Are cortical tubers epileptogenic? Evidence from electrocorticography

Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Epilepsia (Impact Factor: 4.57). 02/2009; 50(1):147-54. DOI: 10.1111/j.1528-1167.2008.01814.x
Source: PubMed


The purpose of this study was to characterize the epileptogenicity of tubers and surrounding cortex in patients with tuberous sclerosis complex (TSC). Three pediatric patients with TSC and intractable epilepsy underwent surgical resection of tubers associated with epileptogenic foci. In all patients, presurgical imaging revealed a prominent tuber that correlated on electroencephalography (EEG) with frequent interictal epileptiform discharges and electrographic seizures. Intracranial electrocorticography (ECoG) was performed using subdural grids placed over the tuber and surrounding cortex and depth electrodes positioned directly within the tuber. In all three patients, the depth electrode within the tuber was electrographically silent, whereas the surrounding cortical tissue showed significant epileptiform activity. The tuber and the electrically active adjacent cortex were resected. The patients experienced a drastic reduction in seizure frequency postsurgery. Epileptogenicity of cortical tubers may derive not from the lesion itself, but rather from the perturbation or abnormal development of the surrounding cortex.

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Available from: Philippe Major, Feb 11, 2015
    • "Although cortical tubers are one of the hallmarks of TSC (Curatolo et al. 2002), there is no consistent correlation between the number and location of tubers, and epileptic seizures (Major et al. 2009) or autistic features (Bolton et al. 2002; Numis et al. 2011). Therefore, it has been suggested that the broad spectrum of TSC clinical phenotypes may arise from abnormal neural connections that are independent of these benign tumors (Tsai and Sahin 2011; Peters, Taquet, Vega, et al. 2013). "
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    ABSTRACT: Tuberous sclerosis complex (TSC) is characterized by benign hamartomas in multiple organs including the brain and its clinical phenotypes may be associated with abnormal neural connections. We aimed to provide the first detailed findings on disrupted structural brain networks in TSC patients. Structural whole-brain connectivity maps were constructed using structural and diffusion MRI in 20 TSC (age range: 3-24 years) and 20 typically developing (TD; 3-23 years) subjects. We assessed global (short- and long-association and interhemispheric fibers) and regional white matter connectivity, and performed graph theoretical analysis using gyral pattern- and atlas-based node parcellations. Significantly higher mean diffusivity (MD) was shown in TSC patients than in TD controls throughout the whole brain and positively correlated with tuber load severity. A significant increase in MD was mainly influenced by an increase in radial diffusivity. Furthermore, interhemispheric connectivity was particularly reduced in TSC, which leads to increased network segregation within hemispheres. TSC patients with developmental delay (DD) showed significantly higher MD than those without DD primarily in intrahemispheric connections. Our analysis allows non-biased determination of differential white matter involvement, which may provide better measures of "lesion load" and lead to a better understanding of disease mechanisms. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Cerebral Cortex 03/2015; DOI:10.1093/cercor/bhv026 · 8.67 Impact Factor
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    • "The epileptogenic activity was propagating across time along the borders of the tuber, and in any instance was crossing the tuber itself. Our findings are in agreement with previous studies indicating that in TSC patients with epilepsy the epileptogenic tissue is predominately localized in the surroundings of the cortical tubers (Weiner, 2004; Xiao et al., 2006; Major et al., 2009), and a single case study published in this issue (Hunold et al., 2014). The high sensitivity of our method allowed us to map the evolution of the epileptiform activity across time with respect to the location of the tuber. "
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    ABSTRACT: Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz Hodge Decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptiform activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of MEG/EEG Data.
    Frontiers in Human Neuroscience 05/2014; 8. DOI:10.3389/fnhum.2014.00338 · 3.63 Impact Factor
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    • "A surgical series using intraoperative electrocorticography (ECoG) indicated that the epileptiform discharges were localized within the cortical tubers (Guerreiro et al., 1998). Other ECoG studies found that the electrographic tubers were silent, and it was the surrounding neural tissue that was epileptogenic (Major et al., 2009). Currently, the epileptogenic zone is conventionally identified using a combination of invasive and non-invasive imaging modalities . "
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    ABSTRACT: Tuberous sclerosis complex (TSC) is a rare disorder of tissue growth and differentiation, characterized by benign hamartomas in the brain and other organs. Up to 90% of TSC patients develop epilepsy and 50% become medically intractable requiring resective surgery. The surgical outcome of TSC patients depends on the accurate identification of the epileptogenic zone consisting of tubers and the surrounding epileptogenic tissue. There is conflicting evidence whether the epileptogenic zone is in the tuber itself or in abnormally developed surrounding cortex. Here, we report the localization of the epileptiform activity among the many cortical tubers in a four-year old patient with TSC-related refractory epilepsy undergoing magnetoencephalography (MEG), electroencephalography (EEG), and diffusion tensor imaging (DTI). For MEG, we used a prototype system that offers higher spatial resolution and sensitivity compared to the conventional adult systems. The generators of interictal activity were localized using both EEG and MEG with equivalent current dipole (ECD) and minimum norm estimation (MNE) methods according to the current clinical standards. For DTI, we calculated four diffusion scalar parameters for the fibers passing through four ROIs defined: (i) at a large cortical tuber identified at the right quadrant, (ii) at the normal appearing tissue contralateral to the tuber, (iii) at the cluster formed by ECDs fitted at the peak of interictal spikes, and (iv) at the normal appearing tissue contralateral to the cluster. ECDs were consistently clustered at the vicinity of the large calcified cortical tuber. MNE and ECDs indicated epileptiform activity in the same areas. DTI analysis showed differences between the scalar values of the tracks passing through the tuber and the ECD cluster. In this illustrative case, we provide evidence supporting the view that epileptiform activity may derive from abnormally developed tissue surrounding the tuber rather than the tuber itself.
    Frontiers in Human Neuroscience 03/2014; 8:175. DOI:10.3389/fnhum.2014.00175 · 3.63 Impact Factor
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