Radiation Myelopathy

Radiation myelopathy is injury to the spinal cord from radiation. It occurs in two forms: a transient early syndrome with Lhermitte sign, and a delayed, usually progressive and irreversible myelopathy.

Early transient myelopathy. Starts 2 to 4 months after radiotherapy to the neck or upper chest with electric shock sensations on neck flexion. It resolves spontaneously over months and does not predict the delayed form.

Delayed myelopathy. Appears from 6 months to 4 years after treatment, with a peak at 9 to 15 months, and rarely later.

Dose relation. Risk is low (under 1%) at 45 to 50 Gy in 2 Gy fractions and rises steeply over 60 Gy. Larger fractions, re-irradiation, spinal length irradiated and concurrent chemotherapy increase risk.

Settings. Treatment of head and neck, lung, oesophageal and spinal tumours, lymphoma mantle fields, and stereotactic spinal radiosurgery.

Pathophysiology.

Early disease reflects transient demyelination from oligodendrocyte injury. Delayed disease reflects vascular injury with endothelial loss, white matter necrosis, demyelination and gliosis.

Damage is usually in the cervical or thoracic cord, within the irradiated segment.

• Early: Lhermitte sign, with tingling down the spine or limbs on neck flexion.
• Delayed: sensory loss, leg weakness, spasticity, gait ataxia, bladder and bowel dysfunction.
• Brown-Sequard pattern in some, and pain is uncommon early.

Red flags.

• Rapidly progressive weakness or sensory level (compression from tumour or collapse).
• Sudden onset or back pain with fever (epidural abscess or haematoma).

• Diagnosis of exclusion with dose and field records showing the cord in the field.
• MRI of the spine with contrast: swelling in the acute phase, T2 hyperintensity over the irradiated segments, possible patchy enhancement, later atrophy.
• Exclude cord metastasis, epidural compression, infection, vascular and demyelinating disease.
• Cerebrospinal fluid analysis, vitamin B12, and spinal vascular imaging when the picture is atypical.

Differential diagnosis. Spinal cord or epidural metastasis, intramedullary tumour, transverse myelitis, multiple sclerosis, paraneoplastic myelopathy, spinal cord infarction, vitamin B12 deficiency, syringomyelia.

• Early transient myelopathy: reassurance and observation only.
• Delayed myelopathy has no proven treatment. Stop further radiation to the segment.
• Dexamethasone 4 mg orally every 6 hours (16 mg daily) for 1 to 2 weeks as a test course, then taper over 4 to 6 weeks to the lowest effective dose or stop if no benefit. Maximum 16 mg daily. Give a proton pump inhibitor. Monitor glucose, blood pressure, mood and infection; caution in diabetes and peptic ulcer; no renal adjustment. Evidence is limited and benefit is often partial.
• Bevacizumab has been reported to help in small series; use only under specialist direction.
• Spasticity: baclofen orally 5 mg three times daily, increased every 3 days by 5 mg each dose to a usual 30 to 75 mg daily in 3 divided doses. Maximum 100 mg daily. Monitor sedation, weakness and mood; withdraw over at least 1 to 2 weeks. Reduce dose and extend the interval when eGFR is under 50, and use with great caution under 30. Caution in epilepsy and peptic ulcer.
• Neuropathic pain: pregabalin orally, 75 mg twice daily, increased after 3 to 7 days to 300 mg daily and, if needed after a further 7 days, to a maximum of 600 mg daily. Review at 4 weeks and stop if no meaningful benefit; withdraw over at least 1 week. Monitor sedation, dizziness, peripheral oedema and misuse. Adjust for renal function: creatinine clearance 30 to 60 mL/min, 75 to 300 mg daily; 15 to 30 mL/min, 25 to 150 mg daily; under 15 mL/min, 25 to 75 mg daily. Avoid in pregnancy unless benefit outweighs risk.
• Immobile patients: enoxaparin 40 mg subcutaneously once daily. Maximum 40 mg daily. Monitor platelets and creatinine. Use 20 mg once daily when creatinine clearance is under 30 mL/min.
• Rehabilitation, bladder and bowel programmes, skin and pressure care.

Monitoring. Neurological review and MRI at 3 to 6 months; bladder function and spasticity review at each visit.

Referral and escalation. Neurology, oncology and rehabilitation; urgent spinal imaging and neurosurgical review for any suspicion of compression; palliative care for advanced disease.