The issue of how chronic temporal lobe epilepsy (TLE) affects brain structure and cognition across the lifespan remains a topic of interest and concern. Tightly controlled prospective investigations of cognition in epilepsy are modest in number and most have a test–retest interval of well below 10 years (Dodrill, 2004; Seidenberg et al., 2007). An emerging view derived from the combination of cross-sectional and prospective studies is that childhood/adolescent onset epilepsy exerts a significant adverse neurodevelopmental effect on cognition and that, over time, persons with persisting pharmacoresistent chronic epilepsy carry their deficits into and through adulthood. A subset of patients exhibit an especially difficult prospective cognitive course—those problems less linked to recorded seizure frequency than baseline sociodemographic characteristics (e.g., age, education, intelligence quotient [IQ]), neuroimaging abnormalities, or the underlying etiology of the epilepsy (Dikmen et al., 1975; Dodrill & Matthews, 1992; Helmsteadter et al., 2003; Piazzini et al., 2006; Hermann et al., 2008; Kaaden & Helmstaedter, 2009; Helmstaedter & Elger, 2009; Baxendale et al., 2010).
With respect to prospective changes in brain structure, a largely comparable state of affairs exists with a limited number of controlled longitudinal investigations, again typically with modest test–retest intervals (e.g., Liu et al., 2003; Liu et al. 2005; Bernhardt et al., 2009; Coan et al., 2009; Bernhardt et al., 2010). Several prospective studies have focused on discrete but important regions of interest in specific epilepsy syndromes, such as the hippocampus in TLE (e.g., Van Paesschen et al., 1998; Briellmann et al., 2002; Fuerst et al., 2003). A number of cross-sectional investigations of prevalent cases have characterized distributed abnormalities in cortical volume or thickness, volumes of subcortical structures and cerebellum (Sisodiya et al., 1997; Bernasconi et al., 2004; Mueller et al., 2006; Lin et al., 2007; Keller & Roberts, 2008; McDonald et al., 2008a,b; Hermann et al., 2009; Bonilha et al., 2010a,b), as well as white matter volume and other measures of connectivity in patients with mesial TLE (Arfanakis et al., 2002; Hermann et al., 2003a,b; Diehl et al., 2008; McDonald et al., 2008a,b,c; Concha et al., 2009; Meng et al., 2010; Riley et al., 2010). How these abnormalities change with age over the broader lifespan is unknown.
In the literature on normal aging, a number of quantitative neuroimaging investigations have examined healthy controls across a broad age range to provide preliminary cross-sectional insight into lifespan trajectories of brain change (e.g., Pfefferbaum et al., 1994; Blatter et al., 1995; Toga et al., 2006; Sowell et al., 2007; Raz et al., 2010; Walhovd et al., 2011). This modeling approach has been used to examine lifespan cognition in epilepsy (Helmstaedter & Elger, 2009; Baxendale et al., 2010), but has not yet attempted to characterize lifespan brain structure in epilepsy. Herein we report the results of a cross-sectional lifespan analysis of brain structure among adult patients with chronic TLE of mean childhood/adolescent onset compared to healthy controls in order to address three questions: (1) what is the broad landscape of anatomic abnormality in middle-aged persons with mean childhood/adolescent onset TLE, (2) what are the patterns of change in cortical and subcortical structure as a function of chronologic age in the epilepsy and control groups, and (3) are age-accelerated brain changes evident in the epilepsy group?