Clinical And Experimental Study On Pathological Mechanism And Reoperation Outcome With Drug Resistant Epilepsy In Children

Objective: To observe pathological changes of epileptogenic foci in children with drugresistant epilepsy, to discuss the potential pathogenesis of drug resistant epilepsy frompathology, and to clear out whether mossy fiber sprouting and synaptic reorganization are thepathogenesis basis of drug resistant epilepsy in children.Methods: After rigorous preoperative evaluation, the cortexes of epileptogenic foci wereobtained from30surgery candidates (under18years) with drug resistant epilepsy whoaccepted resective surgery. The specimens were observed under the light microscope and thetransmission electron microscope.Results:1. Pathological Changes:1) Under the light microscope,30specimens had differentdegrees of decrease in neuron number and of increase in glial cell number. Cortical dysplasiawas identified in14(47%) patients. Hippocampal sclerosis was found in11patients (37%),the dysembryoplastic neuroepithelial tumor (DNT), ganglioglioma, and encephalomalaciawere observed in1(3%),1(3%) and3(10%) patients, respectively.2) The ultrastructurechanges of epileptogenic foci in hippocampus were similar to those in extra-hippocampalcortices, including changes of synaptic quantity and structure, pycnotic and decreasedneurons, hydropic and degenerative astrocytes, and damaged mitochondrial structures.Overall,22of30patients (73%) improved after operation:16patients (53%) achieved EngelⅠclass, and6patients (20%) were Engel Ⅱ class, while8of30patients (27%) seizuresdecresad indistinctively, in which7patients (24%) were Engel Ⅲ class, and1patient (3%)were Engel Ⅳ class, who relieved seizure severity but remained unchanged with seizure frequency.7of11patients (64%) achieved seizure freedom after anteromesial temporalresection, whereas9of19patients (47%) gained seizure freedom after extratemporal cortexesresection. There wasn’t significant difference between surgery types and operation outcome(Fisher probabilities, P=0.833).Conclusions:1. Although there are maybe different in clinical manifestations and etiologiesof drug resistant epilepsy, neuron degeneration and gliosis are the characteristics of allepileptogenic foci.2. The primary manifestation of synapse reorganization is mossy fibersprouting in hippocampus with temporal lobe epilepsy, while there is an increase ofasymmetry synaptics in cortex with extratemporal lobe epilepsy. Therefore synapsereorganization may be a morphological basis of recurrently spontaneous seizures, which isrelated to the destroyed balance between excitatory and inhibitory neuron transmission.3. Thetheoretical basis of epilepsy surgery is:1) on the base of guaranteeing patients’ importantbrain functions, to resect the largest extent of epileptogenic brain tissue after exactlylocalizing seizure focus;2) to eliminate “epileptogenic cell” for the purpose of achievingseizure freedom. Objective: To analyze seizure outcome of reoperation in children with drug resistant epilepsyafter failedly resective surgery or reccurrence, to identify predictors of seizure outcome ofreoperation and inspiration of epilepsy resective surgery.Methods: After systematically analyzed the results of comprehensive preoperativeevaluations before the first surgery, and before reoperation,4children from30patients whowere studied in the first part of our study underwent resective reoperation.Results: Four cases all underwent extended resective reoperation during the study period(mean follow-up11.25months). Types of resection included temporoparietooccipital (3/4)and frontal (1/4). One had seizure freedom (Engel class Ⅰ),and three had seizure reduction(Engel class Ⅱ) at last follow up, in addition, none of them had significant or unacceptable complication.Conclusions: Patients with drug resistant epilepsy after the first failed epilepsy surgery canregain seizure freedom outcome when they underwent reoperation after comprehensivereevaluation. Predictors with likelihood of seizure freedom after reoperation are1) retainedmedial temporal structures or relevant MRI structural lesion;2) original surgery suboptimal;3) preceding evaluation suggests solitary identified focus;4) semiology relate to preoperativeseizures.