Epilepsy Surgery Outcome in Children with Focal Epilepsy due to Tuberous Sclerosis Complex

Abstract

kinsonism and dementia. Brain MRI show iron in the substantia nigra and globus pallidus, as well as a halo of T1 hyperintense signal in the substantia nigra and cerebral peduncles. Male and female patients were phenotypically similar. Conclusion: We describe the first X-lined form of NBIA, due to mutations in WDR45. The phenotypic similarity between the sexes is likely due to somatic mosaicism in surviving males. WDR45 encodes a beta-propeller protein postulated to play a role in autophagy, a novel disease mechanism in NBIA. The newly termed BPAN (beta-propellar associated neurodegenera-tion) appears to be a significant cause of NBIA. Objectives: The hypothesis of epileptic encephalopathy posits that epileptiform discharge promotes changes in the connection between neurons in early childhood due to ongoing developmental structural plasticity. The presence of remodelled cortical architecture is evaluated in infants following presentation with 'idiopathic' WS. Methods: Cross-sectional study. Quantitative magnetic resonance imaging (3D structural MRI and diffusion tensor imaging) data was compared for 22 patients with newly diagnosed WS and 12 healthy age controls using voxel based morphometry (VBM) and tract-based spatial statistics (TBSS). Results: WS patients showed decreased white matter volume of the temporal lobes compared to controls (p<0.005), but did not show difference in white matter integrity on DTI metrics (frac-tional anisotropy and mean diffusivity). WS patients showed increased temporal lobe grey matter density (p<0.005), particularly in the perirhinal cortex. The structural changes occurred bilaterally. Conclusions: Following idiopathic West Syndrome a number of persistent neurological deficits referable to the temporal lobe are observed, including impaired receptive language, and combined visual-and-auditory agnosia. These are likely to reflect an altered connection pattern within the temporal lobe that is demonstrated here. The changes were found despite successful resolution of infantile spasm seizures on treatment, highlighting a need for treatment options that prevent the alteration of connection architecture in WS. Objective: To review the clinical features determining the offer of epilepsy surgery and surgical outcome in children with Tuberous Sclerosis Complex (TSC). Methods: Clinical data of 122 patients with TSC and complex epilepsy, referred to Great Ormond Street Hospital for epilepsy surgery from 2000 to 2012, were reviewed retrospectively. Pre-surgical evaluation included ictal video electroencephalogram (EEG) monitoring and brain Magnetic Resonance Imaging (MRI) in all, with selected patients undergoing ictal/interictal Single Photon Emission Computed Tomography (SPECT) and/or intracranial EEG. Patients undergoing surgery were followed at 6 months, 1 and 2 years post-operatively; seizure outcome was measured using Modified Engel classification. Results: Of the 122 patients screened, 53 were discussed at the Epilepsy Surgery Meeting based on the presence of continuing seizures, latera...

Pulsed Arterial Spin-Labeled MR Imaging Evaluation of Tuberous Sclerosis

“…These include electroencephalography, PET imaging, ictal SPECT, and magnetoencephalography. 13,15,18,[33][34][35][36][37][38][39][40] Each isolated technique had variable success to correctly identify the problematic cortical tuber. However, the favored approach is to use multiple complementary imaging modalities to accurately and confidently localize the epileptogenic focus before surgical resection.…”

“…However, the favored approach is to use multiple complementary imaging modalities to accurately and confidently localize the epileptogenic focus before surgical resection. 13,15,18,[33][34][35]37,[39][40][41] When seizures can be localized to a single epileptogenic tuber, surgical resection has proved beneficial, with significant reductions in seizure frequency. 15,18,33,[35][36][37][38] Future studies with PASL could localize the epileptogenic tuber by establishing the baseline perfusion values of the cortical hamartomas and evaluating the perfusion change associated with the ictal or postictal state similar to nuclear medicine SPECT examinations.…”

Epilepsy surgery and tuberous sclerosis complex: special considerations

“…Over the 40 years since that report, the published literature has consistently found that traditional resective epilepsy surgery can be very successful in reducing the seizure burden in carefully selected patients with TSC who harbor a single tuber and associated epileptogenic focus. 3,5,8,18,[26][27][28]34,35,37,41,52,57,75 Patients not meeting this selection criterion for surgery were offered a palliative approach, such as corpus callosotomy. 18 A review of the TSC epilepsy surgery literature indicates that patients with a well-localized single tuber and corresponding epileptogenic zone are excellent surgical candidates, but children not fitting this profile are often excluded from operative treatment because a poor outcome was anticipated.…”

“…Therefore, early identification of potential surgical candidates is critical for seizure control and optimal development. However, the published literature primarily contains reports on older children, 3,5,8,18,[26][27][28]34,35,37,41,52,57,75 with very few younger patients included in these series. This raises the question of whether a potential benefit is not seen because surgery is delayed beyond a potentially important developmental window.…”

“…25,72 Based on the experience of several investigators over the last 20 years, the efficacy of surgery is well established for controlling seizures in patients with TSC with concordant and localized neuroimaging and electrophysiological data. 3,5,8,18,[26][27][28]34,35,37,41,42,52,57,75 Independent investigators at a variety of international comprehensive epilepsy centers have come to the conclusion that epilepsy surgery is an excellent treatment option for the appropriately selected child with TSC. 3,5,8,18,[26][27][28]34,35,37,41,52,57,75 The goal of epilepsy treatment in TSC, as in the treatment of other types of epilepsy, is the elimination of seizures as soon as possible to optimize cognitive development and improve behavior and quality of life.…”