Jayne Viets-Upchurch, MD

Case

A 60-year-old man with stage IV hormoneindependent prostate cancer, with widely metastatic disease to the bone, presents to the ED with increased weakness and new onset of numbness in the lower extremities, which he states began earlier that day. After failing several lines of chemotherapy, he is currently being treated with hormonal therapy alone. Patient first noted weakness in the left lower extremity 5 days before presentation, which progressed to bilateral involvement, making ambulation difficult and requiring the use of a walker. He denies back pain or urinary or fecal incontinence. Regarding pain management, he had been recently treated at one of the pain clinics in the hospital and has continued on opioid medication at another institution. Until the past week, he states he had back pain without neurological deficits.

His vital signs are stable at presentation. Patient is obese but in no acute distress. His cardiopulmonary examination is unremarkable; abdominal examination is benign; and back examination is normal. On neurological examination, iliopsoas flexion is 4/5 bilaterally; the rest of the motor examination is normal, with toes downgoing bilaterally upon plantar stimulation. Diminished sensation to light touch is noted at the T4-T6 sensory level and below; patient also has diminished proprioception in his lower extremities.

Patient had undergone a whole body scan one month prior to presentation, which revealed increased tracer uptake of Technetium-99m in multiple areas in the thoracic and lumbar spine. The radiologist also reported bilateral involvement in the wrists, femurs, tibias, and humeri—all in concordance with multifocal bone disease noted in previous computed tomography scans.

How should you approach this case?

Overview of Metastatic Spinal Cord Compression
Malignant or metastatic spinal cord compression (MSCC) of the thecal sac is an ominous complication of advanced cancer and an oncologic emergency presenting clinically in approximately 3% to 10% of cancer-related deaths.1,2 Cancer patients have a median survival of 3 to 6 months from diagnosis of MSCC.1,3,4 This disease causes significant disability due to paralysis, sensory loss, protracted pain, and sphincter dysfunction.5 If left untreated, MSCC has the potential to cause paraplegia in almost all affected patients; therefore, prompt recognition and treatment are essential to maintain mobility and neurological function. Generally speaking, any cancer patient who presents with new or worsening back pain—even in the absence of neurological deficits—merits evaluation for spinal cord compression.6 Nevertheless, individual risk assessment is warranted.7

Epidemiology

In the United States, more than 20,000 cases of MSCC are reported each year.8 According to postmortem studies, this condition affects 5% to 36% of cancer patients.9,10 In a US nationwide study of 15,367 cases of MSCC,2 the mean age at hospitalization was 62 years, with 37% of cases occurring in women. In approximately 20% of cases, MSCC was the initial presentation of cancer4; this has been reflected in our experience at MD Anderson Cancer Center.

Cancers of the breast, lung, prostate, and multiple myeloma are the most frequent underlying conditions in MSCC.2,8 Its prevalence varies depending on tumor type, occurring in 0.2% of pancreatic cancers; however, MSCC may affect up to 7.9% to 15% of myelomas1,2 and 13% of lymphomas.2 Interestingly, 5.5% of patients with prostate cancer develop MSCC.2 According to a study by Lu et al,11 historical risk factors include known nonvertebral bony metastases and stage IV disease at the time of diagnosis.

The most common location of MSCC is the thoracic spine (69% of cases); 29% of cases occur at the lumbosacral level and 10% at the cervical area.12 Most likely this pattern follows the lymphatic drainage, as metastases from breast and lung cancers tend to be found in the thoracic spine. Pelvic and intra-abdominal malignancies most commonly migrate to the lumbar spine. Multiple spinal epidural metastases were noted in 31% of those who underwent complete imaging of the spine.12

Pathophysiology

Most cases of MSCC are epidural in origin, arising from the vertebral column in 85% of patients.8 Epidural spread is caused mainly by hematogenous mechanism through the Batson venous plexus,13 debilitating the bone and eventually causing vertebral collapse with compression of the spinal canal. Epidural spread is less likely caused by direct tumor extension (ie, erosion through the bone) or by direct deposition of tumor cells into the epidural space.14 Ultimate neuronal injury is thought to involve vasogenic edema,15 leading to ischemia13 through venous infarction, but there has been debate regarding this last phenomenon.16 In cases of paralysis, demyelination is striking.16

Clinical Presentation

Even though cancer accounts for less than 1% of episodes of low back pain, it is the most common systemic disease affecting the spine.17 An important clinical inquiry is to determine whether back pain in an established cancer patient can be ruled out without extensive imaging. Unfortunately, clinical examination alone cannot exclude MSCC. Because of the high specificity (0.98), any cancer patient with new back pain should be considered to have metastasis until proven otherwise.17

 

Symptoms in MSCC at presentation can be motor, sensory, and/or autonomic. Back pain varies depending on the site of metastasis, which can be referred, local, radicular, or a combination of all three.18 The primary complaint is pain in 83% to 96% of cases,19,20 though this is a nonspecific sign.

Back pain is typically experienced for a median of 62 days prior to treatment of MSCC, usually due to considerable delays in diagnosis and treatment21; patients presenting with radiculopathy are usually symptomatic an average of 9 weeks prior to diagnosis.22 Tenderness is often present over the affected area and, as with mechanical back pain, pain associated with MSCC may worsen with loads, which bear pressure on the vertebral column.23 In contrast to mechanical back pain, rest in a supine position frequently exacerbates pain in MSCC,17 often disrupting sleep. In addition, weakness follows pain with an estimated 35% to 85% of patients endorsing the symptom.24

Previous studies have shown 40% to 64% of patients were not ambulatory at the time of diagnosis.19,25 Recent case series, however, report an increased number of ambulatory patients—possibly due to increased clinician awareness.26 In other cases, only 9% of patients were able to walk independently without aid.27 Loss of sensation, dense paraplegia, and incontinence are late findings and likely signal some degree of permanent disability.19

Misdiagnosis is a common issue in the ED setting. In an interesting retrospective study of 63 patients with spinal cord compression28 (not necessarily malignant), 18 (29%) were misdiagnosed.28 Consequently, there was a significant delay in diagnosis despite obvious neurological deficits at presentation.

Evaluation and Imaging

A detailed physical examination is essential to diagnosing MSCC. A thorough neurological examination, including sensation, strength, and reflexes should be carefully documented. If spinal instability is suspected, range-of-motion testing is contraindicated. The modified Frankel classification,29 adapted from the traumatic spine cord injury work by Frankel, et al,30 may be used to assess the degree of disability (Table).

Lu et al11 noted hyperreflexia and upward going Babinski reflex as common findings. Moreover, risk factors of decreased rectal sphincter tone and bladder were determinant for poor outcomes.

Incidental discovery of MSCC on imaging in the absence of neurological findings is rare. Approximately 26% to 29% of total metastatic deposits are occult and not visible on X-ray.4,10 Prior to the 1990s, spinal cord compression was diagnosed by my elography.31 Fortunately, this uncomfortable procedure has been replaced by magnetic resonance imaging (MRI) (Figure 1).32 While gadolinium-enhanced MRI can help to determine intradural tumor or leptomeningeal disease, it is not required for cord compression studies. Unenhanced MRI is equal to myelography in detecting epidural disease and is more sensitive at detecting vertebral metastasis,33 justifying its use and reducing procedure time compared to gadolinium-enhanced studies.

MRI studies should include the entire spine—not just the perceived area of interest— as up to 38% of patients have multiple-site metastases12 (Figure 1). Sensory deficits and mechanical pain may be present two to four vertebral levels away from the actual lesion.11 If MRI suggests cord compression, severity can be graded using the MSCC scale34 (Figure 2). Several scoring systems have been developed to aid in decision making concerning surgical treatment.

Management and Outcomes

The goal of therapy is symptom control and preservation of function. This requires a multidisciplinary approach and may involve radiation therapy and surgery, as well as medical efforts. Upon diagnosis and initiation of therapy, serial neurological evaluation should be undertaken. Neurovital signs should be scheduled to coincide with other nursing efforts to ease the burden of care and minimize patient discomfort.

The mainstay of medical therapy is treatment with corticosteroids.35 Initial trials have demonstrated that corticosteroids improve functional status in MSCC, but controversy exists regarding the effective dose. In a randomized, controlled trial by Sorensen et al,36 which sought to evaluate functional outcomes of highdose corticosteroids as an adjunct to radiotherapy, 57 patients received either high-dose dexamethasone or no corticosteroid therapy. Fifty-nine percent of patients in the dexamethasone group were ambulatory 6 months after treatment compared to 39% in the group who did not receive steroids.36

The use of high-dose corticosteroids was once a common practice, but is no longer considered standard of care and should be avoided based on increased side effects with no improvement in outcome compared with low-dose corticosteroids. 37 At our institution, moderate doses of corticosteroids are recommended concomitantly with radiation therapy or/and surgery. Our patients generally receive 10 mg of dexamethasone as a loading dose, followed by 16 mg daily in divided doses. Gastrointestinal (GI) prophylaxis should be initiated to reduce GI tract toxicity, and special attention should be given to glucose control in patients with diabetes.

 

A patient without a biopsy-confirmed cancer diagnosis in need of corticosteroid treatment presents a dilemma. Plasmacytomas, thymomas, lymphomas, multiple myeloma, germ-cell tumors are very sensitive to corticosteroid therapy in patients with MSCC.38 However, corticosteroids given before tissue samples are obtained may hinder proper diagnosis and complicate future management.39,40 In the absence of neurological deficit, corticosteroids may be withheld and emergent consultation with neurosurgery and oncology should be obtained. If there is any question regarding the nature of the lesion, tissue diagnosis must be obtained without delay.

Strict bed rest (including logroll and bedpan use) should be instituted if there is suspicion of spinal cord instability. Patients with suspected involvement of the cervical spine should have a Philadelphia collar placed until spinal stability has been confirmed. In the United Kingdom, the National Institutes for Health Care Excellence guidelines recommend all patients with suspected cord compression be nursed in a flat position.22 Other institutions, however, do not believe that strict bed rest is necessary, as it is presumed that MSCC is inherently different from that caused by trauma. Authors supporting this position contend that the increased incidence of deep vein thrombosis, infection (particularly from the urinary tract), and decubitus ulcers outweighs the benefit of bed rest. Patient preference should be taken into consideration as those with good functional status may be quite resistant to bed rest. In cases where cord compression is strongly suspected, these patients should be educated on proper bed rest. The greatest predictors of outcome are ambulatory and functional status at the time of diagnosis (generally based on an Eastern Cooperative Oncology Group scale). Patients with a good functional status, limited disease, and a life expectancy of greater than 3 to 6 months may benefit from surgery.41 However, emergent surgical evaluation is required in patients not responding to radiotherapy or who received received only limited doses of radiotherapy, as well as those with spinal instability, direct cord compression due to a bony fragment, impending sphincter dysfunction, unknown primary tumor, or no paraplegia for >48 hours.15

Unfortunately, surgery is only indicated in 10% to 15% of MSCC cases.42 In the past two decades, significant improvements regarding new aggressive surgical techniques have been made, and include circumferential decompression of the spine and staged or single stage anterior posterior surgery with stabilization. 43 Additionally, the combination of surgery with radiotherapy has improved outcomes.44

Most patients benefit from short-course radiotherapy45 even when given palliatively. 46 Longer courses of radiotherapy are highly recommended for patients with a more favorable prognosis.47 Up to 10% of patients diagnosed with spinal cord compression will require treatment for disease recurrence.42 There is a limited role for chemotherapy, and in seminomas and lymphomas, results can be quite dramatic.38

The average lifespan after development of MSCC is usually less than 6 months.1,3,4 However, patients with limited disease and good functional status may survive for years.43 Patients with poor functional status or those in the late stages of disease may be referred to palliative care for the management of symptoms.48 Given the poor prognosis of MSCC in general, endof- life discussions are warranted. In a retrospective study of 88 patients with MSCC at MD Anderson Cancer Center,49 “do not resuscitate” orders were in place in only 9% of the patients during their hospital admission. Improved doctor-patient communication in the ED setting will facilitate the patient’s coping with future losses.

Prevention

Lu et al11 found that only 54% of patients were aware that back pain should be reported to their physician. Delays in diagnosis and treatment are common and well described in the literature.21 Patients should be instructed to call their physician within 24 hours from the development of any new or worsening back pain, and should be advised to seek immediate care if they develop any neurological symptoms. To facilitate appropriate and prompt management of MSCC, hospitals should develop diagnostic algorithms to minimize delays in referral to a comprehensive center for further treatment.

Case Conclusion

Based on this patient’s symptoms and status at presentation, the emergency team determined he was at high risk for MSCC. An initial dosage of 10 mg dexamethasone was administered intravenously (IV), followed by 4 mg IV every 6 hours prior to imaging. An MRI without contrast of the cervical, thoracic, and lumbar spine showed cord compression with mild cord edema at T4 level, along with diffused osseous metastasis.

Upon diagnosis, patient was referred to radiation oncology for radiotherapy of the T2-T6 vertebral bodies. Three days after initiation of radiation therapy, his neurological function deteriorated with paraplegia and incontinence, and he was emergently evaluated for neurosurgery. Although T4 laminectomy and decompression of the spinal cord were performed without complication, patient did not recover neurological function. His hospital course was complicated by Ogilvie syndrome and episodes of delirium, and he was discharged to a rehabilitation facility 23 days after admission; paraplegia and urinary and bowel incontinence remained unchanged.

Case

A 60-year-old man with stage IV hormoneindependent prostate cancer, with widely metastatic disease to the bone, presents to the ED with increased weakness and new onset of numbness in the lower extremities, which he states began earlier that day. After failing several lines of chemotherapy, he is currently being treated with hormonal therapy alone. Patient first noted weakness in the left lower extremity 5 days before presentation, which progressed to bilateral involvement, making ambulation difficult and requiring the use of a walker. He denies back pain or urinary or fecal incontinence. Regarding pain management, he had been recently treated at one of the pain clinics in the hospital and has continued on opioid medication at another institution. Until the past week, he states he had back pain without neurological deficits.

His vital signs are stable at presentation. Patient is obese but in no acute distress. His cardiopulmonary examination is unremarkable; abdominal examination is benign; and back examination is normal. On neurological examination, iliopsoas flexion is 4/5 bilaterally; the rest of the motor examination is normal, with toes downgoing bilaterally upon plantar stimulation. Diminished sensation to light touch is noted at the T4-T6 sensory level and below; patient also has diminished proprioception in his lower extremities.

Patient had undergone a whole body scan one month prior to presentation, which revealed increased tracer uptake of Technetium-99m in multiple areas in the thoracic and lumbar spine. The radiologist also reported bilateral involvement in the wrists, femurs, tibias, and humeri—all in concordance with multifocal bone disease noted in previous computed tomography scans.

How should you approach this case?

Overview of Metastatic Spinal Cord Compression
Malignant or metastatic spinal cord compression (MSCC) of the thecal sac is an ominous complication of advanced cancer and an oncologic emergency presenting clinically in approximately 3% to 10% of cancer-related deaths.1,2 Cancer patients have a median survival of 3 to 6 months from diagnosis of MSCC.1,3,4 This disease causes significant disability due to paralysis, sensory loss, protracted pain, and sphincter dysfunction.5 If left untreated, MSCC has the potential to cause paraplegia in almost all affected patients; therefore, prompt recognition and treatment are essential to maintain mobility and neurological function. Generally speaking, any cancer patient who presents with new or worsening back pain—even in the absence of neurological deficits—merits evaluation for spinal cord compression.6 Nevertheless, individual risk assessment is warranted.7

Epidemiology

In the United States, more than 20,000 cases of MSCC are reported each year.8 According to postmortem studies, this condition affects 5% to 36% of cancer patients.9,10 In a US nationwide study of 15,367 cases of MSCC,2 the mean age at hospitalization was 62 years, with 37% of cases occurring in women. In approximately 20% of cases, MSCC was the initial presentation of cancer4; this has been reflected in our experience at MD Anderson Cancer Center.

Cancers of the breast, lung, prostate, and multiple myeloma are the most frequent underlying conditions in MSCC.2,8 Its prevalence varies depending on tumor type, occurring in 0.2% of pancreatic cancers; however, MSCC may affect up to 7.9% to 15% of myelomas1,2 and 13% of lymphomas.2 Interestingly, 5.5% of patients with prostate cancer develop MSCC.2 According to a study by Lu et al,11 historical risk factors include known nonvertebral bony metastases and stage IV disease at the time of diagnosis.

The most common location of MSCC is the thoracic spine (69% of cases); 29% of cases occur at the lumbosacral level and 10% at the cervical area.12 Most likely this pattern follows the lymphatic drainage, as metastases from breast and lung cancers tend to be found in the thoracic spine. Pelvic and intra-abdominal malignancies most commonly migrate to the lumbar spine. Multiple spinal epidural metastases were noted in 31% of those who underwent complete imaging of the spine.12

Pathophysiology

Most cases of MSCC are epidural in origin, arising from the vertebral column in 85% of patients.8 Epidural spread is caused mainly by hematogenous mechanism through the Batson venous plexus,13 debilitating the bone and eventually causing vertebral collapse with compression of the spinal canal. Epidural spread is less likely caused by direct tumor extension (ie, erosion through the bone) or by direct deposition of tumor cells into the epidural space.14 Ultimate neuronal injury is thought to involve vasogenic edema,15 leading to ischemia13 through venous infarction, but there has been debate regarding this last phenomenon.16 In cases of paralysis, demyelination is striking.16

Clinical Presentation

Even though cancer accounts for less than 1% of episodes of low back pain, it is the most common systemic disease affecting the spine.17 An important clinical inquiry is to determine whether back pain in an established cancer patient can be ruled out without extensive imaging. Unfortunately, clinical examination alone cannot exclude MSCC. Because of the high specificity (0.98), any cancer patient with new back pain should be considered to have metastasis until proven otherwise.17

 

Symptoms in MSCC at presentation can be motor, sensory, and/or autonomic. Back pain varies depending on the site of metastasis, which can be referred, local, radicular, or a combination of all three.18 The primary complaint is pain in 83% to 96% of cases,19,20 though this is a nonspecific sign.

Back pain is typically experienced for a median of 62 days prior to treatment of MSCC, usually due to considerable delays in diagnosis and treatment21; patients presenting with radiculopathy are usually symptomatic an average of 9 weeks prior to diagnosis.22 Tenderness is often present over the affected area and, as with mechanical back pain, pain associated with MSCC may worsen with loads, which bear pressure on the vertebral column.23 In contrast to mechanical back pain, rest in a supine position frequently exacerbates pain in MSCC,17 often disrupting sleep. In addition, weakness follows pain with an estimated 35% to 85% of patients endorsing the symptom.24

Previous studies have shown 40% to 64% of patients were not ambulatory at the time of diagnosis.19,25 Recent case series, however, report an increased number of ambulatory patients—possibly due to increased clinician awareness.26 In other cases, only 9% of patients were able to walk independently without aid.27 Loss of sensation, dense paraplegia, and incontinence are late findings and likely signal some degree of permanent disability.19

Misdiagnosis is a common issue in the ED setting. In an interesting retrospective study of 63 patients with spinal cord compression28 (not necessarily malignant), 18 (29%) were misdiagnosed.28 Consequently, there was a significant delay in diagnosis despite obvious neurological deficits at presentation.

Evaluation and Imaging

A detailed physical examination is essential to diagnosing MSCC. A thorough neurological examination, including sensation, strength, and reflexes should be carefully documented. If spinal instability is suspected, range-of-motion testing is contraindicated. The modified Frankel classification,29 adapted from the traumatic spine cord injury work by Frankel, et al,30 may be used to assess the degree of disability (Table).

Lu et al11 noted hyperreflexia and upward going Babinski reflex as common findings. Moreover, risk factors of decreased rectal sphincter tone and bladder were determinant for poor outcomes.

Incidental discovery of MSCC on imaging in the absence of neurological findings is rare. Approximately 26% to 29% of total metastatic deposits are occult and not visible on X-ray.4,10 Prior to the 1990s, spinal cord compression was diagnosed by my elography.31 Fortunately, this uncomfortable procedure has been replaced by magnetic resonance imaging (MRI) (Figure 1).32 While gadolinium-enhanced MRI can help to determine intradural tumor or leptomeningeal disease, it is not required for cord compression studies. Unenhanced MRI is equal to myelography in detecting epidural disease and is more sensitive at detecting vertebral metastasis,33 justifying its use and reducing procedure time compared to gadolinium-enhanced studies.

MRI studies should include the entire spine—not just the perceived area of interest— as up to 38% of patients have multiple-site metastases12 (Figure 1). Sensory deficits and mechanical pain may be present two to four vertebral levels away from the actual lesion.11 If MRI suggests cord compression, severity can be graded using the MSCC scale34 (Figure 2). Several scoring systems have been developed to aid in decision making concerning surgical treatment.

Management and Outcomes

The goal of therapy is symptom control and preservation of function. This requires a multidisciplinary approach and may involve radiation therapy and surgery, as well as medical efforts. Upon diagnosis and initiation of therapy, serial neurological evaluation should be undertaken. Neurovital signs should be scheduled to coincide with other nursing efforts to ease the burden of care and minimize patient discomfort.

The mainstay of medical therapy is treatment with corticosteroids.35 Initial trials have demonstrated that corticosteroids improve functional status in MSCC, but controversy exists regarding the effective dose. In a randomized, controlled trial by Sorensen et al,36 which sought to evaluate functional outcomes of highdose corticosteroids as an adjunct to radiotherapy, 57 patients received either high-dose dexamethasone or no corticosteroid therapy. Fifty-nine percent of patients in the dexamethasone group were ambulatory 6 months after treatment compared to 39% in the group who did not receive steroids.36

The use of high-dose corticosteroids was once a common practice, but is no longer considered standard of care and should be avoided based on increased side effects with no improvement in outcome compared with low-dose corticosteroids. 37 At our institution, moderate doses of corticosteroids are recommended concomitantly with radiation therapy or/and surgery. Our patients generally receive 10 mg of dexamethasone as a loading dose, followed by 16 mg daily in divided doses. Gastrointestinal (GI) prophylaxis should be initiated to reduce GI tract toxicity, and special attention should be given to glucose control in patients with diabetes.

 

A patient without a biopsy-confirmed cancer diagnosis in need of corticosteroid treatment presents a dilemma. Plasmacytomas, thymomas, lymphomas, multiple myeloma, germ-cell tumors are very sensitive to corticosteroid therapy in patients with MSCC.38 However, corticosteroids given before tissue samples are obtained may hinder proper diagnosis and complicate future management.39,40 In the absence of neurological deficit, corticosteroids may be withheld and emergent consultation with neurosurgery and oncology should be obtained. If there is any question regarding the nature of the lesion, tissue diagnosis must be obtained without delay.

Strict bed rest (including logroll and bedpan use) should be instituted if there is suspicion of spinal cord instability. Patients with suspected involvement of the cervical spine should have a Philadelphia collar placed until spinal stability has been confirmed. In the United Kingdom, the National Institutes for Health Care Excellence guidelines recommend all patients with suspected cord compression be nursed in a flat position.22 Other institutions, however, do not believe that strict bed rest is necessary, as it is presumed that MSCC is inherently different from that caused by trauma. Authors supporting this position contend that the increased incidence of deep vein thrombosis, infection (particularly from the urinary tract), and decubitus ulcers outweighs the benefit of bed rest. Patient preference should be taken into consideration as those with good functional status may be quite resistant to bed rest. In cases where cord compression is strongly suspected, these patients should be educated on proper bed rest. The greatest predictors of outcome are ambulatory and functional status at the time of diagnosis (generally based on an Eastern Cooperative Oncology Group scale). Patients with a good functional status, limited disease, and a life expectancy of greater than 3 to 6 months may benefit from surgery.41 However, emergent surgical evaluation is required in patients not responding to radiotherapy or who received received only limited doses of radiotherapy, as well as those with spinal instability, direct cord compression due to a bony fragment, impending sphincter dysfunction, unknown primary tumor, or no paraplegia for >48 hours.15

Unfortunately, surgery is only indicated in 10% to 15% of MSCC cases.42 In the past two decades, significant improvements regarding new aggressive surgical techniques have been made, and include circumferential decompression of the spine and staged or single stage anterior posterior surgery with stabilization. 43 Additionally, the combination of surgery with radiotherapy has improved outcomes.44

Most patients benefit from short-course radiotherapy45 even when given palliatively. 46 Longer courses of radiotherapy are highly recommended for patients with a more favorable prognosis.47 Up to 10% of patients diagnosed with spinal cord compression will require treatment for disease recurrence.42 There is a limited role for chemotherapy, and in seminomas and lymphomas, results can be quite dramatic.38

The average lifespan after development of MSCC is usually less than 6 months.1,3,4 However, patients with limited disease and good functional status may survive for years.43 Patients with poor functional status or those in the late stages of disease may be referred to palliative care for the management of symptoms.48 Given the poor prognosis of MSCC in general, endof- life discussions are warranted. In a retrospective study of 88 patients with MSCC at MD Anderson Cancer Center,49 “do not resuscitate” orders were in place in only 9% of the patients during their hospital admission. Improved doctor-patient communication in the ED setting will facilitate the patient’s coping with future losses.

Prevention

Lu et al11 found that only 54% of patients were aware that back pain should be reported to their physician. Delays in diagnosis and treatment are common and well described in the literature.21 Patients should be instructed to call their physician within 24 hours from the development of any new or worsening back pain, and should be advised to seek immediate care if they develop any neurological symptoms. To facilitate appropriate and prompt management of MSCC, hospitals should develop diagnostic algorithms to minimize delays in referral to a comprehensive center for further treatment.

Case Conclusion

Based on this patient’s symptoms and status at presentation, the emergency team determined he was at high risk for MSCC. An initial dosage of 10 mg dexamethasone was administered intravenously (IV), followed by 4 mg IV every 6 hours prior to imaging. An MRI without contrast of the cervical, thoracic, and lumbar spine showed cord compression with mild cord edema at T4 level, along with diffused osseous metastasis.

Upon diagnosis, patient was referred to radiation oncology for radiotherapy of the T2-T6 vertebral bodies. Three days after initiation of radiation therapy, his neurological function deteriorated with paraplegia and incontinence, and he was emergently evaluated for neurosurgery. Although T4 laminectomy and decompression of the spinal cord were performed without complication, patient did not recover neurological function. His hospital course was complicated by Ogilvie syndrome and episodes of delirium, and he was discharged to a rehabilitation facility 23 days after admission; paraplegia and urinary and bowel incontinence remained unchanged.

Case

A 60-year-old man with stage IV hormoneindependent prostate cancer, with widely metastatic disease to the bone, presents to the ED with increased weakness and new onset of numbness in the lower extremities, which he states began earlier that day. After failing several lines of chemotherapy, he is currently being treated with hormonal therapy alone. Patient first noted weakness in the left lower extremity 5 days before presentation, which progressed to bilateral involvement, making ambulation difficult and requiring the use of a walker. He denies back pain or urinary or fecal incontinence. Regarding pain management, he had been recently treated at one of the pain clinics in the hospital and has continued on opioid medication at another institution. Until the past week, he states he had back pain without neurological deficits.

His vital signs are stable at presentation. Patient is obese but in no acute distress. His cardiopulmonary examination is unremarkable; abdominal examination is benign; and back examination is normal. On neurological examination, iliopsoas flexion is 4/5 bilaterally; the rest of the motor examination is normal, with toes downgoing bilaterally upon plantar stimulation. Diminished sensation to light touch is noted at the T4-T6 sensory level and below; patient also has diminished proprioception in his lower extremities.

Patient had undergone a whole body scan one month prior to presentation, which revealed increased tracer uptake of Technetium-99m in multiple areas in the thoracic and lumbar spine. The radiologist also reported bilateral involvement in the wrists, femurs, tibias, and humeri—all in concordance with multifocal bone disease noted in previous computed tomography scans.

How should you approach this case?

Overview of Metastatic Spinal Cord Compression
Malignant or metastatic spinal cord compression (MSCC) of the thecal sac is an ominous complication of advanced cancer and an oncologic emergency presenting clinically in approximately 3% to 10% of cancer-related deaths.1,2 Cancer patients have a median survival of 3 to 6 months from diagnosis of MSCC.1,3,4 This disease causes significant disability due to paralysis, sensory loss, protracted pain, and sphincter dysfunction.5 If left untreated, MSCC has the potential to cause paraplegia in almost all affected patients; therefore, prompt recognition and treatment are essential to maintain mobility and neurological function. Generally speaking, any cancer patient who presents with new or worsening back pain—even in the absence of neurological deficits—merits evaluation for spinal cord compression.6 Nevertheless, individual risk assessment is warranted.7

Epidemiology

In the United States, more than 20,000 cases of MSCC are reported each year.8 According to postmortem studies, this condition affects 5% to 36% of cancer patients.9,10 In a US nationwide study of 15,367 cases of MSCC,2 the mean age at hospitalization was 62 years, with 37% of cases occurring in women. In approximately 20% of cases, MSCC was the initial presentation of cancer4; this has been reflected in our experience at MD Anderson Cancer Center.

Cancers of the breast, lung, prostate, and multiple myeloma are the most frequent underlying conditions in MSCC.2,8 Its prevalence varies depending on tumor type, occurring in 0.2% of pancreatic cancers; however, MSCC may affect up to 7.9% to 15% of myelomas1,2 and 13% of lymphomas.2 Interestingly, 5.5% of patients with prostate cancer develop MSCC.2 According to a study by Lu et al,11 historical risk factors include known nonvertebral bony metastases and stage IV disease at the time of diagnosis.

The most common location of MSCC is the thoracic spine (69% of cases); 29% of cases occur at the lumbosacral level and 10% at the cervical area.12 Most likely this pattern follows the lymphatic drainage, as metastases from breast and lung cancers tend to be found in the thoracic spine. Pelvic and intra-abdominal malignancies most commonly migrate to the lumbar spine. Multiple spinal epidural metastases were noted in 31% of those who underwent complete imaging of the spine.12

Pathophysiology

Most cases of MSCC are epidural in origin, arising from the vertebral column in 85% of patients.8 Epidural spread is caused mainly by hematogenous mechanism through the Batson venous plexus,13 debilitating the bone and eventually causing vertebral collapse with compression of the spinal canal. Epidural spread is less likely caused by direct tumor extension (ie, erosion through the bone) or by direct deposition of tumor cells into the epidural space.14 Ultimate neuronal injury is thought to involve vasogenic edema,15 leading to ischemia13 through venous infarction, but there has been debate regarding this last phenomenon.16 In cases of paralysis, demyelination is striking.16

Clinical Presentation

Even though cancer accounts for less than 1% of episodes of low back pain, it is the most common systemic disease affecting the spine.17 An important clinical inquiry is to determine whether back pain in an established cancer patient can be ruled out without extensive imaging. Unfortunately, clinical examination alone cannot exclude MSCC. Because of the high specificity (0.98), any cancer patient with new back pain should be considered to have metastasis until proven otherwise.17

 

Symptoms in MSCC at presentation can be motor, sensory, and/or autonomic. Back pain varies depending on the site of metastasis, which can be referred, local, radicular, or a combination of all three.18 The primary complaint is pain in 83% to 96% of cases,19,20 though this is a nonspecific sign.

Back pain is typically experienced for a median of 62 days prior to treatment of MSCC, usually due to considerable delays in diagnosis and treatment21; patients presenting with radiculopathy are usually symptomatic an average of 9 weeks prior to diagnosis.22 Tenderness is often present over the affected area and, as with mechanical back pain, pain associated with MSCC may worsen with loads, which bear pressure on the vertebral column.23 In contrast to mechanical back pain, rest in a supine position frequently exacerbates pain in MSCC,17 often disrupting sleep. In addition, weakness follows pain with an estimated 35% to 85% of patients endorsing the symptom.24

Previous studies have shown 40% to 64% of patients were not ambulatory at the time of diagnosis.19,25 Recent case series, however, report an increased number of ambulatory patients—possibly due to increased clinician awareness.26 In other cases, only 9% of patients were able to walk independently without aid.27 Loss of sensation, dense paraplegia, and incontinence are late findings and likely signal some degree of permanent disability.19

Misdiagnosis is a common issue in the ED setting. In an interesting retrospective study of 63 patients with spinal cord compression28 (not necessarily malignant), 18 (29%) were misdiagnosed.28 Consequently, there was a significant delay in diagnosis despite obvious neurological deficits at presentation.

Evaluation and Imaging

A detailed physical examination is essential to diagnosing MSCC. A thorough neurological examination, including sensation, strength, and reflexes should be carefully documented. If spinal instability is suspected, range-of-motion testing is contraindicated. The modified Frankel classification,29 adapted from the traumatic spine cord injury work by Frankel, et al,30 may be used to assess the degree of disability (Table).

Lu et al11 noted hyperreflexia and upward going Babinski reflex as common findings. Moreover, risk factors of decreased rectal sphincter tone and bladder were determinant for poor outcomes.

Incidental discovery of MSCC on imaging in the absence of neurological findings is rare. Approximately 26% to 29% of total metastatic deposits are occult and not visible on X-ray.4,10 Prior to the 1990s, spinal cord compression was diagnosed by my elography.31 Fortunately, this uncomfortable procedure has been replaced by magnetic resonance imaging (MRI) (Figure 1).32 While gadolinium-enhanced MRI can help to determine intradural tumor or leptomeningeal disease, it is not required for cord compression studies. Unenhanced MRI is equal to myelography in detecting epidural disease and is more sensitive at detecting vertebral metastasis,33 justifying its use and reducing procedure time compared to gadolinium-enhanced studies.

MRI studies should include the entire spine—not just the perceived area of interest— as up to 38% of patients have multiple-site metastases12 (Figure 1). Sensory deficits and mechanical pain may be present two to four vertebral levels away from the actual lesion.11 If MRI suggests cord compression, severity can be graded using the MSCC scale34 (Figure 2). Several scoring systems have been developed to aid in decision making concerning surgical treatment.

Management and Outcomes

The goal of therapy is symptom control and preservation of function. This requires a multidisciplinary approach and may involve radiation therapy and surgery, as well as medical efforts. Upon diagnosis and initiation of therapy, serial neurological evaluation should be undertaken. Neurovital signs should be scheduled to coincide with other nursing efforts to ease the burden of care and minimize patient discomfort.

The mainstay of medical therapy is treatment with corticosteroids.35 Initial trials have demonstrated that corticosteroids improve functional status in MSCC, but controversy exists regarding the effective dose. In a randomized, controlled trial by Sorensen et al,36 which sought to evaluate functional outcomes of highdose corticosteroids as an adjunct to radiotherapy, 57 patients received either high-dose dexamethasone or no corticosteroid therapy. Fifty-nine percent of patients in the dexamethasone group were ambulatory 6 months after treatment compared to 39% in the group who did not receive steroids.36

The use of high-dose corticosteroids was once a common practice, but is no longer considered standard of care and should be avoided based on increased side effects with no improvement in outcome compared with low-dose corticosteroids. 37 At our institution, moderate doses of corticosteroids are recommended concomitantly with radiation therapy or/and surgery. Our patients generally receive 10 mg of dexamethasone as a loading dose, followed by 16 mg daily in divided doses. Gastrointestinal (GI) prophylaxis should be initiated to reduce GI tract toxicity, and special attention should be given to glucose control in patients with diabetes.

 

A patient without a biopsy-confirmed cancer diagnosis in need of corticosteroid treatment presents a dilemma. Plasmacytomas, thymomas, lymphomas, multiple myeloma, germ-cell tumors are very sensitive to corticosteroid therapy in patients with MSCC.38 However, corticosteroids given before tissue samples are obtained may hinder proper diagnosis and complicate future management.39,40 In the absence of neurological deficit, corticosteroids may be withheld and emergent consultation with neurosurgery and oncology should be obtained. If there is any question regarding the nature of the lesion, tissue diagnosis must be obtained without delay.

Strict bed rest (including logroll and bedpan use) should be instituted if there is suspicion of spinal cord instability. Patients with suspected involvement of the cervical spine should have a Philadelphia collar placed until spinal stability has been confirmed. In the United Kingdom, the National Institutes for Health Care Excellence guidelines recommend all patients with suspected cord compression be nursed in a flat position.22 Other institutions, however, do not believe that strict bed rest is necessary, as it is presumed that MSCC is inherently different from that caused by trauma. Authors supporting this position contend that the increased incidence of deep vein thrombosis, infection (particularly from the urinary tract), and decubitus ulcers outweighs the benefit of bed rest. Patient preference should be taken into consideration as those with good functional status may be quite resistant to bed rest. In cases where cord compression is strongly suspected, these patients should be educated on proper bed rest. The greatest predictors of outcome are ambulatory and functional status at the time of diagnosis (generally based on an Eastern Cooperative Oncology Group scale). Patients with a good functional status, limited disease, and a life expectancy of greater than 3 to 6 months may benefit from surgery.41 However, emergent surgical evaluation is required in patients not responding to radiotherapy or who received received only limited doses of radiotherapy, as well as those with spinal instability, direct cord compression due to a bony fragment, impending sphincter dysfunction, unknown primary tumor, or no paraplegia for >48 hours.15

Unfortunately, surgery is only indicated in 10% to 15% of MSCC cases.42 In the past two decades, significant improvements regarding new aggressive surgical techniques have been made, and include circumferential decompression of the spine and staged or single stage anterior posterior surgery with stabilization. 43 Additionally, the combination of surgery with radiotherapy has improved outcomes.44

Most patients benefit from short-course radiotherapy45 even when given palliatively. 46 Longer courses of radiotherapy are highly recommended for patients with a more favorable prognosis.47 Up to 10% of patients diagnosed with spinal cord compression will require treatment for disease recurrence.42 There is a limited role for chemotherapy, and in seminomas and lymphomas, results can be quite dramatic.38

The average lifespan after development of MSCC is usually less than 6 months.1,3,4 However, patients with limited disease and good functional status may survive for years.43 Patients with poor functional status or those in the late stages of disease may be referred to palliative care for the management of symptoms.48 Given the poor prognosis of MSCC in general, endof- life discussions are warranted. In a retrospective study of 88 patients with MSCC at MD Anderson Cancer Center,49 “do not resuscitate” orders were in place in only 9% of the patients during their hospital admission. Improved doctor-patient communication in the ED setting will facilitate the patient’s coping with future losses.

Prevention

Lu et al11 found that only 54% of patients were aware that back pain should be reported to their physician. Delays in diagnosis and treatment are common and well described in the literature.21 Patients should be instructed to call their physician within 24 hours from the development of any new or worsening back pain, and should be advised to seek immediate care if they develop any neurological symptoms. To facilitate appropriate and prompt management of MSCC, hospitals should develop diagnostic algorithms to minimize delays in referral to a comprehensive center for further treatment.

Case Conclusion

Based on this patient’s symptoms and status at presentation, the emergency team determined he was at high risk for MSCC. An initial dosage of 10 mg dexamethasone was administered intravenously (IV), followed by 4 mg IV every 6 hours prior to imaging. An MRI without contrast of the cervical, thoracic, and lumbar spine showed cord compression with mild cord edema at T4 level, along with diffused osseous metastasis.

Upon diagnosis, patient was referred to radiation oncology for radiotherapy of the T2-T6 vertebral bodies. Three days after initiation of radiation therapy, his neurological function deteriorated with paraplegia and incontinence, and he was emergently evaluated for neurosurgery. Although T4 laminectomy and decompression of the spinal cord were performed without complication, patient did not recover neurological function. His hospital course was complicated by Ogilvie syndrome and episodes of delirium, and he was discharged to a rehabilitation facility 23 days after admission; paraplegia and urinary and bowel incontinence remained unchanged.