Focal Cortical Dysplasia:Clinical Manifestations And Imaging Analysis As Well As Multimodal Presurgical Evaluation

Epilepsy is a complex of chronic neurological dysfunction characterized by disordered neuronal discharge;up to 30%are medically refractory epilepsy even though receieving enough antiepileptic drugs therapeutic strategy.Focal cortical dysplasia is one of cortical development disorders,which is one of the most common cause of medically refractory epilepsy both in children and adult.Focal resective surgery is the most promising treatment for this group,and seizure-free rates vary from 40%-75%after the resection?The diagnosis and classification of pathological FCD were made according to the Intermational league against epilepsy(ILAE)guidelines in 2011:FCD type ? referring mainly architectural disturbances of cortical lamination in various directions,presenting either as radial,tangential or bothh of them,which were called type ?a,type ?b and type?c in sequence;FCD type ? characterizing by cortical dyslamination and dysmorphic neurons without or with balloon cells,which were called type ?a and type ?b successively;and FCD type ? occurring in cortical lamination abnormalities associated with a principal lesion such as hippocampal sclerosis,epilepsy-related tumor,vascular malformation and epileptogenie lesions acquired in early life(i.e.,infection,ischemic injury in perinatal period and so on).Howerver,most of previous studies as to cortical development disorders focused on FCD type ?.The clinical-sugrical characteristics of FCD type ? related epilepsy and its subgroups are still unclear.Moreover,the classification of FCD has been widely used according to various standards among previous studies.There were few studies about FCD-related epilepsy according to 2011 ILAE FCD classification.Designed to address the aforementioned limitations,the current part one aimed at evaluating clinical-surgical outcome characteristics and predictors of FCD type ? and ? in a large cohort of patients.High-resolution MRI scans is a common tool to identify leisons for patients with epilepsy.However,50%-80%of FCD are too subtle to detect by conventional visual analysis of MRI scans,especially in FCD type ?.Accurately to locate the responsible lesions is the key point for surgical success.The previous study has demonstrated that negative-MRI was the independent risk ratio of surgical recurrence in patients with epilepsy,and MRI-positive patients had seizure-free outcome twice as high as MRJ-negative patients.Recent studies found brain MRI postprocessing technique could improve the detection of potentially dysplastic abnormalities.A voxel-based MRI morphometric analysis prograr(MAP)is a software algorithms consisted of several MRI postprocessing technique to increase detection of subtle abnormalities as to FCD.The localizing ratios of MAP in MRI-positive FCD ranged from 98-100%and in MRI-negative FCD ranged from 43-48%(mainly based on FCD type ?).Additionally,previous literatures based on MRI-negative groups,limited subjects as well as enrolled patients with pathological-confirmed FCD type ?.There is no MAP study exploring the epileptogenic zone in FCD type ?.Therefore,a second part of our study was to examine the role of MAP in patients with pathological-identified FCD type ? and ?.FCD is the most common underlying pathology in epilepsies with negative MRI scans.Accurate localization of epilepsies with normal MRI scans presents significant challenges.Substantial efforts have been made to improve detection of subtle abnormalities and multimodal investigation have been widely used for presurgical evaluation,which is helpful for making the hypothesis about epileptogenic zone as well as the plan of implanted invasive electrode.In the third and forth part of this study,we systematically explored the localization values of noninvasive multimodal tests for patients with epilepsies from two specific anoatomy(cingulate and insular-operculum areas).Part OneClinical characteristic-surgical outcome characteristics andpredictors of pharmacoresistant epilepsy caused by focal cortical dysplasia type ? and ?ObjectiveThis study aimed to determine clinical-siurgical outcome chharacteristics of pharmacoresistant epilepsy eaused by FCD as well as its subgroups and to identify the important predictors of poor surgical outcomes.MethodsWe retrospectively analyzed the data of pharmacoresistant epilepsy patients with histologically proven FCD type ? and ? jfrom Second Affiliated Hospital of Zhejiang University and Cleveland Clinic with at least 1-year postoperatative follow-up(Engel Class one was regarded as seizure-free outcome).Univarivate analysis and multivariate logistic regression model were used to evaluate the seizure-free rates,clinical predictiors and prognosis.ResultsTwo hundrend thirty-eight patients with FCD were enrolled(147 FCD type ?;91 FCD type ?),the estimated chance of seizure freedom was 65.5%[95%confidence intervals(CI),59.5%-71.5%]at 1 year after surgery.FCD type Ic(P=0.029)and presence of interictal epileptiform discharges(IEDs)on 3-6 months postoperative electroencephalography(EEG)(P<0.001)were independent predictors of seizure recurrence.Binary logistic regression analysis showed,compared to FCD type ?,FCD type ? were common in the group with older onset age(P=0.043),more seizure types(P=0.004),temporal lobe epilepsy(TLE)(P<0.001),higher rate of ICEEG performed(P=0.001).The estimated change of seiure freedom was 62.6%(95%Cl,54.8%-70.4%)in epilepsies with FCD type ?,and multilober resection(P=0.013)and presence of IEDs on 3-6 months postoperative EEG(P=0.002)are powerful predictive factors for postsurgical seizure recurrence,and presence of aura(P=0.037)is an independent factor of seizure-free outcome.The estimated change of seizure freedom was 70.3%(95%Cl,60.9%-79.7%)in patients with FCD type ?,presence of secondary generalized tonic clonic seizures(sGTCS)(P=0.010)is independently associated with unfavorable outcome.ConclusionFocal resection was favorable treatment in pharmacoresistant epilepsies with FCD,FCD type Ic and presence of IEDs on 3-6 months postoperative EEG were independent factors for seizure recurrence after surgery.Compared to FCD type ?,FCD type ? were common in the group with poor outcome,older onset age,more seizure types,TLE,higher rate of ICEEG performed;multilober resection and presence of IEDs on 3-6 months postoperative EEG were powerful predictive factors for postsurgical seizure recurrence,and aura was an independent factor of seizure-free outcome.sGTCS was independently associated with unfavorable outcome in patients with FCD type ?.Part TwoDiagnostic yield of morphometric analysis program in Focal Cortical Dysplasia Type ? and ?ObjectiveHigh-resolution MRI is a common tool in detecting subtle epileptic pathologies.However,there are still 83%of FCD type ? and 33%of type ? non-visible on MRI because of subtle lesions.This study aimed to determine localization value of morphometric analysis program(MAP)in detecting the epileptogenic zone in patients with pathological-confirmed FCD type ? and ?MethodsTwo hundrend thirty-eight patients with pharmacoresistant epilepsy and histologically proven FCD type ? and ? from two different epilepsy centers(Second Aff iliated Hospital of Zhejiang University and Cleveland Clinical Foundation)were respectively included in the study with at least 1-year of follow-up(Engel class one was regarded as seizure-free outcome).A series of MRI post-processing of presurgical 3D T1 MRI scans was using a fully automated MAP 18 carried out within Matlab2015b,which was then co-registered with other presurcial MRI sequences(such as flair and T2).We analysed blindedly the z-score features maps from MAP18.In all MAP+patients,we used SPM12 to co-register preoperative T1-weighted,MAP-Junction file and postoperative Tl-weigted images or CT(only four patients had postsurgical cerebral CT)in order to identify whether the location of the MAP+regions was included in the resection.ResultsAmong 238 patients with pathological-confirmed FCD(147 FCD type ? and 91 FCD type ?),167 were non-visible on radiological reports,and 124 were considered as FCD-related epilepsies during patient management conferences(PMC).Subgroup analysis showed FCD type ?b(P<0.001)and ?c(P=0.002)would not be found during PMC while FCD type ?b(P<0.001)would.MAP was positive in 118(49.6%)of the 238 patients.Of the 118 patients,32.0%was FCD type ? including 23.7%FCD type ?b and 46.3%FCD type ?c;78%was FCD type ?,including 55.6%FCD type ?a and 87.5%FCD type ?b.Additionally,MAP showed 88%positive rate in patients with bottom-of sulcus FCD.Subgroup analysis found that PMC-suspected subtle findings were more likely to be detected by MAP compared to PMS-negative fingdings.Fully-resected MAP positive region was an independent factor for seizure-free outcome.ConclusionMAP can be a valuable and cost-free tool to identify subtle epileptogenic abnormalities in patients with FCD,giving patients with MRI-suspicious/negative FCD second opportunity to be identified,which should be considered to add to the presurgical evaluation tests.Part ThreeMultimodal non-invasive evaluation in MRI-negativeoperculo-insular epilepsyObjectivePresurgical evaluation of patients with operculo-insular epilepsy and negative MRIs presents major challenges.FCD is the most common underlying pathology in epilepsies with negative MRI scans.Here we examined the yield of noninvasive modalities such as voxel-based morphometric MRI post-processing(MAP),FDG-PET,subtraction ictal SPECT co-registered to MRI(SISCOM)and magnetoencephalography(MEG),in a cohort of patients with operculo-insular epilepsy and negative MRI.MethodsTwenty-two MRI-negative patients were included who had focal ictal onset from the operculo-insular cortex on intracranial EEG,and underwent focal resection limited to the operculo-insular cortex.MRI post-processing was applied to presurgical T1 volumetric MRI using Morphometric Analysis Program(MAP).Individual and combined localization yields of MAP,FDG-PET,MEG and SISCOM were compared with ictal onset location on ICEEG.Seizure outcome was reported at 1 year and 2 years(when available)using Engel's Classification.ResultsA Ten patients(45.5%,10/22)had operculo-insular abnormalities on MAP;5(23.8%,5/21)had operculo-insular hypometabohsm on FDG-PET;4(26.7%,4/15)had operculo-insular hyperperfusion on SISCOM;and 6(30.0%,6/20)had a MEG cluster within the operculo-insular cortex.The highest yield of two-test combination was 59.1%,seen with MAP+ SISCOM,followed by 54.5%of MAP+FDG-PET/MEG,FDG-PET+MEG/SISCOM(36.4%,8/22).The highest yield of three-test combination was 68.2%,seen with MAP+MEG+SISCOM,followed by MAP+FDG-PET+SISCOM(63.6%,14/22),MAP+FDG-PET+MEG(59.1%,13/22),FDG-PET+SISCOM+MEG(45.5%,10/22).The yield of four-test combination remained at 68.2%.When all other tests were negative/non-localizing,unique information was provided by MAP in 5,MEG in 1,SISCOM in 2 and FDG-PET in none of the patients.Year 1 follow-up was available in all patients,and showed 68.2%seizure-free outcome.Year 2 follow-up was available in 19 patients,and showed 47.4%seizure-free outcome.FCD type ? cases were successfully detected using MAP,while only one of FCD type ? cases were successfully detected.ConclusionOur study highlights the individual and combined values of multiple noninvasive modalities for the evaluation of nonlesional operculo-insular epilepsy.The three-test combination of MAP,MEG and SISCOM represented structural,interictal and ictal localization information,and constituted the highest yield.MAP showed the highest yield of unique information when other tests were negative.Part FourMultimodal non-mvasive evaluation in the diagnostic yield ofMRI-negative cingulate epilepsyObjectiveDue to its mesial and deep loeation from the cerebral surface as well as the absence of unique ictal manifestations,scalp video-electroencephalography(EEG)may be misleading or non-localizable.The fast propagation of seizure activities originating from cingulate cortex(CC)within the limbic network,complicated functional connectivity between homotopic cingulate and sensorimotor cortex,and diffuse bilaterally secondary synchrony of epileptiform discharges from cingulate lesions,all contribute to the difficulty in localizing CE.FCD is the most common underlying pathology in epilepsies with negative MRI scans.Therefore,surgical management of patients with cingulate epilepsy(CE)is highly challenging,especially in the setting of negative MRI.This study aims to use a multimodal non-invassive evaluation such as MAP,FDG-PET,SISCOM and MEG,to facilitate detection of epileptogenic lesions in CE with a negative pre-surgical MRI.MethodsIncluded in this retrospective study were 6 patients with negative MRI and 3 patients with subtly lesional MRI with cingulate epilepsy who underwent surgery and became seizure-free or had marked improvement with 1-year follow-up from the Cleveland Clinic(January 2008 to December 2016)and Second Affiliated Hospital of Zhejiang University(September 2012 to December 2016)surgical databases(Engel class ? and ? were regarded as marked improvement of seizure frequency).Morphometric analysis was applied to pre-surgical T1-weighted volumetric sequence using a fully automated MATLAB script(MAP18),which was then co-registered with other imaging modalities.We analyzed the z-score feature maps from MAP 18,as well as the automatic focal cortical dysplasia(FCD)detection probability map by artificial neural networks.The MAP finding was then coregistered and compared with other non-invasive imaging imaging tests(FDG-PET,SPECT and MEG),intracranial EEG ictal onset,surgery location and histopathology.ResultsSingle MAP+abnormalities were found in 6 patients,including 3 patients with negative MRI and 3 patients with subtly lesional MRI.Out of these 6 MAP+patients,4 patients became seizure-free after complete resection of the MAP+abnormalities;2 patients didn't become seizure-free following laser ablation that only partially overlapped with the MAP+abnormalities.FCD was identified in all patients' surgical pathology except for two cases of laser ablation with no tissue available(2 FCD type ?a,3 FCD type ?b,2 FCD type ?b).All MAP+foci were concordant with intracranial EEG when performed.FDG-PET was performed in all 9 patients;in only 2 patients,hypometabolism overlapped with(and also extend beyond)the cingulate cortex(PI and P9).SISCOM was successfully obtained in 4 of the 9 patients;the hyperperfusion areas contained the cingulate cortex only in one patient(PI).MEG was performed in 5 of the 9 patients;only 2 patients had MEG findings overlapping with the cingulate cortex(PI and P2).ConclusionThe localization value of FDG-PET,SPECT and MEG was limited.MAP provided helpful information for identifying subtle epileptogenic abnormalities in patients with noulesional cingulate epilepsy.MRI postprocessing should be considered to add to the presurgical evaluation test battery of noulesional cingulate epilepsy.