilepsy in children has not been defined. The purpose of this study was to assess neuropsychologic performance in children with frontal lobe epilepsy. Intelligence and executive functions were examined in eight children (age 6 7/12 years to 13 11/12 years) with frontal lobe epilepsy. Performance was related to the focus side, seizure frequency, and age of epilepsy onset. Frontal lobe epilepsy was associated with a range of frontal dysfunctions, but IQ was generally spared. Left focus was associated with deficits in categorization, verbal long-term memory, and detailed visuospatial analysis. Frequent seizures correlated with attention difficulties and inability to inhibit impulsive responses. Children whose epilepsy appeared before age 6 years had reduced ability to change behavioral strategies. Frontal epileptic activity alone can cause selective frontal deficits, the severity and nature of which are related to side, seizure frequency, and age of epilepsy onset. These findings require confirmation on larger series of selected children.     

The impact of self-efficacy,alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: A moderated mediation analysis

This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas.     

Abnormal behavior in children with temporal lobe epilepsy and ganglioglioma

Temporal lobe epilepsy in childhood is characterized by great clinical, electroencephalographic, and etiological diversity. The prognosis after temporal lobe epilepsy surgery in childhood is usually good, with most patients achieving complete seizure control. However, in some children behavior deteriorates postoperatively. We report two girls (2 and 6 years of age) with refractory seizures due to temporal lobe ganglioglioma. They exhibited aggression and hyperactivity since the beginning of their epilepsy. In both patients, behavioral disturbances worsened postoperatively, despite complete seizure control. Patients and parents should be advised about possible behavioral disturbances after epilepsy surgery, especially in the presence of a temporal lobe developmental tumor, even when seizure control is achieved postoperatively.     

Seizure frequency, patient-perceived seizure severity and the psychosocial consequences of intractable epilepsy.

It is generally recognised that the assessment of treatment effects in epilepsy using seizure frequency as the only outcome measure may lack sensitivity. A patient-based seizure severity scale has been developed and initial results confirm its reliability and validity. As part of the further development of this scale it is important to explore the relationship between seizure severity, seizure frequency and the psychosocial consequences of intractable epilepsy. One hundred patients with medically refractory partial seizures completed a quality of life questionnaire including measures of physical (seizure severity and frequency), social and psychological well-being (anxiety, depression, self-esteem, locus of control and happiness). Multivariate analysis demonstrated that individual psychological variables were best predicted by other psychological variables. However, when these were removed from analysis, seizure severity was the most significant predictor of self-esteem (P = 0.005), locus of control P = 0.039) and anxiety (P = 0.048). Seizure frequency did not contribute significantly to the variance of any of the psychological factors. These results highlight the importance of considering seizure severity when assessing treatment effects in epilepsy and provide further evidence for the construct validity of a novel patient-based seizure severity scale.     

The use of psychotropic drugs in epilepsy: what every neurologist should know

Psychiatric disorders, such as mood, anxiety, attention deficit, and psychotic disorders, are among the most frequent comorbidities experienced by patients with epilepsy. While these psychiatric disorders have typically been considered as one of its complications, there is increasing evidence of a bidirectional relationship between the seizure disorder and mood and ADHD. Indeed, not only are patients with epilepsy at greater risk of developing these two disorders, but patients with mood and attention deficit disorders are at greater risk of developing epilepsy. Comorbid psychiatric disorders have a negative impact on the quality of life of patients with epilepsy. For patients with pharmacoresistant epilepsy, mood disorders are a stronger predictor of a worse perception of their quality of life than is their seizure frequency and severity. Thus, the use of psychotropic drugs is often necessary in patients with epilepsy, be they children or adults. Unfortunately, there are many misconceptions regarding the safety of psychotropic drugs, particularly of antidepressants and central nervous system stimulants, which are often erroneously thought of as being "proconvulsant." Such misconceptions have resulted in the undertreatment of psychiatric comorbidities in patients with epilepsy. This article provides a practical review of the use of antidepressants, central nervous system stimulants, and antipsychotic drugs in patients with epilepsy.     

Determinants of outcome in childhood epilepsy

Possible outcomes with regard to seizures include remission (i.e. no seizures without drug treatment), conditional remission (i.e. no seizures under treatment) and treatment resistance. Several factors have been identified which are associated with favourable or unfavourable outcomes. These include syndrome diagnosis (benign vs severe epilepsy syndromes), seizure types (kind and number), severity of epilepsy, response to treatment (immediate vs delayed, monotherapy vs combinations), and concomitant neurological and psychiatric disorders. However, the quality of disease management by caretakers also has an important influence on the outcome. To determine full remission in patients who are seizure-free with treatment, antiepileptic drugs need to be tapered; generally speaking, this seems to be less risky in children than in adults. However, even if remission without treatment has been reached, an elevated risk of seizures may persist compared with that of the general population. The outcome of epilepsy should not be considered with respect to seizures alone, but should also include more global aspects of performance and quality of life. These may depend on the causes of epilepsy as much as, or more than, on the seizure disorder itself, but may also be related to treatment.     

The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy

PURPOSE: To determine the independent effects of depression and anxiety on health-related quality of life (HRQOL) in epilepsy as well as the relative explanatory power of psychiatric comorbidity compared with demographic and clinical epilepsy variables (e.g., seizure frequency, severity, and chronicity). METHODS: Subjects (n = 87) with temporal lobe epilepsy completed self-report measures of depression, anxiety, HRQOL, and seizure severity. Information was derived regarding subjects' seizure frequency, duration, and treatment. HRQOL status (QOLIE-89) was examined in relation to self-reported symptoms of anxiety and depression, clinical seizure features, and demographic characteristics. RESULTS: Depression and anxiety were independently associated with reduced HRQOL. Psychiatric comorbidity explained more variance in HRQOL than did combined groups of clinical seizure or demographic variables. Although weaker in explanatory power than psychiatric comorbidity, several epilepsy factors were nonetheless significantly related to HRQOL, including seizure frequency, severity, and chronicity. CONCLUSIONS: Interictal anxiety and depression exert independent adverse effects on HRQOL. In addition, frequent, severe, and chronic seizures reduce HRQOL, but appear less powerful predictors of HRQOL than interictal psychiatric symptoms. Recognition and treatment of comorbid depression and anxiety is an important consideration in improving quality of life in epilepsy.