Does the clopidogrel CYP2C19 genotype assay predict postprocedure stenosis in cerebral aneurysms treated with a flow diverter?

OBJECTIVE: Flow diverters have emerged as a popular modality for treating cerebral aneurysms but require dual antiplatelet therapy (DAPT) after placement. Clopidogrel is a common choice but is a prodrug that some patients may not convert into an active metabolite. The CYP2C19 genotype assay is used to predict activation speed; however, limited data exist showcasing whether this genotype accurately predicts postprocedure complications after flow diversion treatment of cerebral aneurysms. Therefore, the authors sought to characterize whether CYP2C19 genotype correlated with the development of postprocedure intimal hyperplasia (stenosis) after flow diverter placement. METHODS: Medical records were reviewed for patients who underwent flow diverter treatment of cerebral aneurysm at a single academic institution between January 1, 2012, and May 31, 2020. Patient demographics and comorbidities were reviewed alongside CYP2C19 genotype assay, DAPT regimen, and postprocedure angiogram data. Stenosis was defined based on review of angiogram data by two independent physicians. RESULTS: In this review of 120 unique cerebral aneurysms, 102 received DAPT with clopidogrel and 18 received DAPT with an alternative agent. Stenosis was present on 3-month follow-up angiogram for 35/102 (34.3%) aneurysms receiving DAPT with clopidogrel and in 11/18 (61.1%) aneurysms receiving an alternative DAPT regimen (p = 0.031). The CYP2C19 genotype did not correlate with postprocedure stenosis (p = 0.35). CONCLUSIONS: Clopidogrel was a significantly more effective DAPT agent for preventing stenosis when compared to nonclopidogrel DAPT regimens. The clopidogrel CYP2C19 genotype did not predict postprocedure stenosis in this cohort of 120 cerebral aneurysms treated with a flow diverter.

Transillumination of an Anterior Fontanelle Dermoid Cyst.

Dermoid cysts are slowly growing benign lesions of ectodermal tissue that often occur in the anterior fontanelle. Clinicians often rely on a negative transillumination test to begin the process of correctly diagnosing a dermoid cyst. However, here the authors present a case of a 7-month-old girl who presents with a transilluminating dermoid cyst.

Cumulative Radiation Exposure in Aneurysmal Subarachnoid Hemorrhage: A Single-Institution Analysis.

OBJECTIVE: Diagnosis and management of aneurysmal subarachnoid hemorrhage (aSAH) depend heavily on imaging modalities that repeatedly expose patients to ionizing radiation. There is limited literature on cumulative radiation exposure in this patient population, which is a problem compounded by wide variation among institutions. The present study quantifies the cumulative cranial exposure to ionizing radiation resulting from diagnostic medical imaging and medical procedures during initial hospitalization for ruptured aSAH at a single academic institution and estimates the risk of future adverse events related to radiation injury. METHODS: We performed a retrospective observational study of adults who presented to our institution during a nearly 3-year period with acute-onset aSAH, which was confirmed with diagnostic imaging, and had the aneurysm treated with either surgical clip ligation or endovascular embolization. RESULTS: A total of 131 patients met the inclusion criteria. Eighty-eight patients (67%) were treated with endovascular embolization and 43 (32%) were treated with clip ligation. We found the average radiation dose to the head during the incident hospitalization for aSAH to be 4.40 Gy (95% confidence interval, 3.91-4.89). Angiography and interventional radiology procedures accounted for most of this exposure. CONCLUSIONS: Most patients were exposed to levels of ionizing radiation that put them at considerable risk of deterministic radiation injury. Providers should be aware of the potential consequences of acute and long-term radiation exposure in this patient population, so they can monitor and counsel individuals accordingly and take steps to safely limit radiation exposure during aSAH management.

Bilateral Decompressive Hemicraniectomy for Diffuse Cerebral Edema and Medically Refractory Elevated Intracranial Pressure in Aneurysmal Subarachnoid Hemorrhage: A Case Series.

Decompressive hemicraniectomy (DCHC) may be indicated in the setting of subarachnoid hemorrhage (SAH) complicated by persistent elevated intracranial pressure (ICP) that is refractory to medical interventions. Outcomes can be variable as indications for surgery can include focal hematomas, infarctions, and regional or diffuse edema. Bilateral DCHC for medically refractory elevated ICP in the setting of SAH is not well described in the literature, and the viability of this option in terms of patient outcomes is unclear. We describe the cases of four patients with medically refractory ICP secondary to diffuse cerebral edema who underwent bilateral DCHC in the setting of SAH. This is a retrospective case review of four patients with aneurysmal SAH who underwent bilateral DCHC for management of diffuse global edema resulting in medically refractory ICP. We describe two patients who made impressive recoveries after bilateral DCHC and two patients who required significant continued care needs despite ICP control in all patients. Bilateral DCHC is a viable option for control of refractory elevated ICP in SAH patients who develop diffuse cerebral edema. Bilateral DCHC in this setting can be considered after exhaustion of other therapeutic options.

Impact of venous thromboembolism during admission for meningioma surgery on hospital charges and postoperative complications.

Surgical resection of meningiomas has been associated with high rates of venous thromboembolic events (VTE) as compared with all other intracranial tumors. There is a paucity of data regarding the clinical complications and comorbidities associated with this cohort yet the underlying pathophysiological mechanism for this tumor-specific finding remains unclear. Our goal was to determine the various impacts of VTE on meningioma surgery in a large cohort of inpatient admissions. This retrospective analysis utilized discharge data from the National Inpatient Sample (NIS) from 2002 to 2010. Patient demographics, comorbidities, length of stay, hospital charges, and postoperative complications were compared between patients with and without VTE. Of 20,259 patients, 426 (2.1%) experienced a VTE. Compared to the non-VTE cohort, patients that experienced a VTE were older (62.7 ±â€¯13.7 vs. 57.2 ±â€¯14.7; p < 0.001), were more commonly male (38.0% vs 30.1%; p = 0.001), had longer hospitalizations (18.8 vs 6.6 days; p < 0.001), and incurred significantly greater hospital charges ($195,837 vs $74,434; p < 0.001). VTE patients experienced significantly higher rates of acute postoperative complications including shock, hemorrhage, wound dehiscence, infection, intracerebral hemorrhage, hemiparesis/hemiplegia, stroke, and death during admission. Odds ratio of aforementioned postsurgical complications remained significantly higher both before and after adjusting for age and sex (all p < 0.01). Occurrence of VTE in patients undergoing meningioma resection portends greater hospital charges, most likely attributed to longer lengths of admission. Increased postoperative complications and mortality in the VTE group warrants further investigation and wariness of the surgeon when treating surgical candidates of meningioma.

Hemorrhagic Complications of External Ventriculostomy in the Aspirin and P2Y12 Response Assay Era.

OBJECTIVE: Hemorrhagic complications reported from external ventricular drain (EVD) placement range from 10% to 44%. There remains limited literature investigating the incidence, risk factors, and mechanisms to prevent its occurrence, especially in the setting of antiplatelet agent use. We investigated EVD-related hemorrhagic complications after the implementation of VerifyNow platelet inhibition assays at our institution. METHODS: Medical records from 445 patients requiring EVD placement during a 2-year period during which our institution used the assays were reviewed. In total 345 patients were included, and 208 of them underwent assay testing. Indications for EVD included complications of cerebrovascular disease (n = 215), traumatic brain injury (n = 74), primary hydrocephalus (n = 23), and tumor (n = 33). Hemorrhage was defined as any new area of hyperdensity adjacent to or immediately along the catheter trajectory on computed tomography. RESULTS: There was no significant decrease in catheter-induced hemorrhage (CIH) between patients who underwent the VerifyNow assay and those who did not. Platelet transfusion did not significantly decrease the risk of CIH. CIH occurred in 17.7% of patients, significantly decreased when compared with our previously published incidence of 33% before platelet inhibition assay use (P < 0.05). Patients with cerebrovascular disease complications exhibited a significant decrease in CIH, 20% versus 39%, before assay use (P < 0.01). CONCLUSIONS: The incidence of hemorrhage is lower in our new cohort when compared with that of our previously published cohort. Despite the overall decreased rate of hemorrhage, there was no significant difference in hemorrhage rates between patients who did or did not undergo the assay. Platelet transfusion did not decrease the incidence of hemorrhage in patients with inhibited platelet function.

Influence of Relative Residence Time on Side-Wall Aneurysm Inception.

BACKGROUND: Relative residence time (RRT) is a marker of disturbed blood flow, marked by low magnitude and high oscillatory wall shear stress (WSS). The relation between solute residence time in proximity to the vascular endothelium and the atherosclerotic process is well appreciated in the literature. OBJECTIVE: To assess the influence of RRT on side-wall aneurysm inception to better understand the role of atherosclerosis in aneurysm formation. METHODS: Fourteen side-wall internal carotid artery aneurysms from the Aneurisk repository which met criteria for parent vessel reconstruction were reconstructed with Vascular Modeling Toolkit. Computational fluid dynamics analysis was carried out in Fluent. RRT was calculated in MATLAB (The MathWorks Inc, Natick, Massachusetts). We analyzed the results for correlations, defined as presence or absence of local elevations in RRT in specific regions of vasculature. RESULTS: RRT was concluded to be negatively correlated with aneurysm inception in this study of side-wall internal carotid artery aneurysms, with 12/14 cases yielding the absence of local RRT elevations within or in close proximity of the removed ostium. Subsequent analysis of WSS showed that 11 of 14 aneurysms were formed in an atheroprotective environment, with only 1 of 14 formed in an atherogenic environment. Two models were found to be of indeterminate environment. CONCLUSION: Atherogenesis and atherosclerosis have long been thought to be a major inciting factor responsible for the formation of aneurysms in the cerebral vasculature. We propose that inception of side-wall aneurysms occurs in hemodynamic environments that promote an atheroprotective endothelial phenotype and that the atheroprotective phenotype is therefore aneurysmogenic.

Internal Maxillary Artery Preoperative Embolization Using n-Butyl Cyanoacrylate and Pushable Coils for Temporomandibular Joint Ankylosis Surgery.

BACKGROUND: Temporomandibular joint (TMJ) ankylosis causes disability through impaired digestion, mastication, speech, and appearance. Surgical treatment increases range of motion with resultant functional improvement. However, substantial perioperative blood loss can occur (up to 3 L) if the internal maxillary artery (IMAX) is injured as it traverses the ankylotic mass. Achieving hemostasis is difficult because of limited proximal IMAX access and poor visualization. Our aim is to investigate the technical feasibility and preliminary safety of preoperative IMAX embolization in patients undergoing TMJ ankylosis surgery. METHODS: Case series using chart reviews of 2 patients who underwent preoperative embolization before TMJ ankylosis surgery. RESULTS: Both patients were women (28 and 51 years old) who had severely restricted mouth opening. Embolization was performed using general anesthesia with nasal intubation on the same day of TMJ surgery. Both patients underwent bilateral IMAX embolization using pushable coils (Vortex, Boston Scientific) of distal IMAX followed by n-butyl-cyanoacrylate (Trufill, Cordis) embolization from coil mass up to proximal IMAX. There were no complications from the embolization procedures. Both patients had normal neurologic examination results. TMJ surgery occurred with minimal operative blood loss (≤300 mL for each surgery). Maximum postoperative mouth opening was 35 mm and 34 mm, respectively. One patient had a postoperative TMJ wound infection that was managed with antibiotics. CONCLUSIONS: Preoperative IMAX embolization before TMJ ankylosis surgery is technically feasible with encouraging preliminary safety. There were no complications from the embolization procedures and surgeries occurred with low volumes of blood loss.

Outcomes of Vestibular Schwannoma Surgery among the Elderly.

Objective To compare comorbidities and in-hospital complications between elderly and nonelderly patients undergoing vestibular schwannoma (VS) surgery. To examine average length of stay (LOS) and hospital charges among elderly patients. Study Design Population-based inpatient registry analysis. Setting Academic medical center. Subjects and Methods Retrospective analysis of the National Inpatient Sample for patients undergoing VS surgery from 2002 to 2010: 4137 patients met inclusion criteria, with 519 (12.5%) in the elderly cohort (≥65 years). Outcomes of elderly and nonelderly (<65 years) patient cohorts were compared. Results Compared with the nonelderly cohort, the elderly cohort had more comorbidities, including diabetes mellitus, hypertension, and pulmonary disease (all P < .001). Elderly patients had longer LOS (6.5 vs 5.4 days; P = .001) but did not incur significantly greater hospital charges. Rates of cerebrospinal fluid leak, meningitis, and facial nerve injury did not vary significantly between groups. The elderly cohort experienced higher rates of in-hospital complications, including acute cardiac events, iatrogenic cerebrovascular infarction/hemorrhage, postoperative bleeding (hemorrhage/hematoma), and in-hospital mortality (all P < .05). In binary logistic regression, correcting for patient demographics and presence of comorbidities, elderly status was associated with 1.848 (95% confidence interval, 1.167-2.927; P = .009) greater odds of medical complications and 13.188 (95% confidence interval, 1.829-95.113; P = .011) greater odds of in-hospital mortality. Conclusion Elderly patients undergoing VS surgery have more comorbidities, in-hospital complications, and longer LOS than nonelderly patients. The elderly cohort had a greater rate of in-hospital mortality, though rare. Interestingly, elderly patients did not have a higher rate of many known complications associated with VS surgery and did not incur more hospital charges.

Flow diverters for intracranial aneurysms.

Flow diverters (pipeline embolization device, Silk flow diverter, and Surpass flow diverter) have been developed to treat intracranial aneurysms. These endovascular devices are placed within the parent artery rather than the aneurysm sac. They take advantage of altering hemodynamics at the aneurysm/parent vessel interface, resulting in gradual thrombosis of the aneurysm occurring over time. Subsequent inflammatory response, healing, and endothelial growth shrink the aneurysm and reconstruct the parent artery lumen while preserving perforators and side branches in most cases. Flow diverters have already allowed treatment of previously untreatable wide neck and giant aneurysms. There are risks with flow diverters including in-stent thrombosis, perianeurysmal edema, distant and delayed hemorrhages, and perforator occlusions. Comparative efficacy and safety against other therapies are being studied in ongoing trials. Antiplatelet therapy is mandatory with flow diverters, which has highlighted the need for better evidence for monitoring and tailoring antiplatelet therapy. In this paper we review the devices, their uses, associated complications, evidence base, and ongoing studies.