Abstracts

Rationale: Lesions during early development and diverse mechanisms of antiepileptic drugs (AED) resistance have been proposed as contributing factors to the pathophysiology of temporal lobe epilepsy (TLE), the prototype of surgically remediable epilepsy. Paraclinical studies and experiments on benzodiazepines (BDZ) in human epileptic neocortex have evidenced alterations in the GABA system, though their clinical correlates have rarely been assessed. The objective of the present study was to evaluate BDZ receptors in epileptic temporal neocortical tissue in relation to the patients clinical history. Methods: We studied twenty surgically treated patients with TLE and standardized presurgical testing (EEG, video EEG, MRI, PET, SPECT, neuropsychological and neuropsychiatric evaluations) at the National Institute of Neurology and Neurosurgery. Lateral temporal neocortical tissue, without evidence of abnormality on high-resolution MRI was obtained during surgery and stored at -70 C until processing. Quantitative autoradiography was performed to evaluate the binding by cortical layers (I-II, III-IV, V-VI) of 3H-flunitrazepam, a ligand for central and peripheral benzodiazepine receptors (CBR, PBR, respectively). Ten autopsy samples of subjects without neurological disease were used as controls. We distinguished between patients with lesional TLE and patients with hippocampal sclerosis (MTLE-HS). BDZ receptor results were correlated with clinical data (age, age at onset, duration of illness, seizure frequency, number of AEDs used, familial history, and neuroinfection, perinatal hypoxia, febrile seizures and head trauma). Results: Fourteen patients were diagnosed as MTLE-HS and 6 as lesional TLE (tumor, cavernoma, cortical dysplasia). All patients showed increased BDZ binding throughout the cortex, significantly in layers I-II and V-VI. Inversely proportional correlations were found between BDZ binding and: (a) age (III-IV), (b) duration of epilepsy (III-IV & V-VI), (c) number of generalized seizures (I-II), (d) monthly seizure rate (III-IV), and (e) the number of AEDs (III-IV & V-VI). In particular, BDZ binding in patients with MTLE-HS showed inversely proportional correlations with: (a) age (V-VI), (b) age at onset (V-VI), (c) seizure frequency (III-IV), (d) monthly seizure rate (III-IV), (e) number of AEDs (I-II). Significant differences existed regarding precipitating injuries in the form of febrile seizures (V-VI) and perinatal hypoxia (I-II). Conclusions: These results may be indicative of tissular injury secondary to epilepsy and/or impaired inhibitory function due to increased dysfunctional GABAergic synapses, a situation probably involved in the initiation and propagation of epileptic activity in the temporal lobe.