Looking beyond lesions for causes of neuropsychological impairment in epilepsy

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) are similar in their epileptology regardless of whether they have a lesion evident on MRI; this study aims to prospectively clarify whether they are also similar in their neuropsychological profiles. METHODS: Participants comprised 152 adults: 79 patients with TLE and 73 healthy controls. Patients and controls did not differ in age, sex, or education (p > 0.05). Sixty-two percent of patients had an MRI-resolvable lesion (39% with presumed hippocampal sclerosis [HS-TLE], 61% with a lesion other than HS [MRI-positive TLE]); the remaining 38% of patients were lesion-negative. Psychometric measures well established in epilepsy were used. RESULTS: Relative to controls, all 3 patient subgroups showed significantly impaired autobiographical, verbal, and visual memory (p < 0.05–0.001) and significantly more depression and anxiety (p < 0.05–0.01). Yet, contrary to expectations, the 3 TLE subgroups did not differ in their severity of memory or mood impairment (p > 0.05). Lower Full-Scale IQ predicted memory impairments across all TLE subtypes, with early age at seizure onset a predictor unique to MRI-negative TLE. CONCLUSIONS: MRI-negative TLE is associated with memory and mood dysfunction equivalent to that seen in patients with hippocampal sclerosis and other MRI-resolvable pathologies. As such, neuropsychological impairments in TLE are not contingent on a macroscopic lesion and might be an intrinsic property of the underlying network disease.