Arterial Bypass in the Treatment of Complex Middle Cerebral Artery Aneurysms: Lessons Learned from Forty Patients.

OBJECTIVE: Complex middle cerebral artery (MCA) aneurysms incorporating parent or branching vessels are often not amenable to standard microsurgical clipping or endovascular embolization treatments. We aim to discuss the treatment of such aneurysms via a combination of surgical revascularization and aneurysm exclusion based on our institutional experience. METHODS: Thirty-four patients with complex MCA aneurysms were treated with bypass and aneurysm occlusion, 5 with surgical clipping or wrapping only, and 1 with aneurysm excision and primary reanastomosis. Bypasses included superficial temporal artery (STA)-MCA, double-barrel STA-MCA, occipital artery-MCA, and external carotid artery-MCA. After bypass, aneurysms were treated by surgical clipping, Hunterian ligation, trapping, or coil embolization. RESULTS: The average age at diagnosis was 46 years. Of the aneurysms, 67% were large and most involved the MCA bifurcation. Most bypasses performed were STA-MCA bypasses, 12 of which were double-barrel. There were 2 wound-healing complications. All but 2 of the aneurysms treated showed complete occlusion at the last follow-up. There were 3 hemorrhagic complications, 3 graft thromboses, and 4 ischemic insults. The mean follow-up was 73 months. Of patients, 83% reported stable or improved symptoms from presentation and 73% reported a functional status (Glasgow Outcome Scale score 4 or 5) at the latest available follow-up. CONCLUSIONS: Cerebral revascularization by bypass followed by aneurysm or parent artery occlusion is an effective treatment option for complex MCA aneurysms that cannot be safely treated by standard microsurgical or endovascular techniques. Double-barrel bypass consisting of 2 STA branches to 2 MCA branches yields adequate flow replacement in most cases.

Proximal Internal Carotid Artery Occlusion and Extracranial-Intracranial Bypass for Treatment of Fusiform and Giant Internal Carotid Artery Aneurysms.

OBJECTIVE: To discuss the treatment of intracranial fusiform and giant internal carotid artery (ICA) aneurysms via revascularization based on our institutional experience. METHODS: An institutional review board-approved retrospective analysis was performed of patients with unruptured fusiform and giant intracranial ICA aneurysms treated from November 1991 to May 2020. All patients were evaluated for extracranial-intracranial (EC-IC) bypass and ICA occlusion. RESULTS: Thirty-eight patients were identified. Initially, patients failing preoperative balloon test occlusion were treated with superficial temporal artery (STA)-middle cerebral artery (MCA) bypass and concurrent proximal ICA ligation. We then treated them with STA-MCA bypass, followed by staged balloon test occlusion, and, if they passed, endovascular ICA coil occlusion. We treat all surgical medically uncomplicated patients with double-barrel STA-MCA bypass and concurrent proximal ICA ligation. The mean length of follow-up was 99 months. Symptom stability or improvement was noted in 85% of patients. Bypass graft patency was 92.1%, and all surviving patients had patent bypasses at their last angiogram. Aneurysm occlusion was complete in 90.9% of patients completing proximal ICA ligation. Three patients experienced ischemic complications and 4 patients experienced hemorrhagic complications. CONCLUSIONS: Not all fusiform intracranial ICA aneurysms require intervention, except when life-threatening rupture risk is high or symptomatic management is necessary to preserve function and quality of life. EC-IC bypass can augment the safety of proximal ICA occlusion. The rate of complete aneurysm occlusion with this treatment is 90.9%, and long-term bypass graft-related complications are rare. Perioperative stroke is a major risk, and continued evolution of treatment is required.

Postoperative Admission of Adult Craniotomy Patients to the Neuroscience Ward Reduces Length of Stay and Cost.

BACKGROUND: The neurointensive care unit (NICU) has traditionally been the default recovery unit after elective craniotomies. OBJECTIVE: To assess whether admitting adult patients without significant comorbidities to the neuroscience ward (NW) instead of NICU for recovery resulted in similar clinical outcome while reducing length of stay (LOS) and hospitalization cost. METHODS: We retrospectively analyzed the clinical and cost data of adult patients undergoing supratentorial craniotomy at a university hospital within a 5-yr period who had a LOS less than 7 d. We compared those admitted to the NICU for 1 night of recovery versus those directly admitted to the NW. RESULTS: The NICU and NW groups included 340 and 209 patients, respectively, and were comparable in terms of age, ethnicity, overall health, and expected LOS. NW admissions had shorter LOS (3.046 vs 3.586 d, P < .001), and independently predicted shorter LOS in multivariate analysis. While the NICU group had longer surgeries (6.8 vs 6.4 h), there was no statistically significant difference in the cost of surgery. The NW group was associated with reduced hospitalization cost by $3193 per admission on average (P < .001). Clinically, there were no statistically significant differences in the rate of return to Operating Room, Emergency Department readmission, or hospital readmission within 30 d. CONCLUSION: Admitting adult craniotomy patients without significant comorbidities, who are expected to have short LOS, to NW was associated with reduced LOS and total cost of admission, without significant differences in postoperative clinical outcome.

Isocitrate Dehydrogenase Mutations in Low-Grade Gliomas Correlate With Prolonged Overall Survival in Older Patients.

BACKGROUND: Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult. OBJECTIVE: To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles. METHODS: We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available. RESULTS: Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P < .001). Older age, seizure at presentation, larger tumor size, IDH wildtype, biopsy only, chemotherapy, and radiation were significantly associated with shorter survival based on univariate analyses. In patients with known IDH status (n = 73), bivariate analysis of IDH mutation status and age showed only IDH status significantly influenced overall survival (HR 0.22 [0.07-0.68], P = .008). Greater surgical resection was predictive of survival, although extent of resection significantly correlated with IDH mutation status (odds ratio 7.5; P < .001). CONCLUSION: We show that genomic alterations in LGG patients ≥40 occur at high rates like the younger population and predict a similar survival advantage. Maximizing surgical resection may have survival benefit, although feasibility of resection is often linked to IDH status. Given the importance of molecular genetics, a redefinition of prognostic factors associated with these tumors is likely to emerge.

Pharmacodynamics of mutant-IDH1 inhibitors in glioma patients probed by in vivo 3D MRS imaging of 2-hydroxyglutarate.

Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2-hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic modifications of gene expression. In this study, we show the initial evidence of the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non-invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0.019) after 1 week of treatment. Importantly, inhibition of mutant IDH1 may lead to the reprogramming of tumor metabolism, suggested by simultaneous changes in glutathione, glutamine, glutamate, and lactate. An inverse correlation between metabolic changes and diffusion MRI indicates an effect on the tumor-cell density. We demonstrate a feasible radiopharmacodynamics approach to support the rapid clinical translation of rationally designed drugs targeting IDH1/2 mutations for personalized and precision medicine of glioma patients.

Stress impairs new but not established relationships in seasonally social voles.

Affiliative social relationships are impacted by stressors and can shape responses to stress. However, the effects of stress on social relationships in different contexts are not well understood. Meadow voles provide an opportunity to study these effects on peer relationships outside of a reproductive context. In winter months, female meadow voles cohabit with peers of both sexes, and social huddling is facilitated by exposure to short, winter-like day lengths in the lab. We investigated the role of stress and corticosterone (cort) levels in social behavior in short day-housed female meadow voles. A brief forced swim elevated cort levels, and we assessed the effects of this stressor on new and established relationships between females. In pairs formed following exposure to swim stress, the stressor significantly reduced the fraction of huddling time subjects spent with a familiar partner. Swim stress did not affect partner preferences in pairs established prior to the stressor. Finally, we examined fecal glucocorticoid metabolite levels via immunoassay in voles housed under short day (10h light) versus long day (14 h light) conditions and detected higher glucocorticoid levels in long day-housed voles. These findings support a role for stress regulation in the formation of social relationships in female meadow voles, and are consistent with a potential role for seasonal variation in cort in the behavioral transition from solitary to social. Together they highlight the importance of stress and possibly glucocorticoid signaling for social behavior.