Diagnosis Of Focal Cortical Dysplasia Research Articles

Application of neuroimaging in diagnosis of focal cortical dysplasia: A survey of computational techniques

Focal Cortical Dysplasia (FCD) is a neurodevelopmental disorder characterized by abnormal neuronal migration, differentiation, and maturation, resulting in a range of clinical symptoms including drug-resistant epilepsy. Accurate and timely diagnosis of FCD is essential for effective treatment and management of patients with this condition. In recent years, there have been significant advances in neuroimaging and machine learning techniques, enabling automated detection of FCD lesions with increasing accuracy and efficiency.In this survey article, we provide an overview of the current state-of-the-art in computational techniques for the automated detection of FCD lesions using neuroimaging. We first introduce some common imaging findings that radiologists look for in FCD lesions, then review the automatic detection techniques studied in the last decade. These techniques have shown promising results in detecting and localizing FCD lesions, improving diagnostic accuracy and reducing misdiagnoses, diagnosis time, and cost of care.We suggest that the use of these types of quantitative image analysis tools and algorithms can play a key role in improving the overall management and outcome of patients with FCD. However, further studies are needed to validate and optimize the performance of these techniques in clinical practice. In summary, the combination of advanced neuroimaging and computational techniques has the potential to revolutionize the diagnosis and treatment of FCD, leading to better outcomes for patients with this condition.

Differential diagnosis of epileptogenic substrates of unknown etiology using a modification of the routine MRI protocol

To evaluate the diagnostic capabilities of modifying the standard MRI protocol as part of an interdisciplinary presurgical examination of patients with epileptogenic substrates of unknown etiology. The results of dynamic MRI of 8 patients with a referral diagnosis of focal cortical dysplasia (FCD) were analyzed. In 7 patients, epilepsy was the reason for a standard MRI of the brain; in another patient with myasthenia, MRI was performed as part of a comprehensive examination. All patients, in addition to standard MRI, underwent a modification of the real-time scanning protocol to include contrast, tractography (DTI), and perfusion techniques (ASL/DSC). In 1 case, with questionable results, the results of a modification of the standard MRI protocol, high-resolution MRI (HR MRI) and hybrid positron emission CT with 11C-methionine (PET/CT with 11C-MET) were combined. Seven patients underwent epileptic surgery and 1 patient was operated on for a tumor. In 4 out of 8 patients, based on the results of a modification of the standard MRI protocol, radiological signs of a neoplastic process were identified, which suggested a low-grade tumor. One of them needed PET/CT to confirm the assumption. The results of pathomorphological examination correlated with the direct diagnosis for surgical treatment. One of the 4 patients was suspected to have dysembryoplastic neuroepithelial tumor (DNET) based on the results of the protocol modification, which was also confirmed by pathological examination. In another 4 patients in whom it was possible to narrow the differential between FCD type II and DNET based on the results of the modification, FCD IIb was pathomorphologically verified. The proposed modification of the standard MRI protocol can significantly facilitate the differential diagnosis between the neoplastic and dysplastic origin of an epileptogenic substrate of unknown etiology, which in turn affects the patient's management tactics.

Children with seizures and radiological diagnosis of focal cortical dysplasia: can drug-resistant epilepsy be predicted earlier?

Focal cortical dysplasia (FCD) is a malformation of cortical development and is associated with drug-resistant epilepsy. Standard indication for epilepsy surgery is drug resistance (as defined by the ILAE). Given the high incidence of drug resistance in these children, this delay may not be warranted. The aim of the study was to determine the proportion of patients with a presumed FCD who develop drug resistance, and evaluate post-operative outcomes. This study incorporated a survey within a regional paediatric epilepsy network and a retrospective database review of a paediatric epilepsy centre serving the network to identify children with epilepsy and a presumed FCD on MRI. The survey revealed that 86% of the patients with epilepsy and presumed FCD on MRI within the network were referred to our centre. Of 139 paediatric patients included in the study, 131 (94.2%) had drug-resistant epilepsy. One hundred and ten (83.9%) patients were referred to epilepsy surgery, of whom 97 underwent surgery. Of 92 with one-year postoperative follow-up, 59.8% had an Engel Class 1 (seizure-free) outcome. Concordance of location between MRI and ictal EEG was strongly associated with Engel Class 1 outcome (p<0.001), as was older age at seizure onset (p=0.03). Time from diagnosis to surgery, number of medications, type of surgery and histology were not associated with improved outcome. Our data suggest that most children presenting with seizures and a radiological diagnosis of FCD will develop drug-resistant epilepsy and are candidates for epilepsy surgery. The main outcome predictors are the correlation between MRI and ictal EEG localization and age at onset. This suggests that patients with FCD and epilepsy may be considered for surgery before traditional criteria of drug resistance are met. This change in practice has the potential to improve quality of life and cognitive function, and reduce burden on epilepsy services.

Automatic Algorithm of Magnetic Resonance Morphometry in the Diagnosis of Focal Cortical Dysplasia

The purpose of the study — to create an original algorithm of MR-morphometry for identifying FCD zones. Based on the use of the ANTs and FSL programs, an algorithm for MR morphometry was developed. It was used to generate maps of the z-index of the blur of the transition of gray and white matter and the thickness of the crust (Junction and thickness maps).An algorithm for automatic detection of focal cortical dysplasia zones has been developed. The MRI morphometry method is a promising technique for additional assessment of pathological changes in focal cortical dysplasia.

P04.23 Multinodular and vacuolating neuronal tumor - advanced MRI features

Abstract BACKGROUND A rare pathology, multinodular and vacuolating neuronal tumors (MVNT) have been first described in 2013 and included in the 2016 World Health Organization Classification of Tumors of the Central Nervous System as having a distinctive radiological and cytoarchitectural appearance. This study aims to evaluate the imaging features of MVNT, it’s differential diagnosis, and possible involvement in adult-onset epilepsy. MATERIAL AND METHODS We present the case of a 29-year-old male, smoker, and drug abuser, who developed a seizure after 25 hours’ sleep deprivation, alcohol, energy drinks, cigarettes, and cocaine consumption. Cerebral CT, MRI, electroencephalogram, MR spectroscopy, and tractography was performed. RESULTS The MRI performed revealed a right, cortico-subcortical pseudo-nodular temporal lesion, non-enhancing, with a slight thickening of the adjacent cortex and right hippocampal involvement. The neurological examination was normal, but the electroencephalogram showed a right temporal irritative pattern. MR- Spectroscopy described a slight increase of choline (Cho), reduction of N-acetylaspartate (NAA), and also increased myo-inositol peak, ruling out a high-grade tumoral substrate. A tractography was also performed, excluding the other alternative diagnosis of focal cortical dysplasia, thus leaving MVNT to be the most probable explanation for the lesion. CONCLUSION Advanced MRI features were useful to increase the diagnosis accuracy. The future management consisted of image surveillance, anticonvulsant treatment, and lifestyle improvement. Adult-onset seizures are among the most frequent discovery possibilities for MVNT. In our case, it is to be seen whether the lifestyle changes and medication will prevent future seizures.

Additional clinical value of voxel-based morphometric MRI post-processing for MRI-negative epilepsies: a prospective study.

Magnetic resonance imaging is of paramount importance in the presurgical evaluation of drug resistant epilepsy. Detection of a potentially epileptogenic lesion significantly improves seizure outcome after surgery. To optimize the detection of subtle lesions, MRI post-processing techniques may be of essential help. In this study, we aimed to evaluate the detection rate of the voxel-based morphometric analysis program (MAP) in a prospective trial. We aimed to study the MAP+ findings in terms of their clinical value in the decision-making process of the presurgical evaluation. We included, prospectively, 21 patients who had negative MRI by visual analysis. In a first step, results of the conventional non-invasive presurgical evaluation were discussed, blinded to the MAP results, in multidisciplinary patient management conferences to determine the possible seizure onset zone and to set surgical or invasive evaluation plans. Thereafter, MAP results were presented, and the change of initial clinical plan was recorded. All MAP detections were reaffirmed by a neuroradiologist with epilepsy expertise. For the 21 patients included, mean age at the time of patient management conference was 26 years (SD 15 +/- years, range: 5-54 years). In total, 4/21 had temporal lobe epilepsy and 17/21 had extra-temporal lobe epilepsy. MAP was positive in 10/21 (47%) patients and in 6/10 (60%) a diagnosis of focal cortical dysplasia was confirmed after neuroradiologist review, corresponding to a 28% detection rate. MAP+ findings had a clear impact on the initial management in 7/10 patients (7/21, 33% of all patients), which included an adaptation of the intracranial EEG plan (6/7 patients), or the decision to proceed directly to surgery (1/7 patients). MRI post-processing using the MAP method yielded an increased detection rate of 28% for subtle dysplastic lesions in a prospective cohort of MRI-negative patients, indicating its potential value in epilepsy presurgical evaluation.

Sociodemographic Factors in Pediatric Epilepsy Surgery

BackgroundDespite documented efficacy of surgical treatment in carefully selected patients, surgery is delayed and/or underutilized in both adult and children with focal onset epilepsy. The reasons for surgical delay are often assumed or theorized, and studies have predominantly targeted the adult population. To focus on a more targeted pediatric population and to determine identifiable reasons for intervention, this study aimed to investigate time to epilepsy surgery among pediatric patients with medically intractable epilepsy associated with focal cortical dysplasia and to identify sociodemographic and clinical associations in time to epilepsy surgery. MethodsWe reviewed 96 consecutive pediatric patients who underwent surgery for medically intractable epilepsy with a diagnosis of focal cortical dysplasia. Descriptive statistics, univariate and multivariate analyses were conducted to study the association of sociodemographic variables of patients with focal cortical dysplasia and time to epilepsy surgery and postoperative seizure control. ResultsWe identified that non-white patients on average had a longer duration of epilepsy before surgery and traveled shorter distances for care. Non-white patients were more likely to have government-funded insurance. Patients who traveled the shortest distance to the surgical center underwent epilepsy surgery at an older age. ConclusionsSociodemographic factors of travel distance, insurance, and race influenced time to epilepsy surgery for children with focal cortical dysplasia. Further research is warranted to target barriers in access to subspecialty care and develop ways to identify earlier the patients who may benefit from evaluation and deployment of surgical intervention.

Presurgical non-invasive diagnosis of focal cortical dysplasia

In recent decades, MRI increased the success rate of the diagnosis and surgical treatment of epilepsy. Approximately 30% of patients with epilepsy suffer from the drug-resistant form of this disease. Focal cortical dysplasia is the most common abnormality of cortical development that is often associated with drug-resistance. Surgery has an important role in the treatment of epilepsy caused by focal cortical dysplasia. Focal cortical dysplasia is classified by its morphological characteristics. By large, focal cortical dysplasia can be diagnosed using the up-to-date neuroimaging tools. The aim of that paper is to review the methods available for the diagnosis of focal cortical dysplasia.

Identification and immunophenotype of abnormal cells present in focal cortical dysplasia type IIb

BackgroundFocal cortical dysplasias (FCDs) are malformations of cortical development that present cortical dyslamination and abnormal cell morphology and are frequently associated with refractory epilepsy. FCD type IIb presents dysmorphic neurons (DNs) and balloon cells (BCs), which are the hallmarks of this dysplasia. Moreover, hypertrophic neurons (HyNs) may be present in FCD types I, II and III. The objective of this study was to perform a detailed morphology and immunophenotype study of BCs, DNs, and HyNs in a cohort of FCD IIb patients.MethodsCortices resected as a treatment for refractory epilepsy from 18 cases of FCD type IIb were analysed using Bielschowsky method and haematoxylin and eosin as routine stains. Immunophenotype was performed using specific antibodies to detect epitopes differentially expressed by abnormal cells.ResultsAll cases showed cortical dyslamination, BCs, DNs, and HyNs. No cell layer or column could be identified, except for cortical layer I. Lesions predominated in the frontal cortex (11 cases). DNs were large neurons and presented a clumped and or displaced Nissl substance towards the cell membrane, and a cytoplasm accumulation of neurofilament that displaced the nucleus to the cell periphery, as shown by Bielschowsky staining and immunohistochemistry. HyNs were as large as DNs, but without alterations of Nissl substance or dense neurofilament accumulation, with a central nucleus. BCs were identified as large, oval-shaped and pale eosinophilic cells, which lacked the Nissl substance, and presented an eccentric nucleus. BCs and DNs expressed epitopes of both undifferentiated and mature cells, detected using antibodies against nestin, vimentin, class III β-tubulin, pan-neuronal filaments, neurofilament proteins, β-tubulin and NeuN. Only BCs expressed GFAP.ConclusionFCDs present with disorganization of the cerebral cortex architecture, abnormal cell morphology, are frequently associated with refractory epilepsy, and their post-surgical prognosis depends on the type of FCD. The diagnosis of focal cortical dysplasia in a surgical specimen relies on the identification of the abnormal cells present in a dysplastic cortex specimen. The current report contributes to the identification of balloon cells, dysmorphic and hypertrophic neurons in the context of focal cortical dysplasia type IIb.

Robotic-Assisted and Image-Guided MRI-Compatible Stereoelectroencephalography.

Stereoelectroencephalography has been in regular use at the Montreal Neurological Institute since 1972. The technique has been in constant evolution to incorporate advances in materials, imaging, and robotics technology. MRI-compatible electrodes were introduced in 2007 and robotics in 2011. Here we report on the technique, safety, and advantages of our current method of stereoelectroencephalography implantation. We retrospectively reviewed all patients who underwent stereoelectroencephalography by the senior author. Technical, clinical, and radiological complications, and postimplantation outcomes were analyzed. Only patients implanted with MRI-compatible electrodes were included to review MRI abnormalities with electrodes in situ. A total of 53 patients were implanted with 550 electrodes (average=10.4 per patient), for an average duration of 14.6 days. There was no mortality, infection, or new neurologic deficit. Two patients had a superficial screw plunge without clinical consequence. Four patients demonstrated asymptomatic MRI abnormalities (7.54% per patient, or 0.72% per electrode). MRI with electrodes in situ was used for neuronavigation in all 29 who underwent resection and yielded a histopathological diagnosis of focal cortical dysplasia in 15 MRI-negative patients. The technique of stereoelectroencephalography described here was associated with no clinical morbidity although not without technical complications or radiologic (MRI) abnormalities. We should therefore remain vigilant in refining the technique and minimizing the number of electrodes required to answer a well-developed hypothesis regarding the epileptogenic zone. The use of MRI-compatible electrodes allowed neuronavigation using the images with the electrodes in situ, which was useful to tailor the eventual definitive resection and in localizing MRI-negative lesions.

Magnetoencephalographic Characteristics of Cortical Dysplasia in Children

Background and RationaleMagnetoencephalography has emerged as a tool for preoperative evaluation in children. We studied magnetoencephalography characteristics in subtypes of focal cortical dysplasia and correlated the findings with postoperative seizure outcome. MethodsInclusion criteria were children ≤18 years who underwent magnetoencephalography during the preoperative evaluation followed by epilepsy surgery and a histopathologic diagnosis of focal cortical dysplasia between February 2008 and February 2013. Patient demographics, MRI, video electroencephalography, and magnetoencephalography data were reviewed. Postoperative seizure outcome data were categorized per International League against Epilepsy definitions. ResultsOf 178 magnetoencephalography studies performed in children during the study period, 33 patients met inclusion criteria. Focal cortical dysplasia type I, II, and III were found on histopathology in 52%, 39%, and 9% of patients, respectively. Thirty patients had positive magnetoencephalography dipoles, including all patients with focal cortical dysplasia type II and III and 82% of patients with focal cortical dysplasia type I. Three patients had magnetoencephalography unique spikes. Brain MRI lesions were noted preoperatively in 21 patients (64%). Twenty-three patients (77%) had surgical resection of magnetoencephalography dipoles and 11 (48%) of them achieved favorable outcome. ConclusionsMagnetoencephalography supplemented scalp electroencephalography data in spike source localization and showed unique spikes in 10% of the focal cortical dysplasia patients. Magnetoencephalography spikes and tight magnetoencephalography clusters were found more frequently in patients with focal cortical dysplasia type II and III as compared with focal cortical dysplasia type I. Presence of an MRI lesion and complete versus incomplete resection of magnetoencephalography cluster did not result in significant difference in postoperative seizure outcome, likely reflecting selection bias of doing magnetoencephalography in only difficult-to-localize epilepsies.

Contributions of EEG-fMRI to Assessing the Epileptogenicity of Focal Cortical Dysplasia.

Purpose: To examine the ability of the BOLD response to EEG spikes to assess the epileptogenicity of the lesion in patients with focal cortical dysplasia (FCD).Method: Patients with focal epilepsy and FCD who underwent 3T EEG-fMRI from 2006 to 2010 were included. Diagnosis of FCD was based on neuroradiology (MRI+), or histopathology in MRI-negative cases (MRI−). Patients underwent 120 min EEG-fMRI recording session. Spikes similar to those recorded outside the scanner were marked in the filtered EEG. The lesion (in MRI+) or the removed cortex (in MRI−) was marked on the anatomical T1 sequence, blindly to the BOLD response, after reviewing the FLAIR images. For each BOLD response we assessed the concordance with the spike field and with the lesion in MRI+ or the removed cortex in MRI−. BOLD responses were considered “concordant” if the maximal t-value was inside the marking. Follow-up after resection was used as gold-standard.Results: Twenty patients were included (13 MRI+, 7 MRI−), but in seven the EEG was not active or there were artifacts during acquisition. In all 13 studied patients, at least one BOLD response was concordant with the spike field; in 9/13 (69%) at least one BOLD response was concordant with the lesion: in 6/7 (86%) MRI+ and in 3/6 (50%) MRI− patients.Conclusions: Our study shows a high level of concordance between FCD and BOLD response. This data could provide useful information especially for MRI negative patients. Moreover, it shows in almost all FCD patients, a metabolic involvement of remote cortical or subcortical structures, corroborating the concept of epileptic network.

Serum MicroRNA-4521 is a Potential Biomarker for Focal Cortical Dysplasia with Refractory Epilepsy.

Early biomarker-based diagnosis of focal cortical dysplasia (FCD) represents a major clinical challenge. The aim of this study was to identify novel brain microRNAs (miRNAs) in patients with refractory epilepsy and FCD as potential biomarkers. We evaluated serum hsa-miR-4521 as a promising novel biomarker in patients with FCD. Tissue for microarray was obtained from nine patients with temporal lobe refractory epilepsy who underwent surgery to remove epileptic foci identified by cortical video electroencephalogram monitoring. Control tissue was collected from eight patients with hypertension who required emergency surgery to remove an intracranial hematoma. The Affymetrix® GeneChip® Command Console® Software (Affymetrix miRNA 4.0) was used to compare miRNA expression in the cerebral cortex of experimental and control patients. Temporal cortex tissue and serum samples were taken from the same patients for verification of hsa-miR-4521 expression by real-time quantitative polymerase chain reaction (RT-qPCR). The experimental and control patients did not differ significantly in terms of age and gender. 19.4 % (148/764) of the total miRNAs were differentially expressed in experimental and control tissue, which is in agreement with the existing literature. We selected miRNA-4521 for further analysis; the fold-change in expression was 14.4707 and the q value was almost 0, which confirmed up-regulation. Significant up-regulation of hsa-miR-4521 was further validated by RT-qPCR. miRNA microarrays can efficiently and conveniently identify differentially expressed miRNAs in epilepsy brain tissue. This is the first study to identify differential expression of hsa-miR-4521 in brain tissue and serum of refractory epilepsy patients and suggests that serum hsa-miR-4521 may represent a potential diagnostic biomarker for FCD with refractory epilepsy.

Combined Ex Vivo 9.4T MRI and Quantitative Histopathological Study in Normal and Pathological Neocortical Resections in Focal Epilepsy.

High‐resolution magnetic resonance imaging (MRI) may improve the preoperative diagnosis of focal cortical dysplasia (FCD) in epilepsy. Quantitative 9.4T MRI was carried out (T1, T2, T2* and magnetization transfer ratio) on 13 cortical resections, representing pathologically confirmed FCD (five cases) and normal cortex. Quantitative immunohistochemistry for myelination (myelin basic protein/SMI94), neuronal populations [microtubule‐associated protein 2 (MAP2), neurofilament (SMI31, SMI32), synaptophysin, NeuN, calbindin], reactive glia (GFAP), microglia (CD68) and blood–brain barrier permeability (albumin) was carried out in 43 regions of interest (ROI) from normal and abnormal white matter and cortex. MRI was spatially aligned and quantitative analysis carried out on corresponding ROI. Line profile analysis (LPA) of intensity gradients through the cortex was carried out on MRI and immunostained sections. An inverse correlation was noted between myelin/SMI94 and T1, T2 (P < 0.005) and T2* (P < 0.05; Spearman's correlation) and a positive correlation between neuronal MAP2 and T1 (P < 0.005) and T2* (P < 0.05) over all ROI. Similar pathology–MRI correlations were observed for histologically unremarkable white matter ROI only. LPA showed altered gradient contours in regions of FCD, reflecting abnormal cortical lamination and myelo‐architecture, including a preoperatively undetected FCD case. This study demonstrates the ability of quantitative 9.4T MRI to detect subtle differences in neuronal numbers and myelination in histologically normal appearing white matter and LPA in the evaluation of cortical dyslamination. These methods may be translatable to the in vivo detection of mild cortical malformations.

Clinical Features of a Series of Non-Surgical Patients with Focal Cortical Dysplasia and Epilepsy

Most published series of patients with focal cortical dysplasia and epilepsy are surgical or pathological series of pediatric cases. Patients have a high frequency of seizure. The description of clinical features and the frequency patterns of non-surgical adult patients are less describe. We retrospectively reviewed the clinical records of adult patients (>18 years of age) that visited the Epilepsy Centre of the Ramos Mejía Hospital in the city of Buenos Aires between 2010 and 2012. We included all cases with confirmed diagnosis of epilepsy and MRI diagnosis of focal cortical dysplasia by standardized 1.5 T MRI. We analyzed the following variables: sex, age at seizure onset, seizure types, seizure frequency, presence of abnormal neurological exam, family history of epilepsy, existence of perinatal insults and electroencephalography or video-EEG with at least one ictal recording. We included 20 patients since 2010–2012. Mean age of our population was 25.9 years (9–46 years), 7 females, 13 males, they all had a negative family history of epilepsy, and only two patients had pathological neurological exam, both with mild contralateral paresis. Mean seizure onset age was 5.71 years (2 months–17 years) and the average frequency was 5.1 seizures per month (0–15). Two patients became seizure-free after adjusting antiepileptic drugs. Focal seizures were presented in the 100% of our population. The low frequency of seizure emphasizes the heterogeneity of these patients and the importance of the correct use of antiepileptic drugs schemes, as well as it can be dynamic over time. A proportion of medically resistant patients with cortical dysplasia are poor surgical candidates because the lesion cannot be completely identify or removed if it involves eloquent areas of the cortex. With the development of new drugs and the correct choice of treatment schedules is expected that more patients with focal cortical dysplasia would be treated successfully.

The relationship between the pathological types and scalp electroencephalography features in patients with focal cortical dysplasia and intractable epilepsy

Objective To study the relationship between different pathological types of focal cortical dysplasia (FCD) and the morphology of epileptiform discharges on electroencephalography (EEG) in patients with intractable epilepsy.Methods Case series of 91 patients (male∶ female =54∶37),aged 12.7 ± 9.76 years,with histo-pathological diagnosis of FCD (based on the consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission).All patients were examined by long-term scalp video EEG monitoring before operation and were followed up at least 6 months after operation.The morphology of the interictal discharges on scalp EEG were divided into 4 types including no epileptiform discharges,spikes,poly-spikes and fast rhythms.The morphology of the seizure onset was also divided into 4 types including spikes,poly-spikes and/or fast rhythms,electro-decremental and unclassified.Results Of 91 patients,there were significant difference between different types of FCD in the morphology of interictal discharges (P =0.013) with polyspikes more common in FCD Ⅱ a and FCD Ⅱ b and fast rhythms more common in FCD]] a and spikes more common in FCD Ⅰ and FCD Ⅲ.But no relationship was found between the morphology of the seizure onset and FCD types (P =0.1976).Conclusions In patients with FCD and intractable epilepsy,the morphology of interictal discharges in scalp EEG is probably related to the pathological types of FCD. Key words: Focal cortical dysplasia; Intractable epilepsy ; Eelctroencephalography; Morphology

Focal cortical dysplasias in autism spectrum disorders

BackgroundPrevious reports indicate the presence of histological abnormalities in the brains of individuals with autism spectrum disorders (ASD) suggestive of a dysplastic process. In this study we identified areas of abnormal cortical thinning within the cerebral cortex of ASD individuals and examined the same for neuronal morphometric abnormalities by using computerized image analysis.ResultsThe study analyzed celloidin-embedded and Nissl-stained serial full coronal brain sections of 7 autistic (ADI-R diagnosed) and 7 age/sex-matched neurotypicals. Sections were scanned and manually segmented before implementing an algorithm using Laplace’s equation to measure cortical width. Identified areas were then subjected to analysis for neuronal morphometry. Results of our study indicate the presence within our ASD population of circumscribed foci of diminished cortical width that varied among affected individuals both in terms of location and overall size with the frontal lobes being particularly involved. Spatial statistic indicated a reduction in size of neurons within affected areas. Granulometry confirmed the presence of smaller pyramidal cells and suggested a concomitant reduction in the total number of interneurons.ConclusionsThe neuropathology is consistent with a diagnosis of focal cortical dysplasia (FCD). Results from the medical literature (e.g., heterotopias) and our own study suggest that the genesis of this cortical malformation seemingly resides in the heterochronic divisions of periventricular germinal cells. The end result is that during corticogenesis radially migrating neuroblasts (future pyramidal cells) are desynchronized in their development from those that follow a tangential route (interneurons). The possible presence of a pathological mechanism in common among different conditions expressing an autism-like phenotype argue in favor of considering ASD a “sequence” rather than a syndrome. Focal cortical dysplasias in ASD may serve to explain the high prevalence of seizures and sensory abnormalities in this patient population.

PP2.5 – 2056 The role of ictal subtraction SPECT for the diagnosis of focal cortical dysplasia in an infant

PP2.5 – 2056 The role of ictal subtraction SPECT for the diagnosis of focal cortical dysplasia in an infant

Focal cortical dysplasia is more common in boys than in girls

Genetics and environment likely contribute to the development of medically intractable epilepsy; however, in most patients the specific combination of etiologies remains unknown. Here, we undertook a multicenter retrospective cohort study of sex distribution in pediatric patients undergoing epilepsy surgery and carried out a secondary analysis of the same population subdivided by histopathologic diagnosis. In the multicenter cohort of patients with intractable epilepsy undergoing surgery regardless of etiology (n=206), 63% were boys, which is significantly more boys than expected for the general population (Fisher exact two-tailed p=0.017). Subgroup analysis found that of the 90 patients with a histopathologic diagnosis of focal cortical dysplasia, 72% were boys, giving an odds ratio (OR) of 2.5 (95% CI, 1.34 to 4.62) for male sex. None of the other etiologies had a male sex predominance. Future studies could examine the biological relevance and potential genetic and pathophysiological mechanisms of this observation.

MRI Findings in Low Grade Tumours Associated with Focal Cortical Dysplasia

Magnetic resonance imaging (MRI) is mandatory to identify the epileptogenic zone in refractory temporal lobe epilepsy (TLE). The correct identification of lesions is essential to obtain good post-surgery seizure control. Low grade tumours (LGT) and focal cortical dysplasia (FCD) are common findings in symptomatic TLE, and frequently coexist. The aim of this study was to identify the MRI characteristics in the diagnosis of FCD associated with LGT. We analyzed 24 subjects with TLE who underwent tailored surgery. They all had LGTs. Two expert neuroradiologists analyzed the imaging data and compared them with histological results, hypothesizing the causes of diagnostic errors in the identification of FCD. We selected three exemplary cases to report the most important causes of errors. In the diagnosis of FCD we reported false positives and false negatives due to different causes. An incomplete MRI protocol, the large dimensions of the tumour, infiltration and related oedema were the most important factors limiting MRI accuracy. MRI can be limited by an incomplete protocol. In addition, the presence of an LGT may limit the neuroradiological diagnosis of FCD in the temporal lobe. Advanced MRI techniques could help reveal subtle lesions that eluded a previous imaging inspection.