Herbert B. Newton, MD, FAAN
Jacob J. Mandel, MD
DESCRIPTION 
Spinal ependymomas (EPN) are intradural tumors that arise from the ependymal lining cells of the central canal of the spinal cord, affecting patients of all ages. They occur most often in the extramedullary portions of the lumbar spine (60%; cauda equina and filum terminale). In 40% of patients, the tumor is intramedullary and develops within the spinal cord parenchyma. The cervical and upper thoracic cord are the most common (65 to 70%) locations for intramedullary EPN. Most EPN are low grade, with less infiltrative capacity than astrocytic tumors. At diagnosis, most EPN span 1 to 2 spinal cord segments.
EPIDEMIOLOGY
Incidence/Prevalence
Spinal cord tumors (SCT) are relatively uncommon, representing only 0.5% of newly diagnosed tumors in adults. Spinal EPN comprise 12 to 15% of all primary SCT, approximately 50 to 60% of all intramedullary SCT, and 30 to 35% of all CNS EPN. They are less common in children, comprising 12 to 15% of all pediatric SCT.
RISK FACTORS
Risk factors for spinal EPN remain unclear, but may be similar to EPN of the intracranial cavity; these include spinal radiation (≥10 Gy), and Neurofibromatosis type 2 (NF2).
Genetics
EPN of the spinal cord are usually sporadic tumors, but can occur in association with NF2.
PATHOPHYSIOLOGY/ETIOLOGY
- Spinal cord EPN are mainly low-grade and although they are not encapsulated, they are typically well demarcated from surrounding neural tissues. Infiltration of spinal cord or nerve roots is uncommon. Histological features include moderate cellularity, monotonous nuclear morphology, ependymal rosettes, perivascular pseudorosettes, rare or absent mitoses, and very infrequent areas of necrosis. Foci of calcification, hemorrhage, and myxoid degeneration may be noted. High-grade tumors are more cellular and have frequent nuclear atypia, mitoses, and regions of necrosis.
- Cytogenetic studies reveal frequent abnormalities of chromosome 22 (30%), including monosomy, deletions, and translocations. Mutations in the MEN1 gene (located at 11q13) are found most often in tumors that do not demonstrate chromosome 22 abnormalities. Less common abnormalities affect chromosomes 9q, 10, 17p, and 13; molecular studies suggest that amplification of oncogenes (e.g., MDM2) and mutation of tumor suppressor genes (e.g., NF-2) are involved in transformation of EPN.
Pregnancy Considerations
Pregnancy does not affect the clinical behavior of spinal EPN.
[Outline]
HISTORY
Spinal cord EPN are usually slow growing tumors, with an insidious onset of symptoms. The time to diagnosis is typically prolonged (i.e., 3 to 5 years). The presentation will vary with tumor location, rate of growth, and amount of edema and compression of regional neural structures. Tumors that arise in the lumbar region typically present with low-back pain, with or without sciatica, lower extremity sensory dysfunction (e.g., numbness, paresthesias), bowel and bladder incontinence, and lower extremity weakness. Intramedullary EPN have a different presentation, with milder, more diffuse back pain, sensory complaints that usually manifest as dysesthesias, and less severe lower extremity weakness and bowel and bladder dysfunction.
PHYSICAL EXAM
The most common neurological sign is mild lower extremity weakness. Intramedullary tumors develop weakness as a late sign and have an upper motor neuron pattern (i.e., spasticity, hyperactive reflexes, Babinski sign); extramedullary tumors develop weakness earlier and have a lower motor neuron pattern (i.e., flaccidity, hypoactive or absent reflexes, flexor plantar responses). Other frequent signs include sensory loss, sphincter dysfunction, gait disturbance, and loss of abdominal reflexes.
DIAGNOSTIC TESTS AND INTERPRETATION
Lab
Initial Lab Tests
Cerebrospinal fluid analysis and evaluation of cytology are diagnostic (in addition to cranial and/or spinal MRI) for those rare spinal EPN (high-grade, myxopapillary) that disseminate to the leptomeninges.
Imaging
Initial Approach
MRI, with and without gadolinium contrast, is the most critical diagnostic test. Axial, coronal, and midsagittal enhanced images should be obtained; MRI is more sensitive than CT for intramedullary and extramedullary SCT. On T1 images, the tumor is usually hypointense or isointense compared to normal spinal cord and causes a well-demarcated, multi-segmental enlargement of the cord or a mass in the cauda equine. On T2 images the mass is hyperintense; spinal EPN have mild to moderate enhancement after administration of gadolinium. Regions of cyst occur frequently in intramedullary EPN (50 to 55%; even cranial–caudal distribution). Peritumoral edema may be noted. CT demonstrates a hypodense enlargement of the spinal cord or a mass in the lumbar region with mild enhancement and edema.
Diagnostic Procedures/Other
Intraoperative neurophysiological monitoring with evoked potentials may be helpful during surgical resection to maximize tumor removal and minimize neurological morbidity. Ultrasound may be helpful for the surgeon to accurately localize the tumor before myelotomy and resection.
Pathological Findings
The World Health Organization (WHO) classifies EPN of the spinal cord similar to those of the brain. Sub-EPN and myxopapillary tumors are classified as WHO grade I and myxopapillary are the most common type of EPN to arise in the cauda equina and filum terminale, typical EPN are classified as WHO grade II, anaplastic or malignant EPN correspond to WHO grade III.
DIFFERENTIAL DIAGNOSIS
Includes other intramedullary and extramedullary enhancing spinal masses such as astrocytoma, metastasis, and abscess; other disorders which can have a similar neurological presentation are syringomyelia, multiple sclerosis, transverse myelitis, herniated disk, and vitamin B12 deficiency.
[Outline]
MEDICATION
First Line
- Dexamethasone (2 to 8 mg/day) may be of benefit to reduce spinal cord edema and often improves pain. It may also relieve transient symptoms of pressure and swelling after surgery or radiation therapy (RT). All patients should be on an H2 blocking drug while receiving chronic dexamethasone.
- Narcotic analgesics may be necessary to control severe pain prior to surgery and/or RT.
Second Line
Chemotherapy has a limited role in the treatment of spinal EPN. It should be considered for patients with incompletely resected tumors and tumors that progress despite RT. Drugs to consider only have modest activity and are the same as those used for EPN of the brain. They include temozolomide, procarbazine, lomustine (CCNU), vincristine, etoposide, cyclophosphamide, cisplatin, and carboplatin. Imatinib has also been reported to have a minor response in a spinal EPN that expressed the platelet-derived growth factor receptors.
ADDITIONAL TREATMENT
General Measures
RT should not be considered for spinal EPN of low-grade that have undergone a complete resection. Similarly, RT should be held in patients with extensive sub-total resection until evidence of tumor progression. All patients with high-grade histology will require involved field RT; the recommended doses are 45 to 50 Gy over 6 weeks using 180 to 200 cGy/day fractions. Patients with high-grade tumors that disseminate to the neuraxis may benefit from palliative RT.
Issues for Referral
May require physical and/or occupational therapy depending on location of tumor and patients amount of weakness.
SURGERY/OTHER PROCEDURES
Surgical resection with gross-total removal is the treatment of choice for all spinal EPN. Even intramedullary tumors can be totally removed in most cases, since a clear cleavage plane is often present. Infiltrative low-grade and all high-grade intramedullary tumors will only allow a sub-total resection. Some myxopapillary EPN of the lumbar region cannot be totally excised due to adherence to, or envelopment of, surrounding nerve roots and vascular structures. Ideal surgical candidates have intact or almost normal gait and neurological function.
IN-PATIENT CONSIDERATIONS
Initial Stabilization
Consists of corticosteroids to control symptoms of spinal cord edema and pain control caused by compression of nerve roots, spinal meninges and other neurovascular structures.
Admission Criteria
Admission is generally reserved for pre-surgical evaluation and resection. Patients can be admitted with progressive spinal neurological dysfunction from tumor growth. Intravenous dexamethasone may be helpful to reduce spinal cord edema and control pain. New treatments may be necessary (e.g., RT, chemotherapy).
Discharge Criteria
Stabilization of the patient and sufficient pain control following surgery will be required before discharge.
[Outline]
FOLLOW-UP RECOMMENDATIONS
Patients are followed with serial MRI scans and assessment of neurological function every 6 to 12 months.
Patient Monitoring
Patients on chemotherapy may require more frequent assessments as well as monitoring of complete blood counts, liver function, and metabolic panel.
PROGNOSIS
- The 5- and 10-year survival rates for patients with low-grade spinal EPN after complete resection (without RT) are 75 to 90% and 65 to 70%, respectively. After incomplete removal plus RT, the survival is lower. The prognosis for patients with high-grade EPN is poor, with typical overall survival ranging from 12 to 18 months.
- The most important prognostic factor is degree of surgical resection. Factors that improve the prognosis for survival and quality of life are complete surgical resection, relatively intact neurological function before and after surgery, and typical low-grade histology. Factors that worsen the prognosis include incomplete removal of tumor, high-grade histology, significant neurological dysfunction with poor performance status, and tumor location within the conus medullaris.
COMPLICATIONS
Pain and neurological deficits, including sensory loss and/or weakness, are possible complications following surgery.
[Outline]
