Bilateral thalamic responsive neurostimulation for multifocal, bilateral frontotemporal epilepsy: illustrative case.

BACKGROUND: Patients with refractory, bilateral, multifocal epilepsy have few treatment options that typically include a combination of antiseizure medications (ASMs) and vagus nerve stimulation (VNS). A man in his 40s presented with epilepsy refractory to a combination of five ASMs plus VNS; he was still experiencing 7-10 seizures per week. His seizure network involved multiple foci in both frontal and temporal lobes. Bilateral depth electrodes were implanted into the centromedian/parafascicular (CM/PF) complex of the thalamus and connected to the responsive neurostimulation (RNS) system for closed-loop stimulation and neurophysiological monitoring. OBSERVATIONS: The patient reported clear improvement in his seizures since the procedure, with a markedly reduced number of seizures and decreased seizure intensity. He also reported stretches of seizure freedom not typical of his preoperative baseline, and his remaining seizures were milder, more often with preserved awareness. Generalized seizures with loss of consciousness have decreased to about one per month. RNS data confirmed a right-sided predominance of the bilateral seizure onsets. LESSONS: In this patient with multifocal, bilateral frontotemporal epilepsy, RNS of the CM/PF thalamic complex combined with VNS was found to be beneficial. The RNS device was able to detect seizures propagating through the thalamus, and stimulation produced a decrease in seizure burden and intensity.

Outcomes for Adults with Metabolic Syndrome Undergoing Elective Carotid Endarterectomy.

BACKGROUND: Metabolic syndrome (MetS) is a disorder characterized by a constellation of cardiometabolic risk factors including abdominal obesity, dyslipidemia, hypertension, and glucose intolerance that has been associated with adverse perioperative outcomes. We evaluated outcomes for patients with MetS after carotid endarterectomy (CEA) in the largest population to date. METHODS: We performed a matched cohort analysis using clinical data from 2012 to 2018 in the American College of Surgeons National Surgical Quality Improvement Program. We used propensity scores to match patients to attain covariate balance and used logistic regression to assess odds of unfavorable outcomes, including a predefined primary outcome of composite cardiovascular incident. RESULTS: We identified 50,423 eligible adult patients, of whom 14.2% qualified for MetS (n = 7156). Patients with MetS tended to have CEA at an earlier age, more functional dependence, and longer operative durations. After matching, MetS remained associated with the primary outcome of combined cardiovascular incident (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.18-1.72; P < 0.001), stroke (OR, 1.44; 95% CI, 1.12-1.85; P = 0.004), prolonged length of stay (OR, 1.31; 95% CI, 1.18-1.44; P < 0.001), and discharge to facility (OR, 1.32; 95% CI, 1.08-1.61; P = 0.007). We also found that obesity alone is protective against combined cardiovascular incident, whereas hypertension with diabetes and MetS increase odds of a cardiovascular complication. CONCLUSIONS: Metabolic syndrome is associated with adverse outcomes for adult patients undergoing elective CEA.

Methylome of skeletal muscle tissue in patients with hypertension and diabetes undergoing cardiopulmonary bypass.

Background: Epigenomic changes occurring during surgery have been neglected in research; diabetes and hypertension can affect the epigenome but little is known about the epigenetics of skeletal muscle (SKM). Methods: DNA methylation was profiled via Illumina MethylationEPIC arrays in SKM samples obtained at the beginning and end of heart surgery with cardiopulmonary bypass. Results: Methylation in patients with hypertension and diabetes was significantly different, more so for uncontrolled diabetes; hypertension alone produced minimal effect. The affected pathways involved IL-1, IL-12, IL-18, TNF-α, IFN-γ, VEGF, NF-κB and Wnt signaling, apoptosis and DNA damage response. Significant changes occurred during surgery and included loci in the Hippo-YAP/TAZ pathway. Conclusion: Cardiopulmonary bypass surgery affects the SKM methylome, and the combination of hypertension and diabetes induces changes in the SKM epigenome in contrast to hypertension alone.

Two-trajectory laser amygdalohippocampotomy: Anatomic modeling and initial seizure outcomes.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. METHODS: We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. RESULTS: The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p < .05). Two-laser trajectories achieved full ablation of MTL cortical structures at physiologically realistic burn radii, whereas one-laser trajectories could not. Five patients with at least 1 year of follow-up (mean = 21.8 months) experienced Engel class I outcomes; 6 patients with less than 1 year of follow-up (mean = 6.6 months) are on track for Engel class I outcomes. SIGNIFICANCE: Our anatomic analyses and initial clinical results suggest that LITT amygdalohippocampotomy performed via two-laser trajectories may promote excellent seizure outcomes. Future studies are required to validate the long-term clinical efficacy and safety of this approach.