Orthopedics

Metastatic Epidural Spinal Cord Compression

Andreas F. Mavrogenis, MD; Spyridon Pneumaticos, MD; George S. Sapkas, MD; Panayiotis J. Papagelopoulos, MD, DSc

Abstract

The epidural space is the most common site of metastases producing injury to the spinal cord.1-4 The incidence is 5% to 10% and up to 40% in patients with pre-existing nonspinal bone metastases. Intramedullary, intradural, or leptomeningeal metastases are a much less frequent cause.1-4

The primary tumors accounting for 15% to 20% of all cases of metastatic epidural spinal cord compression are prostate, breast, and lung cancer.5-7 Non-Hodgkin’s lymphoma, renal cell cancer, and multiple myeloma account for 5% to 10%; the remaining cases are due to gastrointestinal carcinomas, sarcomas, and unknown primary tumors.2,3,8,9 In children, the most common tumors that may cause metastatic epidural spinal cord compression are sarcomas (particularly Ewing’s sarcoma), neuroblastomas, germ cell tumors, and Hodgkin’s disease.2,3,10

Approximately 10% to 15% of metastatic epidural spinal cord compression occurs in the cervical spine, 60% to 70% in the thoracic spine, and 20% to 25% in the lumbosacral spine.8 Multiple lesions are reported to occur in 17% to 30% of patients.2,11

In more than 85% of patients with metastatic epidural spinal cord compression the tumor reaches the spinal cord and spreads to the epidural spread by an initial hematogenous metastasis to the vertebral body through the Batson plexus or through arterial seeding and embolization.12,13 Less commonly, epidural extension occurs from direct growth of a paravertebral tumor such as lymphomas and neuroblastomas into the spinal canal through an intervertebral foramen; rarely, tumors may metastasize directly to the epidural space.14 After the metastatic cells expand into the medullary cavity of the vertebra, they escape into the spinal canal by traveling within basivertebral veins or other penetrating vessels. Acute metastatic epidural spinal cord compression occurs when there is direct cortical bone destruction that causes vertebral body collapse and displacement of bone fragments into the epidural space and extradural mass formation.12

Compression damages the cord by demyelination and axonal damage, and secondary vascular compromise. Stenosis and occlusion of the epidural venous plexus results in vasogenic edema. At this stage, the edema and associated neurological dysfunction can be partially or completely reversed by corticosteroid administration. In late stages of compression, arterial blood flow to the spinal cord is impaired, which causes cord ischemia by increased synthesis of prostaglandin E2, interleukin-1 and 6 and serotonin, and, eventually, infarction and irreversible damage.4,12,15

Metastatic epidural spinal cord compression is the first manifestation of cancer in approximately 20% of patients. This is particularly true for lung cancer, where 30% of metastatic epidural spinal cord compression occurs in patients without a prior diagnosis. Patients with prostate and breast cancer are less likely to develop metastatic epidural spinal cord compression as the initial manifestation of the tumor.2,3,8,9

Before diagnosis, 83% to 95% of patients experience back or neck pain, which often is referred, obscuring the site of compression. Metastatic epidural spinal pain is caused when the enlarging mass invades the periosteum, paravertebral soft tissues, or nerves, and also by the mass effect of the spinal cord compression, spinal instability, pathological fracture, and the inflammatory and nociceptor stimulating substances that malignant cells secrete. Pain is usually absent with intradural and intramedullary metastases.8 Back or neck pain usually occurs at an average of 7 weeks before other neurological deficits.4,8,9,16 Pain may be unilateral or bilateral, it is localized to the region of the spine affected by the metastases, is worse at night and when the patient is recumbent due to lengthening of the spine and distension of the spinal epidural venous plexus, and progressively increases in intensity over time.4

Radicular pain due to compression or invasion of the nerve roots is less common than back pain; it may radiate unilaterally or bilaterally to…

The epidural space is the most common site of metastases producing injury to the spinal cord.1-4 The incidence is 5% to 10% and up to 40% in patients with pre-existing nonspinal bone metastases. Intramedullary, intradural, or leptomeningeal metastases are a much less frequent cause.1-4

The primary tumors accounting for 15% to 20% of all cases of metastatic epidural spinal cord compression are prostate, breast, and lung cancer.5-7 Non-Hodgkin’s lymphoma, renal cell cancer, and multiple myeloma account for 5% to 10%; the remaining cases are due to gastrointestinal carcinomas, sarcomas, and unknown primary tumors.2,3,8,9 In children, the most common tumors that may cause metastatic epidural spinal cord compression are sarcomas (particularly Ewing’s sarcoma), neuroblastomas, germ cell tumors, and Hodgkin’s disease.2,3,10

Approximately 10% to 15% of metastatic epidural spinal cord compression occurs in the cervical spine, 60% to 70% in the thoracic spine, and 20% to 25% in the lumbosacral spine.8 Multiple lesions are reported to occur in 17% to 30% of patients.2,11

Pathophysiology

In more than 85% of patients with metastatic epidural spinal cord compression the tumor reaches the spinal cord and spreads to the epidural spread by an initial hematogenous metastasis to the vertebral body through the Batson plexus or through arterial seeding and embolization.12,13 Less commonly, epidural extension occurs from direct growth of a paravertebral tumor such as lymphomas and neuroblastomas into the spinal canal through an intervertebral foramen; rarely, tumors may metastasize directly to the epidural space.14 After the metastatic cells expand into the medullary cavity of the vertebra, they escape into the spinal canal by traveling within basivertebral veins or other penetrating vessels. Acute metastatic epidural spinal cord compression occurs when there is direct cortical bone destruction that causes vertebral body collapse and displacement of bone fragments into the epidural space and extradural mass formation.12

Compression damages the cord by demyelination and axonal damage, and secondary vascular compromise. Stenosis and occlusion of the epidural venous plexus results in vasogenic edema. At this stage, the edema and associated neurological dysfunction can be partially or completely reversed by corticosteroid administration. In late stages of compression, arterial blood flow to the spinal cord is impaired, which causes cord ischemia by increased synthesis of prostaglandin E2, interleukin-1 and 6 and serotonin, and, eventually, infarction and irreversible damage.4,12,15

Clinical Presentation

Metastatic epidural spinal cord compression is the first manifestation of cancer in approximately 20% of patients. This is particularly true for lung cancer, where 30% of metastatic epidural spinal cord compression occurs in patients without a prior diagnosis. Patients with prostate and breast cancer are less likely to develop metastatic epidural spinal cord compression as the initial manifestation of the tumor.2,3,8,9

Before diagnosis, 83% to 95% of patients experience back or neck pain, which often is referred, obscuring the site of compression. Metastatic epidural spinal pain is caused when the enlarging mass invades the periosteum, paravertebral soft tissues, or nerves, and also by the mass effect of the spinal cord compression, spinal instability, pathological fracture, and the inflammatory and nociceptor stimulating substances that malignant cells secrete. Pain is usually absent with intradural and intramedullary metastases.8 Back or neck pain usually occurs at an average of 7 weeks before other neurological deficits.4,8,9,16 Pain may be unilateral or bilateral, it is localized to the region of the spine affected by the metastases, is worse at night and when the patient is recumbent due to lengthening of the spine and distension of the spinal epidural venous plexus, and progressively increases in intensity over time.4

Radicular pain due to compression or invasion of the nerve roots is less common than back pain; it may radiate unilaterally or bilaterally to upper or lower limbs (in cervical or lumbar lesions) or bilaterally around the chest or upper abdomen (in thoracic lesions). At the stage of radicular pain, depression of tendon reflexes, weakness, and sensory changes may be found in the distribution of the roots injured by epidural metastases. Mechanical back pain is associated with spinal instability caused by vertebral body collapse and is relatively uncommon; it is made worse by movement and partially relieved by rest.3,17

Symptoms and signs of spinal cord dysfunction such as weakness, sensory disturbances, and bowel and bladder disorders, typically follow the onset of pain.3 Weakness secondary to motor deficits occurs in 60% to 85% of patients at diagnosis. The magnitude of the motor deficits depend on the location of the epidural spinal cord compression; as the thoracic cord is the most common site of epidural metastases weakness and usually involves the lower limbs causing gait disorders.8 Weakness can progress to paraplegia; approximately 50% to 68% of patients are unable to walk at diagnosis of metastatic epidural spinal cord compression. Pyramidal signs such as hyperreflexia, spasticity, Babinski sign, and clonus can be found.18 Lesions at the level of the conus medullaris (L1-L2) usually result in flaccid paresis and early sphincter involvement, while lesions below this level (cauda equina) usually result in asymmetric sensory and motor impairment of peripheral type, with absent hyporeflexia and pyramidal signs.3

Less common clinical findings at presentation include sensory deficits, ataxia of gait, autonomic symptoms such as urinary retention or constipation, and systemic manifestations.4,8 Loss of sensation typically begins distally in the toes and ascends in a stocking distribution as the disease advances, eventually reaching 1 to 5 segments below the anatomic level of cord compression. Early signs of decreased vibration and position sense can gradually progress to pain and temperature loss.8,14 Sphincter disturbances including impotence, bowel and bladder disorders with lumbar compression, and Horner’s syndrome with cervical or upper thoracic compression are associated with a poor prognosis.3,4,8,14 The most serious systemic manifestations of metastatic epidural spinal cord compression are respiratory depression with upper cervical compression that may require ventilation assistance, and hypotension that is mainly orthostatic and may become symptomatic.19

Diagnosis

New onset of back or neck pain in cancer patients should be evaluated to rule out metastatic epidural spinal cord compression. A detailed medical history and physical examination are the first steps prior to adequate imaging studies.20,21 Vertebral abnormalities such as pedicle erosion, vertebral collapse, and bone dislocation are seen in radiographs in 70% to 80% of patients with metastatic epidural spinal cord compression. However, radiographs of the spine have insufficient sensitivity or specificity and a 10% to 17% false-negative rate for diagnosis of metastatic epidural spinal cord compression.20,21 At least a 50% erosion of bone must be present for a change to be seen on a plain radiograph; in this case, the likelihood of epidural tumor is 87%.14 The disk space, in contrast to infectious causes of vertebral collapse, usually remains intact.3

Before the widespread availability of magnetic resonance imaging (MRI), diagnosis by myelography was the gold standard. However, for many patients, coagulopathies, brain masses, or thrombocytopenia precluded myelography. Additionally, myelography has the rare risk of causing pressure shifts leading to neurological decline if a complete subarachnoid spinal block is present, and a 15% risk of exacerbating an existing neurological deficit. In addition, the presence of a spinal subarachnoid block prevents visualization of the entire thecal sac.2,22,23

Magnetic resonance imaging is the imaging modality of choice for screening and diagnosis of metastatic epidural spinal cord compression. Magnetic resonance imaging is superior to myelography in demonstrating the extent of epidural metastases, multiple epidural metastases, and the extent of the neoplastic tissues around the spine (Figure 1). With a sensitivity of 93% and specificity of 97%, MRI of the whole spine is recommended if spinal cord compression is suspected.24 In approximately 50% of patients, the MRI information changes the radiation plan and can therefore affect treatment.25,26

Figure 1A: Radiation therapy was administered
Figure 1B: Postoperatively, the patient had complete neurological recovery

Figure 1: A 50-year-old man with renal cell carcinoma and incomplete paraplegia (Frankel scale: C). Sagittal T1-weighted (left) and T2-weighted (right) MRIs of the thoracic spine show T5 metastatic epidural spinal cord compression and a second lesion at the T10 vertebra. Radiation therapy was administered (A). Preoperative embolization was performed through selective catheterization of the left fifth intercostal artery using Gelfoam (300-500 µm). Through the posterior approach, extensive T5 laminectomy, partial T5 corpectomy, and T3-T7 posterolateral fusion were performed using transpedicular screws and rods. Postoperatively, the patient had complete neurological recovery (Frankel scale: E) (B).

Nuclear scintigraphy provides an overall survey of the skeletal system and is sensitive for the diagnosis of bone metastases. Bone scan is more sensitive but less specific than radiographs in detecting metastatic epidural spinal cord compression.27 It has been reported that if both radiographs and bone scans are negative in cancer patients with spinal symptoms, the risk of epidural spinal cord compression is only 2%.28 Positron emission tomography scanning is increasingly being used as a tool for whole body metastatic survey or as a staging tool for some types of cancer.29 However, the resolution of the currently available techniques is too poor to be used for diagnosis or direct treatment of metastatic epidural spinal cord compression.4,30

In cancer patients the differential diagnosis of metastatic epidural spinal cord compression should include radiotherapy-induced myelopathy, chemotherapy-induced peripheral neuropathy, primary tumors of the spinal cord, abscesses, hematomas, vertebral collapse or lipomas induced by steroids, foci of extramedullary hematopoiesis, steroid myopathy, and intramedullary or leptomeningeal metastases that are approximately 50-fold less frequent than the epidural seeds.1,15,17

Prognosis

The median expected survival time from diagnosis ranges from 3 to 6 months.31,32 Factors associated with longer survival include the pre-treatment motor function of the patient, the slow onset of motor deficits, radiosensitive tumor histologies such as multiple myeloma, germ-cell tumors, lymphomas, or small-cell carcinomas, no visceral or brain metastases, and a single site of epidural cord compression.4,19,33-35 Patients with breast carcinoma have the longest survival, patients with lung cancer have the shortest survival, and patients with prostatic carcinoma have an intermediate expected length of survival. However, ambulatory patients, either at presentation or after therapy have a significantly longer survival when compared to nonambulatory patients.19,32

Once a neurological deficit appears, most patients do not recover; they usually progress to paraplegia over a 48-hour period (22% of patients) or within 7 to 10 days (65% of patients). Only 16% of patients who were nonambulant pre-treatment became ambulant following radiation therapy. The prognosis is poor for patients who show rapid deterioration of motor function in the 48 hours preceding radiation therapy.1,31 The systemic spread of the neoplastic disease is also related to survival; the presence of multiple epidural spinal metastases and/or bladder and bowel dysfunction has been associated with a poorer survival.11

Treatment

Corticosteroids, analgesics and supportive measures, radiation therapy, and surgery are the modalities available to treat metastatic epidural spinal cord compression; for selected tumors chemotherapy and hormones also have a role. Functional outlook is related to the degree of neurological involvement at diagnosis and treatment should be undertaken without delay. A multidisciplinary team approach by a neurologist, radiologist, oncologist, orthopedic surgeon, and neurosurgeon is necessary.16 The goals of treatment are the ability to walk, pain relief, spinal stability, and increased length of survival.

Corticosteroids

Prompt administration of corticosteroids is a standard option if symptomatic spinal cord compression is confirmed or strongly suspected clinically. Corticosteroids reduce edema, prevent neurological deterioration in the short term, and could have an analgesic and an oncolytic effect on leukemia, lymphomas, and, sometimes, breast cancer. Dexamethasone is the most commonly used corticosteroid, although methylprednisolone has also been used. Dexamethasone inhibits prostaglandin E2 and vascular endothelial growth factor production and activity, and therefore decreases vasogenic edema.1,16,36-38

The general consensus is that corticosteroids are beneficial. Studies in humans with metastatic epidural spinal cord compression have shown a positive effect; 81% of patients treated with dexamethasone were ambulatory post-treatment compared to 63% of patients receiving radiation therapy only. However, they failed to establish the optimum loading and maintenance doses of corticosteroids. Currently, dexamethasone is administered into high dose (100 mg loading dose, then 96 mg/day) in patients who cannot walk at diagnosis or have rapidly progressive motor symptoms, or moderate dose (10 mg loading dose, then 16 mg/day) in ambulatory patients who have minimum or non-progressive motor findings.4 To avoid side effects, steroid administration must be tapered during or after radiation therapy, depending on neurological symptoms.3,16

Analgesics and Supportive Measures

Pain must be addressed early and aggressively. Although some patients benefit from nonsteroidal anti-inflammatory drugs, most require opioids delivered through a patient-controlled analgesia device for satisfactory pain relief.2,14,30 Nonsteroidal anti-inflammatory drugs are safest for younger patients who have no history of gastrointestinal bleeding and normal renal function, and for patients who poorly tolerate opioid-induced adverse effects. If neuropathic pain is present, a combination of analgesics (mainly narcotics) and adjuvants for neuropathic pain such as amitriptyline, gabapentin, and pregabalin are suitable.3,39,40 To minimize sedation, these agents should be started at a low dose and titrated to effect. Tricyclic antidepressant agents, which putatively act via a different mechanism than anticonvulsant agents, can be used at bedtime because most induce sedation.40

Bisphosphonates such as zoledronic acid and pamidronate may be a useful adjunctive measure for neuropathic and bone pain. Zoledronic acid, a third generation bisphosphonate, given intravenously every 3 weeks significantly reduced skeletal-related events compared to placebo.41 Bisphosphonates may also decrease the risk of metastatic epidural spinal cord compression in some patients who are expected to survive for a long time, although this has not been proven conclusively.42

Constipation due to autonomic dysfunction, inactivity, or opioids should be treated by a stool softener, a stimulant and an osmotic laxative, or by a regimen of polyethylene glycol and a daily stimulant, suppository for patients with diminished sphincter control.14 Despite no specific studies on preventing venous thromboembolism in patients with metastatic epidural spinal cord compression, prophylactic anticoagulation with subcutaneous heparin, low-molecular-weight heparin, or, at a minimum, sequential compression devices, is reasonable given the hypercoagulable state of cancer patients.2,14,30 Physical therapy will not diminish the pain related to tumor or pathological fracture and may accentuate fracture pain, so it should not be used before radiation or surgery. Spinal braces are principally needed for those with spinal instability. Braces, however, may improve comfort by providing external support.16

Radiation Therapy

External beam radiotherapy has been the standard treatment for metastatic epidural spinal cord compression.8,34,43,44 Indications for radiation therapy include patients with radiosensitive tumors, ambulatory at diagnosis, expected survival of less than 3 to 4 months, total neurological deficit below the level of compression for more than 24 to 48 hours, and multilevel or diffuse spinal involvement.8,34,36,43,44 Results are excellent in patients with radiosensitive tumors such as lymphoma, Ewing’s sarcoma, neuroblastoma, myeloma, good in patients with breast, prostate or small-cell lung cancer, and usually poor in patients with renal cell carcinoma and melanoma.3,45

Radiation therapy alone completely relieves or improves pain in nearly 75% of patients.45 Additionally, for patients who only have pain, the overwhelming majority do not become paraplegic after radiation, and most remain ambulatory for the remainder of their lives.31 Compared to laminectomy, radiation therapy alone has shown similar or superior results, although limited comparison has been made with more complex surgical techniques such as posterior, lateral, or anterior decompression plus stabilization of the spine.46 Prospective observational studies have shown a significantly better outcome and a 60% to 90% of pain relief and maintenance of ambulation with radiation therapy and dexamethasone.19,45

The standard radiation volume should include the site of cord compression and should extend 2 vertebral bodies above and below. Paravertebral tumor masses should be included in the radiation volume whenever possible.1,3 Standard external beam radiation therapy usually consists of 30 Gy in 10 fractions; regimens of >30 Gy do not improve outcomes. However, treatment regimens can be more prolonged (25-40 Gy in 10-20 fractions over 2-4 weeks) in patients with long expected survival, shorter (4 Gy/d for 7 days), or much shorter (8 Gy once or 4 Gy for 5 sessions, or 8 Gy for 2 sessions 1 week apart) in patients with short expected survival.1,4,14,47,48 However, the high daily doses might be more toxic and less effective for the treatment of acute compression and prevention of recurrence, and patients develop more in-field recurrences, less bone recalcification, and shortened survival compared with patients receiving longer courses.48-50 Higher doses, such as 40 Gy in 20 fractions may be considered in patients with a long history of stable metastatic disease.46

Myelosuppression can occur if multiple spinal sites are treated. Dosing schedules are designed to have a <5% chance of inducing radiation myelopathy.19,48 Radiation-induced myelopathy rarely develops within a median latency of 1 to 2 years. Therefore, for patients likely to survive <1 year, the benefits of reirradiation likely exceed the risks.51,52

The median survival for patients undergoing radiation therapy for metastatic epidural spinal cord compression is approximately 6 months with a 28% probability of 1-year survival.45 The local recurrence rate for metastatic epidural spinal cord compression after successful radiation therapy of the initial compression is 7% to 14%, and this risk directly relates to length of survival.24,53 The site of recurrence might be outside the area of the original radiation field; in these cases, the choices for treatment are the same as those for the original episode of metastatic epidural spinal cord compression. However, if the site of compression is within the original radiation field, the options for treatment are usually reduced. Reirradiation is suitable for recurrent metastatic epidural spinal cord compression. However, many clinicians are hesitant to advise reirradiation in patients who relapse locally because of concern for delayed radiation myelopathy. This risk-benefit ratio depends on the time from first radiotherapy, initial dose, life expectancy, and probability of yielding worthwhile benefit.52,54

A retrospective analysis has shown that reirradiation to a median total dose of 54 Gy frequently preserves ambulation and carries minimal risk of radiation myelopathy during the patient’s lifetime; the median survival time for all patients after reirradiation was 4.2 months.52 In these patients, the use of the new radiation therapy technologies to deliver higher intense focal radiation doses to the recurrent tumor with less exposure to the spinal cord and healthy tissue is desirable, however, their effectiveness has yet to be established.

High-Precision Radiation Therapy Techniques

With conventional external beam radiation, a significant amount of healthy tissue including the spinal cord is exposed to radiation. Therefore, if radiation could be delivered to the target while decreasing the amount delivered to healthy tissue, injuries to the spinal cord would theoretically be reduced. The introduction of new sophisticated computer planning and portal imaging of treatment fields has decreased the normal tissue margins.36,55-58 Conformational radiation therapy plans are now three-dimensional, and, with the advent of intensity-modulated radiation therapy (the ability to vary dose delivery during a treatment session), higher radiation doses can be delivered to the target, sparing normal spinal and paraspinal tissues.59 When combined with high-precision tumor targeting using stereotactic technology, it has enabled the safe delivery of single-dose radiation using minimal safety margins of 2 mm that do not result in clinically relevant damage in the surrounding tissue.60 This level of accuracy has enabled the delivery of high-dose, single-fraction radiation therapy within close proximity to the spinal cord without toxicity. Intensity-modulated radiation therapy is ideally suited to creation of the concave dose distributions necessary for cord-sparing treatment plans. Image-guided verification provides a mechanism to minimize the uncertainties associated with traditional radiation therapy. The combination of intensity-modulated radiation therapy and image-guided techniques takes full advantage of the conformal potential of intensity-modulated radiation therapy to provide high-dose radiation therapy with low normal tissue exposure and a high degree of confidence.58

Tomotherapy is another high-precision technique that uses a rotating linear accelerator to deliver intensity-modulated radiation therapy. Stereotactic radiosurgery (CyberKnife, Novalis Shaped Beam Surgery; Accuray, Sunnyvale, California) is a highly focal radiation modality that delivers focused radiation to large lesions.60,61 Stereotactic radiosurgery can be administered in 1 or 2 sessions on an outpatient basis. Stereotactic localization is used to achieve accurate targeting for multiple radiation beams to converge on the lesion of interest at a high dose, while limiting the exposure of adjacent normal tissues. Total doses typically range from 8 to 18 Gy.62 Stereotactic radiosurgery can be used alone or following external-beam radiation or surgery.52,59,63 Radiosurgery alone provided pain relief in 74% to 89% of patients.62,64,65 The effectiveness and the highest tolerable doses of spinal stereotactic radiosurgery, however, particularly in acute metastatic epidural spinal cord compression, has not been rigorously tested against other current therapies.30,66

Surgery

Although radiation remains the therapy offered to most patients, surgery is increasingly being offered to patients with metastatic epidural spinal cord compression.9,67,68 Current indications for surgical treatment of patients with metastatic epidural spinal cord compression include unknown primary tumor, recurrence after radiation therapy, progression of deficit while on radiation therapy, spinal instability, intractable pain unresponsive to medical treatment, and patients with radio-insensitive primary tumors, displacement of spinal cord seen on MRI, a single area of cord compression, and no total paraplegia for >48 hours.3,4,36

Before radiation therapy, simple laminectomy was the only surgical treatment option for patients with metastatic epidural spinal cord compression. Laminectomy is indicated to establish a diagnosis, to treat a relapse if the patient is unable to undergo further radiation therapy, to relieve spinal cord compression by posterior and lateral radioresistant tumors, and if symptoms progress during radiation therapy. In addition, laminectomy is suitable for children with soft tissue or bone sarcomas and those with severe cord compression. These patients usually present with posterior cord compression resulting from vertebral foramen invasion.3,36 With the advent of radiation therapy, decompressive laminectomy followed by radiation therapy was recommended. However, multiple studies have found no benefit in neurological outcome of laminectomy alone or in combination with radiation therapy.1,46,69,70 In addition, radiation therapy alone has shown similar or superior results to laminectomy for metastatic epidural spinal cord compression.46

Decompressive laminectomy is not indicated in patients with anterior epidural cord compression, who make up the majority of cases. In addition, when tumor causes vertebral body collapse, the posterior elements are commonly the only ones that are intact, and laminectomy may cause spinal instability and worsen neurological symptoms; thus, decompressive laminectomy alone without supplemental internal fixation should not be used in patients with metastatic spinal disease, except in cases in which the disease is confined to the lamina and spinous process.4,36

As surgeons realized the limitations of laminectomy, they began to decompress the ventral spinal cord, which is the most common site of metastatic spread. Thus, circumferential spinal cord decompression began to emerge. To achieve a circumferential decompression, surgical approaches have been tailored to the location of the tumor with respect to the spinal cord, tumor histology, and type of spinal reconstruction or stabilization that will be required once the tumor is resected.36 Approaches can be broadly classified as anterior such as transthoracic or retroperitoneal, posterior, and posterolateral such as laminectomy, transpedicular, costotransversectomy, or lateral extracavitary.17,30,36,71-74

Since metastatic tumor is located anterior to the spinal cord and extends dorsally in 85% of cases, anterior approaches provide the best access to metastatic tumors that cause epidural spinal cord compression. Anterior direct decompression and stabilization is suitable for selected patients in good medical condition, expected survival of >3 months, focal anterior metastatic epidural spinal cord compression, and paraparesis. In a prospective randomized series,67 first-line treatment with surgery was found superior compared to radiation therapy alone; 80% of patients with metastatic epidural spinal cord compression treated with direct decompressive surgery and postoperative radiation therapy improved both in terms of pain relief and ambulatory status compared with 19% patients treated with radiation therapy alone.

Surgical treatment also increased survival time. In addition, there was no excess mortality or morbidity due to surgery.67 Combined anteroposterior direct decompression and stabilization is often performed, either in a single setting or staged.17,30,36 Vascular tumors such as renal cell, thyroid, and hepatocellular carcinoma that are approached surgically may be considered for preoperative embolization to diminish intraoperative blood loss (Figure 1). Intraoperative neurophysiologic monitoring with somatosensory and/or motor-evoked potentials might be useful adjuncts in surgically treating patients with metastatic epidural spinal cord compression. In addition to spinal cord direct decompression, spinal stabilization is necessary as anterior and posterior approaches to the spinal cord are significantly destabilizing.30

Different surgical techniques have also been reported. Most often, total vertebral body resection with stabilization is performed (Figures 2-5). The pathological vertebral body is usually replaced by polymethylmethacrylate or a metallic prosthesis attached to the adjacent vertebral bodies.49 More recently, expandable titanium cages have been used to facilitate anterior and middle column stabilization through a transpedicular approach of this type, in addition to pedicle screws.30 However, spinal column stabilization with methylmethacrylate is preferred because radiation therapy can start 1 week after insertion, whereas bone grafting must be allowed 6 weeks to fuse before delivery of radiation therapy.14

Figure 2A: L3 metastatic epidural spinal cord compression Figure 2B: An intervertebral cage at L3 was done Figure 2C: Local tumor recurrence

Figure 2: A 48-year-old woman with incomplete paraplegia (Frankel scale: D). Diagnostic work-up and staging showed renal cell carcinoma. Axial CT scan (left) and T2-weighted MRI (right) of the lumbar spine show L3 metastatic epidural spinal cord compression (A). Through a 2-stage posterior and anterior approach, decompression by extensive L3-L4 laminectomy, complete L3 corpectomy, posterior T12-L5 segmental instrumentation, and an intervertebral cage at L3 was done. Postoperatively, the patient had radiation therapy and complete neurological recovery (Frankel scale: E) (B). At 3 years postoperatively, coronal (left) and sagittal (right) T1-weighted MRIs of the lumbar spine show local tumor recurrence. The patient died 2 months later (C).


Figure 3A: T11 metastatic epidural spinal cord compression Figure 3B: Plate fixation was performed

Figure 3: A 51-year-old woman with incomplete paraplegia (Frankel scale: C). Diagnostic work-up and staging showed carcinoma of the uterus. Sagittal T1-weighted MRI of the thoracolumbar spine shows T11 metastatic epidural spinal cord compression (A). Through an anterolateral approach, extensive T11 laminectomy, T11 corpectomy, posterior T9-L1 segmental instrumentation sparing the pedicles of T11, and anterolateral T10-T12 plate fixation were performed. Postoperatively, the patient had radiation therapy and incomplete neurological recovery (Frankel scale: D) (B).


Figure 4A: T12 metastatic epidural spinal cord compression Figure 4B: Postoperatively, the patient had radiation therapy and complete neurological recovery

Figure 4: A 46-year-old woman with breast cancer and incomplete paraplegia (Frankel scale: D). Sagittal T1-weighted MRI of the thoracolumbar spine shows T12 metastatic epidural spinal cord compression (A). Through an anterolateral approach, extensive T12 laminectomy, T12 corpectomy, posterior T10-L2 segmental instrumentation, anterolateral T11-L1 plate fixation, and an intervertebral cage at T12 were performed. Postoperatively, the patient had radiation therapy and complete neurological recovery (Frankel scale: E). At 10 years postoperatively, there was no evidence of disease (B).


Figure 5A: T10-11 metastatic epidural spinal cord compression Figure 5B: Postoperative recovery was incomplete

Figure 5: A 55-year-old woman with breast cancer and complete paraplegia (Frankel scale: A). Sagittal T2-weighted MRIs of the thoracolumbar spine show T10-11 metastatic epidural spinal cord compression (A). Through an anterolateral approach, extensive T10-T11 laminectomy, complete T10 and T11 corpectomy, posterior T8-L1 segmental instrumentation, anterolateral T9-T12 plate fixation, and an intervertebral cage at T10-T11 were performed. Postoperative recovery was incomplete (Frankel scale: C) (B).

Direct decompression is difficult and carries a 10% to 53% risk of major complications including infection, hemorrhage, wound dehiscence and stabilization failure, respiratory failure, intra-abdominal vascular or visceral injury, or cerebrospinal fluid leak, and a perioperative mortality of 3% to 10% even in selected patients.75 Complication rates are significantly related to age older than 65 years, history of prior radiation therapy, and paraparesis.67,75-79 Radiation therapy should be delayed for 3 to 6 weeks after direct decompressive surgery to lessen the risk of postoperative complications.80

Chemotherapy and Hormonal Therapy

Chemotherapy and hormonal therapies have been used in individual patients with spinal cord compression from Hodgkin and non-Hodgkin lymphomas, germ cell tumors, breast or prostate carcinomas, and neuroblastomas. A blood-central nervous system barrier does not protect epidural metastases, so they may be treated with the same chemotherapeutic agents and hormonal therapies used for systemic tumors.9,14,81 However, chemotherapy rarely has a place in the acute management of patients with metastatic epidural spinal cord compression because, even with chemosensitive tumors, the response is too slow and unpredictable to be reliable. Chemotherapy might have a role in the treatment of chemosensitive tumors when given in combination with radiation therapy, and also in recurrent metastatic epidural spinal cord compression previously irradiated patients who are not candidates for further radiation therapy or surgery.4,81

Chemotherapy alone is suitable for adults with chemosensitive tumors (lymphoma, myeloma, breast, or germ cell tumors) who are not candidates for surgery or radiation. Adjuvant chemotherapy after radiation therapy is suitable for adults with highly chemosensitive tumors. Recovery of neurological function and regression of the tumor in response to chemotherapy has been reported in children with neuroblastoma, germ cell tumors, or Hodgkin’s disease; in these patients, results were similar or better than those observed after laminectomy or radiation.82,83 Hormonal chemotherapy is suitable for hormone-dependent tumors such as breast and prostate carcinoma. Metastatic epidural spinal cord compression from these lesions may be treated with tamoxifen or androgen blockade, respectively.84,85

In general, since many of the solid malignancies that frequently cause metastatic epidural spinal cord compression are either initially resistant or develop resistance to chemotherapy, it is recommended that chemotherapy and/or hormonal therapy be used in combination with more rapidly effective modalities such as radiation therapy or surgery.2 In addition, emergency decompression is required in cases of neurologic progression during chemotherapy or hormonal therapy.4,81,86

Rehabilitation

Rehabilitation is helpful in patients treated with radiation therapy, surgery, or both, for quality of life, less depression, strengthening, mobility training, and persistent decrease in pain.87,88 Critical to the success of rehabilitation is integration of patient and family efforts with those of the multidisciplinary team. In rehabilitation units, paraplegic patients receive instruction in transfers, incentive spirometry, nutrition, bowel and bladder management, and skin care.16,87

Conclusion

Metastatic epidural spinal cord compression is an emergency complication of systemic cancer. Early diagnosis and appropriate management will prevent paraplegia in most patients. Corticosteroids and radiation as adjuvant or primary therapy is a treatment option for the majority of patients. Circumferential direct decompressive surgery should be considered for selected patients. The role of high-precision radiation therapy techniques is promising for local tumor control and helps the patient avoid surgery. Survival and quality of life are directly related to the patients’ pretreatment ambulatory status. Treatment results are better in ambulatory patients with preserved bladder and bowel control.

References

  1. Quinn JA, DeAngelis LM. Neurologic emergencies in the cancer patient. Semin Oncol. 2000; 27(3):311-321.
  2. Gabriel K, Schiff D. Metastatic spinal cord compression by solid tumors. Semin Neurol. 2004; 24(4):375-383.
  3. Spinazzé S, Caraceni A, Schrijvers D. Epidural spinal cord compression. Crit Rev Oncol Hematol. 2005; 56(3):397-406.
  4. Cole JS, Patchell RA. Metastatic epidural spinal cord compression. Lancet Neurol. 2008; 7(5):459-466.
  5. Bilsky MH, Boland P, Lis E, Raizer JJ, Healey JH. Single-stage posterolateral transpedicle approach for spondylectomy, epidural decompression, and circumferential fusion of spinal metastases. Spine. 2000; 25(17):2240-2250.
  6. Gerszten PC, Welch WC: Current surgical management of metastatic spinal disease. Oncology. 2000; 14(7):1013-1024.
  7. Healey JH, Brown HK: Complications of bone metastases. Cancer. 2000; 88(Suppl 12):2940-2951.
  8. Helweg-Larsen S. Clinical outcome in metastatic spinal cord compression. A prospective study in 153 patients. Acta Neurol Scand. 1996; 94(4):269-275.
  9. Tazi H, Manunta A, Rodriguez A, Patard JJ, Lobel B, Guillé F. Spinal cord compression in metastatic prostate cancer. Eur Urol. 2003; 44(5):527-532.
  10. Tasdemiroglu E, Patchell RA, Kryscio R. Neurologic complications of childhood malignancies. Acta Neurochir (Wie). 1999; 141(12):1313-1321.
  11. Schiff D, O’Neill BP, Wang CH, O’Fallon JR. Neuroimaging and treatment implications of patients with multiple epidural spinal metastases. Cancer. 1998; 83(8):1593-1601.
  12. Arguello F, Baggs RB, Duerst RE, Johnstone L, McQueen K, Frantz CN. Pathogenesis of vertebral metastases and epidural spinal cord compression. Cancer. 1990; 65(1):98-106.
  13. Algra PR, Heimans JJ, Valk J, et al. Do metastases in vertebrae begin in the body or the pedicles? Imaging study in 45 patients. AJR Am J Roentgenol. 1992; 158(6):1275-1279.
  14. Schiff D. Spinal cord compression. Neurol Clin. 2003; 21(1):67-86, viii.
  15. Nelson KA, Walsh D, Abdullah O, et al. Common complications of advanced cancer. Semin Oncol. 2000; 27(1):34-44.
  16. Abrahm JL, Banffy MB, Harris MB. Spinal cord compression in patients with advanced metastatic cancer: “all I care about is walking and living my life”. JAMA. 2008; 299(8):937-946.
  17. Bilsky M, Smith M. Surgical approach to epidural spinal cord compression. Hematol Oncol Clin North Am. 2006; 20(6):1307-1317.
  18. Levack P, Graham J, Collie D, et al; and Scottish Cord Compression Study Group. Don’t wait for a sensory level-listen to the symptoms: a prospective audit of the delays in diagnosis of malignant cord compression. Clin Oncol (R Coll Radiol). 2002; 14(6):472-480.
  19. Helweg-Larsen S, Sørensen PS, Kreiner S. Prognostic factors in metastatic spinal cord compression: a prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int J Radiat Oncol Biol Phys. 2000; 46(5):1163-1169.
  20. Kienstra GE, Terwee CB, Dekker FW, et al. Prediction of spinal epidural metastases. Arch Neurol. 2000; 57(5):690-695.
  21. Ruckdeshel JC. Early detection and treatment of spinal cord compression. Oncology (Williston Park). 2005; 19(1):81-86.
  22. Carmody RF, Yang PJ, Seeley GW, Seeger JF, Unger EC, Johnson JE. Spinal cord compression due to metastatic disease: diagnosis with MR imaging versus myelography. Radiology. 1989; 173(1):225-229.
  23. Helweg-Larsen S, Wagner A, Kjaer L, et al. Comparison of myelography combined with postmyelographic spinal CT and MRI in suspected metastatic disease of the spinal canal. J Neurooncol. 1992; 13(3):231-237.
  24. Chamberlain MC, Kormanik PA. Epidural spinal cord compression: a single institution’s retrospective experience. Neuro Oncol. 1999; 1(2):120-123.
  25. Husband DJ, Grant KA, Romaniuk CS. MRI in the diagnosis and treatment of suspected malignant spinal cord compression. Br J Radiol. 2001; 74(877):15-23.
  26. Cook AM, Lau TN, Tomlinson MJ, Vaidya M, Wakeley CJ, Goddard P. Magnetic resonance imaging of the whole spine in suspected malignant spinal cord compression: impact on management. Clin Oncol (R Coll Radiol). 1998; 10(1):39-43.
  27. Gosfield E III, Alavi A, Kneeland B. Comparison of radionuclide bone scans and magnetic resonance imaging in detecting spinal metastases. J Nucl Med. 1993; 34(12):2191-2200.
  28. Portenoy R, Galer B, Salamon O, et al. Identification of epidural neoplasm: radiography and bone scintigraphy in the symptomatic and asymptomatic spine. Cancer. 1989; 64(11):2207-2213.
  29. Francken AB, Hong AM, Fulham MJ, Millward MJ, McCarthy WH, Thompson JF. Detection of unsuspected spinal cord compression in melanoma patients by 18F-fluorodeoxyglucose-positron emission tomography. Eur J Surg Oncol. 2005; 31(2):197-204.
  30. Witham TF, Khavkin YA, Gallia GL, Wolinsky JP, Gokaslan ZL. Surgery insight: current management of epidural spinal cord compression from metastatic spine disease. Nat Clin Pract Neurol. 2006; 2(2):87-94.
  31. Rades D, Blach M, Bremer M, Wildfang I, Karstens JH, Heidenreich F. Prognostic significance of the time of developing motor deficits before radiation therapy in metastatic spinal cord compression: one year results of a prospective trial. Int J Radiat Oncol Biol Phys. 2000; 48(5):1403-1408.
  32. Solberg A, Bremnes RM. Metastatic spinal cord compression: diagnostic delay, treatment, and outcome. Anticancer Res. 1999; 19(1B):677-684.
  33. Rades D, Dunst J, Schild SE. The first score predicting overall survival in patients with metastatic spinal cord compression. Cancer. 2008; 112(1):157-161.
  34. Klimo P, Thompson CJ, Kestle JR, Schmidt MH. A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro Oncol. 2005; 7(1):64-76.
  35. Tomita K, Kawahara N, Kobayashi T, Yoshida A, Murakami H, Akamaru T. Surgical strategy for spinal metastases. Spine. 2001; 26(3):298-306.
  36. Klimo P Jr, Kestle JR, Schmidt MH. Treatment of metastatic spinal epidural disease: a review of the literature. Neurosurg Focus. 2003; 15(5):E1.
  37. Rades D, Schild SE. Spinal cord compression. Eur J Cancer. 2007; 5(suppl): 359-370.
  38. Prasad D, Schiff D. Malignant spinal-cord compression. Lancet Oncol. 2005; 6(1):15-24.
  39. Caraceni A, Zecca E, Bonezzi C, et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. J Clin Oncol. 2004; 22(14):2909-2917.
  40. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: elvidence-based recommendations. Pain. 2007; 132(3):237-251.
  41. Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002; 94(19):1458-1468.
  42. Ross JR, Saunders Y, Edmonds PM, et al. A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess. 2004; 8(4):1-176.
  43. Gilbert RW, Kim JH, Posner JB. Epidural spinal cord compression from metastatic tumor: diagnosis and treatment. Ann Neurol. 1978; 3(1):40-51.
  44. Rades D, Fehlauer F, Schulte R, et al. Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol. 2006; 24(21):3388-3393.
  45. Maranzano E, Latini P. Effectiveness of radiation therapy without surgery in metastatic spinal cord compression: final results from a prospective trial. Int J Radiat Oncol Biol Phys. 1995; 32(4):959-967.
  46. Ciezki JP, Komurcu S, Macklis RM. Palliative radiotherapy. Semin Oncol. 2000; 27(1):90-93.
  47. Schmidt MH, Klimo P, Vrionis FD. Metastatic spinal cord compression. J Natl Compr Canc Netw. 2005; 3(5):711-719.
  48. Rades D, Karstens JH, Hoskin PJ, et al. Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2007; 67(2):525-531.
  49. Loblaw DA, Perry J, Chambers A, et al. Systematic review of the diagnosis and management of malignant extradural spinal cord compression. J Clin Oncol. 2005; 23(9):2028-2037.
  50. Maranzano E, Bellavita R, Rossi R, et al. Short-course versus split course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005; 23(15):3358-3365.
  51. Maranzano E, Bellavita R, Floridi P, et al. Radiation-induced myelopathy in long-term surviving metastatic spinal cord compression patients after hypofractionated radiotherapy: a clinical and magnetic resonance imaging analysis. Radiother Oncol. 2001; 60(3):281-288.
  52. Schiff D, Shaw EG, Cascino TL. Outcome after spinal reirradiation for malignant epidural spinal cord compression. Ann Neurol. 1995; 37(5):583-589.
  53. van der Sande JJ, Boogerd W, Kröger R, Kappelle AC. Recurrent spinal epidural metastases: a prospective study with complete follow up. J Neurol Neurosurg Psychiatry. 1999; 66(5):623-627.
  54. Rades D, Stalpers LJ, Veninga T, Hoskin PJ. Spinal reirradiation after short-course RT for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2005; 63(3):872-875.
  55. Bernier J, Hall EJ, Giaccia A. Radiation oncology: A century of achievements. Nat Rev Cancer. 2004; 4(9):737-747.
  56. Gerszten PC, Ozhasoglu C, Burton SA, et al. Cyberknife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery. 2004; 55(1):89-99.
  57. Guckenberger M, Meyer J, Wilbert J, et al. Precision required for dose-escalated treatment of spinal metastases and implications for image-guided radiation therapy (IGRT). Radiother Oncol. 2007; 84(1):56-63.
  58. Yamada Y, Bilsky MH, Lovelock DM, et al. High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions. Int J Radiat Oncol Biol Phys. 2008; 71(2):484-490.
  59. Rock JP, Ryu S, Yin F-F, Schreiber F, Abdulhak M. The evolving role of stereotactic radiosurgery and stereotactic radiation therapy for patients with spine tumors. J Neurooncol. 2004; 69(1-3):319-334.
  60. Lovelock DM, Hua C, Wang P, et al. Accurate setup of paraspinal patients using a noninvasive patient immobilization cradle and portal imaging. Med Phys. 2005; 32(8):2606-2614.
  61. Klimo P Jr, Schmidt MH. Surgical management of spinal metastases. The Oncologist. 2004; 9(2):188-196.
  62. Degen JW, Gagnon GJ, Voyadzis J, et al. CyberKnife sterotactic radiosurgical treatment of spinal tumors for pain control and quality of life. J Neurosurg Spine. 2005; 2(5):540-549.
  63. Rock JP, Ryu S, Shukairy MS, et al. Postoperative radiosurgery for malignant spinal tumors. Neurosurgery. 2006; 58(5):891-898.
  64. Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine. 2007; 32(2):193-199.
  65. Gagnon GJ, Henderson FC, Gehan EA, et al. CyberKnife radiosurgery for breast cancer spine metastases: a matched-pair analysis. Cancer. 2007; 110(8):1796-1802.
  66. Ryu S, Jin J, Jin R, et al. Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery. Cancer. 2007; 109(3):628-636.
  67. Patchell RA, Tibbs PA, Regine WF, et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet. 2005; 366(9486):643-648.
  68. Knisely J, Strugar J. Can decompressive surgery improve outcome in patients with metastatic epidural spinal-cord compression? Nat Clin Pract Oncol. 2006; 3(1):14-15.
  69. Findlay G. Adverse effects of the management of malignant spinal cord compression. J Neurol Neurosurg Psychiatry. 1984; 47(8):761-768.
  70. Young R, Post E, King G. Treatment of spinal epidural metastases. Randomized prospective comparison of laminectomy and radiotherapy. J Neurosurg. 1980; 53(6):741-748.
  71. Gokaslan ZL, York JE, Walsh GL, et al. Transthoracic vertebrectomy for metastatic spinal tumors. J Neurosurg. 1998; 89(4):599-609.
  72. Fourney DR, Gokaslan ZL. Thoracolumbar spine: surgical treatment of metastatic disease. Curr Opin Orthopaed. 2003; 14(3):144-152.
  73. Wang JC, Boland P, Mitra N, et al. Single-stage posterolateral transpedicular approach for resection of epidural metastatic spine tumors involving the vertebral body with circumferential reconstruction: results in 140 patients. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2004. J Neurosurg Spine. 2004; 1(3):287-298.
  74. Akeyson EW, McCutcheon IE. Single-stage posterior vertebrectomy and replacement combined with posterior instrumentation for spinal metastasis. J Neurosurg. 1996; 85(2):211-220.
  75. Sundaresan N, Sachdev VP, Holland JF, et al. Surgical treatment of spinal cord compression from epidural metastasis. J Clin Oncol. 1995; 13(9):2330-2335.
  76. Harrington KD. Anterior decompression and stabilization of the spine as a treatment for vertebral collapse and spinal cord decompression from metastatic malignancy. Clin Orthop Relat Res. 1988; (233):177-197.
  77. Moore AJ, Uttley D. Anterior decompression and stabilization of the spine in malignant disease. Neurosurgery. 1989; 24(5):713-717.
  78. Tomita K, Kawahara N, Baba H, Tsuchiya H, Nagata S, Toribatake Y. Total en bloc spondylectomy for solitary spinal metastases. Int Orthop. 1994; 18(5):291-298.
  79. Chen YJ, Chang G, Chen H, et al. Surgical results of metastatic spinal cord compression secondary to non-small cell lung cancer. Spine. 2007; 32(15):E413-E418.
  80. Gokaslan ZL. Spine surgery for cancer. Curr Opin Oncol. 1996;8(3):178-181.
  81. Wong ET, Portlock CS, O’Brien JP, DeAngelis LM. Chemosensitive epidural spinal cord disease in non-Hodgkins lymphoma. Neurology. 1996; 46(6):1543-1547.
  82. Mora J, Wollner N. Primary epidural non-Hodgkin lymphoma: spinal cord compression syndrome as the initial form of presentation in childhood non-Hodgkin lymphoma. Med Pediatr Oncol. 1999; 32(2):102-105.
  83. Plantaz D, Rubie H, Michon J, et al. The treatment of neuroblastoma with intraspinal extension with chemotherapy followed by surgical removal of residual disease. A prospective study of 42 patients-results of the NBL 90 Study of the French Society of Pediatric Oncology. Cancer. 1996; 78(2):311-319.
  84. Katagiri H, Takahashi M, Inagaki J, et al. Clinical results of nonsurgical treatment for spinal metastases. Int J Radiat Oncol Biol Phys. 1998; 42(5):1127-1132.
  85. McDonald AC, Nicoll JA, Rampling RP. Non-Hodgkin’s lymphoma presenting with spinal cord compression; a clinicopathological review of 25 cases. Eur J Cancer. 2000; 36(2):207-213.
  86. Papagelopoulos PJ, Savvidou OD, Galamis EC, et al. Advances and challenges in diagnosis and management of skeletal metastases. Orthopedics. 2006; 29(7):609-620.
  87. Ruff RL, Adamson VW, Ruff SS, Wang X. Directed rehabilitation reduces pain and depression while increasing independence and satisfaction with life for patients with paraplegia due to epidural metastatic spinal cord compression. J Rehabil Res Dev. 2007; 44(1):1-10.
  88. Ruff RL, Ruff SS, Wang X. Persistent benefits of rehabilitation on pain and life quality for nonambulatory patients with spinal epidural metastasis. J Rehabil Res Dev. 2007; 44(2):271-278.

Authors

Drs Mavrogenis, Sapkas, and Papagelopoulos are from the First Department of Orthopedics, Attikon University General Hospital, and Dr Pneumaticos is from the Third Department of Orthopedics, Athens University Medical School, Athens, Greece.

The material presented in any Vindico Medical Education continuing education activity does not necessarily reflect the views and opinions of Vindico Medical Education or Orthopedics. Neither Vindico Medical Education or Orthopedics nor the authors endorse or recommend any techniques, commercial products, or manufacturers. The authors may discuss the use of materials and/or products that have not yet been approved by the US Food and Drug Administration. All readers and continuing education participants should verify all information before treating patients or using any product.

Correspondence should be addressed to: Panayiotis J. Papagelopoulos, MD, DSc, Athens University Medical School, 4 Christovassili St, 15451, Neo Psychikon, Athens, Greece.

DOI: 10.3928/01477447-20090511-20

10.3928/01477447-20090511-20

Sign up to receive

Journal E-contents