Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.

This article introduces the concept of \'cognitive comorbidity,\' which lays emphasis on common cognitive deficits that cut across different disorders. The concept is illustrated with the help of two commonly reported overlapping conditions (autism and epilepsy). It is further explained by concentrating on two important cognitive processes of facial emotional recognition and emotional memory, shown to be compromised in both conditions; and their underlying neural substrates. Cognitive comorbidity is then contrasted with \'comorbidity,\' a term which is more commonly used for describing cognitive disorders. The paper closes by providing directions for rehabilitative and theoretical efforts that could be inspired by the newly introduced concept.