Abstracts

Fast Ripple (FR) oscillations in the frequency range of 200 to 500 Hz have been identified in epileptogenic hippocampus, entorhinal cortex and subiculum of mesial temporal lobe epilepsy patients and in a kainic acid rat model of epilepsy with spontaneous recurrent seizures (Bragin et al., J, Neurosci., 2002). We wished to determine if mesial temporal lobe (MTL) atrophy (as indicated by volumetric measurement) might form an anatomical substrate for this abnormal activity.
This study included 27 male and female patients with a median age of 35.3 years who were diagnosed with medically intractable seizures and monitored with depth electrodes for determination of the seizure onset location. Spontaneous interictal wide band activity was recorded from microelectrodes in hippocampus, entorhinal cortex and subiculum, and computer detection of FR oscillations was carried out to determine their distribution and rate. Volumetric measurement of the hippocampus, amygdala and entorhinal cortex was performed using dedicated software for stereotactic surgery planning and image analsysis, (@ Target, Brainlab, Heimstteten, Germany). A blinded investigator performed the volumetric measurements using criteria developed at Montreal Neurological Institute (Cendes et al., Neurology,1993; Bernasconi et al., Neurology, 1999,). Mean volumes of the MTL structures and recorded FR rates were subjected to t-test and were correlated with the recorded FR rates.
Of the 27 patients, an extra-temporal focus was identified in 2 and bilateral or non-localized seizure onset was observed in 9. Unilateral mesial temporal seizure onsets were identified in 16 patients. FR activity was detected in 57 microelectrodes in the epileptogenic (side of seizure onset) and contralateral MTL. The mean volumes of both the hippocampus and the amygdala were significantly smaller in the temporal lobe of seizure onset (epileptogenic) than the contralateral temporal lobe (p[lt].0005 and [lt].03 respectively) but no significant difference was found between entorhinal corticies. FR rates were significantly greater in the epileptogenic MTL structures (p[lt].017). There was an inverse correlation between FR rates and hippocampal volumes that was also significant (p[lt].0009, Spearman rank correlation).
FR rate was significantly higher in the epileptogenic MTL containing atrophic hippocampi and amygdala than in contralateral MTL, providing evidence that FR can provide a diagnostic marker for epileptogenic areas created by cell loss and synaptic reorganization associated with hippocampal sclerosis. The presence of FR in adjacent entorhinal cortex and subiculum as well as hippocampus suggests that a network supporting synchronization of high frequency oscillations may provide a critical substrate for epileptogenesis.
[Supported by: NIH grants NS-02808 and NS-33310]