Atlantoaxial facet fixation using cervical facet cage: technical case report and review of the literature.

In 1994, the use of interfacet spacer placement was for joint distraction, reduction, and fusion to supplement atlantoaxial or occipitocervical fixation. Here, we present a unique case of bilateral atlantoaxial interfacet fixation using cervical facet cages (CFC) in a pediatric patient with basilar invagination. In addition, we review the literature on atlantoaxial facet fixation. We present a 12-year-old boy with Wiedemann-Steiner syndrome who presented with multiple episodes of sudden neck jerking, described as in response to a sensation of being shocked, and guarding against neck motion, found to have basilar invagination with cervicomedullary compression. He underwent an occiput to C3 fusion with C1-C2 CFC fixation. We also conducted a literature review identifying all publications using the following keywords: "C1" AND "C2" OR "atlantoaxial" AND "facet spacer" OR "DTRAX." The patient demonstrated postoperative radiographic reduction of his basilar invagination from 6.4 to 4.1 mm of superior displacement above the McRae line. There was a 4.5 mm decrease in the atlantodental interval secondary to decreased dens retroflexion. His postoperative course was complicated by worsening of his existing dysphagia but was otherwise unremarkable. His neck symptoms completely resolved. We illustrate the safe use of CFC for atlantoaxial facet distraction, reduction, and instrumented fixation in a pediatric patient with basilar invagination. Review of the literature demonstrates that numerous materials can be safely placed as a C1-C2 interfacet spacer including bone grafts, titanium spacers, and anterior cervical discectomy and fusion cages. We argue that CFC may be included in this arsenal even in pediatric patients.

A cost analysis of MR-guided laser interstitial thermal therapy for adult refractory epilepsy.

OBJECTIVE: MR-guided laser interstitial thermal therapy (LITT) is used increasingly for refractory epilepsy. The goal of this investigation is to directly compare cost and short-term adverse outcomes for adult refractory epilepsy treated with temporal lobectomy and LITT, as well as to identify risk factors for increased costs and adverse outcomes. METHODS: The National Inpatient Sample (NIS) was queried for patients who received LITT between 2012 and 2019. Patients with adult refractory epilepsy were identified. Multivariable mixed-effects models were used to analyze predictors of cost, length of stay (LOS), and complications. RESULTS: LITT was associated with reduced LOS and overall cost relative to temporal lobectomy, with a statistical trend toward lower incidence of postoperative complications. High-volume surgical epilepsy centers had lower LOS overall. Longer LOS was a significant driver of increased cost for LITT, and higher comorbidity was associated with non-routine discharge. SIGNIFICANCE: LITT is an affordable alternative to temporal lobectomy for adult refractory epilepsy with an insignificant reduction in inpatient complications. Patients may benefit from expanded access to this treatment modality for both its reduced LOS and lower cost.

Stereotactic laser interstitial thermal therapy for the treatment of pediatric drug-resistant epilepsy: indications, techniques, and safety.

BACKGROUND: MRI-guided laser interstitial thermal therapy (MRgLITT) is a promising alternative to open surgery for treatment of drug-resistant epilepsy, offering significant advantages over traditional approaches for candidate patients, including minimally invasive approach, shorter hospitalization, and decreased patient post-operative discomfort. LITT uses a stereotactically placed fiber optic laser probe to ablate tissue under real-time MR thermometry. METHODS: Retrospective chart review of intraoperative and perioperative characteristics was performed for 28 cases of MRgLITT in 25 pediatric patients, ages 4-21 years old, at our institution between 2019 and 2021. MRgLITT ablation of the mesial temporal lobe was performed in 8 cases, extratemporal epileptogenic foci in 9 cases, and for corpus callosotomy in 11 cases. RESULTS: At 1 year of follow-up, 53% of all patients experienced improvement in seizure frequency (Engel I or II) (class I: 38%, class II: 15%, class III: 17%, class IV: 31%), including 37% of MTL ablations and 80% extratemporal SOZ ablations. After MRgLITT corpus callosotomy, 71% of patients were free from atonic seizures at most recent follow-up. Median length of hospitalization was 2 days (1-3), including a median ICU stay of 1 day (1-2). CONCLUSION: This series demonstrates the safety of MRgLITT as an approach for seizure control in drug-resistant epilepsy. We provide additional evidence that MRgLITT is an effective procedure that is well-tolerated by pediatric patients and is accompanied by an acceptable rate of complications and relatively short hospital stay.

Receipt of brachytherapy is an independent predictor of survival in glioblastoma in the Surveillance, Epidemiology, and End Results database.

INTRODUCTION: There has been a resurgence of interest in brachytherapy as a treatment for glioblastoma, with several currently ongoing clinical trials. To provide a foundation for the analysis of these trials, we analyze the Surveillance, Epidemiology, and End Results (SEER) database to determine whether receipt of brachytherapy conveys a survival benefit independent of traditional prognostic factors. MATERIALS AND METHODS: We identified 60,456 glioblastoma patients, of whom 362 underwent brachytherapy. We grouped patients based on receipt of brachytherapy and compared clinical and demographic variables between groups using Student's t-test and Pearson's chi-squared test. We assessed survival using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Median overall survival was 16 months in patients who received brachytherapy compared to 9 months in those who did not (log-rank p < 0.001). Patients who underwent brachytherapy tended to be younger (p < 0.001), suffered from smaller tumors (< 4 cm, p < 0.001), and were more likely to have undergone gross total resection (GTR, p < 0.001). In univariable Cox models, these variables were independently associated with improved overall survival. Additionally, improved survival was associated with known receipt of chemotherapy (HR 0.459, p < 0.001), external beam radiation (HR 0.447, p < 0.001), and brachytherapy (HR 0.637, p < 0.001). The association between brachytherapy and improved survival remained robust (HR 0.859, p = 0.031) in a multivariable model that adjusted for patient age, tumor size, tumor location, GTR, receipt of chemotherapy, and receipt of external beam radiation. CONCLUSION: Our SEER analysis indicates that brachytherapy is associated with improved survival in glioblastoma after controlling for age, tumor size/location, extent of resection, chemotherapy, and external beam radiation.

Association between medical academic genealogy and publication outcome: impact of unconscious bias on scientific objectivity.

BACKGROUND: Our previous studies suggest that the training history of an investigator, termed "medical academic genealogy", influences the outcomes of that investigator's research. Here, we use meta-analysis and quantitative statistical modeling to determine whether such effects contribute to systematic bias in published conclusions. METHODS: A total of 108 articles were identified through a comprehensive search of the high-grade glioma (HGG) surgical resection literature. Analysis was performed on the 70 articles with sufficient data for meta-analysis. Pooled estimates were generated for key academic genealogies. Monte Carlo simulations were performed to determine whether the effects attributed to genealogy alone can arise due to chance alone. RESULTS: Meta-analysis of the HGG literature without consideration for academic medical genealogy revealed that gross total resection (GTR) was associated with a significant decrease in the odds ratio (OR) for the hazard of death after surgery for both anaplastic astrocytoma (AA) and glioblastoma (AA: log [OR] = - 0.04, 95% CI [- 0.07 to - 0.01]; glioblastoma log [OR] = - 0.36, 95% CI [- 0.44 to - 0.29]). For the glioblastoma literature, meta-analysis of articles contributed by members of a genealogy consisting of mostly radiation oncologists revealed no reduction in the hazard of death after GTR [log [OR] = - 0.16, 95% CI [- 0.41 to 0.09]. In contrast, meta-analysis of published articles contributed by members of a genealogy consisting of mostly neurosurgeons revealed that GTR was associated with a significant reduction in the hazard of death [log [OR] = - 0.29, 95% CI [- 0.40 to 0.18]. Monte Carlo simulation revealed that the observed discrepancy between the articles contributed by the members of these two genealogies was unlikely to arise by chance alone (p < 0.006). CONCLUSIONS: Meta-analysis of articles contributed by authors belonging to the different medical academic genealogies yielded distinct and contradictory pooled point-estimates, suggesting that genealogy contributes to systematic bias in the published literature.

Survival trends of oligodendroglial tumor patients and associated clinical practice patterns: a SEER-based analysis.

There is limited information on the management strategies and survival trends for oligodendroglioma patients. Here we used the Surveillance, Epidemiology and End Results (SEER, 1999-2012) database to analyze the historical trends of oligodendroglioma patient survival and correlate these trends to evolving clinical practice of radiation therapy (RT) use and surgical practice of gross total resection (GTR). We identified 2689 World Health Organization (WHO) grade II oligodendroglioma (abbreviated as O2) and 1191 WHO grade III oligodendroglioma (abbreviated as O3). Time-trend analyses were performed for overall survival, radiation treatment (RT) use, and extent of surgical resection (EOR). In multivariable Cox models that accounted for age, race, sex, tumor size, tumor location, EOR, and RT status, the hazard of dying from O3 has significantly decreased over the study period (p  <  0.01), while the hazard of dying from O2 has remained largely unchanged. A search of the published literature revealed articles reporting results largely supportive of these observations. The pattern of surgical practice and RT for O3 patients remained unchanged throughout the study period, suggesting that the survival improvement may be related to evolving patterns of medical management. Results from the SEER database indicate significant gains have been made in survival for O3 patients between 1999 and 2012. Such gains were not observed for O2 patients during this study period.

A novel classification and management scheme for craniocervical junction disorders with ventral neural element compression.

OBJECTIVE: Craniocervical junction (CCJ) pathologies with ventral neural element compression are poorly understood, and appropriate management requires accurate understanding, description, and a more uniform nomenclature. The aim of this study was to evaluate patients to identify anatomical clusters and better classify CCJ disorders with ventral compression and guide treatment. METHODS: A retrospective review of adult and pediatric patients with ventral CCJ compression from 2008 to 2022 at a single center was performed. The incidence of anatomical abnormalities and compressive etiologies was assessed. Surgical approach, radiographic data, and outcomes were recorded. Association rules analysis (ARA) was used to assess variable clustering. RESULTS: Among 51 patients, the main causes of compression were either purely bony (retroflexed dens [n = 18]; basilar invagination [BI; n = 13]) or soft tissue (degenerative pannus [n = 16]; inflammatory pannus [n = 2]). The primary cluster in ARA was a retroflexed dens, platybasia, and Chiari malformation (CM), and the secondary cluster was BI, C1-2 subluxation, and reducibility. These, along with degenerative pannus, formed the three major classes. In assessing the optimal treatment strategy, reducibility was evaluated. Of the BI cases, 12 of the 13 patients had anterolisthesis of C1 that was potentially reducible, compared with 2 of the 18 patients with a retroflexed dens (both with concomitant BI), and no pannus cases. The mean C1-2 facet angle was significantly higher in BI at 32.4°, compared with -2.3° in retroflexed dens and 8.1° in degenerative pannus (p < 0.05). Endonasal decompression with posterior fixation was performed in 48 (94.0%) of the 51 patients, whereas posterior reduction/fixation alone was performed in 3 patients (6.0%). Of 16 reducible cases, open posterior reduction alone was successful in 3 (60.0%) of 5 cases, with all successes containing isolated BI. Reduction was not attempted if vertebral anatomy was unfavorable (n = 9) or the C1 lateral mass was absent (n = 5). The mean follow-up was 28 months. Symptoms improved in 88.9% of patients and were stable in the remaining 11.1%. Tracheostomy and percutaneous G-tube placement occurred in 7.8% and 11.8% of patients, respectively. Reoperation for an endonasal CSF leak repair or posterior cervical wound revision both occurred in 3.9% of patients. CONCLUSIONS: In classifying, one cluster caused decreased posterior fossa volume due to an anatomical triad of retroflexed dens, platybasia, and CM. The second cluster caused pannus formation due to degenerative hypertrophy. For both, endonasal decompression with posterior fixation was ideal. The third group contained C1 anterolisthesis characterized by a steep C1-2 facet angle causing reducible BI. Posterior reduction/fixation is the first-line treatment when anatomically feasible or endonasal decompression with in situ posterior fixation when anatomical constraints exist.

Endoscopic endonasal resection of Rathke cleft cysts: a single-institution analysis of 148 consecutive patients.

OBJECTIVE: The traditional treatment of sellar Rathke cleft cysts (RCCs) generally involves transsellar drainage; however, suprasellar RCCs present unique challenges to appropriate management and technical complexity. Reports on overall outcomes for the endoscopic endonasal approach (EEA) for this pathology are limited. The EEA for RCCs allows three surgical techniques: marsupialization, fenestration, and fenestration with cyst wall resection. METHODS: The authors performed a retrospective review of consecutive patients with RCCs that had been treated via an EEA at a single institution between January 2004 and May 2021. Marsupialization entailed the removal of cyst contents while maintaining a drainage pathway into the sphenoid sinus. Fenestration involved the removal of cyst contents, followed by separation from the sphenoid sinus, often with a free mucosal graft or vascularized nasoseptal flap. Cyst wall resection, either partial or complete, was added to select cases. RESULTS: A total of 148 patients underwent an EEA for RCC. Marsupialization or fenestration was performed in 88 cases (59.5%) and cyst wall resection in 60 (40.5%). Cysts were classified as having a purely sellar origin (43.2%), sellar origin with suprasellar extension (37.8%), and purely suprasellar origin (18.9%). Radiological recurrence was demonstrated in 22 cases (14.9%) at an average 39.7 months' follow-up (median 45 months, range 0.5-99 months), including 13 symptomatic cases (8.8%). Cases with cyst wall resection had no significantly different rate of recurrence (11.7% vs 15.9%, p = 0.48) or postoperative permanent anterior pituitary dysfunction (21.6% vs 12.5%, p = 0.29) compared to those of fenestrated and marsupialized cases. There was no significant difference in postoperative permanent posterior pituitary dysfunction based on technique, although such dysfunction tended to worsen with cyst wall resection (13.6% vs 4.0%, p = 0.09). Based on cyst location, purely suprasellar cysts were more likely to have a radiological recurrence (28.6%) than sellar cysts with suprasellar extension (12.5%) and purely sellar cysts (9.4%; p = 0.008). Most notably, of the 28 purely suprasellar cysts, selective cyst wall resection significantly improved the long-term (10-year) recurrence risk compared to fenestration alone (17.4% vs 80.0%, p = 0.0005) without any significant added risk of endocrinopathy. CONCLUSIONS: Endoscopic endonasal marsupialization or fenestration of sellar RCCs may be the ideal treatment strategy, whereas purely suprasellar cysts benefit from partial cyst wall resection to prevent recurrence. Selective cyst wall resection reduced long-term recurrence rates without significantly increasing rates of hypopituitarism.

Increased risk for ex-vacuo ventriculomegaly with leukoencephalopathy (EVL) in whole brain radiation therapy and repeat radiosurgery treated brain metastasis patients.

INTRODUCTION: Cerebral atrophy with leukoencephalopathy is a known morbidity after whole brain radiation therapy (WBRT), resulting in ex-vacuo ventriculomegaly with leukoencephalopathy (EVL). Here we studied the correlation between WBRT, stereotactic radiosurgery (SRS), and risk for EVL in brain metastases patients. METHODS: In a retrospective study, we identified 195 patients (with 1,018 BM) who underwent SRS for BM (2007-2017) and had > 3 months of MRI follow-up. All patients who underwent ventriculoperitoneal shunting were excluded. Cerebral atrophy was measured by ex-vacuo-ventriculomegaly, defined based on Evans' criteria. Demographic and clinical variables were analyzed using logistic regression models. RESULTS: Ex-vacuo ventriculomegaly was observed on pre-radiosurgery imaging in 29.7% (58/195) of the study cohort. On multivariate analysis, older age was the only variable associated with pre-radiosurgery ventriculomegaly. Of the 137 patients with normal ventricular size before radiosurgery, 27 (19.7 %) developed ex-vacuo ventriculomegaly and leukoencephalopathy (EVL) post-SRS. In univariate analysis, previous whole brain radiation therapy was the main factor associated with increased risk for developing EVL (OR = 5.08, p < 0.001). In bivariate models that included prior receipt of WBRT, both the number of SRS treatments (OR = 1.499, p = 0.025) and WBRT (OR = 11.321, p = 0.003 were independently associated with increased EVL risk. CONCLUSIONS: While repeat radiosurgery contributes to the risk of EVL in BM patients, this risk is ∼20-fold lower than that associated with WBRT.

Racial disparity in recommendation for surgical resection of skull base chondrosarcomas: A Surveillance, Epidemiology, and End Results (SEER) analysis.

INTRODUCTION: There is increased appreciation of racial disparities in the delivery of neurosurgical care. Here, we explore whether race influences surgical recommendations in the management of skull base chondrosarcomas. METHODS: We identified 493 patients with skull base chondrosarcoma using the Surveillance, Epidemiology, and End Results (SEER) registry (November 2017 submission). Regression analyses were performed to identify demographic variables associated with recommendation against surgery. Univariate and multivariate cox proportional hazards models were used for survival analysis. RESULTS: In a univariate analysis, we found that the African-American race was associated with an increased likelihood of surgeon recommendation against surgery (OR = 4.416, 95% CI = 1.893-10.302, p = 0.001). This association remained robust in the multivariate model that controlled for other covariates, including age of diagnosis (OR = 5.091, 95% CI = 2.127-12.187, p < 0.001). For patients who received a recommendation against surgery, the likelihood of dying from non-chondrosarcoma causes was comparable between Caucasian and African-American patients, suggesting that the prevalence and severity of medical conditions that increase the risk of death were comparable between these cohorts (HR = 0.466, 95% CI = 0.057-3.802, p = 0.475). The likelihood of dying from chondrosarcoma was comparable between Caucasian and African-American patients who underwent surgery (HR = 0.982, 95% CI = 0.353-2.732, p = 0.973), suggesting absence of race-specific surgical benefits. CONCLUSION: We identified a racial disparity against African-Americans in recommendations for surgical resection of skull base chondrosarcomas.

Hearing Impairment and Cognitive Decline in Older, Community-Dwelling Adults.

BACKGROUND: Hearing impairment is prevalent among older adults and has been identified as a risk factor for cognitive impairment and dementia. We evaluated the association of hearing impairment with long-term cognitive decline among community-dwelling older adults. METHODS: A population-based longitudinal study of adults not using hearing aids who had hearing acuity and cognitive function assessed in 1992-1996, and were followed for a maximum of 24 years with up to five additional cognitive assessments. Hearing acuity was categorized based on pure-tone average (PTA) thresholds: normal (PTA ≤ 25 dB), mild impairment (PTA > 25-40 dB), moderate/severe impairment (PTA > 40 dB). RESULTS: Of 1,164 participants (mean age 73.5 years, 64% women), 580 (49.8%) had mild hearing impairment and 196 (16.8%) had moderate/severe hearing impairment. In fully adjusted models, hearing impairment was associated with steeper decline on the Mini-Mental State Examination (MMSE) (mild impairment ß = -0.04, p = .01; moderate/severe impairment ß = -0.08, p = .002) and Trails B (mild impairment ß = 1.21, p = .003; moderate/severe impairment ß = 2.16, p = .003). Associations did not differ by sex or apolipoprotein E (APOE) ϵ4 status and were not influenced by social engagement. The MMSE-hearing association was modified by education: mild hearing impairment was associated with steeper decline on the MMSE among participants without college education but not among those with college education. Moderate/severe hearing impairment was associated with steeper MMSE decline regardless of education level. CONCLUSIONS: Hearing impairment is associated with accelerated cognitive decline with age, and should be screened for routinely. Higher education may provide sufficient cognitive reserve to counter effects of mild, but not more severe, hearing impairment.

Comparison of Frame-Based Versus Frameless Intracranial Stereotactic Biopsy: Systematic Review and Meta-Analysis.

BACKGROUND: Frame-based stereotaxy has generally been considered the reference standard for brain biopsies. However, frameless stereotaxy might expedite the efficiency of the clinical work flow. Conflicting findings have been reported regarding the relative efficacy and safety of frame-based and frameless needle biopsy of brain lesions. We performed a meta-analysis of the reported data to compare the relative efficacy, safety, and time efficiency of frame-based and frameless stereotactic needle biopsy. METHODS: The PubMed database was searched for studies comparing frame-based and frameless biopsy. Of the 5248 reports found, 15 were included in the present meta-analysis. RESULTS: The 15 studies included in the present meta-analysis included 2400 patients. Our analysis found no statistically significant differences between frame-based and frameless biopsy in the diagnostic yield (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.71-1.41), morbidity (OR, 1.13; 95% CI, 0.76-1.66), mortality (OR, 0.94; 95% CI, 0.40-2.17), postbiopsy hemorrhage (OR, 1.16; 95% CI, 0.68-1.96), and postbiopsy neurological deficit (OR, 1.01; 95% CI, 0.62-1.65). The results from our integrated analysis indicated that frameless biopsies are associated with a shorter procedural time relative to frame-based biopsy (standard difference in the mean, 0.64; 95% CI, 0.24-1.04; P = 0.002; I2 [Higgins inconsistency index] = 86.66%). CONCLUSIONS: The results from our meta-analysis suggest no significant differences exist between frame-based and frameless biopsy in diagnostic yield, morbidity, and mortality. Frameless biopsy is associated with shorter procedural times relative to frame-based biopsy. We have also discussed the relative merits of frame-based and frameless biopsies.

Stereotactic Laser Ablation as Treatment of Brain Metastases Recurring after Stereotactic Radiosurgery: A Systematic Literature Review.

BACKGROUND: The optimal treatment of brain metastases recurring after radiosurgery (BMRS) remains an area of active investigation. Stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy) has recently emerged as a potential treatment option. OBJECTIVE: To summarize the available literature on SLA as treatment of BMRS and synthesize findings on local control, overall survival, neurologic outcome, imaging findings, morbidity, and postprocedure clinical course. METHODS: We performed a comprehensive search of PubMed for articles investigating SLA as treatment of BMRS. RESULTS: Thirteen peer-reviewed publications met our search criteria. Local control was a function of the percentage of tumor that was thermally ablated. In completely ablated tumors, 3-month local control was 80%-100%. Median survival ranged from 5.8 to 19.8 months. About two-thirds of treated lesions showed postablation expansion of contrast-enhancing volume and fluid-attenuated inversion recovery volume. Expansion could start within an hour of treatment, and resolution typically occurred within 6 months. Notably, maximal expanded contrast-enhancing volume could reach >3-fold the preoperative lesion volume. The incidence of SLA-related permanent neurologic injuries was <10%. The most common complications were hemorrhage, thermal injury causing neurologic deficit, and malignant cerebral edema. Nearly all patients were treated with dexamethasone, but there was variability in the dose and duration of therapy. Median hospital stay was 1-2 days (range, 1-5 days), and most treated patients were discharged home (range, 59.5%-100%). CONCLUSION: Our analysis provides support for continued development of SLA as a treatment of BMRS. Standardization of periprocedural management will be needed.

A Pilot Proof-Of-Principle Analysis Demonstrating Dielectrophoresis (DEP) as a Glioblastoma Biomarker Platform.

Extracellular vesicles (EVs) are small, membrane-bound particles released by all cells that have emerged as an attractive biomarker platform. We study the utility of a dielectrophoretic (DEP) micro-chip device for isolation and characterization of EVs derived from plasma specimens from patients with brain tumors. EVs were isolated by DEP chip and subjected to on-chip immunofluorescence (IF) staining to determine the concentration of glial fibrillary acidic protein (GFAP) and Tau. EVs were analyzed from the plasma samples isolated from independent patient cohorts. Glioblastoma cell lines secrete EVs enriched for GFAP and Tau. These EVs can be efficiently isolated using the DEP platform. Application of DEP to clinical plasma samples afforded discrimination of plasma derived from brain tumor patients relative to those derived from patients without history of brain cancer. Sixty-five percent (11/17) of brain tumor patients showed higher EV-GFAP than the maximum observed in controls. Ninety-four percent (16/17) of tumor patients showed higher EV-Tau than the maximum observed in controls. These discrimination thresholds were applied to plasma isolated from a second, independent cohort of 15 glioblastoma patients and 8 controls. For EV-GFAP, we observed 93% sensitivity, 38% specificity, 74% PPV, 75% NPV, and AUC of 0.65; for EV-Tau, we found 67% sensitivity, 75% specificity 83% PPV, 55% NPV, and AUC of 0.71 for glioblastoma diagnosis. This proof-of-principle study provides support for DEP-IF of plasma EVs for diagnosis of glioblastoma.

Prognostic Importance of Age, Tumor Location, and Tumor Grade in Grade II Astrocytomas: An Integrated Analysis of the Cancer Genome Atlas and the Surveillance, Epidemiology, and End Results Database.

BACKGROUND: Previous work in anaplastic astrocytoma (AA) demonstrated that the survival benefit from gross total resection (GTR) is modified by age and tumor location. Here, we determined the influence of age and tumor location on survival benefit from GTR in diffuse astrocytoma (DA). METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database (1999-2010). We used Kaplan-Meier curves and Cox survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. We determined the prevalence of the mutated isocitrate dehydrogenase (mIDH) using The Cancer Genome Atlas (TCGA). RESULTS: We identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P = 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P = 0.002; age >50 years HR, 0.78; P = 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P = 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P = 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P = 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P = 0.49). CONCLUSIONS: Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey nonredundant prognostic information in select clinical contexts.

Cystic Formation After Stereotactic Radiosurgery of Brain Metastasis.

BACKGROUND: Limited information is available on the natural history and etiology of cystic formation after stereotactic radiosurgery (SRS) for brain metastases (BM). We aimed to characterize the natural history of cyst formation after SRS of BM and analyze potential risk factors. METHODS: We retrospectively reviewed 214 consecutive patients who underwent a total of 1106 SRSs for BM. Demographic, clinical, dosimetric, and magnetic resonance imaging MRI data were reviewed. Statistical analysis was accomplished using Student's t test, and univariate and multivariate logistic regression. RESULTS: The median patient age was 61 years (range, 19-91 years), and the median duration of follow-up was 424 days (range, 91-2934 days). Eleven cases of cyst formation (0.9% of 1106 treated lesions) were identified at SRS-treated BM sites among 9 patients (2 patients developed cysts at independent sites). The median interval between first SRS and first evidence of cyst was 218 days. Seven of the 9 patients (78%) sustained progressive cyst expansion and neurologic decline requiring steroid treatment. Four of these 7 patients (57%) experienced continued neurologic decline and needed surgical fenestration. On univariate analysis, receipt of >4 rounds of SRS was the sole variable associated with an increased risk of cyst formation (odds ratio, 16.58; P = 0.001). This association remained robust after adjusting for duration of follow-up (odds ratio, 13.59; P = 0.003). CONCLUSIONS: In our experience with 1106 SRS-treated cases of BM, cyst formation was a rare phenomenon. However, 1 in 3 patients who underwent >4 rounds of SRS sustained cyst formation. A high proportion (78%) of SRS-associated cysts progressively expanded and required medical or surgical treatment.

Risk Factors for Readmission with Cerebrospinal Fluid Leakage Within 30 Days of Vestibular Schwannoma Surgery.

BACKGROUND: Cerebrospinal fluid (CSF) leak is a well-recognized complication after surgical resection of vestibular schwannomas and is associated with a number of secondary complications, including readmission and meningitis. OBJECTIVE: To identify risk factors for and timing of 30-d readmission with CSF leak. METHODS: Patients who had undergone surgical resection of a vestibular schwannoma from 1995 to 2010 were identified in the California Office of Statewide Health Planning and Development database. The most common admission diagnoses were identified by International Classification of Disease, ninth Revision, diagnosis codes, and predictors of readmission with CSF leak were determined using logistic regression. RESULTS: A total of 6820 patients were identified. CSF leak, though a relatively uncommon cause of admission after discharge (3.52% of all patients), was implicated in nearly half of 490 readmissions (48.98%). Significant independent predictors of readmission with CSF leak were male sex (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.32-2.25), first admission at a teaching hospital (OR 3.32, 95% CI 1.06-10.39), CSF leak during first admission (OR 1.84, 95% CI 1.33-2.55), obesity during first admission (OR 2.10, 95% CI 1.20-3.66), and case volume of first admission hospital (OR of log case volume 0.82, 95% CI 0.70-0.95). Median time to readmission was 6 d from hospital discharge. CONCLUSION: This study has quantified CSF leak as an important contributor to nearly half of all readmissions following vestibular schwannoma surgery. We propose that surgeons should focus on technical factors that may reduce CSF leakage and take advantage of potential screening strategies for the detection of CSF leakage prior to first admission discharge.

Virtual Integration Environment as an Advanced Prosthetic Limb Training Platform.

Background: Despite advances in prosthetic development and neurorehabilitation, individuals with upper extremity (UE) loss continue to face functional and psychosocial challenges following amputation. Recent advanced myoelectric prostheses offer intuitive control over multiple, simultaneous degrees of motion and promise sensory feedback integration, but require complex training to effectively manipulate. We explored whether a virtual reality simulator could be used to teach dexterous prosthetic control paradigms to individuals with UE loss. Methods: Thirteen active-duty military personnel with UE loss (14 limbs) completed twenty, 30-min passive motor training sessions over 1-2 months. Participants were asked to follow the motions of a virtual avatar using residual and phantom limbs, and electrical activity from the residual limb was recorded using surface electromyography. Eight participants (nine limbs), also completed twenty, 30-min active motor training sessions. Participants controlled a virtual avatar through three motion sets of increasing complexity (Basic, Advanced, and Digit) and were scored on how accurately they performed requested motions. Score trajectory was assessed as a function of time using longitudinal mixed effects linear regression. Results: Mean classification accuracy for passive motor training was 43.8 ± 10.7% (14 limbs, 277 passive sessions). In active motor sessions, >95% classification accuracy (which we used as the threshold for prosthetic acceptance) was achieved by all participants for Basic sets and by 50% of participants in Advanced and Digit sets. Significant improvement in active motor scores over time was observed in Basic and Advanced sets (per additional session: ß-coefficient 0.125, p = 0.022; ß-coefficient 0.45, p = 0.001, respectively), and trended toward significance for Digit sets (ß-coefficient 0.594, p = 0.077). Conclusions: These results offer robust evidence that a virtual reality training platform can be used to quickly and efficiently train individuals with UE loss to operate advanced prosthetic control paradigms. Participants can be trained to generate muscle contraction patterns in residual limbs that are interpreted with high accuracy by computer software as distinct active motion commands. These results support the potential viability of advanced myoelectric prostheses relying on pattern recognition feedback or similar controls systems.