Keywords
nervous system metastasis, CNS metastasis, brain metastasis, skull-base metastasis, leptomeningeal metastasis, spinal cord metastasis, peripheral nervous system metastasis, neurolymphomatosis, muscle metastasis, metastasis, malignant disease
The entire nervous system is potentially vulnerable to metastatic disease, typically occurring in the setting of a known disseminated systemic malignancy. Approximately 45 percent of patients with systemic cancer and neurologic deficits are found to have metastatic involvement of the nervous system. The most common cancer-related neurologic diagnosis is brain metastasis (16%), followed by bone metastasis (10%) and epidural metastasis (9%). The incidence of metastatic involvement of the nervous system continues to rise due to improved treatment strategies directed towards primary cancers and systemic metastases. In 2012, estimated new cancer cases in the United States totaled 1.6 million people.
Metastatic involvement of the central nervous system, including its overlying structures, and the peripheral nervous system causes significant neurologic morbidity and mortality. The skeletal muscles are affected only rarely. Early diagnosis and treatment may prevent disability in these groups of patients, who have a limited life expectancy.
Metastases to the Central Nervous System and Related Structures
Brain
Epidemiology
Approximately 150,000 new cases of brain metastases occur annually in the United States, making metastases the most common intracranial tumor in adults. Brain metastases are more common in African-Americans than other ethnic groups. Two population-based studies demonstrated that 8 to 10 percent of patients diagnosed with a single primary cancer develop brain metastases during their lifetime. The incidence is highest for lung cancer (20%), followed by melanoma (7%) and then by renal (7%), breast (5%) and colorectal (2%) cancer. Unknown primary sources account for up to 14 percent of cases.
Pathophysiology
The most common mechanism of spread to the brain is hematogenous dissemination. The “anatomic or mechanical” hypothesis states that the distribution of metastases is related to the amount of blood flow to the brain. This phenomenon explains the predilection for brain metastases to involve the cerebral hemisphere in 80 percent, cerebellum in 15 percent, and brainstem in 5 percent of cases. As cancer cells travel through the arterial circulation, they become trapped in the end arteries at the gray-white matter junction ( Fig. 26-1 ). Only about two-thirds of metastases can be explained by blood flow alone, suggesting that other factors play a role. The “seed and soil” mechanism postulates that appropriate tumor cells or “seeds” grow in site-specific hosts or “soil.” Brain metastases are hypothesized to result from neurotropic factors facilitating “brain-homing” and direct interaction with neural substance. The vascular basement membrane of preexisting blood vessels promotes nonsprouting angiogenesis and proliferation of metastatic tumor cells by means of tumor cell vascular endothelial growth factor (VEGF). Contiguous brain invasion from intracranial dural and skull-base metastases is another mechanism by which brain metastases occur.
Pathology
Grossly, metastatic tumors in the brain are well circumscribed and surrounded by edematous white matter; cystic degeneration, necrosis, and hemorrhage can be seen. Metastatic lesions from melanoma, choriocarcinoma, and renal cell carcinoma have a high tendency for intratumoral hemorrhage. Microscopically, brain metastases are usually well demarcated and generally appear histologically similar to the primary tumor. Vascular proliferation within the lesions and reactive astrocytosis in the surrounding brain parenchyma may be encountered. Metastases from breast, kidney, and colon are usually solitary, whereas multiple metastases are common from melanoma and lung carcinoma.
Clinical Features
Neurologic manifestations in patients with brain metastases may be focal, resulting from local displacement or destruction of the surrounding parenchyma by the tumor or edema, or generalized due to increased intracranial pressure (ICP) or hydrocephalus. Patients usually present with subacute or chronic progressive neurologic signs and symptoms. Headache, typically worse in the morning, is the most common presenting symptom, affecting approximately 50 percent of patients. Focal neurologic deficits are present in 30 to 40 percent of patients, and seizures are the presenting feature in 15 to 20 percent ; nearly 15 percent are asymptomatic.
Over 80 percent of patients diagnosed with brain metastases have a known systemic malignancy or a metachronous presentation. In 5 to 10 percent, brain metastases are diagnosed at the same time as the primary malignancy and in another 5 to 10 percent the brain metastases are the presenting manifestation. A majority of patients (more than 30%) have multiple metastases with more than four lesions, 20 to 30 percent have two to three lesions (“oligometastases”), and another 20 to 30 percent have a solitary metastasis.
Diagnostic Studies
Magnetic resonance imaging (MRI) is the diagnostic modality of choice for the evaluation and monitoring of patients with brain metastases and is much more sensitive than computed tomography (CT) in detecting the number, size, location, and secondary effects of the lesions. Brain metastases tend to be multiple, spherical, and located at the gray-white matter junction, with surrounding vasogenic edema. These lesions appear isointense or hypointense on precontrast T1-weighted MRI sequences and enhance avidly upon contrast administration due to a disrupted blood–brain barrier. The surrounding edema is hyperintense on T2-weighted and fluid attenuated inversion recovery (FLAIR) sequences ( Fig. 26-1 ). The amount of surrounding edema is often disproportionate to the size of the lesions. Intratumoral hemorrhage within the tumor, when present, is evident on precontrast T1 and gradient recalled echo (GRE) sequencing ( Fig. 26-2 ). CT studies are generally utilized in acute settings to determine the presence of hemorrhage, herniation, or hydrocephalus. For patients previously treated with radiation, the differentiation of tumor recurrence from radiation effects with routine MRI may be challenging. Increased glucose metabolism with [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) studies is characteristic for brain metastases, whereas lesions composed of radiation necrosis are frequently hypometabolic; MR perfusion imaging may also allow this distinction.
A search for primary malignancy should be performed in patients with suspected brain metastases without a known systemic cancer. CT of the chest takes precedence over abdominal and pelvic evaluation because of the high frequency of brain metastases originating from the lungs. Whole-body FDG-PET is also helpful in investigating the primary source, although it has low specificity in differentiating malignant from benign inflammatory lesions. Biopsy of tumors discovered upon systemic evaluation is often easier than biopsy or resection of the brain lesion.
Differential Diagnosis
Several conditions mimic the radiologic findings of brain metastases including high-grade glioma, lymphoma, abscess, stroke, and demyelinating disorders. Different imaging techniques and special characteristics of the lesions may help distinguish between these clinical entities. An elevated cerebral blood volume in perfusion studies reflects tumor vascularity and is diminished in edema, radiation necrosis, or infarct. MR spectroscopy (MRS) detects the metabolic characteristics of these lesions, differentiating spectra of metastases, gliomas, vasogenic edema, or gliosis, and other mass lesions. Diffusion-weighted imaging (DWI) detects areas of the brain with decreased proton mobility, while the apparent diffusion coefficient (ADC) characterizes the rate of diffusional motion; unrestricted diffusion in DWI and high ADC value in the center of a ring-enhancing mass are suggestive of a necrotic mass as seen in metastasis or high-grade glioma. Restricted diffusion represents cytotoxic edema in an acute infarct, and is also seen in highly cellular lesions such as cerebral abscess, infectious encephalitis, or primary CNS lymphoma, In many cases, brain biopsy is required for definitive diagnosis.
Prognostic Variables
Classifying patients with brain metastases based on prognosis helps clinicians maximize survival while avoiding unnecessary treatments. Important factors that predict outcomes are age, performance status, status of primary tumor, and extent of extracranial disease. The Radiation Therapy Oncology Group (RTOG) used recursive partitioning analysis (RPA) to categorize patients into three prognostic classes. Patients harboring all four favorable prognostic factors (age less than 65 years, Karnofsky performance status (KPS) of at least 70, controlled primary tumor, and no extracranial metastases) had the best prognosis, with expected median survival of 7.1 months. Patients with KPS of 70 or more but at least one other unfavorable factor have an intermediate prognosis, with expected median survival of 4.2 months. A KPS of less than 70 is a poor prognostic factor, with median survival of 2.3 months ( Table 26-1 ). Important prognostic factors also vary depending on tumor type. The KPS, age, presence of extracranial metastases, and number of brain metastases are prognostic factors for patients with lung cancer; KPS and number of brain metastases are prognostic factors for melanoma and renal cell carcinoma; tumor subtype, KPS, and age for breast cancer; and KPS alone for gastrointestinal cancer.
| RPA Class | Factors | Median Survival |
|---|---|---|
| 1 | Age<65 years old KPS ≥ 70 Controlled primary tumor No extracranial metastases | 7.1 months |
| 2 | All patients not in class 1 or 3 | 4.2 months |
| 3 | KPS<70 | 2.3 months |
Treatment
Management includes supportive care for palliation of symptoms and definitive treatment directed toward the metastases, aiming to prolong survival while preserving quality of life. Most patients die from their systemic disease rather than from their metastases.
Supportive Treatment
Dexamethasone is the corticosteroid of choice in controlling vasogenic edema, as it has a long half-life, the best CNS penetration, the fewest mineralocorticoid side effects, and is the least protein bound. The recommended starting dose is 4 to 8 mg daily for symptomatic patients, and this can be increased up to 16 mg daily for patients presenting with acute signs of increased ICP. Its therapeutic effects are usually evident within 24 to 72 hours. Once clinical benefit occurs, dexamethasone should be titrated down to the lowest possible dose that provides relief of symptoms, in order to minimize adverse effects. Prophylactic treatment for peptic ulcers is generally not recommended, except for patients with a history of previous ulcer, those taking concurrent nonsteroidal anti-inflammatory drugs, or the elderly. Among patients with brain metastases, 20 percent experience seizures, and antiepileptic drugs (AEDs) should be given when they occur. Older AEDs such as phenytoin, phenobarbital, and carbamazepine induce cytochrome P450 hepatic enzymes, which potentially can accelerate the metabolism of many chemotherapeutic agents. Because of these drug interactions, nonenzyme-inducing AEDs such as levetiracetam are preferable. Evidence has failed to show benefit of prophylactic AEDs in decreasing the incidence of new-onset seizures, and therefore prophylaxis is not recommended. The evidence of benefit for prophylactic AEDs taken only in the perioperative period is equivocal; when AEDs are utilized in this manner, they should be discontinued 1 to 2 weeks postoperatively.
Surgery
Resection of brain metastases is performed to achieve local disease control, provide a histologic diagnosis, promote decompression from elevated ICP, and allow tapering of corticosteroids. Three randomized controlled trials have addressed the benefit of surgery combined with whole-brain radiation therapy (WBRT) compared to WBRT alone in patients with a solitary brain metastasis; a fourth randomized trial compared both treatments to surgery alone. These studies demonstrated significant benefits in local disease control and prolongation of functional independence from combination treatment compared to resection or radiotherapy alone, when given to patients with a single metastasis who were 60 years old or less and had controlled systemic disease and good KPS ( Table 26-2 ). For patients with more than one metastasis, surgery is generally limited to removal of the dominant, life-threatening lesion, and to obtain a histologic diagnosis.
| Population Studies | Median Survival | Duration of Functional Independence | ||||
|---|---|---|---|---|---|---|
| Test Group | Standard | Result | Test Group | Standard | Result | |
| Surgery+WBRT vs WBRT N =48 [Ref 25] | 40 weeks | 15 weeks | S | 38 weeks | 8 weeks | S |
| Surgery+WBRT vs WBRT N =63 [Ref 26] | 12 months | 7 months | S | 9 months | 4 months | S |
| Surgery+WBRT vs WBRT N =84 [Ref 27] | 5.6 months | 6.3 months | NS | – | – | – |
| Surgery+WBRT vs Surgery N =95 [Ref 28] | 48 weeks | 43 weeks | NS | 37 weeks | 35 weeks | NS |
Whole-Brain Radiotherapy
Treatment with WBRT targets both gross and microscopic metastases. Significant reduction of local and remote intracranial recurrence has been demonstrated in patients with solitary and oligometastases who received WBRT following surgical resection or stereotactic radiosurgery (SRS); however, overall survival and preservation of functional independence did not differ between those with or without adjuvant WBRT. Neurocognitive complications from radiation therapy range from mild short-term memory loss to severe irreversible dementia, which may occur acutely or may be delayed for years. Severe radiation-induced dementia is more frequent in patients who receive a short course of radiotherapy given in daily fractions, and the risk is increased for higher daily doses, particularly those exceeding 2 Gy. Because of the lack of significant benefit in overall survival and function, it is recommended to withhold WBRT after local control with either surgery or SRS. At present, there is no recommended standard dose-fractionation schedule, but 30 Gy divided into 10 fractions and 20 Gy divided into 5 fractions are commonly utilized regimens. For patients with multiple metastases, WBRT is used for palliation of symptoms and is standard treatment, prolonging overall survival for up to 3 to 4 months.
Stereotactic Radiosurgery
Stereotactic radiosurgery (SRS) is focused radiotherapy in which high-dose, single-fraction irradiation is directed at metastases while sparing the surrounding normal brain tissues from radiation exposure. SRS can be delivered by linear accelerator or gamma knife. It is beneficial in treating lesions less than 3 cm in size that are located in the eloquent areas, in the deep structures of the brain, or both, when these are not amenable to surgery. The risk of radiation-induced neurocognitive dysfunction is markedly less than with WBRT. For patients with unresectable solitary or oligometastases with good prognostic factors (RPA class I), SRS following WBRT confers better local control of lesions and stabilization or improvement of performance status compared to WBRT alone. Randomized controlled trials comparing SRS alone to SRS followed by WBRT showed improved local and remote intracranial control with combined treatment; however, overall survival and performance status were similar in both groups. Based on these randomized trials, close monitoring without WBRT following SRS is a reasonable option for patients with one to four brain metastases and good performance status.
Chemotherapy
Chemotherapy is recommended as first-line treatment for chemosensitive brain metastases such as germ cell tumors and non-Hodgkin lymphoma. For tumors not highly responsive to chemotherapy such as breast cancer, non–small cell lung cancer (NSCLC), and melanoma, chemotherapy is utilized as salvage therapy after radiotherapy has been exhausted. Treatment response is higher for chemotherapy-naïve tumors, but as most of these patients have already failed previous chemotherapy, radiotherapy is a more effective option in the treatment of brain metastases. Agents such as capecitabine for breast cancers, temozolomide for NSCLC, and fotemustine, temozolomide, and dacarbazine for melanoma may be used.
Targeted Therapies
Molecular targeted therapies have shown promising roles in the treatment of recurrent brain metastases, including gefitinib and erlotinib (epidermal growth factor receptor [EGFR] inhibitors) for NSCLC, lapatinib (EGFR and HER2 inhibitors) for HER2-positive breast cancer, sunitinib and sorafenib (VEGF receptor and platelet-derived growth factor [PDGFR] inhibitors) for renal cell carcinoma, and dabrafenib (a B-raf inhibitor) for melanoma.
Other Therapeutic Options
Local forms of both adjuvant chemotherapy and radiotherapy have shown some benefit in controlling local tumor recurrence. Local chemotherapy with carmustine wafers (Gliadel) placed directly in the tumor bed has shown low local recurrence rates following resection and radiotherapy. Brachytherapy is a form of localized radiotherapy where a radioactive source is placed in the surgical cavity; brachytherapy using the GliaSite Radiotherapy System has demonstrated local control comparable to WBRT and SRS.
Prophylactic Cranial Irradiation
In malignancies with a high predilection to metastasize to the brain such as small cell lung cancer (SCLC), prophylactic cranial radiation may be used. Patients with SCLC and limited or extensive systemic disease who respond to chemotherapy have decreased incidence of brain metastases from 40 to 14.6 percent, improvement of disease-free survival from 12 to 14.7 weeks, and overall survival improvement from 5.4 to 6.7 months with prophylactic cranial irradiation. This prophylactic strategy did not show the same degree of benefit in NSCLC. In long-term survivors of operable NSCLC treated with neoadjuvant chemoradiotherapy, neurocognitive function was not affected by whether prophylactic cranial irradiation was provided.
Skull Base
Definition and Epidemiology
The base of the skull forms the floor of the cranial cavity and is composed of the ethmoid, sphenoid, occipital, paired frontal, and paired parietal bones. Metastases to the skull base may involve the cranial nerves and blood vessels that pass through foramina in these bones. Skull-base metastases occur in 4 percent of cancer patients, frequently late in the course of the disease. The most common responsible primary malignancies are prostate (38.5%), breast (20.5%), lymphoma (8%), and lung (6%).
Pathophysiology
The skull base may become involved directly from hematogenous spread of malignant cells or by retrograde seeding through the Batson plexus, a common route in prostate carcinoma. Osseous metastases may entrap and compress the nearby cranial nerves and vessels, producing neurologic signs and symptoms. Direct extension from head and neck malignancies may also involve the skull base.
Clinical Features
Skull-base metastases produce symptoms when they enlarge and compress surrounding structures, causing pain and neurologic deficits. The development of cranial neuropathies or craniofacial pain in patients with malignancy should raise the suspicion of skull-base metastases. Cranial neuropathies are the presenting symptom in 28 percent of patients with such metastases. The anatomic location involved can lead to specific clinical syndromes, including parasellar and sellar syndromes in 29 percent, middle fossa syndromes in 6 percent, and jugular foramen syndromes in 3.5 percent of patients ( Table 26-3 ).
| Skull-Base Syndromes | Cranial Neuropathies | Associated Findings | Common Primary Malignancies |
|---|---|---|---|
| Orbital syndrome | CN II, III, IV, VI and V-1 | Supraorbital frontal headache, pain, diplopia, proptosis, periorbital swelling, decreased vision | Prostate cancer Lymphoma Breast cancer |
| Parasellar/Cavernous sinus syndrome | CN III, IV, VI and V-1 and V-2 | Supraorbital frontal headache, no proptosis, vision may be affected late in the course | Lymphoma |
| Middle fossa/Gasserian ganglion syndrome | CN V-2 and V-3 sensory and motor roots; CN III, IV, VI and VII (less common) | Lightning-like facial pain, sparing the forehead; headache is uncommon | Breast cancer Lung cancer |
| Jugular foramen syndrome | CN IX, X and XI (Vernet syndrome) plus CN XII (Collet–Sicard syndrome) | Unilateral occipital and postauricular pain; Horner syndrome (Villaret syndrome) | Breast cancer Melanoma Ewing sarcoma Prostate cancer |
| Occipital condyle | CN XII | Occipital pain, stiff neck | Breast cancer Prostate cancer |
| Numb chin syndrome | Mental nerve | Unilateral anesthesia of chin and lower lip | Breast cancer Lymphoma Melanoma Lung cancer Prostate |
Diagnostic Studies
Advances in MRI techniques have greatly improved the identification and evaluation of the extent of skull-base metastases, including bone marrow invasion, perineural spread, and cranial nerve, leptomeningeal, and brain parenchymal involvement ( Fig 26-3 ). Radionuclide bone scanning can detect skull-base metastases in 30 to 50 percent of these patients, but it has a relatively poor sensitivity in detecting purely lytic lesions. CT using bone windowing is the best means of detecting lytic bone destruction. Dual-isotope single-photon emission computed tomography (SPECT) may show increased uptake in the skull base. CSF examination and biopsy are sometimes indicated to establish the diagnosis of skull-base metastases.
Differential Diagnosis
Primary skull tumors, such as osteoma and chondrosarcoma, and benign tumor-like lesions including fibrous dysplasia may appear radiographically similar to skull-base metastases. Patients with metastases are generally older, with a median age of 70 years, have shorter duration of symptoms (median of 2 months), and present less frequently with neurologic deficits than patients with these other lesions.
Treatment
Radiation therapy is the standard treatment, providing pain relief and improvement of cranial nerve dysfunction. The beneficial effects parallel the timing of irradiation—87 percent of patients who receive radiation within 1 month of symptom onset show clinical improvement compared with 25 percent of patients treated after 3 months. Stereotactic radiosurgery provides clinical improvement in 62 percent and tumor control in 67 percent of patients, and can be used as an initial treatment, especially for lesions near neural structures and for previously irradiated tumors. For chemosensitive tumors such as breast and prostate carcinomas, chemotherapy and hormonal therapy in combination with radiation therapy offer survival benefits. Surgery may be considered for radioresistant tumors such as melanoma, renal cell carcinomas, and sarcomas, as well as in patients with rapid neurologic decline, such as visual loss, with the goal of preserving neurologic status and symptom relief.
Prognosis
Skull-base metastases are typically seen in disseminated malignancies, and the overall median survival is 31 months. Patients with metastases from breast carcinoma have the best survival (60 months); prostate carcinoma and lymphoma, intermediate survival; and lung and colon carcinomas the worst survival (2.5 and 2.1 months, respectively).
Intracranial Dura
Definition and Epidemiology
Carcinomatous infiltration of the dura and epidural space is found at autopsy in 9 percent of patients with primary malignancies. Common primary tumors include breast, prostate, and lung carcinomas. They are more common in women; the mean age at diagnosis is 59 years.
Pathophysiology
A majority of patients develop intracranial dural metastases by direct extension from skull metastases, whereas hematogenous spread accounts for 33 to 43 percent. Nontraumatic subdural hematoma occurs in 15 to 40 percent of patients, presumably due to rupture of fragile tumor vessels and to mechanical obstruction of external dural vessels leading to dilation and rupture of dural capillaries. Chronic subdural hematoma alters the barrier properties of the dura, promoting tumor infiltration.
Clinical Features
Dural metastases produce symptoms through traction of the dura, invasion of venous sinuses, elevation of ICP, and compression of the underlying brain parenchyma, cavernous sinus, and surrounding neural structures. Common presentations include headache, cranial neuropathies, visual changes, altered mentation, and seizures. The presence of new or localized headache in these patients is suggestive of subdural hematoma and should prompt imaging. Between 11 and 20 percent of patients are asymptomatic, diagnosed incidentally on imaging or at autopsy.
Diagnostic Studies and Differential Diagnosis
Gadolinium-enhanced MRI is the imaging study of choice for identification of dural metastases. These lesions typically enhance homogeneously and may be single or multiple. They may appear as localized or diffuse thickening or nodular enhancement of the dura ( Fig. 26-4 ). CT scan can detect bony involvement. The main differential diagnosis is meningioma, which also presents as an extraaxial, well-circumscribed, hyperdense, contrast-enhancing lesion with a dural tail and hyperostosis of overlying bone. High lipid signal in MR spectroscopy, a low relative cerebral blood volume in dynamic contrast (perfusion) MRI, increased FDG-PET uptake, and accumulation of tracer in octreotide brain scintigraphy all favor metastasis over meningioma. Pachymeningeal metastases demonstrate dural enhancement localized under the inner table of the skull and do not follow the contour of the gyri in contrast to leptomeningeal involvement.
Treatment
Surgical resection improves overall survival and should be considered as initial treatment for patients with controlled systemic disease and a single, symptomatic, resectable intracranial dural metastasis. Systemic chemotherapy also prolongs progression-free survival perhaps due to breakdown of the blood–brain barrier in dural metastases. For patients who are not candidates for surgery, have poor performance status, and short life expectancy, focal or whole-brain radiation is considered.
Prognosis
The overall median survival is 6 to 9.5 months and progression-free survival is 3.7 months with dural metastases. Patients with primary hematologic malignancies or breast and prostate carcinomas have relatively favorable courses compared to those with other primary cancers. Poor performance status and lung carcinoma are adverse prognostic factors, while treatment with resection and chemotherapy is associated with improved overall and progression-free survival.
Spine and Spinal Cord
Epidemiology
Bone is the most common site of metastases, and the axial skeleton is the most frequent site affected. Autopsy series reveal spinal metastasis in more than 70 percent of patients with disseminated cancer. The incidence is greatest for breast (73%) and prostate (68%) cancers, followed by thyroid (42%), kidney (35%), and lung (36%) cancers. Spinal metastases are 20 times more common than primary spinal tumors.
Classification by Anatomic Location
Spinal tumors are classified according to anatomic location ( Table 26-4 ). Extradural metastases account for more than 94 percent of secondary spinal tumors. Most arise from the vertebral bodies and extend to the spinal canal, eventually compressing the spinal cord or cauda equina. Intradural extramedullary metastases are rare and usually represent tertiary spread via CSF from cerebral metastases to the cauda equina, termed “drop metastasis.” Intramedullary metastases account for about 3.5 percent of spinal metastases and are increasing in frequency, likely due to improvement in detection.
| Anatomic Locations | Tumors |
|---|---|
| Extradural | Metastases Chordomas Sarcomas Lymphomas Plasmacytomas and multiple myeloma |
| Intradural, extramedullary | Meningioma Nerve sheath tumors |
| Intramedullary | Ependymomas Astrocytomas Metastases |
Epidural Spinal Cord Compression
Epidemiology
The annual incidence of hospitalization related to epidural spinal cord compression among patients with cancer is 3.4 percent. The most common primary sources are lung and prostate cancer, and multiple myeloma. The thoracic spine is most commonly involved (70%), followed by the lumbar (20%) and cervical (10%) spine; this distribution reflects the number and volume of vertebral bodies in each spinal segment. Multiple noncontiguous lesions are common, occurring in 10 to 40 percent of cases.
Pathophysiology
Epidural spinal cord compression results from several mechanisms. Hematogenous spread is the most common route, occurring in 85 percent of cases. The Batson venous plexus drains the vertebrae and skull and forms anastomoses with veins draining the thoracic, abdominal, and pelvic organs and breast. This valveless venous system serves as a pathway to transmit metastatic cells to the spinal column. Tumor cells may also seed via the arterial circulation to the vertebral bodies, which have a relatively large blood flow. Metastatic cells cause vertebral bone destruction, mass expansion within the vertebral body, and eventual outgrowth into the epidural space. Less commonly, tumor cells from the paraspinal region reach the epidural space directly through the intervertebral foramen, particularly in patients with lymphoma and neuroblastoma. Direct hematogenous metastasis to the epidural space is rare.
Direct mechanical injury to the axons and myelin, along with secondary vascular compromise of the epidural venous plexus and spinal arteries, results in spinal cord edema, infarction, and subsequent dysfunction. Tumor production of VEGF is also associated with spinal cord hypoxia. In addition, tumor invasion of the bony spine can harm the spinal cord by destabilization of the spinal column.
Clinical Features
Back pain is the most common presenting symptom, affecting more than 95 percent of patients with epidural spinal cord compression. The pain is initially localized over the involved vertebral bodies and is attributable to stretching of the periosteum and other adjacent pain-sensitive structures. It is typically chronic, with a median duration of 2 months, and increases in severity over time. It is frequently worse with the Valsalva maneuver and recumbency as a result of distention of the venous plexus. When nerve roots are involved, patients may complain of radicular pain or a tight band around the chest and abdomen. Acute pain raises the suspicion of pathologic compression fracture. Motor deficits are the second most common symptom (60 to 85%) followed by sensory symptoms (60%). The weakness may be upper motor neuron in type from compression of the spinal cord when the lesion is above the L1-2 vertebral bodies, or lower motor neuron in type from compression of the cauda equina when the lesion is below this level. More than half of patients with epidural spinal cord compression are nonambulatory upon diagnosis. Spinal cord compression produces a sensory level at or above the level of epidural involvement, and nerve root compression results in a dermatomal pattern of sensory deficits. Patients with compression of the posterior columns in the cervical and upper thoracic segments of the spinal cord may experience Lhermitte phenomenon. Autonomic symptoms, including bowel and bladder dysfunction, sexual disturbance, and orthostatic hypotension, tend to occur late in the course of epidural spinal cord compression.
Diagnostic Studies
Epidural spinal cord compression is a neuro-oncologic emergency as neurologic deficits may progress rapidly. MRI is optimal for detecting the lesion, with an overall accuracy of at least 95 percent. Because multiple lesions are common, the entire spine should be imaged. Vertebral metastases appear hypointense on T1-weighted MRI sequences, hyperintense on T2-weighted sequences, and show postgadolinium enhancement ( Fig. 26-5 ). Increased T2 signal within the spinal cord represents venous congestion or ischemia. For patients in whom MRI is contraindicated, CT myelography is an acceptable alternative. Plain radiography, bone scans, and spinal CT do not adequately depict the tumor, spinal cord, and paraspinal region. Around 80 percent of patients with epidural spinal cord compression have a known systemic malignancy, and immediate treatment should be initiated once the diagnosis is made. For patients without prior history of cancer, biopsy of the paraspinal or vertebral lesion to make a tissue diagnosis is warranted.
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