Epileptic spasms are associated with increased SEEG derived functional connectivity in tuberous sclerosis complex

Abstract

Objective:

Epileptic Spasms (ES) are common in Tuberous Sclerosis Complex (TSC). However the underlying network alterations and relationship with epileptogenic tubers are poorly understood. We examined interictal functional connectivity (FC) using stereo-EEG (SEEG) in patients with TSC to investigate the relationship between tubers, epileptogenicity and ES.

Methods:

We analysed 18 patients with TSC who underwent SEEG (mean age 11.5 years). The dominant tuber (DT) was defined as the most epileptogenic tuber using the Epileptogenicity Index. Epileptogenic Zone (EZ) organisation was quantitatively separated into focal (isolated DT) and complex (all other patterns). Using a 20 minute interictal recording, FC was estimated with non-linear regression, h2. We calculated i) intrazone FC within all sampled tubers and normal appearing cortical zones respectively, and ii) interzone FC involving connections between DT, other tubers and normal cortex. The relationship between FC and i) presence of ES as a current seizure type at the time of SEEG, ii) EZ organisation, iii) epileptogenicity was analysed using a mixed generalized linear model. Spike rate and distance between zones were considered in the model as covariates

Results:

Six patients had ES as a current seizure type at time of SEEG. ES patients had a great number of tubers with FLAIR hypointense centre (p < 0.001) and none had TSC1 mutations. The presence of ES was independently associated with increased FC within both intrazone (p = 0.033) and interzone (p = 0.011) networks. Post-hoc analyses identified that increased FC was associated with ES across tuber and non-tuber networks. EZ organisation and epileptogenicity biomarkers were not associated with FC.

Significance:

Increased cortical synchrony amongst both tuber and non-tuber networks is characteristic of patients with ES and independent of both EZ organisation and tuber epileptogenicity. This further supports the prospect of FC biomarkers aiding treatment paradigms in TSC.

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