Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network

Area of Science:

• Neuroscience
• Epileptology
• Medical Imaging

Background:

• Tuberous sclerosis complex (TSC) affects approximately 1 in 30,000 individuals.
• Infantile spasms (IS) are a severe epilepsy syndrome occurring in ~50% of TSC patients, often leading to poor neurological outcomes.
• While increased tuber burden is a risk factor for IS, the role of specific tuber locations and their network connectivity remains unclear.

Purpose of the Study:

• To investigate the association between tuber location, network connectivity, and the development of infantile spasms in TSC.
• To determine if specific tuber locations or their connections predict IS risk more accurately than overall tuber burden.

Main Methods:

• Voxelwise lesion symptom mapping and lesion network mapping were used to analyze tuber location and connectivity in 123 children with and without IS.
• Logistic regression and cross-validation were employed to assess the predictive power of identified associations.

Main Results:

• No single tuber location was significantly associated with IS, indicating heterogeneous origins.
• However, over 95% of tubers linked to IS showed functional connectivity to the globi pallidi and cerebellar vermis.
• Globus pallidus connectivity was a stronger predictor of IS (OR=1.96) than tuber burden (OR=1.65), with a cross-validated AUC of 0.73.

Conclusions:

• Functional connectivity between tubers and the bilateral globi pallidi is significantly associated with infantile spasms in TSC.
• These findings offer insights into the pathophysiology of IS in TSC and may aid in identifying at-risk individuals.