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.

Download full-text


Available from: Philippe Major, Feb 11, 2015
16 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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 · 2.99 Impact Factor
  • Source
    • "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 . "
    [Show abstract] [Hide abstract]
    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 · 2.99 Impact Factor
  • Source
    • "However, the electrophysiological correlates of structural abnormalities in TSC remain elusive. There is one report of high gamma ([50 Hz) activity in the brain area surrounding cortical tubers (Irahara et al. 2012), and the presence of tubers has been correlated with increased epileptiform activity (Gallagher et al. 2009; Major et al. 2009; Jacobs et al. 2008). However, potential effects of structural abnormalities on fundamental aspects of neurodynamics, such as dominant brain rhythms and their spatio-temporal distributions , have not been investigated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The electrophysiological correlates of cognitive deficits in tuberous sclerosis complex (TSC) are not well understood, and modulations of neural dynamics by neuroanatomical abnormalities that characterize the disorder remain elusive. Neural oscillations (rhythms) are a fundamental aspect of brain function, and have dominant frequencies in a wide frequency range. The spatio-temporal dynamics of these frequencies in TSC are currently unknown. Using a novel signal decomposition approach this study investigated dominant cortical frequencies in 10 infants with TSC, in the age range 18-30 months, and 12 age-matched healthy controls. Distinct spectral characteristics were estimated in the two groups. High-frequency [in the high-gamma (>50 Hz) and ripple (>80 Hz) ranges], non-random EEG components were identified in both TSC and healthy infants at 18 months. Additional components in the lower gamma (30-50 Hz) ranges were also identified, with higher characteristic frequencies in TSC than in controls. Lower frequencies were statistically identical in both sub-groups. A significant shift in the high-frequency spectral content of the EEG was observed as a function of age, independently of task performance, possibly reflecting an overall maturation of developing neural circuits. This shift occurred earlier in healthy infants than in TSC, i.e., by age 20 months the highest dominant frequencies were in the high gamma range, whereas in TSC dominant frequencies above 100 Hz were still measurable. At age 28-30 months a statistically significant decrease in dominant high frequencies was observed in both TSC and healthy infants, possibly reflecting increased myelination and neuronal connection strengthening with age. Although based on small samples, and thus preliminary, the findings in this study suggest that dominant cortical rhythms, a fundamental aspect of neurodynamics, may be affected in TSC, possibly leading to impaired information processing in the brain.
    Journal of Autism and Developmental Disorders 07/2013; 45(2). DOI:10.1007/s10803-013-1887-7 · 3.06 Impact Factor
Show more