Revision and removal of vagus nerve stimulation systems: twenty-five years' experience.

BACKGROUND: Epilepsy, a disease characterized by recurrent seizures, is a common chronic neurologic condition. Antiepileptic drugs (AED) are the mainstay of treatment for epilepsy. Vagus nerve stimulation (VNS) surgery is an adjuvant therapy for the treatment of drug refractory epilepsy (DRE). VNS revision and implant removal surgeries remain common. METHODS: Using a single neurosurgeon data registry for epilepsy surgery, we retrospectively analyzed a total of 824 VNS surgeries. Patients were referred to two Level IV Comprehensive Epilepsy centers (from 08/1997 to 08/2022) for evaluation. Patients were divided into four groups: new device placement, revision surgery, removal surgery, and battery replacement for end-of-life of the generator. The primary endpoint was to analyze the reasons that led patients to undergo revision and removal surgeries. The time period from the index surgery to the removal surgery was also calculated. RESULTS: The median age of patients undergoing any type of surgery was 34 years. The primary reason for revision surgeries was device malfunction, followed by patients' cosmetic dissatisfaction. There was no statistical sex-difference in revision surgeries. The median age and body mass index (BMI) of patients who underwent revision surgery were 38 years and 26, respectively. On the other hand, the primary reason for removal was lack of efficacy, followed again by cosmetic dissatisfaction. The survival analysis showed that 43% of VNS device remained in place for 5 years and 50% of the VNS devices were kept for 1533 days or 4.2 years. CONCLUSIONS: VNS therapy is safe and well-tolerated. VNS revision and removal surgeries occur in less than 5% of cases. More importantly, attention to detail and good surgical technique at the time of the index surgery can increase patient satisfaction, minimize the need for further surgeries, and improve acceptance of the VNS technology.

Carotid artery dissection and non-aneurysmal subarachnoid hemorrhage following carotid endarterectomy.

Stroke continues to be a major public health issue resulting in high mortality and severe long-term disability. Carotid endarterectomy (CEA) plays an important role in the prevention of ischemic stroke. Complications associated with CEA can be life threatening and prompt recognition is crucial. In this report, we present a patient who presented to the hospital with progressive headache, 2 weeks following CEA. He was neurologically intact and hypertensive. Non-contrast head computed tomography (CT) scan showed convexity subarachnoid hemorrhage (SAH). He was found to have a left internal carotid artery dissection. Patients who present to the hospital following CEA with headache and hypertension benefit from a non-contrast head CT scan. The presence of SAH can be a warning sign of cerebral hyperperfusion syndrome. Carotid artery dissection is also a disease entity that can occur in the post-operative period. Prompt recognition and treatment is crucial for the management of these disease entities.

Cannabis and Craniotomy for Glioblastoma: Impact on Complications and Health Care Utilization.

OBJECTIVE: Despite advances in treatment of glioblastomas (GBMs), the median survival remains 14-16 months. In the United States, 52.5 million people ≥12 years of age used cannabis in 2021. We aim to elucidate differences in complications after craniotomy for resection of GBM between users and nonusers of cannabis. METHODS: Merative MarketScan Research Data (2008-2019) (includes >265 million patients) were used to extract adults (≥18 years of age) with GBM diagnosis (International Classification of Diseases-9 code 191.x and International Classification of Diseases-10 code C71.x) who had a craniotomy (Current Procedure Terminology code 61510) from inpatient admission data. The inverse probability treatment weighted analysis balanced the groups of cannabis abuse disorder (CAD) and no CAD in terms of age, gender, insurance coverage, comorbidities, and prior 12-month opioid dependence. RESULTS: Individuals with CAD were younger (median, 37 vs. 51 years; P < 0.0001). There was a lower percentage of women (19% vs. 45%; P < 0.0001). In the CAD group, opioid abuse pattern for ≥12 months was higher (16% vs. 5%; P = 0.001) and the rate of complications was higher (32% vs. 15%; P = 0.001) during index hospital stay. At 6 months postdischarge, neurologic complications were higher among the CAD group (27% vs. 8%; P < 0.001). At 1 year postdischarge, patients with CAD sought fewer outpatient services (P = 0.012). More neurologic complications were seen in the CAD group (31% vs. 12%; P < 0.001). CONCLUSIONS: This retrospective population-based study sounds a higher rate of neurologic complications among patients using cannabis who also had a newly diagnosed GBM. This suggests the lack of a protective effect from use of cannabis in patients with primary malignant brain tumors.

Analysis of the discontinuation and nonpublication of neurooncological randomized clinical trials.

Background: Premature discontinuation and nonpublication of clinical trials contribute to research waste and compromise our ability to improve patient outcomes. However, the extent to which these problems exist in neurooncological randomized clinical trials (RCTs) is not known. This study aimed to evaluate the prevalence of discontinuation and nonpublication of neurooncological RCTs, identify contributing factors, and assess trial characteristics associated with each. Methods: We performed a retrospective, cross-sectional study of neurooncological RCTs registered in Clinicaltrials.gov before March 7, 2023. Data were collected from Clinicaltrials.gov and associated publications were located. We attempted to contact authors for all trials without associated publications or an identified reason for discontinuation. Results: Of 139 included RCTs, 57 (41%) were discontinued. The most common reason for discontinuation identified was slow enrollment or accrual (23%), though 30 trials (53%) were discontinued for unknown reasons. Trials funded by sources other than industry or the National Institutes of Health were more likely to be discontinued (odds ratio 4.2, 95% confidence interval 1.3-13.8). In total, 67 of the 139 (48%) RCTs were unpublished, including 50 of the 57 (88%) discontinued studies and 17 of the 82 (21%) completed studies. Conclusions: In our study, discontinuation of neurooncological clinical trials was common and often occurred for unknown reasons. Trials were also frequently unpublished, particularly those that were discontinued. Addressing these findings may provide an opportunity to reduce research waste and improve outcomes for patients with neurological cancers.

Impact of Management Strategies on New-Onset Mental Health Disorders and Associated Health Care Utilization in Patients with Vestibular Schwannoma.

OBJECTIVE: To compare the impact of different management strategies on diagnosis of new-onset mental health disorders (MHDs) in patients with vestibular schwannoma (VS) and health care utilization at 1-year follow-up. METHODS: MarketScan databases were queried using the International Classification of Diseases, Ninth Revision and Tenth Revision and Current Procedural Terminology, Fourth Edition, 2000-2020. We included patients ≥18 years old with a diagnosis of VS who underwent clinical observation, surgery, or stereotactic radiosurgery (SRS) with at least 1 year of follow-up. We looked at health care outcomes and MHDs at 3-month, 6-month, and 1-year follow-up. RESULTS: The database search identified 23,376 patients. Of these, 94.2% (n = 22,041) were managed conservatively with clinical observation at the initial diagnosis, and 2% (n = 466) underwent surgery. The surgery cohort had the highest incidence of new-onset MHDs followed by SRS and clinical observation cohorts at 3 months (surgery: 17%; SRS: 12%; clinical observation: 7%), 6 months (surgery: 20%; SRS: 16%; clinical observation: 10%), and 12 months (surgery: 27%; SRS: 23%; clinical observation: 16%) (P < 0.0001). The median difference in combined payments between patients with and without MHDs was highest in the surgery cohort followed by SRS and clinical observation cohorts at all time points (12 months: surgery: $14,469; SRS: $10,557; clinical observation: $6439; P = 0.0002). CONCLUSIONS: Compared with clinical observation only, patients who underwent surgery for VS were 2 times more likely and patients who underwent SRS were 1.5 times more likely to develop MHDs with corresponding increase in health care utilization at 1-year follow-up.

Unsaturated glycoceramides as molecular carriers for mucosal drug delivery of GLP-1.

The incretin hormone Glucagon-like peptide 1 (GLP-1) requires delivery by injection for the treatment of Type 2 diabetes mellitus. Here, we test if the properties of glycosphingolipid trafficking in epithelial cells can be applied to convert GLP-1 into a molecule suitable for mucosal absorption. GLP-1 was coupled to the extracellular oligosaccharide domain of GM1 species containing ceramides with different fatty acids and with minimal loss of incretin bioactivity. When applied to apical surfaces of polarized epithelial cells in monolayer culture, only GLP-1 coupled to GM1-ceramides with short- or cis-unsaturated fatty acids trafficked efficiently across the cell to the basolateral membrane by transcytosis. In vivo studies showed mucosal absorption after nasal administration. The results substantiate our recently reported dependence on ceramide structure for trafficking the GM1 across polarized epithelial cells and support the idea that specific glycosphingolipids can be harnessed as molecular vehicles for mucosal delivery of therapeutic peptides.

Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1.

The glycosphingolipid GM1 binds cholera toxin (CT) on host cells and carries it retrograde from the plasma membrane (PM) through endosomes, the trans-Golgi (TGN), and the endoplasmic reticulum (ER) to induce toxicity. To elucidate how a membrane lipid can specify trafficking in these pathways, we synthesized GM1 isoforms with alternate ceramide domains and imaged their trafficking in live cells. Only GM1 with unsaturated acyl chains sorted efficiently from PM to TGN and ER. Toxin binding, which effectively crosslinks GM1 lipids, was dispensable, but membrane cholesterol and the lipid raft-associated proteins actin and flotillin were required. The results implicate a protein-dependent mechanism of lipid sorting by ceramide structure and provide a molecular explanation for the diversity and specificity of retrograde trafficking by CT in host cells.