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Neurology > Neuro-oncology
Brainstem Gliomas
Article Last Updated: Aug 29, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Joseph Landolfi, DO, Assistant Professor, Department of Neurology, Division of Neuro-Oncology, Neuroscience Institute, JFK Medical Center, Seton Hall University
Joseph Landolfi is a member of the following medical societies: Alpha Omega Alpha
Coauthor(s):
Anita Venkataramana, MBBS, Clinical Instructor, Department of Neurology, Division of Neuroimmunology/HIV, Johns Hopkins University
Editors: Edward Hogan, MD, Professor, Department of Neurology, Medical College of Georgia; Emeritus Professor and Chair, Department of Neurology, Medical University of South Carolina; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Jorge Kattah, MD, Head, Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Author and Editor Disclosure
Synonyms and related keywords:
brainstem tumors, pontine lesions, tectal lesions, hydrocephalus, cervicomedullary lesions, neurofibromatosis, intrinsic pontine gliomas, tectal gliomas, cervicomedullary gliomas, intracranial tumors
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, 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.
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.
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.
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.
Race
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.
Sex
Some reports have suggested a slight male preponderance, whereas others have failed to observe any sex predilection.
Age
- 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.
History
- Common presenting symptoms include double vision, weakness, unsteady gait, difficulty in swallowing, dysarthria, headache, drowsiness, nausea, and vomiting. Rarely, behavioral changes or seizures may be seen in children. Older children may have deterioration of handwriting and speech.
- Pontine lesions usually present with any or all of the above signs and symptoms, depending on location and extension. Midbrain and lower brainstem/upper spinal cord signs and symptoms may be seen with extension of the neoplasm to involve these structures.
- In infants and children presenting with failure to thrive, pontine glioma should be considered in the differential diagnosis.
- Tectal lesions typically present with headache, nausea, and vomiting.
- Hydrocephalus is a common presentation, especially for tumors in periaqueductal or fourth ventricle outflow locations, because these regions have less tolerance of growth and higher risk of obstructive hydrocephalus.
- Cervicomedullary lesions usually present with dysphagia, unsteadiness, nasal speech, vomiting, and weakness.
Physical
- Common clinical findings 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. Involvement of cranial nerve III or IV suggests a mesencephalic component.
- Tectal lesions may present with diplopia reflecting an internuclear ophthalmoplegia, indicating involvement of the medial longitudinal fasciculus. Parinaud syndrome also may be seen, with paralysis of upward gaze and accommodation, light-near dissociation (loss of pupillary reflex to light with preservation of pupilloconstriction in response to convergence), eyelid retraction, and convergence-retraction nystagmus.
- Cervicomedullary lesions may present with sensory loss of the face (involvement of the trigeminal nucleus), dysphagia and/or dysphonia from lower cranial nerve involvement (commonly IX and X), long tract signs, and ataxia. Downbeating nystagmus and oculomyoclonus often are seen with medullary involvement.
Causes
- Although no familial tendency is prominent overall, an increased incidence of brainstem glioma has been observed consistently in patients with neurofibromatosis (up to 14% in some reports).
- Thus far, no genetic or molecular markers have been recognized for brainstem gliomas.
- In children irradiated for tinea capitis, an increased incidence of CNS tumors, especially meningiomas, gliomas, and nerve sheath tumors, has been reported. No specific reference is made in these reports to tumors of the brain stem. Radiotherapy-induced neoplasms tend to be more aggressive in their natural history than their de novo counterparts.
Arteriovenous Malformations
Ependymoma
Glioblastoma Multiforme
Low-Grade Astrocytoma
Medulloblastoma
Meningioma
Metastatic Disease to the Brain
Neurosarcoidosis
Tolosa-Hunt Syndrome
Other Problems to be Considered
Hemangioblastoma
Lab Studies
- Lab studies of blood chemistry and related body fluids are not helpful as a rule, though cerebrospinal fluid (CSF) examination is often important for differential diagnosis. The protein content of CSF may be elevated. Because of the risk of increased intracranial pressure due to obstructive hydrocephalus, caution in clinical and imaging assessment prior to lumbar puncture is stressed.
- Tissue confirmation is frequently not feasible with infiltrating, expansile tumors unless an exophytic component exists, and even then, biopsy cannot always be obtained.
Imaging Studies
- MRI
- MRI of the head is the diagnostic test of choice. MRI can differentiate vascular malformations and other processes that can be misdiagnosed as a brainstem glioma on CT scan.
- The typical MRI appearance of a brainstem glioma is an expansile, infiltrative process with low-to-normal signal intensity on T1-weighted images and heterogeneous high-signal intensity on T2-weighted images, with or without contrast enhancement (see Images 1-2).
- MRI can delineate the extent of infiltration of the leptomeninges and the surrounding structures.
- High midbrain tumors, especially those arising in the tectum, are typically low-grade lesions by histologic criteria. They commonly appear hypointense on T1 and hyperintense on T2 images even without contrast enhancement.
- The occurrence of contrast enhancement in a tectal lesion should raise suspicion of a metastatic lesion, especially in an adult, with or without a known history of cancer.
- CT scan
- Although CT imaging is an appropriate choice when MRI is not available, the appearance of brainstem gliomas is variable on CT scan, and the sensitivity of and characterization of tumors by CT are poorer.
- CT identifies calcifications, cystic changes, and displacement of the ventricular system; however, lower brainstem lesions are often not apparent on CT scan.
Other Tests
- Arteriography occasionally is useful in differentiating vascular lesions, including tumors, from gliomas.
Procedures
- Patients with hydrocephalus may require ventriculostomy or ventriculoperitoneal shunting for symptomatic relief.
- Patients with difficulties in swallowing and diminished gag reflex may need feeding by gastrostomy such as the percutaneous esophagogastrostomy (PEG).
- Those patients who have had multiple upper respiratory infections, pneumonia, or altered voice may need postoperative ventilatory assistance.
Histologic Findings
The histopathology is variable; most gliomas in the brain stem are fibrillary, pilocytic astrocytomas, or the more malignant glioblastoma multiforme. Hemorrhage and necrosis are associated with the more malignant forms. Cysts may be seen with either the high- or low-grade forms.
Medical Care
- Treatment of brainstem gliomas has been frustrating; at this point, new therapies have yielded little benefit over conventional treatment with radiotherapy alone.
- Adjuvant chemotherapy is not used in children because efficacy has not been proved. Its efficacy in adults is similarly unproven, and at present, postradiotherapy adjuvant chemotherapy cannot be recommended. The effectiveness of chemotherapy at relapse is uncertain, but it may benefit some patients.
- Focal radiotherapy is the cornerstone of treatment of brainstem gliomas and can improve or stabilize the patient's condition. The conventional dose of radiotherapy ranges from 54-60 Gy, with doses up to 72 Gy given with hyperfractionation. At present, no benefit has been demonstrated with doses greater than 72 Gy; however, this therapy has not demonstrated efficacy in children.
- Response to radiotherapy, in addition to the dose of radiation, depends on several variables such as tumor location, histologic type, and response to early treatment. Patients who underwent radiation therapy for exophytic tumors have been reported to have better survival rates than those treated for tumors without an exophytic component.
- Radiotherapy should be administered to any patient with significant and progressive neurologic symptoms. Some adult patients with a tectal or cervicomedullary lesion, or with mild symptoms of long duration, may be candidates for observation alone; radiotherapy can be reserved for patients with clear evidence of tumor progression.
Surgical Care
Surgical resection is performed in conjunction with radiation and/or chemotherapeutic agents.
- Surgery is most appropriate in 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, and finally, benign tumors (ie, those with slow clinical progression).
- Typically, biopsy and/or surgery are not required for diagnosis or treatment of diffuse intrinsic pontine or tectal gliomas and cannot be recommended routinely; diagnosis can be made by MRI alone.
Consultations
- Neuro-oncologist: The neuro-oncologist should be the primary physician supervising the care of these patients. If a neuro-oncologist is not available, a medical oncologist with expertise in treating brain tumors may be consulted for guidance. Otherwise, the patient should be referred to a reputable institution that specializes in the care of patients with CNS neoplasms.
- Neurosurgeon: The treating neurosurgeon should have significant experience in resection of CNS neoplasms.
- Radiation oncologist
- Neuropathologist
- Neuroradiologist
- Neuropsychologist for pretreatment and posttreatment evaluations, when clinically indicated
- Rehabilitation medicine specialist
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Drug Category: Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
| Drug Name | Dexamethasone (Decadron) |
|---|
| Description | Can be used to reduce tumor- and radiotherapy-associated cerebral edema. |
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| Adult Dose | 24 mg IV bolus followed by maintenance dose of 4 mg PO tid/qid; for intracranial neoplasms, higher doses may be required in patients with severe cerebral edema or herniation syndrome secondary to tumor |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; systemic fungal infections; documented hypersensitivity |
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| Interactions | Coadministration with warfarin or heparin increases risk of bleeding |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Increases risks of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications |
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Further Inpatient Care
- Typically, patients are monitored for worsening signs/symptoms. Admission to the hospital may be required to enable therapeutic intervention and stabilization.
Further Outpatient Care
- Follow-up neuroimaging with MRI (unless contraindicated) is recommended within 72 hours after surgery and every 2-3 months to monitor response to therapy and progression of disease. This should be considered standard care for these patients.
Complications
- Hydrocephalus, commonly obstructive
- Growth and developmental delay (in children)
- Cerebral herniation
- Deep cerebral vein thrombosis
- Paralysis/paresis
- Cranial nerve deficits
- Meningitis
- Radiation necrosis
- Hypopituitarism/hypothyroidism
- Bone marrow suppression
- Cognitive dysfunction
Prognosis
- Pontine tumors are the most common variety of brainstem tumor. They also carry the worst prognosis; in children, the median survival duration is 9-12 months even with treatment. Kaplan et al reported a 37% survival rate at 1 year, 20% at 2 years, and 13% at 3 years, with a median survival of 10 months. Only 9 of 119 patients in their study were alive for more than 3 years after diagnosis.
- Squires et al, in a study of 12 children with midbrain tectal tumors, reported a median survival duration of more than 50 months.
- Favorable prognostic factors include (1) neurofibromatosis, (2) symptoms of at least 12 months' duration before diagnosis, (3) exophytic location, (4) pathology suggestive of low-grade tumor histology, (5) focal tectal and cervicomedullary tumors, and (6) calcification on CT scan.
- Poor prognostic indicators include (1) age younger than 2 years, (2) multiple brainstem signs, (3) cranial nerve palsies, (4) diffuse intrinsic lesions of the pons, (5) short duration of signs and symptoms prior to the time of diagnosis, and (6) high-grade histology on tumor biopsy.
- Hydrocephalus and tumor necrosis do not affect survival.
- Race and gender do not affect survival.
- The limited available data suggest that adults fare better than children with brainstem gliomas.
- Grigsby et al reported a 10-year disease-free survival rate of 15.4% for adult patients with gliomas involving the midbrain, thalamus, or hypothalamus, and 29.6% for adults with pontine or medullary tumors. However, thalamic/hypothalamic neoplasms are not included historically in the classification of brainstem tumors.
- Landolfi et al studied 19 adults with brainstem gliomas, which included 13 diffuse intrinsic pontine, 4 cervicomedullary, and 2 tectal gliomas. They noted a trend that higher Karnofsky performance status conferred a better prognosis. Other factors did not affect survival. Median survival duration of patients in this study was 54 months, with a 5-year survival rate of 45%.
- Hamilton et al studied 16 adults with focal midbrain gliomas; they reported a median survival of 84 months. This indolent growth pattern is in marked contradistinction to the natural history of this disease in children. This is also the reverse of the usual behavior of hemispheric gliomas in which children typically fare better than older patients.
- No explanation has been identified for the better outcome in adults; however, the possibility of prolonged survival with limited neurologic impairment must be recognized when counseling adults with brainstem gliomas.
Patient Education
- Patients and families of patients acquire information from multiple sources, including, but not limited to, physician, patients, support groups, pharmaceutical companies, and the Internet. Physicians should be aware of this and have an open, informative relationship with their patients, empowering patients to become active members of the team with regard to the decision-making process involving their care.
Medical/Legal Pitfalls
- Failure to identify presenting signs and symptoms, thus causing a delay in, or missing, the diagnosis
- Not recognizing the limitation of ones' knowledge and failing to obtain MRI imaging studies or to call upon appropriate consultations, especially in neuroradiology and neurosurgery, and occasionally in psychiatry or psychology, for patients whose symptoms are misinterpreted as being "functional"
| Media file 1:
T2-weighted image of a diffuse intrinsic pontine glioma. |
 |  View Full Size Image | |
Media type: MRI
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Brainstem Gliomas excerpt Article Last Updated: Aug 29, 2006
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