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Clinical presentation, diagnosis, and initial surgical management of high-grade gliomas

Clinical presentation, diagnosis, and initial surgical management of high-grade gliomas
Literature review current through: Jan 2024.
This topic last updated: Jan 08, 2024.

INTRODUCTION — High-grade gliomas are malignant, often rapidly progressive primary brain tumors. The most common high-grade gliomas in adults are isocitrate dehydrogenase (IDH)-wildtype glioblastoma (grade 4), grade 3 and 4 IDH-mutant astrocytoma, and grade 3 IDH-mutant, 1p/19q-codeleted oligodendroglioma. (See "Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors", section on 'Histopathologic and molecular classification'.)

The clinical manifestations, prognostic factors, and initial surgical approach to patients with high-grade gliomas will be reviewed here.

Other patient management topics that are covered separately include:

The diagnostic approach to patients with suspected brain tumors (see "Overview of the clinical features and diagnosis of brain tumors in adults")

Adjuvant radiation therapy and chemotherapy following initial surgery (see "Radiation therapy for high-grade gliomas" and "Initial treatment and prognosis of IDH-wildtype glioblastoma in adults")

Postoperative therapy for IDH-mutant astrocytomas (see "Treatment and prognosis of IDH-mutant astrocytomas in adults")

Postoperative therapy for oligodendrogliomas (see "Treatment and prognosis of IDH-mutant, 1p/19q-codeleted oligodendrogliomas in adults")

Glioblastoma in older adults (see "Management of glioblastoma in older adults")

Recurrent high-grade gliomas (see "Management of recurrent high-grade gliomas")

CLINICAL FEATURES — Patients with high-grade glioma typically present with subacute neurologic signs and symptoms that progress over days to weeks and vary according to the location of the tumor within the brain. Magnetic resonance imaging (MRI) of the brain provides confirmatory evidence of a mass lesion, but a tissue diagnosis is ultimately required to distinguish high-grade gliomas from other primary and metastatic brain tumors.

Presenting signs and symptoms — The presenting signs and symptoms of high-grade gliomas are dependent upon the location and size of the lesion and are similar to those produced by other primary and metastatic brain tumors. Patients typically present with progressive neurologic symptoms that evolve over the course of days to weeks. (See "Overview of the clinical features and diagnosis of brain tumors in adults".)

Among patients with high-grade gliomas, the most common presenting symptoms include [1]:

Headache (50 to 60 percent)

Seizures (20 to 50 percent)

Focal neurologic symptoms such as memory loss, motor weakness, visual symptoms, language deficit, and cognitive and personality changes (10 to 40 percent)

Focal neurologic deficits are more common with glioblastoma compared with lower-grade gliomas, whereas seizures occur less frequently as a presenting symptom of glioblastoma than with lower-grade gliomas. Large tumors may be associated with significant edema, mass effect, and increased intracranial pressure. (See "Overview of the clinical features and diagnosis of brain tumors in adults", section on 'Increased intracranial pressure'.)

Rarely, high-grade gliomas can present with meningeal dissemination [2,3]. This finding is more commonly diagnosed later in the natural history of the disease or at autopsy [4,5]. Presenting symptoms of meningeal gliomatosis are back pain with or without radicular symptoms, mental status changes, cranial nerve palsies, myelopathy, cauda equina syndrome, and headache with symptomatic hydrocephalus.

Family history and risk factors — The vast majority of patients with high-grade glioma have no family history of brain tumors or identifiable risk factors for glioma.

In rare cases, glioblastoma and other high-grade gliomas are a manifestation of a tumor predisposition syndrome such as Li-Fraumeni syndrome, Lynch syndrome (hereditary nonpolyposis colorectal cancer), or constitutional mismatch repair-deficiency syndrome. In most of these cases, the family history is notable for multiple first- and second-degree family members with early-onset cancers. Such patients are typically offered a referral for genetic counseling. Little is known about the genetic factors underlying apparently sporadic high-grade gliomas and families with clustering of brain tumors in the absence of a recognized genetic syndrome. (See "Risk factors for brain tumors", section on 'Genetic predisposition syndromes'.)

Aside from genetic factors, the only established risk factor for glioblastoma and other high-grade gliomas is exposure to ionizing radiation, as occurs from therapeutic radiation therapy for childhood brain tumors or leukemia. The latency between irradiation and the development of a glioma varies from five years to several decades. Data on other environmental exposures including electromagnetic radiation, radiofrequency radiation from cell phones, and head trauma are inconclusive. (See "Risk factors for brain tumors", section on 'Ionizing radiation'.)

Neuroimaging — Contrast-enhanced MRI is superior to computed tomography (CT) for the characterization of brain tumors.

On MRI, high-grade gliomas are typically hypointense on T1-weighted images and enhance heterogeneously following contrast administration. Glioblastomas typically have a pattern of intense rim enhancement with central clearing, indicative of necrosis (image 1). Enhancing tumor can be distinguished from the surrounding hypointense signal of edema on T1-weighted sequences (image 2). Regardless of the histologic grade, high-grade gliomas generally show increased T2 and fluid-attenuated inversion recovery (FLAIR) signal intensity; however, some grade 3 gliomas do not manifest contrast enhancement [6].

Many high-grade gliomas are characterized by areas of infiltrative, nonenhancing tumor that may be multifocal. Infiltrative tumor typically appears as expansile T2 hyperintense signal abnormality involving both cortex and underlying white matter. Such areas may or may not be contiguous with enhancing portions of the tumor. Grade 3 (anaplastic) oligodendrogliomas may have areas of internal calcification. (See "Clinical features, diagnosis, and pathology of IDH-mutant, 1p/19q-codeleted oligodendrogliomas", section on 'Neuroimaging'.)

On magnetic resonance spectroscopy (MRS), high-grade gliomas are typically characterized by increased choline and decreased N-acetylaspartate. Evidence of increased blood volume is often present on magnetic resonance perfusion imaging. Like other malignancies, high-grade gliomas have increased metabolic activity and usually show increased uptake of fluorodeoxyglucose on positron emission tomography (PET).

DIAGNOSTIC EVALUATION — Patients with a suspected high-grade glioma should undergo history and physical examination to evaluate for symptoms and neurologic deficits associated with the tumor. The degree of deficits and the clinical stability of the patient guide the urgency of neurosurgical evaluation and treatment and need for corticosteroids. (See "Overview of the clinical features and diagnosis of brain tumors in adults", section on 'Role of glucocorticoids'.)

Brain MRI with contrast is often the only study required preoperatively. Patients with a contraindication to brain MRI should undergo head CT with contrast. Screening for systemic malignancy is not necessary when the clinical and radiographic suspicion for high-grade glioma is high (algorithm 1). The initial evaluation and differential diagnosis of brain tumors in adults is reviewed in detail separately. (See "Overview of the clinical features and diagnosis of brain tumors in adults".)

Patients presenting with a seizure or who have a history suggestive of previously unreported or unrecognized seizures should be treated with an antiseizure medication. Prophylactic antiseizure medications in patients who have not had a seizure are not indicated outside of the perioperative period [7]. (See "Seizures in patients with primary and metastatic brain tumors", section on 'Approach to management' and "Seizures in patients with primary and metastatic brain tumors", section on 'Indications for antiseizure medication therapy'.)

A tissue diagnosis in patients with a presumed high-grade glioma is essential. This can be accomplished either at the time of surgical resection or in a separate biopsy procedure. Biopsy alone is used in situations where the lesion is not amenable to resection, a meaningful amount of tumor tissue cannot be removed, or the patient's overall clinical condition will not permit surgery. In the remaining cases, maximal safe resection is the preferred initial approach to both diagnosis and management. For patients who undergo surgery, repeat brain MRI should be obtained within 24 to 48 hours postoperatively to determine the extent of resection. (See 'Deep-seated or multifocal tumors' below and 'Surgically accessible tumors' below.)

PATHOLOGY — Gliomas are classified based not only on histopathologic appearance but also on molecular parameters, including isocitrate dehydrogenase (IDH) mutation status and the presence or absence of 1p/19q codeletion (table 1 and table 2) [8,9]. Astrocytic and oligodendroglial tumors are grouped together as diffuse gliomas, on the basis of growth pattern, behavior, and shared IDH genetic status (algorithm 2).

Histopathology — Astrocytic tumors are composed of cells with elongated or irregular, hyperchromatic nuclei and eosinophilic, glial fibrillary acidic protein (GFAP)-positive cytoplasm. By contrast, oligodendrogliomas have rounded nuclei, often with perinuclear halos, calcification, and delicate, branching blood vessels (picture 1). As tumors increase in histologic grade, additional features of malignancy are noted. In general, nuclear atypia and increased mitotic activity characterize grade 3 (anaplastic) tumors (picture 2), while microvascular proliferation and necrosis define grade 4 tumors (eg, glioblastoma) (picture 3). (See "Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors", section on 'General features'.)

Key molecular tests — Molecular characterization of gliomas is critical for accurate diagnosis, prognostication, and treatment [10]. Routine pathologic evaluation of high-grade glioma specimens should include IDH mutational testing and, in selected cases, testing for 1p/19q codeletion to allow for an integrated diagnosis (algorithm 2 and table 1). (See 'Integrated diagnosis' below.)

Immunohistochemistry (IHC) for the most common IDH mutation in gliomas, IDH1 R132H, captures approximately 90 percent of IDH mutations in gliomas. If R132H-mutant IDH1 IHC is negative, sequencing of IDH1 and IDH2 should be prioritized in all patients with grade 3 gliomas and in younger patients (<55 years) with suspected glioblastoma, as the distinction between IDH-mutant and IDH-wildtype tumors has prognostic implications and is central to an integrated diagnosis. Sequencing of IDH in patients with glioblastoma who are older than 55 years is not required because IDH mutations in glioblastoma are considered rare in this age group.

Testing for 1p/19q codeletion is indicated in all tumors with oligodendroglial histopathologic features. An integrated diagnosis of both grade 2 and grade 3 (anaplastic) oligodendroglioma requires confirmation of 1p/19q codeletion as well as mutant IDH1 or IDH2 (table 1). In IDH-mutant gliomas, homozygous deletion of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) is a negative prognostic marker and establishes a higher grade, independent of histologic features. (See "Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors", section on '1p/19q codeletion'.)

Glioblastoma specimens of sufficient size should also be tested for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. While not required for diagnosis, results are useful for prognostication and are predictive of response to alkylating-agent chemotherapy. (See "Initial treatment and prognosis of IDH-wildtype glioblastoma in adults", section on 'MGMT methylation status'.)

Additional testing that can provide useful information in the characterization of high-grade gliomas is summarized in the table (table 2) and discussed in more detail separately. (See "Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors".)

Integrated diagnosis — The 2021 WHO classification classifies diffuse gliomas in adults according to histopathologic and molecular features [8]. Diffuse gliomas are subdivided into IDH-mutant and IDH-wildtype tumors; within each category exist various tumor grades according to histopathologic features. The most commonly encountered high-grade gliomas include (table 1):

Glioblastoma, IDH-wildtype

Astrocytoma, IDH-mutant, grade 4

Astrocytoma, IDH-mutant, grade 3

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted, grade 3

The diagnosis of mixed oligoastrocytoma no longer exists for fully characterized tumors. Tumors with mixed histology require information on both IDH and 1p/19q codeletion status to be categorized as either astrocytoma or oligodendroglioma based on their molecular signature. (See "Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors", section on 'Oligoastrocytoma (historical entity)'.)

The pathologic diagnosis of gliomas is reviewed in detail separately. (See "Classification and pathologic diagnosis of gliomas, glioneuronal tumors, and neuronal tumors", section on 'Histopathologic and molecular classification'.)

Role of tumor genome sequencing — Next-generation sequencing panels on cancer specimens have become more affordable and more widely available; however, routine sequencing of glioma specimens is yet to be proven to be of clinical benefit [11].

Panels tailored for glioma specimens often include screening for the most frequent cancer genes, some of which are occasionally identified in glioblastoma (eg, BRAF V600E) and may allow access to clinical trials of relevant targeted drugs [12-14]. Screening for oncogenic gene fusions, such as neurotrophic receptor tyrosine kinase (NTRK) fusions or fibroblast growth factor receptor 3-transforming acidic coiled-coil containing protein 3 (FGFR3-TACC3), can also identify relevant targets [15-17]. (See "Management of recurrent high-grade gliomas", section on 'Genotype-directed therapies'.)

SURGERY

Deep-seated or multifocal tumors — The combined use of computerized imaging and stereotactic devices has allowed neurosurgeons to perform deep brain biopsies with accurate tumor localization. Frameless stereotaxy establishes a computerized link between the preoperative three-dimensional tumor volume and the surface landmarks of the patient. This link permits the neurosurgeon to be aware of the three-dimensional position of surgical instruments within the intracranial space during the biopsy based upon the preoperative imaging.

Stereotactic image-guided brain biopsy is an accurate and safe diagnostic procedure in patients with focal lesions in nonresectable areas of the brain such as the basal ganglia or thalamus. Diagnostic yield is approximately 90 percent. Complications occur in up to 15 percent of cases, most commonly transient neurologic deficits (10 percent), biopsy-site hemorrhage (8 percent), and permanent neurologic deficits (4 percent) [18]. The procedure-related mortality rate is 1 to 2 percent. Although rare, tumor seeding along the stereotactic biopsy tract has been described [19,20].

For tumors that contain both enhancing and nonenhancing components, biopsy should target the enhancing areas in an effort to obtain diagnostic tissue that is representative of the highest-grade portion of the tumor.

Both positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) have been used to identify metabolically active areas of tumor, thereby increasing the accuracy of stereotactic brain biopsy [21-24]. These techniques are primarily research tools and are not in widespread clinical use for this purpose, as structural MRI typically provides sufficient information to guide optimal biopsy site.

Surgically accessible tumors — The initial treatment for high-grade gliomas in accessible locations is resection [25]. Maximal resection with preservation of neurologic function is an important goal in the initial management of patients with high-grade gliomas, and the extent of surgery must be balanced with preservation of neurologic function.

The available observational evidence suggests that aggressive resection is associated with improved functional status and possibly with prolonged survival [26,27]. Various preoperative and intraoperative advances are being incorporated into patient management to facilitate these goals. (See 'Extent of resection' below.)

A review of over 38,000 surgical admissions for supratentorial brain tumors from the Nationwide Inpatient Sample between 1988 and 2000 showed three important trends: decreasing inpatient mortality over time for brain tumor operations, centralization of care with higher-volume centers performing an ever larger percentage of all such surgeries, and reduced mortality at high-volume hospitals [28]. For craniotomy, mortality at hospitals with five or fewer admissions per year was 4.5 percent, compared with 1.5 percent at hospitals with 42 or more admissions per year. It is not known whether these trends affect long-term outcome.

Preoperative imaging — Preoperative functional MRI and diffusion tractography may be used to optimize tumor volume definition and minimize operative injury to eloquent (eg, speech and motor) areas by allowing preoperative definition of affected and normal brain areas and functional mapping of brain tissue [29-32]. In addition to localization of functional cortical areas such as motor cortex via functional MRI, diffusion tensor imaging enables the visualization of subcortical tracts that carry eloquent task information from speech, motor, and visual pathways [33].

Intraoperative techniques — Several intraoperative techniques are used to improve the extent of surgical resection while minimizing collateral damage to normal brain [34]. In some cases, tumors that appear inoperable on preoperative functional imaging are amenable to a substantial amount of safe resection using intraoperative techniques including direct electrical stimulation [35].

Awake craniotomy For tumors located in eloquent areas, awake craniotomy combining frameless computer-guided stereotaxis with intraoperative direct electrical stimulation and repetitive neurologic and language assessments may facilitate aggressive resection while minimizing postoperative neurologic dysfunction [35-37]. Traditionally, this approach has used repetitive testing, with resection discontinued at the first evidence of neurologic dysfunction. Alternatively, local stimulation has been used to induce language dysfunction, with tumor resection proceeding only in areas not involving language centers. (See "Anesthesia for awake craniotomy", section on 'Indications'.)

Intraoperative MRI – Specially designed operating rooms that are equipped with MRI can guide the resection in "real time." In contrast to frame-based or frameless stereotaxy, this advancement allows actual assessment of tumor volume in its current anatomic location, rather than relying on preoperative data [38]. Intraoperative imaging is used to identify residual tumor after the initial resection and thus can be used to guide further surgery. Such techniques have been shown to increase the proportion of patients that have a gross total resection on postoperative MRI but may not necessarily improve survival in patients with high-grade gliomas [39].

The effectiveness of intraoperative MRI was assessed in a trial in which 58 patients were randomly assigned to surgery with or without intraoperative MRI [40]. At surgery, 49 patients had high-grade gliomas and were evaluable. In 8 of 24 cases using intraoperative MRI, imaging revealed residual tumor and led to additional tumor resection. Overall, significantly more patients managed with intraoperative MRI had a complete resection compared with those managed without MRI (96 versus 68 percent). There was no increase in neurologic deficits with this more aggressive surgical approach.

5-aminolevulinic acid (ALA) – Some centers have expertise in the use of ALA, which is an oral optical imaging agent that helps to visualize malignant tissue during surgery with use of specialized surgical microscopes and light source filters [41]. ALA was approved by the US Food and Drug Administration in 2017 for use as an intraoperative agent in patients with suspected high-grade glioma [42]. Similar to intraoperative MRI, use of ALA as an adjunct to surgery improves intraoperative tumor visualization and thus enables greater extent of resection [43-48]. ALA can be combined with other operative techniques, including intraoperative MRI, to help achieve maximal resection with preservation of neurologic function [49].

Despite these advances in surgical techniques, local recurrences are frequent even in patients undergoing an apparently complete removal of the tumor. High-grade gliomas are characterized by poorly defined tumor margins with infiltration of neoplastic cells along white matter fibers and the perivascular spaces, which can extend well beyond the tumor margin as defined by the surgeon or by radiographic studies.

Extent of resection — The goal of surgery in patients with high-grade glioma is to confirm a pathologic diagnosis and achieve maximal safe resection consistent with preservation of neurologic function. Gliomas are infiltrative tumors, and resection requires removal of both tumor and involved brain tissue. The feasibility of resection depends heavily on the location of the tumor in relation to eloquent cortex.

In the absence of randomized trials, a large body of observational data suggests that extent of resection is a strong prognostic factor in patients with high-grade glioma, even after adjusting for variables known to be related to both surgical decision-making and outcome, such as age, functional status, and tumor size and location [26,43,44,50-60].

As an example, in a Surveillance, Epidemiology, and End Results (SEER) registry study that included over 20,000 adults with glioblastoma diagnosed between 1998 and 2009, extent of resection was categorized as gross total resection, subtotal resection (including partial resection and excisional biopsy), or no surgery [61]. Thirty percent of the cohort underwent gross total resection, and the likelihood of undergoing gross total resection decreased with advancing age. Compared with subtotal resection, gross total resection was associated with an approximately two- to three-month improvement in overall survival across all age groups. For patients age 45 to 59 years, for example, median overall survival times after gross total resection, subtotal resection, and no surgery were 15, 12, and 7 months, respectively (adjusted hazard ratio [HR] for gross total versus subtotal resection 0.82, 95% CI 0.77-0.89).

Other studies have attempted to determine whether a survival benefit may exist for significant subtotal resection of the gadolinium-enhancing portions of the tumor, for cases in which gross total resection is not possible. In retrospective analyses of hundreds of surgical cases, a survival benefit has been suggested for resections above a threshold of 70 to 80 percent [62]. For glioblastoma, a four-tiered categorization of extent of resection based on the amount of enhancing and nonenhancing residual tumor volume has been proposed [63].

The presence of a mutation in isocitrate dehydrogenase (IDH) type 1 or type 2 may be another factor relevant to the association between extent of resection and overall survival. In one large series of high-grade astrocytomas, maximal resection of both enhancing and nonenhancing total tumor volume conferred a significant survival advantage for IDH1-mutant tumors; for IDH1-wildtype tumors, complete resection of enhancing tumor volume but not total tumor volume was associated with improved survival [64]. Others have suggested that age is more important than IDH1/2 status, and that maximal resection of nonenhancing plus enhancing tumor volume confers improved survival in younger patients (age ≤65 years) with glioblastoma, independent of IDH1/2 status [59].

Beyond survival, potential benefits of maximal resection rather than biopsy also include the following:

Resection rather than biopsy provides a larger, more representative sample for detailed analysis, thereby increasing the likelihood of an accurate diagnosis, which can help to direct further therapy.

Debulking surgery may facilitate rapid tapering and discontinuation of corticosteroids, thereby reducing the likelihood of steroid-related complications.

Limited role of carmustine wafers — Carmustine polymer wafers (Gliadel) implanted at the time of surgical resection of high-grade glioma have been approved for use by regulatory agencies [65]. They have not been directly compared with concurrent and adjuvant temozolomide, and data are lacking to support a clear survival advantage in patients with newly diagnosed glioblastoma. In addition, the safety of carmustine wafers in combination with radiation plus temozolomide has not been fully established, and some patients develop significant peritumoral edema after wafer placement [66-69]. We therefore do not recommend use of carmustine polymer wafers in patients with newly diagnosed glioblastoma outside of the context of a clinical trial.

Experience with carmustine wafers in recurrent high-grade glioma is discussed separately. (See "Management of recurrent high-grade gliomas", section on 'Reoperation'.)

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".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Brain cancer (The Basics)" and "Patient education: Astrocytoma (The Basics)" and "Patient education: Glioblastoma (The Basics)")

Beyond the Basics topics (see "Patient education: Low-grade glioma in adults (Beyond the Basics)" and "Patient education: High-grade glioma in adults (Beyond the Basics)" and "Patient education: Meningioma (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

High-grade glioma – High-grade gliomas are malignant, often rapidly progressive primary brain tumors. The most common high-grade gliomas in adults are isocitrate dehydrogenase (IDH)-wildtype glioblastoma (grade 4), grade 3 and 4 IDH-mutant astrocytoma, and grade 3 IDH-mutant, 1p/19q-codeleted oligodendroglioma (algorithm 2).

Clinical features – Patients with high-grade glioma present with neurologic signs and symptoms that vary according to the location of the tumor within the brain. MRI of the brain provides confirmatory evidence of a mass lesion, but a tissue diagnosis is ultimately required to distinguish high-grade gliomas from other primary and metastatic brain tumors. (See 'Clinical features' above.)

Preoperative evaluation – Brain MRI with contrast is often the only study required preoperatively. Patients with a contraindication to brain MRI should undergo a brain CT with contrast. Screening for systemic malignancy is not necessary when the clinical and radiographic suspicion for high-grade glioma is high. (See 'Diagnostic evaluation' above.)

Pathologic diagnosis – A histologic diagnosis is required for optimal treatment of patients with brain tumors. This can be accomplished either at the time of surgical resection or by more limited biopsy. (See 'Pathology' above.)

Surgical resection – For patients with a newly diagnosed high-grade glioma, we recommend maximal surgical resection with preservation of neurologic function rather than biopsy (Grade 1B). Although gross total resection is preferred whenever possible, subtotal resection or biopsy alone may be required depending upon the location and extent of the tumor. (See 'Deep-seated or multifocal tumors' above and 'Surgically accessible tumors' above.)

Postoperative imaging – For patients who undergo surgery, a brain MRI should be obtained within 24 to 48 hours postoperatively to determine the extent of resection. (See 'Extent of resection' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William T Curry, Jr, MD, and Tracy Batchelor, MD, MPH, who contributed to an earlier version of this topic review.

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Topic 5228 Version 58.0

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