Introduction

Metastatic spinal cord compression (MSCC) occurs in 3–5% of patients with cancer. Prostate, breast and lung cancer each account for 15–20% of cases; lymphoma, myeloma and renal cell cancer account for 10% and the remainder is due to colorectal cancers, sarcomas and cancers of unknown primary. Although more frequent in patients with known malignancy, MSCC is the presenting feature in up to 20% of patients with no prior diagnosis of cancer, particularly lung cancer.

Aetiology

The mechanisms by which MSCC may develop include:

Early stage compression of the cord results in oedema, venous congestion and demyelination, and neurological recovery may still be possible during this phase with prompt decompression. Continued compression causes secondary vascular injury and irreversible infarction. The most common location of compression is thoracic (50–70%) followed by lumbo-sacral (20–30%) and cervical spine (10–20%). Up to 85% patients have multiple vertebral metastases and importantly, around 17% of patients have two or more levels of compression at presentation.

Spinal cord metastases can be of three types depending on the location of tumour deposit:

Clinical features

Back pain is the most frequent (95%) first symptom, which commonly precedes the diagnosis of MSCC by up to 3 months in patients with known cancer and up to 5 months in those without a known malignancy. The pain may be localized or neurogenic and is typically worse when the patient is supine.

Limb weakness is the second most common symptom. Up to 85% of patients will have abnormal power in the limbs at presentation, which depends on the neurologic level of compression.

Sensory deficit may manifest itself as paraesthesia or sensory loss and is present in up to 65% of patients with MSCC. Up to 50% of patients will have a dermatomal sensory level, although this may vary by several dermatomes above or below the true level of compression.

Autonomic dysfunction is a late complication affecting up to 50% of patients with MSCC. It includes impotence, bladder and bowel dysfunction, with constipation occurring most frequently.

There are two clinical variants of MSCC, which require early recognition:

Investigations

MRI of the whole spine is the investigation of choice for suspected MSCC. CT is used only when MRI is contraindicated. A sagittal screening of the whole spine with T1 and short T1 inversion recovery (STIR) images should be done to ensure that multiple levels of compression are not missed and also to identify asymptomatic metastases. T2 weighted images help to detect the degree of compression by a soft tissue component and intramedullary lesions (Figure 23.1).

Figure 23.1 Imaging in cord compression. MRI scan shows spinal cord compression due to a collapsed vertebra (A,B) and an intramedullary metastasis from lung cancer (C).

In patients who have not been previously diagnosed with cancer, a histological diagnosis is required before definitive treatment can be planned. Patients should be investigated like any other patient with cancer of unknown primary and an appropriate area most amenable to biopsy should be established. However, treatment should not be delayed during these investigations and prompt neurosurgical involvement should be established if biopsy is not possible.

Management

The aim of treatment is to preserve or improve neurological function and achieve pain control. 70–100% patients who are ambulant at the beginning of treatment remain ambulant with prompt treatment, whereas only 30–50% patients who are non-ambulant regain the ability to walk and only 5–10% of paraplegic patients become ambulant. Hence it is important to have definitive treatment within 24 hours of presentation with suspected cord compression. Patients with MSCC secondary to a vascular event will not respond to treatment.

Specific measures

Definite treatment of MSCC depends on the histologic type and associated spinal stability. In patients with no prior history of cancer, surgical decompression with histologic confirmation is appropriate. If surgical decompression is not possible, a CT guided biopsy is needed.

Surgery may involve decompression, stabilization and or resection and reconstruction of the spinal canal. The patient’s overall prognosis and performance status should be taken into consideration and patients who have had no distal neurological function for >24 h should not be considered for surgery (Boxes 23.1 and 23.2).

Box 23.1
Patients with MSCC according to outcome after surgical intervention

Good surgical candidates	Poor surgical candidates
‘Good prognosis tumours’ e.g. breast cancer, testicular cancer etc.	‘Poor prognosis tumours’ e.g. lung cancer, melanoma
Single level of compression with solitary or few vertebral metastases	Multiple levels affected or multiple spinal metastases
Absence of visceral metastases	Presence of visceral metastases
Good neurological function	Poor neurological function
No previous radiotherapy	Recurrence following radiotherapy
Minimal co-morbidity	Medically unfit for surgery
Unknown primary or no histopathological diagnosis	Prognosis <3 months

Box 23.2
Indications for surgical treatment*

• Relapse after radiotherapy

• Progression while on radiotherapy

• Radiation resistant tumours

• Unknown primary tumour

• Unstable spine or pathological fractures

^* With a single site of cord compression and no total paraplegia for longer than 48 h.

Radiotherapy is the treatment most frequently used and is most effective for patients with radiosensitive tumours who are ambulatory at the beginning of treatment. For those without mechanical pain or structural instability, radiotherapy may significantly improve pain control and neurological function. The most commonly used regimes are 20 Gy in five fractions (more appropriate for patients with expected short survival) or 30 Gy in 10 fractions (Box 23.3). Some patients may deteriorate during radiotherapy when the steroid dose may be increased or they may be considered for surgery if appropriate. Patients with established paraplegia are treated with an 8 Gy single fraction for pain control.

Box 23.3
Radiotherapy in spinal cord compression

• Position – supine or prone

• Treatment volume – one vertebra above and below MRI proven compression

• Ensure that all paravertebral disease is enclosed in the volume if feasible

• Direct posterior beam 6 MV (parallel lateral in cervical region if feasible)

• Prescription point – anterior spinal canal (either measured from MRI or arbitrary, see Figure 23.2)

• Dose – 30 Gy in 10 fractions or 20 Gy in five fractions

Figure 23.2 Radiotherapy in spinal cord compression – anatomical landmarks and arbitrary radiotherapy dose prescription points.

The issue of whether surgery or radiotherapy or a combination of both gives best functional outcome is yet to be resolved. A randomized study compared radiotherapy (30 Gy in 10 fractions) started within 24 hours of onset of MSCC with surgery within 24 hours followed by radiotherapy within 2 weeks of surgery. Results showed that initial surgery followed by radiotherapy offers a longer period with ability to walk compared with those treated with radiotherapy alone (median, 126 days vs. 35 days, p = 0.006). This study showed that surgery permits most patients to remain ambulatory and continent for the remainder of their lives, while patients treated with radiation alone spend approximately two-thirds of their remaining time unable to walk and incontinent. However, results of this study may not be extended to all patients as the study was limited to patients with less radiosensitive tumours and with different tumour types and presentations.

Chemotherapy alone is not an option for treatment even in chemosensitive tumours as the response to treatment is often slow and unpredictable. Hence MSCC in chemosensitive tumours is treated with a combination of radiotherapy and chemotherapy.

Prognosis

The median survival following a diagnosis of MSCC is 3–6 months, with 17% of patients alive at 1 year and 10% alive at 18 months. Pre-treatment motor function is an important predictor of the ambulatory outcome. Patients who develop motor dysfunction more slowly also may have a better outcome.

Recurrence of spinal cord compression

7–14% of patients can present with recurrence of spinal cord compression after initial decompression. If the second cord compression is in a different area, treatment is the same as that of the original compression. However, if patients present with spinal cord compression at the initial radiation portal, surgical decompression is the initial option, particularly if the recurrence is within three months of initial treatment. If they are not a candidate for surgery, re-irradiation may be considered. It is important to make sure that the total dose to spinal code is kept below 100 Gy₂ (biologically equivalent dose of 100 Gy when delivered as 2 Gy per fraction). Many clinicians use a dose of 20 Gy in 8–10 fractions.

Paediatric spinal cord compression

Paediatric MSCC differs from adult MSCC in that it is often caused by chemosensitive histological types not seen in adults such as neuroblastoma, Wilms’ tumour (p. 323). The usual pathogenesis is the direct invasion of tumour through neural foramina. The most common histologic type is neuroblastoma, which responds to chemotherapy. Decompressive surgery is offered when patients present with rapid progression or progress during chemotherapy. Radiotherapy is only offered when there is no response after chemotherapy and/or surgery and for those who require palliation after failure of multiple systemic regimens.

Intramedullary spinal cord metastasis

This is rare (1% incidence) and lung cancer is the most common primary. Sensory deficit (79%), sphincter dysfunction (60%) and weakness (91%) are common manifestations. Up to 40% patients will have brain metastases. Treatment is with corticosteroids and radiotherapy.

Introduction

Encephalopathy is an important complication of cancer, which presents with an acute confusional state or delirium subsequent to abnormal brain function resulting from interference with brain metabolism. A number of aetiological factors can contribute to the development of encephalopathy in cancer patients. Generally, these are due to infection, metabolic abnormalities (such as hyponatraemia, hypercalcaemia) and drugs. A number of anti-neoplastic agents such as ifosfamide, methotrexate, cisplatin, vincristine, cytosine arabinoside etc. can cause encephalopathy.

Clinical features

The usual presentation is cognitive and behavioural changes. Patients can present with insomnia followed by acute confusion and delirium. Occasionally focal signs such as ataxia may predominate.

Clinical examination shows an altered level of consciousness, abnormalities of respiration, small reactive pupils and spontaneously roving eye movements. Grading of encephalopathy is as follows:

Management

Investigations include biochemical tests, infection screening, MRI brain, EEG and CSF examination and drug level estimation in selected cases.

In most cases of anti-neoplastic induced encephalopathy, the management is cessation of the drug and continuation supportive measures until recovery, and a re-challenge is seldom attempted. One exception is ifosfamide.

Ifosfamide encephalopathy can occur within minutes or hours of starting ifosfamide, or up to 24 hours after the completion of ifosfamide. The risk factors for ifosfamide encephalopathy are pelvic tumour, low albumin, impaired renal function, previous cisplatin, high dose of ifosfamide and CNS disease. In patients on ifosfamide, encephalopathy can be prevented by prophylactic dose of methylene blue (50 mg IV 4 times daily).

In patients with ifosfamide encephalopathy, treatment is based on the grade of the encephalopathy:

Optic neuropathy

Anti-neoplastic drug-induced optic neuropathy (ON) can be acute with rapidly progressive loss of vision. Cisplatin, carboplatin, carmustine, 5-fluorouracil, methotrexate, vinca-alkaloids, paclitaxel, tamoxifen and bisphosphonates are reported to cause optic neuropathy.

Clinical examination reveals reduced visual acuity in the affected eye and there may be associated field defects. Eye pain can also occur secondary to optic nerve sheath oedema. If papilloedema is present this suggests anterior optic neuritis, but this sign will be absent in retrobulbar neuritis.

Investigations may be normal but MRI can exclude intracranial metastases. Visual evoked potentials may display reduced amplitudes and increased latency suggesting optic nerve involvement.

Treatment of drug-induced optic neuritis involves the immediate withdrawal of the drug and exclusion of other causes. Intravenous methylprednisolone has been used but there are no randomized data to support this. Recovery can occur with drug withdrawal. However, the majority of patients have some permanent visual deficit.

Choroidal metastasis

Choroidal metastasis can result in sudden loss of vision. It is most common with breast and lung cancer and up to 20% may be bilateral. Cancer patients presenting with visual symptoms require detailed ophthalmologic assessment including a slit lamp examination. CT scan or MRI of the brain is needed to rule out brain metastasis.

Urgent radiotherapy is needed to avoid further visual deterioration and maintain useful vision. The entire choroid and retina of the affected eye is treated with a dose of 20 Gy in five fractions or 30 Gy in 10 fractions at 2.5 cm depth using a posteriorly angled lateral beam (to avoid opposite lens).

Introduction

Febrile neutropenia is defined as an oral or tympanic membrane temperature of ≥38°C on two occasions, at least one hour apart within a 12 h period or a single temperature of >38.5°C with an absolute neutrophil count of ≤0.5 × 10⁹/l or ≤1.0 × 10⁹/l with a predictable decline to ≤0.5 × 10⁹/l in 24–48 h.

Febrile neutropenia is one of the most common complications of cancer treatment. 50–60% of patients with febrile neutropenia have an established or occult infection and 20% of patients with a neutrophil count ≤1.0 × 10⁹/l have bacteraemia.

Susceptibility to infection increases as the neutrophil count drops below 1.0 × 10⁹/l. The frequency and severity of infection are inversely proportional to the absolute neutrophil count, with the duration of neutropenia also contributing to overall risk. The timing of the neutrophil nadir depends on the type of chemotherapy and generally, it occurs 5–10 days after the last dose. Usually the neutrophil count recovers 5 days after the nadir.

In the majority of cases, bacterial pathogens are responsible for febrile neutropenic episodes with fungal (Figure 23.3), viral and protozoal infections occurring more commonly as secondary events. Currently, Gram-positive bacteria account for 60–70% of microbiologically detected infections, which may in part be due to the prevalent use of quinolones as prophylactic antibiotics. Other possible causes of this change in trend include widespread use of intravenous catheters, along with more profound and prolonged neutropenia due to intensive and recurrent treatment regimes.

Figure 23.3 CT scan of the chest shows diffuse fungal infection in a neutropenic patient.

Clinical presentation and assessment