Natural history and volumetric analysis of meningiomas in neurofibromatosis type 2.

OBJECTIVE: The objective of this paper was to describe the volumetric natural history of meningiomas in patients with neurofibromatosis type 2 (NF2). METHODS: The authors performed a retrospective descriptive study by reviewing NF2 patients with meningiomas at their institution between 2000 and 2019. Demographic data were collected from the electronic medical records. Tumor volume was collected using volumetric segmentation software. Imaging characteristics including peritumoral brain edema (PTBE) and tumor calcification were collected for each patient from their first to most recent MRI at the authors' institution. An increase of 15% or more per year from original tumor size was used as the cutoff to define growth. RESULTS: A total of 137 meningiomas from 48 patients were included in the analysis. The average number of tumors per person was 2.9. Ninety-nine (72.3%) tumors were in female patients. The median length of follow-up from first imaging to last imaging was 32 months (IQR 10.9, 68.3 months). Most tumors were located in the cerebral convexity (24.8%), followed by the falcine region (18.2%) and spine (10.2%). The median tumor growth was 0.12 cm3/yr (IQR 0.03, 0.52 cm3/yr). At the time of first imaging, 21.9% of tumors had calcifications, while 13.9% of meningiomas had PTBE. Of 137 tumors, 52 showed growth. Characteristics associated with tumor growth included PTBE (OR 9.12, 95% CI 1.48-56.4), tumor volume (per cm3) at first imaging (OR 0.91, 95% CI 0.83-0.99), and 10-year increased age at first imaging (OR 0.57, 95% CI 0.43-0.74). PTBE had the shortest median time to growth at 9.2 months. CONCLUSIONS: Although the majority of NF2-associated meningiomas do not grow in the short term, a wide range of growth patterns can be seen. Younger age at first imaging and presence of PTBE are associated with growth. Patients with these characteristics likely benefit from closer follow-up.

Treatment patterns of children with spine and spinal cord tumors: national outcomes and review of the literature.

BACKGROUND: Tumors of the spine in children are rare, and further clinical description is necessary. OBJECTIVE: This study investigated epidemiology, interventions, and outcomes of pediatric patients with spine and spinal cord tumors. METHODS: The National Inpatient Sample and Kids' Inpatient Database were used for the study. Outcomes were studied, and bivariate significant trends were analyzed in a multivariate setting. RESULTS: Analysis of 2870 patients between 2000 and 2009 found a median age of diagnosis of 11 years (Tables 1 and 2). Most were white (65.2%) and had private insurance (62.3%), and 46.8% of procedures were emergent operations. Treatment occurred at teaching (93.6%) and non-children's hospitals (81.1%). Overall mortality rate was 1.7%, non-routine discharges occurred at a rate 19.9%, complications at 21.1%, and average total charges were $66,087. A majority of patients (87.5%) had no intervention, and of those patients receiving treatment, 78.2% underwent surgery and 23.1% had radiotherapy. Treatment with surgery alone increased significantly over time (p < 0.0001). Odds ratio (OR) of mortality was significantly higher in 2006 (OR 3.5) and 2009 (OR 2.6) when compared to 2000. Complications (OR 7.9) and disease comorbidities (OR 1.5) were associated with significantly increased odds of mortality. CONCLUSIONS: Hospital characteristics, length of stay, and charges remained relatively unchanged. In recent years, there has been a decreasing incidence of spine and spinal cord tumors in children. Notably, a higher mortality rate is evident over time in addition to an increase in the proportion of patients undergoing surgery. The high percentage of emergent operations suggests a weak recognition of spine tumors in children and should prompt a call for increased awareness of this cancer. In spite of these findings, lack of tumor type identification was a limitation to this study.

Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms.

Peritumoral brain edema (PTBE) is mediated by blood-brain barrier breakdown. PTBE results from interstitial vasogenic brain edema due to vascular endothelial growth factor and other inflammatory products of brain tumors. Glucocorticoids (GCs) are the mainstay for treatment of PTBE despite significant systemic side effects. GCs are thought to affect multiple cell types in the edematous brain. Here, we review preclinical studies of GC effects on edematous brain and review mechanisms underlying GC action on tumor cells, endothelial cells, and astrocytes. GCs may reduce tumor cell viability and suppress vascular endothelial growth factor (VEGF) production in tumor cells. Modulation of expression and distribution of tight junction proteins occludin, claudin-5, and ZO-1 in endothelial cells likely plays a central role in GC action on endothelial cells. GCs may also have an effect on astrocyte angiopoietin production and limited effect on astrocyte aquaporin. A better understanding of these molecular mechanisms may lead to the development of novel therapeutics for management of PTBE with a better side effect profile.

Preoperative Radiographic Features Independently Predict High Blood Loss During Intracranial Meningioma Resection: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Surgical resection of intracranial meningioma carries the risk of several complications, including intraoperative blood loss. The objective of this study was to investigate preoperative clinical and radiographic factors predictive of intraoperative estimated blood loss (EBL). METHODS: This case-control study evaluated EBL for all adults who underwent intracranial meningioma resection from January, 2010 to December, 2021 at our institution. Fifty cases of high EBL (i.e., ≥500 milliliters [mL]) and seventy-five instances of low EBL (i.e., <500mL) were randomly selected. Patients were excluded if they had a recurrent meningioma, preoperative embolization, or lack of imaging data. A multivariable logistic regression model of high EBL likelihood was created. RESULTS: A total of 92 patients met eligibility criteria, with 48 (52%) cases of high EBL. Bivariable analyses identified maximal tumor diameter, intratumoral flow voids, skull base location, and dural venous sinus invasion as potential predictors of high EBL. Multivariable regression found intratumoral flow voids (aOR=5.68 [1.52-21.23], p=0.009), maximal tumor diameter (aOR=1.58 [1.11-2.25] per one-centimeter increase, p=0.01), and skull base location (aOR=3.35 [1.19-9.41], p=0.02) to be independent predictors of high EBL. CONCLUSION: Intratumoral flow voids, larger maximal tumor diameter, and skull base location were independently predictive of EBL ≥500mL. Intratumoral flow void presence was the strongest predictor, with 5.68 times the odds of high EBL. Each one-centimeter increase in tumor diameter had 58% greater odds of high EBL. Skull base location was associated with 3.35 times the odds of high EBL. These results can inform preoperative patient counseling and blood management preparation.

Exoscopic supracerebellar approach to the pineal region.

The advent of the 3D exoscope represents a significant technological breakthrough in contemporary surgical practice. While the operating microscope has long been the preferred surgical visualization tool, its limitations in accessibility and ergonomics have prompted the development of a more advanced, 3D version [1,2]. The 3D exoscope has been one such recent development aimed at addressing these limitations. By delivering intense illumination and magnification to the deepest parts of the surgical field, 3D exoscopes are high-definition digital camera systems that give surgeons high-magnification views of the operative field [2]. Additionally, the design of the 3D exoscope allows for improved surgeon ergonomics, decreasing overall fatigue while providing a similar view of the procedure for all personnel in the operating room [3,4]. In this article, we discuss the advantages and limitations of the 3D exoscope in neurosurgery and highlight its use in a patient case. This is a case of a 25-year old female who was noted to have an incidental 13 mm pineal cystic mass on imaging work up for a first time generalized seizure. We discuss the use of an exoscopic supracerebellar approach to the pineal gland for resection of the mass and highlight the various considerations for use of an exoscope in such a case.

Orbital reconstruction and volume in the correction of proptosis after resection of spheno-orbital meningiomas.

OBJECTIVE: The objective of this study was to evaluate the effect of reconstruction and orbital volume on the reduction of proptosis in patients undergoing resection for spheno-orbital meningiomas. Additionally, potential predictors of optimal proptosis reduction after surgery were evaluated. METHODS: Patients with spheno-orbital meningiomas who underwent resection at the authors' institution between 2005 and 2020 were evaluated retrospectively. The exophthalmos index (EI) was measured on pre- and postoperative imaging to quantify proptosis and calculate the primary outcome measure of proptosis reduction. Patients were excluded if they had no preoperative proptosis (i.e., EI < 1.1), prior resection, or insufficient imaging available for analysis. Clinical and surgical characteristics were collected, including sex, extent of resection, WHO grade, and rigid orbital reconstruction, and assessed as predictors of greater proptosis reduction. Additionally, orbital volumes of the affected and contralateral orbits were measured to correlate postoperative orbital volumes with proptosis reduction. RESULTS: Thirty-three patients, with a mean age of 53 years, met inclusion criteria. The majority of the patients were female (23, 69.7%), and most tumors were classified as WHO grade 1 (29, 87.9%). Six patients (18.2%) underwent rigid orbital reconstruction. The mean EI across all patients decreased from 1.36 ± 0.18 to 1.19 ± 0.15 (p < 0.001). Patients who underwent reconstruction had on average a 76.4% greater reduction in the EI (p = 0.036) and a 9.1 times higher odds of achieving a normal EI (< 1.1) compared with those who did not receive reconstruction (OR 9.1, p = 0.025). Additionally, patients without residual hyperostotic bone compressing the orbit had a 2.16 times greater reduction in EI (p = 0.039). A linear relationship between orbital volume ratios (affected/unaffected orbit) and proptosis reduction was observed (p = 0.029, r = 0.529), including at ratios > 1.0. This suggests that greater orbital volumes postoperatively correlated with greater reductions in proptosis. CONCLUSIONS: Three factors were identified that optimize proptosis correction. First, all abnormal bone compressing the orbital contents must be removed completely. Second, rigid orbital reconstruction leads to improved proptosis correction, possibly by preventing frontal lobe and dural reconstruction from descending onto the compressed orbit. Third, aiming for an orbital volume slightly larger than the contralateral normal side leads to improved proptosis correction.

Radiological Differentiation Between Intracranial Meningioma and Solitary Fibrous Tumor/Hemangiopericytoma: A Systematic Literature Review.

BACKGROUND: Intracranial solitary fibrous tumor (SFT) is characterized by aggressive local behavior and high post-resection recurrence rates. It is difficult to distinguish between SFT and meningiomas, which are typically benign. The goal of this study was to systematically review radiological features that differentiate meningioma and SFT. METHODS: We performed a systematic review in accordance with PRISMA guidelines to identify studies that used imaging techniques to identify radiological differentiators of SFT and meningioma. RESULTS: Eighteen studies with 1565 patients (SFT: 662; meningiomas: 903) were included. The most commonly used imaging modality was diffusion weighted imaging, which was reported in 11 studies. Eight studies used a combination of diffusion weighted imaging and T1- and T2-weighted sequences to distinguish between SFT and meningioma. Compared to all grades/subtypes of meningioma, SFT is associated with higher apparent diffusion coefficient, presence of narrow-based dural attachments, lack of dural tail, less peritumoral brain edema, extensive serpentine flow voids, and younger age at initial diagnosis. Tumor volume was a poor differentiator of SFT and meningioma, and overall, there were less consensus findings in studies exclusively comparing angiomatous meningiomas and SFT. CONCLUSIONS: Clinicians can differentiate SFT from meningiomas on preoperative imaging by looking for higher apparent diffusion coefficient, lack of dural tail/narrow-based dural attachment, less peritumoral brain edema, and vascular flow voids on neuroimaging, in addition to younger age at diagnosis. Distinguishing between angiomatous meningioma and SFT is much more challenging, as both are highly vascular pathologies. Tumor volume has limited utility in differentiating between SFT and various grades/subtypes of meningioma.

Rathke's cleft cyst presenting with recurrent aseptic meningitis and inflammatory apoplexy: illustrative case.

BACKGROUND: Rathke's cleft cyst (RCC) is a benign sellar/suprasellar lesion often discovered incidentally. Rarely, symptomatic cases can present with headache and may exhibit concomitant aseptic meningitis or apoplexy. The authors describe a patient with an RCC presenting with recurring episodes of aseptic meningitis and ultimately inflammatory-type apoplexy. OBSERVATIONS: A 30-year-old female presented with three episodes of intractable headaches over 2 months. Each episode's clinical picture was consistent with meningitis though cerebrospinal fluid cultures, and viral tests remained negative. Imaging demonstrated a sellar lesion, initially thought to be coincidental. On the third presentation, there was rapid interval growth of the lesion, adjacent cerebritis, and new endocrinopathy. Resection was then performed via an endoscopic endonasal approach. Pathology showed an RCC with acute and chronic inflammation and no evidence of hemorrhage. Cultures were negative for organisms. The patient received several weeks of antibiotic treatment with the resolution of all symptoms and no recurrence. LESSONS: Recurrent aseptic meningitis with apoplexy-like symptoms is a rare presentation of RCC. The authors propose the term inflammatory apoplexy to describe such a presentation without evidence of abscess, necrosis, or hemorrhage. The mechanism is unclear although may be due to intermittent microleakage of cyst contents into the subarachnoid space.

A Single-Center Retrospective Analysis of Intracranial and Spinal Solitary Fibrous Tumor/Hemangiopericytoma Clinical Outcomes: Sex Association With Aggressiveness.

BACKGROUND: Solitary fibrous tumor/hemangiopericytoma (SFT/HPCT) is a rare tumor characterized by high recurrence rate and metastatic potential, even after surgical resection. We report on the clinical outcomes and risk factors for metastasis and progression-free survival (PFS) of patients diagnosed with SFT/HPCT. METHODS: We retrospectively identified patients with intracranial or spinal SFT/HPCT who underwent surgical resection and/or radiation therapy at our institution between 1995 and 2021. Baseline demographics, tumor characteristics, and outcome data were collected, and factors associated with PFS and metastasis were analyzed. RESULTS: Thirty-four subjects (mean age, 46.4 years; 44% female) with a histopathologically proven diagnosis of SFT/HPCT were included; the median follow-up was 89.7 months. Twenty-two tumors were supratentorial (67%), 6 (18%) were infratentorial, and 5 (15%) were spinal. Eleven patients had documented occurrence of metastasis (32%). Detailed preoperative and postoperative data were available for 25 patients (74%) who received treatment at our institution after their initial diagnosis. Of those, 20 (80%) underwent gross total resection (GTR), and 12 (48%) received either adjuvant or salvage radiotherapy. Univariate analyses revealed that males had a shorter mean PFS compared with females (25 months vs. 78 months; P = 0.01), and that patients who underwent GTR had a longer mean PFS compared with those who underwent subtotal resection (54 months vs. 23 months; P = 0.02). Male sex was the sole risk factor for metastasis (odds ratio, 6.75; 95% confidence interval, 1.19-38.02). CONCLUSIONS: Our data demonstrate a strong association between male sex and the outcomes of shorter PFS and higher risk for metastases. Further research is warranted to understand the clinical characteristics and outcomes of this rare tumor.

Beyond the Surgical Margin: Patterns of Recurrence in World Health Organization Grade 2 Intracranial Meningiomas.

OBJECTIVE: To characterize and classify the location of recurrence in surgically resected World Health Organization (WHO) grade 2 intracranial meningiomas that did not receive adjuvant radiation and compare the recurrence pattern of those who underwent gross total resection (GTR) versus subtotal resection (STR). METHODS: We performed a retrospective review of patients who underwent surgical resection of a newly diagnosed WHO grade 2 meningioma at our institution between 1996 and 2019. Patients who were observed postoperatively without adjuvant radiation and subsequently developed a recurrence were included in the study. All patients who received adjuvant therapy were excluded. Recurrence was defined as any evidence of radiographic progression on postoperative surveillance magnetic resonance imaging. Location of recurrence was categorized as follows: 1) central-growth observed inside the area of the previously resected tumor more than 1 cm inside the original tumor margin; 2) marginal-growth observed within 1 cm (inside or outside) of the original tumor margin; and 3) remote-growth observed >1 cm outside the original tumor margin. Patterns of recurrence were evaluated by 2 observers after coregistering preoperative and postoperative magnetic resonance imaging, and any differences were reconciled by discussion. RESULTS: A total of 22 patients matched the inclusion criteria. Twelve (55%) underwent GTR, and 10 (45%) underwent STR. In 12 patients in whom GTR was achieved, the mean preoperative tumor volume was 50.6 cm3, with 5 (41.7%) in a skull base location. The average time to recurrence for these tumors was 22.7 months, with a mean recurrent tumor volume of 9.0 cm3. Ten patients (83.3%) had central recurrence, 11 patients (91.7%) had marginal recurrence, and only 4 patients (33.3%) had remote recurrence. In 10 patients in whom STR was achieved, mean preoperative tumor volume was 44.8 cm3, with 7 (70.0%) in a skull base location. The average time to recurrence for these tumors was 23.0 months, with a mean recurrent tumor volume of 21.8 cm3. Of these 10 patients, 9 (90.0%) had central recurrence, all 10 (100.0%) had marginal recurrence, and only 4 (40.0%) patients had remote recurrence. CONCLUSIONS: The present study evaluating patterns of recurrence for WHO grade 2 meningiomas after surgical resection (GTR or STR) showed that recurrence occurred centrally and/or at the original tumor margin, with only a few recurring >1 cm outside the original tumor margin. The results of this study suggest that treatment, whether initial surgical resection or adjuvant radiation, may benefit from including at least a 1-cm dural margin when safe, to optimize tumor control, but further clinical study is needed.

Percutaneous Rhizotomy of the Gasserian Ganglion in Patients With Mass Lesion-Associated Trigeminal Neuralgia: A Case Series.

BACKGROUND: Patients with trigeminal neuralgia (TN) secondary to mass lesions are typically treated by directly addressing the underlying pathology. In cases of TN not alleviated by treatment of the pathology, percutaneous balloon compression (PBC) and glycerol rhizotomy (Gly) are simple and effective ways to alleviate pain. However, there is limited literature on the use of these techniques for patients with TN caused by mass lesions. OBJECTIVE: To describe the use of PBC/Gly to treat mass lesion-related TN. METHODS: We report a retrospective, single-institution, descriptive case series of patients who presented with TN secondary to tumor or mass-like inflammatory lesion from 1999 to 2021. Patients with primary, idiopathic, or multiple sclerosis-related TN were excluded. Outcomes included Barrow Neurological Institute (BNI) pain intensity and hypesthesia scores, pain persistence, and postoperative complications. RESULTS: A total of 459 procedures were identified, of which 16 patients met the inclusion criterion (14 PBC and 2 Gly). Of the 15 patients with tumors, 12 had TN pain despite prior tumor-targeted radiation. Short-term (<3 months) BNI pain intensity improvement occurred in 15 (93.8%) patients. The mean follow-up was 54.4 months. Thirteen (81.3%) patients were pain-free (Barrow Neurological Institute pain intensity scale: IIIa-50%; I-25.0%; II-6.3%) for a mean of 23.8 (range 1-137) months. Ten patients (62.5%) had pain relief for ≥6 months from first procedure. New facial numbness developed immediately postprocedure in 8 (50%) patients. Transient, partial abducens nerve palsy occurred in 1 patient. CONCLUSION: PBC/Gly is an effective option for medically refractory TN in patients with mass-associated TN and is a viable option for repeat treatment.

Immediate Titanium Mesh Cranioplasty After Debridement and Craniectomy for Postcraniotomy Surgical Site Infections and Risk Factors for Reoperation.

BACKGROUND: We previously published a novel strategy for management of postcraniotomy bone flap infection consisting of single stage debridement, bone flap removal, and immediate titanium mesh cranioplasty. METHODS: Postcraniotomy patients with surgical site infections treated with surgical debridement, bone flap removal, and immediate titanium mesh cranioplasty were retrospectively reviewed. The primary outcome measure was reoperation due to persistent infection or wound healing complications from the titanium mesh. RESULTS: We included 48 patients, of which 15 (31.3%) were female. The most common primary diagnoses were glioblastoma (31.3%), meningioma (18.8%), and vascular/trauma (16.7%). Most patients had a history of same-site craniotomy prior to the surgery complicated by surgical site infection and 47.9% had prior cranial radiation. Thirty-six (75.0%) patients achieved resolution of their infection and did not require a second operation. Twelve (25.0%) patients required reoperation: 6 (12.5%) patients were found to have frank intraoperative purulence on reoperation, whereas 6 (12.5%) had reoperation for poor wound healing without any evidence of persistent infection. Cochran Armitage trend test revealed that patients with increasing number of wound healing risk factors had significantly higher risk of reoperation (P = 0.001). Prior intensity modulated radiotherapy alone was a significant risk factor for reoperation (6.5 [1.40-30.31], P = 0.002). Median follow-up time was 20.5 weeks. CONCLUSIONS: Immediate titanium mesh cranioplasty at the time of debridement and bone flap removal is an acceptable option in the management of post-craniotomy bone flap infection. Patients with multiple wound healing risk factors are at higher risk for reoperation.

Laser Interstitial Thermal Therapy in the Treatment of Thalamic Brain Tumors: A Case Series.

BACKGROUND: Surgical options for patients with thalamic brain tumors are limited. Traditional surgical resection is associated with a high degree of morbidity and mortality. Laser interstitial thermal therapy (LITT) utilizes a stereotactically placed laser probe to induce thermal damage to tumor tissue. LITT provides a surgical cytoreduction option for this challenging patient population. We present our experience treating thalamic brain tumors with LITT. OBJECTIVE: To describe our experience and outcomes using LITT on patients with thalamic tumors. METHODS: We analyzed 13 consecutive patients treated with LITT for thalamic tumors from 2012 to 2017. Radiographic, clinical characteristics, and outcome data were collected via review of electronic medical records. RESULTS: Thirteen patients with thalamic tumors were treated with LITT. Most had high-grade gliomas, including glioblastoma (n = 9) and anaplastic astrocytoma (n = 2). The average tumor volume was 12.0 cc and shrank by 42.9% at 3 mo. The average hospital stay was 3.0 d. Median ablation coverage as calculated by thermal damage threshold (TDT) lines was 98% and 95% for yellow (>43°C for >2 min) or blue (>10 min), respectively. Median disease-specific progression-free survival calculated for 8 patients in our cohort was 6.1 mo (range: 1.1-15.1 mo). There were 6 patients with perioperative morbidity and 2 perioperative deaths because of intracerebral hematoma. CONCLUSION: LITT is a feasible treatment for patients with thalamic tumors. LITT offers a cytoreduction option in this challenging population. Patient selection is key. Close attention should be paid to lesion size to minimize morbidity. More studies comparing treatment modalities of thalamic tumors need to be performed.

Hemangioblastomatosis-associated negative-pressure hydrocephalus managed with improvised shunt.

Low-pressure hydrocephalus (LPH) is a rare clinical diagnosis, characterized by neurologic decline and ventriculomegaly that persists despite normal to low intracranial pressure. LPH is typically managed by negative-pressure drainage via ventriculostomy, followed by low-resistance shunt insertion. We present the case of a middle-aged man with a history of hemangioblastomatosis who had spontaneous subarachnoid hemorrhage. He was treated with a ventriculoperitoneal shunt and then underwent resection of a Meckel's cave hemangioblastoma and whole brain irradiation. One month later, he presented to us with worsening symptoms and hydrocephalus despite shunt interrogations and revisions revealing no malfunction. Ventriculostomy drainage at negative-pressure was required for resolution of symptoms and ventriculomegaly, leading us to a diagnosis of LPH. This was successfully treated using an improvised ultra-low pressure valveless ventriculoperitoneal shunt, with maintained resolution of LPH for over one year. The system was created by ligating the distal slit valve end of a peritoneal catheter to prevent reflux and allow sub-zero pressure drainage by siphoning.

Simulating vasogenic brain edema using chronic VEGF infusion.

OBJECTIVE To study peritumoral brain edema (PTBE), it is necessary to create a model that accurately simulates vasogenic brain edema (VBE) without introducing a complicated tumor environment. PTBE associated with brain tumors is predominantly a result of vascular endothelial growth factor (VEGF) secreted by brain tumors, and VEGF infusion alone can lead to histological blood-brain barrier (BBB) breakdown in the absence of tumor. VBE is intimately linked to BBB breakdown. The authors sought to establish a model for VBE with chronic infusion of VEGF that can be validated by serial in-vivo MRI and histological findings. METHODS Male Fischer rats (n = 182) underwent stereotactic striatal implantation of MRI-safe brain cannulas for chronic infusion of VEGF (2-20 µg/ml). Following a preinfusion phase (4-6 days), the rats were exposed to VEGF or control rat serum albumin (1.5 µl/hr) for as long as 144 hours. Serial MRI was performed during infusion on a high-field (9.4-T) machine at 12-24, 24-36, 48-72, and 120-144 hours. Rat brains were then collected and histological analysis was performed. RESULTS Control animals and animals infused with 2 µg/ml of VEGF experienced no neurological deficits, seizure activity, or abnormal behavior. Animals treated with VEGF demonstrated a significantly larger volume (42.90 ± 3.842 mm3) of T2 hyper-attenuation at 144 hours when compared with the volume (8.585 ± 1.664 mm3) in control animals (mean difference 34.31 ± 4.187 mm3, p < 0.0001, 95% CI 25.74-42.89 mm3). Postcontrast T1 enhancement in the juxtacanalicular region indicating BBB breakdown was observed in rats undergoing infusion with VEGF. At the later time periods (120-144 hrs) the volume of T1 enhancement (34.97 ± 8.99 mm3) was significantly less compared with the region of edema (p < 0.0001). Histologically, no evidence of necrosis or inflammation was observed with VEGF or control infusion. Immunohistochemical analysis demonstrated astrocyte activation, vascular remodeling, and increased claudin-5 expression in juxtacanalicular regions. Aquaporin-4 expression was increased in both control and VEGF animals in the juxtacanalicular regions. CONCLUSIONS The results of this study show that chronic brain infusion of VEGF creates a reliable model of VBE. This model lacks necrosis and inflammation that are characteristic of previous models of VBE. The model allows for a precise investigation into the mechanism of VBE formation. The authors also anticipate that this model will allow for investigation into the mechanism of glucocorticoid action in abrogating VBE, and to test novel therapeutic strategies targeting PTBE.