Systemic Infection and Brain Resilience in Patients With Seizures: An Inverse-Model Hypothesis From a Retrospective Cohort Study

Introduction : Systemic infection and seizures frequently co-occur in patients. Nevertheless, the association between seizures, its triggers and concurrent systemic infectious diseases (CSIDs) other than central nervous system infections remains unclear. Methods : This retrospective cross-sectional study evaluated 216 inpatients with ongoing seizures at a tertiary center in Taiwan in 2018. Clinical, radiological, and microbiological characteristics were compared between the patients with or without CSIDs. Results : CSIDs were identified in 72.6% of the patients. Those with CSIDs were older (p = 0.0020), and had more dementia (p = 0.0180), hippocampal atrophy (p = 0.0167), chronic brain injury (p = 0.0091), and greater cerebral small vessel disease (CSVD) burden (CT, p = 0.0373; MRI, p = 0.0373). Interestingly, those with severe CSIDs (septic shock, bacteremia) had lower CSVD burden (p = 0.0365, white matter lesion positivity; p = 0.0190, deep white matter Fazekas score) than mild CSIDs.Multivariate logistic regression confirmed this inverse relationship (adjusted OR: 10.2, p = 0.0448) for deep white matter Fazekas score. Additionally, seizures associated with Gram-positive cocci (GPC) infections occurred in patients with lower burden of chronic brain injury (p = 0.0099) and hippocampal atrophy (p = 0.0391) compared to Gram-negative bacilli (GNB)infections. Conclusion : Thesefindings support an “Inverse model” hypothesis where systemic inflammation and diminished brain resilience are linked in seizure manifestation. Consequently, in older adults with chronic brain lesions, seizures may occur even in the setting of mild infections. In contrast, more severe infections tend to be associated with seizures in patients with uncompromised brains. Seizure risk was higher in patients with GPC infections than in those with GNB infections. These results underscore the importance of screening for systemic infections in older patients or those with dementia or higher chronic brain lesion burden who present with seizures, even in the absence of fever.