Patient-Specific Characteristics Associated with Favorable Response to Vagus Nerve Stimulation.

OBJECTIVE: The expansion in treatments for medically refractory epilepsy heightens the importance of identifying patients who are likely to benefit from vagus nerve stimulation (VNS). Here, we identify predictors with a positive VNS response. METHODS: We present a retrospective analysis of 158 patients with medically refractory epilepsy. Patients were categorized as VNS responders or nonresponders. Baseline characteristics and time to VNS response were recorded. Univariate and multivariate Cox regression were used to identify predictors of response. Recursive partitioning analysis was used to identify likely VNS responders. RESULTS: Eighty-nine (56.3%) patients achieved ≥50% seizure frequency reduction. Left-hand dominance (hazard ratio [HR] 1.703, P = 0.038), age at epilepsy onset ≥15 years (HR 2.029, P = 0.005), duration of epilepsy ≥8 years (HR 1.968, P = 0.007) and age at implantation ≥35 years (HR 1.809, P = 0.020), and baseline seizure frequency <5/month (HR 1.569, P = 0.044) were significant univariate predictors of VNS response. Following multivariate Cox regression, left-hand dominance, age at epilepsy onset ≥15 years, and duration of epilepsy ≥8 years remained significant. With recursive partitioning analysis, patients with either age at epilepsy onset ≥15 years, left-hand dominance, or baseline seizure frequency <5/month were stratified into Group A and had a 73.9% responder rate; the remaining patients stratified into Group B had a 43.8% responder rate. CONCLUSIONS: Patients with age at epilepsy onset ≥15 years, left-hand dominance, or baseline seizure frequency <5/month are ideal candidates for VNS.

Molecular Structure of 1-Isocyano-1-silacyclopent-3-ene: A Combined Microwave Spectral and Theoretical Study.

The microwave spectrum of 1-isocyano-1-silacyclopent-3-ene has been obtained from broad-band chirped-pulse Fourier transform microwave spectroscopy. The rotational constants (RCs) for the standard abundant isotopic species are A = 3328.4182(23), B = 1017.69404(53), and C = 1012.33297(58) MHz. The symmetric quartic centrifugal distortion constants, using the Ir representation in CS symmetry for ΔJ,ΔJK, ΔK, and δJ, have been evaluated; similarly, the 14N nuclear quadrupole coupling has been determined. Several singly substituted isotopologues observed in natural abundance enabled most of the heavy atom substructure to be determined. The five-membered ring is close to planar, but the orientation of the isocyanate unit, derived from the N13CO spectrum, unexpectedly lies above the ring center in a cis C2,5-Si-N═C conformation. Our initial equilibrium structural searches led to a trans orientation of the C2,5-Si-N═C unit, i.e., bending away from the ring. When the cis conformation was applied, the final equilibrium structure, assuming CS symmetry, gave RC values of 3221.3 ( A), 1037.0 ( B), and 1031.3 ( C) MHz, very close to the MW values. This enabled the full-equilibrium structure to be determined with confidence. The principal bond lengths were 1.7157 (Si-N), 1.8696 (Si-C), 1.1998 (N═C), and 1.1737 (C═O) Å, with angles 163.3 (Si-N═C), 178.1 (N═C═O), 96.5 (C-Si-C), and 118.7° (C-C═C), respectively. The extensive widening of the SiNC angle is particularly notable; the SiNCO unit has a trans dihedral angle. The cis orientation implies a (weak) attractive force between the ring and isocyanate groups by a through-space interaction. An atoms in molecule study, where the local minima of electron density are determined, fails to disclose the exact nature of the interaction; however, a highly polarized skeleton was obtained. A systematic theoretical study of the Si-N═C angle potential energy surface (PES) relative to the ring gave a very shallow double minimum with the barrier being less than 1 cm-1; a polynomial fit to the surface shows major contributions of both harmonic and quartic components. A similar study of the XSiN angle, where X is at the ring center, also gave a PES with considerable quartic character.