Focal Cortical Dysplasia:Clinical-imaging Characteristic And Surgical Outcome

Epilepsy is a group of chronic neurological disease characterized by recurrent and unprovoked seizure.Although about 30%patients with epilepsy receiving the antiepileptic drugs,those patients can not achieve seizure freedom which named medically refractory epilepsy.Focal cortical dysplasia is a common type of malformation of cortical development,which is one of the most common cause of medically refractory epilepsy.The diagnosis and classification of pathological FCD were made according to the International league against epilepsy(ILAE)guidelines.FCD type Ⅰ showing mainly abnormal cortical lamination in various directions;FCD type Ⅱ with dysmorphic neurons or with additional balloon cells;and FCD type Ⅲrefers to cortical lamination abnormalities associated with a principal lesion.Epilepsy surgery is the most promising treatment option to achieve seizure freedom in this patient group.The rate of seizure free after resection varied between 52 and 68.9%.However,most previous studies were cross section,and the data from developing countries were very limited.In addition,most studies were based on classification of Palmini.Herein,in our first part,we aimed to determine the long-term surgical outcome and to identify the important predictors of favorable surgical outcome in a large cohort of patients with histologically proven FCD.FCD type Ⅱ is a major cause of pharmacoresistery extratemporal lobe epilepsy.The absence of a discrete lesion on MRI has consistently been shown as a predictor for surgical failure.Postoperative seizure outcomes of patients with positive MRI are significantly better than those with negative MRI.Therefore,it is important to improve detection of FCD type Ⅱ lesions.Recently,despite improvements in MRI resolution,some FCD type Ⅱ lesions are too subtle to be detected by conventional visual analysis of MRI scans.A voxel-based morphometry(VBM)post-processing method,which showed favorable results in detecting FCD.However,VBM methods have some inherent limitations.Herein,it is necessary to find a new method to improve detection of FCD type Ⅱ lesions.In our second part,we aimed to use a new method to detect FCD type Ⅱ lesion,and evaluate the clinic value of this new method.Sleep-related epilepsy(SHE)was defined as more than 90%of patients’ total seizures occurring during sleep.SRE may be an independent risk factor for sudden unexpected death in epilepsy.There is a close correlation between SRE and FCD type Ⅱ,The existence of FCD type Ⅱ independently increased the risk of SRE.However,the neuroimaging or clinical data from patients with SRE were rarely.Therefore,in our third part,we hypothesize that there are three potential factors influencing the occurrence of SRE:size of lesion,spatial/lobar distribution of lesion,and volume of thalamus.We set out to test the significance of these three factors in the overall FCD type Ⅱ group.Part OneA longitudinal study of surgical outcome of pharmacoresistant epilepsy causedby focal cortical dysplasiaObjectiveThis study aimed to determine the long-term surgical outcome of pharmacoresistant epilepsy caused by FCD and to identify the important predictors of the favorable surgical outcome.MethodsWe retrospectively analyzed the data of pharmacoresistant epilepsy patients with histologically proven FCD from Second Affiliated Hospital of Zhejiang University and Beijing Sanbo Brain Hospital of Capital Medical University.It included 120 patients with a mean follow-up of 34.6 months.Survival analysis and multivariate regression with Cox proportional hazards model were used to evaluate the rate,stability,and predictors of seizure freedom.ResultsThe estimated chance of seizure freedom was 73.0%[95%confidence intervals(CI);65.2-80.8%]at 1 year after surgery,70.0%(95%CI,62.2-77.8%)at 2 years,and 65%(95%CI,53.2-76.7%)at 5 years and beyond.Most seizure recurrences(85.7%)happened within 12 months after surgery.The incomplete resection of FCD,presence of interictal epileptiform discharges(IEDs)on 3-6 months postoperative electroencephalography(EEG),and presence of habitual acute postoperative seizure(APOS)were independent predictors of seizure recurrence.However,other factors,such as the FCD type and sleep-related epi-lepsy,did not significantly influence the surgical outcome.Before becoming pharmacoresistant epilepsy,30(25%)patients responded to antiepileptic drugs with a seizure-free duration of more than 1 year.ConclusionThe surgical outcome is favorable in patients with FCD,which is comparable to that reported in developed countries.The incomplete resection of FCD,presence of IEDs on 3-6 months post-operative EEG,and presence of habitual APOS are powerful predictive factors for seizure recurrence after surgery.Part TwoAutomated Detection of Focal Cortical Dysplasia Type II with Surface-based MRI Post-processing and Machine LearningObjectiveThis study aimed to determine the role of surface-based MRI morphometry and machine learning for automated lesion detection.MethodsSixty-one patients with pharmacoresistant epilepsy and histologically proven FCD type II from three different epilepsy centers(Second A liated Hospital of Zhejiang University,the Beijing Tiantan Hospital of Capital Medical University,and Cleveland Clinical Foundation)were included in the study.The patients had been evaluated at three different epilepsy centers using 3 different MRI scanners.A normal control database was constructed with 120 normal controls.We also included 35 healthy test controls and 15 disease test controls with histologically confirmed hippocampal sclerosis to assess specificity.Automated lesion detection was performed using an artificial neural network classifier implemented in MATLAB R2015b.We optimized the threshold of the output probability map from the classifier by performing ROC analysis.Success of detection was defined by overlap between the final cluster and the manual labeling.Performance was evaluated using 5-fold cross-validation.ResultsThe threshold of 0.9 showed optimal sensitivity of 73.7%and specificity of 90.0%.The area under the curve for the ROC analysis was 0.75 which suggests a discriminative classifier.Sensitivity and specificity were not significantly different for patients from different centers,suggesting robustness of performance.Correct detection rate was significantly lower in patients with initially normal MRI than patients with unequivocally positive MRI.Subgroup analysis showed the size of training group and normal control database impacted classifier performance.ConclusionAutomated surface-based MRI morphometry equipped with machine learning showed robust performance across cohorts from different centers and scanners.The proposed method may be a valuable tool to improve FCD detection in presurgical evaluation for patients with pharmacoresistant epilepsy.Part ThreeSmall Lesion Size Is Associated with Sleep-Related Epilepsy in Focal Cortical Dysplasia Type ⅡObjectiveTo investigate the neuroimaging and clinical features associated with sleep-related epilepsy(SRE)in patients with focal cortical dysplasia(FCD)type Ⅰ.MethodsPatients with histopathologically proven FCD type II were included from three epilepsy centers(Second Affiliated Hospital of Zhejiang University,the Beijing Tiantan Hospital of Capital Medical University,and Cleveland Clinical Foundation).SRE was de ned according to the video EEG ndings and seizure history.Cortical surface reconstruction and volume calculation were performed using FreeSurfer.The lesions were manually delineated on T1 volumetric MRI using the ITK-SNAP software.The lesions were classi ed as small or large by placing a threshold based on quantitative(whether the lesion was detected on MRI report)and qualitative(volume)criteria.ResultsA total of 77 consecutive patients were included.Of them,36 had SRE and 41 had non-SRE.An earlier age of epilepsy onset,high seizure frequency,regional interictal EEG ndings,and favorable surgical outcome were characteristic in both groups.Small lesions were de ned as those having a volume<3,217 mm3.In total,60.9%of the patients with small FCD lesion(25/41)had SRE,which was signicantly higher than the large lesion group(9/34,26.5%,p= 0.005),Small lesion size was the only predictor signi cantly associated with SRE in the overall type Ⅱ group by multivariate analyses(p= 0.016).Although the proportion of patients who had frontal FCD and SRE was higher than non-frontal FCD(54.5 vs.27.3%,p= 0.043),the relationship between SRE and lesion location was not con rmed by multivariate analysis.Thalamic voltume and seizure semiology were not statistically different between the SRE and non-SRE group.The significant association between lesion size and SRE was reproducible in type Ⅱb and Ⅱa subgroups.ConclusionSRE is common in patients with FCD type Ⅱ.Small FCD type Ⅱ lesions are signi cantly associated with SRE.When evaluating patients with SRE,potential existence of small FCD type Ⅱ lesions should be considered.After re-reviewing the MRI with integrated information of functional imaging and electroclinical data,the percentage of positive MRI increased by 26%in our cohort.erefore,a thorough imaging re-review,accompanied...