Focal Cortical Dysplasia IIa Research Articles

Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures

Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.

Alteration of GABAergic neurons and abnormality of NKCC1/KCC2 in focal cortical dysplasia (FCD) type Ⅱ lesions

BackgroundThe current conclusions of molecular genetics still cannot satisfactorily explain the pathogenesis of focal cortical dysplasia (FCD) and the reason for drug resistance. The interneurons of GABA deserve attention. To observe the distribution and changes of GABAergic neurons and to explore the expression of cation chloride cotransporter NKCC1/KCC2 in focal cortical dysplasia (FCD) type II lesions is a highly significant job. MethodsThe expressions of GAD67(a marker of active GABAergic neuron), NKCC1 and KCC2 were detected by immunohistochemistry and immunohistochemistry double staining in 10 cases of FCD Ⅱa and 10 cases of FCD Ⅱb. The number of GAD67 positive neurons was counted, and the average absorbance (IA) of NKCC1 positive expression was measured, using Image Pro-Plus7.0 software. The data were statistically analyzed. ResultsThe density of GABAergic neuron in focal dysplastic regions was significantly lower than that in the histologically “normal” cerebral cortex, regions from the same specimen (p < 0.0001, t-test). Compared to the NKCC1 staining intensity of neurons in the control group (measuring 1000 cells each), the IA value of dysmorphic neurons was significantly increased (p < 0.05, t′-test Cochran & Cox method). Intracytoplasmic concentration of KCC2 was evident in dysmorphic neurons but not in the other mature neurons. Most of the balloon cells were negative for NKCC1, except for few balloon cells showing sparse colored particles. The expression of KCC2 was negative in all balloon cells. ConclusionsThe changes in the expression of NKCC1 and KCC2 may indicate that dysmorphic neurons were in a state similar to that of immature neurons. This state may be related to the abnormal electrophysiology of epilepsy. The difference between the number of GAD67 positive cells in the lesion site and the remote site of the same case may be an evaluation index of the effectiveness of surgery.

Clinical case of a patient with focal cortical dysplasia IIa adjacent to the speech center: diagnostic and therapeutic algorithms

A clinical case of a patient with pharmacoresistant epilepsy due to focal cortical dysplasia (PCD) directly adjacent to the speech zone in the left temporal region is presented. The diagnostic search and transition from MRI-negative form to structural focal epilepsy progressed for more than 6 years. It was accounted for by the fact that type IIa vs. IIb FCD is visualized much worse, magnetic resonance imaging (MRI) signs of type IIa FCD are not so prominent, so that this type of dysplasia is often omitted. Functional research methods in epileptology, such as video-electroencephalography monitoring, brain positron emission tomography with 18F-fluorodeoxyglucose, functional MRI of speech zones, allow to more accurately verify the form of epilepsy and determine a scope of surgical treatment. Surgical intervention in carefully selected patients may contribute to favorable outcome of epilepsy (Engel 1, 51-months follow-up), which will lead to improved quality of life.

Lesion Detection Through MRI Postprocessing in Pathology-Proven Focal Cortical Dysplasia: Experience at a Single Institution in the Republic of Korea.

Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy, and necessitates a multimodal evaluation to ensure optimal surgical treatment. This study aimed to determine the supportive value of the morphometric analysis program (MAP) in detecting FCD using data from a single institution in Korea. To develop a standard reference for the MAP, normal-looking MRIs by two scanners that are frequently used in this center were chosen. Patients with drug-resistant epilepsy and FCD after surgery were candidates for the analysis. The three-dimensional T1-weighted MRI scans of the patients were analyzed as test cases using the MAP. The MRI scans of 87 patients were included in the analysis. The radiologist detected abnormal findings correlated with FCD (RAD positive [RAD(+)]) in 34 cases (39.1%), while the MAP could detect FCD in 25.3% of cases. A combination of the MAP (MAP[+] cases) with interpretations by the radiologist increased the detection to 42.5% (37 cases). The lesion detection rate was not different according to the type of reference scanners except in one case. MAP(+)/RAD(-) presented in three cases, all of which had FCD type IIa. The detection rate was slightly higher using the same kind of scanner as a reference, but not significantly (35.0% vs. 22.4% p=0.26). The results of postprocessing in the MAP for detecting FCD did not depend on the type of reference scanner, and the MAP was the strongest in detecting FCD IIa. We suggested that the MAP could be widely utilized without developing institutional standards and could become an effective tool for detecting FCD lesions.

Localizing and Lateralizing Value of Seizure Onset Pattern on Surface EEG in FCD Type II

BackgroundSurface ictal electroencephalographic (EEG) monitoring has an important role in the presurgical evaluation of patients with focal cortical dysplasia (FCD). This study aimed to examine the characteristics of seizure onset pattern (SOP) on surface ictal EEG. This information will be useful for invasive monitoring planning. MethodsWe reviewed 290 seizures from 31 patients with intractable seizures related to FCD type II (6 patients with FCD IIa and 25 patients with FCD IIb). We categorized the SOPs into five patterns and evaluated the relationships between the SOPs and the location and pathology of the FCD II subtype. ResultsThe most common SOP was no apparent change (39.0%), followed by rhythmic slow wave and repetitive spikes/sharp waves. The SOP of rhythmic slow wave was associated with FCD II in the temporal lobe (P < 0.001), and the SOP of no apparent change was associated with FCD II in the occipital lobe (P = 0.012). The SOPs of rhythmic slow waves and fast activity were most common in FCD IIa, P < 0.001 and 0.031, respectively. The repetitive spikes/sharp waves SOP was the most common pattern in FCD IIb (P < 0.001). The surface SOPs provided correct localization and lateralization of epileptic foci in FCD in 62.1% and 62.7%, respectively. In 61.3% of the patients, over 50% of the SOPs in each patient indicated accurate localization. ConclusionsSOPs in surface EEG monitoring are beneficial for presurgical evaluation and lead to localization of epileptic foci and pathologic subtypes of FCD.

Clinical Application of 7T Magnetic Resonance Imaging in Patients with Focal Cortical Dysplasia IIa and Epilepsy

Background: Focal cortical dysplasia (FCD) is one of the most important pathogenic findings in patients with extratemporal lobe epilepsy. Magnetic resonance imaging (MRI)-negative is the most important negative factor to predict postoperative seizure freedom; however, FCD-I and part of FCD-IIa are MRI-negative on routine MRI. Objectives: To explore the diagnostic values of 7T MRI and its new scan sequences in epilepsy patients with FCD-IIa. Methods: To include patients with focal seizure and suspicious focal abnormal imaging on 3T MRI during preoperative evaluation and perform a 7T MRI scan with white matter-suppressed (WMS) and gray-white matter tissue border enhancement (GWBE) sequences, resective epilepsy surgery, and postoperative pathological finding of FCD-IIa. The preoperative qualitative and localization significance of 7T MRI and 3T MRI in lesions with FCD-IIa was compared, and then, the imaging characteristics of lesions with FCD-IIa on 7T MRI were analyzed. Results: Ten cases were enrolled in this study. Seven tesla MRI presented high spatial resolutions and a high signal-to-noise ratio. WMS and GWBE could selectively suppress the signal of special tissue and improved the possibility of FCD findings. FCD-IIa showed abnormal thickness of gray matter and a blurring border and was hypointense on 7T MRI compared with 3T MRI. Seven patients showed improvement in the qualitative diagnosis strength grade of FCD, and 6 subjects showed improvement in the localization strength grade of the lesion border after careful reading of the 7T MR images. Significant differences were found in the qualitative diagnosis of FCD (p < 0.05) and localization of the lesion border (p < 0.05) between the neuroimaging diagnoses based on 3T MRI and the findings based on 7T MRI. Conclusion: 7T MRI with WMS and GWBE sequences shows application value in the preoperative imaging diagnosis of lesions with FCD-IIa in epilepsy patients.

Cingulate gyrus epilepsy: semiology, invasive EEG, and surgical approaches.

The semiology of cingulate gyrus epilepsy is varied and may involve the paracentral area, the adjacent limbic system, and/or the orbitofrontal gyrus. Invasive electroencephalography (iEEG) recording is usually required for patients with deeply located epileptogenic foci. This paper reports on the authors' experiences in the diagnosis and surgical treatment of patients with focal epilepsy originating in the cingulate gyrus. Eighteen patients (median age 24 years, range 5-53 years) with a mean seizure history of 23 years (range 2-32 years) were analyzed retrospectively. The results of presurgical evaluation, surgical strategy, and postoperative pathology are reported, as well as follow-up concerning functional morbidity and seizures (median follow-up 7 years, range 2-12 years). Patients with cingulate gyrus epilepsy presented with a variety of semiologies and scalp EEG patterns. Prior to ictal onset, 11 (61%) of the patients presented with aura. Initial ictal symptoms included limb posturing in 12 (67%), vocalization in 5, and hypermotor movement in 4. In most patients (n = 16, 89%), ictal EEG presented as widespread patterns with bilateral hemispheric origin, as well as muscle artifacts obscuring the onset of EEG during the ictal period in 11 patients. Among the 18 patients who underwent resection, the pathology revealed mild malformation of cortical development in 2, focal cortical dysplasia (FCD) Ib in 4, FCD IIa in 4, FCD IIb in 4, astrocytoma in 1, ganglioglioma in 1, and gliosis in 2. The seizure outcome after surgery was satisfactory: Engel class IA in 12 patients, IIB in 3, IIIA in 1, IIIB in 1, and IVB in 1 at the 2-year follow-up. In this study, the authors exploited the improved access to the cingulate epileptogenic network made possible by the use of 3D electrodes implanted using stereoelectroencephalography methodology. Under iEEG recording and intraoperative neuromonitoring, epilepsy surgery on lesions in the cingulate gyrus can result in good outcomes in terms of seizure recurrence and the incidence of postoperative permanent deficits.

Differential Expression Hallmarks of Interneurons in Different Types of Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is the main cause of medically intractable pediatric epilepsy. Previous studies have suggested that alteration of cortical interneurons and abnormal cytoarchitecture have been linked to initiation and development for seizure. However, whether each individual subpopulation of cortical interneurons is linked to distinct FCD subtypes remains largely unknown. Here, we retrospectively analyzed both control samples and epileptic specimens pathologically diagnosed with FCD types Ia, IIa, or IIb. We quantified three major interneuron (IN) subpopulations, including parvalbumin (PV)-, somatostatin (Sst)-, and vasoactive intestinal peptide (Vip)-positive INs across all the subgroups. Additionally, we calculated the ratio of the subpopulations of INs to the major INs (mINs) by defining the total number of the PV-, Sst-, and Vip-INs as mINs. Compared with the control, the density of the PV-INs in FCD type IIb was significantly lower, and the ratio of PV/mINs was lower in the superficial part of the cortex of the FCD type Ia and IIb groups. Interestingly, we found a significant increase in the ratio of Vip/mINs only in FCD type IIb. Overall, these results suggest that in addition to a reduction in PV-INs, the increase in Vip/mINs may be related to the initiation of epilepsy in FCD type IIb. Furthermore, the increase in Vip/mINs in FCD type IIb may, from the IN development perspective, indicate that FCD type IIb forms during earlier stages of pregnancy than FCD type Ia.

Ultra-High-Field Targeted Imaging of Focal Cortical Dysplasia: The Intracortical Black Line Sign in Type IIb.

Conventional MR imaging has limitations in detecting focal cortical dysplasia. We assessed the added value of 7T in patients with histologically proved focal cortical dysplasia to highlight correlations between neuropathology and ultra-high-field imaging. Between 2013 and 2019, we performed a standardized 7T MR imaging protocol in patients with drug-resistant focal epilepsy. We focused on 12 patients in whom postsurgical histopathology revealed focal cortical dysplasia and explored the diagnostic yield of preoperative 7T versus 1.5/3T MR imaging and the correlations of imaging findings with histopathology. We also assessed the relationship between epilepsy surgery outcome and the completeness of surgical removal of the MR imaging-visible structural abnormality. We observed clear abnormalities in 10/12 patients using 7T versus 9/12 revealed by 1.5/3T MR imaging. In patients with focal cortical dysplasia I, 7T MR imaging did not disclose morphologic abnormalities (n = 0/2). In patients with focal cortical dysplasia II, 7T uncovered morphologic signs that were not visible on clinical imaging in 1 patient with focal cortical dysplasia IIa (n = 1/4) and in all those with focal cortical dysplasia IIb (n = 6/6). T2*WI provided the highest added value, disclosing a peculiar intracortical hypointense band (black line) in 5/6 patients with focal cortical dysplasia IIb. The complete removal of the black line was associated with good postsurgical outcome (n = 4/5), while its incomplete removal yielded unsatisfactory results (n = 1/5). The high sensitivity of 7T T2*-weighted images provides an additional tool in defining potential morphologic markers of high epileptogenicity within the dysplastic tissue of focal cortical dysplasia IIb and will likely help to more precisely plan epilepsy surgery and explain surgical failures.

Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence.

Oxidative stress (OS) occurs in brains of patients with epilepsy and coincides with brain inflammation, and both phenomena contribute to seizure generation in animal models. We investigated whether expression of OS and brain inflammation markers co-occurred also in resected brain tissue of patients with epileptogenic cortical malformations: hemimegalencephaly (HME), focal cortical dysplasia (FCD) and cortical tubers in tuberous sclerosis complex (TSC). Moreover, we studied molecular mechanisms linking OS and inflammation in an in vitro model of neuronal function. Untangling interdependency and underlying molecular mechanisms might pose new therapeutic strategies for treating patients with drug-resistant epilepsy of different etiologies. Immunohistochemistry was performed for specific OS markers xCT and iNOS and brain inflammation markers TLR4, COX-2 and NF-κB in cortical tissue derived from patients with HME, FCD IIa, IIb and TSC. Additionally, we studied gene expression of these markers using the human neuronal cell line SH-SY5Y in which OS was induced using H2 O2 . OS markers were higher in dysmorphic neurons and balloon/giant cells in cortex of patients with FCD IIb or TSC. Expression of OS markers was positively correlated to expression of brain inflammation markers. In vitro, 100µM, but not 50µM, of H2 O2 increased expression of TLR4, IL-1β and COX-2. We found that NF-κB signaling was activated only upon stimulation with 100µM H2 O2 leading to upregulation of TLR4 signaling and IL-1β. The NF-κB inhibitor TPCA-1 completely reversed this effect. Our results show that OS positively correlates with neuroinflammation and is particularly evident in brain tissue of patients with FCD IIb and TSC. In vitro, NF-κB is involved in the switch to an inflammatory state after OS. We propose that the extent of OS can predict the neuroinflammatory state of the brain. Additionally, antioxidant treatments may prevent the switch to inflammation in neurons thus targeting multiple epileptogenic processes at once.

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.

Somatic Depdc5 deletion recapitulates electroclinical features of human focal cortical dysplasia type IIA.

Epileptogenic mechanisms in focal cortical dysplasia (FCD) remain elusive, as no animal models faithfully recapitulate FCD seizures, which have distinct electrographic features and a wide range of semiologies. Given that DEPDC5 plays significant roles in focal epilepsies with FCD, we used in utero electroporation with clustered regularly interspaced short palindromic repeats gene deletion to create focal somatic Depdc5 deletion in the rat embryonic brain. Animals developed spontaneous seizures with focal pathological and electroclinical features highly clinically relevant to FCD IIA, paving the way toward understanding its pathogenesis and developing mechanistic-based therapies. Ann Neurol 2018;83:140-146.

Intraoperative Magnetic-Resonance Tomography and Neuronavigation During Resection of Focal Cortical Dysplasia Type II in Adult Epilepsy Surgery Offers Better Seizure Outcomes.

Focal cortical dysplasia (FCD) is one important cause of drug-resistant epilepsy potentially curable by epilepsy surgery. We investigated the options of using neuronavigation and intraoperative magnetic-resonance tomographical imaging (MRI) to avoid residual epileptogenic tissue during resection of patients with FCD II to improve seizure outcome. Altogether, 24 patients with FCD II diagnosed by MRI (16 female, 8 male; mean age 34 ± 10 years) suffered from drug-resistant electroclinical and focal epilepsy for a mean of 20.7 ± 5 years. Surgery was performed with preoperative stereoelectroencephalography (in 15 patients), neuronavigation, and intraoperative 1.5T-iopMRI in all 24 investigated patients. In 75% of patients (18/24), a complete resection was performed. In 89% (16/18) of completely resected patients, we documented an Engel I seizure outcome after a mean follow-up of 42 months. All incompletely resected patients had a worse outcome (Engel II-III, P < 0.0002). Patients with FCD IIB had also significant better seizure outcome compared with patients diagnosed as having FCD IIA (82% vs. 28%, P < 0.02). In 46% (11/24) of patients, intraoperative second-look surgeries due to residual lesions detected during the intraoperative MRI were performed. In these 11 patients, there were significant more completely seizure free patients (73% vs. 38% Engel IA), compared with 13 patients who finished surgery after the first intraoperative MRI (P < 0.05). Excellent seizure outcome after surgery of patients with FCD II positively correlated with the amount of resection, histologic subtype, and the use of intraoperative MRI, especially when intraoperative second-look surgeries were performed.

Putting the new ILAE classification of focal cortical dysplasia into practice in western China

PurposeTo re-examine drug-resistant epilepsy cases using the revised 2011 ILAE classification of focal cortical dysplasia (FCD). MethodsPatients with drug-resistant epilepsy who have undergone epilepsy surgery in West China Hospital between July 2012 and Jun 2014 were included. Clinical histories, pathological diagnoses, and surgical outcomes were reviewed. A questionnaire was developed to investigate the clinical practice of the new classification. A short-term training program on FCD was carried out to improve pathological diagnosis accuracy. Results260 consecutive cases (177 male and 83 female) were included. Pathological diagnosis was changed in 70 cases (26.9%) after re-examination. The five most common pathological types were hippocampal sclerosis (19.2%, 50/260), brain tumors (17.7%, 46/260), vascular malformations (16.2%, 42/260), glial scars (11.2%, 29/260) and FCD (10.0%, 26/260). The most common subtype of isolated FCD was FCD IIb (53.8%, 14/26), followed by FCD IIa (42.3%, 11/26) and FCD Ib (3.8%, 1/26). In addition, forty-five cases were diagnosed as associated FCD type III (17.3%, 45/260). Half of patients with FCD achieved Engel class I at two-year follow-up. Questionnaire investigation suggested most participant pathologists lack sufficient knowledge on the new classification. The diagnostic sensitivity for different FCD subtypes was significantly improved by two to six folds after short-term training. ConclusionsFCD is an important etiology of drug-resistant epilepsy in western China. It is essential to provide continuing trainings to improve diagnostic precision of FCD in developing countries.

Clinical characteristics and epilepsy outcomes following surgery caused by focal cortical dysplasia (type IIa) in 110 adult epileptic patients.

The aim of the present study was to investigate the effects of surgical intervention of focal cortical dysplasia (FCD) IIa on the outcome of epilepsy, and to evaluate the prognostic factors of seizure freedom. Patient data from epilepsy surgeries were retrospectively reviewed at the Second Affiliated Hospital of Dalian Medical University between 2007 and 2015. A total of 110 patients with a definite pathological diagnosis of FCD IIa were included. Moreover, the clinical characteristics, seizure outcome and quality of life in adults with FCD IIa were evaluated. The Engel seizure outcome achievements were class I in 72, class II in 20, class III in 11 and class IV in 7 patients. In addition, the Engel seizure outcome was relevant with the resection range of the lesions (P=0.028). The assessments of electrocorticography (ECoG) patterns and magnetic resonance imaging (MRI) are relevant to determining the extent of the resection, which may influence the surgery outcome (P=0.001 and P=0.023). Using multivariate regression analyses, the extent of resection, seizure frequency, preoperative ECoG and location of resection were the most important risk factors for seizure recurrence. The results of quality of life in epilepsy-10 scoring revealed that the quality of life improved significantly following surgery (P<0.01). Moreover, surgical intervention, EcoG, MRI positioning and complete resection helped to have improved seizure control, relief of anxiety and quality of life. All these observations strongly recommend an early consideration of epilepsy surgery in FCD IIa patients.

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality.

To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD). We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies. Rates of pathology subtypes differed between TLE and ETLE (χ2 (3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ2 (1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ2 (1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ2 (6) = 13.07, p = 0.042). Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy.

Metabotropic Glutamate Receptor Type 5 (mGluR5) Cortical Abnormalities in Focal Cortical Dysplasia Identified In Vivo With [11C]ABP688 Positron-Emission Tomography (PET) Imaging.

Metabotropic glutamate receptor type 5 (mGluR5) abnormalities have been described in tissue resected from epilepsy patients with focal cortical dysplasia (FCD). To determine if these abnormalities could be identified in vivo, we investigated mGluR5 availability in 10 patients with focal epilepsy and an MRI diagnosis of FCD using positron-emission tomography (PET) and the radioligand [11C]ABP688. Partial volume corrected [11C]ABP688 binding potentials (BPND) were computed using the cerebellum as a reference region. Each patient was compared to homotopic cortical regions in 33 healthy controls using region-of-interest (ROI) and vertex-wise analyses. Reduced [11C]ABP688 BPND in the FCD was seen in 7/10 patients with combined ROI and vertex-wise analyses. Reduced FCD BPND was found in 4/5 operated patients (mean follow-up: 63 months; Engel I), of whom surgical specimens revealed FCD type IIb or IIa, with most balloon cells showing negative or weak mGluR5 immunoreactivity as compared to their respective neuropil and normal neurons at the border of resections. [11C]ABP688 PET shows for the first time in vivo evidence of reduced mGluR5 availability in FCD, indicating focal glutamatergic alterations in malformations of cortical development, which cannot be otherwise clearly demonstrated through resected tissue analyses.

Type II focal cortical dysplasia: Ex vivo 7T magnetic resonance imaging abnormalities and histopathological comparisons.

In the present report, the correlations between ex vivo high-resolution imaging and specific histological and ultrastructural patterns in type II focal cortical dysplasia (FCD) have been studied to explain the differences in the magnetic resonance imaging (MRI) detection of dysplasia and to contribute to the presurgical imaging evaluation of this pathology. Surgical specimens from 13 patients with FCD IIa/b were submitted to 7T MRI scanning, and then analyzed histologically and ultrastructurally to compare the results with the MRI findings. Region of interest (ROI)-based measures on T2-weighted images (T2wi) were quantitatively evaluated in the lesion and in adjacent perilesional gray and white matter. Matched histological sections and 7T T2wi showed that the core of the lesion was characterized by patchy aggregates of abnormal cells and fiber disorganization related to inhomogeneity of intracortical signal intensity. The quantitative approach on T2wi can help to distinguish the lesions and perilesional areas even in a clinical MRI-negative case. The ultrastructural study showed that the strong signal hyperintensity in the white matter of FCD IIb was related to a dysmyelination process associated with severe fiber loss and abnormal cells. Less severe histopathological features were found in FCD IIa, thus reflecting their less evident MRI alterations. We suggest that white matter abnormalities in type IIb FCD are due to defects of the myelination processes and maturation, impaired by the presence of balloon cells. To reveal the presence and the border of type II cortical dysplasia on MRI, a quantitative ROI-based analysis (coefficient of variation) is also proposed.

Disconnective surgery in posterior quadrantic epilepsy: a series of 12 paediatric patients.

To assess the surgical outcomes of temporo-parieto-occipital (TPO) and parieto-occipital (PO) disconnection surgery for children with intractable posterior quadrantic epilepsy and a unilateral posterior quadrant lesion based on MRI and functional imaging abnormality in the TPO region on one side. A retrospective review of data of 12 children who underwent TPO or PO disconnective surgery was carried out from September 2009 to September 2012. Three-dimensional surface reconstructions of MRI scans and intraoperative electrophysiological monitoring were used during surgery. Drugs were not discontinued after surgery in any patient. The affected hemisphere was the left in seven patients and the right in five patients. The mean ages at seizure onset and at surgery were four years and 12.3 years, respectively. At the time of surgery, 3 children had atonic seizures, 4 had symptomatic epilepsy with focal seizures and alteration of conscioussness, 4 had secondarily generalised seizures, and 1 child had spasms and tonic seizures. All patients had developmental delay. A pure TPO disconnection was performed in 11 patients and a PO disconnection was performed in the remaining patient. On pathological examination, 3 patients were shown to have focal cortical dysplasia (FCD) Ib, 2 with FCD IIa, 5 with FCD IIb, 1 with gliosis, and 1 with gliosis plus FCD IIa. Following surgery, 2 patients had oedema; 1 required another operation to resect the occipital lobe. At a mean follow-up of 34.5 months, 9 patients (75%) were classified as Engel class I, 2 as Engel Class II, and 1 as Engel class III. All 12 children had contralateral hemianopia postoperatively and improvement in median IQ (p=0.04) was reported three months postoperatively. With respect to the limits of a retrospective and relatively small sample size series TPO and PO disconnection are safe and effective motor-sparing epilepsy surgical procedures in selected patients with the epileptiform zone located in the posterior quadrant on one side.

Clinical characteristics, pathological features and surgical outcomes of focal cortical dysplasia (FCD) type II: correlation with pathological subtypes.

Focal cortical dysplasia (FCD) type II is a major cause of drug-resistant epilepsy. In order to gain insight into the possible correlations between FCD II pathological pattern and different clinical characteristics (including clinical information, imaging characteristics and surgical outcomes), different clinicopathological characteristics in two types of FCD II were analyzed (especially in FCD IIb). The mean age of seizure onset and disease duration of 78 patients was 11.0 and 11.2 years, respectively. Patients with FCD type IIb had earlier seizure onset compared with those with FCD type IIa. Pathological subtype IIb was predominantly in frontal lobe and subtype IIa was predominantly seen in temporal. Type IIb demonstrated significantly more signal abnormalities in fluid attenuated inversion recovery (FLAIR) images and T2 images than Type IIa. The rate of satisfactory seizure outcome was 67.64 % in the FCD IIa group, while relative higher, 88.63 %, in the FCD IIb group. All these characteristics may assist in their earlier diagnosis and improve the predictability of surgical management.