The astrocytoma is the most common intra-axial brain tumor. Astrocytomas are classified on a four-grade scale.122,123Grades I and II are considered low-grade gliomas, grade III is anaplastic, and grade IV is glioblastoma multiforme. Grades III and IV are considered high-grade gliomas.

Histologically, the diagnosis of low-grade gliomas is based on minimal hypercellularity and pleomorphism, with no vascular proliferation or necrosis. (See Figure 6). These characteristics escalate to excessive pleomorphism, increased mitotic activity, necrosis, pseudopalisading, and endothelial proliferation in glioblastoma multiforme. Generally, most gliomas stain positively for glial fibrillary acidic protein (GFAP).

Astrocytoma
 
Figure 6. Low-grade astrocytoma. 200. Hematoxylineosin (H&E) stain of mildly atypical neoplastic glial cells with a fibrillar and myxoid background.

Cortical astrocytomas may arise from different cell lineages than white-matter astrocytomas. Piepmeier et al. showed that type I cortical astrocytomas had different expression of GFAP and gangliosides than type II fibrillary astrocytomas. This may affect the differing prognosis of astrocytoma subtypes.

Distribution and presentation

In adults, low-grade gliomas have been more frequently associated with seizure disorder than glioblastoma multiforme, but both can be epileptogenic. Most cases present between the ages of 21 and 40 years, but low-grade gliomas are also a significant cause of epilepsy in children. Seizures are the most common presentation of low-grade glioma, and the low-grade glioma is the most common neoplasm responsible for tumor-related intractable  epilepsy.21

The anatomic distribution of low-grade gliomas in several reports20,40,45,113–115 (not including locations spanning two lobes, such as frontoparietal) was:

  • Frontal—83
  • Temporal—119 (see Figure 1)
  • Parietal—31
  • Occipital—14

In Fried’s study of 65 patients with limbic and neocortical gliomas, 63% of low-grade gliomas were temporal, 18% were occipital, and 11% were frontal.124 These tumors show indolent behavior, with an average 15-year history of seizures. After a 17-year follow-up, only one patient had died from the tumor. Gross total resection gains excellent seizure control, and subtotal resection is the most important factor in the failure to control seizures and tumor recurrence.26,114

Treatment and prognosis

Glioblastoma multiforme, which is less likely than low-grade astrocytomas to produce seizures, primarily affects white matter and deeper structures (see Figure 4). These tumors have greater rapidity of growth associated with destruction of neural elements. In one study, only two of 24 patients became seizure-free after resection.21 Gross total resection does not generally control seizures, and surgery alone may be inadequate treatment of the tumor without adjuvant radiation and chemotherapy.

High-grade gliomas tend to recur. Treatment of recurrences depends on the patient’s clinical status and the anatomic accessibility of the lesion. If the area is surgically accessible, the recurrence is usually addressed with a second resection and adjuvant whole-brain radiation, stereotactic radiosurgery (SRS), or chemotherapy. A second resection can increase survival by an average of 36 weeks, with 28% of patients showing an improvement in the Karnofsky Performance Scale.127 Adjuvant SRS can also improve survival.128 When compared to brachytherapy, median survival data are similar, but SRS offers the advantage of an outpatient procedure versus the need for a 1-week hospital stay for interstitial brachytherapy.129

In children, supratentorial glial tumors tend to be grade I or II. Hirsch and colleagues reported that epilepsy was the presenting symptom in 76% of children who had astrocytomas or oligodendrocytic tumors.113 After tumor resection alone, there was no tumor recurrence in 82% of patients, and 81% of patients were seizure-free. Berger and coworkers reported total seizure relief in 93% of children who underwent resection of the tumor and epileptic focus using electrocorticography (ECog).40

In a separate study comparing postoperative seizure outcome in children versus adults, all 13 pediatric patients became seizure-free and 11 of them were able to discontinue antiepileptic drugs (AEDs). In the adult group, 47% required AEDs to maintain seizure freedom.45 Low-grade glioma in a child has a 10-year survival of 87%.130 Gross total resection of low-grade gliomas is the treatment of choice for children, and adjuvant radiation and chemotherapy are reserved for recurrence. For children, adjuvant whole-brain radiation therapy is not efficacious in preventing recurrence, and it is generally not prescribed because of the risk of cognitive deterioration.130

Although histologically identical to tumors in adults, high-grade gliomas in children tend to have a better prognosis, and survival seems to be based on completeness of resection. In one study of 31 children, those who received a gross total resection had a progression-free survival of 7 years. Progression-free survival was 5 months in those who had only a biopsy, and 11.5 months in those who had a subtotal resection.126 Patients who presented with long-standing symptoms, seizures, and tumors in the cerebral hemispheres had longer survival and better prognosis.

Stereotactic radiosurgery, although not without complications, is a promising therapy that limits radiation exposure to a developing brain. It can be used to surgically treat incurable gliomas in children.78 In a study by Grabb and colleagues, 25 children who underwent surgical resection or biopsy subsequently had SRS for treatment of tumors. Of 13 children with benign gliomas, 11 showed tumor control after SRS, and all 13 were alive at a median follow-up of 21 months. Of 12 children with malignant tumors, 7 died after a median survival of 6 months, and only 3 showed tumor control after SRS.

Adapted from: Mangano FT, McBride AE, and Schneider SJ. Brain tumors and epilepsy. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;175–194.
With permission from Elsevier (www.elsevier.com). 

Authored By: 
Steven C. Schachter MD
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Authored Date: 
03/2004