Clinical manifestations

Presentation and course

Neurologic features. Local back pain and radicular or referred pain in a limb are the most common initial symptoms (05; 50). Aggravation of pain with cough, straining at stool, deep inspiration and straight leg raising, and vertebral percussion tenderness are often present. These features, so typical of extradural compression of a nerve root, probably come about as a result of the frequent location of intramedullary metastatic tumor in the dorsal horn of the spinal cord (13; 04). Weakness of one arm or leg, another common early symptom, develops with tumor in the medial portion of the lateral column or in the ventral horn.

Later in the course of the illness, a variety of spinal syndromes may appear:

Several classic neurologic features of intramedullary glioma have not been reported in spinal cord metastasis, including muscle atrophy and fasciculations, syringomyelic dissociation of sensory loss, sacral sparing, and early, rather than late, involvement of bladder and bowel function.

The course of the myelopathy is subacutely progressive in most patients. The median duration of symptoms before diagnosis is 3 weeks, with a range of one day to six years (44). The neurologic deficit develops in less than a week in 17% of patients, less than a month in 58%, and less than six months in 97% (05). The rate of progression of the deficit is often uneven. There may be sudden changes in signs and symptoms. Symptoms may be stable for weeks and then worsen quickly. A patient who has had only pain for weeks may develop paraplegia over a few days' time (03; 18; 15; 05; 08; 45). The reason for this is that intramedullary spinal cord metastases are well demarcated. As they grow, they displace but do not infiltrate the surrounding neural tissue. Clinical symptoms may be minor. When the tumor reaches a certain size, it interferes with the vascular supply of the spinal cord and causes infarction of the segments that contain tumor and are adjacent to tumor. When this occurs, the signs and symptoms progress rapidly (03). Rarely, the disease pursues a chronic, slowly progressive course (50; 22).

Oncologic features. In a literature review of 138 cases of intramedullary spinal cord metastasis, the most common primary tumors were lung and breast cancer and melanoma (44), similar to what is noted with brain metastases. The median age of the patients was 56 years, with a range of four to 82 years. Children have seldom been reported (06). More men are affected than women because lung cancer, the most common primary tumor, is more prevalent in men (44; 43).

Most patients are known to have cancer when spinal cord symptoms begin. The median interval between the diagnosis of cancer and the appearance of symptoms of intramedullary spinal cord metastatic tumor is 16 months, but the interval may be several years (44). Intramedullary spinal cord metastasis usually occurs in the setting of widespread metastatic disease outside the nervous system. Tumor is present in lung, bone, and other sites in 55% of patients (44). The spinal cord is occasionally the first site of metastatic disease, particularly in long-term survivors of lung cancer (11; 05; 09; 10). The reason is that the blood-central nervous system barrier is relatively impermeable to chemotherapeutic agents; therefore, the spinal cord becomes a sanctuary for growing tumor cells. In 19% to 26% of patients diagnosed with intramedullary spinal cord metastasis, it is the presenting feature of an occult malignancy (44; 26). This high figure is surprising and probably reflects publication bias. Myelopathy of unknown cause is a dramatic presentation that may prompt complete diagnostic evaluation or transfer to a tertiary care facility and subsequent report. In contrast, patients with widespread metastatic disease who develop paraplegia as a terminal event may not be worked up but given only palliative care (11).

In many patients, the spinal cord is not the only site of metastasis in the central nervous system. Brain metastasis is present in 61% of patients (44). Leptomeningeal metastatic disease has been found in 17% of patients, mainly in those with small cell carcinoma of the lung (19). It is not clear whether the intramedullary spinal cord metastasis resulted from independent, blood-borne spread or from the direct extension of meningeal tumor (48; 33; 41).

Prognosis and complications

The median survival of patients with intramedullary spinal cord metastasis is four months (range, 4 days to 5 years) (44). Two studies concluded that patients with breast cancer survive longer than those with lung cancer, but the studies were retrospective and had few patients; therefore, the conclusion is probably not reliable (41; 24). Untreated, metastatic tumor destroys the spinal cord; hence, the prognosis for preservation or recovery of spinal cord function in untreated patients is poor. The cause of death is usually widespread systemic and cerebral metastatic disease (05).

Specific complications of intramedullary spinal cord metastases are not mentioned in the literature. Patients who survive long are susceptible to all the complications of chronic spinal cord injury.

Clinical vignette

A 49-year-old smoker noticed clubbing of his fingers late in 1989. His work up disclosed non-small-cell carcinoma of the lung, metastatic to the adrenal glands and the brain.

His brain metastases were asymptomatic. He was treated with cranial irradiation and, between December 1989 and April 1990, received four cycles of systemic chemotherapy. He was without neurologic symptoms until mid-April 1990, when he noticed low back pain and numbness and tingling in both great toes. Over the next 3 weeks, the paresthesias spread throughout the lower limbs. He also noticed weakness in both lower limbs and an unsteady gait. Micturition, defecation, sexual function, and his upper limbs were normal. When examined on May 11, 1990, his mental status and cranial nerves were normal. There was mild weakness of the left iliopsoas, quadriceps, tibialis anterior, and right quadriceps muscles. There was no spasticity or muscle atrophy. The deep tendon reflexes were absent at the knees, 3+ at the ankles, and 2+ in the upper limbs. The plantars were flexor. Light touch and pinprick were decreased bilaterally in L3, L4, and L5 dermatomes. Dermatomes above and below were spared. MRI was consistent with an intramedullary metastatic tumor.

Dexamethasone and spinal cord radiation therapy were started. By June 1, he could no longer walk because of worsening leg weakness. Numbness had risen to his buttocks, but the penis and scrotum were spared. On June 4, a bladder catheter was required because of urinary retention. The tumor was surgically excised on June 18, 1990. He died of progressive metastatic disease on September 21, 1990. His surgery did not improve but did stabilize his spinal cord function.

Biological basis

Etiology

The spread of malignant cells from solid tumors outside the spinal cord is the cause of intramedullary spinal cord metastasis.

Pathology and pathogenesis

Two pathologically distinct forms of intramedullary metastatic tumor occur and indicate spread to the spinal cord by 2 different routes. In most patients, a mass lies deep within the cord, the result of hematogenous spread of tumor.

Less often, focal or multifocal direct extension of leptomeningeal metastatic tumor across the pia mater into the parenchyma of the cord occurs (49; 04).

Jayakumar and colleagues described a third mechanism of spreadperineural invasion (17). They reported a patient with breast cancer that had metastasized to the left brachial plexus. She developed paraparesis, and MRI showed an intramedullary metastasis at C6-C7. There was no pathological verification, but the authors' idea, that tumor reached the spinal cord by perineural spread, as in head and neck cancer, is reasonable.

In large series, blood-borne metastases were evenly distributed along the length of the spinal cord (44). Intramedullary metastases are multiple in at least 15% to 23% of patients. This is likely an underestimate because the cervical cord is seldom examined at autopsy and because many metastases are microscopic in size and easily missed at autopsy (04; 05; 33). The spinal cord may be grossly distorted. It may be evenly or unevenly enlarged and fusiform or irregular in outline (04; 11; 05). If the tumor is small, the uncut cord appears grossly normal (13; 04). The dorsal root may be enlarged as the result of centrifugal spread of tumor from the cord into it (04). On cut section, the tumor is round, well demarcated from the surrounding spinal cord tissue, and may occupy many adjacent segments (13; 04; 05).

Most often, the tumor lies in the ventral part of the dorsal horn or the medial portion of the lateral column, with sparing of the lateral portion (13; 04).

Clinical correlates of that include the frequent early occurrence of ipsilateral segmental pain, paresthesias, and monoparesis (05; 50). The center of the tumor is usually necrotic.

Necrosis of the spinal cord may occur as a complication of the tumor (13; 04). It plays a part in the progression of the myelopathy and is responsible for sudden changes in neurologic signs, sudden acceleration in the pace of deterioration, and a discrepancy between the segmental level of the clinical deficit and that of the tumor. A cone-shaped or pencil-shaped zone of necrosis may extend above and below the tumor (13; 04; 50).

This unusual infarct is probably due to compression of the central artery of the spinal cord by the intramedullary tumor (15; 13). The rising front of necrosis may lead to a rising sensory level on the trunk and may turn paraplegia into tetraplegia (50). Descending necrosis may cause spastic, hyperreflexic paraplegia to become flaccid and areflexic (50). Cavitation of the zone of necrosis may give rise to a secondary syringomyelia, as in intramedullary gliomas (08). Hemorrhage above and below the tumor, similar to pencil-shaped necrosis in location and probably cause, and bleeding into the tumor itself can also occur as complications (20; 13).

Epidemiology

In large autopsy studies, the frequency of intramedullary spinal cord metastasis ranges widely, from 0.9% to 2.1% of patients with cancer (04; 33). There are 2 reasons for the discrepancy. The first is selection bias. Some series were prospective, with every spinal cord examined, but others were retrospective, with exclusion of many cancer patients because their cords had not been removed at autopsy (49; 04). An even greater problem common to all autopsy studies is the sampling procedure. Many metastases are microscopic, and an indeterminate number of them will be overlooked when only a few blocks of spinal cord are examined microscopically (04).

Autopsy series by their very nature present a picture of end stage disease and the presence of micrometastatic disease at time of death may not hold substantial clinical relevance. A comparison with metastatic epidural spinal cord compression gives a clearer, more workable, and more accurate idea of the frequency of intramedullary spinal cord metastasis as a cause of clinical myelopathy among cancer patients. In four retrospective studies of spinal cord metastases, 94% to 97% of patients had epidural spinal cord compression, and 3% to 6% of patients had intramedullary metastasis (See Table 1).

Table 1. Relative Frequency of Intramedullary Spinal Cord Metastatic Tumor and Metastatic Epidural Spinal Cord Compression

Approximately 300 cases of intramedullary spinal cord metastasis have been reported (44). The primary tumor in half of these patients was lung carcinoma. The next most common were breast cancer (16%), melanoma (6%), renal-cell carcinoma (5%), colorectal cancer (5%), and lymphoma (5%). Costigan and Winkelman provided data on the frequency with which specific tumors spread to the cord: melanoma (5.6%), lung (2.8%), and breast cancer (1.3%). Small cell was the most frequent histologic type of lung cancer to spread to the spinal cord (04).

Differential diagnosis

Confusing conditions

In patients known to have cancer. The diagnosis of intramedullary spinal cord metastasis in a patient known to have cancer is a different clinical problem than in a patient not known to have a malignancy. A myelopathy that arises during the course of a systemic malignancy is most often due to compression by an epidural metastatic tumor. There are few oncologic or neurologic differences between intramedullary metastasis and epidural compression. Certain tumors (eg, adenocarcinoma of the prostate, sarcomas, and myeloma) commonly spread to the spinal column and then extend to the spinal epidural space but rarely metastasize to the intramedullary spinal cord (02). The neurologic deficit of intramedullary metastasis often evolves over weeks, whereas that of epidural cord compression more often progresses over days (05). Intramedullary spinal cord metastasis frequently presents as a Brown-Sequard syndrome, whereas metastatic epidural spinal cord compression rarely does (41). However, metastatic epidural spinal cord compression is so much more common than intramedullary metastasis that it must always be considered the more likely diagnosis until excluded by MRI or myelography. Once metastatic epidural spinal cord compression has been eliminated from the differential diagnosis, the physician is faced with a clinical problem that can be formulated as a noncompressive myelopathy in a patient with cancer. Intramedullary spinal cord metastasis, delayed radiation myelopathy, paraneoplastic myelopathy, immune checkpoint inhibitor-associated myelitis, and leptomeningeal metastasis are the major causes.

Intramedullary metastasis versus radiation myelopathy. The neurologic features by which these differ are the presence of pain, the mode of onset, and the tempo of progression. Pain, as an early or prominent symptom, favors the diagnosis of intramedullary metastasis. Local back or neck pain, deep aching pain referred to a limb, or frank radicular pain is the most common initial symptom. In contrast, pain is generally absent early in the course of radiation myelopathy and is never a prominent symptom. Local pain and root pain are particularly unusual. The onset of radiation myelopathy is insidious, and the progression is slow, over a period of months to years. The disease may become arrested before paraplegia supervenes. In contrast, the symptoms of intramedullary metastasis begin abruptly and progress steadily, over a period of days to weeks, to paraplegia. But exceptional patients with a slow progression of symptoms, over months or years, have been reported (06; 50; 22); so, a slow tempo favors the diagnosis of radiation myelopathy, but it does not exclude intramedullary metastasis.

The location of the primary tumor and past exposure to therapeutic radiation are oncologic features useful in separating intramedullary metastasis from radiation myelopathy. Sixty-four percent of patients with intramedullary metastasis have lung or breast cancer, and less than 1% have tumors of the head and neck (44). In contrast, more than 80% of patients with radiation myelopathy have tumors of the head and neck, and only 6% have carcinoma of the lung or breast (50). This is probably due to the low frequency with which head and neck tumors spread hematogenously and to the large doses of radiation used to treat them.

The diagnosis of radiation myelopathy should not be based on a vague incrimination of a past course of radiation therapy. The occurrence of radiation myelopathy is dose-related. The risk increases with a higher total and fractional dose of radiation, a shorter treatment time, and a greater length of spinal cord irradiated. A total dose of 5000 cGy given in 25 fractions over 5 weeks is safe for most patients. A delay of at least 4 months between exposure and the onset of spinal symptoms is characteristic. In addition, the full extent of the spinal cord lesion, determined by clinical means, must fall within the portal of radiation for the diagnosis to be tenable. Increased bone marrow signal on T1-weighted MR images is helpful in identifying the spinal levels irradiated. MRI may show abnormal signal in spinal cord segments just outside the radiation portal, most likely representing edema, but the major focus of the lesion and gadolinium enhancement lies within the portal (30; 29).

Both intramedullary metastasis and radiation myelopathy typically show increased signal on T2-weighted MR images, decreased signal on T1-weighted images, and a central area of diffuse, ring, or crescent-shaped enhancement, and both can cause secondary syringomyelia (08; 47; 35; 21). Two MRI features are of differential value. The spinal cord may be normal in size or enlarged in both diseases, but it undergoes atrophy in radiation myelopathy and appears small on imaging 8 to 10 months after the onset of symptoms (29; 47). Many patients with radiation myelopathy have normal MRI (01), but few with intramedullary spinal cord metastatic tumor do.

Intramedullary metastasis versus paraneoplastic myelopathy. Paraneoplastic necrotizing myelopathy was first described in 1964, by Mancall and Rosales. The neurologic features by which it differs from intramedullary spinal cord metastatic tumor are the presence of pain and the mode of progression of the myelopathy. Pain is absent or mild in necrotizing myelopathy, but it is a major symptom in intramedullary metastasis. The pathologic process of necrotizing myelopathy begins in the thoracic portion of the spinal cord and then ascends and descends in the cord (27). The descending progress is reflected clinically by paraplegia that changes from spastic and hyperreflexic to flaccid and areflexic or that is flaccid from the beginning and never becomes spastic. The ascending progress reveals itself as a sensory level rising segment by segment or as paraplegia becoming tetraplegia. Although this pattern of progression is characteristic of necrotizing myelopathy, the clinical deficit of intramedullary metastasis can progress in an identical manner, by 2 different mechanisms: the accumulation of metastases throughout the cord and progressive, so-called pencil-shaped necrosis of the spinal segments above and below the tumor (11; 50). Thus, although an ascending or descending progression of spinal signs is characteristic of necrotizing myelopathy, it is not pathognomonic, and its presence does not favor that diagnosis over intramedullary metastasis.

The presence of cerebral metastases is the only oncologic feature of value in separating intramedullary metastasis from necrotizing myelopathy. Cerebral metastases, often asymptomatic, are present in 61% of patients with intramedullary spinal cord metastasis but have been absent in all reported cases of paraneoplastic necrotizing myelopathy (50; 44). The myelographic and MRI features of intramedullary metastasis and necrotizing myelopathy are too similar to be of differential value (31; 46).

Flanagan and colleagues described paraneoplastic isolated myelopathy (07). Most patients, unlike those with intramedullary spinal cord metastatic tumor, have cerebrospinal fluid pleocytosis, and many have unique oligoclonal bands. Most patients also have neuronal autoantibodies in serum, mainly anti-Hu, anti-CRMP, or anti-amphiphysin. MRI shows symmetric, often enhancing and longitudinally extensive signal abnormality in long tracts or gray mattervery different from the MRI appearance of intramedullary spinal cord metastasis (40).

The same group of investigators from the Mayo Clinic described paraneoplastic myeloneuropathy (42). It resembles isolated paraneoplastic myelopathy, except that there are also clinical and electromyographic findings of polyneuropathy, in the form of polyradiculoneuropathy, sensorimotor polyneuropathy, or sensory ganglionopathy. MRI often shows enhancement of lumbar nerve roots. Like isolated paraneoplastic myelopathy, this illness differs from intramedullary spinal cord metastatic tumor in its MRI, cerebrospinal fluid, and serologic aspects.

Intramedullary spinal cord metastasis versus immune checkpoint inhibitor-associated myelitis. Immune checkpoints are cell-surface proteins that prevent T-lymphocytes from attacking the bodys normal tissue, but they also protect malignant tissue. Immune checkpoint inhibitors, a class of cancer chemotherapy, allow T-cells to attack cancer cells, but the drugs can create autoimmune diseases as side effects, of which 1% to 3% are neurologic. Myositis, peripheral neuropathy, and myasthenia gravis are the most common, but myelitis has been reported (28; 36), often associated with paraneoplastic neuronal autoantibodies in serum (23; 28). This myelitis resembles paraneoplastic isolated myelopathy and paraneoplastic myeloneuropathy in its clinical, MRI, cerebrospinal fluid, and serologic features, thus, distinguishing it from intramedullary spinal cord metastatic tumor should be relatively easy.

Intramedullary spinal cord versus leptomeningeal metastases. The characteristic picture of leptomeningeal metastasis is a combination of cerebral signs, cranial nerve palsies, and spinal radiculopathies; corticospinal tract signs are absent. Therefore, most cases of leptomeningeal metastasis are not mistaken for a focal, intramedullary lesion of the spinal cord, such as a metastatic tumor, with its upper border of segmental spinal signs, long-tract signs below, and absence of neurologic abnormalities above. However, 2 presentations of leptomeningeal metastasis can mimic intramedullary spinal cord metastasis. The cauda equina syndrome of leptomeningeal carcinomatosis is almost identical to the conus medullaris syndrome of a metastatic tumor, and leptomeningeal metastatic involvement of one or several neighboring spinal roots can cause the same localized root pain, segmental paresthesias, or monoparesis as a small metastatic tumor in the dorsal or ventral horn of the spinal cord. Such tumors may be too small for visualization by MRI. CSF examination will be positive for tumor cells in most patients with leptomeningeal metastasis. Of course, some patients have both intramedullary spinal and leptomeningeal metastatic tumor. The treatment of leptomeningeal metastasis consists of radiation directed to the site of major clinical involvement and, sometimes, intrathecal or intraventricular chemotherapy or systemic therapy. The treatment of intramedullary spinal cord metastasis is radiation therapy. If doubt remains as to which of these is the diagnosis, radiation therapy, with the portal determined by clinical localization of the spinal lesion, can be started while further diagnostic studies are carried out.

In patients not known to have cancer. Intramedullary spinal cord metastasis should be considered in the differential diagnosis of any acute or subacute myelopathy, especially in middle-aged or elderly patients. Rapid progression of an intramedullary metastatic tumor will suggest postinfectious, viral, or idiopathic transverse myelitis. Painful paraplegia appears so suddenly in some patients that the initial diagnosis may be myelomalacia or hematomyelia. A slowly growing metastatic tumor mimics spinal glioma or syringomyelia. A course denoting progressive, segment-by-segment destruction of the spinal cord will raise the question of acute or subacute necrotizing myelopathy. Although a sensitive test for intramedullary spinal lesions, MRI does not provide a specific diagnosis. Most patients with intramedullary spinal cord metastasis have primary or metastatic lung cancer and many have cerebral metastases; therefore, a search for underlying malignancy should include chest and head imaging.

Diagnostic workup

Experience with imaging intramedullary spinal cord metastases has been recorded with oil-based myelography, myelography with water-soluble contrast and subsequent CT scanning, and MRI. Oil-based myelograms are normal in up to 50% of patients because the tumor is too small to enlarge the cord (05). CT-myelography is more sensitive, but false negatives remain (37). The most common myelographic abnormality is fusiform enlargement of the portion of the spinal cord that contains the tumor, sometimes with subarachnoid block (11). If the intramedullary tumor grows into the subarachnoid space or if leptomeningeal tumor invades the spinal cord, nodular filling defects or lobulated excrescences on the surface of the cord are seen (38). Sometimes, dilated tortuous veins like an arteriovenous malformation are present on the surface of the cord above the tumor (11).

MRI is the diagnostic procedure of choice. It shows the same gross alterations of size and shape as myelography, but it is more sensitive because it directly images the intramedullary spinal cord and detects tumors both large and small (37; 40) The tumor and the edematous or necrotic tissue around it appear hypointense to isointense on T1-weighted images and isointense to hyperintense on T2-weighted images.

With the infusion of gadolinium, the tumor enhances with a uniform or ring pattern, but the surrounding abnormal tissue does not. MRI also may show formation of a syringomyelic cavity adjacent to the tumor or hemorrhage in or around it. Other advantages of MRI over myelography include visualization of areas between myelographic blocks and easy imaging of the entire CNS, in order to diagnose asymptomatic metastases (37; 21).

The term longitudinally extensive spinal cord lesion refers to a continuous intramedullary lesion that is at least 3 contiguous vertebral segments long. Many types of myelitis can cause that MRI picture, including neuromyelitis optics, multiple sclerosis, acute disseminated encephalomyelitis, neurosarcoidosis, paraneoplastic isolated myelopathy, and myeloneuropathy. An intramedullary spinal cord metastatic tumor surrounded by segments of edematous or necrotic spinal cord tissue looks the same way, until contrast enhancement reveals the bright spherical mass in the center (40; 25).

Rykken and colleagues described 3 signs on contrast-enhanced MRI that can distinguish intramedullary metastatic from primary spinal cord tumors (39). The rim sign denotes the especially intense enhancement of a thin rim of the border of an enhancing metastatic tumor. The flame sign refers to a flame-shaped region of enhancement at the superior or inferior margin of an enhancing metastatic tumor. The central dot sign is a punctate focus of contrast enhancement in or near the center of an enhancing intramedullary mass. It is seen in some metastatic tumors and less often in primary ones.

PET can distinguish a metabolically active lesion, such as a tumor, from an inactive one, such as an area of necrotic tissue. The technique can at times be useful in distinguishing recurrent brain tumor from cerebral radiation necrosis. Likewise, it may help in separating intramedullary spinal cord metastatic tumor from radiation myelopathy, necrotizing myelopathy, and other spinal cord lesions (32).

Nonspecific abnormalities are usually found in the CSF of patients with intramedullary spinal cord metastatic tumor. In the largest series of patients, the median protein content was modestly increased (91 mg/dL) and ranged from normal to 1350 mg/dL (41). It is less than 200 mg/dL in most cases (06; 18; 05). Markedly elevated values reflect spinal subarachnoid block or extension of tumor into proximal nerve roots or the leptomeninges. In the large series of Schiff and O'Neill, the median leukocyte count was 3 cells/mm3 and ranged from 0 to 32 cells/mm3 (41). Most patients do not have a pleocytosis, and rarely is it greater than 20 cells/mm3 (18; 04). The cause of the pleocytosis is not known. Glucose levels are normal. Malignant cells are not found. In patients with both intramedullary spinal cord and leptomeningeal metastases, the CSF profile is in keeping with the latter disorder (41).

In patients not known to have cancer, part of the diagnosis of intramedullary metastasis consists in finding the primary tumor or metastases in other organs. Most patients have tumor in the lung, either primary or metastatic, and many patients have brain metastases as well (44). Imaging of the chest and head will usually show them. Biopsy of the spinal cord may be necessary if an underlying systemic malignancy is not found.

Management

Radiation therapy. The literature on intramedullary spinal cord metastasis consists of several retrospective series of fewer than 10 patients, one series of 40 patients, also retrospective (41), and many literature reviews (11; 19; 44). No prospective controlled trials of treatment have been performed, and the condition is so uncommon that probably none ever will be. Although these are weak grounds for recommendations for treatment, certain things can be said with some confidence. Radiation therapy is an effective treatment for intramedullary metastatic tumors. Most patients will have stabilization of spinal cord function, and some patients will improve (19; 12). The effect of treatment is not short-lived; it usually lasts as long as the patient survives. The response to radiotherapy depends mainly on the degree and duration of the neurologic deficit when the patient enters treatment and much less on the radiosensitivity of the tumor (50; 41). Patients who cannot walk before treatment rarely walk afterward, but the ability to walk is usually preserved in those who can (41). Paraplegia that is present for days will not respond to treatment, but a minor deficit, such as segmental pain, paresthesias, or mild paraparesis, may resolve completely (50). A large tumor may disappear on MRI, but the patient may remain paraplegic. Most likely, the tumor has destroyed the segments of the cord that lodge it and caused necrosis of the adjacent ones as a complication. The tumor responds to radiation therapy, but the necrosis, of course, does not. In view of these points, the following formulation seems justified. Untreated, intramedullary spinal cord metastasis causes rapidly progressive paraplegia or tetraplegia. Radiation therapy can prevent that, but only if it is given early. Thus, intramedullary metastasis, like epidural spinal cord compression, qualifies as a neuro-oncologic emergency. Therefore, the diagnosis should be made and treatment started as soon as possible.

The spinal cord contains more than one intramedullary metastatic tumor in 20% of patients (40). Therefore, some authors have recommended that the entire spinal cord, not just the clinically involved portion, be treated with radiation, in order to prevent relapse elsewhere in the spinal cord and to avoid overlapping fields of consecutive courses of radiotherapy (50). However, only a few instances of such relapse have been recorded, and most patients will not survive long enough to develop delayed radiation myelopathy as a result of overlapping radiation portals (50). Thus, the risk of bone-marrow suppression from whole spinal cord irradiation probably outweighs the possible benefit. Focal radiation to the metastatic tumor and its margins should be given. The construction of the portal can be based on the MRI or myelogram or, if radiologic studies are normal, on the clinical localization of the tumor. Gadolinium enhancement on MRI localizes the tumor; abnormal signal intensity identifies not only the tumor, but also the edematous or necrotic segments of the spinal cord that surround it; hence, gadolinium enhancement should guide construction of the radiation portal. Patients should be followed closely for the appearance of symptoms of other metastatic tumors in the spinal cord, so that a second course of radiation therapy can be given while the neurologic deficit is still minor (50). Intrathecal or intraventricular chemotherapy can be given to patients who also have leptomeningeal metastatic disease.

Stereotactic radiosurgery was first applied to intramedullary spinal cord metastasis in 2004 and may be more effective than external-beam radiotherapy (14).

Surgery. Surgical removal of metastatic tumors from the spinal cord has been attempted. Some have concluded it is more effective than radiotherapy (26). The studies were small, retrospective, and uncontrolled; therefore, the conclusions are probably unreliable. Most patients with intramedullary metastases have widespread systemic and CNS metastatic disease and, therefore, will not be considered for surgery. At this time, surgery can be recommended for patients not known to have systemic cancer, because they need a tissue diagnosis, and for those whose neurologic deficit progresses during or after radiotherapy. It might be considered in a patient with no other metastases in the CNS, with well-controlled systemic disease, and with a radioresistant type of tumor. Once paraplegic, a patient should probably not be subjected to surgery because even extirpation of the tumor will not restore spinal cord function.

Systemic therapy. Some cancers are driven by oncogenes, ie, mutated genes that promote the uncontrolled growth of malignant tissue. Targeted therapy refers to inhibiting the products of those genes and has shown good results in non-small cell lung cancers. Pellerino and colleagues reported a patient with non-small cell lung cancer with the anaplastic lymphoma kinase oncogene who developed intramedullary spinal cord metastases (34). Treatment with the anaplastic lymphoma kinase inhibitors ceritinib and lorlatinib led to a complete response that lasted more than a year. Likewise, Horiuchi and colleagues reported a patient with lung adenocarcinoma whose intramedullary spinal cord metastasis responded to osimertinib, an inhibitor of epidermal growth factor receptor (16). If these or other targets, such as BRAF, are present in the primary tumor, the corresponding systemic targeted therapy should be considered because many have demonstrated CNS activity. Targeted therapy may prove to be an effective way to treat CNS metastatic disease, including intramedullary spinal cord metastases.

Special considerations

Pregnancy

No data are available in the literature on patients with intramedullary spinal cord metastases who are pregnant.

Anesthesia

There are no specific considerations concerning anesthesia in patients with intramedullary spinal cord metastases. Certain precautions must be observed in all patients with chronic spinal cord injuries, and they apply to patients with intramedullary metastatic tumors.