Faculty Bibliography

OBJECTIVE: The goal of the work described here was to assess the efficacy and safety of vagus nerve stimulation in a cohort of patients with tuberous sclerosis complex with refractory epilepsy. Furthermore, we examined the impact of vagus nerve stimulation failure on the ultimate outcome following subsequent intracranial epilepsy surgery. METHODS: A retrospective review was performed on 19 patients with refractory epilepsy and TSC who underwent vagus nerve stimulator (VNS) implantation. There were 11 (58%) females and 8 (42%) males aged 2 to 44 years when the VNS was implanted (mean: 14.7+/-12 years). Twelve patients underwent primary VNS implantation after having failed a mean of 7.1 antiepileptic drugs. Two patients (17%) had generalized epilepsy, one had a single seizure focus, three (25%) had multifocal epilepsy, and six (50%) had multifocal and generalized epilepsy. Seven patients were referred for device removal and evaluation for intracranial procedures. One patient in the primary implantation group was lost to follow-up and excluded from outcome analysis. RESULTS: All implantations and removals were performed without permanent complications. The duration of treatment for primary VNS implants varied from 8.5 months to 9.6 years (mean: 4.9 years). Mean seizure frequency significantly improved following VNS implantation (mean reduction: 72%, P<0.002). Two patients had Engel Class I (18%), one had Class II (9%), seven had Class III (64%), and one had Class IV (9%) outcome. Three patients with poor response to vagus nerve stimulation therapy at our center underwent resection of one or more seizure foci (Engel Class I, two patients; Engel Class III, one patient). Seven patients referred to our center for VNS removal and craniotomy underwent seizure focus resection (6) or corpus callosotomy (1) (Engel Class II: 2, Engel III: 2; Engel IV: 3). In total, 8 of 10 (80%) patients experienced improved seizure control following intracranial surgery (mean reduction: 65%, range: 0-100%, P<0.05). CONCLUSIONS: VNS is a safe and effective treatment option for medically refractory epilepsy in patients with tuberous sclerosis complex. Nine of 11 patients (82%) experienced at least a 67% reduction in seizure burden. Lack of response to vagus nerve stimulation does not preclude subsequent improvement in seizure burden with intracranial epilepsy surgery

The electroencephalogram (EEG) is a mainstay of clinical neurology and is tightly correlated with brain function, but the specific currents generating human EEG elements remain poorly specified because of a lack of microphysiological recordings. The largest event in healthy human EEGs is the K-complex (KC), which occurs in slow-wave sleep. Here, we show that KCs are generated in widespread cortical areas by outward dendritic currents in the middle and upper cortical layers, accompanied by decreased broadband EEG power and decreased neuronal firing, which demonstrate a steep decline in network activity. Thus, KCs are isolated 'down-states,' a fundamental cortico-thalamic processing mode already characterized in animals. This correspondence is compatible with proposed contributions of the KC to sleep preservation and memory consolidation

Measurement of the blood-oxygen-level dependent (BOLD) response with fMRI has revolutionized cognitive neuroscience and is increasingly important in clinical care. The BOLD response reflects changes in deoxy-hemoglobin concentration, blood volume, and blood flow. These hemodynamic changes ultimately result from neuronal firing and synaptic activity, but the linkage between these domains is complex, poorly understood, and may differ across species, cortical areas, diseases, and cognitive states. We describe here a technique that can measure neural and hemodynamic changes simultaneously from cortical microdomains in waking humans. We utilize a 'laminar optode,' a linear array of microelectrodes for electrophysiological measures paired with a micro-optical device for hemodynamic measurements. Optical measurements include laser Doppler to estimate cerebral blood flow as well as point spectroscopy to estimate oxy- and deoxy-hemoglobin concentrations. The microelectrode array records local field potential gradients (PG) and multi-unit activity (MUA) at 24 locations spanning the cortical depth, permitting estimation of population trans-membrane current flows (Current Source Density, CSD) and population cell firing in each cortical lamina. Comparison of the laminar CSD/MUA profile with the origins and terminations of cortical circuits allows activity in specific neuronal circuits to be inferred and then directly compared to hemodynamics. Access is obtained in epileptic patients during diagnostic evaluation for surgical therapy. Validation tests with relatively well-understood manipulations (EKG, breath-holding, cortical electrical stimulation) demonstrate the expected responses. This device can provide a new and robust means for obtaining detailed, quantitative data for defining neurovascular coupling in awake humans

We describe the anesthetic management of a morbidly obese patient with obstructive sleep apnea who underwent awake craniotomy. The patient's personal continuous positive airway pressure (CPAP) machine was used to support ventilation intraoperatively. Dexmedetomidine was used as the primary sedative. During cortical mapping, the CPAP was discontinued. The patient was comfortable and able to cooperate with language testing

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