Focal Cortical Dysplasia Cases Research Articles

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.

Acquisition and Analysis of Excised Neocortex from Pediatric Patients with Focal Cortical Dysplasia Using Mesoscale Diffusion MRI.

Non-invasive classification of focal cortical dysplasia (FCD) subtypes remains challenging from a radiology perspective. Quantitative imaging biomarkers (QIBs) have the potential to distinguish subtypes that lack pathognomonic features and might help in defining the extent of abnormal connectivity associated with each FCD subtype. A key motivation of diagnostic imaging is to improve the localization of a "lesion" that can guide the surgical resection of affected tissue, which is thought to cause seizures. Conversely, surgical resections to eliminate or reduce seizures provided unique opportunities to develop magnetic resonance imaging (MRI)-based QIBs by affording long scan times to evaluate multiple contrast mechanisms at the mesoscale (0.5 mm isotropic voxel dimensions). Using ex vivo hybrid diffusion tensor imaging on a 9.4 T MRI scanner, the grey to white matter ratio of scalar indices was lower in the resected middle temporal gyrus (MTG) of two neuropathologically confirmed cases of FCD compared to non-diseased control postmortem fixed temporal lobes. In contrast, fractional anisotropy was increased within FCD and also adjacent white matter tracts. Connectivity (streamlines/mm3) in the MTG was higher in FCD, suggesting that an altered connectivity at the lesion locus can potentially provide a tangible QIB to distinguish and characterize FCD abnormalities. However, as illustrated here, a major challenge for a robust tractographical comparison lies in the considerable differences in the ex vivo processing of bioptic and postmortem samples. Mesoscale diffusion MRI has the potential to better define and characterize epileptic tissues obtained from surgical resection to advance our understanding of disease etiology and treatment.

Surgical planning, histopathology findings and postoperative outcome in MR-negative extra-temporal epilepsy using intracranial EEG, functional imaging, magnetoencephalography, neuronavigation and intraoperative MRI

ObjectiveMRI-negative drug-resistant epilepsy presents a challenge when it comes to surgical planning, and surgical outcome is worse than in cases with an identified lesion. Although increasing implementation of more powerful MRI scanners and artificial intelligence has led to the detection of previously unrecognizable lesions, in some cases even postoperative pathological evaluation of electrographically epileptogenic zones shows no structural alterations. While in temporal lobe epilepsy a standardized resection approach can usually be performed, the surgical management of extra-temporal lesions is always individual. Here we present a strategy for treating patients with extra-temporal MRI-negative epilepsy focus and report our histological findings and patient outcome. MethodsPatients undergoing epilepsy surgery in the Department of Neurosurgery at the University Hospital Erlangen between 2012 and 2020 were included in the study. Inclusion criteria were: (1) failure to identify a structural lesion on preoperative high-resolution 3 Tesla MRI with a standardized epilepsy protocol and (2) preoperative intracranial EEG (iEEG) diagnostics. ResultsWe identified 8 patients corresponding to the inclusion criteria. Second look MRI analysis by an experienced neuroradiologist including the most recent analysis algorithm utilized in our clinic revealed a possible lesion in two patients. One of the patients with a clear focal cortical dysplasia (FCD) finding on a second look was excluded from further analysis. Of the other 7 patients, in one patient iEEG was performed with subdural electrodes, whereas the other 6 were evaluated with depth electrodes. MEG was performed preoperatively in all but one patient. An MEG focus was implemented in resection planning in 3 patients. FDG PET was performed in all, but only implemented in one patient. Histopathological evaluation revealed one non-lesional case, 4 cases of FCD and 2 cases with mild developmental malformation. All patients were free from permanent neurological deficits and presented with Engel 1A or 1B outcome on the last follow-up. ConclusionWe demonstrate that extra-temporal MRI-negative epilepsy can be treated successfully provided an extensive preoperative planning is performed. The most important diagnostic was stereo-EEG, whereas additional data from MEG was helpful and FDG PET was rarely useful in our cohort.

Unexpected Effect of IL-1β on the Function of GABAA Receptors in Pediatric Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) type II is an epileptogenic malformation of the neocortex, as well as a leading cause of drug-resistant focal epilepsy in children and young adults. The synaptic dysfunctions leading to intractable seizures in this disease appear to have a tight relationship with the immaturity of GABAergic neurotransmission. The likely outcome would include hyperpolarizing responses upon activation of GABAARs. In addition, it is well-established that neuroinflammation plays a relevant role in the pathogenesis of FCD type II. Here, we investigated whether IL-1β, a prototypical pro-inflammatory cytokine, can influence GABAergic neurotransmission in FCD brain tissues. To this purpose, we carried out electrophysiological recordings on Xenopus oocytes transplanted with human tissues and performed a transcriptomics analysis. We found that IL-1β decreases the GABA currents amplitude in tissue samples from adult individuals, while it potentiates GABA responses in samples from pediatric cases. Interestingly, these cases of pediatric FCD were characterized by a more depolarized EGABA and an altered transcriptomics profile, that revealed an up-regulation of chloride cotransporter NKCC1 and IL-1β. Altogether, these results suggest that the neuroinflammatory processes and altered chloride homeostasis can contribute together to increase the brain excitability underlying the occurrence of seizures in these children.

Safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy in the treatment of drug-resistant epilepsy

Objective: To investigate the safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the treatment of drug-resistant epilepsy. Methods: Patients with drug-resistant epilepsy treated with a domestic MRgLITT system in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University from October 2020 to April 2021 were prospectively enrolled. The damage volume ratio was assessed immediately after surgery, and perioperative complications were recorded and followed up. The clinical safety and short-term efficacy were evaluated using the Engel classification. Results: A total of 22 patients were included, including 12 males and 10 females, aged from 3 to 45 years old [(24±13) years]. There were 5 cases of medial temporal lobe epilepsy (MTLE), 3 cases of hypothalamic hamartoma (HH), 7 cases of focal cortical dysplasia (FCD), and 7 cases of other types, respectively. The mean operation time and blood loss was (173±49) min and (3.7±1.6) ml. The postoperative length of hospital stay was (5.5±1.8) days, and the average damage volume ratio was 92.6%. Among them, only 2 patients (FCD of the parietal lobe) showed transient contralateral limb weakness, without any serious complications such as symptomatic intracranial hemorrhage and cerebral infarction. The follow-up time was 14 to 168 days. There were 13 Engel class Ⅰ cases (59.1%), 2 Engel class Ⅱ cases (9.1%), 2 Engel class Ⅲ cases (9.1%) and 5 Engel class Ⅳ cases (22.7%), respectively. Short-term incident-free rates were MTLE 5/5and FCD4/7, respectively. Conclusion: Domestic MRgLITT system is stable, reliable and safe in the treatment of drug-refractory epilepsy, and has better short-term efficacy in MTLE and FCD patients.

Interpretation of epileptogenic lesions: Its limitations in medico-legal experts’ reports

Focal cortical dysplasia (FCD) is the third leading cause of pharmacoresistant epilepsy diagnosed by epilepsy surgery and is a common malformation of cerebral cortical development. It is marked by abnormalities of cortical lamination, neuronal differentiation, and neuronal maturation. These epileptogenic lesions have proven anatomical and clinical correlations. Only one case of incidental FCD had been described. Incidental findings highlight infrequent lesions that go unnoticed when a person is alive. It can be an important finding for pathologists as well as for the forensic expert. The difficulty of the expertise will be in cases where these incidental lesions are known to cause symptoms that may be the cause of death. We wish to argue if they can be used in a medico-legal procedure. We report two cases demonstrating discrepancies between anatomical and clinical features, which should encourage the medical expert to use caution when interpreting neuropathological reports. La dysplasie corticale focale (DCF) est la troisième cause d’épilepsie pharmacorésistante diagnostiquée par chirurgie de l’épilepsie. Il s’agit d’une malformation courante du développement cortical cérébral. Elle est marquée par des anomalies de la stratification corticale, de la différenciation neuronale et de la maturation neuronale. Ces lésions épileptogènes ont des corrélations anatomiques et cliniques prouvées. Un seul cas de DCF de découverte fortuite à l’imagerie a été décrit dans la littérature. Ces découvertes fortuites mettent en évidence des lésions peu fréquentes qui passent inaperçues lorsqu’une personne est en vie. Or, ces lésions sont une découverte importante pour les pathologistes ainsi que pour l’expert médico-légal. La difficulté de l’expertise se situera dans les cas où ces lésions incidentelles sont connues pour provoquer des symptômes pouvant être la cause du décès. Nous souhaitons discuter s’ils peuvent être utilisés dans une procédure médico-légale. Nous rapportons deux cas démontrant des divergences entre les caractéristiques anatomiques et cliniques, ce qui devrait inciter l’expert médical à faire preuve de prudence dans l’interprétation des rapports neuropathologiques.

GATOR1-related focal cortical dysplasia in epilepsy surgery patients and their families: A possible gradient in severity?

Variants of GATOR1-genes represent a recognised cause of focal cortical dysplasia (FCD), the most common structural aetiology in paediatric drug-resistant focal epilepsy. Reports on familial cases of GATOR1-associated FCD are limited, especially with respect to epilepsy surgery outcomes. We present phenotypical manifestations of four unrelated patients with drug-resistant focal epilepsy, FCD and a first-degree relative with epilepsy. All patients underwent targeted gene panel sequencing as a part of the presurgical work up. Literature search was performed to compare our findings to previously published cases. The children (probands) had a more severe phenotype than their parents, including drug-resistant epilepsy and developmental delay, and they failed to achieve seizure freedom post-surgically. All patients had histopathologically confirmed FCD (types IIa, IIb, Ia). In Patient 1 and her affected father, we detected a known pathogenic NPRL2 variant. In patients 2 and 3 and their affected parents, we found novel likely pathogenic germline DEPDC5 variants. In family 4, we detected a novel variant in NPRL3. We identified 15 additional cases who underwent epilepsy surgery for GATOR1-associated FCD, with a positive family history of epilepsy in the literature; in 8/13 tested, the variant was inherited from an asymptomatic parent. The presented cases displayed a severity gradient in phenotype with children more severely affected than the parents. Although patients with GATOR1-associated FCD are considered good surgical candidates, post-surgical seizure outcome was poor in our familial cases, suggesting that accurate identification of the epileptogenic zone may be more challenging in this subgroup of patients.

The added value of double inversion recovery magnetic resonance imaging of the brain in evaluation of patients with epilepsy

BACKGROUND: The double inversion recovery (DIR) pulse sequence was introduced several years ago and since that it grew important value in clinical neuroimaging. We aimed to assess the added value of double inversion recovery in evaluation of epileptic patients.AIM OF THE WORK:The aim of this study is to assess the added value of double inversion recovery MRI to the basic brain MRI protocols in assessment of patients with epilepsy.PATIENTS AND METHODS:Twenty five patients presented with epilepsy were examined by MRI. Examination was done using 3T MRI machines including conventional MRI epilepsy protocol sequences (T1, T2 & FLAIR) as well as double inversion recovery.RESULTS:In mesial temporal sclerosis, the measured contrast parameters (SNR, CR, CNR & AI) were found to be significantly higher in the DIR than in the FLAIR and T2 sequences.In the cases of focal cortical dysplasia, significantly higher CNR and AI in the DIR than in the T2 and FLAIR. Also DIR showed higher detection of the increased cortical thickness and cortical signal intensity than the T2 and FLAIR sequences.In tuberous sclerosis cases, the DIR showed higher visibility of the lesions than the T2 and FLAIR. Also DIR showed higher ability to detected grey-white matters junction blurring.CONCLUSIONS:Our study concluded that the greatest value of the double inversion recovery sequence is its higher ability in detecting multiple characteristics of the lesions in a one sequence.

Enhanced MR Conspicuity of Type IIb Focal Cortical Dysplasia by T1WI With CHESS

Focal cortical dysplasia (FCD) is a congenital developmental anomaly that is one of the leading causes of refractory epilepsy. MRI is an essential examination and T1WI, T2WI, and FLAIR images are commonly used MR sequences for delineating FCD.1 However, these MRI findings are often insufficiently clear. We experienced two FCD cases that were much better visualized by using T1WI with chemical shift selective (CHESS) than with T2WI and FLAIR images. CHESS is the most frequently used fat suppression pulse in clinical practice. We report two cases in which CHESS clearly demonstrated FCD, and compare the cases9 pathology and MRI findings.

Surgical histopathologic findings of 232 Chinese children cases with drug-resistant seizures.

ObjectivesThe drug‐resistant seizures are characterized by frequent and severe onset of seizures in childhood. There is only little literature had extensively explored the types of pathological brain damage in Chinese children cases. The present study aims to investigate the histopathologic findings and seizure outcomes of drug‐resistant seizures in cases of 0–14‐year‐old children.Materials and MethodsAbout 232 children cases were retrospectively who underwent epilepsy surgery. The medical records, onset age, age of surgery, disease course, seizure type, pathological reports, and seizure outcomes of these patients were retrospectively analyzed.ResultsThe most common categories were malformations of cortical development (focal cortical dysplasia (FCD) was the most common type (94.36%, 67/71), found in 30.60% of the patients, tumors in 18.11%, glial scar in 12.50%, and encephalitis in 11.63%). It was found that the effective seizure outcome of FCD cases with shorter duration of epilepsy (<2 years, 87.23%) was better than that with longer duration (≥2 years, 60.00%) and the difference was statistically significant (χ 2 = 4.76, p < .05). Patients with FCD I, FCD II, and tumor showed the relatively better postsurgical seizure outcome than patients with other pathological types.ConclusionThe malformations of cortical development (MCD) (most FCD) were the most common pathological type for children cases in China with drug‐resistant seizures. It was speculated further that the FCD patients with shorter duration of epilepsy before surgery seem to have a higher ratio of being seizure‐free after surgery.

Case of focal cortical dysplasia in a tertiary rural hospital

Case of focal cortical dysplasia in a tertiary rural hospital

Neuro-Edu-Techno (NET) Approach in Studies on Educational Therapy for Developmental Delays: A Case of Focal Cortical Dysplasia

Focal cortical dysplasia (FCD) may vary in size and be located in any area of the human brain. In general, FCD causes epilepsy and it is usually associated with mental retardation. Even in case of epilepsy various types of treatment are identified, there is no complete educational therapy for developmental delays caused by FCD. Moreover, there are no works that synthetically discuss the possibilities of supporting such therapy by technology-based solutions. Method: Here, we investigate this issue using a systematic literature review. Results: Despite the fact that we were dealing with the lack of studies on technology-based educational therapy for students with cognitive problems due to FCD, we point out several potential benefits of this type of assistance. Discussion and conclusions: Our study clearly demonstrates that technology may strongly enhance educational therapy for developmental delays caused by focal cortical dysplasia and that there is a need for further neuro-edu-techno (NET) studies on this topic.

Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients.

Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) (n = 1), Tuberous sclerosis complex (TSC) (n = 2), Focal cortical dysplasia (FCD) (n = 4), and Rasmussen encephalitis (RE) (n = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set. More than 85 percent of the CD45+ cells isolated from resected RE brain tissue comprised T cells; by contrast NK cells and myeloid cells constituted 80–95 percent of the CD45+ cells isolated from the TSC and the FCD brain specimens. Three populations of myeloid cells made up >50 percent of all of the myeloid cells in all of the samples of which a population of HLA-DR+ CD11b+ CD4− cells comprised the vast majority of myeloid cells in the BIL fractions from the FCD and TSC cases. CD45RA+ HLA-DR− CD11b+ CD16+ NK cells constituted the major population of NK cells in the blood from all of the cases. This subset also comprised the majority of NK cells in BILs from the resected RE and HME brain tissue, whereas NK cells defined as CD45RA− HLA-DR+ CD11b− CD16− cells comprised 86–96 percent of the NK cells isolated from the FCD and TSC brain tissue. Thirteen different subsets of CD4 and CD8 αβ T cells and γδ T cells accounted for over 80% of the CD3+ T cells in all of the BIL and PBMC samples. At least 90 percent of the T cells in the RE BILs, 80 percent of the T cells in the HME BILs and 40–66 percent in the TSC and FCD BILs comprised activated antigen-experienced (CD45RO+ HLA-DR+ CD69+) T cells. We conclude that even in cases where there is no evidence for an infection or an immune disorder, activated peripheral immune cells may be present in epileptogenic areas of the brain, possibly in response to seizure-driven brain inflammation.

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.

Comparative analysis of cytokine/chemokine regulatory networks in patients with hippocampal sclerosis (HS) and focal cortical dysplasia (FCD)

Experimental and clinical evidence have demonstrated aberrant expression of cytokines/chemokines and their receptors in patients with hippocampal sclerosis (HS) and focal cortical dysplasia (FCD). However, there is limited information regarding the modulation of cytokine/chemokine-regulatory networks, suggesting contribution of miRNAs and downstream transcription factors/receptors in these pathologies. Hence, we studied the levels of multiple inflammatory mediators (IL1β, IL1Ra, IL6, IL10, CCL3, CCL4, TNFα and VEGF) along with transcriptional changes of nine related miRNAs and mRNA levels of downstream effectors of significantly altered cytokines/chemokines in brain tissues obtained from patients with HS (n = 26) and FCD (n = 26). Up regulation of IL1β, IL6, CCL3, CCL4, STAT-3, C-JUN and CCR5, and down regulation of IL 10 were observed in both HS and FCD cases (p < 0.05). CCR5 was significantly up regulated in FCD as compared to HS (p < 0.001). Both, HS and FCD presented decreased miR-223-3p, miR-21-5p, miR-204-5p and let-7a-5p and increased miR-155-5p expression (p < 0.05). As compared to HS, miR-204-5p (upstream to CCR5 and IL1β) and miR-195-5p (upstream to CCL4) were significantly decreased in FCD patients (p < 0.01). Our results suggest differential alteration of cytokine/chemokine regulatory networks in HS and FCD and provide a rationale for developing pathology specific therapy.

Neuropathologic findings in intractable epilepsy: a clinicopathologic analysis of 822 cases

Objective: To investigate the clinicopathologic characteristics of intractable epilepsy. Methods: Based on the classification criteria proposed by the International League Against Epilepsy (ILAE), a retrospective analysis of the pathological characteristics was done in 822 patients who underwent epilepsy surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to December 2012. Results: The mean age of epilepsy onset was 9.9 years, mean duration of epilepsy was 11.9 years. Complex partial seizures were the main presenting features. Histopathological study showed 33 cases (4.01%) with mild forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20 cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without significant pathological changes, 5 gyral malformations and 2 hamartoma). Among the 690 FCD cases, 106 were FCD typeⅠ, 91 were FCD typeⅡ and 493 were FCDⅢ(Ⅲa: 160, Ⅲb: 106, Ⅲc: 26 and Ⅲd: 201). Conclusions: FCDⅢd is the most common histopathological subtype causing intractable epilepsy, mainly due to focal hypoxia/ischemia in the perinatal period, which results in scarring of local brain tissue; this is followed by other isolated forms of FCD (FCDⅠand FCDⅡ), and then FCD Ⅲa and FCD Ⅲb. The reason to distinguish isolated forms of FCD (types Ⅰ and Ⅱ) from FCD Ⅲ and to subclassify FCD Ⅲ is to allow better definition of cortical dyslamination. Therefore, the pathogenic factors of intractable epilepsy can be grouped in greater details, and facilitate the diagnosis and potential curative treatment of intractable epilepsy.

A dehabilitating case of focal cortical dysplasia

A dehabilitating case of focal cortical dysplasia

Increased subcortical oligodendroglia‐like cells in pharmacoresistant focal epilepsy in children correlate with extensive epileptogenic zones

Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy. We examined the surgical specimens from 30 children who underwent epilepsy surgery (1.8- to 16.9-years-old; mean age 9.7 years). Immunohistochemical assays of OLCs were performed using Olig2, which is a marker of OLC. OLC populations in three sites (gray matter, gray-white matter junction, and white matter) were counted. We also performed immunohistochemical staining with neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) for neuronal and astroglial markers, respectively. NeuN- and GFAP-positive cells were distinguished from OLCs. OLC results were compared with seizure types, scalp and intracranial video-electroencephalography (EEG), magnetic resonance imaging (MRI), surgical resection area, histopathologic diagnosis, and seizure outcome. Histopathologic diagnosis consisted of 14 cases of focal cortical dysplasia (FCD; type I; 4, type II; 9, type III; one); 6 cases of oligodendrogliosis; 6 cases of astrocytic gliosis; 2 cases of hyaline protoplasmic astrocytopathy; and 2 cases of tuberous sclerosis. Fifteen children (50%) underwent multiple-lobe resections after intracranial video-EEG. There was a positive correlation between the number of resected electrodes and the OLC population in the white matter (correlation coefficient 0.581, p = 0.001) and at the gray-white matter junction- (correlation coefficient 0.426, p = 0.027). OLC populations in both areas were increased significantly in nine children with epileptic spasms (ES) (gray-white matter junction [p = 0.021] and white matter [p = 0.025]), and nine nonfocal ictal scalp EEG findings (gray-white matter junction [p = 0.04] and white matter [p = 0.042]). The OLC population in white matter was significantly increased in children with 11 nonfocal interictal scalp EEG findings (p = 0.01), with 15 multiple-lobe resections (p = 0.028). Pharmacoresistant epilepsy in children with increased OLCs presented with nonfocal epileptiform discharges on scalp EEG and ES, and they required multiple-lobe resections. We found increased populations of subcortical OLCs in the extensive epileptogenic zone.

A case of episodic derealisation in focal cortical dysplasia: First looks at the whole elephant?

Derealisation remains a bewildering and obscure phenomenological entity with shifting identities on the dissociation spectrum of disorders. A consensus seems to have emerged that the symptom can be produced by a variety of agents which finally act through a common pathway whose identity remains elusive and whose components have thus far only emerged piecemeal. Temporal lobe dysfunction, a covert epileptogenic process and aberrations within a network comprising the amygdala, the anterior cingulate and the prefrontal cortices have all been implicated, however independently none account holistically for the peculiar phenomenology of derealisation. We present a case of focal cortical dysplasia of the right supramarginal gyrus, who reported with three distinct symptoms – panic episodes, a heightening of baseline anxiety and recurrent derealisation, all of which responded well to antiepileptic drugs. This represents the first case with evidence of dysfunction in all areas of the heteromodal association cortex (HASC), a neural network responsible for integration of sensory input and required to understand the significance of events and objects in the external environment. Derangements in the HASC have produced non-modality specific neuropsychiatric deficits, and the component anatomy can account well for the aberrations in emotion, perception and memory characteristic of derealisation. Collectively, the model provides a credible basis with which to explain the curious symptoms encountered in derealisation and provides a promising line of enquiry.

Clinicopathologic study of intractable epilepsy-related encephalitis

To investigate the clinicopathologic features of intractable epilepsy related encephalitis. The clinical and pathologic findings of 15 cases of intractable epilepsy after functional neurosurgical treatment were reviewed and analyzed retrospectively. All patients, including four male and 11 female, had medically intractable epilepsy. The mean age of onset for seizure was 5.3 years (1-15 years) and the disease duration was 4.7 years (0.5-15 years). A definite past history was identified in 11 patients, including viral encephalitis in nine patients, anoxia in utero and head trauma in one patient respectively. The extent and sites of involvement were different, including single cerebral hemisphere diffusely in five cases, multiple lobes in seven cases, and single lobe in three cases. Temporal lobe was involved in 13 cases, frontal lobe in eight, parietal lobe in eight, occipital lobe in seven, and insular lobe in four. Microscopically, all cases were characterized by perivascular inflammatory cells infiltration in the subarachnoid space. The focal cerebral cortex showed obvious atrophy with various degrees of the neuronal loss and glial proliferation, eventually leading to glial scar formation. In addition, microglia nodules, lymphatic cuff and neuronophagia were also observed. Seven cases of focal cortical dysplasia were identified among the 11 cases with adequate perilesional cerebral cortex. Hippocampus sclerosis was found in two cases. Intranuclear inclusions were seen in six cases, and these were immunopositive of cytomegalovirus-late antigen, and three cases also showed multinucleated giant cells and calcifications. Encephalitis is one of the common causes of refractory epilepsy, and may result in refractory epilepsy as a sequel.