Is two-staged gamma knife surgery a reasonable management option for very large cerebellar metastases? A case series of three patients.

OBJECTIVE: Two-staged gamma knife surgery (GKS) is a method that may extend the upper tumor volume limit for using GKS in the management of brain metastases. However, the safety of treating very large posterior fossa lesions with this technique has not been well demonstrated. Therefore, we analyzed our experience in treating cerebellar metastases larger than 12 cm3 with two-staged GKS. METHODS: Four consecutive patients harboring 12 to 30 cm3 cerebellar metastases scheduled two-staged GKS were included in the study, and all but one patient completed the treatment. The treatment doses were 10-13 Gy. All patients were followed with regular MR imaging and clinical assessments, and the tumor volumes were measured on all treatment and follow-up images. RESULTS: Tumor progression was not demonstrated in any of the patients. Tumor volumes decreased by, on average, more than half between the two stages. The median survival was 22 months, and no patient died due to intracranial tumor progression. Peritumoral edema at the first GKS resolved in all patients, replaced by asymptomatic mild T2 changes in two of them not requiring any treatment. No radiation-induced complication has developed thus far. CONCLUSION: Staged GKS seems to be a feasible management option for very large cerebellar metastases.

Laser Interstitial Thermal Therapy for the Treatment of Primary and Metastatic Brain Tumors: A Systematic Review and Meta-Analysis.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive treatment option for intracranial tumors that are challenging to treat via traditional methods; however, its safety and efficacy are not yet well validated in the literature. The objectives of the study were to assess the available evidence of the indications and adverse events (AEs) of LITT and 1-year progression-free survival and 1-year overall survival in the treatment of primary and secondary brain tumors. METHODS: A comprehensive literature search was conducted through the databases PubMed, Embase, and the Cochrane Library until October 2021. Comparative and descriptive studies, except for case reports, were included in the meta-analysis. Separate analyses by tumor type (high-grade gliomas, including World Health Organization grade 4 astrocytomas [which include glioblastomas] as a specific subgroup; low-grade gliomas; and brain metastases) were conducted. Pooled effect sizes and their 95% confidence intervals (CI) were generated via random-effects models. RESULTS: Forty-five studies met the inclusion criteria, yielding 826 patients for meta-analysis. There were 829 lesions in total, of which 361 were classified as high-grade gliomas, 116 as low-grade gliomas, 337 as metastatic brain tumors, and 15 as nonglial tumors. Indications for offering LITT included deep/inaccessible tumor (12 studies), salvage therapy after failed radiosurgery (9), failures of ≥2 treatment options (3), in pediatric patients (4), patient preference (1); indications were nonspecific in 12 studies. Pooled incidence of all (minor or major) procedure-related AEs was 30% (95% CI, 27%-40%) for all tumors. Pooled incidence of neurologic deficits (minor or major) was 16% (12%-22%); postprocedural edema 14% (8%-22%); seizure 6% (4%-9%); hematoma 20% (14%-29%); deep vein thrombosis 19% (11%-30%); hydrocephalus 8% (5%-12%); and wound infection 5% (3%-7%). One-year progression-free survival was 18.6% (11.3%-29.0%) in high-grade gliomas, 16.9% (11.6%-24.0%) among the grade 4 astrocytomas; and 51.2% (36.7%-65.5%) in brain metastases. One-year overall survival was 43.0% (36.0%-50.0%) in high-grade glioma, 45.9% (95% CI, 37.9%-54%) in grade 4 astrocytomas; 93.0% (42.3%-100%) in low-grade gliomas, and 56.3% (47.0%-65.3%) in brain metastases. CONCLUSIONS: New neurologic deficits and postprocedural edema were the most reported AEs after LITT, albeit mostly transient. This meta-analysis provides the best statistical estimates of progression and survival outcomes based on the available information. LITT is generally a safe procedure for selected patients, and future well-designed comparative studies on its outcomes versus the current standard of care should be performed.

Survival Prediction After Neurosurgical Resection of Brain Metastases: A Machine Learning Approach.

BACKGROUND: Current prognostic models for brain metastases (BMs) have been constructed and validated almost entirely with data from patients receiving up-front radiotherapy, leaving uncertainty about surgical patients. OBJECTIVE: To build and validate a model predicting 6-month survival after BM resection using different machine learning algorithms. METHODS: An institutional database of 1062 patients who underwent resection for BM was split into an 80:20 training and testing set. Seven different machine learning algorithms were trained and assessed for performance; an established prognostic model for patients with BM undergoing radiotherapy, the diagnosis-specific graded prognostic assessment, was also evaluated. Model performance was assessed using area under the curve (AUC) and calibration. RESULTS: The logistic regression showed the best performance with an AUC of 0.71 in the hold-out test set, a calibration slope of 0.76, and a calibration intercept of 0.03. The diagnosis-specific graded prognostic assessment had an AUC of 0.66. Patients were stratified into regular-risk, high-risk and very high-risk groups for death at 6 months; these strata strongly predicted both 6-month and longitudinal overall survival ( P < .0005). The model was implemented into a web application that can be accessed through http://brainmets.morethanml.com . CONCLUSION: We developed and internally validated a prediction model that accurately predicts 6-month survival after neurosurgical resection for BM and allows for meaningful risk stratification. Future efforts should focus on external validation of our model.

A Prognostic Model Using Post-Steroid Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Primary Central Nervous System Lymphoma.

Background: Ratios of differential blood counts (hematological indices, HIs) had been identified as prognostic variables in various cancers. In primary central nervous system lymphomas (PCNSLs), higher baseline neutrophil-lymphocyte ratio (NLR) in particular was found to portend a worse overall survival. However, it was often observed that differential counts shift drastically following steroid administration. Moreover, steroids are an important part of the arsenal against PCNSL due to its potent lymphotoxic effects. We showed that the effect of steroids on differential blood cell counts and HIs could be an early biomarker for subsequent progression-free (PFS) and overall survival (OS). Methods: This study retrospectively identified all adult patients who received a brain biopsy from 2008 to 2019 and had histologically confirmed PCNSL, and included only those who received chemoimmunotherapy, with documented use of corticosteroids prior to treatment induction. Different blood cell counts and HIs were calculated at three time-points: baseline (pre steroid), pre chemoimmunotherapy (post steroid) and post chemoimmunotherapy. Tumor progression and survival data were collected and analyzed through Kaplan−Meier estimates and Cox regression. We then utilized selected variables found to be significant on Kaplan−Meier analysis to generate a decision-tree prognostic model, the NNI-NCCS score. Results: A total of 75 patients who received chemoimmunotherapy were included in the final analysis. For NLR, OS was longer with higher pre-chemoimmunotherapy (post-steroid) NLR (dichotomized at NLR ≥ 4.0, HR 0.42, 95% CI: 0.21−0.83, p = 0.01) only. For platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR), OS was better for lower post-chemoimmunotherapy PLR (dichotomized at PLR ≥ 241, HR 2.27, 95% CI: 1.00 to 5.18, p = 0.05) and lower pre-chemoimmunotherapy (post-steroid) LMR (dichotomized at LMR ≥25.7, HR 2.17, 95% CI: 1.10 to 4.31, p = 0.03), respectively, only. The decision-tree model using age ≤70, post-steroid NLR >4.0, and pre-steroid (baseline) NLR <2.5 and the division of patients into three risk profiles­low, medium, and high­achieved good accuracy (area-under-curve of 0.78), with good calibration (Brier score: 0.16) for predicting 2-year overall survival. Conclusion: We found that post-steroid NLR, when considered together with baseline NLR, has prognostic value, and incorporation into a prognostic model allowed for accurate and well-calibrated stratification into three risk groups.

Intraoperative Magnetic Resonance Imaging for Low-Grade and High-Grade Gliomas: What Is the Evidence? A Meta-Analysis.

BACKGROUND: The benefit of intraoperative magnetic resonance imaging (iMRI) in gliomas remains unclear. We performed a meta-analysis of outcomes with iMRI-guided surgery in high-grade gliomas (HGGs) and low-grade gliomas (LGGs). METHODS: Databases were searched until November 29, 2018 for randomized controlled trials (RCTs) and observational studies (OBS) comparing iMRI use with conventional neurosurgery. Pooled risk ratios (RRs) or hazard ratios were evaluated with the random-effects model. Outcomes included extent of resection (EOR), gross total resection (GTR), progression-free survival (PFS), overall survival (OS), and length of surgery (LOS), stratified by study design and glioma grade. RESULTS: Fifteen articles (3 RCTs and 12 OBS) were included. In RCTs, GTR was higher in iMRI compared with conventional neurosurgery (RR, 1.42; 95% confidence interval [CI], 1.17-1.73; I2, 7%) overall, for LGGs (1.91; 95% CI, 1.19-3.06), but not HGGs (1.24; 95% CI, 0.89-1.73), with no difference in EOR, PFS, OS, and LOS. For OBS, GTR was higher (RR, 1.65; 95% CI, 1.43-1.90; I2, 4%) overall, and for LGGs (1.63; 95% CI, 1.17-2.28; I2, 0%) and HGGs (1.62; 95% CI, 1.36-1.92; I2, 19%). EOR was greater with iMRI (6%; 95% CI, 4%-8%; I2, 44%) overall, in LGGs (5%; 95% CI, 2%-8%; I2, 37%) and HGGs (7%; 95% CI, 4%-10%; I2, 13%). There was no difference in PFS, OS, and LOS with iMRI. CONCLUSIONS: IMRI use improved GTR in gliomas, including LGGs. However, no PFS and OS benefit was shown in the meta-analysis.

Motor deficits at presentation and predictors of overall survival in central nervous system lymphomas.

PURPOSE: Central nervous system lymphomas (CNSL) can present with motor and non-motor symptoms. In many central nervous system tumors, motor deficits are associated with significant morbidity and functional impairment, and correlate with worse prognosis. CNSLs however, often exhibit remarkable response to chemotherapy and radiotherapy with corresponding symptom improvement. We investigate the survival outcomes and trajectories of motor and functional recovery in a cohort of patients presenting with and without initial motor deficits. METHODS: Patients who underwent biopsy and with a histologically confirmed CNSL between 2008 and 2019 were retrospectively identified. Baseline demographic variables, comorbidities, presenting symptoms, histological type, neuroimaging features (location and number of lesions), and treatment administered (pre- and post-operative steroid use and chemotherapy regime) were recorded. Dates of death were obtained from the National Registry of Births and Deaths. Motor power and performance status at admission, 1 month and 6 months were determined. RESULTS: We identified 119 patients, of whom 34% presented with focal motor deficits. The median overall survival (OS) was 26.6 months. Those with focal motor deficits had longer OS (median 42.4 months) than those without (median 23.3 months; p = 0.047). In multivariate Cox analysis, age (HR 1.04 per year; p = 0.003), CCI (HR 1.31 per point; p < 0.001), leptomeningeal/ependymal involvement (HR 2.53; p = 0.016), thalamus involvement (HR 0.34; p = 0.019), neutrophil:lymphocyte ratio (HR 1.06 per point; p = 0.034), positive HIV status (HR 5.31; p = 0.003), preoperative steroids use (HR 0.49; p = 0.018), postoperative high-dose steroids (HR 0.26; p < 0.001) and postoperative low-dose steroids (HR 0.28; p = 0.010) were significant predictors of OS. By one month, 43% of surviving patients had full power, increasing to 61% by six months. CONCLUSION: A significant proportion of patients with initial motor deficits recovered in motor strength by six months. In our population, those presenting with motor deficits had paradoxically better overall survival.

Surgical management of vertebral metastatic gastrointestinal stromal tumor: Case illustration, literature review, and pooled analysis.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) very rarely metastasize to the vertebrae. Tyrosine kinase inhibitors (TKIs) confer favorable long-term survival and durable disease control for metastatic disease. Here, we reviewed a case and the literature to determine the various management options, and neurological outcomes for these patients. CASE DESCRIPTION: A 63-year-old Chinese female with metastatic jejunal GIST previously treated with various TKIs presented with the left lower limb weakness and a sensory level at T10. MRI revealed a T9 vertebral body tumor with cord compression. The tumor was excised and surgical fixation was performed. She received 30Gy of fractionated adjuvant radiotherapy. She achieved near-complete neurological recovery but died 2 months later from systemic disease progression. CONCLUSION: Based on this case and a review of the literature, surgical intervention and treatment with TKIs with adjuvant RT can lead to comparable survival and neurological outcomes.

Gender Differences in Preoperative Opioid Use in Spine Surgery Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Opioids are frequently used in spine surgeries despite their adverse effects, including physical dependence and addiction. Gender difference is an important consideration for personalized treatment. There is no review assessing the prevalence of opioid use between men and women before spine surgeries. DESIGN: We compared the prevalence of preoperative opioid use between men and women. SETTING: Spine surgery. SUBJECTS: Comparison between men and women. METHODS: PubMed, Embase, and Cochrane were searched from inception to November 9, 2018. Clinical characteristics and prevalence of preoperative opioid use were collected. Where feasible, data were pooled from nonoverlapping studies using random-effects models. RESULTS: Four studies with nonoverlapping populations were included in the meta-analysis (one prospective, three retrospective cohorts). The prevalence of preoperative opioid use was 0.64 (95% CI = 0.40-0.83). Comparing men with women, no statistically significant difference in preoperative opioid use was detected (relative risk [RR] = 0.99, 95% CI = 0.96-1.02). Surgery location (cervical, lumbar) and study duration (more than five years or five years or less) did not modify this association. All involved open spine surgery. Only one secondary analysis provided data on both pre- and postoperative opioid use stratified by gender, which showed a borderline significantly higher prevalence of postoperative use in women than men. CONCLUSIONS: The prevalence of opioid use before spine surgery was similar between men and women, irrespective of surgery location or study duration. More studies characterizing the pattern of opioid use between genders are still needed.

Long-Term Opioid Prescriptions After Spine Surgery: A Meta-Analysis of Prevalence and Risk Factors.

BACKGROUND: Opioids are frequently prescribed for back pain, but the prevalence of and risk factors for long-term opioid use after spine surgery were not clearly reported. We conducted a systematic review and meta-analysis to summarize the evidence for long-term opioid use (>90 days) among adults who underwent spine surgery. METHODS: PubMed, EMBASE, and Cochrane indexing databases were searched until November 9, 2018 for studies reporting the prevalence of and risk factors for long-term opioid use after spine surgery. Separate meta-analyses were conducted for commercial claims databases or registries (claims/registries) and nonclaims observational studies using the random-effects model to estimate the pooled odds ratio (OR). Prevalence meta-analysis was performed in a clinically homogeneous subset of these patients who underwent lumbar spine surgery. RESULTS: Eight claims and 5 nonclaims were meta-analyzed to avoid double-counting participants. The meta-analysis showed that preoperative opioid users (OR, 5.59; 95% confidence interval [CI], 3.37-9.27 vs. OR 4.21; 95% CI, 2.72-6.51) and participants with preexisting depression and/or anxiety (OR, 1.86, 95% CI, 1.43-2.42 and OR, 1.20; 95% CI, 0.83-1.74, respectively) had a statistically significantly higher odds of long-term postoperative opioids, compared with their peers. Males showed lower odds of long-term postoperative opioid use in the claims group (OR, 0.85; 95% CI, 0.79-0.92), but not in the nonclaims group (OR, 0.99; 95% CI, 0.71-1.39). The pooled prevalence of post-lumbar spine surgery long-term opioid use was 63% (95% CI, 50%-74%) in claims and 47% (95% CI, 38%-56%) in nonclaims. CONCLUSIONS: Patients undergoing spine surgery represent a high-risk surgical population requiring special attention and targeted interventions, with the strongest evidence for those treated with opioids before surgery and those with psychiatric comorbidities.

Aqueductal Compression by Dilated Virchow-Robin Spaces in the Mesencephalic-Pontine Region Presenting with Symptoms Mimicking Normal Pressure Hydrocephalus: A Case Report and Review of Literature.

BACKGROUND: Dilatation of Virchow-Robin spaces (dVRS) have been described in the development of hydrocephalic syndromes. We report an unusual case of a type III dVRS presenting as a mimic of normal pressure hydrocephalus (NPH), due to distortion at the level of the cerebral aqueduct. CASE DESCRIPTION: A 59-year-old woman presented with mild traumatic brain injury and possible NPH, due to a history of progressive gait disturbance, recurrent falls, and cognitive decline over a year, in the context of ventriculomegaly. Detailed structural imaging of the brain revealed multiple dilated cystic lesions consistent with dVRS causing distortion at the level of the cerebral aqueduct. Cerebrospinal fluid examination was negative for infection. The patient was treated with endoscopic third ventriculostomy; at 12 months postoperatively, she demonstrated a sustained improvement in gait and stabilization of cognitive decline. CONCLUSIONS: This is an illustrative case of a subacute obstructive hydrocephalus due to a collection of periaqueductal dVRS, leading to an insidious clinical presentation mimicking NPH. We reviewed the literature for key clinical presentations and describe neuroanatomical considerations as well as primary treatment strategies. Various hydrocephalic syndromes may present with classic symptoms from Hakim's triad; such symptoms are not specific to idiopathic NPH. Both endoscopic third ventriculostomy and shunting may be efficacious. In our case, dVRS may serve as both a cause of and compensatory mechanism in a subacute obstructive hydrocephalus of unknown etiology. Our case highlights the need to understand the neuroanatomy of aberrant cerebrospinal fluid spaces in hydrocephalic syndromes. Further studies of dVRS would provide valuable insights into the pathogenesis of hydrocephalus.