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The aim of this study was to describe the electroclinical and prognostic characteristics, and to investigate the role of leukoaraiosis in outpatients with new-onset elderly focal epilepsy aged ≥60 years, referred to a tertiary epilepsy center between 2005 and December 31, 2020. Among the 720 patients who were referred to the center, we retrospectively selected 162 consecutive outpatients, with a first referral for recent-onset focal epilepsy of unknown cause (UC) or structural cause (SC), and collected a clinical and standard-Electroencephalogram (S-EEG), 24-h ambulatory EEG (A-EEG), and neuroimaging data. We also analyzed the seizure prognosis after titration of the first antiseizure medication (ASM). One hundred and four UC and 58 SC patients, followed up for 5.8 ± 5.3 years (mean ± SD), were included. Compared with the SC group, the patients with UC showed a predominance of focal seizures with impaired awareness (51.9% of cases) and focal to bilateral tonic-clonic seizures during sleep (25%); conversely, the SC group, more frequently, had focal to bilateral tonic-clonic seizures during wakefulness (39.6%) and focal aware seizures (25.8%) (p < 0.0001). Oral or gestural automatisms were prevalent in UC epilepsy (20.2 vs. 6.9% in the SC group, p = 0.04). In UC compared to patients with SC, interictal epileptiform discharges showed a preferential temporal lobe localization (p = 0.0007), low expression on S-EEG, and marked activation during deep Non-Rapid Eye Movement (NREM) sleep (p = 0.003). An overall good treatment response was found in the whole sample, with a probability of seizure freedom of 68.9% for 1 year. The cumulative probability of seizure freedom was significantly higher in the UC compared with the SC group (p < 0.0001). The prognosis was worsened by leukoaraiosis (p = 0.012). In the late-onset focal epilepsy of unknown cause, electroclinical findings suggest a temporal lobe origin of the seizures. This group showed a better prognosis compared with the patients with structural epilepsy. Leukoaraiosis, per se, negatively impacted on seizure prognosis.

Objective: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) may involve extrahippocampal areas of structural damage and dysfunction. The accuracy of medium-term spatial memory can be tested by Memory Guided Saccades (MGS), to evaluate a functional impairment of the parahippocampal cortex, while Voxel Based Morphometry (VBM) analysis can be used to detect a structural damage of the latter region. Methods: MGS with 3 and 30 second memorization delays were compared between 7 patients affected by right MTLE-HS, 6 patients affected by left MTLE-HS, and 13 healthy controls. The same subjects underwent brain MRI for a VBM analysis. Correlation analysis was performed between the results of VBM and MGS and with patients’ clinical data. Results: Right MTLE-HS patients showed impaired accuracy of leftward MGS with a 30 second memorization delay; their grey matter volume was reduced in the right hippocampus and inferior temporal gyrus, and bilaterally in the cerebellum. Left MTLE-HS patients had normal MGS accuracy; their grey matter volume was reduced in the left hippocampus, in the right inferior temporal gyrus and corpus callosus, and bilaterally in the insular cortex and in the cerebellum. The difference between right and left parahippocampal volume correlated with MGS accuracy, while right and left hippocampal volume did not. Hippocampal and parahippocampal volume did not correlate with clinical variables such as febrile seizures, age at disease onset, disease duration and seizure frequency. Conclusions: MGS abnormalities suggested the functional involvement of the right parahippocampal cortex in patients with right MTLE-HS, supporting a right lateralization of spatial memory control and showing a relation between functional impairment and degree of atrophy.