Matrix-assisted laser desorption/ionization mass spectrometry imaging as a new tool for molecular histopathology in epilepsy surgery.

OBJECTIVE: Epilepsy surgery is a treatment option for patients with seizures that do not respond to pharmacotherapy. The histopathological characterization of the resected tissue has an important prognostic value to define postoperative seizure outcome in these patients. However, the diagnostic classification process based on microscopic assessment remains challenging, particularly in the case of focal cortical dysplasia (FCD). Imaging mass spectrometry is a spatial omics technique that could improve tissue phenotyping and patient stratification by investigating hundreds of biomolecules within a single tissue sample, without the need for target-specific reagents. METHODS: An in situ proteomic technique called matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is here investigated as a potential new tool to expand conventional diagnosis on standard paraffin brain tissue sections. Unsupervised and region of interest-based MALDI-MSI analyses of sections from 10 FCD type IIb (FCDIIb) cases were performed, and the results were validated by immunohistochemistry. RESULTS: MALDI-MSI identified distinct histopathological features and the boundaries of the dysplastic lesion. The capability to visualize the spatial distribution of well-known diagnostic markers enabling multiplex measurements on single tissue sections was demonstrated. Finally, a fingerprint list of potential discriminant peptides that distinguish FCD core from peri-FCD tissue was generated. SIGNIFICANCE: This is the first study that explores the potential application of MALDI-MSI in epilepsy postsurgery fixed tissue, by utilizing the well-characterized FCDIIb features as a model. Extending these preliminary analyses to a larger cohort of patients will generate spectral libraries of molecular signatures that discriminate tissue features and will contribute to patient phenotyping.

Application of preoperative MRI lesion identification algorithm in pediatric and young adult focal cortical dysplasia-related epilepsy.

OBJECTIVE: The purpose of this study was to evaluate the performance and generalizability of an automated, interpretable surface-based MRI classifier for the detection of focal cortical dysplasia. METHODS: This was a retrospective cohort incorporating MRIs from the epilepsy surgery (FCD and MRI-negative) and neuroimaging (healthy controls) databases at Children's National Hospital (CNH), and a publicly-available FCD Type II dataset from Bonn, Germany. Clinical characteristics and outcomes were abstracted from patient records and/or existing databases. Subjects were included if they had 3T epilepsy-protocol MRI. Manually-segmented FCD masks were compared to the automated masks generated by the Multi-centre Epilepsy Lesion Detection (MELD) FCD detection algorithm. Sensitivity/specificity were calculated. RESULTS: From CNH, 39 FCD pharmacoresistant epilepsy (PRE) patients, 19 healthy controls, and 19 MRI-negative patients were included. From Bonn, 85 FCD Type II were included, of which 68 passed preprocessing. MELD had varying performance (sensitivity) in these datasets: CNH FCD-PRE (54 %); Bonn (68 %); MRI-negative (44 %). In multivariate regression, FCD Type IIB pathology predicted higher chance of MELD automated lesion detection. All four patients who underwent resection/ablation of MELD-identified clusters achieved Engel I outcome. SIGNIFICANCE: We validate the performance of MELD automated, interpretable FCD classifier in a diverse pediatric cohort with FCD-PRE. We also demonstrate the classifier has relatively good performance in an independent FCD Type II cohort with pediatric-onset epilepsy, as well as simulated real-world value in a pediatric population with MRI-negative PRE.

Severe Epilepsy in an Individual With a TSC2 R905Q Variant Prompting Late Diagnosis in Affected Family Members.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared with TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected. METHODS: We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant. RESULTS: Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3-diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4-diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis. CONCLUSIONS: This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.

Contribution of the Activated mTOR-STAT3 Pathway to the Pathogenesis of Focal Cortical Dysplasia Type IIIa in Pediatric Patients through Astrocyte Proliferation Mediation.

OBJECTIVE: The aim of this study was to detect the association between the mTOR-STAT3 pathway and focal cortical dysplasia type IIIa (FCD IIIa) in children. METHODS: A retrospective review was conducted based on 26 pediatric patients diagnosed with FCD IIIa who underwent surgical intervention. These patients were selected from a cohort of 157 individuals presenting with temporal lobe epilepsy. For comparative analysis, a control group consisting of 5 children who underwent intracranial decompression was established. Immunohistochemistry, immunofluorescence, and western blot techniques were used to assess the expression levels of mTOR, P-mTOR, P-70s6k, STAT3, P-STAT3, and GFAP in brain tissue specimens obtained from the two groups. RESULTS: The mTOR-STAT3 pathway exhibited activation in the FCD IIIa group (all P < 0.01). Additionally, immunofluorescence analysis revealed that cells positive for PSTAT3 were identified as astrocytes. Moreover, within the FCD IIIa group, there was a marked elevation in the expression of the mTOR-STAT3 pathway in the hippocampus compared to the brain cortex tissue. CONCLUSION: The mTOR-STAT3 pathway was demonstrated to be substantially associated with FCD IIIa in pediatric patients. The activation of the mTOR-STAT3 signaling pathway may contribute to the pathogenesis of FCD IIIa in pediatric patients by modulating the proliferation of astrocytes.

Focal cortical dysplasia lesion segmentation using multiscale transformer.

OBJECTIVES: Accurate segmentation of focal cortical dysplasia (FCD) lesions from MR images plays an important role in surgical planning and decision but is still challenging for radiologists and clinicians. In this study, we introduce a novel transformer-based model, designed for the end-to-end segmentation of FCD lesions from multi-channel MR images. METHODS: The core innovation of our proposed model is the integration of a convolutional neural network-based encoder-decoder structure with a multiscale transformer to augment the feature representation of lesions in the global field of view. Transformer pathways, composed of memory- and computation-efficient dual-self-attention modules, leverage feature maps from varying depths of the encoder to discern long-range interdependencies among feature positions and channels, thereby emphasizing areas and channels relevant to lesions. The proposed model was trained and evaluated on a public-open dataset including MR images of 85 patients using both subject-level and voxel-level metrics. RESULTS: Experimental results indicate that our model offers superior performance both quantitatively and qualitatively. It successfully identified lesions in 82.4% of patients, with a low false-positive lesion cluster rate of 0.176 ± 0.381 per patient. Furthermore, the model achieved an average Dice coefficient of 0.410 ± 0.288, outperforming five established methods. CONCLUSION: Integration of the transformer could enhance the feature presentation and segmentation performance of FCD lesions. The proposed model has the potential to serve as a valuable assistive tool for physicians, enabling rapid and accurate identification of FCD lesions. The source code and pre-trained model weights are available at https://github.com/zhangxd0530/MS-DSA-NET . CRITICAL RELEVANCE STATEMENT: This multiscale transformer-based model performs segmentation of focal cortical dysplasia lesions, aiming to help radiologists and clinicians make accurate and efficient preoperative evaluations of focal cortical dysplasia patients from MR images. KEY POINTS: The first transformer-based model was built to explore focal cortical dysplasia lesion segmentation. Integration of global and local features enhances the segmentation performance of lesions. A valuable benchmark for model development and comparative analyses was provided.

Cortical and subcortical morphometric changes in patients with frontal focal cortical dysplasia type II.

PURPOSE: This study investigates the morphometric changes in the brains of patients with frontal focal cortical dysplasia (FCD) Type II, distinguishing between right and left FCD, using voxel-based morphometry (VBM), surface-based morphometry (SBM), and subcortical shape analysis. METHODS: The study included 53 patients with frontal lobe FCD Type II (28 left-sided, 25 right-sided) and 66 age- and gender-matched healthy controls. VBM and SBM analyses were conducted using Computational Anatomy Toolbox 12.8 (CAT12.8) and Statistical Parametric Mapping 12 (SPM12). Subcortical structures were segmented using FSL-FIRST. Statistical analyses were performed using non-parametric tests, with a significance threshold of p < 0.05. RESULTS: VBM revealed increased gray matter volume in the bilateral ventral diencephalon, left putamen, and left thalamus in the left FCD group. SBM indicated reduced sulcal depth in the right precentral, postcentral, and caudal middle frontal gyrus in the right FCD group. Subcortical shape analysis showed internal deformation in the left hippocampus and external deformation in bilateral putamen in the left FCD group, and external deformation in the left caudate nucleus, left putamen, and right amygdala in the right FCD group. CONCLUSION: Morphometric changes in frontal FCD Type II patients vary depending on the hemisphere. Right FCD Type II is associated with sulcal shallowing and external deformation in contralateral subcortical structures, while left FCD Type II shows internal and external deformations in the hippocampus and putamen, respectively, along with increased gray matter volume in the basal ganglia. These findings highlight the need for hemisphere-specific analyses in epilepsy research.

Microsurgical lesionectomy for drug-resistant insular cortex epilepsy in focal cortical dysplasia type IIB: a pediatric case report.

Introduction and importance: Focal cortical dysplasia (FCD) is a significant cause of drug-resistant epilepsy, often necessitating surgical intervention. Type IIb FCD poses challenges due to its strong association with drug-resistant seizures. Effective management involves advanced imaging, intraoperative neurophysiological monitoring, and precise surgical techniques. This case study illustrates these strategies in an 11-year-old female with drug-resistant epilepsy attributed to Type IIb FCD. Case presentation: The patient, an 11-year-old female, had drug-resistant seizures despite various anticonvulsant treatments. Preoperative 3 Tesla (3T) MRI revealed an ill-defined lesion in the right frontal operculum. The surgical team used neuro-navigation for intraoperative guidance and electrocorticography for lesionectomy. Pathology confirmed Type IIb FCD with rare concentric calcifications. Clinical discussion: Drug-resistant seizures in FCD often require surgery when medications fail. This case highlights the importance of comprehensive preoperative evaluations and advanced imaging, such as 3T MRI, to accurately identify lesions. Intraoperative neurophysiological monitoring, including electrocorticography, ensures precise resection of the epileptogenic zone. The unusual finding of concentric calcifications in Type IIb FCD is noteworthy, suggesting the need for further research to understand their impact on the disease. Conclusion: Microsurgical lesionectomy is crucial for managing drug-resistant seizures in Type IIb FCD. Combining advanced imaging with intraoperative monitoring improves surgical precision and outcomes. The rare pathological finding of calcifications highlights the diversity of FCD manifestations, warranting further study. These techniques can significantly enhance seizure control and quality of life in patients with drug-resistant epilepsy.

The utility of Multicentre Epilepsy Lesion Detection (MELD) algorithm in identifying epileptic activity and predicting seizure freedom in MRI lesion-negative paediatric patients.

AIM: Paediatric patients with drug-resistant focal epilepsy (DRFE) who have no clear focal lesion identified on conventional structural magnetic resonance imaging (MRI) are a particularly challenging cohort to treat and form an increasing part of epilepsy surgery programs. A recently developed deep-learning-based MRI lesion detection algorithm, the Multicentre Lesion Detection (MELD) algorithm, has been shown to aid detection of focal cortical dysplasia (FCD). We applied this algorithm retrospectively to a cohort of MRI-negative children with refractory focal epilepsy who underwent stereoelectroencephalography (SEEG) to determine its accuracy in identifying unseen epileptic lesions, seizure onset zones and clinical outcomes. METHODS: We retrospectively applied the MELD algorithm to a consecutive series of MRI-negative patients who underwent SEEG at our tertiary Paediatric Epilepsy Surgery centre. We assessed the extent to which the identified MELD cluster or lesion area corresponded with the clinical seizure hypothesis, the epileptic network, and the positron emission tomography (PET) focal hypometabolic area. In those who underwent resective surgery, we analysed whether the region of MELD abnormality corresponded with the surgical target and to what extent this was associated with seizure freedom. RESULTS: We identified 37 SEEG studies in 28 MRI-negative children in whom we could run the MELD algorithm. Of these, 14 (50 %) children had clusters identified on MELD. Nine (32 %) children had clusters concordant with seizure hypothesis, 6 (21 %) had clusters concordant with PET imaging, and 5 (18 %) children had at least one cluster concordant with SEEG electrode placement. Overall, 4 MELD clusters in 4 separate children correctly predicted either seizure onset zone or irritative zone based on SEEG stimulation data. Sixteen children (57 %) went on to have resective or lesional surgery. Of these, only one patient (4 %) had a MELD cluster which co-localised with the resection cavity and this child had an Engel 1 A outcome. CONCLUSIONS: In our paediatric cohort of MRI-negative patients with drug-resistant focal epilepsy, the MELD algorithm identified abnormal clusters or lesions in half of cases, and identified one radiologically occult focal cortical dysplasia. Machine-learning-based lesion detection is a promising area of research with the potential to improve seizure outcomes in this challenging cohort of radiologically occult FCD cases. However, its application should be approached with caution, especially with regards to its specificity in detecting FCD lesions, and there is still work to be done before it adds to diagnostic utility.

Superior lesion detection on 3D FSE T1WI with magnetization transfer and CHESS preparation pulses in children with focal epilepsy: Preliminary results.

In childhood drug-resistant focal epilepsy, the identification of a magnetic resonance imaging lesion significantly affects the management and prognosis, although it is often challenging. Herein we report the preliminary results of a modified MR sequence, in which both magnetization transfer and chemical shift selective preparation pulses are added to a 3D fast spin echo T1-weighted sequence to recognize focal cortical dysplasia. The scan time is short, and the images have expected uniform suppression of the background normal gray and white matter. We report four children with focal epilepsy, in whom the focal cortical and subcortical lesions are superiorly conspicuous on the aforementioned MR sequence compared to the high-resolution fluid-attenuated inversion recovery images obtained with typical epilepsy MR protocols.

Pathophysiological mechanisms underlying the development of focal cortical dysplasia and their association with epilepsy: Experimental models as a research approach.

Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD.

From Alpha-Thalassemia Trait to NPRL3-Related Epilepsy: A Genomic Diagnostic Odyssey.

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband's episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene's introns.

Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy.

Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioural seizures. The mosaic burdens ranged from approximately 1000 to 40 000 neurons expressing the mTOR mutant in the somatosensory or medial prefrontal cortex. Surprisingly, approximately 8000-9000 neurons expressing the MTOR mutant, extrapolated to constitute 0.08%-0.09% of total cells or roughly 0.04% of variant allele frequency in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.

Evaluating intraoperative ultrasound (IOUS) in focal cortical dysplasia (FCD) resection surgery: A systematic review.

Background: Surgery is the best approach to treating focal cortical dysplasia (FCD)-related epilepsy; yet, it has suboptimal outcomes because distinguishing the boundaries between the FCD region and normal brain tissue intraoperatively poses a challenge. The use of intraoperative ultrasound (IOUS) helps demarcate FCD lesion borders leading to more accurate intraoperative resection. In this review, the use of IOUS for the resection of FCD was evaluated. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Medline, Embase, Cochrane Library, Scopus Library, and Dynamed Library databases were searched, and two independent reviewers examined the articles. The search terms related to "drug-resistant epilepsy" and "intraoperative ultrasound." The results between January 2008 and April 2022 were abridged for FCD type, ultrasound resolution, extent of lesion resection, correction of brain shift, postoperative neurological deficits, and postoperative seizure freedom (Engel classification). Results: Ten articles were included in the study. The parameters used to assess the efficacy of IOUS in FCD surgery were ultrasound resolution, demarcation of lesion boundaries, correction of brain shift, postoperative neurological deficits, and seizure freedom. Most studies have shown that IOUS produces high-resolution images. Surgery for Type 2 FCD patients had better outcomes than surgery for Type 1 FCD patients due to better visualization by IOUS. Patients were classified as Engel class 1 or class 2 postoperatively. Eight studies found that IOUS was superior to magnetic resonance imaging in brain shift correction. Conclusion: The preliminary results look promising, especially for the international league against epilepsy class 2 FCD. However, there is a need for more high-quality research evaluating the use of IOUS in FCD and comparing it to other intraoperative imaging modalities.

Focal cortical dysplasia II caused by brain somatic mutation of IRS-1 is associated with ERK signaling pathway activation.

Somatic mutations have been identified in 10% to 63% of focal cortical dysplasia type II samples, primarily linked to the mTOR pathway. When the causative genetic mutations are not identified, this opens the possibility of discovering new pathogenic genes or pathways that could be contributing to the condition. In our previous study, we identified a novel candidate pathogenic somatic variant of IRS-1 c.1791dupG in the brain tissue of a child with focal cortical dysplasia type II. This study further explored the variant's role in causing type II focal cortical dysplasia through in vitro overexpression in 293T and SH-SY5Y cells and in vivo evaluation via in utero electroporation in fetal brains, assessing effects on neuronal migration, morphology, and network integrity. It was found that the mutant IRS-1 variant led to hyperactivity of p-ERK, increased cell volume, and was predominantly associated with the MAPK signaling pathway. In vivo, the IRS-1 c.1791dupG variant induced abnormal neuron migration, cytomegaly, and network hyperexcitability. Notably, the ERK inhibitor GDC-0994, rather than the mTOR inhibitor rapamycin, effectively rescued the neuronal defects. This study directly highlighted the ERK signaling pathway's role in the pathogenesis of focal cortical dysplasia II and provided a new therapeutic target for cases of focal cortical dysplasia II that are not treatable by rapamycin analogs.

[Focal cortical dysplasia: visual assessment of MRI and MR morphometry data]. / Fokal'naya kortikal'naya displaziya: sravnitel'nyi analiz vizual'noi otsenki dannykh magnitno-rezonansnoi tomografii i magnitno-rezonansnoi morfometrii.

OBJECTIVE: Assessing the diagnostic significance of MR morphometry in determining the localization of focal cortical dysplasias (FCD). MATERIAL AND METHODS: The study included 13 children after surgery for drug-resistant epilepsy caused by FCD type II and stable postoperative remission of seizures (Engel class IA, median follow-up 56 months). We analyzed the results of independent expert assessment of native MR data by three radiologists (HARNESS protocol) and MR morphometry data regarding accuracy of FCD localization. We considered 2 indicators, i.e. local cortical thickening and gray-white matter blurring. RESULTS: FCD detection rate was higher after MR morphometry compared to visual analysis of native MR data using the HARNESS protocol. MR morphometry also makes it possible to more often identify gray-white matter blurring as a sign often missed by radiologists (p<0.05). CONCLUSION: MR morphometry is an additional non-invasive method for assessing the localization of FCD.

[Differential diagnosis of epileptogenic substrates of unknown etiology using a modification of the routine MRI protocol]. / Differentsial'naya diagnostika epileptogennykh substratov neyasnoi etiologii s pomoshch'yu modifikatsii protokola standartnoi MRT.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Identification and treatment of surgically-remediable causes of infantile epileptic spasms syndrome.

INTRODUCTION: Infantile epileptic spasms syndrome (IESS) is a common developmental and epileptic encephalopathy with poor long-term outcomes. A substantial proportion of patients with IESS have a potentially surgically remediable etiology. Despite this, epilepsy surgery is underutilized in this patient group. Some surgically remediable etiologies, such as focal cortical dysplasia and malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), are under-diagnosed in infants and young children. Even when a surgically remediable etiology is recognised, for example, tuberous sclerosis or focal encephalomalacia, epilepsy surgery may be delayed or not considered due to diffuse EEG changes, unclear surgical boundaries, or concerns about operating in this age group. AREAS COVERED: In this review, the authors discuss the common surgically remediable etiologies of IESS, their clinical and EEG features, and the imaging techniques that can aid in their diagnosis. They then describe the surgical approaches used in this patient group, and the beneficial impact that early epilepsy surgery can have on developing brain networks. EXPERT OPINION: Epilepsy surgery remains underutilized even when a potentially surgically remediable cause is recognized. Overcoming the barriers that result in under-recognition of surgical candidates and underutilization of epilepsy surgery in IESS will improve long-term seizure and developmental outcomes.

Surgical outcomes in children with drug-resistant epilepsy and hippocampal sclerosis.

BACKGROUND: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. OBJECTIVE: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. METHODS: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. RESULTS: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. CONCLUSIONS: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.