Immunohistochemical expression of fibroblast growth factor (FGF)‐2 in epilepsy‐associated malformations of cortical development (MCDs)

To elucidate the biological significance of dysplastic cells in malformations of cortical development, an immunohistochemical study was performed to investigate fibroblast growth factor‐2 (FGF‐2) expression in corticectomy specimens from epilepsy patients, including focal cortical dysplasia (FCD) with balloon cells (BCs) (n = 4; age/sex = 2M, 14F, 24M, 45M), tubers of tuberous sclerosis complex (TSC‐tubers) (n = 2; 1F, 3F), FCD without BCs (n = 3; 23F, 23M, 25M), and gliotic lesions (n = 3; 12M, 25M, 29M). The nucleus and/or cytoplasm of astrocytes in all cases examined were positive for FGF‐2; however, FGF‐2 immunoreactivity was not detected in oligodendroglial cells. In all dysplastic lesions, FGF‐2 was detected in the astrocytic nuclei, and cytoplasm and/or nuclei of BCs. Dysplastic neurons (DNs) in FCD with BCs and TSC‐tubers were variably positive for FGF‐2 in the cytoplasm, but FGF‐2 was not detected in the neurons of FCD without BCs. The number of FGF‐2 immunoreactive cells (FGF‐2‐IR%) in FCD with BCs (46.0 ± 4.1%) was higher than that in FCD without BCs (19.8 ± 3.1%) and gliotic lesions (19.5 ± 3.3%) with statistical significance (P < 0.001). These results, together with previous reports showing FGF‐2 expression in neuroblasts and glioblasts in human fetal brain, and mainly in astrocytes in adult brain, suggest that FGF‐2 expression in MCDs reflects incomplete differentiation and maturation of dysplastic cells, and that FGF‐2‐IR% is associated with histological subtypes of MCD, reflecting the timing of insults underlying the pathogenesis of each disorder.     

Expression patterns of glial fibrillary acidic protein (GFAP)-delta in epilepsy-associated lesional pathologies

Aims: Glial fibrillary acidic protein (GFAP)‐δ is a novel isoform that differs in its C‐terminal sequence from other GFAP isoforms. Previous studies suggest restriction of expression to the subpial layer, subventricular zone and the subgranular zone astrocytes, with an absence in pathological conditions causing reactive gliosis. GFAP‐δ is speculated to have roles in regulation of astrocyte size and motility and a subpopulation of GFAP‐δ‐positive glia may be multipotent stem cells. The aim of this study was to investigate its expression in common causes of lesion‐related refractory epilepsy. Methods: Hippocampal sclerosis (HS), focal cortical dysplasia (FCD) type IIB, cortical tuberous sclerosis (TSC) lesions, gangliogliomas, grey matter heterotopias and hemimegalencephaly from a wide age range of patients using both surgical and post mortem tissue specimens were studied. Results: GFAP‐δ expression was observed in CA4 and CA1 astrocytes in HS with less frequent labelling in the granule cell layer, even where granule cell dispersion was present. No significant labelling was noted in the subiculum in HS cases or in any subfields in non‐HS epilepsy cases. Balloon cells in FCDIIB and hemimegalencephaly, giant cells in TSC and the astrocytic component of gangliogliomas showed immunoreactivity, colocalizing with conventional GFAP. No neuronal expression for GFAP‐δ was seen in any of the pathologies. Quantitative analysis in 10 FCDIIB and five TSC cases revealed greater numbers of GFAP‐δ‐positive balloon cells than conventional GFAP. There was no GFAP‐δ expression within nodular heterotopia. Conclusions: GFAP‐δ expression patterns in HS overall appears to mirror regional reactive gliosis. It is a useful marker for the demonstration of balloon cells in FCD and TSC, which may be relevant to their abnormal size and localization. The lack of GFAP‐δ within heterotopia supports their composition from cells destined for deeper cortical layers.     

Tuberous sclerosis complex coexistent with hippocampal sclerosis

Tuberous sclerosis and hippocampal sclerosis are both well-defined entities associated with medically intractable epilepsy. To our knowledge, there has been only one prior case of these two pathologies being co-existent. We report a 7-month-old boy who presented with intractable seizures at 2 months of age. MRI studies showed diffuse volume loss in the brain with bilateral, multiple cortical tubers and subcortical migration abnormalities. Subependymal nodules were noted without subependymal giant cell astrocytoma. Genetic testing revealed TSC2 and PRD gene deletions. Histopathology of the hippocampus showed CA1 sclerosis marked by loss of neurons in the CA1 region. Sections from the temporal, parietal and occipital lobes showed multiple cortical tubers characterized by cortical architectural disorganization, gliosis, calcifications and increased number of large balloon cells. Focal white matter balloon cells and spongiform changes were also present. The patient underwent resection of the right fronto-parietal lobe and a subsequent resection of the right temporal, parietal and occipital lobes. The patient is free of seizures on anti-epileptic medication 69 months after surgery. Although hippocampal sclerosis is well documented to be associated with coexistent focal cortical dysplasia, the specific co-existence of cortical tubers and hippocampal sclerosis appears to be rare.     

Activation of leukocyte immunoglobulin-like receptor B2 signaling pathway in cortical lesions of pediatric patients with focal cortical dysplasia type IIb and tuberous sclerosis complex

BackgroundsFocal cortical dysplasia type IIb (FCD IIb) and tuberous sclerosis complex (TSC) are very frequently associated with epilepsy in pediatric patients. Human leukocyte immunoglobulin-like receptor B2 (LILRB2) participates in the process of neurite growth, synaptic plasticity, and inflammatory reaction, suggesting a potential role of LILRB2 in epilepsy. However, little is known about the distribution and expression of LILRB2 in cortical lesions of FCD IIb and cortical tubers of TSC.MethodsIn this study, we have described the distribution and expression of LILRB2 signaling pathway in cortical lesions of pediatric patients with FCD IIb (n = 15) and TSC (n = 12) relative to age-matched autopsy control samples (CTX, n = 10), respectively. The protein levels of LILRB2 pathway molecules were assessed by western blotting and immunohistochemistry. The expression pattern was investigated by immunohistochemistry and double labeling experiment. Spearman correlation analysis to explore the correlation between LILRB2 protein level and seizure frequency.ResultsThe protein levels of LILRB2 and its downstream molecules POSH, SHROOM3, ROCK1, ROCK2 were increased in cortices of patients compared to CTX. Protein levels of LILRB2 negatively correlated with the frequency of seizures in FCD IIb and TSC patients, respectively. Moreover, all LILRB2 pathway molecules were strongly expressed in dysmorphic neurons, balloon cells, and giant cells, LILRB2 co-localized with neuron marker and astrocyte marker.ConclusionTaken together, the special expression patterns of LILRB2 signaling pathway in cortical lesions of FCD IIb and TSC implies that it may be involved in the process of epilepsy.     

Expression of tuberin and hamartin in tuberous sclerosis complex-associated and sporadic cortical dysplasia of Taylor's balloon cell type

Focal cortical dysplasia (FCD) type IIB is a malformation of cortical development characterized by presence of balloon cells. These cells share phenotypic features of giant cells found in tuberous sclerosis complex (TSC), but the relationship between FCD type IIB and TSC is not well established. TSC is an autosomal dominant disorder caused by mutation in either of two genes: TSC1, encoding hamartin, and TSC2, encoding tuberin. Both proteins form a complex inhibiting mTOR signalling pathway and thus regulate cell size and proliferation. In this study, tuberin and hamartin expression was evaluated under a confocal microscope in six cases of Taylor's balloon cell type FCD. Three patients met the clinical criteria for TSC. In three other patients, TSC was excluded based on a panel of clinical and radiological examinations. Additionally, two cases of FCD type I and 3 samples of normal brain tissue were used as a reference group. We found loss of tuberin and hamartin expression in FCD type IIB lesions from patients with TSC. In sporadic FCD type IIB cases, only a few tuberin and hamartin positive cells were detected in the white-grey matter junction and in deeper parts of the white matter. Cortical balloon cells showed loss of both tuberin and hamartin. In contrast, the expression of tuberin and hamartin in FCD type I samples was strong, similarly to normal brain tissue. In conclusion, loss of TSC1 and TSC2 products expression in balloon cells of both cortical dysplasia type IIB in TSC-related and sporadic patients suggests that FCD type IIB may represent the focal form of TSC.     

Widespread frontal lobe cortical dysplasia or partial hemimegalencephaly: a continuum of the spectrum

Focal cortical dysplasia (FCD) type II and hemimegalencephaly (HME) are currently considered as a continuum of pathology, the most important distinction being the extent or the size/volume of the lesion. While partial HME involving the posterior cortex has been well described, we present an unusual case with a dysplastic lesion of the whole frontal lobe. A 17‐year‐old boy had focal seizures from the age of nine years. Apart from diminished right‐hand dexterity, his neurological and cognitive status were unremarkable. The course of his epilepsy exhibited a relapsing‐remitting pattern, with prolonged periods of remission. Imaging showed dysplastic left frontal lobe (including paracentral lobule) thickened cortex with an abnormal gyration pattern resembling polymicrogyria, as well as dystrophic calcifications and hypodensity scattered throughout the white matter. This patient represents an intermediate case within the FCD type II/HME spectrum. Localization of the lesion in the frontal lobe as well as clinical characteristics (childhood onset, relapsing‐remitting epilepsy, without hemiparesis and overt cognitive impairment) are more consistent with FCD type II, while a range of MRI features is shared between HME and FCD type II.     

Focal cortical dysplasia coexisting with diffuse astrocytoma in childhood: A case report and reappraisal of the glial component in archival FCD cases

We report a rare case of focal cortical dysplasia (FCD) concurring with diffuse astrocytoma and arachnoid cyst, and also re‐evaluate the glial component in archival FCD cases for the differential diagnosis of diffuse gliomas. A 7‐year‐old boy with a 9‐month history of psychomotor seizures disclosed a hyperintense area accompanied by a cystic lesion in the left temporal lobe on MRI. The surgical specimen displayed dyslamination of the cortices and ectopic neurons in the white matter, associated with dysmorphic neurons, indicating FCD type IIA. Additionally, the lesion showed diffuse proliferation and infiltration of glial cells, immunopositive for infiltrating glioma markers (nestin, doublecortin, MAP‐2e) and p53, and MIB‐1 index was 2.0%. These findings indicated coexisting diffuse astrocytoma. Coexistence of diffuse glioma with FCD is unusual, but we often notice increased population of small glial cells in FCD lesions. Re‐evaluation of archival FCD cases with diverse markers revealed that reactive microglia significantly proliferate in the white matter lesions. Therefore, a careful pathological assessment has to be made to define a rare case of diffuse glioma occurring in FCD.     

Characteristic expression of p57/Kip2 in balloon cells in focal cortical dysplasia

Balloon cells are a pathognomonic cellular feature of various cortical malformations, including focal cortical dysplasia type IIb (FCD IIb), cortical tubers of tuberous sclerosis (TSC) and hemimegalencephaly (HME). In the present study, we investigated the immunohistochemical expression of p57/Kip2, a member of the Cip/Kip family of cyclin‐dependent kinase inhibitory proteins, in balloon cells in surgical specimens taken from 26, 17 and six patients with FCD IIb, TSC and HME, respectively. Characteristic dot‐like reactivity with a faint, intense, reticular and process‐like pattern was confined to the proximal portion of the cytoplasmic processes of the cells. Immunoelectron microscopy revealed the p57/Kip2 reactivity on intermediate filaments in the proximal portion of the processes. The immunohistochemical profile appeared similar to that of CD34; however, a double immunofluorescence study demonstrated that no cells showed reactivity for both p57/Kip2 and CD34. The frequencies of the p57/Kip2‐positive cells in FCD IIb and HME were significantly higher than those in TSC, suggesting that the balloon cells may be heterogeneous. These findings suggest some functional significance of the protein on the cytoplasmic processes of balloon cells and appear consistent with the notion that the cells are abnormally differentiated progenitor cells.     

Ictal haemodynamic changes in a patient affected by “subtle” Epilepsia Partialis Continua

We report on a 64 year-old woman presenting with Epilepsia Partialis Continua (EPC) affecting the left hand since the age of 24 without neurological deficit. Structural MRI showed a region of focal cortical dysplasia (FCD) over the right central gyrus and lesions in the mesial frontal and occipital cortex secondary to perinatal hypoxic injury. Ictal spike haemodynamic mapping using simultaneous EEG-fMRI revealed significant BOLD signal changes prominent in the region of FCD (larger cluster), occipital cortex (global statistical maximum), prefrontal cortex and cerebellum. The cluster over FCD was in good agreement with the result of EEG source analysis.Our findings provide an interesting illustration of the ability of EEG-fMRI to reveal epileptogenic networks confirming the intrinsic epileptogenic properties of dysplastic neurons.     

Activation of extracellular regulated kinase and mechanistic target of rapamycin pathway in focal cortical dysplasia

Neuropathology of resected brain tissue has revealed an association of focal cortical dysplasia (FCD) with drug‐resistant epilepsy (DRE). Recent studies have shown that the mechanistic target of rapamycin (mTOR) pathway is hyperactivated in FCD as evidenced by increased phosphorylation of the ribosomal protein S6 (S6) at serine 240/244 (S^240/244), a downstream target of mTOR. Moreover, extracellular regulated kinase (ERK) has been shown to phosphorylate S6 at serine 235/236 (S^235/236) and tuberous sclerosis complex 2 (TSC2) at serine 664 (S⁶⁶⁴) leading to hyperactive mTOR signaling. We evaluated ERK phosphorylation of S6 and TSC2 in two types of FCD (FCD I and FCD II) as a candidate mechanism contributing to mTOR pathway dysregulation. Tissue samples from patients with tuberous sclerosis (TS) served as a positive control. Immunostaining for phospho‐S6 (pS6^240/244 and pS6^235/236), phospho‐ERK (pERK), and phospho‐TSC2 (pTSC2) was performed on resected brain tissue with FCD and TS. We found increased pS6^240/244 and pS6^235/236 staining in FCD I, FCD II and TS compared to normal‐appearing tissue, while pERK and pTSC2 staining was increased only in FCD IIb and TS tissue. Our results suggest that both the ERK and mTOR pathways are dysregulated in FCD and TS; however, the signaling alterations are different for FCD I as compared to FCD II and TS.     

Cortical neuronal densities and lamination in focal cortical dysplasia

Focal cortical dysplasia (FCD) is considered to represent a malformation due to abnormal cortical development (MCD) and is an important cause of focal epilepsy. The histopathological features include abnormal laminar architecture, the presence of hypertrophic and dysmorphic neurones in FCD type IIA and additional balloon cells in FCD type IIB. The events causing these sporadic lesions are unknown, but abnormal progenitor cell proliferation occurring late in corticogenesis has been proposed. FCD-like lesions have, however, also been described following a cerebral injury early in life. We carried out a stereological assessment on 15 cases of FCD on NeuN- and Nissl-stained sections from patients with a wide age range, and identified a significant reduction in the neuronal density in all cases in the region of dysplasia compared to the adjacent unaffected cortex (mean neuronal densities 19.2×10³/mm³ in the region of dysplasia; 42.8×10³/mm³ in the adjacent cortex). Relative differences in neuronal density and size in FCD cases between the superficial (layer I and II) and deep cortical laminae (layer V and VI) were similar to that observed in other pathologies including mild MCD, temporal neocortex adjacent to hippocampal sclerosis as well as in a non-epilepsy surgical control group. The lower overall neuronal densities observed in FCD may reflect neuropil expansion, a local failure of neuronal migration, proliferation or secondary neuronal loss. The preservation of relative differences in neuronal densities between cortical layers and laminar patterns of neurofilament staining in FCD would support the view that the temporal sequence of lamination is not affected.     

CD34-immunoreactive balloon cells in cortical malformations

Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylors type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). Whether this intriguing cell type results from similar pathogenetic pathways remains to be shown. Here, we analyzed the immunohistochemical distribution pattern of the CD34 epitope in surgical specimens from 34 patients with FCD IIb, compared to that of 6 patients with TSC and 3 patients with HME. In normal brain, CD34 occurs only transiently during neurulation, but cannot be detected in mature neuroectodermal cell progenies. In contrast, 58% of our patients showed CD34 immunoreactivity within a subpopulation of balloon cells. Interestingly, CD34-positive balloon cells were confined to the white matter, but never observed in neocortical layers. Furthermore, balloon cells expressing neurofilament protein were also restricted to white matter, whereas GFAP-positive balloon cells were observed either in white or gray matter location. Clinical characteristics did not significantly differ between patients with CD34-positive versus CD34-negative lesions. No significant correlation was found between CD34 expression and genetic alterations of the TSC1 gene, which is affected in many FCD and TSC patients and which plays a role in the regulation of cell size. Further studies are warranted to clarify the restricted expression of CD34 in balloon cells of the white matter.     

Clinicopathological and immunohistochemical findings in an autopsy case of tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder caused by mutations in either the TSC1 or TSC2 genes and characterized by developmental brain abnormalities. In the present study we discuss the neuropathological findings of a 32‐year‐old patient with a germ‐line mutation in the TSC2 gene. Post mortem MRI combined with histology and immunocytochemical analysis was applied to demonstrate widespread anatomical abnormalities of gray and white matter structure. TSC brain lesions were analyzed for loss of heterozygosity (LOH) on chromosome 16p13. The neuropathological supratentorial abnormalities were represented by multiple subependymal nodules (SENs) and cortical tubers. In addition to cerebral cortical lesions, cerebellar lesions and hippocampal sclerosis were also observed. LOH was not found in the cortical tubers and SENs of this patient. Immunocytochemical analysis of the TSC brain lesions confirmed the cell‐specific activation of the mTOR pathway in cortical tubers, SENs and cerebellum, as well as differential cellular localization of hamartin and tuberin, the TSC1 and TSC2 gene products. Examination of the pathological brain regions revealed activated microglial cells and disruption of blood‐brain barrier permeability. Predominant intralesional cell‐specific distribution was also detected for the multidrug transporter protein P‐gp, possibly explaining the mechanisms underlying the pharmacoresistance to antiepileptic drugs. Autopsy findings confirm the complexity of the brain abnormalities encountered in TSC patients and proved useful in clarifying certain aspects of the pathogenesis, epileptogenesis and pharmacoresistance of TSC lesions.     

Doublecortin immunoreactivity in giant cells of tuberous sclerosis and focal cortical dysplasia

Cerebral cortical lesions of tuberous sclerosis (TSC) and focal cortical dysplasia (FCD) show disturbances in laminar architecture and cellular differentiation. We immunohistochemically studied the expression of doublecortin, a fetal neuronal protein that regulates neuronal migration, in the surgical specimens of five TSC and eight FCD patients. In both TSC and FCD, bizarre giant cells showed a variable degree of doublecortin immunoreactivity. Both cytomegalic neurons and balloon cells were positive. The staining tended to be more intense in TSC than in FCD, although there were exceptional cases in both groups. Doublecortin immunoreactivity of normal-sized neural cells was restricted to a small number of astrocytes, and comparable to that in control patients. The persistent expression of doublecortin by giant cells in the postnatal cerebrum is additional evidence of abnormal differentiation, which may be relevant to the pathogenesis of cortical disarray in TSC and FCD.     

脑皮质发育不良继发顽固性癫痫的病理分型及手术治疗

目的 探讨局灶性脑发育不良(FCD)的临床特征、病理学、影像学的特点及手术疗效.方法 42例外科手术切除致痫灶并经病理证实为FCD的患者中,根据Palmini病理学分型进行分类,并对其临床特征、影像学特点及手术疗效进行回顾性分析.结果 42例患者中,按致痫灶部位分类颢叶24例、额叶14例、顶叶6例及枕叶3例,其中多脑叶5例.术前影像学检查阳性率62%.组织学分型FCDⅠA型9例,FCDⅠB型21例,FCDⅡA型5例,FCDⅡB型7例,其中以FCD Ⅰ B型最为常见,多位于颞叶且常伴有海马硬化.所有患者术后至少随访1年以上,癫痫术后治愈率FCD位于颞叶67%,颞叶以外43%(EngleⅠa).结论 FCD是难治性癫痫常见的病理学改变,其病理分型与临床特征和致痫灶部位存在相关性,为制定手术方案和判定手术效果提供了依据.     

Doublecortin‐like (DCL) expression in focal cortical dysplasia and cortical tubers

Purpose: Focal cortical dysplasia type IIB (FCD IIB) and cortical tubers of patients with tuberous sclerosis complex (TSC) are malformations of cortical development that are frequently associated with intractable epilepsy. Their histopathologic and molecular features suggest developmental abnormalities during the early stages of cortical development, which may involve neural progenitor cells. The aim of our study was to define the expression and cell‐specific distribution of doublecortin‐like (DCL), a protein critically involved in neuronal division and radial migration during early corticogenesis, in both FCD and TSC. Methods: DCL was studied in epilepsy surgery cases with FCD IIB (n = 8) and TSC (cortical tubers; n = 8) using immunocytochemistry, confocal analysis, and Western blotting. Results: Autopsy and surgical control neocortical specimens were characterized by modest DCL immunoreactivity (IR) throughout all cortical layers, but DCL IR was not detectable in the white matter. Balloon cells (BCs) in FCD and giant cells (GCs) in TSC expressed strong DCL IR. Most of the large dysplastic neurons (DNs) were positive for DCL in both FCD and TSC. Coexpression of DCL with the neural progenitor or neuroblast markers nestin, GFAPδ, and doublecortin was observed in both FCD and TSC specimens. The increased DCL expression within the dysplastic cortex, compared to control cortex, was confirmed by Western blot analysis. Discussion: The prominent postnatal expression of DCL by BCs/GCs and DNs in FCD and TSC supports an important role for this microtubule associated protein, also during early human cortical development, which could be relevant to the pathogenesis of these developmental glioneuronal malformations.     

The role of voxel-based morphometry in the detection of cortical dysplasia within the temporal pole in patients with intractable mesial temporal lobe epilepsy

Purpose: To determine whether voxel‐based morphometry (VBM) might contribute to the detection of cortical dysplasia within the temporal pole in patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE/HS). Methods: Eighteen patients with intractable MTLE/HS and 30 sex‐ and age‐matched healthy controls were included in the study. All of the patients fulfilled the diagnostic criteria for MTLE/HS and underwent anteromedial temporal resection. VBM without a modulation step was applied to the magnetic resonance (MR) images of the brain. Statistical parametric maps were used to compare structural characteristics such as gray matter concentration (GMC) within the temporal pole among patients and controls separately. The acquired data were then statistically analyzed to determine the congruency between visually inspected MR imaging (MRI) scans and VBM results in the detection of morphologic abnormalities in the temporal pole compared to postoperative histopathologic findings of cortical dysplasia. Key Findings: Histopathologic examination revealed cortical dysplasia within the temporal pole in 11 patients. In detail, according to Palmini’s classification, mild malformations of cortical development (mMCDs) were disclosed in three patients, focal cortical dysplasia (FCD) type Ia in three patients, and FCD type Ib in five patients. Some type of structural temporal pole abnormality was suggested by VBM in 14 patients and by visually inspected MRI scans in 11 patients. The results of VBM were in agreement with the presence/absence of cortical dysplasia in 13 patients (72.2%); this correspondence was significant (p = 0.047). In one case, VBM was false negative and in four cases it was false positive. There was congruence between the results of visual analysis and histologic proof in 55.6% of examined patients, which was not significant. Significance: We found that VBM made a superior contribution to the detection of temporopolar structural malformations (cortical dysplasia) compared to visual inspection. The agreement with postoperative histopathologic proof was clearly significant for VBM results and nonsignificant for visual inspection.     

重度局灶性皮层发育不良和皮层错构性肿瘤病变的临床病理分析

目的 观察癫痫手术切除脑病变中,重度局灶性脑皮层发育不良(FCD Ⅱ B)与皮层错构性癫痫相关肿瘤(神经元和混合性神经元-胶质瘤)的临床病理特点.探讨两者的形态学变化及相瓦关系.方法 手术切除脑癫痫病灶,新鲜标本进行测量、切开、照相,显微镜下形态学观察.按脑皮质发育不良的病理诊断标准分类.应用一组免疫组化和特染指标协助诊断.结果 在133例癫痫脑病变切除病例中,典型FCD Ⅱ B者5例,皮层错构性癫痫相关肿瘤6例.在5例FCDⅡB中,存在重度脑皮层分层紊乱,典型的不成熟神经元、巨大神经元、异常神经元和气球样细胞.在6例脑皮层错构性癫痫相关肿瘤中,同样有以上病变,另外出现胶质神经元瘤样增生,DNT有黏液性背景、胶质增生及神经元减少.结论 FCD Ⅱ B与皮层错构性癫痫相关肿瘤有许多相似的病理变化,两者可能是癫痫脑病理谱系的连续病变,有待深入研究.     

Sturge-Weber综合征伴皮层发育不良1例并文献复习

目的探讨Sturge-Weber综合征的临床特点、影像学特征、病理诊断及鉴别诊断。方法分析1例8岁女性Sturge-Weber综合征病人的临床资料、影像学特征,光镜下观察病理学形态并行免疫组化染色检查。结果CT显示左侧顶枕叶条索状钙化;MRI示左侧顶枕叶软脑膜病变,增强后强化明显,强化沿脑回分布。病理学特点表现为软脑膜的静脉性血管瘤,病变皮层下沿脑回呈带状分布的钙化灶,同时伴有皮层发育不良。免疫组化结果：发育不良神经元核抗原阳性,皮层内增生胶质细胞的胶质纤维酸性蛋白和S-100蛋白阳性。结论结合临床病史、影像学资料及病理学形态进行综合性分析才能正确诊断Sturge-Weber综合征。     

Insulin signaling pathways in cortical dysplasia and TSC-tubers: tissue microarray analysis

To evaluate the possible roles of the Akt/PKB-mTOR-p70S6K-S6 and cap-dependent translation (eIF4G) pathways in the pathogenesis of tuberous sclerosis complex (TSC)-associated cortical tubers and focal cortical dysplasia (FCD), we performed qualitative and semiquantitative immunohistochemical evaluation on surgically resected corticectomy specimens to detect phosphorylated molecules as activated downstream targets of the signaling pathways. A tissue microarray paraffin block was constructed from 63 archival specimens of surgically resected TSC tubers, FCDs with balloon cells, cortical dysplasia without balloon cells, and histologically normal-appearing neocortex obtained from cases with Rasmussen encephalitis, cystic-gliotic encephalopathy, and temporal lobe epilepsy. Abnormal neuroglial cells were positive for phospho-S6 and phospho-eIF4G with various staining intensities in FCDs and TSC tubers. Both proteins were much less abundantly expressed in normal-appearing neocortex. Phospho-mTOR expression was observed in neurons in all groups. The expression of phospho-S6 and phospho-eIF4G was associated with dysplastic lesions (p < 0.05), and the cytoplasmic phospho-p70S6K expression was most specific for and abundant in TSC tubers and much less prominent in other groups (p < 0.01). These results suggest that constitutive activation of cytoplasmic p70S6K plays a pivotal role in the pathogenesis of TSC tubers and that FCDs possess a distinct mechanism for activation of S6 and eIF4G.