Clinical neurophysiological correlates of histopathological abnormalities in epilepsy surgery

Abstract

In search for variables that determine outcome in patients with pharmacoresistant epilepsy who undergo epilepsy surgery, we identified specific combinations of clinical neurophysiological findings with their underlying histopathology. These findings may have important surgical consequences. In a sample of patients with frontal lobe epilepsy, about 50% had an underlying diagnosis of focal cortical dysplasia. The pathology was not related to the surgical outcome. However, we found that contralateral head version, eye deviation and autonomic manifestions as ictal symptoms were associated with a poor outcome, whereas a focal abnormality on neuroimaging was related to a favourable outcome. Intraoperative electrocorticography (ECoG) in these patients revealed that dense epileptiform patterns (consisting of continuous spiking, bursts of spikes or recruiting discharges) in the preresection recordings were associated with a diagnosis of focal cortical dysplasia (sensitvity 94%, specificity 75%, positive predictive value 80%). The abolition of these patterns on postresection recordings was associated with a favourable outcome, whereas persistence of sporadic spikes and incomplete removal of histopathological abnormalities did not affect outcome. When studying the ECoG and histopathological findings in a sample of patients with neurodevelopmental lesions, we found that dense epileptiform ECoG patterns occurred in patients with focal cortical dysplasia, but also in those with a glioneuronal tumour (ganglioglioma or dysembryoplastic neuroepithelial tumour). One of these patterns, i.e. continuous spiking, was seen significantly more often in focal cortical dysplasia and this pattern was highly specific (96%) for the presence of a disorganized cortical architecture in the whole sample of patients. When studying patients with a cavernoma we found that dense epileptiform patterns occurred to a similar degree as in those with a neurodevelopmental lesion. In both patients with a neurodevelopmental lesion and cavernoma continuous spiking in the neocortex seems characteristic of early onset of seizures and such patterns may involve the hippocampus in time. We thus concluded that, in general, such patterns are not specific for neurodevelopmental lesions. We consider the expression of continuous neocortical spiking in the ECoG to be a marker of early disruption of functional systems in the developing brain. To investigate whether unilateral recognition memory was related to the neuronal integrity of the mesial temporal structures, metabolite ratios [NAA/(Cr+PCr), NAA/Cho, and NAA/(Cr+PCr+Cho)] from proton MR Spectroscopy were correlated with hemispheric memory scores from the Wada test. The total memory score, memory for objects and faces, and NAA/(Cr+PCr) were significantly lower for the hemisphere ipsilateral to the resection. Furthermore, we found positive correlations between unilateral memory for words and the NAA/(Cr+PCr) ratio from medial temporal structures in patients with mesial temporal sclerosis. The findings suggest that medial temporal structures play a significant role in recognition memory in humans, particularly for words and raise the question whether MR Spectroscopy can be used for presurgical memory lateralisation.