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Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex.

ABSTRACT: OBJECTIVE:To identify whether abnormal electroencephalography (EEG) connectivity is present before the onset of epileptic spasms (ES) in infants with tuberous sclerosis complex (TSC). METHODS:Scalp EEG recordings were collected prospectively in infants diagnosed with TSC in the first year of life. This study compared the earliest recorded EEG from infants prior to ES onset (n = 16) and from infants who did not develop ES (n = 28). Five minutes of stage II or quiet sleep was clipped and filtered into canonical EEG frequency bands. Mutual information values between each pair of EEG channels were compared directly and used as a weighted graph to calculate graph measures of global efficiency, characteristic path length, average clustering coefficient, and modularity. RESULTS:At the group level, infants who later developed ES had increased EEG connectivity in sleep. They had higher mutual information values between most EEG channels in all frequency bands adjusted for age. Infants who later developed ES had higher global efficiency and average clustering coefficients, shorter characteristic path lengths, and lower modularity across most frequency bands adjusted for age. This suggests that infants who went on to develop ES had increased local and long-range EEG connectivity with less segregation of graph regions into distinct modules. SIGNIFICANCE:This study suggests that increased neural connectivity precedes clinical ES onset in a cohort of infants with TSC. Overconnectivity may reflect progressive pathologic network synchronization culminating in generalized ES. Further research is needed before scalp EEG connectivity measures can be used as a potential biomarker of ES risk and treatment response in pre-symptomatic infants with TSC.

SUBMITTER: Davis PE

PROVIDER: S-EPMC6687536 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex.

Davis Peter E PE Kapur Kush K Filip-Dhima Rajna R Trowbridge Sara K SK Little Elaina E Wilson Andrew A Leuchter Andrew A Bebin Elizabeth M EM Krueger Darcy D Northrup Hope H Wu Joyce Y JY Sahin Mustafa M Peters Jurriaan M JM

Epilepsia 20190712 8

<h4>Objective</h4>To identify whether abnormal electroencephalography (EEG) connectivity is present before the onset of epileptic spasms (ES) in infants with tuberous sclerosis complex (TSC).<h4>Methods</h4>Scalp EEG recordings were collected prospectively in infants diagnosed with TSC in the first year of life. This study compared the earliest recorded EEG from infants prior to ES onset (n = 16) and from infants who did not develop ES (n = 28). Five minutes of stage II or quiet sleep was clippe ...[more]

PMID: 31297797

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Project description:ObjectiveEpileptic 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-electroencephalography (SEEG) in patients with TSC to investigate the relationship between tubers, epileptogenicity, and ES.MethodsWe analyzed 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) organization was quantitatively separated into focal (isolated DT) and complex (all other patterns). Using a 20-min interictal recording, FC was estimated with nonlinear regression, h2 . We calculated (1) intrazone FC within all sampled tubers and normal-appearing cortical zones, respectively; and (2) interzone FC involving connections between DT, other tubers, and normal cortex. The relationship between FC and (1) presence of ES as a current seizure type at the time of SEEG, (2) EZ organization, and (3) epileptogenicity was analyzed using a mixed generalized linear model. Spike rate and distance between zones were considered in the model as covariates.ResultsSix patients had ES as a current seizure type at time of SEEG. ES patients had a greater number of tubers with a fluid-attenuated inversion recovery hypointense center (p < .001), and none had TSC1 mutations. The presence of ES was independently associated with increased FC within both intrazone (p = .033) and interzone (p = .011) networks. Post hoc analyses identified that increased FC was associated with ES across tuber and nontuber networks. EZ organization and epileptogenicity biomarkers were not associated with FC.SignificanceIncreased cortical synchrony among both tuber and nontuber networks is characteristic of patients with ES and independent of both EZ organization and tuber epileptogenicity. This further supports the prospect of FC biomarkers aiding treatment paradigms in TSC.

Dataset Information

Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex.

Publications

Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex.

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