Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings

Objective: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. Methods: We investigated 123 participants—23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME—who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. Results: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. Significance: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset

Biomarkers of Epileptogenesis: Psychiatric Comorbidities (?)

The last decade has witnessed a significant shift on our understanding of the relationship between psychiatric disorders and epilepsy. While traditionally psychiatric disorders were considered as a complication of the underlying seizure disorder, new epidemiologic data, supported by clinical and experimental research, have suggested the existence of a bidirectional relation between the two types of conditions: not only are patients with epilepsy at greater risk of experiencing a psychiatric disorder, but patients with primary psychiatric disorders are at greater risk of developing epilepsy. Do these data suggest that some of the pathogenic mechanisms operant in psychiatric comorbidities play a role in epileptogenesis? The aim of this article is to review the epidemiologic data that demonstrate that primary psychiatric disorders are more frequent in people who develop epilepsy, before the onset of the seizure disorder than among controls. The next question looks at the available data of pathogenic mechanisms of primary mood disorders and their potential for facilitating the development and/or exacerbation in the severity of epileptic seizures. Finally, we review data derived from experimental studies in animal models of depression and epilepsy that support a potential role of pathogenic mechanisms of mood disorders in the development of epileptic seizures and epileptogenesis. The data presented in this article do not yet establish conclusive evidence of a pathogenic role of psychiatric comorbidities in epileptogenesis, but raise important research questions that need to be investigated in experimental, clinical, and population-based epidemiologic research studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13311-014-0271-4) contains supplementary material, which is available to authorized users