Physiology of human cortical neurons adjacent to cavernous malformations and tumors

Purpose: Focal neocortical seizures can be associated with a number of specific pathologies including supratentorial tumors and cavernous malformations (CMs), both of which are highly epileptogenic. Methods: To begin to address the question of whether these lesions have different mechanisms of epileptogenesis, we used intracellular recordings from neurons adjacent to intracerebral neoplasms and cerebral CMs. Developmental anomalies were not included in this study. Results: Neurons adjacent to CMs had a greater propensity to show large (>5 mV), complex spontaneous synaptic events than did neurons neighboring neoplastic substrates (50 vs. 4.7% of cells and 75 and 8% of patients, respectively; p < 0.004; p < 0.05). Both spontaneous excitatory and inhibitory events were noted. In contrast, in tissue adjacent to tumors, low-amplitude (<3 mV) spontaneous excitatory activity predominated. Neurons neighboring CMs also exhibited more excitable responses to synaptic stimulation, with multiple action potentials riding on prolonged excitatory postsynaptic potentials (EPSPs) being evoked in 71% of these cells, versus 32% of cells from the tumor group; p < 0.05. In studies using hippocampal tissue, we noted a similar pattern of spontaneous activity in tissue adjacent to CMs. Conclusions: These data suggest that CMs may induce seizure activity via a different pathophysiologic mechanism(s) than glial tumors.