Adjuvant convection-enhanced delivery for the treatment of brain tumors.

BACKGROUND: Malignant gliomas are a therapeutic challenge and remain nearly uniformly fatal. While new targeted chemotherapeutic agentsagainst malignant glioma have been developed in vitro, these putative therapeutics have not been translated into successful clinical treatments. The lack of clinical effectiveness can be the result of ineffective biologic strategies, heterogeneous tumor targets and/or the result of poortherapeutic distribution to malignant glioma cells using conventional nervous system delivery modalities (intravascular, cerebrospinal fluid and/orpolymer implantation), and/or ineffective biologic strategies. METHODS: The authors performed a review of the literature for the terms "convection enhanced delivery", "glioblastoma", and "glioma". Selectclinical trials were summarized based on their various biological mechanisms and technological innovation, focusing on more recently publisheddata when possible. RESULTS: We describe the properties, features and landmark clinical trials associated with convection-enhanced delivery for malignant gliomas.We also discuss future trends that will be vital to CED innovation and improvement. CONCLUSION: Efficacy of CED for malignant glioma to date has been mixed, but improvements in technology and therapeutic agents arepromising.

Endoscopic Endonasal Transpterygoid Approach and the Need for Myringotomy.

OBJECTIVE: The expanded endonasal transpterygoid approach (EETA) is used to access the middle and posterior fossa through the pterygoid process. Traditionally, the eustachian tube (ET) was resected during EETA, which often required subsequent myringotomy for inner ear drainage. Anterolateral transposition of the ET was proposed to decrease potential morbidity associated with resection. However, a comparison of resection versus transposition regarding the need for subsequent myringotomy has not been reported. METHODS: This is a retrospective cohort study of patients who underwent an EETA. Patient demographics, tumor characteristics, management of ET with resection versus transposition, and need for subsequent myringotomy were collected. Analysis was performed with JMP software in standard fashion and univariate and multivariate logistic regression analysis performed with a p < 0.05 was considered significant. RESULTS: Ninety-one patients underwent EETA for various malignant and benign tumors. Twenty-seven patients required myringotomy, with tumors of the pterygopalatine fossa accounting for the most common location (n = 8). Malignant pathology had the highest myringotomy rate compared to benign tumors (48.9% vs. 10.9%, p < 0.001), as did receiving postoperative radiation (p < 0.001), ET resection (p < 0.001), and increasing CPK class. Multivariate analysis of these variables suggests that only ET resection significantly correlated with the need for myringotomy (LR 7.97, p = 0.005). CONCLUSIONS: ET resection during EETA can lead to ET dysfunction and require myringotomy post-operatively, and patients should be counseled of this risk. Radiation treatment, malignant pathology, and CPK class, all reflecting situations where more extensive surgery was needed, were associated with the need for myringotomy on univariate analysis but did not reach significance with multivariate analysis. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1203-1207, 2024.

Intradural Pituitary Hemitransposition: Technical Note and Case Series Illustration.

BACKGROUND AND OBJECTIVES: Lesions located in the retrosellar region, interpeduncular cistern, and petroclival region are among the most difficult to access in neurosurgery. Transcranial approaches are useful; however, the large distance between the surgeon and the lesion as well as the presence of major neurovascular structures surrounding the lesion may limit surgical exposure. A midline transsphenoidal route avoids transgression of the neurovascular plane and provides direct access to the interpeduncular cistern. To safely access the interpeduncular fossa, it requires mobilization of the pituitary gland. The pituitary hemitransposition technique permits mobilization of the gland, while preserving its venous drainage and arterial supply to the gland on one of its sides, preserving gland function. The authors aim to describe the intradural pituitary hemitransposition technique and to demonstrate its safe application for resection of skull base tumors in the retrosellar space. METHODS: The authors describe the surgical technique and illustrate its application in 5 cases of different types of skull base tumors, including a video demonstrating all the steps to perform this approach. In addition, the authors discuss the advantages and limitations of this technique compared with other approaches to the retrosellar space. RESULTS: The intradural pituitary hemitransposition technique was used to safely resect a chondrosarcoma, chordoma, craniopharyngioma, teratoma, and meningioma involving the parasellar and retrosellar spaces, while minimizing endocrine morbidity. We had one patient with mild, albeit permanent hyperprolactinemia and hypothyroidism after surgery. No other patients had permanent dysfunction related to surgery. CONCLUSION: The endonasal endoscopic intradural pituitary hemitransposition approach is an effective technique for resection of lesions located within the retrosellar and petroclival regions, allowing adequate exposure while potentially optimizing the preservation of the pituitary function.

Surgical Characteristics of Intracranial Biopsy Using a Frameless Stereotactic Robotic Platform: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Cranial robotics are a burgeoning field of neurosurgery. To date, all cranial robotic systems described have been computerized, arm-based instruments that take up significant space in the operating room. The Medtronic Stealth Autoguide robot has a smaller operating room footprint and offers multiaxial, frame-based surgical targeting. The authors set out to define the surgical characteristics of a novel robotic platform for brain biopsy in a large patient cohort. METHODS: Patients who underwent stereotactic biopsy using the Stealth Autoguide cranial robotic platform from July 2020 to March 2023 were included in this study. Clinical, surgical, and histological data were collected and analyzed. RESULTS: Ninety-six consecutive patients (50 female, 46 male) were included. The mean age at biopsy was 53.7 ± 18.0 years. The mean target depth was 68.2 ± 15.3 mm. The biopsy diagnostic tissue acquisition rate was 100%. The mean time from incision to biopsy tissue acquisition was 15.4 ± 9.9 minutes. Target lesions were located throughout the brain: in the frontal lobe (n = 32, 33.3%), parietal lobe (n = 21, 21.9%), temporal lobe (n = 22, 22.9%), deep brain nuclei/thalamus (n = 13, 13.5%), cerebellum (n = 7, 7.3%), and brainstem (n = 1, 1.0%). Most cases were gliomas (n = 75, 78.2%). Patients were discharged home on postoperative day 0 or 1 in 62.5% of cases. A total of 7 patients developed postoperative complications (7.2%). CONCLUSION: This cranial robotic platform can be used for efficient, safe, and accurate cranial biopsies that allow for reliable diagnosis of intracranial pathology in a minimally invasive setting.

A modern approach to olfactory groove meningiomas.

OBJECTIVE: Management of olfactory groove meningiomas (OGMs) has changed significantly with the advances in extended endoscopic endonasal approaches (EEAs), which is an excellent approach for patients with anosmia since it allows early devascularization and minimizes retraction on the frontal lobes. Craniotomy is best suited for preservation of olfaction. However, not infrequently, a tumor presents after extending outside the reach of an EEA and a solely transcranial approach would require manipulation and retraction of the frontal lobes. These OGMs may best be treated by a staged EEA-craniotomy approach. In this study the authors' goal was to present their case series of patients with OGMs treated with their surgical approach algorithm. METHODS: The authors conducted an IRB-approved, nonrandomized historic cohort including all consecutive cases of OGMs treated surgically between 2010 and 2020. Patient demographic information, presenting symptoms, operative details, and complications data were collected. Preoperative and postoperative tumor and T2/FLAIR intensity volumes were calculated using Visage Imaging software. RESULTS: Thirty-one patients with OGMs were treated (14 craniotomy only, 11 EEA only, and 6 staged). There was a significant difference in the distribution of patients presenting with anosmia and visual disturbance by approach. Tumor size was significantly correlated with preoperative vasogenic edema. Gross-total resection was achieved in 90% of cases, with near-total resection occurring twice with EEA and once with a staged approach. T2/FLAIR hyperintensity completely resolved in 90% of cases and rates did not differ by approach. Complication rates were not significantly different by approach and included 4 CSF leaks (p = 0.68). CONCLUSIONS: A staged approach for the management of large OGMs with associated anosmia and significant lateral extension is a safe and effective option for surgical management. Through utilization of the described algorithm, the authors achieved a high rate of GTR, and this strategy may be considered for large OGMs.

Epileptic versus neuro-oncological focus of management in pediatric patients with concurrent primary brain lesion and seizures: a systematic review.

OBJECTIVE: Seizures can be a debilitating manifestation of underlying neoplastic intracranial pathology. Existing literature offers a paucity of scientific consensus regarding risk factors, seizure semiology, operative techniques, and tumor characteristics in pediatric patients with a concurrent diagnosis of primary intracranial neoplasm and seizures. To address the limited evidence in current literature, the authors systematically reviewed published literature on current clinical characteristics and management strategies for patients presenting concurrently with seizures and a newly diagnosed brain lesion, while aiming to synthesize a potential management protocol or set of recommendations for these patients. METHODS: An initial search revealed 792 papers, of which 196 studies were excluded, leaving 596 studies available for abstract review. After further stratification, 546 studies were eliminated, leaving 50 studies for eligibility assessment. Of the 50 studies, 12 met the criteria for outcome extraction. RESULTS: The results indicate that patients with a mean age of 9 years with a newly diagnosed brain tumor and presenting symptoms of seizure are likely to present with daily seizures of the complex partial subtype, with the most likely primary epileptogenic and neoplastic foci occurring in the temporal lobe. The most common tumor subtypes were low-grade gliomas, ganglioglioma, dysembryoplastic neuroepithelial tumor, or astrocytoma. With the aim of gross-total resection, 77.54% of patients are likely to achieve seizure freedom. CONCLUSIONS: This study highlights the demographic, clinical, seizure, tumor, and postoperative outcomes for pediatric patients presenting with a primary brain tumor and concurrent seizures. Further prospective multicenter studies are necessary to understand and compare varying treatment approaches and to develop standardized guidelines for these patients, with the goal of optimizing neuro-oncological and seizure-related outcomes.

Association between systemic treatment with immune checkpoint inhibitor therapy in renal cell carcinoma and reduced risk of brain metastasis development.

OBJECTIVE: Immune checkpoint inhibitor (ICI) efficacy in the treatment of metastatic renal cell carcinoma (RCC) without brain metastases (BMs) is well established in several clinical trials; however, patients with BMs were typically excluded from these trials. Therefore, the efficacy of ICI in the treatment or prevention of BM remains unclear. The primary aim of the study was to address the efficacy of ICI in treatment of patients with RCC BMs compared with patients receiving targeted therapies. A secondary aim was to evaluate the risk of RCC BM development among patients who received ICI versus targeted therapies early in their treatment course. METHODS: A retrospective single-center review between 2011 and 2018 identified 425 patients treated for metastatic RCC. The study group included patients who received ICI and/or targeted therapies during their disease. Data analyzed included demographic information, systemic treatments, overall survival from RCC diagnosis (OSRCC) and from BM diagnosis (OSBM), and BM development. Fisher's exact test was used to evaluate the frequency of BM occurrence. Survival was assessed using Kaplan-Meier curves and log-rank tests. RESULTS: Of the 425 patients, 125 received ICI and 300 were treated with molecular targeted agents only during their clinical course. BMs occurred in 113 (9.5%) of the 425 patients. Among patients with BMs, OSRCC was improved with the use of ICI (77.2 vs 25.2 months, p < 0.001), with 1-, 2-, and 5-year survival rates of 93.9%, 81.8%, and 62.6%, respectively. The use of ICI was associated with increased OSBM (21.7 vs 8.9 months, p = 0.001). The rate of BM development was lower when patients were treated with ICI (8/100 [8.0%]) compared with targeted therapy (47/267 [17.6%]) (OR 0.41, 95% CI 0.18-0.89; p = 0.021). CONCLUSIONS: ICI was associated with improved OSRCC and OSBM in patients with BMs and decreased the probability of BM development in patients with metastatic RCC. Prospective trials are needed to further evaluate optimal use of ICI in treatment of RCC BMs.

Supratotal Surgical Resection for Low-Grade Glioma: A Systematic Review.

Low-grade gliomas (LGGs) are optimally treated with up-front maximal safe surgical resection, typically defined as maximizing the extent of tumor resection while minimizing neurologic risks of surgery. Supratotal resection of LGG may improve outcomes beyond gross total resection by removing tumor cells invading beyond the tumor border as defined on MRI. However, the evidence regarding supratotal resection of LGG, in terms of impact on clinical outcomes, such as overall survival and neurologic morbidities, remains unclear. Authors independently searched the PubMed, Medline, Ovid, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases for studies evaluating overall survival, time to progression, seizure outcomes, and postoperative neurologic and medical complications of supratotal resection/FLAIRectomy of WHO-defined LGGs. Papers in languages other than English, lacking full-text availability, evaluating supratotal resection of WHO-defined high-grade gliomas only, and nonhuman studies were excluded. After literature search, reference screening, and initial exclusions, 65 studies were screened for relevancy, of which 23 were evaluated via full-text review, and 10 were ultimately included in the final evidence review. Studies were evaluated for quality using the MINORS criteria. After data extraction, a total of 1301 LGG patients were included in the analysis, with 377 (29.0%) undergoing supratotal resection. The main measured outcomes were extent of resection, pre- and postoperative neurological deficits, seizure control, adjuvant treatment, neuropsychological outcomes, ability to return to work, progression-free survival, and overall survival. Overall, low- to moderate-quality evidence was supportive of aggressive, functional boundary-based resection of LGGs due to improvements in progression-free survival and seizure control. The published literature provides a moderate amount of low-quality evidence supporting supratotal surgical resection along functional boundaries for low-grade glioma. Among patients included in this analysis, the occurrence of postoperative neurological deficits was low, and nearly all patients recovered within 3 to 6 months after surgery. Notably, the surgical centers represented in this analysis have significant experience in glioma surgery in general, and supratotal resection specifically. In this setting, supratotal surgical resection along functional boundaries appears to be appropriate for both symptomatic and asymptomatic low-grade glioma patients. Larger clinical studies are needed to better define the role of supratotal resection in LGG.

Impact of Etiology on Seizure and Quantitative Functional Outcomes in Children with Cerebral Palsy and Medically Intractable Epilepsy Undergoing Hemispherotomy/Hemispherectomy.

OBJECTIVE: To compare functional and seizure outcomes in children with vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy following functional hemispherotomy or anatomic hemispherectomy. METHODS: Consecutive patients satisfying inclusion criteria from 07/01/2015 to 12/01/2019 were reviewed for demographic data and seizure (Engel classification) and functional (Functional Independence Measure for Children) outcomes. RESULTS: After a mean follow-up of 2 years 8 months (1 year 2 months), 11 of 18 patients achieved post-operative seizure freedom without significant difference between vascular (5/7) and dysplastic (6/11) etiologies (P = 0.64). Functional assessments were completed for 15 of 18 of subjects, split comparably between groups. Mean change in the Functional Independence Measure for Children from pre-operative baseline to inpatient rehabilitation admission (vascular, -35.3 [13.2]; malformation of cortical development{MCD}, -34.5 [25.0]; P = 0.69), inpatient rehabilitation admission to discharge (vascular, 18.7 [9.0]; MCD, 20.8 [11.4]; P = 0.60), and pre-operative evaluation to clinic follow-up (vascular, -7.6 [9.7]; MCD, -3.6 [19.3]; P = 0.61) did not differ between groups. CONCLUSION: Quantitative functional and seizure outcomes following functional hemispherotomy or anatomic hemispherectomy did not differ significantly between vascular and dysplastic etiologies of cerebral palsy and medically intractable epilepsy in this study. Hemispheric surgery resulted in minor functional declines from baseline following comprehensive multidisciplinary therapy.

Neoadjuvant Arterial Embolization of Spine Metastases Associated With Improved Local Control in Patients Receiving Surgical Decompression and Stereotactic Body Radiotherapy.

BACKGROUND: Spine metastases often cause significant pain, instability, and/or neurological morbidity. Local control (LC) of spine metastases has been augmented with advances in systemic therapies, radiation, and surgical technique. Prior reports suggest an association between preoperative arterial embolization and improved LC and palliative pain control. OBJECTIVE: To further elucidate the role of neoadjuvant embolization on LC of spine metastases and the potential for improved pain control in patients receiving surgery and stereotactic body radiotherapy (SBRT). METHOD: A retrospective single-center review between 2012 and 2020 identified 117 patients with spinal metastases from various solid tumor malignancies managed with surgery and adjuvant SBRT with or without preoperative spinal arterial embolization. Demographic information, radiographic studies, treatment characteristics, Karnofsky Performance Score, Defensive Veterans Pain Rating Scale, and mean daily doses of analgesic medications were reviewed. LC was assessed using magnetic resonance imaging obtained at a median 3-month interval and defined as progression at the surgically treated vertebral level. RESULTS: Of 117 patients, 47 (40.2%) underwent preoperative embolization, followed by surgery and SBRT and 70 (59.8%) underwent surgery and SBRT alone. Within the embolization cohort, the median LC was 14.2 months compared with 6.3 months among the nonembolization cohort ( P = .0434). Receiver operating characteristic analysis suggests ≥82.5% embolization predicted significantly improved LC (area under the curve = 0.808; P < .0001). Defensive Veterans Pain Rating Scale mean and maximum scores significantly decreased immediately after embolization ( P < .001). CONCLUSION: Preoperative embolization was associated with improved LC and pain control suggesting a novel role for its use. Additional prospective study is warranted.

Comparing pre-operative versus post-operative single and multi-fraction stereotactic radiotherapy for patients with resectable brain metastases.

Background: The standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. Methods: A multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined as patients with one of the following adverse events: 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results: 279 patients were eligible for analysis. The median follow-up time was 9 months. 87 % of patients received fractionated treatment. 29 % of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0 %, 17 %, 15 %, and 7.5 %, respectively. Conclusions: In our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

Surgical Management of Recurrent Brain Metastasis: A Systematic Review of Laser Interstitial Thermal Therapy.

The incidence of recurrent metastatic brain tumors is increasing due to advances in local therapy, including surgical and radiosurgical management, as well as improved systemic disease control. The management of recurrent brain metastases was previously limited to open resection and/or irradiation. In recent years, laser interstitial thermal therapy (LITT) has become a promising treatment modality. As systemic and intracranial disease burden increases in a patient, patients may no longer be candidates for surgical resection. LITT offers a relatively minimally invasive option for patients that cannot tolerate or do not want open surgery, as well as an option for accessing deep-seated tumors that may be difficult to access via craniotomy. This manuscript aims to critically review the available data regarding the use of LITT for recurrent intracranial brain metastasis. Ten of seventy-two studies met the criteria for review. Generally, the available literature suggests that LITT is a safe and feasible option for the treatment of recurrent brain metastases involving supratentorial and cortical brain, as well as posterior fossa and deep-seated locations. Among all studies, only one directly compared craniotomy to LITT in the setting of recurrent brain metastasis. Prospective studies are needed to better elucidate the role of LITT in the management of recurrent brain metastases.

Fractionated pre-operative stereotactic radiotherapy for patients with brain metastases: a multi-institutional analysis.

BACKGROUND: The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD. METHODS: A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN. RESULTS: 53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24-25 Gy in 3-5 fractions. There were 0 LFs, 3 Grade 2-3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate. CONCLUSIONS: In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49-60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.

A Case Report of Siblings with Dystonia: A Potential Link Between DYT11 Mutation and Platelet Dysfunction.

Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder due to a mutated epsilon-sarcoglycan gene (SGCE) at the dystonia 11 (DYT11) locus on chromosome 7q21-31. ε-sarcoglycan has been identified in vascular smooth muscle and has been suggested to stabilize the capillary system. This report describes two siblings with MDS treated with bilateral globus pallidus interna deep brain stimulation. One patient had a history of bleeding following dental procedures, menorrhagia, and DBS placement complicated by intraoperative bleeding during cannula insertion. The other sibling endorsed frequent epistaxis. Subsequent procedures were typically treated perioperatively with platelet or tranexamic acid transfusion. Hematologic workup showed chronic borderline thrombocytopenia but did not elucidate a cause-specific platelet dysfunction or underlying coagulopathy. The bleeding history and thrombocytopenia observed suggest a potential link between MDS and platelet dysfunction. Mutated ε-sarcoglycan may destabilize the capillary system, thus impairing vasoconstriction and leading to suboptimal platelet aggregation.

Survival benefit with resection of brain metastases from renal cell carcinoma in the setting of molecular targeted therapy and/or immune therapy.

Patient survival with renal cell carcinoma (RCC) has improved with the use of molecular targeted agents and immunotherapy. Given the potential activity of these agents in treating brain metastases, the role of aggressive local management with surgery and/or radiation may diminish. The aim of this study was to evaluate the role of aggressive local therapy for RCC brain metastasis in the setting of molecular targeted agents and/or checkpoint inhibitor therapy. A retrospective single-center review between 2011-2018 identified patients that developed brain metastasis from RCC. Data analyzed included demographic information, systemic treatments, intracranial interventions, progression free survival and overall survival (OS). Of 1194 patients, 108(9.0%) were diagnosed with brain metastasis from RCC. OS from diagnosis of brain metastasis (OSBM) was 12.3 months. OSBM was analyzed based on three treatment groups: systemic therapy (ST) only (2.0 months, n = 23), systemic and radiotherapy (RT + ST) (12.3 months, n = 52), and systemic and radiotherapy plus resection (Surg + RT + ST) (21.7 months, n = 33). Survival benefit was seen with Surg + RT + ST compared to ST (P = 0.001), but not RT + ST (P = 0.081). Progression free survival was significantly prolonged with Surg + RT + ST compared to RT + ST (10.9 vs 5.9 months, respectively, P = 0.04). Variables such as performance status and number of brain metastases at the time of brain metastasis diagnosis did not differ significantly. In the setting of molecular targeted agents and immunotherapy, resection may benefit the appropriate surgical candidate. Prospective clinical trials are necessary to better understand the role of aggressive RCC brain metastasis treatment. Micro Abstract • Renal cell brain metastasis is often excluded from studies and brain metastases effect a large portion of RCC patients. • Retrospective study of 1194 RCC patients, 108 patients had brain metastasis, determination of the role of surgical resection in the setting of recent advances in checkpoint inhibitors. • A benefit was seen in overall survival in patients that had surgical while undergoing radiation therapy and systemic therapies. • In the setting of molecular targeted agents and immunotherapy, resection may benefit the appropriate surgical candidate(s).

Intraoperative 3 T MRI is more correlative to residual disease extent than early postoperative MRI.

PURPOSE: Extent of resection of low grade glioma (LGG) is an important prognostic variable, and may influence decisions regarding adjuvant therapy in certain patient populations. Immediate postoperative magnetic resonance image (MRI) is the mainstay for assessing residual tumor. However, previous studies have suggested that early postoperative MRI fluid-attenuated inversion recovery (FLAIR) (within 48 h) may overestimate residual tumor volume in LGG. Intraoperative magnetic resonance imaging (iMRI) without subsequent resection may more accurately assess residual tumor. Consistency in MRI techniques and utilization of higher magnet strengths may further improve both comparisons between MRI studies performed at different time points as well as the specificity of MRI findings to identify residual tumor. To evaluate the utility of 3 T iMRI in the imaging of LGG, we volumetrically analyzed intraoperative, early, and late (~ 3 months after surgery) postoperative MRIs after resection of LGG. METHODS: A total of 32 patients with LGG were assessed retrospectively. Residual tumor was defined as hyperintense T2 signal on FLAIR. Volumetric assessment was performed with intraoperative, early, and late postoperative FLAIR via TeraRecon iNtuition. RESULTS: Perilesional FLAIR parenchymal abnormality volumes were significantly different comparing intraoperative and early postoperative MRI (2.17 ± 0.45 cm3 vs. 5.47 ± 1.07 cm3, respectively (p = 0.0002)). A significant difference of perilesional FLAIR parenchymal abnormality volumes was also found comparing early and late postoperative MRI (5.47 ± 1.07 cm3 vs. 3.22 ± 0.64 cm3, respectively (p = 0.0001)). There was no significant difference between intraoperative and late postoperative Perilesional FLAIR parenchymal abnormality volumes. CONCLUSIONS: Intraoperative 3 T MRI without further resection appears to better reflect the volume of residual tumor in LGG compared with early postoperative 3 T MRI. Early postoperative MRI may overestimate residual tumor. As such, intraoperative MRI performed after completion of tumor resection may be more useful for making decisions regarding adjuvant therapy.

A case of multiple synchronously diagnosed brain metastases from alveolar soft part sarcoma without concurrent lung involvement.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a propensity for early hematogenous dissemination to the lungs and frequent brain metastasis. The development of lung metastasis almost invariably precedes intracranial involvement. There are no previously reported cases in which a patient was synchronously diagnosed with ASPS and multiple brain metastasis without lung involvement. CASE DESCRIPTION: A 29-year-old gentleman was found to have three intracranial lesions following the onset of generalized seizures. Staging studies identified a soft-tissue mass in the left thigh and an adjacent femoral lesion. Biopsy of the soft-tissue mass was consistent with ASPS. The patient then underwent neoadjuvant stereotactic radiotherapy to all three brain lesions, followed by en bloc resection of the dominant lesion. The patient was then started on a programmed death-ligand 1 (PD-L1) inhibitor. Subsequent surgical resection of the primary lesion and femur metastasis demonstrates a histopathologic complete response of the bony metastasis and partial response of the primary lesion. At present, the patient has received 14 cycles of atezolizumab without recurrence of the primary or bony lesions and the irradiated intracranial disease has remained stable without recurrence of the resected dominant lesion. CONCLUSION: While intracranial involvement is relatively common in ASPS, a case with multiple, synchronously diagnosed brain metastasis without concurrent lung metastasis has not been described. The presented case discusses the safety and efficacy of aggressive management of intracranial disease in the setting of atezolizumab. Prospective evaluation of the efficacy of checkpoint inhibitors and the prognostic value of PD-L1 expression in ASPS with brain metastasis are necessary.

Venous infarction secondary to congestive encephalopathy from central venous occlusive disease in a chronic hemodialysis patient: A case report.

Central venous occlusive disease secondary to chronic hemodialysis catheterization rarely progresses to encephalopathy, cerebral infarction, and/or hemorrhage. A 59-year-old male with 15 years of haemodialysis-dependent end-stage renal disease presented with acutely altered mental status, extensor rigidity with left hemiparesis and equal, but small and nonreactive pupils. Magnetic resonance imaging demonstrated infarction and cerebral edema. Cranial angiogram through right brachial artery injection revealed right subclavian vein opacification via a patent AV-fistula and retrograde flow to the right internal jugular vein and superior sagittal sinus secondary to occlusion of the brachiocephalic vein. All cerebral and right upper extremity venous drainage occurred via the contralateral venous outflow tract. Internal carotid artery injections revealed significant venous congestion. Despite successful angioplasty with stenting and resolution of venous flow reversal, the patient failed to recover neurologically. The devastating nature of the presented case emphasizes the need for frequent neurologic evaluation of such patients to avoid catastrophic cerebrovascular injury.

Sex differences in the effects of early life stress exposure on mast cells in the developing rat brain.

Early life stress leads to long lasting effects on behavior. Neuroimmune cells have been implicated as key mediators of experience-induced changes in brain and behavioral development, in that they are highly responsive to stress. Mast cells are one such type of neuroimmune cell, but little is known about their role in brain development or following early life stress. Here, we assessed the impact of three different early life stress exposure paradigms on mast cell dynamics in the developing brain of male and female rats, focusing on the hippocampus and hypothalamus, where most mast cells reside. We found that exposure to two weeks of chronic variable stress during gestation led to increased mast cell number and activation in the female offspring hypothalamus on the day of birth. Acute exposure to maternal separation stress on postnatal day (PN) 2 led to significant decreases in mast cells within the hypothalamus and hippocampus of females, but not males. In contrast, one week of exposure to brief daily maternal separation stress (e.g., handling), increased mast cell numbers in the female, but not male, hippocampus. We found significant sex differences in mast cell number and activation, including males having more mast cells than females in the hippocampus on the day of birth and males having significantly more degranulated mast cells on PN11. Thus, mast cells may be an unappreciated mediator of sex-specific brain development in response to early life perturbations.