Correlation between initial tumor enlargement and magnetic resonance imaging characteristics following linear accelerator-based stereotactic radiosurgery for acoustic neuromas.

BACKGROUND: Initial tumor enlargement (or pseudoprogression) instead of true tumor progression is a common phenomenon in patients with acoustic neuromas who are treated with stereotactic radiosurgery (SRS). This phenomenon can affect clinical decision-making and patient management. This study assessed the correlation between initial tumor enlargement and magnetic resonance imaging characteristics in patients with acoustic neuromas who were treated with linear accelerator (LINAC)-based SRS. The long-term tumor control outcomes were also analyzed. MATERIALS AND METHODS: In total, 330 patients with sporadic acoustic neuromas who were treated with LINAC SRS between March 2006 and March 2020 were retrospectively evaluated to assess their initial tumor enlargement. The tumors were divided into homogeneously enhanced, heterogeneously enhanced, and cystic types based on the morphological characteristics noted on magnetic resonance images. Tumor control was assessed in 275 patients with a follow-up duration of more than 2 years. RESULTS: Initial enlargement was observed in 137 of 330 (41.5%) tumors as early as 3 months after LINAC SRS. Data analysis revealed that postoperative tumors with a residual volume lower than 2.5 cm3 had a lower incidence of initial enlargement (p = 0.039). No correlation was noted between the initial enlargement and morphological characteristics of tumors. In patients with a mean follow-up duration of 82.8 ± 37.2 months, heterogeneously enhanced tumors exhibited a lower control rate than homogeneously enhanced and cystic tumors (p = 0.045). No correlation was noted between initial enlargement and tumor control. CONCLUSION: Initial enlargement can occur as early as 3 months after SRS. Postoperative residual tumors with a volume lower than 2.5 cm3 exhibit a lower incidence of initial enlargement. Heterogeneously enhanced tumors have a lower local control rate.

Neuropsychological impairment in primary malignant brain tumor patients with awake craniotomy: a hospital-based registration study.

PURPOSE: Neuroplasticity is an ability to maintain neural circuit function when facing damages. It is one of the reasons that making brain tumors notorious. Therefore, we evaluated the characteristics of patients with primary brain tumors, compared neuropsychological deficits between patients who had awake craniotomy with left- or right-sided tumors, and analyzed the association between white matter tracts and neuropsychological deficits in patients with right-sided tumors. METHODS: Using the registration dataset of Chang Gung Memory Hospital between 2014 and 2020, this study included a total of 698 adult patients who received craniotomy for primary brain tumors (538 of conventional craniotomy; 160 of awake craniotomy). Neuropsychological assessments were arranged in patients as preoperative evaluation for awake craniotomies. RESULTS: A lower proportion of right-sided tumors was noted in patient who had awake craniotomy than those who had conventional craniotomy (33.8% and 51.5%, p < 0.001). In awake craniotomy, 88.7% of patients with left-sided tumors and 77.8% of patients with right-sided tumors had neuropsychological impairment. Patients with left-sided tumors had worse preoperative performance compared to those with right-sided tumors in global function (36.2% and 8.0%, p < 0.001), language domain (57.6% and 22.2%, p < 0.001), and attention (36.0% and 18.5%, p = 0.02). Furthermore, in those with right-sided low-grade gliomas, patients involving pathway of superior longitudinal fasciculus (SLF) I had a higher risk of deficits than those without involvement in verbal memory (p = 0.001, Odd ratio = 11.2, 95% CI = 1.8 ~ 71.4) and visual memory (p = 0.048, Odd ratio = 10.5, 95% CI = 1.0 ~ 111). CONCLUSION: In awake craniotomy, patients with left-sided brain tumors had worse cognitive function than those with right-sided tumors in terms of global function, language, and attention. 77% of patients with right-sided tumors had neuropsychological impairment. Therefore, a comprehensive neuropsychological evaluation and awake craniotomy are necessary for patients with brain tumors.

Predictors for delayed awakening in adult glioma patients receiving awake craniotomy under monitored anesthesia care.

PURPOSE: Delayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown. METHODS: This retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles. RESULTS: After propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate. CONCLUSION: Our retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate.

The impact of patient factors and tumor characteristics on language neuroplasticity in left hemispheric diffuse gliomas prior to surgical resection.

PURPOSE: Language networks are reorganized during glioma growth, leading to varying language performance in patients with gliomas located in or around language-eloquent areas. Therefore, pre-treated language performance reflects the neuroplasticity potential. Different domains of language processing, such as speech expression, repetition, and comprehension, involving different neural networks. We analyzed the effects of patient factors and tumor characteristics on the pre-treated performance to investigate neuroplastic potential of different language domains. METHODS: Patient age, sex, education level, tumor grade, language pathway involvement, T1 contrast enhanced (C+), and FLAIR (T2) volume were selected as variables. The correlation with abnormal language performance was verified using univariate and multivariate logistic regression. RESULTS: In total, 104 left hemispheric glioma patients were enrolled in this study. 44% of patients had repetitive abnormalities, 34.9% had comprehensive abnormalities, and 32.1% had expressive abnormalities. The proportion of normal language performance was 60% in grade 2 and 3 gliomas and 16% in grade 4 gliomas. Tumor grade (p = 0.006) and T2 volume (p = 0.008) were associated with abnormal performance in the expressive domain, education level (p = 0.004) and T1 C+ volume (p = 0.049) in the repetitive domain, and education level (p = 0.013), T2 volume (p = 0.011), and tumor grade (p = 0.089) in the comprehensive domain. CONCLUSION: Different clinical and radiological factors affected the abnormal performance of the three language domains, indicating their functional connectivity and neuroplastic potential are inherently varied. The dynamic interactions between patient factors, tumor characteristics, and language processing should be considered when resecting left hemispheric gliomas.

Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.

INTRODUCTION: Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). METHODS: We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. RESULTS: In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. CONCLUSION: Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.

A mass spectrometry imaging and lipidomic investigation reveals aberrant lipid metabolism in the orthotopic mouse glioma.

Lipids perform multiple biological functions and reflect the physiology and pathology of cells, tissues, and organs. Here, we sought to understand lipid content in relation to tumor pathology by characterizing phospholipids and sphingolipids in the orthotopic mouse glioma using MALDI MS imaging (MSI) and LC-MS/MS. Unsupervised clustering analysis of the MALDI-MSI data segmented the coronal tumoral brain section into 10 histopathologically salient regions. Heterogeneous decrease of the common saturated phosphatidylcholines (PCs) in the tumor was accompanied by the increase of analogous PCs with one or two additional fatty acyl double bonds and increased lyso-PCs. Polyunsaturated fatty acyl-PCs and ether PCs highlighted the striatal tumor margins, whereas the distributions of other PCs differentiated the cortical and striatal tumor parenchyma. We detected a reduction of SM d18:1/18:0 and the heterogeneous mild increase of SM d18:1/16:0 in the tumor, whereas ceramides accumulated only in a small patch deep in the tumoral parenchyma. LC-MS/MS analyses of phospholipids and sphingolipids complemented the MALDI-MSI observation, providing a snapshot of these lipids in the tumor. Finally, the proposed mechanisms responsible for the tumoral lipid changes were contrasted with our interrogation of gene expression in human glioma. Together, these lipidomic results unveil the aberrant and heterogeneous lipid metabolism in mouse glioma where multiple lipid-associated signaling pathways underline the tumor features, promote the survival, growth, proliferation, and invasion of different tumor cell populations, and implicate the management strategy of a multiple-target approach for glioma and related brain malignancies.

Risk factors for peritumoral edema after radiosurgery for intracranial benign meningiomas: a long-term follow-up in a single institution.

OBJECTIVE: Peritumoral edema (PTE) is recognized as a complication following stereotactic radiosurgery (SRS). The aim of this paper was to evaluate the risk of post-SRS PTE for intracranial benign meningiomas and determine the predictive factors. METHODS: Between 2006 and 2021, 227 patients with 237 WHO grade I meningiomas were treated with Novalis linear accelerator SRS. All patients were treated with a single-fraction dose of 11-20 Gy (median 14 Gy). The median tumor volume was 3.32 cm3 (range 0.24-51.7 cm3). RESULTS: The median follow-up was 52 months (range 12-178 months). The actuarial local tumor control rates at 2, 5, and 10 years after SRS were 99.0%, 96.7%, and 86.3%, respectively. Twenty-seven (11.9%) patients developed new or worsened post-SRS PTE, with a median onset time of 5.2 months (range 1.2-50 months). Only 2 patients developed post-SRS PTE after 24 months. The authors evaluated factors related to new-onset or worsened PTE after SRS. In univariate analysis, initial tumor volume > 10 cm3 (p = 0.03), total marginal dose > 14 Gy (p < 0.001), preexisting edema (p < 0.0001), tumor location (p < 0.001), parasagittal location (p < 0.0001), superior sagittal sinus (SSS) involvement (p < 0.0001), and SSS invasion (p < 0.015) were found to be significant risk factors. In multivariate analysis, total marginal dose > 14 Gy (HR 3.38, 95% CI 1.37-8.33, p = 0.008), preexisting SRS edema (HR 12.86, 95% CI 1.09-4.15, p < 0.0001), tumor location (HR 2.13, 95% CI 1.04-3.72, p = 0.027), parasagittal location (HR 8.84, 95% CI 1.48-52.76, p = 0.017), and SSS invasion (HR 0.34, 95% CI 0.13-0.89, p = 0.027) were significant risk factors. Twelve (5.3%) patients were symptomatic. Ten of 27 patients had complete resolution of neurological symptoms and edema improvement with steroid treatment. Steroid treatment failed in 2 patients, who subsequently required resection for PTE. CONCLUSIONS: Radiosurgery is a safe and effective method of treating benign intracranial meningiomas according to long-term follow-up. We also identified total marginal dose > 14 Gy, preexisting PTE, parasagittal location, and SSS invasion as predictors of post-SRS PTE. Risk factors for post-SRS PTE should be considered in meningioma treatment.

Sonogenetic-Based Neuromodulation for the Amelioration of Parkinson's Disease.

Sonogenetics is a promising strategy allowing the noninvasive and selective activation of targeted neurons in deep brain regions; nevertheless, its therapeutic outcome for neurodegeneration diseases that need long-term treatment remains to be verified. We previously enhanced the ultrasound (US) sensitivity of targeted cells by genetic modification with an engineered auditory-sensing protein, mPrestin (N7T, N308S). In this study, we expressed mPrestin in the dopaminergic neurons of the substantia nigra in Parkinson's disease (PD) mice and used 0.5 MHz US for repeated and localized brain stimulation. The mPrestin expression in dopaminergic neurons persisted for at least 56 days after a single shot of adeno-associated virus, suggesting that the period of expression was long enough for US treatment in mice. Compared to untreated mice, US stimulation ameliorated the dopaminergic neurodegeneration 10-fold and mitigated the PD symptoms of the mice 4-fold, suggesting that this sonogenetic strategy has the clinical potential to treat neurodegenerative diseases.

Irisin, an exercise myokine, potently suppresses tumor proliferation, invasion, and growth in glioma.

Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G2 /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.

Integrin α2ß1-targeting ferritin nanocarrier traverses the blood-brain barrier for effective glioma chemotherapy.

BACKGROUND: Ferritin, the natural iron storage protein complex, self-assembles into a uniform cage-like structure. Human H-ferritin (HFn) has been shown to transverse the blood-brain barrier (BBB) by binding to transferrin receptor 1 (TfR1), which is abundant in endothelial cells and overexpressed in tumors, and enters cells via endocytosis. Ferritin is easily genetically modified with various functional molecules, justifying that it possesses great potential for development into a nanocarrier drug delivery system. RESULTS: In this study, a unique integrin α2ß1-targeting H-ferritin (2D-HFn)-based drug delivery system was developed that highlights the feasibility of receptor-mediated transcytosis (RMT) for glioma tumor treatment. The integrin targeting α2ß1 specificity was validated by biolayer interferometry in real time monitoring and followed by cell binding, chemo-drug encapsulation stability studies. Compared with naïve HFn, 2D-HFn dramatically elevated not only doxorubicin (DOX) drug loading capacity (up to 458 drug molecules/protein cage) but also tumor targeting capability after crossing BBB in an in vitro transcytosis assay (twofold) and an in vivo orthotopic glioma model. Most importantly, DOX-loaded 2D-HFn significantly suppressed subcutaneous and orthotopic U-87MG tumor progression; in particular, orthotopic glioma mice survived for more than 80 days. CONCLUSIONS: We believe that this versatile nanoparticle has established a proof-of-concept platform to enable more accurate brain tumor targeting and precision treatment arrangements. Additionally, this unique RMT based ferritin drug delivery technique would accelerate the clinical development of an innovative drug delivery strategy for central nervous system diseases with limited side effects in translational medicine.

Can we predict intraoperative blood loss in meningioma patients? Application of dynamic susceptibility contrast-enhanced magnetic resonance imaging.

PURPOSE: To evaluate the potential of quantitative dynamic susceptibility contrast (DSC) perfusion MR imaging parameters as imaging biomarkers for predicting intraoperative blood loss in meningioma. METHODS: Fifty-one non-embolized meningioma patients who had undergone preoperative DSC perfusion MR imaging were retrospectively included. The corrected relative cerebral blood volume (rCBV) and leakage coefficient (K2) of the entire enhanced tumor were obtained using leakage correction. Tumor volume, location, grade, and other clinical variables, were also analyzed. To investigate the vascularity and vascular permeability of meningiomas, and their correlation with predicting estimated blood loss (EBL) using preoperative DSC perfusion MR imaging, the authors proposed an index reflecting the inherent tendency of meningiomas to bleed after controlling volume (i.e., EBL/cm3). Simple regression was performed to identify predictors of EBL/cm3; subsequently, the relevant variables included in the stepwise multiple linear regression. RESULTS: On univariate analysis, EBL/cm3 was correlated with rCBV (r=0.677; P<0.001), K2 (r=0.294; P=0.036), and tumor volume (r=-0.312, P=0.026). EBL/cm3 was not correlated with age (P=0.873), sex (P=0.404), tumor location (P=0.327), or histological grade (P=0.230). On multiple linear regression, rCBV (ß=0.663 [0.463-0.864], B=1.293 [0.903-1.684; P<0.001) and K2 (ß=0.260 [0.060-0.460], B=2.277 [0.523-4.031], P=0.012), were the only independent predictors of EBL/cm3. CONCLUSION: The rCBV and K2 derived from DSC perfusion MR imaging in meningiomas may serve as feasible tools for clinicians to predict intraoperative blood loss and facilitate surgical planning.

Editorial: advances in neuro-oncology and clinical treatment-from ASNO 2019.

The 16th Annual Meeting of the Asian Society for Neuro-Oncology was successfully held in Taipei, September 26-29. The diverse, in-depth experiences sharing in the conference contributed the fruitful result. Here we selected several important manuscripts to represent the advance of neuro-oncology and clinical treatment in Asia.

Transmastoid presigmoid retrolabyrinthine approach for removal of pontine cavernous malformation: how I do it.

BACKGROUND: Bleeding of brainstem cavernous malformations (BSCM) cause high morbidity and should be treated surgically whenever possible. METHOD: We present a 56-year-old man, who was diagnosed with a BSCM at right pons, which caused functional impairments of dorsal column, spinothalamic tract, cochlear nucleus, and middle cerebellar peduncle. A transmastoid presigmoid retorlabyrinthine approach via the lateral pontine zone (LPZ), with an assistance of imaging guidance and intraoperative neurophysiological monitoring, was performed to completely resect the BSCM. The patient recovered despite a transient worsening of cerebellar sign and hemiparesthesia for 1 week, without surgical complications. CONCLUSIONS: A transmastoid presigmoid retrolabyrinthine approach through LPZ is safe and effective for lateral pontine BSCM resection.

Microbubble-facilitated ultrasound pulsation promotes direct α-synuclein gene delivery.

Intra-neuronal α-synuclein (αSNCA) aggregation are the leading cause of dopaminergic neuron degeneration in Parkinson's disease (PD). Most PD patients is linked with αSNCA gene mutations. Gene therapy shows therapeutic potential by packing gene into viral vectors to improve gene expression through stereotactic brain injections. However, through intracranial injection, the gene expression is typically limited with tissue distribution tightly adjacent to the injection track, when expressing therapeutic genes for a wider CNS region is preferable. We use microbubble-facilitated ultrasound pulsations (MB-USP) as a new gene delivering tool to enhance the limit gene delivery of local injection in brain and evaluate the feasibility using αSNCA as model gene. We demonstrate that MB-USP can transfect naked constructs DNA of αSNCA gene into two types of neuron cells and enhance the gene expression. We confirm α-synuclein fusion protein functionality, showing that α-synuclein fusion protein significantly reduce the mitochondrial activity. We show MB-USP improves in vivo gene transfer in the brain with naked construct local injection, significantly enhances α-synuclein expression level to 1.68-fold, and broaden its distribution to 25-fold. In vivo fused α-synuclein protein aggregation is also found in gene-injected mice brains by MB-USP. MB-USP provides an alternative to α-synuclein over expression in vitro and in vivo model for investigation of α-synuclein related PD therapeutic strategies.

Baseline multicentric tumors, distant recurrences and leptomeningeal dissemination predict poor survival in patients with recurrent glioblastomas receiving bevacizumab.

PURPOSE: There are no widely accepted MRI markers that predict treatment outcomes of bevacizumab among patients with recurrent glioblastoma (GB). We aimed to determine if conventional MRI features of recurrent GB predict survival of patients receiving bevacizumab. METHODS: Patients with recurrent GB were retrospectively included if they received bevacizumab monotherapy between 2008 and 2017 after failure of standard treatment. Their MRI studies obtained at baseline and tumor recurrence, prior to bevacizumab treatment, were evaluated for multiple MRI features including measurable tumor, baseline multicentric tumors, distant recurrence, non-contrast-enhancing tumor, deep white matter invasion, multiple parenchymal tumors, bilateral cerebral involvement, ependymal extension and leptomeningeal dissemination. Predictive values of MRI features and patient characteristics on patient survival were statistically analyzed. RESULTS: A total of 103 patients were included. Baseline multicentric tumors (OR = 4.07; P = 0.042) and distant recurrence (OR = 28.5; P < 0.001) were two significant predictors of 3-month progression-free survival (PFS) rate. Distant recurrence (HR = 3.94; P < 0.001) was the only independent predictor of PFS. Baseline multicentric tumors (HR = 1.97; P = 0.028), distant recurrence (HR = 4.73; P < 0.001) and leptomeningeal dissemination (HR = 2.28; P = 0.044) were three independent predictors of overall survival. CONCLUSIONS: Baseline multicentric tumors, distant recurrence and leptomeningeal dissemination predicted poor survival among patients receiving bevacizumab for recurrent GB. Conventional MRI may help selecting patients with recurrent GB for bevacizumab treatment.

Awake craniotomies for epileptic gliomas: intraoperative and postoperative seizure control and prognostic factors.

PURPOSE: Awake craniotomy is well-established for tumors resected in eloquent brain areas. Whether awake craniotomy provides improved seizure control in patients with epileptic gliomas has not been well evaluated. This study analyzed the incidence, risk factors and outcome of seizures during and following awake craniotomies for patients presenting with epilepsy and glioma. METHODS: Forty-one patients undergoing awake craniotomies for epileptic gliomas were retrospectively analyzed. Postoperative seizure was defined as either early (postoperative day 7 + before) or late onset (after postoperative day 7). Neurologic function was assessed with modified Rankin Scales (mRS) and seizure outcome was assessed using International League Against Epilepsy (ILAE) classification. Multivariable logistic regression was used for clinical variables associated with postoperative seizures. RESULTS: Three patients (7.3%) had intraoperative seizures however did not fail the awake craniotomies. Mean mRS before and after the awake craniotomies were 2.4 and 2.1, respectively (P = 0.032). Fourteen (34.1%) patients had early seizures, which caused longer hospitalization than those without early seizures (P = 0.03). Surgical resection to isocitrate dehydrogenase 1 (IDH1) mutation tumors, comparing to IDH1 wild type tumors, caused better postoperative seizure control. 6-month late seizure freedom was achieved in 33 patients (80.5%). Early seizure recurrence (odds ratio = 30.75; P = 0.039) and postoperative mRS ≥ 3 (odds ratio = 7.00; P = 0.047) were independent risk factors for late seizures. CONCLUSIONS: Intraoperative seizures could be well-controlled during awake craniotomies. Early postoperative seizures extended hospitalization and strongly predicted late seizure recurrence. Awake craniotomies benefited long-term seizure control in patients with epileptic gliomas.

Intraoperative linguistic performance during awake brain surgery predicts postoperative linguistic deficits.

INTRODUCTION: Awake craniotomy pursues a balance between extensive tumor resection and preservation of postoperative language function. A dilemma exists in patients whose tumor resection is restricted due to signs of language impairment observed during awake craniotomy. In order to determine the degree to which recovery of language function caused by tumor resection can be achieved by spontaneous neuroplasticity, the change in postoperative language function was compared to quantified intraoperative linguistic performance. METHODS: The modified, short-form Boston Diagnostic Aphasia Examination (sfBDAE) was used to assess pre- and postoperative language functions; visual object naming (DO 80) and semantic-association (Pyramid and Palm Tree Test, PPTT) tests assessed intraoperative linguistic performance. DO 80 and PPTT were performed alternatively during subcortical functional monitoring while performing tumor resection and sfBDAE was assessed 1-week postoperatively. RESULTS: Most patients with observed language impairment during awake surgery showed improved language function postoperatively. Both intraoperative DO 80 and PPTT showed significant correlation to postoperative sfBDAE domain scores (p < 0.05), with a higher correlation observed with PPTT. A linear regression model showed that only PPTT predicted the postoperative sfBDAE domain scores with the adjusted R2 ranging from 0.51 to 0.89 (all p < 0.01). Receiver operating characteristic analysis showed a cutoff value of PPTT that yielded a sensitivity of 80% and specificity of 100%. CONCLUSION: PPTT may be a feasible tool for intraoperative linguistic evaluation that can predict postoperative language outcomes. Further studies are needed to determine the extent of tumor resection that optimizes the postoperative language following neuroplasticity.

Symptomatic cord compression by paraspinal musculature following cervical laminectomy: rare complication.

PURPOSE: Cervical laminectomy is an effective treatment for multilevel cervical compressive myelopathy. Symptomatic spinal cord compression (SSCC) by paraspinal musculature (PSM) following cervical laminectomy is rarely reported. The aim of this study was to evaluate the frequency and pathogenesis of this complication after cervical laminectomy. METHODS: Between 2007 and 2016, the medical records of 1309 cervical laminectomy patients were reviewed. From these 1309 records, seven patients (five men and two women; average age, 64.12 years; range 48-78 years) with SSCC by PSM following cervical laminectomy were identified. The incidence and possible risk factors of this rare condition were evaluated. RESULTS: The frequency of SSCC by PSM following cervical laminectomy was 0.53%. Presenting symptoms included paralyses and paresthesias, depending on the level and severity of cervical spinal cord compression. The initial onset of neurologic deterioration varied from 12 h to 21 days after operation. Most patients recovered well after surgical management with an average Barthel index of 74.3 at 6 months after surgery. In comparison with 63 controls, this rare complication was associated with preoperative cervical kyphosis, prior antiplatelet therapy, and posterior decompression with prone position. CONCLUSIONS: SSCC by PSM is a rare but devastating complication following cervical laminectomy, especially in those patients with preoperative kyphosis, prior antiplatelet treatment, and decompression with prone position. MRI is an ideal tool to identify this complication. Rapid cervical cord decompression and avoidance of recurrent compressive events can achieve a good clinical outcome. These slides can be retrieved under Electronic Supplementary Material.

Focused Ultrasound Enhances Central Nervous System Delivery of Bevacizumab for Malignant Glioma Treatment.

Purpose To demonstrate that magnetic resonance (MR) imaging-monitored transcranial focused ultrasound can enhance the delivery of the antiangiogenic monoclonal antibody bevacizumab into the central nervous system (CNS) for glioblastoma multiforme (GBM) treatment. Materials and Methods All animal experiments were approved by the animal committee and adhered to experimental animal care guidelines. Transcranial focused ultrasound exposure in the presence of microbubbles was used to open the blood-brain barrier (BBB) to enhance bevacizumab penetration into the CNS in healthy and glioma-bearing mice. Bevacizumab concentration was quantitated with high-performance liquid chromatography, and Western blot testing was performed to confirm the specific biologic form in the CNS. Penetration of bevacizumab into brain tissue was estimated in vivo by means of contrast material-enhanced MR imaging and quantitative gallium 68 ((68)Ga)-bevacizumab micro-positron emission tomography, and glioma progression was longitudinally followed with T2-weighted MR imaging. Hematoxylin-eosin staining and cluster of differentiation 31 immunostaining were used to assess morphologic changes and vascular inhibition at histologic examination. The two-tailed Student t test and the Mantel-Cox log-rank test were used for statistical analyses, with a significance level of .05. Results Focused ultrasound significantly enhanced bevacizumab penetration into the CNS by 5.7- to 56.7-fold compared with that in nonexposed brain (both P < .0001). Contrast-enhanced MR imaging indexes correlated with bevacizumab concentration (r = 0.748-0.857) in vivo. Focused ultrasound-enhanced bevacizumab delivery significantly retarded glioma progression, with a significantly increased median survival (median increase in survival time = 135% in the group treated with bevacizumab and focused ultrasound, P < .0001; as compared with 48% in the group treated with bevacizumab alone, P = .0002). Conclusion Focused ultrasound-enhanced bevacizumab delivery can provide an antivascularization normalization effect to suppress glioma. (©) RSNA, 2016 Online supplemental material is available for this article.