Abstracts

Rationale: It remains unclear whether drug-resistant temporal lobe epilepsy (TLE) is associated with cumulative brain damage, with no expert consensus nor quantitative synthesis of the available evidence. MRI provides quantitative markers with biological validity and high test-retest reliability, representing an objective framework to test for disease progression. We conducted a systematic review and meta-analysis of previous MRI studies addressing progressive atrophy in TLE.  Methods: We searched PubMed and Ovid Medline databases for cross-sectional and longitudinal MRI studies on drug-resistant TLE, and included (1) studies conducted on human cohorts, with (2) participants evaluated using quantitative MRI methods and (3) analyses addressing disease progression through correlations with epilepsy duration, correlations with seizure counts, or longitudinal design. Animal studies, case reports or case series with n≤5 were excluded. Manual searches on reference lists of the included studies and a grey literature search were also conducted. The evaluation of hippocampal atrophy and its association with epilepsy duration and seizures employed meta-analytical methods and was conducted with R. Meta-analytical models were based on the Pearson correlation coefficient as unit of analysis. The evidence provided by studies on all brain structures other than the hippocampus was summarized using narrative synthesis. Quality of evidence was assessed according to the GRADE framework. Results: We screened 2976 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=979 patients) yielded a pooled effect size of r =-0.42 for ipsilateral atrophy related to epilepsy duration (95%CI: -0.51 to -0.32; p < 0.0001; I2 =65.22%; Figure 1) and r =-0.35 related to seizure frequency (95%CI -0.47 to -0.22; p < 0.0001; I2 =61.97%; Figure 1). Funnel plots appeared symmetric, and Galbraith plots did not indicate the presence of outliers in effect size. Several sensitivity analyses did not change the results. Narrative synthesis of 25/3 cross-sectional/longitudinal studies on whole-brain atrophy (n=1504 patients) indicated that >