Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The U.S. E-37 Trial.

OBJECTIVES: The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and long- term clinical outcomes of the device stimulating in all modes. MATERIALS AND METHODS: The E-37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR(®) in subjects with drug-resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events. RESULTS: Twenty implanted subjects (ages 21-69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3). CONCLUSIONS: The Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements.

Oxcarbazepine in infants and young children with partial seizures.

In this open-label study, the safety, tolerability, and pharmacokinetics of oxcarbazepine as monotherapy or adjunctive therapy were studied in infants and young children with partial seizures. In a 30-day treatment phase, oxcarbazepine was titrated from 10 mg/kg/day to 60 mg/kg/day. Blood samples for analysis of the oxcarbazepine metabolite, the 10-monohydroxy derivative (MHD), were obtained at regular intervals. Patients completing the treatment phase entered a 6-month extension phase. Safety and tolerability were assessed throughout the study. Twenty-four patients (mean [range] age, 20.4 [2-45] months) were enrolled. Nineteen (79%) patients completed the treatment phase and, together with one patient who discontinued prematurely during the treatment phase, entered the extension phase. Thirteen of 20 (65%) patients completed the extension phase. The most common adverse events were pyrexia, ear infection, and irritability. Whether patients (n = 23) received enzyme-inducing antiepileptic drugs or not, MHD concentrations were consistent with those predicted from a linear, one-compartment, population-pharmacokinetic model based on a model previously fitted for 3- to 17-year-old children. Oxcarbazepine was safe and well tolerated in infants and young children. The pharmacokinetic profile of MHD was predicted by extension of a model based on older children.

Intraoperative monitoring for intracranial aneurysms: the Michigan experience.

Intraoperative neurophysiological monitoring is routinely used during the repair (endovascular or microsurgical) of intracranial aneurysms at major centers. There is a continued need of data sets from institutions with dedicated intraoperative neurophysiological monitoring services to further define the predictive factors of postoperative neurological deficits. We retrospectively reviewed and analyzed our database of all patients who underwent repair of intracranial aneurysms (endovascular or microsurgical). A total of 406 patients underwent 470 procedures. The changes were noted during monitoring in 3.83% of the cases. Most of the changes were first detected in somatosensory evoked potential (88.89%) followed by brainstem auditory evoked potential (16.67%). Changes were completely reversible in 44.44%, only partly reversible in 22.22%, and irreversible in 33.33% of cases. Intraoperative neurophysiological monitoring changes demonstrated high sensitivity, specificity, and negative predictive value for postoperative neurological deficits. The association between intraoperative neurophysiological monitoring changes and Glasgow outcome scale was significant for reversible changes compared against irreversible and partly reversible changes. Presence of any intraoperative neurophysiological monitoring modality change during repair of intracranial aneurysm may suggest a higher risk for postoperative neurological deficits. Reversibility of the changes is a favorable marker, whereas irreversible changes are predictive of postoperative neurological deficits with deterioration of Glasgow outcome scale on a longer follow-up.

Formulation of current density weighted indices for correspondence between functional MRI and electrocortical stimulation maps.

OBJECTIVE: Accurate localization of functionally significant brain regions reduces risks of post-operative neurological deficits. The gold standard for presurgical brain mapping is subdural electrocortical stimulation (ECS), which is an open-cranium surgical procedure. Functional MRI (fMRI) may be a noninvasive alternative if it can be shown that fMRI and ECS maps are spatially consistent. We formulate new 3D current density weighted ECS-fMRI correspondence indices and illustrate their use on human data. METHODS: Current density maps were computed for simulated and human datasets by solving the electrostatic Laplace equation. The proposed indices were characterized and compared with fixed radii and Euclidean distance indices. RESULTS: Results from simulated datasets showed that the proposed indices quantify correspondence between fMRI and the ECS truth predictably, and provide conspicuous sensitivity increase from fixed radii indices, whereas Euclidean distances may not be suitable measures of the correspondence. CONCLUSIONS: The proposed indices reflect contextual information from surrounding electrodes and may be physiologically more meaningful in evaluating ECS-fMRI correspondence. SIGNIFICANCE: To identify safe limits of resection, an ECS map requires placement of electrodes on a patient's brain. Our proposed indices accurately quantify ECS-fMRI correspondence and may be used to evaluate fMRI as a noninvasive alternative for defining resection limits.