Clinical features and diagnosis of neoplastic epidural spinal cord compression

INTRODUCTION — Neoplastic epidural spinal cord compression (ESCC) is a relatively common complication of cancer that can cause pain, mechanical instability of the spine, and potentially irreversible loss of neurologic function. Early recognition and diagnosis of ESCC facilitates definitive and palliative therapies, which aim to maximize function, treat pain, and prevent further neurologic complications.

The epidemiology, pathophysiology, clinical features, and diagnosis of ESCC will be reviewed here. The treatment and prognosis of this disorder are discussed separately. (See "Treatment and prognosis of neoplastic epidural spinal cord compression".)

TERMINOLOGY — The degree of thecal sac compression required for the designation of ESCC has been variably defined. Throughout this topic, the term "ESCC" is used to mean any radiologic evidence of indentation of the thecal sac or spinal cord compression, whether or not there are neurologic signs and symptoms associated with compression (figure 1 and image 1) [1,2].

In adults, the tip of the spinal cord usually lies at the L1 vertebral level; below this level, the lumbosacral nerve roots form the cauda equina, which floats in cerebrospinal fluid (CSF). Since the pathophysiology of compression of the thecal sac at the level of the cauda equina does not differ significantly from that of more rostral compression of the spinal cord itself, compression of the cauda equina is included in the discussion of ESCC.

EPIDEMIOLOGY — ESCC is a relatively common complication of cancer. In population-based studies, the annual incidence of symptomatic ESCC is approximately 3 to 5 percent among patients dying from cancer [3-5].

Although metastatic tumors from any primary site can cause ESCC, approximately half of cases arise from common cancers such as prostate, lung, and breast, which have a propensity to involve and metastasize to bone. Among over 15,000 hospitalizations for ESCC in the United States from 1998 to 2006, the most prevalent underlying cancers were lung cancer (25 percent), prostate cancer (16 percent), multiple myeloma (11 percent), and breast cancer (7 percent) [4]. Cancer-specific annual incidence rates among patients dying from cancer were highest for multiple myeloma (15 per 100), Hodgkin and non-Hodgkin lymphoma (6 to 8 per 100), prostate and kidney (5 per 100), and thyroid (2 per 100).

ESCC is the initial manifestation of malignancy in approximately 20 percent of patients [6,7]. The distribution of primary tumors in this setting differs from that seen in patients with ESCC and known cancer. Synchronous presentations are more common in lung cancer, cancer of unknown primary site, multiple myeloma, and non-Hodgkin lymphoma, whereas ESCC is usually a later complication of advanced breast and prostate cancer [6].

Among patients with metastatic cancer and known vertebral metastases, rates of ESCC vary depending on cancer type, length of follow-up, and whether radiographic or clinical definitions of ESCC are used. In a prospective trial that included 420 males with asymptomatic spinal metastases from prostate cancer and no spinal magnetic resonance imaging (MRI) in the preceding year, approximately one-third of patients were found to have ESCC of any grade on spine MRI [8]. The rate of symptomatic ESCC at one year was much lower, ranging from 4 to 7 percent.

The tumors responsible for ESCC in children are different. Sarcomas (especially Ewing sarcoma) and neuroblastomas are the most frequent causes, followed by germ cell neoplasms and Hodgkin lymphoma [9].

PATHOPHYSIOLOGY — Spinal cord compression is a function of spinal anatomy. The spinal cord is enclosed by a protective ring of bones comprised of the vertebral body anteriorly, the pedicles laterally, and the lamina and spinous process posteriorly. Within this ring is the thecal sac, the outermost layer of which is comprised of dura. Between the bone and dura lies the epidural space, which normally contains fat and the venous plexus. (See "Anatomy and localization of spinal cord disorders".)

At each spinal level, nerve roots exit lateral to the spinal cord and posterior to the vertebral body (figure 2). ESCC occurs when tumor invades the epidural space and compresses the thecal sac. The degree of thecal sac compression can result in a range of presentations from asymptomatic to paraplegia.

Approximately 85 to 90 percent of cases of ESCC are due to metastatic tumor in the vertebral bones, but the mechanism of metastasis varies. Potential mechanisms include the following:

●Arterial seeding of bone probably accounts for most cases.

●For pelvic tumors, particularly prostate cancer, Batson venous plexus probably plays an important role. When abdominal pressure is increased by the Valsalva maneuver, venous drainage from the abdomen and pelvis is shunted to the epidural venous plexus, which promotes vertebral metastases.

●In approximately 10 percent of cases, a paraspinal mass gains access to the epidural space via the neural foramen; this scenario is particularly common with lymphoma.

●Rarely, tumor appears to emanate from the epidural space without a bony or paraspinal component.

When bone is the source of an epidural mass, the vertebral body is involved in over 80 percent of cases, with involvement of the posterior elements being much less common. Thus, the bulk of tumor is anterior or anterolateral to the thecal sac in most cases of ESCC [10,11].

As tumor grows in the epidural space, it generally takes the path of least resistance and encircles the thecal sac. As the epidural venous plexus becomes obstructed, vasogenic edema may develop in the white matter and eventually the gray matter of the spinal cord. The beneficial actions of glucocorticoids in ESCC may be related to resolution of vasogenic edema. If the epidural tumor is unchecked, spinal cord infarction eventually ensues [12].

CLINICAL FEATURES — The cardinal clinical features of ESCC are symptomatic spinal cord or nerve root compression and mechanical instability of the spinal column. Early diagnosis of spinal metastases prevents the development of neurologic deficits and severe structural instability.

Clinical presentation — The majority of patients with ESCC have pain as the initial symptom, prior to the onset of sensory, motor, or bowel and bladder dysfunction. Delayed recognition and therapy of ESCC may result in the development or progression of neurologic deficits.

ESCC most commonly arises in the thoracic spine. Approximately 60 to 70 percent of cases occur in the thoracic spine, 20 to 30 percent in the lumbosacral spine, and 10 percent in the cervical spine [13]. These percentages are in rough proportion to the combined volumes of the vertebral bodies in each region.

In older series, most patients with newly diagnosed ESCC were not ambulatory at diagnosis [5,14-19]. Fortunately, wide availability of MRI facilitates early diagnosis of ESCC and has led to a significantly decreased proportion of patients presenting with loss of ambulation at the time of diagnosis [20]. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Importance of early detection'.)

Symptoms and signs

Pain — Pain is usually the first symptom of ESCC, present in 80 to 95 percent of patients at the time of diagnosis [5,10,21]. On average, pain precedes other neurologic symptoms of ESCC by seven weeks.

Affected patients usually notice a severe local back pain, at the level of the lesion, which progressively increases in intensity. However, referred pain from ESCC is common and can be misleading in terms of localizing the lesion. One example is thoracolumbar junction (T11-L1) vertebral metastases manifesting as pain in the lower lumbar spine or in the area of the sacroiliac joint. Another example is compression of ascending spinal cord tracts in the cervical cord manifesting as sciatic pain; this phenomenon is sometimes called funicular pain [22].

Pain from ESCC is often worse at night, possibly related to diurnal variation in levels of endogenous corticosteroids [23]. Local pain may be due to disruption of the periosteum or dural nerves, the spinal cord, or paravertebral soft tissue. The frequent alleviation of pain with corticosteroids suggests that inflammation or neural irritation plays a significant role [10].

Over time, the pain may develop a radicular quality. It may, for example, radiate into a limb with movement of the spine or Valsalva maneuver. Radicular pain is more common in lumbosacral lesions than in thoracic lesions [21]. Thoracic radicular pain is commonly bilateral and wraps around anteriorly in a bandlike fashion. Abrupt worsening of pain may herald a pathologic compression fracture.

Pain present only on movement suggests mechanical spinal instability resulting from a spine fracture, a finding that may demand a surgical approach for optimal relief of pain [24-26]. The movements that elicit mechanical pain vary according to the spinal level of the tumor [27,28]:

●Unstable cervical metastases cause neck and/or interscapular pain with flexion/extension/rotation of the neck.

●Unstable thoracic metastases cause pain while lying down.

●Lumbar mechanical instability is generally manifested through a mechanical radiculopathy, a severe radicular pain elicited by axial loading while ambulating or standing.

The Spine Instability Neoplastic Score (SINS) was developed in order to aid in the detection of potential spinal instability and to facilitate decisions about surgical evaluation (table 1) [29]. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Mechanical (spinal stability)'.)

Motor findings — Motor findings represent advanced stages of ESCC [15,21]. The severity of weakness tends to be greatest in patients with compressive thoracic metastases [21]. Unless there is profound weakness or severe pain with movement, the motor examination should include standing and walking to be complete.

When the site of compression is at or above the conus medullaris, weakness is from corticospinal tract dysfunction and has the typical pyramidal pattern, preferentially affecting the flexors in the lower extremities (ie, weakness of hip flexion, knee flexion, and ankle dorsiflexion with relative preservation of hip extension, knee extension, and plantar flexion strength). If compression is in the cervical spine, the extensors of the upper extremities may also be affected (ie, more pronounced weakness in the triceps and wrist extensors than in the deltoid and biceps). Hyperreflexia below the level of the compression and extensor plantar responses may be seen.

ESCC at or above the conus medullaris generally produces fairly symmetric lower extremity weakness. A laterally situated epidural lesion may preferentially affect a nerve root exiting the neural foramen and produce a superimposed or isolated motor radiculopathy. Compressive lesions at the level of the cauda equina tend to produce more asymmetrical and patchy weakness. (See 'Cauda equina syndrome' below.)

The progression of motor findings prior to diagnosis of ESCC typically consists of increasing weakness followed sequentially by loss of gait function and then paralysis [21]. In advanced stages of ESCC, loss of ambulation is usually due to weakness. However, neoplastic spinal mechanical instability may cause severe pain with movement, thereby rendering patients unable to ambulate in the absence of neurologic deficits.

Sensory findings — Sensory findings are very common, and a sensory level is typically present prior to the onset of weakness [21]. Patients frequently report a pattern of ascending numbness and paresthesias if questioned and examined carefully. Proprioceptive loss can also occur, although this is less common and usually occurs later.

When a spinal sensory level is present, it is typically one to five levels below the actual level of cord compression [10]. Saddle sensory loss is commonly present in cauda equina or conus medullaris lesions, while lesions above the cauda equina frequently result in sparing of sacral dermatomes to pinprick.

Sensory loss can occur in a radicular distribution. It has been suggested that radicular pain with sensory complaints is particularly common with lumbar ESCC, whereas bilateral leg weakness with back pain is typical of thoracic ESCC [21].

Lhermitte phenomenon, the experience of electricity down the spine with neck flexion, may occasionally be reported when compression is in the cervical spine, although it is not specific for ESCC. Lhermitte phenomenon is more commonly seen in multiple sclerosis, cervical spondylotic myelopathy, cisplatin-induced neurotoxicity, radiation-induced myelopathy, and neck trauma [30,31]. (See "Cervical spondylotic myelopathy" and "Complications of spinal cord irradiation".)

The mechanism of numbness in ESCC is related to compression of the spinothalamic tracts, which are located in the anterior spinal cord. Since most ESCC arises from the anterior vertebral body, these fibers are preferentially compressed early in the natural history of ESCC. Proprioceptive function localizes to the posterior columns, which are typically spared from early direct compression. Loss of proprioception complicates recovery, as it is often persistent and is functionally disabling for achieving normal ambulation, even with a normal motor examination.

Bladder and bowel dysfunction — Bladder and bowel dysfunction due to ESCC is generally a late finding that was present in as many as one-half of patients in older series [21]. Urinary retention as a manifestation of autonomic dysfunction is the most common finding and is rarely the sole symptom of ESCC [10].

One exception is when compression occurs at the level of the conus medullaris, which can manifest as relatively isolated back pain and urinary/bowel symptoms. Sacral metastases may also cause isolated bowel/bladder incontinence and perineal sensory deficits due to localized compression of the sacral nerve roots. The saddle anesthesia (ie, perineal numbness) associated with these two presentations helps to differentiate them from other common causes of bowel and bladder dysfunction, such as opioids and prostatic hypertrophy.

Ataxia — New-onset gait ataxia in the setting of back pain in a cancer patient should raise suspicion of ESCC [32]. In the absence of demonstrable sensory loss, spinocerebellar tract dysfunction has been presumed to account for the ataxia.

Preferential compression of the spinocerebellar tracts is also implicated in "numb clumsy hand" syndrome due to a high-cervical myelopathy. On examination, patients appear to have an apraxia, as their hand intrinsic strength and sensory functions are normal despite not being able to perform simple tasks like buttoning a shirt.

Cauda equina syndrome — Patients with compressive lesions in the lumbosacral spine below the level of the conus medullaris may present with signs and symptoms of cauda equina syndrome. Symptoms are due to compression of multiple nerve roots of the cauda equina and may include pain radiating into one or both legs (radicular pain), paresthesias and sensory loss in the distribution of one or more nerve roots (figure 3), and patchy and asymmetrical weakness and loss of reflexes (figure 4). Bilateral lower extremity pain is the classic presentation that raises concern for cauda equina syndrome. Bowel and bladder dysfunction may occur with compression of the lower sacral nerve roots. Elevated post-void residual volume on bladder scan may be a particularly sensitive marker of urinary retention in this setting [33].

Weakness tends to be less severe and asymmetrical with ESCC in the lumbosacral region compared with thoracic lesions. Cauda equina syndrome is not specific for ESCC, and leptomeningeal metastases (carcinomatous meningitis) must also be considered, particularly in patients with known metastatic cancer and preexisting central nervous system metastases. Among the more common non-neoplastic causes are acute large disc herniations and osteoporotic fractures. (See 'Differential diagnosis' below.)

DIAGNOSTIC EVALUATION — The diagnosis of ESCC depends upon the demonstration of tumor that compresses the thecal sac. MRI of the entire spine without and with contrast is the preferred modality for diagnosis. In patients where MRI is contraindicated (eg, some electromagnetic cardiac devices, metallic foreign body in orbit), computed tomography (CT) myelography of the entire spine is the second-line option. Plain radiographs of the spine have no role in the diagnosis of ESCC.

Magnetic resonance imaging of the spine

Imaging protocol and timing — MRI of the entire (ie, cervical, thoracic, and lumbar) spine without and with contrast is recommended for the diagnosis of ESCC. Imaging should be obtained as soon as possible and within 24 hours in patients suspected of having ESCC [34]. This may require transferring the patient to another facility.

Sagittal T1 and/or short tau inversion recovery (STIR) sequences of the entire spine are performed to look for metastases. Sagittal T2-weighted sequences may also be performed to evaluate the degree of cord compression and to detect lesions within the cord itself. Dedicated axial images are usually acquired through abnormalities detected on the sagittal plane. While the degree of intraosseous tumor is well delineated on noncontrast sequences, intravenous contrast is routinely given to define the extent of epidural, foraminal, and paraspinal tumor and to evaluate for the presence of intramedullary or leptomeningeal disease. (See 'Other neurologic complications of cancer' below.)

In some instances when recumbent pain prevents the patient from lying still for imaging, a bolus of glucocorticoids may relieve pain sufficiently to allow the procedure. In some patients, general anesthesia is necessary.

In retrospective observational series using myelography as the reference standard, MRI has been reported to demonstrate high sensitivity (93 to 100 percent) and specificity (90 to 97 percent) in diagnosing spinal cord compression [35,36].

Whole-spine imaging is important in patients with ESCC to:

●Assess for other sites of the spine that may be at risk. Bone metastases are rarely limited to a single site, and multiple epidural tumor deposits are present in approximately one-third of patients with ESCC [2,37-39]. The presence of multiple sites of disease significantly affects both prognosis and treatment planning [2,37].

●Anatomically localize the involved spinal cord level as clinical evaluation may be imprecise. The compressive lesion may be several levels higher than what is suggested by a sensory level. (See 'Sensory findings' above.)

The importance of imaging the entire spine is illustrated by a retrospective study of 337 cases [2]. In this report, failure to image the cervical spine in patients with symptomatic thoracic or lumbar epidural lesions would have missed secondary epidural lesions in only 1 percent of patients. However, failure to image either the thoracic or lumbosacral spine missed lesions in 21 percent of cases when symptomatic disease was located elsewhere.

MRI features and grading — Whole-spine MRI without and with contrast provides the best depiction of the extent of disease involving vertebra, spinal canal, neural foramina, and paravertebral soft tissues.

Axial T2-weighted images at the level of the lesion are used to assign an ESCC score, which can be used to describe the extent of epidural tumor [40]. The system consists of the following grades (figure 1 and image 1):

●Grade 0 – Tumor confined to bone (not considered ESCC).

●Grade 1 – Tumor with epidural extension without contact with the spinal cord or just spinal cord abutment without displacement.

•Grade 1a: Epidural tumor without thecal sac compression

•Grade 1b: Epidural tumor with thecal sac compression but no cord contact

•Grade 1c: Epidural tumor with thecal sac compression and cord contact without compression

●Grade 2 – Tumor that displaces or compresses the spinal cord, without circumferential tumor extension or obliteration of the cerebrospinal fluid (CSF) space.

●Grade 3 – Tumor with circumferential epidural extension and/or that causes severe spinal cord compression with obliteration of the CSF space.

Grades 2 and 3 represent high-grade spinal cord compression, whereas grade 1 represents low-grade ESCC. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Neurologic (high- versus low-grade ESCC)'.)

Computed tomography myelography — CT myelography is the alternative imaging option in patients with suspected ESCC who cannot undergo MRI (eg, electromagnetic cardiac device, metallic foreign body in orbit). CT myelography is only performed in practice settings where neurosurgical expertise is readily available as patients can, rarely, deteriorate following the procedure and require urgent spinal decompression.

CT myelography involves the direct injection of iodinated contrast into the thecal sac, usually by image-guided lumbar puncture. A C1-2 approach may be used if a lumbar approach is not feasible or to define the superior extent of compression if a complete block is detected from lumbar injection. Following the injection of intrathecal contrast, patients undergo CT imaging of the cervical, thoracic, and lumbar spine. Volumetric thin (<3 mm) section imaging with multiplanar sagittal and coronal reformations in both soft tissue and bone algorithms are routinely performed. Intravenous contrast is not administered.

Diagnostic performance of CT myelography has not been directly measured, but the examination appears to demonstrate comparable sensitivity and specificity to MRI with contrast for the diagnosis of spinal cord compression [41].

Aside from evaluating patients with a contraindication to MRI, CT myelography may also be useful in:

●Patients with indwelling spinal orthopedic hardware. Significant artifact preventing clear visualization of the spinal cord can be encountered with either CT or MRI in regions of prior spinal reconstruction. If MRI proves nondiagnostic, CT may sometimes yield better images in the area of clinical concern. Imaging with MRI or CT should be performed using metal artifact reduction techniques if possible.

●Patients undergoing treatment planning for radiosurgery or radiation therapy.

Rarely, patients with complete subarachnoid block deteriorate neurologically when CSF pressure below the block has been reduced by the lumbar puncture. For this reason, neurosurgical input is usually obtained prior to CT myelography. Complete block may also necessitate injection of contrast using a C1-2 approach to visualize the cephalad extent of the cord.

Assessment of spinal stability — An important component of the decision-making process when considering definitive therapy is assessment of spinal stability, which refers to the integrity of the vertebral spine to resist progressive deformity and/or neural compromise under physiologic loads [29]. Treatment of ESCC differs in those patients whose spine is unstable compared with those with a stable spine.

Stability is best assessed by a spine surgeon based on radiographic features and clinical symptoms, most importantly the presence or absence of movement-related pain (table 1). Regardless of radiographic findings, clinicians should consider every patient with pain caused by movement to be unstable until proved otherwise. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Mechanical (spinal stability)'.)

Cancer staging and role of diagnostic biopsy — In most patients presenting with ESCC who have known metastatic cancer, biopsy of the compressive lesion is not necessary for treatment planning, and a vertebral lesion with a typical appearance can be presumed to be metastatic. An updated noninvasive cancer staging evaluation, typically by contrast-enhanced CT of the chest, abdomen, and pelvis or 18-F fluorodeoxyglucose positron emission tomography (FDG-PET)/CT, aids in clinical decision-making in these patients. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Baseline assessment'.)

The evaluation of patients with no, or a remote, history of cancer is more complex and must include a prompt search for the primary site; contrast-enhanced CT of the chest, abdomen, and pelvis tailored for visceral organ evaluation plus a bone scan or FDG-PET/CT may be used for comprehensive staging evaluation.

For neurologically stable patients without high-grade compression in whom a likely primary tumor is identified, a diagnostic biopsy of the primary tumor or the most accessible metastatic lesion should generally be performed prior to definitive treatment of ESCC, in order to guide selection of the most appropriate treatment modality.

In patients with high-grade ESCC, in whom surgical decompression and stabilization may be considered, multidisciplinary review with a radiologist and spine surgeon is indicated to determine whether image-guided needle biopsy of the compressive vertebral lesion is appropriate prior to surgery.

●For cases in which there is high suspicion radiographically for lymphoma or myeloma, a core needle biopsy with expedited pathologic review may be appropriate, as confirmation of a radiosensitive neoplasm would spare the patient an unnecessary decompressive spine surgery.

●For patients with high-grade ESCC in whom the comprehensive staging evaluation is suspicious for a radioresistant primary tumor such as renal cell or melanoma, diagnostic tissue can be obtained at the time of surgical decompression and stabilization.

●In patients presenting with high-grade ESCC with associated myelopathy or cauda equina syndrome who do not have a known diagnosis, surgical decompression and stabilization is the preferred treatment over needle biopsy. There is often a delay in obtaining a needle biopsy and receiving definitive pathology results. Patients who are neurologically symptomatic at presentation can rapidly decline and become paralyzed even while being treated with high-dose steroids. Thus, even if the tumor is markedly radiosensitive, neurologic recovery takes precedence and is best achieved with surgery. (See "Treatment and prognosis of neoplastic epidural spinal cord compression", section on 'Patients with unknown or synchronous primary'.)

DIFFERENTIAL DIAGNOSIS — Aside from ESCC, cancer patients are prone to a variety of other malignant and nonmalignant causes of back pain and neurologic dysfunction.

Other causes of back pain in cancer patients — Benign or nonmalignant causes of back pain that should be considered, especially in patients without evidence of ESCC on initial imaging of the spine, include muscle spasm, intervertebral disk disease, and spinal stenosis. (See "Lumbar spinal stenosis: Pathophysiology, clinical features, and diagnosis".)

One feature that is sometimes helpful in differentiating pain of ESCC from benign causes of back pain is thoracic localization; the benign causes generally occur in the lumbar or cervical spine. One exception is osteoporotic compression fractures, which often occur in the thoracic as well as lumbar spine. The patient whose spine pain worsens while supine should not be presumed to have a benign cause. Nocturnal pain and pain with neurologic deficit serve as "red flag" symptoms that warrant early spinal MRI, since neoplastic pain often worsens at night and pain with neurologic deficit may signal neoplasm or infection.

Other neurologic complications of cancer — A number of other manifestations of metastatic disease can cause severe back pain with or without neurologic deficits:

●Intramedullary metastases occur much less frequently than epidural metastases and are most commonly associated with lung cancer. They produce pain, weakness, and numbness similar to ESCC. Unlike ESCC, they often produce a hemicord syndrome of unilateral weakness below the level of the lesion with contralateral diminution of pinprick and temperature discrimination; continued growth can lead to subsequent bilateral spinal cord dysfunction [42,43]. Intramedullary metastases may be missed on noncontrast imaging and are best visualized with contrast-enhanced spine MRI.

●Leptomeningeal metastases can produce a cauda equina syndrome, which may coexist with mental status changes, headache, and cranial nerve palsies [44,45]. Local back pain may not be present, but affected patients usually complain of radicular leg pain. MRI demonstrates no epidural tumor and may show pathologic thickening and nodular enhancement of the cauda equina nerve roots and leptomeningeal enhancement along the surface of the spinal cord. Cerebrospinal fluid (CSF) examination is usually diagnostic. (See "Clinical features and diagnosis of leptomeningeal disease from solid tumors", section on 'Diagnostic evaluation'.)

●Malignant plexopathy may involve the brachial or lumbosacral plexus. In most cases, the major clinical feature of malignant plexopathy is severe unrelenting local or radicular pain. Later, weakness and focal sensory disturbances occur in the distribution of the involved plexus [46]. In the absence of a palpable mass or ipsilateral extremity swelling, these symptoms can mimic ESCC. The paraspinal location of the plexus means that ESCC and malignant plexopathy often coexist. Specialized MRI or CT scanning tailored to evaluate the involved plexus can differentiate between these possibilities. Brachial plexopathy most commonly occurs in patients with breast and lung cancers. Lumbosacral plexopathy is usually due to colorectal and gynecologic tumors, sarcomas, and lymphomas. (See "Brachial plexus syndromes", section on 'Neoplastic' and "Lumbosacral plexus syndromes", section on 'Neoplastic invasion'.)

●Radiation myelopathy should be considered in patients who have previously received radiation to the spine or nearby structures. Rarely, patients may develop a chronic progressive radiation myelopathy that shares clinical features with ESCC. The total previous radiation dose and fraction size are important risk factors. The latency following radiotherapy is typically 9 to 15 months. (See "Complications of spinal cord irradiation".)

Affected patients usually develop painless ascending numbness and upper motor neuron findings that often have a hemicord localization, presumably because radiation has produced a vascular lesion [47,48]. The presence of a Brown-Sequard syndrome is helpful diagnostically. MRI or myelography distinguishes this entity from ESCC.

Other causes of spinal cord compression — A number of other disorders can simulate some of the findings in ESCC:

●Degenerative spine disease – Intervertebral disc herniation, synovial cysts, and cervical or lumbar spondylosis can cause acute or subacute myelopathy and radiculopathy, along with pain. Spondylotic myelopathy is the most common cause of myelopathy in older adults. MRI of the spine in the appropriate clinical context is diagnostic. (See "Cervical spondylotic myelopathy" and "Lumbar spinal stenosis: Treatment and prognosis".)

●Vertebral compression fracture with retropulsed bone – Osteoporotic vertebral compression fractures, which most commonly occur in the thoracolumbar spine, occasionally present with spinal cord compression due to retropulsed bone fragments in the spinal canal. Symptoms vary depending on the level of the fracture and degree of compression and may include cauda equina syndrome for lumbar fractures.

Distinguishing benign from metastatic (pathologic) vertebral fractures can be difficult. Features that help suggest a benign etiology include the presence of coexisting healed benign fractures at other levels, at least partial preservation of normal marrow signal, and visible fluid and/or air-filled fracture lines; features suggesting a malignant etiology include the presence of a paraspinal or epidural mass, destructive vertebral lesions at other levels, loss of normal marrow signal, and convexity or expansion of the posterior vertebral body contour [49]. (See "Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment".)

●Spinal epidural abscess – Spinal epidural abscess is an important condition to recognize and distinguish from ESCC. Predisposing factors include intravenous drug use, vertebral osteomyelitis, and hematogenous infection. The clinical manifestations may be indistinguishable from rapidly progressive metastatic ESCC. Neuroimaging usually can identify a likely infectious etiology but, in some cases, biopsy will be necessary for diagnosis. Tuberculosis and fungal infections in particular can mimic tumor. (See "Spinal epidural abscess".)

The leading bacterial pathogen causing spinal epidural abscess is Staphylococcus aureus, which accounts for approximately two-thirds of cases of bacterial etiology. Other infectious causes include Mycobacterium tuberculosis, which is responsible for up to 25 percent of cases. (See "Bone and joint tuberculosis".)

●Vascular malformation – Vascular malformations of the spinal cord, such as dural arteriovenous fistulas, can cause an acute or chronic progressive spinal cord syndrome with local back pain or radiculopathy [50]. The diagnosis can be suggested by spine MRI with contrast but generally requires magnetic resonance angiography and spinal angiography to confirm.

●Spinal epidural hematoma – Nontraumatic, spontaneous spinal epidural hematomas occurring in the presence of anticoagulant therapy, arteriovenous malformations, or inherited or acquired bleeding disorders are a rare cause of spinal compression [51]. The diagnosis can usually be established by MRI [52].

●Intradural extramedullary tumor – Meningiomas and nerve sheath tumors can compress the spinal cord and produce radicular and myelopathic syndromes. Their intradural location is usually apparent on spine MRI with contrast.

●Extramedullary hematopoiesis – Spinal cord compression can rarely be induced by extramedullary hematopoiesis due to thalassemia or chronic myeloproliferative or myelodysplastic disorders [53,54].

●Systemic inflammatory diseases – Rare cases of epidural involvement by rheumatoid arthritis, sarcoidosis, and tophaceous gout have been described [55-57].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Neoplastic epidural spinal cord compression" and "Society guideline links: Cancer pain".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Cauda equina syndrome (The Basics)" and "Patient education: Bone metastases (The Basics)").

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Neoplastic epidural spinal cord compression (ESCC), also referred to as epidural thecal sac compression, is a relatively common complication of cancer that can cause pain and potentially irreversible loss of neurologic function. The most common malignancies causing ESCC are prostate cancer, breast cancer, lung cancer, and multiple myeloma. (See 'Epidemiology' above.)

●Terminology – The degree of thecal sac compression required for the designation of ESCC has been variably defined. We use the term "ESCC" to mean any radiologic evidence of indentation of the thecal sac, whether or not there are neurologic signs and symptoms associated with compression (figure 1 and image 1). (See 'Terminology' above.)

●Signs and symptoms – The most frequent presenting symptom of ESCC is back pain, which almost always precedes neurologic dysfunction. Pain present only on movement frequently indicates mechanical instability of the spine. Spine Instability Neoplastic Score (SINS) facilitates recognition of spinal instability and appropriate referral for surgical evaluation (table 1). (See 'Pain' above.)

Motor findings represent advanced stages of ESCC. Unless there is profound weakness or severe pain with movement, the motor examination in patients with ESCC must include standing and walking in order to detect subtle weakness or ataxia. (See 'Motor findings' above.)

Urinary retention is the most common manifestation of autonomic dysfunction due to ESCC. It is usually a late finding and is rarely the sole symptom. (See 'Bladder and bowel dysfunction' above.)

●Diagnosis – MRI of the entire (cervical, thoracic, and lumbar) spine without and with contrast is recommended in patients with suspected ESCC. Imaging should be obtained as soon as possible and within 24 hours in patients suspected of having ESCC. This may require transferring the patient to another facility. (See 'Magnetic resonance imaging of the spine' above.)

CT myelography is the alternative imaging option in patients with suspected ESCC who cannot undergo MRI (eg, some electromagnetic cardiac devices, metallic foreign body in orbit). The procedure involves the direct injection of iodinated contrast into the thecal sac by either lumbar or, if necessary, cervical puncture, followed by CT imaging of the cervical, thoracic, and lumbar spine. (See 'Computed tomography myelography' above.)

●Role of biopsy – In most patients presenting with ESCC who have known metastatic cancer, biopsy of the compressive lesion is not necessary for treatment planning, and a vertebral lesion with a typical appearance can be presumed to be metastatic. Select patients require image-guided needle biopsy of the vertebral lesion for diagnosis and treatment planning. (See 'Cancer staging and role of diagnostic biopsy' above.)

●Differential diagnosis – Aside from ESCC, cancer patients are prone to a variety of other malignant and nonmalignant causes of back pain and neurologic dysfunction, all of which can frequently be distinguished from ESCC by history, examination, and MRI. (See 'Differential diagnosis' above.)