The Neuroimaging Study Of Classification And Cognitive Dysfunction In Childhood Epilepsy With Centrotemporal Spikes

Epilepsy is one of the most common and serious neurological diseases.The majority of epilepsy patients are children or adolescents.Childhood epilepsy with centrotemporal spikes（ECTS）is the most common epilepsy syndrome in children,accounting for up to 16%of pediatric epilepsy.Although ECTS was initially described as a benign syndrome,the current studies have reached a consensus that ECTS could show adverse symptoms such as high frequency of seizures and cognitive dysfunction.Therefore,it is important to investigate the severity and cognitive dysfunction of ECTS patients for targeted treatment.A significant number of ECTS patients can evolve to an atypical form,characterized by high seizure frequencies with multiple seizure types and poor neuropsychological outcomes.Identifying the subtypes of ECTS is crucial for the management of patients.However,the identification of ECTS subtypes mostly depends on the evaluation of clinical symptoms,and lacks quantitative neuroimaging evidence in clinical practice.Meanwhile,a large amount of epileptic discharges was found during the interictal period in ECTS patients.Frequent epileptic discharges lead to cognitive decline,especially in processing speed.Processing speed refers to the ability to identify,integrate,make decisions and respond to visual,language and motor information.The weaker the processing speed,the lower the efficiency of thinking and learning.Compared with other cognitive complications,there are few studies on the processing speed of ECTS patients.Like other cognitive abilities,processing speed can be trained,learned and improved.Therefore,it is important to explore the neuropsychological mechanism of processing speed in ECTS patients for precision treatment.In recent years,functional neuroimaging technology has been widely used in the studies of cognitive function in epilepsy patients.Resting state functional magnetic resonance imaging（rs-f MRI）is an important approach to analyze brain function.Rs-f MRI can explore the integration of brain function and explore the abnormal network changes between brain regions.¹⁸F-fluorodeoxyglucose positron emission tomography(¹⁸F-FDG PET)can detect the abnormality of brain glucose metabolism caused by epileptic activity,and the brain glucose metabolic rate can directly reflect the activity of neurons and glia.To our knowledge,no previous study has explored the classification of ECTS subtypes and neuroimaging mechanism of slowed processing speed in patients with ECTS.In this study,we aimed to comprehensively investigate the glucose metabolic differences between typical and atypical ECTS using ¹⁸F-FDG PET imaging,and explore whether these differences can help distinguish.In addition,we combined¹⁸F-FDG PET and rs-f MRI imaging techniques to explore the neuroimaging mechanism of cognitive dysfunction in ECTS patients.Part 1:Brain metabolic characteristics distinguishing typical andatypical Childhood epilepsy with centrotemporal spikesObjectivesAtypical childhood epilepsy with centrotemporal spikes（ECTS）have much less favorable outcomes than typical ECTS,and thus should be accurately identified for adequate treatment.We aimed to investigate the glucose metabolic differences between typical and atypical ECTS using ¹⁸F-fluorodeoxyglucose(¹⁸F-FDG)positron emission tomography（PET）imaging,and explore whether these differences can help distinguish.MethodsForty-six patients with typical ECTS,31 patients with atypical ECTS and 23controls who underwent ¹⁸F-FDG PET examination were retrospectively involved.Absolute asymmetry index（|AI|）was applied to evaluate severity of metabolic abnormality.Glucose metabolic differences were investigated among typical ECTS,atypical ECTS and controls using Statistical Parametric Mapping（SPM）.Logistic regression analyses were performed based on clinical,PET and hybrid features.ResultsThe|AI|was found significantly higher in the atypical ECTS than the typical ECTS（P=0.040）.Atypical ECTS showed more hypo-metabolism regions than typical ECTS,mainly located in the frontal,parietal and limbic lobes.The PET model had significantly higher area under the curve（AUC）than the clinical model（0.91 vs.0.70,P=0.006）.The hybrid model had the highest sensitivity（0.90）,specificity（0.85）and accuracy（0.87）of all three models.ConclusionAtypical ECTS showed more widespread and severe hypo-metabolism than typical ECTS,depending on which the two groups can be well distinguished.The combination of metabolic characteristics and clinical variables has the potential to be used clinically to distinguish between typical and atypical ECTS.Part 2: Cognitive dysfunction in childhood epilepsy with centrotemporal spikes: A 18F-FDG PET and resting f MRI studyObjectives Patients with ECTS can show delayed cognitive and behavioral maturation,in which the underlying cause of processing speed dysfunction was not fully understood.This study aimed to investigate the alterations of glucose metabolism and functional connectivity of cortico-striatal-thalamic loop circuit in ECTS patients and their relationships with processing speed.Methods Twenty-eight ECTS patients who had completed the 18F-FDG PET,functional MRI（f MRI）,structure MRI（s MRI）and neuropsychological examinations were recruited in the study.Twenty age-matched healthy children were recruited as controls for MRI image analysis and 20 age-matched children with normal glucose metabolism were selected as controls for PET image analysis.The PET image analysis investigated glucose metabolism of cortical-striatal-thalamic loop circuit by determining standardized uptake value ratio（SUVR）.Abnormal functional connectivity（FC）within cortical-striatal-thalamic loop circuit of ECTS patients were also calculated through network based analysis（NBS）.Correlation analysis was performed to explore the relationship between SUVR,FC and processing speed index（PSI）.Results Patients with ECTS showed significantly decreased PSI compared with controls（P = 0.04）.The SUVRs of putamen（P = 0.002）,caudate（P = 0.037）,nucleus accumbens（NAc）（P = 0.007）and pallidum（P = 0.001）were significantly decreased in ECTS patients than those of controls.Both SUVRs of putamen（P = 0.025）and caudate（P =0.027）were positively correlated with the PSI in ECTS patients,while those of NAc（P = 0.052）and pallidum（P = 0.860）were not correlated with PSI.NBS analysis showed that the absolute values of 27 FCs were significantly decreased in ECTS patients,and the mean value of these FCs was positively correlated with the PSI（P = 0.026）.The FCs of bilateral precentral gyri（P = 0.005）and postcentral gyri（P < 0.001）were positively correlated with PSI.The SUVR of caudate was negatively correlated with the FC from caudate to ROIs related to PSI（P = 0.033）.Conclusions The reduced PSI in ECTS patients was related to decreased metabolism and FC of cortical-striatal-thalamic loop circuit,in which caudate played an important role.The epileptic discharges in Rolandic areas could lead dysfunctions of cortical-striatal-thalamic loop circuit.