Elsevier

The Lancet Neurology

Volume 15, Issue 1, January 2016, Pages 106-115
The Lancet Neurology

Review
Comorbidities of epilepsy: current concepts and future perspectives

https://doi.org/10.1016/S1474-4422(15)00225-2Get rights and content

Summary

The burden of comorbidity in people with epilepsy is high. Several diseases, including depression, anxiety, dementia, migraine, heart disease, peptic ulcers, and arthritis are up to eight times more common in people with epilepsy than in the general population. Several mechanisms explain how epilepsy and comorbidities are associated, including shared risk factors and bidirectional relations. There is a pressing need for new and validated screening instruments and guidelines to help with the early detection and treatment of comorbid conditions. Preliminary evidence suggests that some conditions, such as depression and migraine, negatively affect seizure outcome and quality of life. Further investigation is needed to explore these relations and the effects of targeted interventions. Future advances in the investigation of the comorbidities of epilepsy will strengthen our understanding of epilepsy and could play an important part in stratification for genetic studies.

Introduction

Young adults have a median of two chronic health conditions, rising to six in people older than 65 years.1 These findings have led some researchers to refer to the co-occurrence of several medical conditions in the same individual as a normal state of affairs.2 A comorbid condition (or comorbidity) is one that occurs during the course of an index disease (eg, epilepsy). Comorbidities are generally defined in broad terms, including distinct clinical diseases and syndromes, and signs or symptoms of the index disease.1

Roughly 50% of adults with active epilepsy have at least one comorbid medical disorder.1, 2 Several large population-based studies report various conditions that are up to eight times more prevalent in people with epilepsy relative to the general population.3, 4 Appreciation of the relevance of these comorbidities is increasing because they affect epilepsy prognosis and quality of life. For example, migraine and psychiatric comorbidities are associated with poor seizure outcome, whereas depression has been linked with reduced quality of life.5, 6 Despite this growing appreciation, few data are available on the most effective methods to screen for comorbidities and the effect of interventions on prognosis.

Here, we describe ideas relevant to the investigation and conceptualisation of the comorbidities of epilepsy. We review the present state of knowledge of comorbidities associated with epilepsy and explore the ways in which research into comorbidities affords new opportunities for improvement in clinical care and scientific discovery.

Section snippets

Measuring comorbidity

A fundamental step in the study of the comorbidities of epilepsy is to understand the ways in which comorbidities are measured. An important measure of comorbidity burden is prevalence, which is generally understood to represent point prevalence—the proportion of individuals at risk with the condition in question at a single point in time.7 When discussing the comorbidities of epilepsy, the emphasis is on whether the prevalence of comorbid conditions in those with epilepsy is different from

Mechanisms of association

Straightforward measurement of associations between different diseases has been referred to as an “empirical statistical phenomenon that has no meaning in itself”.17 Measurement of associations is only the first step in a process in which an additional goal is to understand why specific conditions are associated, which in turn might change our understanding of epilepsy and its clinical care.

Several models have been generated to account for the relation between comorbid disorders.17, 18, 19 Such

The burden of comorbidity

Several large and comprehensive studies have examined the comorbidity burden in people with epilepsy, and we now describe this research and the relevance of such comorbidities in the context of the concepts underpinning comorbidity research discussed above. These large studies have used population-based cohorts and administrative databases in the UK,36 Canada,37, 38 and the USA,39, 40, 41, 42, 43 and have consistently shown a higher prevalence of several somatic and psychiatric conditions in

Screening and diagnosis

One of the more fundamental features of the comorbidities of epilepsy is their effects on the time of detection of the index disease since they might act as an iatrotropic stimulus.1 Regular neurological follow-up in individuals with a known brain neoplasm, for example, will enable earlier detection of a seizure disorder.

Understanding which comorbidities might develop in people with epilepsy is equally relevant. A report by the US Institute of Medicine emphasised the importance of the early

Future directions

Two major ways in which the investigation of comorbidities offers opportunities to further our understanding of epilepsy relate to the evolving notion of epilepsy as a spectrum, or part of a spectrum, and to their use as an important instrument in the study of genetics.

We have generally referred to epilepsy as a single, implicitly uniform entity, but epilepsy is, in fact, highly heterogeneous in terms of its cause, demographics, clinical manifestations, treatment, and prognosis. It is best

Conclusions

The comorbidities of epilepsy represent a substantial burden for people with epilepsy. The clinical and scientific community should continue to move forward, not only to focus on the description of the statistical relation between different conditions, but also to deconstruct the causal mechanisms for these comorbidities, while bearing in mind the risk of artifactual comorbidity. Screening instruments and guidelines should be developed to help translate the knowledge we have acquired into

Search strategy and selection criteria

We searched two electronic databases: Ovid MEDLINE (1946–Nov 25, 2014) and Ovid Embase (1947–Nov 25, 2014) for articles with the MeSH and Emtree terms “comorbidity” and “epilepsy”. We additionally searched for titles, abstracts, and keywords using the terms: comorbid*, epilepsy*, seizure*, convuls*, and epileptic*. The search was not limited by language of publication. Animal studies were excluded. Our initial search identified 3843 records after the removal of duplicates. The title and

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