Objective: It remains unclear whether drug-resistant temporal lobe epilepsy (TLE) is associated
with cumulative brain damage, with no expert consensus and no quantitative syntheses of the
available evidence.
Methods: We conducted a systematic review and meta-analysis of MRI studies on progressive
atrophy, searching PubMed and Ovid MEDLINE databases for cross-sectional and longitudinal
quantitative MRI studies on drug-resistant TLE.
Results: We screened 2,976 records and assessed eligibility of 248 full-text articles. Forty-two
articles met the inclusion criteria for quantitative evaluation. We observed a predominance of
cross-sectional studies, use of different clinical indices of progression, and high heterogeneity
in age-control procedures. Meta-analysis of 18/1 cross-sectional/longitudinal studies on hippocampal
atrophy (n 5 979 patients) yielded a pooled effect size of r 5 20.42 for ipsilateral atrophy
related to epilepsy duration (95% confidence interval [CI] 20.51 to 20.32; p , 0.0001; I
2 5
65.22%) and r 5 20.35 related to seizure frequency (95% CI 20.47 to 20.22; p , 0.0001; I
2 5
61.97%). Sensitivity analyses did not change the results. Narrative synthesis of 25/3 crosssectional/longitudinal
studies on whole brain atrophy (n 5 1,504 patients) indicated that
.80% of articles reported duration-related progression in extratemporal cortical and subcortical
regions. Detailed analysis of study design features yielded low to moderate levels of evidence for
progressive atrophy across studies, mainly due to dominance of cross-sectional over longitudinal
investigations, use of diverse measures of seizure estimates, and absence of consistent age
control procedures.
Conclusions: While the neuroimaging literature is overall suggestive of progressive atrophy in
drug-resistant TLE, published studies have employed rather weak designs to directly demonstrate
it. Longitudinal multicohort studies are needed to unequivocally differentiate aging from
disease progression