Temporal trends indicate an epidemiological shift in the pathology of mesial temporal lobe epilepsy.

Background: Recent multicenter studies suggest a temporal trend of a decreasing number of patients with classic early-onset mesial temporal lobe epilepsy (mTLE) with ammon's horn sclerosis (mTLE-AHS). In parallel, the awareness of late-onset mTLE patients with suspected limbic encephalitis (sLE) is increasing. To evaluate a potential epidemiological shift, a large cohort of mTLE patients collected over 4 decades was analyzed.

Methods: Anonymized data sets of a monocentric cohort of 1,556 patients with the diagnosis of mTLE, who underwent their very first neuropsychological assessment between 1986 and 2024 in the Department of Epileptology at the University Hospital Bonn in Germany, were retrospectively evaluated in regard to temporal trends of age, age at epilepsy onset, neuropsychological performance, and MRI pathology. Five-year intervals were evaluated.

Results: Most significant was a trend of an increasing age at epilepsy onset over time (from 12 to 36 years), education and IQ increased over time, impairments became less global, and verbal/figural memory impairments became less marked and discriminative over time. While the number of patients with mTLE remained quite stable since 1996 (50-60% of all TLE patients seen), patients with early-onset mTLE-AHS (n = 1079, average age at epilepsy onset: 16 years) faded over time (from 100 to 32%), while the patients with late-onset mTLE suspicious of limbic encephalitis (N = 477, average age at epilepsy onset: 40 years) became increasingly prevalent (from 0 to 68%).

Conclusions: Trends of changing etiologies as well as altering clinical and neuropsychological features of patients with mTLE suggest an epidemiological shift over the past decades. Overlapping distributions of fading early-onset classic mTLE-AHS and an increasing influx of late-onset sLE fit the clinical observations and demand retrospective follow-up studies in other countries/regions to disentangle triggering factors. Prospective studies should investigate temporal trends in autoantibody subgroups of patients with sLE.