Focal Cortical Dysplasia Lesions Research Articles

Automatic detection and localization of Focal Cortical Dysplasia lesions in MRI using fully convolutional neural network

Focal cortical dysplasia (FCD) is the leading cause of drug-resistant epilepsy in both children and adults. At present, the only therapeutic approach in patients with drug-resistant epilepsy is surgery. Hence, the quantification of FCD via non-invasive imaging techniques helps physicians to decide on surgical interventions. The properties like non-invasiveness and capability to produce high-resolution images makes magnetic resonance imaging an ideal tool for detecting the FCD to an extent. The FCD lesions vary in size, shape, and location for different patients and make the manual detection time consuming and sensitive to the experience of the observer. Automatic segmentation of FCD lesions is challenging due to the difference in signal strength in images acquired with different machines, noise, and other kinds of distortions such as motion artifacts. Most of the methods proposed in the literature use conventional machine learning and image processing techniques in which their accuracy relies on the trained features. Hence, feature extraction should be done more precisely which requires human expertise. The ability to learn the appropriate features/representations from the training data without any human interventions makes the convolutional neural network (CNN) the suitable method for addressing these drawbacks. As far as we are aware, this work is the first one to use a CNN based model to solve the aforementioned problem using only MRI FLAIR images. We customized the popular U-Net architecture and trained the proposed model from scratch (using MRI images acquired with 1.5T and 3T scanners). FCD detection rate (recall) of the proposed model is 82.5 (33/40 patients detected correctly).

Clinical Value of Machine Learning in the Automated Detection of Focal Cortical Dysplasia Using Quantitative Multimodal Surface-Based Features.

Objective: To automatically detect focal cortical dysplasia (FCD) lesion by combining quantitative multimodal surface-based features with machine learning and to assess its clinical value.Methods: Neuroimaging data and clinical information for 74 participants (40 with histologically proven FCD type II) was retrospectively included. The morphology, intensity and function-based features characterizing FCD lesions were calculated vertex-wise on each cortical surface and fed to an artificial neural network. The classifier performance was quantitatively and qualitatively assessed by performing statistical analysis and conventional visual analysis.Results: The accuracy, sensitivity, specificity of the neural network classifier based on multimodal surface-based features were 70.5%, 70.0%, and 69.9%, respectively, which outperformed the unimodal classifier. There was no significant difference in the detection rate of FCD subtypes (Pearson’s Chi-Square = 0.001, p = 0.970). Cohen’s kappa score between automated detection outcomes and post-surgical resection region was 0.385 (considered as fair).Conclusion: Automated machine learning with multimodal surface features can provide objective and intelligent detection of FCD lesion in pre-surgical evaluation and can assist the surgical strategy. Furthermore, the optimal parameters, appropriate surface features and efficient algorithm are worth exploring.

Ultrasonographic features of focal cortical dysplasia and their relevance for epilepsy surgery.

OBJECTIVE Surgery has proven to be the best therapeutic option for drug-refractory cases of focal cortical dysplasia (FCD)-associated epilepsy. Seizure outcome primarily depends on the completeness of resection, rendering the intraoperative FCD identification and delineation particularly important. This study aims to assess the diagnostic yield of intraoperative ultrasound (IOUS) in surgery for FCD-associated drug-refractory epilepsy. METHODS The authors prospectively enrolled 15 consecutive patients with drug-refractory epilepsy who underwent an IOUS-assisted microsurgical resection of a radiologically suspected FCD between January 2013 and July 2016. The findings of IOUS were compared with those of presurgical MRI postprocessing and the sonographic characteristics were analyzed in relation to the histopathological findings. The authors investigated the added value of IOUS in achieving completeness of resection and improving postsurgical seizure outcome. RESULTS The neurosurgeon was able to identify the dysplastic tissue by IOUS in all cases. The visualization of FCD type I was more challenging compared to FCD II and the demarcation of its borders was less clear. Postsurgical MRI showed residual dysplasia in 2 of the 3 patients with FCD type I. In all FCD type II cases, IOUS allowed for a clear intraoperative visualization and demarcation, strongly correlating with presurgical MRI postprocessing. Postsurgical MRI confirmed complete resection in all FCD type II cases. Sonographic features correlated with the histopathological classification of dysplasia (sonographic abnormalities increase continuously in the following order: FCD IA/IB, FCD IC, FCD IIA, FCD IIB). In 1 patient with IOUS features atypical for FCD, histopathological investigation showed nonspecific gliosis. CONCLUSIONS Morphological features of FCD, as identified by IOUS, correlate well with advanced presurgical imaging. The resolution of IOUS was superior to MRI in all FCD types. The appreciation of distinct sonographic features on IOUS allows the intraoperative differentiation between FCD and non-FCD lesions as well as the discrimination of different histological subtypes of FCD. Sonographic demarcation depends on the underlying degree of dysplasia. IOUS allows for more tailored resections by facilitating the delineation of the dysplastic tissue.

Morphological analysis of brain MRI and its application in focal cortical dysplasia

Objective To investigate the clinical value of MRI morphological analysis in identification of focal cortical dysplasia (FCD) in presurgical evaluation of epileptogenic zone (EZ). Methods We retrospectively analyzed the clinical data of 53 patients who were admitted to Epilepsy Center, Tsinghua University Yuquan Hospital and underwent surgical removal of epileptic foci and were pathologically confirmed as FCD Ⅰ or FCD Ⅱ. Morphometric analysis programme was used to post-process presurgical high-resolution MRI to obtain the gray-white matter junction imaging (MAP+ region) and statistical analysis was used to determine the consistency of the MAP+ region and surgical site and postoperative epilepsy control. Results In this series, the probability of postoperative seizure-free (67.9%, 36/53) was higher in patients whose MAP+ regions were resected than that (7.5%, 4/53) in patients whose MAP+ regions were not resected (P=0.002). In the MRI-negative group, the probability of postoperative seizure-free (62.5%, 20/32) was higher in patients whose MAP+ regions were resected than that (9.4%, 3/32) in patients whose MAP+ regions were not resected (P=0.006). In the MRI positive group, MAP+ regional resection was not associated with the clinical outcome (P=0.352). Conclusions The gray-white matter junction imaging could improve the detection rate of FCD lesions, which might have clinical value in localization of EZ and resection of EZ and making electrode plan of stereotactic electroencephalogram (SEEG). Key words: Epilepsy; Malformations of cortical development; Gray matter and white matter junction imaging; Morphometric analysis programme

Multimodality Image Post-processing in Detection of Extratemporal MRI-Negative Cortical Dysplasia.

Purpose: To determine the diagnostic value of individual image post-processing techniques in a series of patients who underwent extratemporal operations for histologically proven, MRI-negative focal cortical dysplasia (FCD).Methods: The morphometric analysis program (MAP), PET/MRI co-registration and statistical parametric mapping (SPM) analysis of PET (SPM-PET) techniques were analyzed in 33 consecutive patients. The epileptogenic zone (EZ) assumed by MAP, PET/MRI, and SPM-PET was compared with the location of the FCD lesions determined by stereoelectroencephalography (SEEG) and histopathological study. The detection rate of each modality was statistically compared.Results: Three lesions were simultaneously detected by the three post-processing methods, while two lesions were only MAP positive, and 8 were only PET/MRI positive. The detection rate of MAP, PET/MRI, SPM-PET and the combination of the three modalities was 24.2, 90.9, 57.6, and 97.0%, respectively. Taking the pathological subtype into account, no type I lesions were detected by MAP, and PET/MRI was the most sensitive method for detecting FCD types II and IIA. During a mean follow-up period of 22.94 months, seizure freedom was attained in 26/33 patients (78.8%) after focal corticectomy.Conclusions: MAP, PET/MRI, and SPM-PET provide complementary information for FCD detection, intracranial electrode design, and lesion resection. PET/MRI was particularly useful, with the highest detection rate of extratemporal MRI-negative FCD.

Abnormal Blood Oxygen Level-Dependent Fluctuations in Focal Cortical Dysplasia and the Perilesional Zone: Initial Findings.

Focal cortical dysplasia is a common cause of intractable epilepsy for which neurosurgery is an option. Delineations of a focal cortical dysplasia lesion on structural brain images may not necessarily reflect the functional borders of normal tissue. Our objective was to determine whether abnormalities in spontaneous blood oxygen level-dependent fluctuations arise in focal cortical dysplasia lesions and proximal regions. Fourteen patients with focal cortical dysplasia-related epilepsy and 16 healthy controls underwent structural and resting-state functional MR imaging. Three known blood oxygen level-dependent measures were determined, including the fractional amplitude of low-frequency fluctuations, regional homogeneity, and wavelet entropy. These measures were evaluated in the lesion and perilesional zone and normalized to the contralateral cortex of patients with focal cortical dysplasia and healthy controls. Patients showed significantly decreased fractional amplitude of low-frequency fluctuations and increased wavelet entropy in the focal cortical dysplasia lesion and the perilesional zone (≤2 cm) relative to the contralateral homotopic cortex and the same regions in healthy controls. Regional homogeneity was significantly increased in the focal cortical dysplasia lesion compared with the contralateral homotopic cortex and healthy controls. Abnormalities in spontaneous blood oxygen level-dependent fluctuations were seen up to 2 cm distant from the radiologically visible boundary. It was demonstrated that functional boundaries go beyond structural boundaries of focal cortical dysplasia lesions. Validation is required to reveal whether this information is valuable for surgical planning and outcome evaluation of focal cortical dysplasia lesions and comparing current results with electrophysiologic analysis.

Voxel-based automated detection of focal cortical dysplasia lesions using diffusion tensor imaging and T2-weighted MRI data

The aim of this study was to automatically detect focal cortical dysplasia (FCD) lesions in patients with extratemporal lobe epilepsy by relying on diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) data. We implemented an automated classifier using voxel-based multimodal features to identify gray and white matter abnormalities of FCD in patient cohorts. In addition to the commonly used T2-weighted image intensity feature, DTI-based features were also utilized. A Gaussian processes for machine learning (GPML) classifier was tested on 12 patients with FCD (8 with histologically confirmed FCD) scanned at 1.5 T and cross-validated using a leave-one-out strategy. Moreover, we compared the multimodal GPML paradigm's performance with that of single modal GPML and classical support vector machine (SVM). Our results demonstrated that the GPML performance on DTI-based features (mean AUC = 0.63) matches with the GPML performance on T2-weighted image intensity feature (mean AUC = 0.64). More promisingly, GPML yielded significantly improved performance (mean AUC = 0.76) when applying DTI-based features to multimodal paradigm. Based on the results, it can also be clearly stated that the proposed GPML strategy performed better and is robust to unbalanced dataset contrary to SVM that performed poorly (AUC = 0.69). Therefore, the GPML paradigm using multimodal MRI data containing DTI modality has promising result towards detection of the FCD lesions and provides an effective direction for future researches.

Small Lesion Size Is Associated with Sleep-Related Epilepsy in Focal Cortical Dysplasia Type II.

To investigate the neuroimaging and clinical features associated with sleep-related epilepsy (SRE) in patients with focal cortical dysplasia (FCD) type II. Patients with histopathologically proven FCD type II were included from three epilepsy centers. SRE was defined according to the video EEG findings and seizure history. Cortical surface reconstruction and volume calculation were performed using FreeSurfer. The lesions were manually delineated on T1 volumetric MRI using the ITK-SNAP software. The lesion volumes were normalized by the intracranial volume of each patient. The lesions were classified as small or large by placing a threshold based on quantitative (whether the lesion was detected on MRI report) and qualitative (volume) criteria. A total of 77 consecutive patients were included. Of them, 36 had SRE and 41 had non-SRE. An earlier age of epilepsy onset, high seizure frequency, regional interictal EEG findings, and favorable surgical outcome were characteristic in both groups. Small lesions were defined as those having a volume <3,217 mm3. In total, 60.9% of the patients with SRE (25/41) had small FCD lesion, which was significantly higher than the non-SRE group (9/34, 26.5%, p = 0.005). Small lesion size was the only predictor significantly associated with SRE in the overall type II group by multivariate analyses (p = 0.016). Although the proportion of patients who had frontal FCD and SRE was higher than non-frontal FCD (54.5 vs. 27.3%, p = 0.043), the relationship between SRE and lesion location was not confirmed by multivariate analysis. Thalamic volume and seizure semiology were not statistically different between the SRE and non-SRE group. The significant association between lesion size and SRE was reproducible in type IIb and IIa subgroups. SRE is common in patients with FCD type II. Small FCD type II lesions are significantly associated with SRE. Although our findings cannot be applied to the entire spectrum of SRE, potential existence of small FCD lesions should be considered when evaluating patients with SRE, and utilization of all other supportive electroclinical information for lesion detection is highly desirable.

Upregulation of HMGB1-TLR4 inflammatory pathway in focal cortical dysplasia type II

BackgroundWe attempted to determine whether the inflammatory pathway HMGB1-TLR4 and the downstream pro-inflammatory cytokines is upregulated in focal cortical dysplasia (FCD) type II and whether there is a correlation between the TLR4 upregulation and disease duration or frequency of epileptic seizures.MethodsFCD type II and peri-FCD paired tissues resected from eight children with refractory epilepsy were collected. Through real-time qPCR, Western blot, and co-immunoprecipitation, we examined the differences between FCD lesions and peri-FCD tissues with respect to mRNA expression, protein expression, and protein interaction in HMGB1-TLR4 pathway biomarker and downstream pro-inflammatory factors in whole brain tissue. Then, we used immunofluorescence to examine the difference between FCD lesions and peri-FCD tissues with respect to protein expression and intracellular distribution of HMGB1-TLR4 pathway biomarker in neurons, astrocytes, and oligodendrocytes. Correlation between level of TLR4 expression and disease duration or frequency of epileptic seizures in patients was also analyzed.ResultsThe protein expression levels of TLR4, cytoplasm HMGB1, TLR4/MyD88 complex, ubiquitination of TRAF6, p-IKK, p-IκB-α, p-NF-κB p65, and IL-1β and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls. Total mRNA expression levels of TLR4, IL-1β, and TNF-α in lesion tissues were significantly higher than those in peri-FCD controls, but HMGB1 had no significant change. In neurons and astrocytes inside the lesions, the expression of TLR4 protein was significantly higher than that in peri-FCD tissues, and HMGB1 was mainly expressed in the cytoplasm, while expressed in the nuclei in peri-FCD tissues. But in oligodendrocytes, there was no upregulation of HMGB1-TLR4 pathway in both lesions and peri-FCD tissues. We did not identify the correlation between the level of TLR4 activation and disease duration or frequency of epileptic seizures.ConclusionThe HMGB1-TLR4 pathway was upregulated in the neurons and astrocytes inside FCD type II lesions, which led to an increase in the release of downstream pro-inflammatory cytokines. Correlation between the level of TLR4 activation and duration or frequency of epileptic seizures was not identified.

Multiple Classifier Fusion and Optimization for Automatic Focal Cortical Dysplasia Detection on Magnetic Resonance Images

In magnetic resonance (MR) images, detection of focal cortical dysplasia (FCD) lesion as a main pathological cue of epilepsy is challenging because of the variability in the presentation of FCD lesions. Existing algorithms appear to have sufficient sensitivity in detecting lesions but also generate large numbers of false-positive (FP) results. In this paper, we propose a multiple classifier fusion and optimization schemes to automatically detect FCD lesions in MR images with reduced FPs through constructing an objective function based on the F-score. Thus, the proposed scheme obtains an improved tradeoff between minimizing FPs and maximizing true positives. The optimization is achieved by incorporating the genetic algorithm into the work scheme. Hence, the contribution of weighting coefficients to different classifications can be effectively determined. The resultant optimized weightings are applied to fuse the classification results. A set of six typical FCD features and six corresponding Z-score maps are evaluated through the mean F-score from multiple classifiers for each feature. From the experimental results, the proposed scheme can automatically detect FCD lesions in 9 out of 10 patients while correctly classifying 31 healthy controls. The proposed scheme acquires a lower FP rate and a higher F-score in comparison with two state-of-the-art methods.

Local Directional Probability Optimization for Quantification of Blurred Gray/White Matter Junction in Magnetic Resonance Image.

The blurred gray/white matter junction is an important feature of focal cortical dysplasia (FCD) lesions. FCD is the main cause of epilepsy and can be detected through magnetic resonance (MR) imaging. Several earlier studies have focused on computing the gradient magnitude of the MR image and used the resulting map to model the blurred gray/white matter junction. However, gradient magnitude cannot quantify the blurred gray/white matter junction. Therefore, we proposed a novel algorithm called local directional probability optimization (LDPO) for detecting and quantifying the width of the gray/white matter boundary (GWB) within the lesional areas. The proposed LDPO method mainly consists of the following three stages: (1) introduction of a hidden Markov random field-expectation-maximization algorithm to compute the probability images of brain tissues in order to obtain the GWB region; (2) generation of local directions from gray matter (GM) to white matter (WM) passing through the GWB, considering the GWB to be an electric potential field; (3) determination of the optimal local directions for any given voxel of GWB, based on iterative searching of the neighborhood. This was then used to measure the width of the GWB. The proposed LDPO method was tested on real MR images of patients with FCD lesions. The results indicated that the LDPO method could quantify the GWB width. On the GWB width map, the width of the blurred GWB in the lesional region was observed to be greater than that in the non-lesional regions. The proposed GWB width map produced higher F-scores in terms of detecting the blurred GWB within the FCD lesional region as compared to that of FCD feature maps, indicating better trade-off between precision and recall.

Characteristics of EEG Seizure-Onset Patterns Recorded From Subdural Electrodes Over MRI-Visible Frontal Focal Cortical Dysplasia Type IIb Lesions.

Focal cortical dysplasia (FCD) is intrinsically epileptogenic, and an MRI-visible lesion typically constitutes the core part of the epileptogenic zone. We aimed to identify ictal EEG patterns that represent the epileptogenic zone by using subdural electrodes placed over the MRI-visible FCD lesion. We selected seven patients with frontal lobe epilepsy caused by pathologically proven FCD type IIb who underwent preoperative intracranial EEG evaluation with subdural electrodes followed by resection surgery with seizure-free outcome. The characteristics of ictal EEG patterns, interictal/ictal high-frequency oscillations, and ictal direct current shifts from intracranial electrodes placed over the MRI-visible lesion were analyzed. Two seizure-onset patterns (low voltage fast activity and fast spike activity) were identified. Low voltage fast activity was seen in all patients with a lateral frontal lesion, and it was always preceded by preictal spikes. Fast spike activity occurred only in patients with a mesial frontal lesion. Interictal/ictal high-frequency oscillations and ictal direct current shifts were seen in all patients. The epileptogenic zone of frontal FCD type IIb may be characterized by EEG seizure-onset patterns consisting of low voltage fast activity and fast spike activity accompanied by ictal high-frequency oscillations and ictal direct current shifts. Further study is needed to determine whether other seizure-onset patterns exist in patients with FCD type IIb.

Comparison of clinical features and surgical outcome in focal cortical dysplasia type 1 and type 2

IntroductionRecent ILAE classification defined focal cortical dysplasia (FCD) patients with accompanying epileptic lesions as a separate group. We investigated data of patients with sole FCD lesions regarding long-term seizure outcome and different characteristics of FCD type 1 and type 2 patients. MethodsEighty children and adult patients underwent surgery for FCD were included to the analysis of factors differentiating FCD type 1 and type 2 groups and their effect on long-term outcome. ResultsFCD type 2 patients had earlier epilepsy onset (8.1 vs. 6.1 years. p=0.019) and underwent surgery younger than type 1 (18.2 vs. 23.7 years. p=0.034). FCD type 2 patients were more prominently MR positive (77.8% vs. 53.8%. p=0.029), which increased within FCD type 2 group as patients become younger (p=0.028). FCD Type 1 lesions showed mostly multilobar extension and FCD type 2 mostly located in frontal lobe. Seizure freedom was achieved in 65.4% of FCD type 1 patients and 70.4% of FCD type 2 patients. Seven patients had permanent de novo neurological deficits. Mean follow-up time was 5.5 years (Range: 1–11 years). ConclusionSurgical intervention in carefully selected patients may facilitate favorable seizure outcome leading to better quality of life. FCD type 1 and type 2 groups present with evident differences, which may promote medical and surgical management of these pathologies.

Elevated Expression of TRPC4 in Cortical Lesions of Focal Cortical Dysplasia II and Tuberous Sclerosis Complex.

Focal cortical dysplasia type II (FCD II) and tuberous sclerosis complex (TSC) are well-known causes of chronic refractory epilepsy in children. Canonical transient receptor potential channels (TRPCs) are non-selective cation channels that are commonly activated by phospholipase C (PLC) stimulation. Previous studies found that TRPC4 may participate in the process of epileptogenesis. This study aimed to examine the expression and distribution of TRPC4 in FCD II (n=24) and TSC (n=11) surgical specimens compared with that in age-matched autopsy control samples (n=12). We found that the protein levels of TRPC4 and its upstream factor, PLC delta 1 (PLCD1), were elevated in FCD II and TSC samples compared to those of control samples. Immunohistochemistry assays revealed that TRPC4 staining was stronger in malformed cells, such as dysmorphic neurons, balloon cells and giant cells. Moderate-to-strong staining of the upstream factor PLCD1 was also identified in abnormal neurons. Moreover, double immunofluorescence staining revealed that TRPC4 was colocalised with glutamatergic and GABAergic neuron markers. Taken together, our results indicate that overexpression of TRPC4 protein may be involved in the epileptogenesis of FCD II and TSC.

Ingmar Blümcke, Harvey B. Sarnat, Roland Coras Surgical Neuropathology of Focal Epilepsies: Textbook and Atlas John Libbey Eurotext, 2015. 157 Pages (hardcover). Price 94.99 (amazon.co.uk). ISBN: 978-2-7420-1399-9

Surgical Neuropathology of Focal Epilepsies: Textbook and Atlas is a 157-page reference handbook written by three leaders in the field of epilepsy neuropathology, Drs. Blümcke, Sarnat and Coras. It fills a gap in the current neuropathology reference literature with a singular focus on epilepsy-associated lesions. In an effort to organize the evidence base for this diverse group of pathologies, the authors have assembled short reviews of the current literature and figures illustrating the typical microscopic findings for each entity. Of particular value to such an effort, Dr. Ingmar Blumcke brings to the text the experience of the German Neuropathology Reference Centre for Epilepsy Surgery, a European brain bank which includes an assemblage of 5603 specimens spanning a range of pathologies. The first section of the book is divided into five chapters covering different aetiologies of epilepsy including hippocampal sclerosis (HS), malformations of cortical development including focal cortical dysplasia (FCD), tumours, encephalitis and vascular lesions. The chapters on HS and FCD include summaries of the consensus classification systems for both from the International League against Epilepsy. References are listed alphabetically at the end of each topic's chapter. After these five overview chapters, the authors move on to a case-based atlas of lesions. These cases comprise 32 patients and are organized by diagnosis, with examples drawn from each of the categories outlined in the opening chapters. The case presentations include epilepsy history as well as relevant imaging findings and beautifully photographed macroscopic photos of the specimens as received and after dissection. This is followed in each case by a multi-panel figure showing the typical microscopic findings for each diagnostic entity, including histochemical and immunostains which can be useful in resolving these diagnoses. The final components of the textbook are two reference chapters. The first is an in depth presentation of the data from the European brain bank cohort. The samples included in this large series were obtained from patients with intractable epilepsy, and the data collected include clinical information such as the patients’ age, sex, age at seizure onset and localization of seizures. The data are presented in several tables, demonstrating the overall frequencies with which certain diagnoses were encountered, the average ages of onset of seizure activity, and the major categories of lesions for both adult and paediatric groups. The final section includes recommendations for processing and work-up of epilepsy specimens. This chapter includes numerous macroscopic photos detailing the handling of brain samples, from initial cut-up to techniques for freezing and processing tissue. Practising neuropathologists will also find information on immunohistochemical staining useful for the work-up of epilepsy cases. The quality of the illustrations is very good throughout the book, and the gross photographs are particularly helpful. Many light microscopic images from low magnification are provided and allow a broad overview of the architecture of the cortex or hippocampus. These images are frequently supplemented by higher magnification panels to show more detailed histopathological findings. Another major asset of this textbook is the inclusion of data from the German reference centre cohort, which allows the reader to have a better sense of the relative prevalence of specific pathologies, and their common clinical features. The structure of the book is somewhat unusual, with the first half dedicated to descriptive chapters, the next portion to case presentations and the remainder presenting reference data. Unfortunately, the book lacks an index which, given its format, would have been particularly useful for cross-referencing among these segments. However, given its short overall length, it is possible to find relevant sections simply by browsing instead. The most frequently used section of this textbook for a practising neuropathologist would likely be the case-based atlas at its centre. In this portion of the book, the high quality macroscopic and microscopic images will provide a very handy reference. The emphasis in this section on the clinical and radiological findings associated with different types of epilepsy-associated lesions certainly broadens the potential audience. In presenting the information in such a format, the authors have created an atlas that will be of interest to many clinicians with an interest in focal epilepsy. This textbook will be a good addition to the library of a practising neuropathologist who handles epilepsy cases with any frequency. Because of its broad scope and case-based approach, it will also provide a nice introduction to the topic for clinical specialists in neurology, neurosurgery or neuroradiology.

Expression of TRPC6 and BDNF in Cortical Lesions From Patients With Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) likely results from abnormal migration of neural progenitor cells originating from the subventricular zone. To elucidate the roles in molecules that are involved in neural migration pathway abnormalities in FCDs, we investigated the expression patterns of transient receptor potential canonical channel 6 (TRPC6) and brain-derived neurotrophic factor (BDNF) in cortical lesions from FCD patients and in samples of normal control cortex. TRPC6 and BDNF mRNA and protein levels were increased in FCD lesions. By immunohistochemistry, they were strongly expressed in microcolumns, heterotopic neurons, dysmorphic neurons, and balloon cells (BCs). Colocalization assays revealed that most of the misshapen TRPC6-positive or heterotopic cells had a neuronal lineage with the exception of TRPC6-positive FCDiib patient BCs, which had both neuronal and glial features. Most TRPC6-positive cells were glutamatergic neurons. There was also greater expression of calmodulin-dependent kinase IV (CaMKIV), the downstream factor of TRPC6, in FCD lesions, suggesting that TRPC6 expression promoted dendritic growth and the development of dendritic spines and excitatory synapses via the CaMKIV-CREB pathway in FCD. Thus, overexpression of BDNF and TRPC6 and activation of the TRPC6 signal transduction pathway in cortical lesions of FCD patients may contribute to FC pathogenesis and epileptogenesis.

Positive Unanimous Voting Algorithm for Focal Cortical Dysplasia Detection on Magnetic Resonance Image.

Focal cortical dysplasia (FCD) is the main cause of epilepsy and can be automatically detected via magnetic resonance (MR) images. However, visual detection of lesions is time consuming and highly dependent on the doctor's personal knowledge and experience. In this paper, we propose a new framework for positive unanimous voting (PUV) to detect FCD lesions. Maps of gray matter thickness, gradient, relative intensity, and gray/white matter width are computed in the proposed framework to enhance the differences between lesional and non-lesional regions. Feature maps are further compared with the feature distributions of healthy controls to obtain feature difference maps. PUV driven by feature and feature difference maps is then applied to classify image voxels into lesion and non-lesion. The connected region analysis then refines the classification results by removing the tiny fragment regions consisting of falsely classified positive voxels. The proposed method correctly identified 8/10 patients with FCD lesions and 30/31 healthy people. Experimental results on the small FCD samples demonstrated that the proposed method can effectively reduce the number of false positives and guarantee correct detection of lesion regions compared with four single classifiers and two recent methods.

Altered expression of neuropeptide Y receptors caused by focal cortical dysplasia in human intractable epilepsy.

Focal cortical dysplasia (FCD) is a common cause of pharmacologically-intractable epilepsy, however, the precise mechanisms underlying the epileptogenicity of FCD remains to be determined. Neuropeptide Y (NPY), an endogenous anticonvulsant in the central nervous system, plays an important role in the regulation of neuronal excitability. Increased expression of NPY and its receptors has been identified in the hippocampus of patients with mesial temporal lobe epilepsy, presumed to act as an endogenous anticonvulsant mechanism. Therefore, we investigated whether expression changes in NPY receptors occurs in patients with FCD. We specifically investigated the expression of seizure-related NPY receptor subtypes Y1, Y2, and Y5 in patients with FCD versus autopsy controls. We found that Y1R and Y2R were up-regulated at the mRNA and protein levels in the temporal and frontal lobes in FCD lesions. By contrast, there was no significant change in either receptor detected in parietal lesions. Notably, overexpression of Y5R was consistently observed in all FCD lesions. Our results demonstrate the altered expression of Y1R, Y2R and Y5R occurs in FCD lesions within the temporal, frontal and parietal lobe. Abnormal NPY receptor subtype expression may be associated with the onset and progression of epileptic activity and may act as a therapeutic candidate for the treatment of refractory epilepsy caused by FCD.

Ictal 99mTc-Ethyl Cysteinate Dimer SPECT Findings of a Girl With Refractory Localization-Related Epilepsy Who Developed Transient Ictal Bradycardia.

Ictal bradycardia, which is considered to be one of the causes of sudden unexplained death in epilepsy, is rare. A 10-year-old girl with focal cortical dysplasia in her right centroparietal region developed transient ictal bradycardia during cluster seizures. Brain magnetic resonance imaging demonstrated a high signal intensity lesion adjacent to the focal cortical dysplasia lesion. Ictal 99mTc-ethyl cysteinate dimer single-photon emission computed tomography (SPECT) detected hyperperfusion in an area containing the high signal intensity lesion, which was located close to the insular cortex. Since the hyperperfusion zone observed on SPECT was considered to reflect seizure propagation, it is possible that the ictal bradycardia experienced in the present case was caused by the following mechanism: The repetitive seizure activity caused the high-intensity lesion seen on MRI to expand into the right insular cortex, which controls cardiac rhythm, resulting in ictal bradycardia.

V27. Distribution of epileptogenicity in focal cortical dysplasias assessed with combined grid and depth electrode sampling

Objectives In focal cortical dysplasia (FCD) lesion boundaries are difficult to delineate on MRI and scalp EEG can be poorly localizing. Therefore, intracranial EEG (iEEG) is often necessary to define the extent of the epileptogenic lesion. While subdural grid electrodes provide high spatial resolution and enable excellent mapping of cortical function, depth electrodes allow for intra-lesional and deep cortical sampling. It was the aim of this study to evaluate the contribution of both modalities in a combined iEEG approach and to assess the utility of a novel semi-automated tool for iEEG analysis, the Epileptogenicity Index (EI) ( Bartolomei et al., 2008 ). Methods 15 patients with intractable epilepsy due to FCD underwent invasive EEG with a combination of subdural grid and depth electrodes. Three habitual seizures were reviewed visually to determine ictal EEG onset. Additionally we computed the EI that takes into account the propensity of brain tissue to generate rapid discharges and the delay until a given structure is involved in the seizure after onset. Thus, a quantifying index ranging from 0 to 1 is generated for each electrode separately. Results 1. Visual analysis. The ictal onset zone was located deep, sampled by the depth electrodes in 6 cases, seizures originated from the gyral surface, sampled by grid or the most lateral depth electrode contacts in 9 patients. Seizures with surface onset first involved electrodes overlying the lesion in 6 cases and electrodes remote from it in 3 cases. Seizures originating from the depth affected only intra-lesional contacts in 3, both intra- and extra-lesional electrodes in 2 and exclusively normal appearing tissue in 1 patient. 2. EI analysis. Compared to visual analysis, EI depicted the time of ictal EEG onset accurately in 13 out of 15 cases. EI localisation of ictal onset was concordant in 6 cases, moderate agreement was reached in 2 cases, while in 7 patients EI failed to capture involved electrodes correctly. Main prerequisite for good applicability of the EI was an ictal pattern consisting of fast activity in the beta and gamma range. High frequency oscillations >70 Hz and rhythmic spikes were largely missed. 3. Impact on surgical decision. Using ictal EEG information from the grids, the epileptogenic zone differed from the MRI lesion in 9 patients; depth electrodes revealed such results in 3 additional cases. Accordingly, proposed resection exceeded imaging pathology in 8 patients while in 4 cases functional cortex overlying the lesion was spared. No surgery was performed in 4 patients due to an overlap between epileptogenic and eloquent cortex. An ILAE class 1 outcome was achieved in 9 patients (82%). Discussion Although intrinsic epileptogenicity is generally assumed in FCD, seizures can also be generated within gyral or deep tissue appearing normal on imaging. In consequence, investigating FDC with a combination of subdural grid and depth electrodes is the most efficient approach to outline the three dimensional epileptogenic lesion. The EI is a helpful additional tool to measure the epileptogenicity and support visual analysis. It is applicable for grid and depth electrodes. However, a specific ictal pattern is prerogative for reliable results.