Elevated TNF-α Levels and CD4 Cell Counts in the Blood of Children with Tuberous Sclerosis Complex (TSC)-Related Refractory Epilepsy

Background/Purpose: Tuberous sclerosis complex (TSC) is a rare multi-system genetic disease caused by loss-of-function mutations in TSC1 or TSC2, resulting in hyperactivation of the mTOR pathway. Epilepsy, neurodevelopmental delay, and TSC-associated neuropsychiatric disorders greatly affect the quality of life of TSC patients; roughly 80% of the children present with refractory epilepsy. Efficient seizure management seems to be crucial for the course of cognitive and behavior development. Here, we evaluated inflammatory cytokines and PBMC populations as potential biomarkers of disease activity to improve diagnostic and prognostic precision of TSC-related epilepsy.

Methods: This observational, monocenter, prospective study included children <18 years of age with TSC-associated focal epilepsy compared with age-matched patients with focal epilepsy of other etiology (controls). Participants were assessed in terms of clinical, EEG and MRI findings, cognition, seizure type, and frequency, as well as ASM. TNF-α and IL-10 plasma levels as well as PBMC subpopulations were analyzed by ELISA and FACS, respectively.

Results: Fifteen patients with TSC-related epilepsy and 20 patients with other type of focal epilepsy (control group) were enrolled. Neurocognitive phenotypes in TSC compared with control patients varied significantly (p = 0.02) from normal cognition (13 vs. 45%) to profound cognitive impairment (40 vs. 10%). TSC patients received more ASM than controls (2.5 vs. 1.8, p = 0.03). Even though, refractory epilepsy was observed in both groups, TSC patients reported more frequently higher seizure frequencies (p = 0.04). Simultaneously, elevated chemokine levels (TNF-α: 5-fold, p = 0.03; IL-10: 3-fold, p = 0.03) and CD4 counts (5-fold, p = 0.04) were observed in patients with TSC-related epilepsy.

Conclusion: Our data imply that TNF-α plasma levels and peripheral CD4 cell counts are related to high seizure frequency in TSC-related epilepsy. However, further studies are required to determine the role of cytokines as biomarkers of a refractory course of TSC-related epilepsy.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
13 November 2023