The Clinical Features And Pathogenesis Of Focal Cortical Dysplasia In Human Temporal Lobe

Epilepsy is one of the common chronic diseases of the central nervoussystem of our country, there are about10million people with epilepsy, newcases each year about40thousand. Of which about30%of patients noteffectively controlled seizures eventually become refractory epilepsy. Focalcortical dysplasia (FCD) is a type of malformations of cortical development, isan important cause of intractable epilepsy. After surgical treatment of epilepsyin children more than75%and about20%of adults with epilepsy exist FCD,about50%of the whole population of patients with epilepsy is caused by FCD.Since its discovery, FCD has been widely applied in various fields amongneuroanatomy, pathology and imaging science.FCD is a series of pathology, clinical manifestations vary, researchershave been trying to classify, so the development of a variety of differentclassification methods depending on the application and evaluation methods.Palmini classified the FCD into type I and type II, based on widespread use inclinical pathology. In2011, International League Against Epilepsy (ILAE) inPalmini classified on the basis of a revised increase of conjugated FCDclassification, hippocampal sclerosis, epilepsy-related tumors, vascularmalformations adjacent FCD named associated FCD. Such FCD divided intoisolated FCD and associated FCD, isolated FCD including simplex type I andtype II, associated FCD type III.As the study under the new classification ILAE rarely, given the roughly50%FCD occurs in the temporal lobe, the study according to the2011ILAEclassification of the clinical features of the temporal lobe FCD varioushistological subtypes, surgical outcomes, radiographic diagnosis andpathogenesis ultrastructural analysis. Part1The clinical characteristics of different subtypes of focal corticaldysplasia in human temporal lobeObjective: To compare the clinical characteristics of different subtypesof FCD in human temporal lobe according to2011ILAE classification.Methods: Patients with temporal lobe epilepsy after surgery according to2011ILAE classification to classify different pathological subtypes of FCD,and seizures in patients with different subtypes of clinical and pathologicalfeatures of the starting age, the prevalence of epilepsy age, age at surgery,seizure frequency, etc.Results: The average age of epilepsy onset associated FCD was19.2years, significantly higher than the isolated FCD, with statistical significance.In patients with associated FCD, average age of epilepsy onset of FCD IIIcwas30.7years, significantly higher than other associated FCD subtypes. Theaverage duration of epilepsy of associated FCD was7.8years, significantlyshorter than the simple type FCD. In pathological subtypes associated FCD,duration of epilepsy of FCD IIIb was3.5years, duration of epilepsy of FCDIIIc was5.3years, significantly shorter than other subtypes of associated FCD.Average age at surgery of FCD IIIc was35.8years, significantly later thanother subtypes of associated FCD. In associated FCD,18cases of FCD IIIapatients with a history of febrile seizures, accounting for44.6%, significantlymore than other subtypes of associated FCD.Conclusion: The average age of epilepsy onset of associated FCD waslate, especially of FCD IIIc. The average duration of epilepsy of associatedFCD was short, especially FCD IIIb and FCD IIIc. In patients with associatedFCD, average age at surgery of FCD IIIc was significantly later than otherassociated FCD. FCD IIIa patients were more prone to febrile seizures.Clinical features of isolated FCD and associated FCD may differ.Part2Surgery effectiveness analysis of different subtypes of focal corticaldysplasia in human temporal lobeObjective: To compare Surgery effectiveness of of different subtypes ofFCD in human temporal lobe according to2011ILAE classification.Methods: The patients with postoperative outpatient, telephone, mail follow-up. After the patients were followed up, according to the seizures inpatients with standard according to Engel classification prognostic evaluation:I, without affecting the function of epileptic seizures (in addition to earlypostoperative seizures); II, only rare epilepsy affect the function of attack;class III, seizures improved considerably (reduction in seizure frequency90%);IV level, seizures obvious improvement.(Engel I+II level) for the good resultsof operations,(Engel III+IV grade) for the surgical results are poor.Results: Postoperative assessment of the efficacy of the standard byEngel classification, Engel I grade35/68(51.4%), II grade18/68(26.5%),10/68(14.7%) III level,5/68(7.3%) IV grade; effective (Engel I+II level) was53/68(77.9%), ineffective (Engel III+IV grade) was19/68(22.1%). effectivein53cases, of which only type FCD17patients (70.8%), associated FCD36patients (81.8%), ineffective in15cases, of which only type FCD7patients(29.2%), associated FCD8cases (19.2%) of isolated FCD rates belowassociated FCD (P<0.05).Conclusion: Surgical treatment is an important way to temporal lobeFCD. The effect of associated FCD is superior to isolated FCD.Part3The diffusion tensor imaging performance analysis of focal corticaldysplasia in human temporal lobeObjective: To explore the diagnostic value of diffusion tensor imaging ofdifferent parameters in different subtypes of FCD.Methods: Patients with diffusion tensor imaging findings were analyzedin axial T1WI figure, taking the most complete display of temporal lobehippocampal level, as well as an upper and lower level, at a fixed location onthe temporal lobe region of interest (ROI), ROI avoid including cavitystructure and scope of the hippocampal formation. The application software "mirror symmetry " method, select the corresponding parts in the contralateralROI,20mm ROI circle diameter, measured on both sides of ADC and FAvalues within the ROI, diffusion tensor imaging to compare different subtypesperformance differences and diffusion tensor the diagnostic value of theamount of different imaging parameters. Results: ADC of isolated FCD uninjure side was9.2±3.4(×10-10mm2/s),ADC of isolated FCD injure side was12.2±5.6(×10-10mm2/s), the ADCdifference of both sides was3.0±1.2(×10-10mm2/s). ADC of associated FCDuninjure side was8.7±3.1(×10-10mm2/s), ADC of associated FCD injure sidewas13.1±4.3(×10-10mm2/s), the ADC difference of both sides was3.4±1.9(×10-10mm2/s). FA of isolated FCD uninjure side was0.245±0.068, FA ofisolated FCD injure side was0.186±0.048, significantly lower than uninjureside (P<0.05); the FA difference between the sides was0.062±0.021. FA ofassociated FCD uninjure side was0.241±0.052, FA of associated FCD injureside was0.156±0.052, significantly lower than the uninjure side (P<0.05);FA difference of both sides of was0.091±0.033, significantly lower thanuninjure side (P<0.05).Conclusion: DTI can be used as an important means of temporal lobeFCD auxiliary examination.In DTI parameters ADC and FA values, FA valueschange more obvious. In different subtypes of FCD, FA of associated FCDchange more obvious.Part4Ultrastructural analysis of of focal cortical dysplasia in humantemporal lobeObjective: Through the various histological subtypes in patients withFCD Electron microscopy and ultrastructural changes FCD, to understand thestructural basis of epilepsy.Methods: Patients were divided into isolated FCD group, associatedFCD group and control group, respectively, were observed by TEM,ultrastructural analysis of change.Results:1isolated FCD group: Abnormal neuronal morphology,organelles significantly reduced or disappeared, some neurons visiblelipofuscin granules. Mitochondria vague, some shortened or missing.Reduction or disappearance of substrate particles. Mitochondrial hypertrophy,mitochondrial membrane rupture. Endoplasmic reticulum. Glial cell swelling,myelinated nerve fibers arranged confusion, myelin membrane structuresparse. Mild separation of the inner and outer layers of myelin.2associated FCD: Neuronal cytoplasm edema, significantly reduced the number oforganelles or disappeared, mitochondrial hypertrophy and hyperplasia. Therough endoplasmic reticulum was dilated. Myelinated nerve myelin significantthickening of stratified hyperplasia, proliferation of myelinated nerve myelinextremely irregular shape, disordered arrangement, smaller cable marrowedema, marrow contents decreased myelin membrane structure sparse. Myelinouter and inner separation, reducing the number of mitochondria andmicrotubules filaments.3control groups: no obvious abnormalities in braintissue, neuronal morphology rules, closely arranged, clear nucleolus,chromatin arrangement uniform.Conclusion: The associated FCD itself may also have induced seizureresistance, with the structural basis of seizures. Associated FCD in myelinatednerve fiber damage significantly, there may be differences in their possiblemechanisms and other epileptic spikes stove.Part5The mammalian target of rapamycin expression analysis of focalcortical dysplasia in human temporal lobeObjective: To detect the mTOR signaling pathway expression ofdifferent subtypes in patients with pathological tissue FCD.Methods: Using immunohistochemistry, immunofluorescence,Western-blot in patients with various subtypes FCD AKT, mTOR, p70S6K,and p-AKT, p-mTOR, p-p70S6K were detected, mTOR signaling pathwaywas observed in various subtypes FCD.Results: AKT, mTOR, p70S6K in normal brain tissue and FCD I typegroups, the FCD IIIa group showed a small amount of weakly expressed cellbodies of pyramidal neurons and astrocytes showed. Observed in FCD IIIatype of p-AKT, p-mTOR, p-p70S6K expression frail in a small pyramidalneurons with FCD I type and degree of expression similar to normal braintissue. In astrocytes p-AKT, p-mTOR, p-p70S6K showed a moderatelypositive expression, expression sites mainly in the cytoplasm, the expressionintensity was stronger than FCD I type and normal brain tissue.Conclusion: FCD IIIa of astrocytes in the p-AKT, p-mTOR, p-P70S6K expression increased, suggesting that PI3K-AKT-mTOR pathway may beinvolved in the abnormal activation of the pathogenesis of FCD IIIa. In FCDIIIa type of astrocytes in the PI3K-AKT-mTOR pathway activationabnormalities, and FCD I PI3K-AKT-mTOR signaling pathway no abnormalactivation, FCD IIIa and FCD I there may be differences in the pathogenesis.