Malignant spinal cord compression (MSCC) is defined as spinal cord or cauda equina compression by direct pressure and/or induction of vertebral collapse or instability by metastatic spread or direct extension of malignancy that threatens or causes neurological disability.¹ MSCC is a neurological emergency that affects 5% of patients with cancer. Early diagnosis is key in prevention of neurological complications. Treatment must be implemented as early as possible to prevent or limit resulting neurological disability. GPs are ideally placed in the community to detect patients at risk of MSCC and initiate urgent referral to improve patient outcomes.

Incidence

MSCC is thought to affect 4,000 patients annually in England and Wales and from autopsy studies it is believed to occur in five per cent of all patients diagnosed with cancer.^1,4

The true incidence of MSCC is unknown as many cancer patients have MSCC that is unrecognised. In some cases, a decision may be made that further investigation is not in the best interest of a patient.

MSCC can occur from any primary site but it is more common in malignancies that are more likely to metastasise to the spinal column. Therefore in adults, lung, prostate and breast cancer account for 15-20% of all cases of MSCC. Non-Hodgkin’s lymphoma, renal cell cancer and multiple myeloma account for a further 5-10%.⁴

Approximately 20-23% of patients present with MSCC as the initial manifestation of the malignancy.^2,3 This is particularly true for lung cancer, where 30% of MSCC diagnoses are made in patients without a previous diagnosis of cancer.⁵ The distribution of lesions causing compression within the spine corresponds to the number of vertebrae in each region, with 60% occurring in the thoracic, 30% in the lumbar and 10% in the cervical spine. However, 20-35% of patients present with compression at multiple sites.⁴

Pathophysiology

At each spinal level, nerve roots exit lateral to the spinal cord and posterior to the vertebral body. MSCC occurs when tumour invades the epidural space and compresses the thecal sac.¹¹ In 15% of cases, growth of a paravertebral tumour directly into the spinal canal causes direct compression. In 85%, the tumour arises from the vertebral body, grows in size and causes secondary compression of the cord.⁴ This process is usually gradual, although it can occur acutely during vertebral collapse and sudden displacement of vertebral fragments. 

Direct compression of the cord causes demyelination, axonal damage and secondary vascular compromise resulting in venous compression and oedema. Administration of corticosteroids at this stage can reduce or reverse oedema-associated neurological dysfunction. As the process progresses with persistent compression, arterial blood supply is impaired resulting in cord ischaemia, infarction and irreversible neurological damage.⁴

Clinical presentation

Back pain is the earliest and most common presentation to GPs and is present in 95% of patients at diagnosis.⁴ It has often been present for up to two months before the diagnosis of MSCC is made.⁷ A Scottish audit showed that there were significant delays from the time when patients first develop symptoms to when GPs and hospital doctors recognise the possibility of MSCC and make an appropriate referral.¹⁷

Localised pain that is confined to the affected region which progressively increases in severity is generally the first symptom. Over time, radicular pain results from compression or invasion of nerve roots and is typically worse at night or on straining. Unilateral pain is common from cervical and lumbar spine involvement. Thoracic involvement is frequently bilateral and characteristically wraps around anteriorly in a band-like fashion. Pain may be new or represent a significant change in the character of longstanding pain.

Weakness is the second most common presenting symptom present in 35-75%. Patients can non-specifically complain of being ‘off their feet’ or of ‘heaviness’ in the limbs. Between 50-68% of patients are unable to walk at the time of diagnosis. The extent of motor deficit is dependent on the location of compression but can involve upper or lower motor neurone weakness.⁴ The development of ataxia, loss of co-ordination or paralysis are usually late findings.

Other clinical findings occur less frequently and are more variable. Sensory disturbances rarely occur in the absence of motor deficits.⁴ Paraesthesia and loss of sensation may develop and typically begin distally and ascend, but can be poorly localised to the site.⁸ Autonomic symptoms causing constipation and/or urinary retention that progress to double incontinence occur late and are rarely the only presenting symptoms.⁸ Sphincter disturbance is a poor prognostic sign.⁴

MSSC should be considered in a patient with:

• History of cancer with or without known bone metastases (particularly lung, prostate or breast)
• New back pain or significant change in the nature of a longstanding pain
• Pain increasing in severity, not responding to analgesia
• Pain described as a ‘tight band’ around the thoracic region
• Pain worse on straining
• Unilateral or bilateral pain
• Limb weakness•
• Beware of patients ‘off their feet’
• Paraesthesia
• Sphincter disturbance.

Diagnosis  

A high index of suspicion is the most effective tool in preventing devastating consequences of this condition. Clinical suspicion should prompt a medical history and examination but clinical features are not sensitive enough to make the diagnosis.⁹ Patients should be urgently referred to the nearest emergency department for assessment and investigation. Magnetic resonance imaging (MRI) of the whole spine is the investigation of choice. It is necessary to image the entire spine as up to one third of patients have compression present at multiple sites. NICE guidelines advise urgent MRI within 24 hours for all patients with suspected MSCC.¹ Several other imaging techniques do not display the accuracy of MRI and are less useful. Plain radiography should not be used as a screening procedure as it has insufficient sensitivity and specificity and can delay MRI.¹⁰

Management

Management includes immediate administration of corticosteroids to reduce oedema in nearly all patients, definitive treatment or surgery or radiotherapy. Systemic therapy may be beneficial in patients with chemo sensitive tumours.

Corticosteroids are contraindicated if there is a significant suspicion of lymphoma. Steroids are usually commenced in the hospital setting but can be commenced in the community. Sorenson et al established the efficacy of steroids in the treatment of MSCC and demonstrated higher ambulatory rates in patients who received high dose dexamethasone and radiotherapy compared to radiotherapy alone.¹³ The optimal dose remains unknown. A Cochrane meta-analysis of three studies concluded that higher doses of corticosteroids were not associated with better outcomes but were associated with a higher incidence of serious adverse events.¹² NICE guidelines advise a loading dose of 16mg of dexamethasone as soon as possible after assessment followed by a short course of 16mg per day until definitive treatment has been implemented. However, in practice, patients usually receive a dose of dexamethasone 8mg twice or three times daily. Blood glucose monitoring is advised in patients on dexamethasone.¹

Radiotherapy

External beam radiotherapy has been the standard treatment for MSCC since the 1950s. It is most effective in patients who have tumours that are radiosensitive and who are ambulatory at the beginning of treatment. Radiation is generally delivered to the involved segment as well as the level above and below. A shorter course of treatment is preferable in patients who have a short expected survival; however long-term local control is better with protracted schedules and preferable for patients with a good performance status.⁴

Surgery

In the past, surgery for the management of MSCC was controversial, but recent advances have established its efficacy in selected patients. A randomised controlled trial in 2005 established that direct decompressive surgery plus post-operative radiotherapy is superior to treatment with radiotherapy alone.¹⁴ Careful selection is required to identify those patients with an adequate life expectancy and good medical status who are potential candidates for surgery. Suitable patients should be offered surgery. Surgical decompression is the preferred approach for patients with an unstable spine and for relatively radio-resistant tumours.¹⁵ NICE guidelines advise that only patients with an expected survival of greater than three months should be considered for surgical treatment.¹

Prognosis

The most important outcomes for patients with MSCC are ambulatory function and length of survival. MSCC usually occurs in the setting of advanced malignancy and retrospective studies have demonstrated that median survival time for patients with MSCC is three to six months.^2,16 The most important prognostic indicator for the prediction of ambulatory outcome is the pre-treatment ambulatory status of the patient. Factors associated with longer survival are single site of compression, absence of visceral or brain metastatic disease, radiosensitive tumours and the ability to walk before and after treatment.⁴

Conclusion

Metastatic spinal cord compression is a devastating complication of cancer and if left undetected or untreated can lead to permanent neurological complications and can shorten survival. Clinical suspicion is the most important factor in diagnosing this condition and urgent MRI is required to make the definitive diagnosis. It is important, therefore, to remain alert for the risk factors and clinical features of MSCC to recognise when to refer for urgent investigation. Although patients may have advanced disease, urgent recognition and management can significantly improve patient outcomes and therefore quality of life. 

Corticosteroids are the first line of treatment, followed by urgent radiotherapy; however surgery is indicated for selected patients. 

References

1. National Institute for Health and Clinical Excellence. Metastatic cord compression: Diagnosis and management of patients at risk of or with metastatic spinal cord compression. (Clinical Guideline 75). London: NICE, 2008. www.nice.org.uk/CG75
2. Loblaw DA, Laperriere NJ, McKillop WJ. A population based study of malignant spinal cord compression in Ontario. Clin Oncol 2003;15;211-217
3. Abrahm JL Assessment and treatment of Patients with Malignant Spinal Cord Compression Journal Of Supportive Oncology 2004 2; 5;377-407
4. Cole JS , Patchell RA. Metastatic epidural spinal cord compression Lancet Neurol 2008;7:459-66
5. Schiff D O’Neill BP, Suman VJ. Spinal Epidural metastases as the initial manifestation of malignancy: clinical features and diagnostic approach Neurology 1997;49:452-56
6. Mak KS, Lee LK, Mak RH et al. Incidence and treatment patterns in hospitalisations for malignant spinal cord compression in the United States 1998-2006 s J Radiat Oncol Biol Phys 2001;80:824
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8. West of Scotland Malignant Spinal Cord Compression Guidelines Development Working Group. West of Scotland Guidelines for Malignant Spinal Cord Compression Oct 2013 71www.woscan.scot.nhs.uk/
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12. George R, Jeba J, Ramkumar G et al. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev 2008; CD006716 
13. Sorernson PS, Helweg-Larsen S, Mouridsen H, Hansen HH. Effect of high dose dexamethasone in carcinomatous metastatic spinal cord compression treated with radiotherapy: a randomised trial. Eur J Cancer 1994;30A:22-27
14. Patchell RA, Tibbs PA, Regine WF et al. Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised control trial. Lancet 2005;366:643-478
15. Schiff D, Brown P Shaffery ME. Treatment and prognosis of neoplastic epidural spinal cord compression, including cauda equina syndrome. Updated on Sep 22,2014 accessed on 10/12/14 www.uptodate.com
16. Rades D, Fehlauer F, Schulte R et al. Prognositc factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol 2006;24:3388-93
17. Levack P, Collie D et al. A prospective audit of diagnosis, management and outcome of malignant spinal cord compression. Clinical Resource and Audit Group (CRAG) 2001