INTRODUCTION — The vasogenic edema that surrounds many brain tumors contributes significantly to morbidity. This edema results from disruption of the blood-brain barrier, allowing protein-rich fluid to accumulate in the extracellular space .
The pathogenesis of peritumoral vasogenic edema and the use of glucocorticoids are reviewed here. The acute treatment of elevated intracranial pressure (ICP) is discussed elsewhere. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'General management' and "Evaluation and management of elevated intracranial pressure in adults", section on 'Specific therapies'.)
Local blood-brain barrier disruption — Tumor-related disruption in the blood-brain barrier is caused by two major mechanisms:
●The local production of factors that increase the permeability of tumor vessels such as vascular endothelial growth factor (VEGF) , glutamate , and leukotrienes .
●The absence of tight endothelial cell junctions in tumor blood vessels. These vessels develop in response to angiogenic factors such as VEGF  and basic fibroblast growth factor (bFGF, FGF2) .
In large part, VEGF is responsible for the loss of integrity of the blood-brain barrier in brain tumors. Gliomas, meningiomas, and metastatic tumors all have upregulation of VEGF [6-9]. VEGF is secreted by tumor cells as well as host stromal cells and binds to its receptors VEGFR1 and VEGFR2, which are located primarily on the surface of endothelial cells. VEGF stimulates the formation of gaps in the endothelium, a process that leads to fluid leakage into the brain parenchyma, thereby resulting in vasogenic edema [10,11].
Vasogenic edema tends to spread more readily in the extracellular space of white matter rather than gray matter, possibly because of lower resistance to flow within the white matter . Tumor-related edema may disrupt synaptic transmission, alter neuronal excitability, and contribute to headaches, seizures, focal neurologic deficits, and encephalopathy. Furthermore, unchecked cerebral edema may result in fatal herniation because the brain is encased in the rigid cranium.
Mechanism of action of glucocorticoids — The mechanism of action of glucocorticoids for control of vasogenic edema is not fully understood.
Dexamethasone upregulates Ang-1, a strong blood-brain barrier-stabilizing factor, and it downregulates VEGF, a strong permeabilizing factor, in astrocytes and pericytes . Dexamethasone also inhibits production of interleukin 1 (IL-1) cytokines from tumor-associated macrophages in glioblastoma models .
EVALUATION — Patients with brain tumor-related vasogenic edema should be evaluated for associated signs and symptoms to determine whether glucocorticoids are necessary. The extent of edema on neuroimaging must be interpreted alongside clinical symptoms, as not all edema requires symptomatic treatment.
Signs and symptoms — Symptoms of vasogenic edema vary based on the location and extent of the edema. In many cases, symptoms are multifactorial and caused by a combination of the local effects of brain edema (usually reversible) and tumor or treatment-related tissue injury (usually irreversible). Glucocorticoids can be expected to provide symptomatic benefit to the extent that symptoms are related to vasogenic edema.
Symptoms of accumulating edema tend to progress in a subacute fashion, with an insidious onset and gradual worsening from one day to the next. Less commonly, patients become symptomatic more abruptly, in a stroke-like fashion (eg, waking up with new deficits), presumably because a symptomatic threshold has been crossed. In such cases, unwitnessed seizure with postictal deficits should also be considered as a possible explanation (in addition to stroke).
Headaches related to vasogenic edema are usually diffuse and bilateral, although they may be felt unilaterally on the side of the tumor. The quality of the pain is often described as dull and throbbing. With more extensive amounts of edema, headaches may have characteristics of increased intracranial pressure (ICP; eg, worse in the mornings, associated with nausea or vomiting). Additional signs of increased ICP may include drowsiness, papilledema, and symptomatic plateau waves, manifest as presyncope or syncope-like events related to a decrease in cerebral perfusion when ICP transiently rises above a certain level. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Clinical manifestations' and 'Symptomatic plateau waves' below.)
Focal deficits vary based on the location of edema. For metastatic brain tumors in particular, focal vasogenic edema is often the dominant cause of symptoms (rather than the tumor itself). As an example, a patient with a new left posterior frontal brain metastasis presenting with a right hemiparesis may experience complete recovery of strength upon initiation of glucocorticoids, before tumor-specific therapy is initiated.
Neuroimaging — Vasogenic edema is hypodense compared with normal gray and white matter on computed tomography (CT). Particularly when extensive, it causes mass effect (ie, effacement of cerebral sulci or subarachnoid spaces, compression or displacement of the ventricles, midline shift [subfalcine herniation], or other types of brain herniation) (image 1).
On magnetic resonance imaging (MRI), vasogenic edema is hypointense on T1-weighted images, is hyperintense on fluid-attenuated inversion recovery (FLAIR) and T2-weighted images, and does not enhance after contrast administration (image 1). In contrast to cytotoxic edema, vasogenic edema is not associated with reduced water diffusivity on diffusion-weighted MRI (image 2). In addition, vasogenic edema tends to respect the boundaries of white matter, in contrast to infiltrative tumor, such as glioma (image 1 and image 3).
Vasogenic edema is reversible, although it lags behind clinical effects of glucocorticoids on neuroimaging by days and up to weeks. Although rare, extensive or longstanding edema can result in irreversible hyperintense signal on FLAIR and T2-weighted MRI, which may persist even with resolution of the underlying process. In this way, acute and chronic edema have a similar appearance on MRI, and the distinction requires clinical correlation and comparison of serial imaging studies, when available.
SYMPTOMATIC TREATMENT — Systemic glucocorticoids are the mainstay of symptomatic therapy for peritumoral edema (algorithm 1). They play a role in stabilizing patients awaiting definitive treatment of the tumor as well as in palliative management of edema related to treatment-refractory tumors.
Emergency management of increased ICP — A significant increase in intracranial pressure (ICP) causing drowsiness and other signs of impending herniation can be a medical emergency, and treatment should be undertaken as expeditiously as possible, typically in an intensive care unit setting. A bolus dose of dexamethasone (eg, 10 mg IV) should be given acutely, followed by 16 mg/day in divided doses. Doses as high as 40 mg/day may be given in the emergency setting for brain tumor-related edema and mass effect. Additional interventions during the first 24 to 72 hours may be required to lower ICP, such as hypertonic saline and mannitol. These approaches are discussed elsewhere. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'General management' and "Evaluation and management of elevated intracranial pressure in adults", section on 'Specific therapies'.)
Initiation of glucocorticoids — Systemic glucocorticoids should be considered in all patients who have symptomatic peritumoral edema. Depending on the location of the tumor and the extent of edema, symptoms may be generalized (eg, headache, nausea, vomiting) or focal (eg, aphasia, hemiparesis), or both. (See 'Signs and symptoms' above.)
Dexamethasone is the standard agent for peritumoral edema management because its high potency and relative lack of mineralocorticoid activity reduce the potential for fluid retention [15-17]. In addition, dexamethasone can be given orally or intravenously (IV) with a 1:1 conversion ratio. (See "Pharmacologic use of glucocorticoids".)
For patients requiring low to moderate amounts of dexamethasone (eg, 4 to 6 mg daily or less), prednisone is sometimes used as an alternative to dexamethasone in patients with steroid myopathy or in those with a history of adrenal insufficiency, as it allows for a taper in smaller increments (table 1). (See 'Steroid myopathy' below and 'HPA axis suppression' below.)
Dexamethasone dose and schedule — The antiedema effects of dexamethasone are dose dependent, and the starting dose should be individualized based on the extent of edema and the severity of symptoms [16,18,19]. Because most side effects are also dose dependent, the goal is always to use the lowest dose necessary to control symptoms.
●In patients with moderate to severe symptoms (eg, severe headache, nausea and vomiting, significant focal neurologic deficits), the usual initial dexamethasone regimen consists of a 10 mg loading dose IV, followed by an initial maintenance dose of 8 to 16 mg daily in divided doses orally (or IV for patients not tolerating oral medications).
●For patients with milder symptoms, a loading dose is usually omitted, and smaller total daily doses (eg, 2 to 4 mg divided once or twice daily) are usually adequate and less toxic.
●Most patients who are asymptomatic do not require steroids, although clinical judgment is required in patients with large amounts of edema, particularly when antitumor therapy has the potential to worsen edema. Increased caution is also required for posterior fossa tumors and edema, which can be associated with rapid deterioration.
Although it has been customary to administer dexamethasone in four divided daily doses, its biologic half-life is sufficiently long (36 to 54 hours) to allow once- or twice-daily dosing, and this approach is preferred for maintenance therapy because it is easier for patients and has not been associated with diminished efficacy [20,21]. We use once-daily morning dosing when possible and avoid late evening and middle-of-the-night dosing to help reduce insomnia caused by glucocorticoids. To minimize complications, subsequent dosing should be modified to use the lowest possible dose necessary to control peritumoral edema. (See 'Complications and prophylaxis' below and 'Approach to taper' below.)
Absorption of oral dexamethasone is excellent and is complete within 30 minutes of administration . Oral and IV dosing is equivalent. IV dosing may be necessary if oral absorption cannot be assured, or if oral intake is unsafe due to altered mentation or other deficits.
Response assessment — Management of peritumoral edema is largely empiric. Clinical response, rather than radiographic changes, should guide most decisions.
Most patients begin to improve symptomatically within hours and achieve a maximum benefit from a given dose of dexamethasone within 24 to 72 hours. In general, headaches tend to respond better and more quickly than focal deficits, in part because edema may not be the only cause of focal deficits. The maximum neuroimaging response lags behind clinical response by days to a week or two. (See 'Neuroimaging' above.)
Inadequate response to initial dose — When patients fail to improve or improve only partially after several days on the initial dose, there are two main possibilities. Either a higher dose is required, or the residual symptoms are caused by factors other than peritumoral edema.
A trial-and-error strategy is often used to help distinguish between the two. For patients on submaximal doses, the dexamethasone dose is typically doubled for two to three days as a trial (usual maximum total daily dose, 16 mg). If the patient improves clinically, the higher dose is continued. The less a patient responds to a doubling of the dose, the less likely it is that symptoms are steroid responsive. If there is no response by 72 hours, the dose can generally be returned to the previous dose level without taper. This strategy helps to avoid excessive steroid dosing and toxicity in the absence of clinical benefit.
If a dexamethasone dose of 16 mg per day is insufficient, the dose may be increased further, although often with diminishing returns and excess toxicity. Alternative options for refractory edema should be considered in such cases. (See 'Refractory edema' below.)
Approach to taper — Once patients have responded and stabilized clinically on a given dose of dexamethasone, a gradual taper should be attempted, if possible [16,23]. This is particularly important for patients on high initial doses of dexamethasone (eg, >8 mg daily), as weight gain and proximal weakness often emerge within weeks at such doses. The likelihood of success and the speed of the taper depend on multiple factors, including the status of the underlying tumor, concurrent therapies, and the duration of steroid therapy. Postoperative steroid tapers in patients who have undergone complete tumor resection can be relatively rapid, for example, whereas efforts to taper steroids in patients with residual or progressive tumors must be approached more cautiously.
Dexamethasone has a long duration of action, and therefore a period of at least three to four days should generally follow each dose decrement to establish clinical tolerance of the lower dose. For patients in good clinical condition whose tumor has been stabilized with recent treatment, a taper may entail a reduction in dose of up to 50 percent every four days. A more protracted taper and chronic treatment may be required for patients with active tumors and those who do not tolerate initial attempts to wean steroids. Patients and caregivers should be educated about signs and symptoms that may signal reaccumulation of symptomatic edema as dexamethasone is being tapered (ie, recurrent or worsening headaches, focal deficits).
Symptoms not caused by recurrence of brain edema may develop during the course of the steroid taper (steroid withdrawal syndrome). These include mild headache and lethargy that may mimic recurrence of brain edema as well as myalgias and arthralgias (steroid pseudorheumatism). All of the symptoms respond to raising the dose slightly and tapering more slowly.
Refractory edema — Management of chronic, symptomatic edema can be challenging. Many patients develop toxicities related to chronic glucocorticoids, which in some cases eventually outweigh the benefits. Surgical debulking of the associated tumor may be indicated in select cases, even when the goal is not curative, in order to help control the underlying cause of the edema. For certain tumor histologies, bevacizumab may be an option to help control edema. If globally elevated ICP is the main source of refractory headaches or symptomatic plateau waves, ventricular shunting may be an option in some patients.
Role of bevacizumab — Since vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of peritumoral edema, anti-VEGF monoclonal antibodies such as bevacizumab or inhibitors of VEGF receptors are useful in reducing edema [24,25]. The steroid-sparing effects of bevacizumab were demonstrated in a randomized phase II study of bevacizumab with or without irinotecan in patients with recurrent glioblastoma, in which 30 to 50 percent of patients had a sustained reduction in glucocorticoid dose and approximately 20 percent achieved a complete taper . Other VEGF inhibitors have shown similar effects .
In patients with recurrent/refractory glioblastoma and symptomatic peritumoral edema, the clinical antiedema effects of bevacizumab can often be observed within days of the first dose. This effect tends to be persistent with ongoing therapy and can improve the likelihood of a successful dexamethasone taper. (See "Management of recurrent high-grade gliomas", section on 'Bevacizumab'.)
Bevacizumab also finds selective use in the management of edema related to radiation necrosis. (See "Delayed complications of cranial irradiation", section on 'Treatment'.)
Symptomatic plateau waves — Plateau waves are sustained pressure waves that normally occur within the brain and are caused by activities that transiently raise the ICP (eg, standing, sneezing, coughing). In the presence of a brain tumor, significant further increases in ICP can temporarily cut off cerebral perfusion, leading to loss of consciousness. The treatment of choice for such cases is glucocorticoids and neurosurgical intervention for cerebrospinal fluid (CSF) diversion, when appropriate.
COMPLICATIONS AND PROPHYLAXIS — Despite the beneficial effect of glucocorticoids, they are associated with a large number of well-known side effects (table 2) (see "Major side effects of systemic glucocorticoids"). The frequency of these complications can be reduced by using the lowest possible dose . Common side effects include insomnia, essential tremor, and hiccups; patients should be warned in advance that they may occur.
Three complications are of particular concern to patients with brain tumors: gastrointestinal complications, steroid myopathy, and opportunistic infections such as Pneumocystis pneumonia (PCP). In addition, retrospective studies have suggested that use of steroids may be associated with decreased overall survival in patients with glioblastoma, independent of potential confounding factors such as tumor size and performance status .
Pneumocystis pneumonia prophylaxis — PCP is a life-threatening opportunistic infection that occurs in immunocompromised hosts, including patients with brain tumors treated with glucocorticoids. (See "Epidemiology of pulmonary infections in immunocompromised patients" and "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV".)
Brain tumor patients receiving or expected to receive more than four weeks of a glucocorticoid dose equivalent to ≥20 mg of prednisone daily (for dexamethasone, approximately 3 mg daily or more) should receive PCP prophylaxis with trimethoprim-sulfamethoxazole or an acceptable alternative regimen (table 3). Because the duration of steroid therapy is often unpredictable and tapers can last longer than initially planned, some clinicians routinely start prophylaxis as soon as dexamethasone is initiated. (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Prophylaxis'.)
The risk of symptomatic PCP infection is increased while glucocorticoids are being tapered [29,30]. Concurrent chemotherapy may be an additional risk factor for the development of PCP . In a retrospective review of 587 patients with primary brain tumors seen at a single institution over an eight-year period, there were 11 histologically documented cases of PCP in 10 patients (1.7 percent) . The patients had been on dexamethasone for a median duration of three months when symptoms first developed. In 8 of 11 episodes, PCP occurred during the steroid taper.
The mechanism by which glucocorticoids predispose to the development of PCP is poorly understood, but suppression of cellular immunity leading to reactivation of latent infection probably plays a role. Why PCP more commonly develops during steroid taper is also unknown. Possible factors include increased immune-mediated lung damage from PCP infection, which had been suppressed by higher doses of glucocorticoids, and a positive effect of glucocorticoids on surfactant phospholipids that are decreased in PCP .
Clinicians caring for patients with brain tumors who are receiving glucocorticoids should maintain a high index of suspicion for PCP. Although the hallmark of PCP is fever and dyspnea with or without a prominent dry cough, the presentation can be subtle and nonspecific. Thus, the diagnosis should be considered in any patient developing respiratory symptoms. (See "Approach to the immunocompromised patient with fever and pulmonary infiltrates".)
The treatment of PCP in patients with brain tumors is the same as in other non-HIV infected patients and is discussed elsewhere. (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Treatment'.)
Gastritis prophylaxis — We usually restrict prophylactic therapy with a proton pump inhibitor to the perioperative period and to patients receiving very high doses of glucocorticoids (eg, >8 mg dexamethasone daily). For other patients, prophylactic therapy is probably unnecessary unless they are at high risk for developing peptic ulceration (eg, previous peptic ulcer disease, concurrent anticoagulation, nonsteroidal antiinflammatory drug [NSAID] therapy). When NSAIDs are necessary, use of a selective cyclooxygenase 2 (COX-2) inhibitor or misoprostol appears to reduce the risk of gastrointestinal complications. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity".)
Glucocorticoids increase the risk of gastrointestinal complications such as gastritis or peptic ulcer disease, especially when used in conjunction with other drugs such as NSAIDs. Concurrent anticoagulation therapy and a prior history of peptic ulcer disease are other factors that can increase the likelihood of gastrointestinal bleeding in patients receiving glucocorticoids.
The effectiveness of prophylactic therapy to prevent peptic ulceration in patients with brain tumors (especially those with gliomas and lymphomas, who often require prolonged therapy with high doses of glucocorticoids) is unknown. In NSAID-treated patients, proton pump inhibitors (eg, omeprazole) can protect against both gastric and duodenal ulcerations. However, there are no studies evaluating the efficacy of these drugs in patients with brain tumors treated with dexamethasone. Standard doses of H2 blockers are not effective for the prevention of NSAID-induced gastric ulcers. (See "NSAIDs (including aspirin): Primary prevention of gastroduodenal toxicity".)
Risk of intestinal perforation — Perforation of the gastrointestinal tract is a serious and less well-recognized complication of glucocorticoid therapy. This is frequently difficult to diagnose because clinical features of peritonitis can be masked by the glucocorticoids. The prevention of severe constipation may decrease the risk of intestinal perforation. A high index of suspicion is important since early diagnosis improves the outcome of this serious complication. Patients receiving concurrent bevacizumab are likely at highest risk. (See "Major side effects of systemic glucocorticoids", section on 'Gastrointestinal effects' and "Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects", section on 'Intestinal perforation/fistula formation'.)
Steroid myopathy — Glucocorticoid-induced myopathy contributes significantly to morbidity in patients with brain tumors. Myopathy is a common complication, with an estimated incidence between 2 and 20 percent. (See "Glucocorticoid-induced myopathy".)
The majority of patients develop proximal weakness between the 9th and 12th weeks of glucocorticoid treatment, although there is marked variation in individual susceptibility. Some patients become weak after a low dose of glucocorticoids for a few weeks, while others never develop myopathy despite receiving large doses of glucocorticoids for months or years. The onset is usually subacute, occurring over several weeks. Symptoms often include difficulty rising from a seated position, difficulty climbing or descending stairs, and gait instability. Muscle pain is not a feature and tendon reflexes are preserved.
Treatment of steroid myopathy is difficult. Ideally, glucocorticoids should be discontinued, but the lowest possible dose should be used if this is not feasible. Recovery after discontinuation of glucocorticoid therapy can be expected within two to three months but may be much slower if treatment is continued, even at a reduced dose. Physical therapy may be useful in preventing and treating muscle weakness in patients receiving glucocorticoids .
Another treatment approach is to change the glucocorticoid preparation. Steroid myopathy has been particularly associated with the use of fluorinated glucocorticoids such as dexamethasone. Although the evidence supporting this relationship is not strong, anecdotal reports suggest that weakness that develops during treatment with a fluorinated glucocorticoid may improve when equivalent doses of a nonfluorinated preparation, such as prednisone, are substituted. (See "Pharmacologic use of glucocorticoids".)
HPA axis suppression — Administration of exogenous glucocorticoids can suppress the hypothalamic-pituitary-adrenal (HPA) axis and lead to adrenal atrophy and loss of cortisol secretory capability. Although the time required to achieve suppression depends upon the dose and varies among patients, suppression can be assumed in any patient receiving more than 20 mg of prednisone a day or the equivalent (for dexamethasone, approximately 3 mg daily) for three weeks or more and in any patient with clinical Cushing syndrome. Abrupt cessation or rapid withdrawal of glucocorticoids in such patients may cause symptoms of adrenal insufficiency.
For most brain tumor patients, the gradual steroid taper necessitated by cerebral edema management is sufficiently slow to protect against adrenal insufficiency when the taper is finished. However, clinicians should maintain a high index of suspicion for adrenal insufficiency in patients with prolonged steroid exposure. When in doubt, the responsiveness of the adrenal gland can be assessed with an adrenocorticotropic hormone (ACTH [cosyntropin]) stimulation test before the glucocorticoid dose is lowered below physiologic replacement levels (approximately 0.5 to 1 mg daily for dexamethasone). (See "Initial testing for adrenal insufficiency: Basal cortisol and the ACTH stimulation test", section on 'ACTH stimulation tests'.)
IMPACT OF STEROIDS ON TUMOR RESPONSE ASSESSMENT — Glucocorticoids can reduce tumor enhancement on neuroimaging studies, which can confound accurate response assessment. In a magnetic resonance imaging (MRI) study of patients with recurrent glioma, 90 percent of patients had a measurable reduction in the size of gadolinium-enhancing region after administration of 16 mg of dexamethasone . Similar observations have been made in patients undergoing computed tomography (CT) imaging .
It is important to consider differences in glucocorticoid dose when determining treatment response, as an increase in steroids can mimic treatment response and steroid reduction can mimic tumor progression. (See "Assessment of disease status and surveillance after treatment in patients with primary brain tumors".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Primary brain tumors".)
SUMMARY AND RECOMMENDATIONS
●Pathogenesis – The vasogenic edema that surrounds many brain tumors contributes significantly to morbidity and requires treatment in conjunction with specific measures directed against the tumor. (See 'Pathogenesis' above.)
●Evaluation – Patients with brain tumor-related vasogenic edema should be evaluated for associated signs and symptoms to determine whether glucocorticoids are necessary. The extent of edema on neuroimaging must be interpreted alongside clinical symptoms, as not all edema requires treatment. (See 'Evaluation' above.)
●Symptomatic therapy – Systemic glucocorticoids are the mainstay of therapy for symptomatic peritumoral edema. Dexamethasone is commonly used for this indication due to its potency and lack of mineralocorticoid activity. (See 'Symptomatic treatment' above.)
•For patients with moderate to severe edema, the usual starting schedule of dexamethasone includes a loading dose of 10 mg, and then 8 to 16 mg per day in one to two divided doses (algorithm 1). Lesser doses (eg, 2 to 4 mg per day) may be used in patients with milder symptoms. (See 'Dexamethasone dose and schedule' above.)
•Most patients who are asymptomatic do not require steroids, although clinical judgment is required in patients with large amounts of edema, particularly when antitumor therapy has the potential to worsen edema, and for posterior fossa tumors.
●Approach to taper – To minimize complications, subsequent dosing should be modified to use the lowest possible dose necessary to control symptoms. The likelihood of success and the speed of the taper depend on multiple factors, including the status of the underlying tumor, concurrent therapies, and the duration of steroid therapy. (See 'Approach to taper' above.)
●Complications and prophylaxis – Appropriate attention should be paid to prevent and treat potential complications of glucocorticoid treatment. (See 'Complications and prophylaxis' above and "Major side effects of systemic glucocorticoids".)
●Refractory edema – Bevacizumab may be helpful in reducing peritumoral edema in patients who are refractory to steroids or have significant steroid-related complications. (See 'Refractory edema' above.)
In patients who have significantly elevated intracranial pressure (ICP), additional measures may be required while waiting for glucocorticoid treatment to become effective. (See 'Emergency management of increased ICP' above and 'Symptomatic plateau waves' above.)
5 : Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas.
6 : Relationship between survival and edema in malignant gliomas: role of vascular endothelial growth factor and neuronal pentraxin 2.
7 : Meningiomas: role of vascular endothelial growth factor/vascular permeability factor in angiogenesis and peritumoral edema.
8 : Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts.
9 : Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis.
10 : Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor.
11 : Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors.
12 : Vascular endothelial growth factor expression, vascular volume, and, capillary permeability in human brain tumors.
13 : Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier.
14 : Tumour-associated macrophage-derived interleukin-1 mediates glioblastoma-associated cerebral oedema.
16 : Anticonvulsant prophylaxis and steroid use in adults with metastatic brain tumors: summary of SNO and ASCO endorsement of the Congress of Neurological Surgeons guidelines.
17 : Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO Clinical Practice Guidelines for prophylaxis, diagnosis, treatment and follow-up.
18 : Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day.
19 : The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline.
20 : The role of steroids in the management of brain metastases: a systematic review and evidence-based clinical practice guideline.
22 : Glucocorticoid maintenance therapy following adrenalectomy: assessment of dosage and preparation.
25 : AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients.
26 : Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study.
27 : Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy.
29 : Steroid myopathy: pathogenesis and effects of growth hormone and insulin-like growth factor-I administration.
33 : Regulation of surfactant phosphatidylcholine secretion from alveolar type II cells during Pneumocystis carinii pneumonia in the rat.
35 : Corticosteroid-induced magnetic resonance imaging changes in patients with recurrent malignant glioma.