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Glioma

(A Patient Information Service)

This is a "family" of tumors, which arise from cells known as "GLIAL CELLS". This series of cells comprises the "glue" cells of the Central Nervous System (CNS), in contradistinction to the "Neurons", which are the "action" cells of the brain and spinal cord. Glial cells are the most common cellular component of the brain. They are five to ten times more frequent than the trillion brain neurons and comprise half the central nervous system (CNS) by volume. There are three (3) different cell types in this cell series. The "Astrocyte" was so named, because it resembles the shape of a star, when looked at under a microscope. The next most common cell in this series is the "Ependymal Cell", which lines the cavities of the brain (called ventricles). These are normal chambers within the brain, where cerebrospinal fluid (CSF) is manufactured. These cells are also found within the central canal (a small cavity) within the spinal cord. The last cell type is the "Oligodendrgogliocyte" (Oligo), which is the cell within the brain and spinal cord responsible for making the insulating material (called Myelin), that surrounds the fibers (axons) which transmit electrical impulses within the brain and spinal cord.

Each of these cell types is capable of forming a tumor. The Neurosurgeons of Neurosurgical Consultants regard ALL OF THESE AS MALIGNANT TUMORS. The degree of malignancy, and therefore, biological aggressiveness can vary from quite indolent to extremely aggressive. These tumors are generally categorized according to their degree of aggressiveness, as judged by a number of factors. Neuropathologists (specialists trained to examine these tumors under powerful microscopes), have tended to "grade" these tumors from 1 to 4, with "4" being the most aggressive and "1" being the least malignant. All of these tumors have a tendency to "infiltrate" within the brain and/or spinal cord by tracking along the fiber pathways that interconnect every part of the brain to every other part of the brain. Very rarely do these tumors ever spread beyond the brain or spinal cord.

Astrocytoma

An Astrocytoma is a tumor that arises from Astrocytes which are the most numerous type of Glial cell. Glial cells have an enormous potential for abnormal growth and are the chief source of CNS tumors. Approximately half of all primary brain tumors are Glial cell neoplasms (tumors) and more than three quarters (3/4) of all Gliomas are Astrocytomas which, themselves, are a heterogeneous group of tumors that are grouped by grades.

SYMPTOMS

The first symptom of a brain tumor of any type can be a headache, caused by increased pressure in the brain and therefore, inside the skull. The headache associated with a brain tumor, is frequently worse in the morning, frequently accompanied by vomiting. Other symptoms of a brain tumor can include seizures (Epilepsy), weakness or numbness of a side or part of the body, or subtle symptoms such as changes in mood, thinking or general state of well being. Increased intracranial pressure can cause blurred, double or lost vision. A first seizure (Epilepsy), in anyone over the age of 21 is considered to be due to a Brain Tumor UNTIL PROVEN OTHERWISE.

DIAGNOSIS

If a patient has any of the above symptoms without any obvious explanation, further work-up is warranted. These tumors can be best seen by Magnetic resonance Imaging (MRI). CT scans can also be used; however, the degree of brain and tumor substance detail that can be picked up by CT is much less than MRI. Once a mass is confirmed by any of the neuroimaging techniques, the diagnosis needs to be established by a biopsy of the mass. The biopsy, which is carried out in conjunction with a more definitive surgical excision, will help differentiate tumor from other types of masses, such as infection. The microscopic structure of the tumor is vitally important in the pathologist’s "grading" of the tumor.

Tumor Grade

Tumor grading is important for prognosis and therapy. Tumors are graded by microscopic examination of the tumor specimen. The specimen is evaluated for the most malignant components. Varying "grades" of tumor cells can be found in any one tumor. The biological behavior of the tumor will relate to the highest grade (worst and most aggressive) component of that tumor, even though that higher grade component comprises a small portion of the entire tumor. In other words, if a tumor is 99.5 % Grade 1 and only 1/2 percent Grade 3 or 4, the biological behavior of that tumor, will be as if the entire tumor is Grade 3 or Grade 4.

Natural History

Astrocytomas are neither histologically or biologically uniform tumors. The borderline between low-grade and Anaplastic (Malignant) Astrocytoma, is at best indistinct. Although many patients with low-grade Astrocytomas survive for extended periods, 50% of surgically treated lesions evolve into Anaplastic Astrocytomas or Glioblastomas. Degeneration into a higher-grade neoplasm is the most common cause of death in patients with low-grade Astrocytomas.

Low-grade Astrocytomas

Low-grade Astrocytomas are uncommon tumors and occur less frequently than their more malignant counterparts. They are generally found in a younger population and have a more favorable prognosis. Their true incidence is difficult to determine, because sampling and grading vary substantially. Low-grade Astrocytoma probably represents 10% to 15% of Gliomas. These are neoplasms of children and adults from 20 to 40 years of age. These tumors are rare in older adults. Low-grade Astrocytomas can present with any of the symptoms previously described.

TREATMENT

Surgery

Surgery is important in order to remove the mass effect and pressure caused by the tumor. However, surgery is rarely curative for most infiltrating hemispheric Gliomas, unless the tumor is located at the anterior (front) portion of either a Temporal or Frontal Lobe. Surgery is the principal treatment in the following situations of low-grade Astrocytomas:
  • Childhood Cystic Cerebellar Astrocytomas.
  • Supratentorial Pilocytic Astrocytomas.
  • Large tumors, or tumor cysts, causing severe pressure on the surrounding brain.
  • Obstruction of cerebrospinal fluid flow.
  • Seizure control for Epilepsy that is refractory to medical therapy.

Radiation Therapy

The primary non-surgical treatment is radiation therapy. Radiation can be administered to the whole brain, or it can be relatively focused to a region of the brain. Radiosurgery (Focused Beam Radiation) allows for very precise focusing of radiation beams into the area of Astrocytoma involvement, with less risk for damage to the surrounding brain. Unfortunately, the energy from radiation is destructive to normal brain cells, as well as, abnormal tumor cells.

Consideration to WITHOLD radiation therapy may be appropriate in cases of gross total surgical removal, or incomplete removal, in cases of Pilocytic Astrocytoma or Cystic Cerebellar Astrocytoma. Meticulous follow up is required, since radiation therapy can be helpful where tumor recurrence or progression is documented.

In cases of incomplete removal of ordinary low-grade Astrocytomas, post-op radiation is probably indicated.

Anaplastic Astrocytomas

Anaplastic Astrocytomas are among the most common primary malignant brain tumors. These tumors represent approximately one third of all Astrocytomas and about one quarter of all Gliomas. They occur at any age but typically are found in older patients. Their peak incidence is in the fifth and sixth decades of life. Seizures and focal neurological deficits are common presenting symptoms. In addition, any of the symptoms described previously, may be present at the time of diagnosis.

Malignant Astrocytomas generally have a poor prognosis, with an average survival of two (2) years. Both types of malignant Glial tumors (Anaplastic Astrocytomas and Glioblastomas) spread through the extracellular space and along the compact white matter tracts that connect each part of the brain with every other part of the brain.

TREATMENT

Surgery

Surgery to reduce the bulk of the tumor, followed by radiation therapy, has become the standard against which other treatments are compared. One must consider that these tumors cannot usually be cured with surgery alone, although the Neurosurgeons of Neurosurgical Consultants are encouraged by their increasing experience with long term survival using a combination of aggressive approaches. The goals of treatment, if "cure" is not possible, should be to prolong survival, together with a higher quality of life.

Because of the infiltrative nature of Astrocytoma, it is unlikely that surgery will ever be the definitive treatment for these neoplasms. However, increasingly safe and aggressive tumor resection is possible with the advent of technological advances such as intra-operative MRI and Ultrasonic imaging systems, as well as, actual tumor-brain interface "visualization", using Fluorescence techniques.

The Neurosurgeons of Neurosurgical Consultants firmly believe that aggressive resection of the tumor, is the first definitive step in the treatment of these tumors. Other steps include Chemotherapy and Radiation Therapy. Some additional technologies have also helped to improve their outcomes. For example, it is now possible to culture the tumor and subject it to sensitivity testing against various chemotherapy agents prior to initiating Chemotherapy.

New Chemotherapies

Traditional management has been to use "standard" forms of chemotherapy. Currently there are some unconventional chemotherapeutic alternatives that offer considerable hope for improved quality and length of survival. New therapies such as Temodar (temozolamide), Avastin (bevacizumab which is an anti-angiogenesis medication) and CPT-11 are currently being used by one of our Neuro-oncologists. Preliminary results have been encouraging. The reader may wish to view the "Virtual Trials" website for additional information.

Ultimately we hope to see the availability of gene therapy to treat Astrocytoma.

In some tumor cases we choose to place a special chamber called an "Ommaya Reservoir" under the scalp, with an attached catheter residing in the "bed" of the tumor, after resection has been completed. This permits the Neuro-oncologist to instill chemotherapeutic medications directly into the tumor bed.

Radiation Therapy

Radiation therapy continues to have an important place in the treatment of many of these tumors. Refinements have been made that make this treatment less toxic than in previous years.

Cerebellar Astrocytomas

Cerebellar Astrocytomas are one of the more common pediatric brain tumors (10%), comprising 27% of pediatric Posterior Cranial Fossa tumors. They are much less common in adults. The post-operative survival is longer than other types of Astrocytomas. Surgical excision of the maximal amount of the tumor that can be removed, without producing neurological deficits, is the appropriate treatment. In tumors composed of a nodule and a cyst, excision of the nodule is usually definitive therapy. These patients generally have a high rate of long term (5 to 10 or more year) survival. Radiation therapy is not recommended in these cases, since the complication rates of radiation therapy in the face of expected 5 or more years of survival, is quite high. Careful attention to follow up is required using repeat MRI scans. Repeat operation is appropriate, if there is a recurrence of the tumor.

Brainstem Glioma

Brainstem Gliomas tend to occur during childhood and adolescence.

The most common initial presenting complaint is that of gait (walking) disturbance. Following this are the complaints of:

  • headache
  • nausea/vomiting
  • double vision
  • facial weakness
  • trouble swallowing
  • hoarse voice
  • motor weakness
  • hydrocephalus
These tumors are primarily diagnosed by MRI scans. Although treatment is usually non-surgical, there are some significant exceptions, such as in cases where there is an exophytic (extending outside the brain stem) component, a large cystic component within the brainstem or a small, discrete lesion that is close to a surface of the brain stem.

Radiation therapy is generally regarded as the primary treatment method with chemotherapy frequently being used as well. In some recent cases we have used Radiosurgery (Focused Beam Radiation) quite effectively.

Ependymoma

Ependymomas are tumors that arise from Ependymal cells, which make up the thin layer of epithelium that lines the ventricular walls of the brain cavities (called "ventricles", where Cerebrospinal Fluid [CSF] is manufactured) and the central canal of the spinal cord. Ependymal cells are the third type of cell in the "glial" cell series, the others being Astrocytes and Oligodendrocytes.

In a manner similar to other "Gliomas", Ependymal Cells can form a tumor known as an "Ependymoma". These tumors can occur within the brain or spinal cord. The commonest sites of origin are:

  • Intracranial: This comprises only 5-6% of all intracranial Gliomas, 69% occur in children (comprise 9% of pediatric brain tumors). These are usually well circumscribed and "benign" - appearing. They commonly arise in the floor of the fourth ventricle (60-70% are infratentorial in region of the 4th ventricle).

  • Spinal: These comprise approximately 60% of spinal cord Gliomas, 96% occur in adults
These tumors have the potential to spread ("seed") through the CSF (Cerebrospinal Fluid) pathway to other areas of the nervous system.

Ependymomas are four to six times more common in children compared to adults. The peak age range is 1 to 5 years but there is a second, smaller peak in the mid-30s.

The symptoms of these tumors are similar to those of other intracranial masses. This includes headache (80%), nausea/vomiting (75%), ataxia (difficulty with balance) or dizziness (vertigo), and seizures.

These tumors are primarily diagnosed by CT or MRI scans. The diagnosis is then confirmed by microscopic examination of the tumor.

TREATMENT

Surgery

The goal of surgery is the resection (removal) of the greatest amount of tumor maximal possible, without causing neurological deficits. When invasion of the surrounding brain is extensive, total excision is not possible, although we have had encouraging long-term experience with the removal of the small portion of tumor that invades the floor of the fourth (4th) ventricle in selected patients. The long term results, in these patients, have been excellent.

Spinal Cord Ependymoma

Spinal Cord Ependymoma is more likely to occur in the thoraco-lumbar junction region and involve the "Cauda Equina". The most common presenting complaint is that of "PAIN". Weakness and/or tingling in the lower extremities, bowel and bladder control may also be noted. MRI scan is the most effective diagnostic screening method and is often done when the tentative diagnosis is thought to be a herniated lumbar disc. Treatment demands surgical excision to the maximum extent possible. Minimally invasive microendoscopic spinal cord removal techniques are now available. Nevertheless, not all tumors can be entirely removed. For those where some residual is known, or believed to be present, then radiation and chemotherapy should be serious considerations.

The Neurosurgeons of Neurosurgical Consultants have a particular interest in and significant experience with Spinal Cord Ependymomas. We invite your attention to our website area devoted to the discussion of this entity.

Radiation Therapy

Ependymomas rank second only to Medulloblastomas in sensitivity to radiation. Radiation Therapy is administered after surgical excision to the tumor bed and if any metastases ("SEDING") through the CSF are found. In 50% of patients survival time was 2 years longer with radiation therapy than without.

The overall 5-year survival rate is 45%. Tumor recurrence or progression at the primary site is by far the most common cause of death in these patients. Spinal seeding is relatively uncommon and occurs later in the course of the disease for most patients.

Glioblastoma Multiforme (GBM)

GBMs are the most common and most malignant of the primary CNS neoplasms, representing 15% to 20% of these tumors. Approximately half of all Astrocytomas are GBMs. GBM is the most common supratentorial neoplasm in adults.

GBMs usually occur in patients over 50 and are unusual in patients under 30. Like Anaplastic Astrocytomas, GBMs can occasionally be found at any age; Anaplastic Astrocytomas and GBMs are among the four most common primary brain tumors in infants and children under 2 years of age. Various symptoms occur with GBM, including seizure, focal neurological deficits, and stroke like syndromes.

The first symptom of a brain tumor of any type can be a headache, since these tumors act as masses within the boney skull and thus cause increased pressure in the brain. The headache associated with a brain tumor, is frequently worse in the morning and is accompanied by vomiting. Other symptoms of a brain tumor can include seizures, weakness or numbness of a side or part of the body, or such subtle symptoms such as changes in mood, thinking or general state of well being. Sometimes increased pressure in the brain can cause blurred, double, or lost vision.

A seizure occurring for the first time in anyone over the age of twenty is regarded as the indication of a brain tumor, until proven otherwise. If a patient has any of the above symptoms, without any obvious explanation, further work-up is warranted. These tumors can be seen best by Magnetic Resonance Imaging (MRI). CT scans can also be used; however, the degree of detail is much less than MRI. As with other tumors and most particularly with any of the Gliomas, once a mass is confirmed by any of the imaging techniques, the diagnosis needs to be established by a biopsy of the mass. The biopsy is done in conjunction with an aggressive resection of the tumor. The biopsy identifies the particularities of the tumor and differentiates it from other types of masses, such as infection.

Along with primary CNS Lymphoma, GBMs have the worst prognosis of all primary brain tumors. GBMs disseminate early, rapidly, and widely. Central Nervous System spread is common, but distant metastasis is rare.

TREATMENT

In selecting the treatment of High Grade Malignant Astrocytomas, it should be kept in mind that the following three (3) statistically independent factors affect the length of survival: 1) age at the time of diagnosis, 2) histological features (Grade of the tumor and additional characteristics such as Mitotic Index), and 3) performance status (the level of the patient's neurological capabilities). Older patients with high grade malignant brain tumors, who are in poor neurological condition at the time of surgery, do less well.

COMPREHENSIVE THERAPY

The primary initial therapy is to gain control of the increased intracranial pressure. Often times, these patients have significant brain swelling, in addition to the presence of and as a consequence of the tumor. Pre-treatment with a course of high dose intravenous steroids, may well improve the condition of the patient prior to surgery. In some cases, this may mean a strategic delay of surgical intervention for three (3) to seven (7) days. The wait can be rewarded by a far better initial outcome.

Surgery

Aggressive surgical excision of the tumor is advocated in most patients. The goal is to reduce the maximum amount of the tumor. In some cases this may mean an extensive Frontal or Temporal Lobectomy. When tumor is within the middle or posterior portions of the Temporal lobe, the Parietal or Anterior or Middle Occipital Lobe, an aggressive internal decompression of the tumor is warranted. There are some advanced technologies that currently assist in the extent of resection. The ability of the surgeon to "visualize" tumor is somewhat limited. Magnification of vision, Intraoperative ultrasound imaging, Intraoperative MRI scanning and Intraoperative Fluorescence techniques are a few of the adjunctive technologies that may be available to assist maximum resection, while limiting the risk of injuring adjacent functioning brain.

The surgeon may choose to reserve a small part of the tumor for tissue culture and sensitivity testing against various chemotherapeutic agents. It can be helpful to know beforehand, if a certain drug has any or limited effectiveness against this particular tumor, in this particular patient.

The surgeon will also have the opportunity to place an "Ommaya Reservoir" within the tumor bed for later use by the Neuro-oncologist, to instill chemotherapeutic medications directly into the tumor bed.

It is imperative to understand that these are "infiltrative" tumors which spread along the interconnecting fiber pathways (tracts) of the brain. As such, these tumors can rarely be entirely removed surgically.

Radiation Therapy

Radiation therapy, of which there are several forms, has become the standard against which other treatments are compared. For most patients, this will be the second major treatment option, in a comprehensive therapeutic program.

Chemotherapy

Chemotherapy is the third arm of this comprehensive effort to prolong and maintain a high quality of life. There are traditional and commonly used regimens. However, one of our Neuro-oncologists has utilized newer medications such as Temodar (temozolamide), Avastin (bevacizumab, an anti-angiogenesis agent) and CPT-11, either alone (or more commonly) in combination or with other drugs, to produce encouraging results. Additional information regarding these treatments is available at the "Virtual Trials" website. Ultimately we continue to hope for the development of specific gene therapies.

Oligodendroglioma

Oligodendrogliomas are uncommon Gliomas which comprise approximately 4% of primary brain tumors. These tumors arise from glial cells, called Oligodendrocytes (the cells that are responsible for creating and maintaining myelin, which is the insulating substance around the axons of brain cell fiber networks). They are much less common than Astrocytes. These are tumors of adults, with the peak incidence being between 35 and 45 years of age. Seizures (epilepsy) are the presenting symptom in 50-80% of cases. The presenting symptoms of this tumor are not specific for Oligodendroglioma. They are more often related to local mass effect and less commonly to a generalized increase in intracranial pressure. These symptoms are similar to those of any intracranial mass lesion and include headaches, mental status changes, and nausea/dizziness. Patients presenting with the above symptoms, should have an evaluation, which includes and MRI or CT scan. Oligodendrogliomas commonly have some calcification within them which can indicate to the surgeon that this tumor has cells of this origin.

TREATMENT

Surgery

The initial treatment for Oligodendroglioma is aggressive removal. The definitive diagnosis is made by microscopic examination of the tumor tissue taken at the time of surgery.

Aggressive resection of this tumor leads to longer survival, and results in fewer side effects than "partial debulking" operations. It is important to recognize that a significant percentage of Astrocytoma tumors may also have an Oligodendroglioma component as well. These tumors are called "Mixed Gliomas". Treatment of a Mixed Glioma is similar to what is described for an Astrocytoma.

Most Oligodendrogliomas are slow-growing tumors. Tumor grade is the single most important prognostic variable. Patients with low-grade lesions have 5- and 10-year survival rates of 74% and 46% respectively; the rates are 41% and 20% for patients with grade 3 or 4 tumors.

Chemotherapy

Most Oligodendrogliomas respond to some form of chemotherapy. Newer forms of medication, such as Temodar (temozolamide) and CPT 11, as well as other agents are being used in addition to, or replacing more conventional drugs such as PCV (procarbazine, CCNU, and vincristine). Information regarding these newer treatments is available.

Radiation Therapy

One of our Neuro-oncologists generally recommends radiation therapy as an adjunct for these tumors. Benefits of postoperative radiation are somewhat controversial, since some studies have shown improved survival, while others have shown no increase in survival.



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This page last edited on 2/20

All content ©2016 by Neurosurgical Consultants, P.A.
Author, Martin L. Lazar, MD, FACS
All Rights Reserved. See Usage Notices.