Faculty Bibliography

This preliminary study sought to localize epileptogenic regions in patients with partial epilepsy by analysis of interictal EEG activity utilizing variable resolution electromagnetic tomography (VARETA), a three-dimensional quantitative electroencephalographic (QEEG) frequency-domain distributed source modeling technique. The very narrow band (VNB) spectra spanned the frequency range 0.39 Hz to 19.1 Hz, in 0.39 Hz steps. These VNB spectra were compared to normative data and transformed to provide Z-scores for every scalp derivation, and the spatial distributions of the probable EEG generators of the most abnormal values were displayed on slices from a probabilistic MRI atlas. Each voxel was color-coded to represent the significance of the deviation relative to age appropriate normative values. We compared the resulting three-dimensional images to the localization of epileptogenic regions based on invasive intracranial EEG recordings of seizure onsets. The VARETA image indicated abnormal interictal spectral power values in regions of seizure onset identified by invasive monitoring, mainly in delta and theta range (1.5 to 8.0 Hz). The VARETA localization of the most abnormal voxel was congruent with the epileptogenic regions identified by intracranial recordings with regard to hemisphere in all 6 cases, and with regard to lobe in 5 cases. In contrast, abnormal findings with routine EEG agreed with invasive monitoring with regard to hemisphere in 3 cases and with regard to lobe in 2 cases. These results suggest that analysis of background interictal EEG utilizing distributed source models should be investigated further in clinical epilepsy

Antiepileptic drug (AED) delivery directly into the neocortex has recently been shown to be able to both prevent and terminate focal seizures in rats. The present clinical experiment aimed to test the local effects of lidocaine delivered onto the pia mater adjacent to epileptogenic zones in human patients. Administration of lidocaine resulted in a marked diminishment of spike counts on all patients, with a decremental effect of lidocaine on the faster frequency elements of individual spikes and overall testing epochs. The direct cortical application of lidocaine appears to affect local epileptogenic activity in human patients with intractable focal epilepsy

OBJECTIVE: To evaluate the safety, efficacy, and utility of a novel surgical strategy consisting of multiple (more than two) operative stages performed during the same hospital admission with subdural grid and strip electrodes in selected pediatric extratemporal epilepsy. METHODS: Subdural grid and strip electrodes were used for multistage chronic electroencephalographic monitoring in 15 pediatric patients (age, <19 yr) with refractory localization-related epilepsy and poor surgical prognostic factors. Initial resective surgery and/or multiple subpial transections were performed, followed by further monitoring and additional resection and/or multiple subpial transections. RESULTS: Mean patient age was 9.7 years. Mean duration of total invasive monitoring was 10.5 days (range, 8-14 d). The first monitoring period averaged 6.5 days, and the second averaged 3.9 days. Additional surgery was performed in 13 of 15 patients. Two patients who did not undergo additional surgery had a Class I outcome. Rationales for reinvestigation included incomplete localization, multifocality, and proximity to eloquent cortex. Complications were minimal, including two transfusions. There were no cases of wound infection, cerebral edema, hemorrhage, or major permanent neurological deficit. Minimum duration of follow-up was 31 months. Outcomes were 60% Engel Class I (9 of 15 patients), 27% Class III (4 of 15 patients), and 13% Class IV (2 of 15 patients). CONCLUSION: In a very select group of pediatric patients with poor surgical prognostic factors, the multistage approach can be beneficial. After failed epilepsy surgery, subsequent reoperation with additional intracranial investigation traditionally is used when a single residual focus is suspected. Our results, however, support the contention that multistage epilepsy surgery is safe, effective, and useful in a challenging and select pediatric population with extratemporal medically refractory epilepsy

PURPOSE: Functional mapping of eloquent cortex with electrical neurostimulation is used both intra- and extraoperatively to tailor resections. In pediatric patients, however, functional mapping studies frequently fail to localize language. Wada testing has also been reported to be less sensitive in children. METHODS: Thirty children (4.7 - 14.9 years) and 18 adult controls (18-59 years) who underwent extraoperative language mapping via implanted subdural electrodes at the NYU Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by neurostimulation mapping and determination of hemispheric language dominance on the Wada test. RESULTS: In children younger than 10.2 years, cortical stimulation identified language cortex at a lower rate than was seen in children older than 10.2 years and in adults (p<0.05). This threshold, demonstrated by survival and chi2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than was extraoperative mapping in this younger age group (p<0.05). CONCLUSIONS: Analysis of our series demonstrates that language cortex is less likely to be identified in children younger than 10 years, suggesting that alternatives to the current methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or 'hypersynchrony' which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization