A search was carried out using PubMED for articles published up to December 2007. Search terms comprised key words related to epilepsy, including “seizure” and “seizure disorder” combined with terms to reflect neurobehavioural comorbidities, such as “depression”, “anxiety”, “cognition”, “social”, and “MRI volumetrics”, to identify potentially relevant studies. Further articles were identified from the reference lists of these papers. Only articles published in English were included. All
ReviewThe neurobehavioural comorbidities of epilepsy: can a natural history be developed?
Introduction
Epilepsy is a prevalent neurological disorder that affects an estimated 50 million people worldwide.1 Although defined by the presence of recurrent seizures, epilepsy can be so much more and might include abnormalities in cognition, psychiatric status, and social adaptive behaviour; these problems are grouped under the term neurobehavioural comorbidities in this Review.
Although increasing clinical and research attention has been directed at these complications, the neurobehavioural comorbidities of epilepsy have a long and at times dispiriting history. Problems in cognition, emotional–behavioural status, and social function, which were variously referred to as the psychosocial complications or the burden of epilepsy, were investigated empirically from the start of the 20th century, when people with epilepsy were frequently segregated in colonies.2 Epileptologists subsequently sought to provide a more representative picture of the consequences of epilepsy in people who lived in the community,3 and patients with epilepsy have been the ongoing concern of national commissions,4 public health agencies,5 and special action groups of national and international health organisations, including the International League Against Epilepsy, World Health Organization, Centers for Disease Control, and Epilepsy Foundation. Recently, at the National Institutes of Health conference Curing Epilepsy 2007: Translating Discoveries into Therapies, the prevention and reversal of the comorbidities of epilepsy were identified as a major new benchmark area for research.
Although undeniably a potentially crucial complication of the epilepsies, the aetiology and course of the neurobehavioural comorbidities—or their natural history—need to be fully characterised. In this Review, we discuss the current knowledge with regard to these complications of epilepsy from a lifespan perspective. First, we give a brief overview of the prevalence of neurobehavioural comorbidities in population-based and other non-selected studies; we then turn to the question of whether the neurobehavioural comorbidities and their course are progressive; finally we discuss neurodevelopmental studies and focus on their onset and development. Although this is an atypical lifespan order, it is one that investigators have pursued to understand the neurobehavioural comorbidities of epilepsy. Because epilepsy is a family of disorders with various aetiologies, age dependence, severity, and other features, we will anchor our presentation throughout this Review to a particularly common form of epilepsy—temporal lobe epilepsy—to emphasise the core points.
Section snippets
The nature of the problem
The term comorbidity refers to the greater than coincidental presence of two conditions in the same individual.6 Comorbidity does not imply direction or causation, and the disorders might co-occur by chance or they could share genetic, environmental, or other mechanisms.7 The association or comorbidity of cognitive, psychiatric, and social problems in patients with epilepsy have frequently been investigated in selected populations; these populations typically comprise patients cared for at
Do comorbidities progress or worsen over time?
Concerns about whether cognition, psychiatric status, or social function deteriorate over time (so-called progression) in the face of chronic epilepsy or markers of epilepsy severity have been voiced for decades. Many cross-sectional studies have investigated the association among cognition and the duration and severity of epilepsy. Although indirect, these studies can be used to examine patterns of cognition or behaviour in patients who have had epilepsy for decades. The outcomes have been
Comorbidities in older patients with epilepsy
The ultimate course of neurobehavioural comorbidities in patients with chronic epilepsy is poorly understood. Research into ageing and epilepsy has focused on new-onset epilepsy in older patients and there are few data on older patients who have lived with epilepsy for decades. We are aware of only four published studies that have objectively assessed cognitive status in older patients with chronic epilepsy.95, 97, 99, 100 Compared with healthy controls (n=27), community-dwelling older patients
When do comorbidities start?
Owing to the nature and severity of the neurobehavioural comorbidities associated with chronic active epilepsy, interest in finding the origin and development of these problems has grown, and at least three sets of evidence suggest a substantial neurodevelopmental contribution.
First is the indirect investigation of the risk of comorbidities as a function of age of epilepsy onset. The results of neuropsychological studies in adults with chronic epilepsy have shown, repeatedly, that earlier age
Children and adolescents with new-onset epilepsy
The cognitive and behavioural status of patients close to the onset of recurrent seizures has been investigated, and abnormalities have been reported by some but not all investigators.137, 138, 139, 140, 141 The results of tests in children with newly diagnosed epilepsy who had not started antiseizure medications showed significantly worse behavioural adjustment and significantly poorer performance in attention, reaction time, and visual memory, with a trend for academic achievement (figure 7).
Before the onset of epilepsy
The findings that suggest that psychiatric, cognitive, and academic problems might even antedate the diagnosis of epilepsy and recognition of the first seizure are interesting and provocative.
Austin and collaborators144, 145 investigated behavioural problems in children with new-onset epilepsy compared with sibling controls and found that parents and teachers reported elevated rates of behavioural disturbances in children with epilepsy during the 6 months before the first recognised seizure. In
A lifespan perspective
Evidence shows that the onset of epilepsy in childhood might be associated with altered patterns of neural and cognitive development, an effect that might affect short-term (educational) and long-term occupational, social, and behavioural development.115 We need to determine whether this early effect increases the risk that subsequent lifetime insults, either related to epilepsy (eg, status epilepticus or number of lifetime generalised tonic–clonic seizures) or not (eg, closed head injury or
Conclusions
This Review suggests clinical and research opportunities to advance the knowledge, treatment, and prevention of the neurobehavioural comorbidities of the epilepsies throughout the lifespan. Although neurobehavioural comorbidities that antedate seizure onset have been identified by several research groups, the aetiology that underlies these comorbidities is unknown. Furthermore, because neurobehavioral comorbidities are present at the time of seizure onset in a proportion of children or
Search strategy and selection criteria
References (153)
- et al.
Living Well II: a review of progress since 2003
Epilepsy Behav
(2006) The pretherapeutic classification of comorbidity in chronic disease
J Chronic Dis
(1970)- et al.
Biologic factors as predictors of social outcome of epilepsy in intellectually normal children: a population-based study
J Pediatr
(1993) - et al.
Prevalence of epilepsy and health status of adults with epilepsy in Georgia and Tennessee: Behavioral Risk Factor Surveillance System, 2002
Epilepsy Behav
(2004) - et al.
Cognitive decline in temporal lobe epilepsy due to unilateral hippocampal sclerosis
Epileps Behav
(2007) Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG?
Lancet Neurol
(2003)- et al.
Chronic epilepsy and cognition
Lancet Neurol
(2004) - et al.
Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder
Biol Psychiatry
(2001) - et al.
Hippocampal and amygdaloid damage in partial epilepsy: a cross-sectional MRI study of 241 patients
Epilepsy Res
(2001) - et al.
Diffusion tensor MRI in temporal lobe epilepsy
Mag Res Imag
(2002)