Singh, Rohin

BACKGROUND Delayed facial palsy (DFP) after vestibular schwannoma resection is a well-documented, yet poorly understood condition. The exact pathophysiological mechanisms of DFP are unknown, although diminished intraoperative nerve response has been shown to be a prognostic factor. To date, no such condition has been described in regard to peripheral nerve schwannomas. OBSERVATIONS Here the authors present the first reported cases of delayed motor weakness (DMW) after peripheral schwannoma resection of the ulnar nerve at the elbow and peroneal nerve in the popliteal fossa. Both patients presented with a mass lesion and radiating paresthesias and had normal motor function preoperatively. Immediately after surgical resection, the patients had full strength. Within 24 hours, both patients exhibited marked weakness that gradually resolved over the course of several weeks. LESSONS DMW after peripheral schwannoma resection is a rare condition likely akin to delayed facial nerve palsy after VS resection. The mechanism of this phenomenon remains unknown, although symptoms appear to self-resolve with time. A better understanding of the processes driving this condition may allow for therapies that can expedite and improve long-term outcomes.

OBJECTIVE Aneurysm occlusion has been used as surrogate marker of aneurysm treatment efficacy. Aneurysm occlusion scales are used to evaluate the outcome of endovascular aneurysm treatment and to monitor recurrence. These scales, however, require subjective interpretation of imaging data, which can reduce the utility and reliability of these scales and the validity of clinical studies regarding aneurysm occlusion rates. Use of a core lab with independent blinded reviewers has been implemented to enhance the validity of occlusion rate assessments in clinical trials. The degree of agreement between core labs and treating physicians has not been well studied with prospectively collected data. METHODS In this study, the authors analyzed data from the Hydrogel Endovascular Aneurysm Treatment (HEAT) trial to assess the interrater agreement between the treating physician and the blinded core lab. The HEAT trial included 600 patients across 46 sites with intracranial aneurysms treated with coiling. The treating site and the core lab independently reviewed immediate postoperative and follow-up imaging (3–12 and 18–24 months, respectively) using the Raymond-Roy occlusion classification (RROC) scale, Meyer scale, and recanalization survey. A post hoc analysis was performed to calculate interrater reliability using Cohen’s kappa. Further analysis was performed to assess whether degree of agreement varied on the basis of various factors, including scale used, timing of imaging, size of the aneurysm, imaging modality, location of the aneurysm, dome-to-neck ratio, and rupture status. RESULTS Minimal interrater agreement was noted between the core lab reviewers and the treating physicians for assessing aneurysm occlusion using the RROC grading scale (k = 0.39, 95% CI 0.38–0.40) and Meyer scale (k = 0.23, 95% CI 0.14–0.38). The degree of agreement between groups was slightly better but still weak for assessing recanalization (k = 0.45, 95% CI 0.38–0.52). Factors that significantly improved degree of agreement were scales with fewer variables, greater time to follow-up, imaging modality (digital subtraction angiography), and wide-neck aneurysms. CONCLUSIONS Assessment of aneurysm treatment outcome with commonly used aneurysm occlusion scales suffers from risk of poor interrater agreement. This supports the use of independent core labs for validation of outcome data to minimize reporting bias. Use of outcome tools with fewer point categories is likely to provide better interrater reliability. Therefore, the outcome assessment tools are ideal for clinical outcome assessment provided that they are sensitive enough to detect a clinically significant change.

OBJECTIVE Glioblastoma (GBM) is a devasting primary brain tumor with less than a 5% 5-year survival. Treatment response assessment can be challenging because of inflammatory pseudoprogression that mimics true tumor progression clinically and on imaging. Developing additional noninvasive assays is critical. In this article, the authors review various biomarkers that could be used in developing liquid biopsies for GBM, along with strengths, limitations, and future applications. In addition, they present a potential liquid biopsy design based on the use of an extracellular vesicle–based liquid biopsy targeting nonneoplastic extracellular vesicles. METHODS The authors conducted a current literature review of liquid biopsy in GBM by searching the PubMed, Scopus, and Google Scholar databases. Articles were assessed for type of biomarker, isolation methodology, analytical techniques, and clinical relevance. RESULTS Recent work has shown that liquid biopsies of plasma, blood, and/or CSF hold promise as noninvasive clinical tools that can be used to diagnose recurrence, assess treatment response, and predict patient outcomes in GBM. Liquid biopsy in GBM has focused primarily on extracellular vesicles, cell-free tumor nucleic acids, and whole-cell isolates as focal biomarkers. GBM tumor signatures have been generated via analysis of tumor gene mutations, unique RNA expression, and metabolic and proteomic alterations. Liquid biopsies capture tumor heterogeneity, identifying alterations in GBM tumors that may be undetectable via surgical biopsy specimens. Finally, biomarker burden can be used to assess treatment response and recurrence in GBM. CONCLUSIONS Liquid biopsy offers a promising avenue for monitoring treatment response and recurrence in GBM without invasive procedures. Although additional steps must be taken to bring liquid biopsy into the clinic, proof-of-principle studies and isolation methodologies are promising. Ultimately, CSF and/or plasma-based liquid biopsy is likely to be a powerful tool in the neurosurgeon’s arsenal in the near future for the treatment and management of GBM patients.

Abstract Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. For this purpose, we conducted a retrospective cohort study between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23-1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70-6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07-1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71-2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17-2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22-2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at primary admission. Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients.

Abstract Due to its anti-fibrinolytic action, tranexamic acid (TXA) can be utilized to help maintain hemostasis during surgical operations. With respect to surgery for intracranial tumors, we hypothesize that TXA could help mitigate blood loss during resection of highly vascular tumors such as meningiomas. We therefore conducted a systematic review of the literature and meta-analysis to analyze the effects of TXA administration in patients undergoing surgical resection of intracranial meningioma. Study inclusion criteria were (1) primary data articles describing use of TXA in surgical resection of meningioma. In this meta-analysis, which included four primary comparative studies, outcome measurements between TXA and non-TXA groups were compared. Primary outcomes included operative length, complications, transfusion requirements, estimated blood loss, and postoperative Hb for TXA versus non-TXA (control) groups. Pooled-comparative analysis was conducted for each of these perioperative variables and formal meta-analysis was applied toward statistically significant parameters. A total of 221 patients were analyzed (110 TXA, 111 non-TXA). Patient age (p = 0.1632), gender (p = 0.8317), and tumor location (p = -.8334) were similar for TXA and control groups. TXA was associated with decreased complication rate (logRR: -0.85; CI95% = -1.49 to -0.22; p = 0.0087), decreased transfusion requirement (logRR: -0.50; CI95% = -0.92 to -0.08; p = 0.0039), reduced blood loss (SMD: -1.76; CI95% = -3.21 to -0.31; p < 0.0001), and increased postoperative Hb (SMD: 0.46; CI95% = -0.15 to 1.07; p < 0.0001). In three trials, TXA was administered intravenously as a loading dose of 20 mg/kg for 20 minutes preoperatively with an intraoperative maintenance rate of 1mg/kg/hr; in one trial, administration design was identical except that infusion rate of the 20 mg/kg preoperative loading dose was unspecified. TXA may be associated with reduced complications, transfusion requirements, perioperative estimated blood loss, and increasedpostoperative Hb when administered perioperatively for surgical resection of intracranial meningiomas.

Abstract Recent literature has primarily focused on the factors influencing postoperative seizures following resection of meningioma, but many patients also suffer seizures preoperatively. This meta-analysis examined patient demographics, tumor characteristics, and preoperative symptoms to determine which factors are most associated with preoperative seizures. A literature search of Pubmed, Web of Science, and Scopus was conducted. All randomized controlled trials, case-control studies, and cohort studies reporting on preoperative seizure in patients with meningioma were included for analysis. The initial search yielded 4129 total studies, 33 of which were included for quantitative analysis. A total of 8221 patients were analyzed and the rate of preoperative seizure was 26%. Patients were classified as adult vs pediatric and male vs female for analysis. Meningiomas were classified as midline/bilateral vs left-sided vs right-sided, WHO grade 1 vs grade 2-3, greater than 4 cm3 vs less than 4 cm3, and skull base vs non-skull base location. The preoperative signs and symptoms analyzed included presence of headaches, tumor-related edematous change, and neurological deficits. Preoperative seizures were more common in pediatric patients (p< .02) and males (p< .0001). Patients with tumors classified as midline (p< .0001), WHO grade 2-3 (p< .0001), larger than 4 cm3 (p< .0001), and skull base location (p< .0001) were more likely to experience preoperative seizures. Preoperative headaches (p< .0001) were less common in patients with preoperative seizures. Edematous change (p< .0001) and neurological deficits (P< .0001) were more common in patients with pre-operative seizures. On assessment of risk for study bias, no publication bias was detected. This meta-analysis displayed that over 20% of meningioma patients suffer from preoperative seizures. Notably, pediatric patients, patients with midline and skull base meningiomas, and males of all ages were more likely to experience preoperative seizure. Interestingly, patients with preoperative seizures were less likely to experience headaches.