Brainstem Gliomas

Updated: Jun 09, 2016
  • Author: Joseph C Landolfi, DO; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Overview

Practice Essentials

Brainstem gliomas are tumors that occur in the region of the brain between the aqueduct of Sylvius and the fourth ventricle. Brainstem gliomas account for approximately 10-20% of all childhood brain tumors. The incidence in adults is lower than that in children younger than 16 years. See the image below.

T2-weighted image of a diffuse intrinsic pontine g T2-weighted image of a diffuse intrinsic pontine glioma.

Signs and symptoms

Common presenting signs and symptoms include the following:

  • Double vision
  • Weakness
  • Unsteady gait
  • Difficulty in swallowing
  • Dysarthria
  • Headache
  • Drowsiness
  • Nausea
  • Vomiting
  • Behavioral changes or seizures in children (rare)
  • Deterioration of handwriting and speech, in older children

Common clinical findings on physical examination can be summarized as constituting a triad of cranial nerve deficits, long tract signs, and ataxia (of trunk and limbs). Papilledema may be seen. Sixth and seventh cranial nerves are involved commonly. Facial sensory loss and a primary-position, upbeating nystagmus may be seen.

Certain manifestations suggest specific tumor locations, as follows:

  • Infants and children with failure to thrive – Pontine gliomas
  • Involvement of cranial nerve III or IV – A mesencephalic component
  • Hydrocephalus – Tumors in periaqueductal or fourth ventricle outflow locations

Patients with tectal lesions may present with the following:

  • Headache, nausea, and vomiting
  • Diplopia
  • Parinaud syndrome

Patients with cervicomedullary lesions may present with the following:

  • Dysphagia, unsteadiness, nasal speech, vomiting, and weakness
  • Sensory loss in the face (involvement of the trigeminal nucleus)
  • Dysphagia and/or dysphonia from lower cranial nerve involvement (commonly IX and X)
  • Long tract signs
  • Ataxia
  • Downbeating nystagmus and oculomyoclonus (medullary involvement)

See Clinical Presentation for more detail.

Diagnosis

The workup for brainstem gliomas may include the following:

  • MRI of the head – Diagnostic test of choice
  • CT scan – Less accurate than MRI, but appropriate when MRI is not available
  • CSF examination – Often important for differential diagnosis
  • Arteriography – Occasionally useful in differentiating vascular lesions, including tumors, from gliomas

Lab studies of blood chemistry and related body fluids are not helpful as a rule. Tissue confirmation is frequently not feasible.

See Workup for more detail.

Management

Treatment of brainstem gliomas may comprise the following:

  • Focal radiotherapy [1]
  • Chemotherapy
  • Surgical resection

Observation alone may be considered for some adult patients with any of the following:

  • A tectal lesion
  • A cervicomedullary lesion
  • Mild symptoms of long duration

Focal radiotherapy

  • The cornerstone of treatment of brainstem gliomas
  • Can improve or stabilize the patient's condition
  • Should be administered to any patient with significant and progressive neurologic symptoms
  • The conventional dose of radiotherapy ranges from 54-60 Gy, with doses up to 72 Gy given with hyperfractionation
  • Reported survival rates with radiation therapy are better in patients with exophytic tumors

Chemotherapy

  • Preradiation chemotherapy may improve survival in pediatric diffuse intrinsic brainstem gliomas [2]
  • Postradiotherapy adjuvant chemotherapy cannot be recommended
  • Chemotherapy at relapse may benefit some patients
  • Chemotherapy may include conventional agents such as temozolomide and carboplatin/vincristine
  • Antiangiogenesis agents (eg, thalidomide, bevacizumab) have been used with success in supratentorial glioblastomas
  • If chemotherapy is desired adjuvantly or concurrently with radiotherapy, particularly in the pediatric population, consider entering the patient into a clinical trial

Surgical resection

Surgical therapy is performed in conjunction with radiation therapy, chemotherapy, or both. It is not required for diagnosis or treatment of diffuse intrinsic pontine or tectal gliomas; it is most appropriate in the following cases:

  • Tumors of the cervicomedullary junction
  • Dorsal exophytic tumors protruding into the fourth ventricle
  • Cystic tumors
  • Enhancing tumors with clear margins that exert a space-occupying effect
  • Benign tumors (ie, those with slow clinical progression)

See Treatment and Medication for more detail.

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Background

Brainstem gliomas are tumors that occur in the region of the brain referred to as the brain stem, which is the area between the aqueduct of Sylvius and the fourth ventricle. Although various systems are used to classify these tumors, the authors have divided brainstem gliomas into 3 distinct anatomic locations—diffuse intrinsic pontine, [3] tectal, and cervicomedullary. Intrinsic pontine gliomas carry a grave prognosis. Longer survival is associated with the tectal and cervicomedullary gliomas. Tumors also are characterized on the basis of site of origin, focality, direction and extent of tumor growth, degree of brainstem enlargement, degree of exophytic growth, and presence or absence of cysts, necrosis, hemorrhage, and hydrocephalus. [4]

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Pathophysiology

These tumors have a predilection to originate from the left side. Most are located in the pons; however, medulla and midbrain may be involved as well. Brainstem gliomas are highly aggressive brain tumors. Anatomic location determines the pathophysiological manifestation of the tumor. With tectal lesions, hydrocephalus may occur as a result of fourth ventricular compression. With pontine and cervicomedullary lesions, cranial nerve or long tract signs are observed commonly.

Histopathologically, brainstem gliomas can range from WHO Grade 1 to 4. Grade 1 is the juvenile pilocytic astrocytoma, Grade 2 is the diffuse astrocytoma, Grade 3 is the anaplastic astrocytoma, and grade 4 is the glioblastoma multiforme. The grading is based on the presence of nuclear atypia, vascular proliferation, mitoses, and necrosis. Typically, the necrosis is seen in Grade 4 (glioblastoma multiforme).

Molecular profiling is now an important part of glioma classification. An IDH1 mutation carries an improved prognosis over the IDH1 wildtype, no matter what the tumor grade. Codeletions of Chromosome 1p and 19q along with an IDH1 mutation indicates an oligodendroglioma in Grade 1-3 gliomas. For pediatric diffuse gliomas, a newly defined entity termed diffuse midline glioma, H3 K27M-mutant is characterized by K27M mutations in the histone H3 gene, a diffuse growth pattern and a midline location. This newly defined entity occurs primarilty in children, but can be seen in adults, and includes tumors previously referred to as diffuse intrinsic pontine glioma (DIPG). [5]

Although biopsy or resection is not typically performed on brainstem gliomas, vascular endothelial growth factor (VEGF) receptors are an important pathway in the invasion and growth of supratentorial glioblastomas by promoting the growth of new blood vessels. Epidermal growth factor receptors (EGFR) are present in 25% of glioblastomas and are important in the growth of these neoplasms as well. The presence of these receptors may aid in the response to various targeted therapies, as is discussed in Medical Care.

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Frequency

United States

Brainstem gliomas have been reported to make up 2.4% of all intracranial tumors in adults and 9.4% of intracranial tumors in children. Brainstem gliomas account for approximately 10-20% of all childhood brain tumors. The incidence in adults is lower than that in children younger than 16 years. A tendency for brainstem gliomas to follow a more indolent course in adults than in children has been noted; in adults, these tumors are more likely to be low grade and remain localized.

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Mortality/Morbidity

Morbidity is due to the location of the space-occupying lesion and compression of surrounding structures; because these structures regulate basic body functions of blood pressure, respiration, and swallowing as well as motor and sensory functions, compression can produce substantial neurological disability.

Sudden death can result from increased intracranial pressure and subsequent cerebral herniation. This may be a consequence either of edema induced by the tumor or of hemorrhage into the neoplasm.

 

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Epidemiology

Race-, sex-, and age-related demographics

CNS tumors vary in incidence by age, sex, ethnic group, and country, and also over time. How much of this variation is due to artifactual influences or etiologic differences has been the subject of many debates.

Some reports have suggested a slight male preponderance, whereas others have failed to observe any sex predilection.

Bimodal age distribution has been noted, with a peak incidence in the latter half of the first decade of life and a second peak in the fourth decade. Approximately three fourths of patients are younger than 20 years.

Neoplasms of the brain stem have been identified in children younger than 1 year.

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