Spinal Cord Tumors - Management of Intradural Intramedullary Neoplasms

Background

Intradural or primary spinal cord tumors (neoplasms) are uncommon lesions and fortunately affect only a minority of the population. However, when lesions grow, they result in compression of the spinal cord, which can cause limb dysfunction, motor and sensation loss, and, possibly, lead to death. Spinal tumors are classified based on their anatomic location as related to the dura mater (lining around the spinal cord) and spinal cord (medullary) as epidural, intradural extramedullary, or intradural intramedullary. Primary spinal tumors are typically intradural in location, where extradural spinal tumors are typically due to metastatic disease.
This article focuses on the evaluation and management of intradural intramedullary spinal cord tumors. The typical histopathological types that account for 95% of these intramedullary neoplasms include astrocytomas, ependymomas, and hemangioblastomas. Spinal cord astrocytomas and ependymomas can be further classified as glial cell neoplasms. See the image below.

This T1-weighted sagittal MRI is from a 19-year-old man with 4-month history of progressive motor loss and an inability to ambulate. He underwent spinal biopsy that confirmed an intramedullary glioblastoma.

History of the Procedure

In 1887, Sir Victor Horsley performed the first successful resection of an intradural neoplasm diagnosed by William Gower. This lesion was an intradural extramedullary tumor that compressed the spinal cord. However, the patient did not survive the intervention. Due to limited operative techniques, the first successful removal of an intradural intramedullary tumor, performed by Eiselsberg-Renzi, did not occur until 1907.

In 1925, Charles Elsberg published the first large series of patients who underwent resections of primary spinal cord neoplasms. Unfortunately, again because of the limited operative techniques of this period, these patients endured significant surgical morbidity and mortality. However, subsequent advances in imaging, sterile operative techniques, microsurgical dissection, operating microscopy, and neurophysiologic monitoring have facilitated removal of these lesions with substantially improved clinical results.

Problem

Spinal cord parenchyma consists of both gray (neurons and supporting glial cells) and white matter (axonal) and tracts that transmit impulses between the brain and body. These tracts, or circuits, control posture, movement, sensation, and autonomic system function, including bowel, bladder, and sexual function.

Neurologic dysfunction develops as the spinal cord tumors enlarge and compress adjacent healthy neural tissue, disrupting these pathways. Upon further compression, patients can lose complete motor function and sensation below the lesion. In addition to weakness and sensory loss, patients may experience pain, particularly at night. This pain is believed to be related to disturbances in venous outflow by the tumor, causing engorgement and swelling of the spinal cord.

Epidemiology

Frequency

Intramedullary spinal cord tumors account for approximately 2% of adult and 10% of pediatric central nervous system neoplasms. In adults, 85-90% of intramedullary tumors are the glial subtypes, astrocytoma or ependymoma. Ependymomas account for approximately 60-70% of all spinal cord tumors found in adults, while, in children, 55-65% of intramedullary spinal cord tumors are astrocytomas. Hemangioblastomas account for 5% of tumors, whereas paragangliomas, oligodendrogliomas, and gangliogliomas account for the remaining lesions.

Etiology

The pathogenesis of spinal neoplasms is unknown, but most arise from normal cell types in the region of the spinal cord in which they develop. A genetic predisposition is likely, given the higher incidence in certain familial or syndromic groups (neurofibromatosis). Astrocytomas and ependymomas are more common in patients with neurofibromatosis type 2, which is associated with an abnormality on chromosome 22. In addition, spinal hemangioblastomas can develop in 30% of patients with von Hippel-Lindau syndrome, which is associated with an abnormality on chromosome 3.

Pathophysiology

The spinal cord consists of numerous nerve bundles that descend from and ascend to the brain. Electrical impulses are carried and transmitted to facilitate movement and sensation. With intramedullary spinal cord tumors, compression and stretching of these fiber tracts results in loss of the motor and sensory function. As the tumors grow, the patient's neurologic function further deteriorates.

Presentation

Patients with intramedullary glial spinal cord tumors (ie, ependymomas, astrocytomas) typically present with back pain referred from the level of the lesion, sensory changes, or worsening function. The symptoms can be of a long duration, since these lesions tend to grow slowly and typically have a benign histopathology. Patients with low-grade astrocytomas tend to experience symptoms over a mean duration of 41 months. This is in contrast to patients with malignant astrocytomas, whose symptoms persist for a mean duration of only 4-7 months before diagnosis.

Tumor-specific characteristics

Ependymomas are associated with the following:

• Mean age at presentation of 43 years
• Slight female predominance
• Pain localized to the spine (65%)
• Pain worse at night or upon awakening
• Dysesthetic pain (burning pain)
• Long history of symptoms
• Myxopapillary variant (mean age of presentation of 21 y; slight male predominance)

Astrocytomas are associated with the following:

• Equal male and female prevalence
• Pain localized to spine
• Pain worse at night or upon awakening
• Paresthesias (abnormal sensation)

Hemangioblastomas are associated with the following:

• Onset of symptoms by the fourth decade of life, 80% symptomatic by age 40 years
• Familial disorder (ie, von Hippel-Lindau syndrome) present in a third of patients
• Decreased posterior column sensation
• Back pain localized over lesion

Physical examination findings

Sensory findings include the following:

• Decreased touch, pain, and/or temperature sensation
• Hyperesthesias
• Decreased proprioception (inability to localize limbs in space)
• Abnormal sensation below the level of lesion
• Abnormal sensation only at level of lesion (suspended level)

Hyperreflexia findings include the following:

• Hoffman sign for cervical lesions
• Clonus
• Extensor plantar response (Babinski sign)

Other findings include the following:

• Motor weakness (late finding)
• Spasticity
• Increased tone
• Muscle atrophy (late finding)

Indications

Intramedullary spinal cord neoplasms or tumors are typically histopathologically "benign" or slow growing. However, patients can have more aggressive neoplasms as well as morbidity due to the location of the lesion. Consequently, compared with similar intracranial neoplasms, patients may have a prolonged survival after diagnosis.

Optimal treatment options depend on the patient's clinical symptoms and neurologic finding. When and whether to treat these lesions as well as perform radiosurgery or surgical excision of lesions remains controversial. However, cures have been reported only after complete surgical resection. Therefore, patients with neurologic symptoms and confirmatory findings from imaging studies may benefit most from surgical excision, with the surgical goal of total gross resection of the lesion.

Relevant Anatomy

Arterial

Understanding the normal spinal cord vascular supply is essential to treating intramedullary spinal cord lesions; specifically because these vessels may have a variable and inconsistent distribution.

The great vessels (aorta, carotids) contribute arterial supply to the spinal cord via segmental arteries, which further branch into medullary and radicular arteries. The radicular artery provides extramedullary blood supply to the nerve root and dura; the medullary artery bifurcates into anterior and posterior divisions to form the spinal arteries. One anterior and 2 posterior spinal arteries then transverse the longitudinal axis of the spinal cord and provide the blood supply to the spinal cord. Neoplasms acquire their blood supply by leaching blood from these vessels.

Venous

The venous plexus of the spinal column, termed the Batson plexus, is unlike other venous systems in the body because the veins do not contain valves. Therefore, blood can have pathologic retrograde flow. This retrograde flow blood can back up and cause venous congestion. This can manifest as venous hypertension. Because oxygenated blood cannot pass through the spinal cord because of the congestion of outflow, patients present with progressive neurologic dysfunction.

Spinal cord

The spinal cord parenchyma consists of a central canal surrounded by an H-shaped gray matter region that contains neurons. Outer myelinated nerve tracts, termed white matter, surround the central gray matter. The central canal represents an embryologic remnant from neurulation of the neural plate and is lined with ependymal cells. Ependymomas arise from these cells and, therefore, are typically located centrally in the spinal cord parenchyma. In contrast, astrocytes support gray matter neurons and white matter axons. Neoplastic transformation of these supporting cells results in the development of astrocytomas and may occur almost anywhere within the cord.

Contraindications

Observation with serial imaging studies over a variable period is a treatment option for patients who pose a high surgical risk, who are elderly, and/or who only have minimal neurologic signs. Patients in whom pathology tissue shows a malignant neoplasm may be best treated with radiotherapy because they are expected to have an accelerated deterioration and complete surgical resection is not possible.

Spinal Cord Tumors - Management of Intradural Intramedullary Neoplasms Workup

Laboratory Studies

Not diagnostic of tumor pathology and reserved as part of preoperative planning

• CBC count
• Sequential Multiple Analysis-7
• Prothrombin time/activated partial thromboplastin time
• Sequential Multiple Analysis-12 (optional)

Imaging Studies

Plain radiography

See the list below:

• Not accurate for diagnosis
• Abnormalities identified in 20% of patients
• Scalloping of the vertebral bodies on lateral radiographs
• Widening of interpedicular distance on anteroposterior radiographs
• Scoliosis in children that results from neuromuscular impairment

Myelography

See the list below:

• Not optimal because it is invasive and can alter spinal fluid dynamics, causing neurologic worsening
• Nonspecific spinal canal and spinal cord widening
• Multisegmental involvement
• Block of contrast dye
• Conus region lesions, possible meniscus around the tumor

CT scan

See the list below:

• Nonspecific spinal canal and spinal cord widening
• Scalloping of vertebral bodies
• Possible intraparenchymal syringomyelia

MRI of spine with and without gadolinium

This is the criterion standard. See the images below.

This T1-weighted sagittal MRI is from a 19-year-old man with 4-month history of progressive motor loss and an inability to ambulate. He underwent spinal biopsy that confirmed an intramedullary glioblastoma.

This T2-weighted MRI is from a 19-year-old man with 4-month history of progressive motor loss and an inability to ambulate. He underwent spinal biopsy that confirmed an intramedullary glioblastoma.

See the list below:

• Most accurate and noninvasive technique
• Gadolinium (contrast) requires evaluation of kidney function because cases of malignant fibrosis reported
• Enlargement of the spinal cord
• Syringomyelia or cystic cavity associated within the lesion

Ependymoma findings are as follows:

• T1-weighted images - Isointense signal with spinal cord
• T2-weighted images - Hyperintense signal
• Strong homogeneous enhancement with contrast

Astrocytoma findings are as follows:

• T1-weighted images - Isointense or hypointense signal with spinal cord
• T2-weighted images - Hyperintense signal
• Cyst formation
• Heterogeneous enhancement with contrast

Hemangioblastoma findings are as follows:

• T1-weighted images - Isointense signal to spinal cord
• T2-weighted images - Hyperintense signal
• Cystic with tumor nodule (50-70%)
• Enhances strongly with contrast
• Extramedullary extension in 15%

Spinal arteriography

This is beneficial only if a hemangioblastoma is suggested as a differential diagnosis. Hemangioblastoma arteriography findings include a vascular blush with a prominent draining vein.

Other Tests

Baseline urodynamics

Findings may assist in diagnosing abnormal bladder function.

Neurophysiologic testing (EMG/NCS/SSEP)

Findings may quantify degree of neurologic injury from tumor.

Diagnostic Procedures

Lumbar puncture is not indicated unless the patient is being evaluated for drop metastasis or leptomeningeal spread of intracranial disease (as in cranial ependymomas). In addition, lumbar puncture may be useful to differentiate if due to infectious or inflammatory myelitis (multiple sclerosis). However, clinical presentation and imaging studies can typically exclude these etiologies.

Neurological deterioration can be precipitated after lumbar puncture if a complete myelographic block is present from changes in the compliance of the lesion and position of the neoplasm.

Spinal Cord Tumors - Management of Intradural Intramedullary Neoplasms Treatment & Management

Medical Therapy

Pharmacological treatment of intramedullary spinal cord tumors is of limited benefit. High-dose intravenous corticosteroid therapy may improve neurologic function transiently but is not appropriate for long-term treatment. Although steroids decrease vasogenic edema, they do not treat the underlying pathologic condition. Prolonged use of steroids can be associated with gastric ulceration, hyperglycemia, and immunosuppression with cushingoid features.

Chemotherapeutic regimens have limited success in the treatment of spinal cord neoplasms. This may be partly due to the inability of the chemotactic agents to cross the blood-brain barrier.

Standard fractionated radiation is used for astrocytomas of residual and recurrent neoplasm.

Stereotactic spinal radiosurgery may be helpful for treating these lesions. Although similar symptomatic control may be achieved over the short term when compared with surgical resection, recurrence and malignant tumor transformation have been observed after radiotherapy. This treatment may be most effective in dealing with malignant lesions only. In the future, stereotactic or intensity-modulated radiosurgery may play larger role in treatment options available for patients. Because of the precision with which the radiation is delivered, radiosurgery helps to minimize spinal cord radiation toxicity and/or necrosis. Recent research has confirmed that the spinal cord is generally tolerant to the doses of radiation normally used in these procedures. 

Surgical Therapy

Patients presenting with neurologic deficits and mass lesions in the spinal cord require histopathology in order to define the neoplasm such that treatment options can be maximized. The surgical approach to these lesions typically consists of preparing for gross total resection. The neoplasm is identified and then biopsy is performed. Surgery then proceeds based on the histology from the frozen specimen as well as the ability to define a surgical plane to resect the lesion. If the lesion is an astrocytoma, then the goal is debulking the tumor while not injuring the normal neural tracts. Ependymomas are attempted to be resected completely as long as a viable plane can be established and normal neural tracts are not disturbed. 

Preoperative Details

Any patient suspected of having an intrinsic spinal cord neoplasm should undergo a detailed history and physical examination. The preoperative evaluation should consist of a detailed neurologic examination and appropriate imaging studies to confirm the diagnosis. Detailed imaging studies should consist of MRI with and without gadolinium. If MRI is not available, myelography with CT scanning should be used. If appropriate, obtain a preoperative medical evaluation.

Intraoperative Details

Surgical resection is performed with the patient under general anesthesia, typically in a prone position. Intraoperative neurophysiological monitoring provides real-time feedback regarding possible ischemia or retraction injury to the spinal cord during the resection and is used by some surgeons.

A laminectomy (laminoplasty in children) is performed after radiographic confirmation of the appropriate spinal level. The laminectomy defect should be of sufficient size to allow visualization of healthy spinal cord above and below the suspected neoplasm.

Some patients have a kyphosis (curve) or straightening of the spine and removing the laminae can cause further progression of this curve. Therefore, some surgeons opt to fuse (arthrodesis) the spine over the area the laminectomy is performed to prevent it from bending forward further.

The dura mater is exposed at the correct levels. An intraoperative ultrasound study can be used to confirm adequate bony decompression and the lesion is center prior to the dural opening. Intraoperative ultrasound can also reveal the extent of the lesion and the degree of resection. Some surgeons are now using more advanced techniques to determine the margins of the tumor, such as inserting an intravenous dye that localizes to the tumor margins and can be visualized on a video camera.  The dura mater is incised or opened in the midline and then secured laterally to maintain the exposure.

Using the intraoperative microscope or magnification, the spinal cord is inspected and the pia mater is opened directly over the tumor exposing the spinal cord. The spinal cord is incised sharply typically through the midline raphe. Once the tumor is exposed, a plane is established at the periphery.

A biopsy specimen is obtained from the center of the lesion and sent for histopathological analysis. If pathologic evaluation confirms a low-grade neoplasm, the median exposure is opened until the full extent of the intraparenchymal lesion can be visualized. The dissection plane is further developed between the tumor and the normal spinal cord parenchyma. Often, cystic cavities help define the caudal and rostral margins of the tumor. Ependymomas tend to be encapsulated, brownish-red, sausage-shaped masses, whereas astrocytomas are ill-defined, whitish enlargements with associated cysts.

The goal for benign or low-grade neoplasms is gross total resection. Once the tumor-spinal cord interface is defined, the tumor can be debulked internally with gentle dissection or an ultrasonic cavitation to reduce spinal cord manipulation. Complete resection of benign neoplasms cannot always be achieved without neurological injury, particularly if the tumor–spinal cord interface is indistinct.

Patients with biopsy-proven high-grade lesions typically have a rapid progression in neurological dysfunction, even after aggressive resections. Consequently, only biopsy and a dural patch graft (to enlarge the space for the spinal cord) may be an alternate approach to attempted resection. When surgical resection is completed, the dura and muscles are closed in layers.

Postoperative Details

Patients are closely monitored in an ICU setting to monitor their neurologic examination and acutely detect and neurologic deterioration. Incisional pain should be minimal and should be relieved with intravenous analgesics. Patients typically have some degree of posterior column dysfunction due to traction and manipulation during surgery. This usually is in the form of "numbness" below the region of resection as well as proprioception difficulty. The proprioception difficulties can be disabling for the patients because they impair ambulation and fine motor control. These deficits tend to progressively improve with time. In Brotchi's series of 239 patients with low-grade spinal tumors, 5% of patients worsened, 50% of patients stabilized, and 40% of patients improved after surgical intervention.  Overall, patients typically maintained their preoperative level of function postoperatively.

Depending on the needs of patients, they are either discharged home or transferred to a rehabilitation facility.

Follow-up

Follow-up care should include serial neurologic examinations and MRI to monitor for recurrence or progressive growth of residual tumor. If patients experience any neurologic worsening, perform contrast-enhanced MRI. The recurrence rate for low-grade tumors is less than 5%; approximately 10% of patients have progression of residual tumor.

Consider radiotherapy or stereotactic radiosurgery for the treatment of malignant neoplasms. Its role in benign neoplasms is unclear, but, typically, serial observation is recommended.

Complications

See the list below:

• Bladder and bowel dysfunction
• Bleeding or hematoma
• Cerebrospinal fluid leak
• Chronic pain
• Injury to central nervous system tissue
• Meningitis
• Paralysis
• Sensory loss
• Sexual dysfunction
• Skin infection or cellulitis
• Spine instability
• Ventilator dependence and death
• Wound dehiscence

Outcome and Prognosis

The 5-year survival rate for patients with benign or low-grade spinal cord neoplasms is greater than 90%. In Brotchi's series of 239 patients with low-grade spinal tumors and operative intervention, 5% worsened, 50% stabilized, and 40% improved.  In the series by Karikari et al, the patients with ependymomas, the more common and less aggressive tumor, had a tumor recurrence rate of 7%. Patients with astrocytoma, the more aggressive and less common tumor type, had a recurrence rate of 48%. A patient's neurologic function after surgical intervention directly depended on his or her preoperative neurological status. Therefore, the goal of surgical treatment is to prevent further neurologic dysfunction from compression by the neoplasm, to obtain a diagnosis, and to potentially cure the neoplastic condition with a complete resection.

A patient's overall prognosis depends on the neoplasm's histopathology. This is the most important predictor of patient outcome because it predicts if the tumor will be resectable and if it will recur.

Future and Controversies

Intraoperative microscopy, neurophysiologic monitoring, and improved neuroimaging have improved the success of surgical intervention. Further advances in technology for tumor resection and neuroimaging may lead to further improvements in surgical outcomes. Better understanding of the genetics of these neoplasms may provide for earlier medical intervention with improved care and treatment of these disorders.

Radiosurgical techniques, specifically the use of stereotactic radiosurgery or IMRT, are improving such that these options will have an increased role in the treatment of benign disease and more aggressive neoplasms. The difficulty with this modality is that a histologic diagnosis should be obtained prior to deciding on treatment. Also, because this is a new technique, further research into the safety and efficacy of the procedure is needed before it becomes a standard of care. The promise of this technique is in its noninvasiveness compared with open surgery.

Other minimally invasive surgical techniques are currently being developed. One involves a "mini-open" procedure that uses a smaller surgical incision, and another uses a minimally invasive retractor system to limit spinal cord manipulation during surgery. The aim of these techniques is to reduce hospitalization time and complications such as infection.