Visual assessment of MRIs from the Human Epilepsy Project 1 (HEP1) found 18% of participants had atrophic brain changes relative to age without known etiology. Here, we identify the underlying factors related to brain volume differences in people with focal epilepsy enrolled in HEP1.
Enrollment data for participants with complete records and brain MRIs were analyzed, including 391 participants ages 12-60. HEP1 excluded developmental or cognitive delay with IQ <70, and participants reported any formal learning disability diagnoses, repeated grades, and remediation. Pre-diagnostic seizures were quantified by semiology, frequency, and duration. T1-weighted brain MRIs were analyzed using the "Sequence Adaptive Multimodal Segmentation" (SAMSEG, Freesurfer v7.2) from which a brain tissue volume to intracranial volume ratio was derived and compared to clinically relevant participant characteristics.
Brain tissue volume changes observable on visual analyses were quantified and a brain tissue volume to intracranial volume ratio was derived to compare with clinically relevant variables. Learning difficulties were associated with decreased brain tissue volume to intracranial volume, with a ratio reduction of 0.005 for each learning difficulty reported (95% CI -0.007 to -0.002, p = 0.0003). Each 10-year increase in age at MRI was associated with a ratio reduction of 0.006 (95% CI -0.007 to -0.005, p < 0.0001). For male participants, the ratio was 0.011 less than female participants (95% CI -0.014 to -0.007, p < 0.0001). There were no effects from seizures, employment, education, seizure semiology, or temporal lobe EEG abnormalities.
This study shows lower brain tissue volume to intracranial volume in people with newly treated focal epilepsy and learning difficulties, suggesting developmental factors are an important marker of brain pathology related to neuroanatomical changes in focal epilepsy. Like the general population, there were also independent associations between brain volume, age, and sex in the study population.

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