Radiation myelopathy

Definition

Radiation therapy (RT) involving or near the spinal cord can lead to toxicity in both the central and peripheral nervous systems. Several syndromes associated with radiation-induced myelopathy have been identified, with the most notable being:

• Transient radiation myelopathy (TRM): a benign and temporary form of myelopathy. It is characterised by Lhermitte’s sign; which is the term used that describes a transient sensation of an electric shock that extends down the spine and extremities upon neck flexion.^r
• Chronic progressive radiation myelopathy (CPRM): a rare but severe late effect of RT. It is a clinical syndrome that manifests with spinal cord signs and symptoms. These can be severe and result in pain, paraesthesia, sensory deficits, paralysis, Brown-Sequard syndrome, and bowel and/or bladder incontinence.^r

Pathophysiology

Radiation myelopathy is attributed to transient demyelination caused by radiation-induced suppression of myelin producing oligodendrocytes in the affected segment of the irradiated spinal cord.^rrr

Incidence/prevalence

The incidence of Lhermitte's sign in TRM is difficult to estimate. It has been reported between 3.6 to 10.3% in patients who have received radiation to the cervical spinal cord.^rr

CPRM is an uncommon development.^r Unlike TRM, CPRM is usually irreversible, and lacks any treatment with proven efficacy.^rr

Onset/duration

Studies suggest the median development time for Lhermitte's sign is 3 months after the completion of RT. It typically resolves over the subsequent 3-6 months without treatment.^r While CPRM is a late effect of radiation treatment and may occur 6-24 months following RT.^r

Risk factors

Risk factors for developing TRM include the extent of the spinal cord included in the treatment field and the dose given per fraction i.e there is an increased risk in patients receiving >2 Gy per fraction per day.^r Concurrent chemotherapy can also increase risk of developing Lhermitte's sign.^r 

The risk of CPRM is related to the total dose of radiation delivered to the spinal cord. When conventional fractionation is used at doses of 1.8 to 2 Gy per fraction to the full thickness of the spinal cord, the estimated risk of myelopathy is 0.2% for a total dose of 50 Gy, 6% for a total dose of 60 Gy and 50% for a total dose of 69 Gy.^r New data indicates that for stereotactic (ultra-hypofractionated) treatments delivered in one to five fractions, the estimated spinal cord point maximum doses (Dmax) associated with a 1 to 5% risk of radiation myelopathy are as follows: 12.4 to 14 Gy in1 fraction, 17 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23 Gy in 4 fractions, and 25.3 Gy in 5 fractions.^rr In addition to radiation dose and field size, evidence suggests that radiosensitising agents, whether administered systemically or intrathecally, may increase the risk of CPRM and reduce the spinal cord’s tolerance to radiation.^rrrr

The development of TRM has not been shown to predict the development of CPRM.^r

Signs and symptoms

Assess the patient for the following signs and symptoms:^r

• Lhermitte's sign
• paraesthesia or other sensory deficits (either unilateral or bilateral)
• paresis or paralysis
• loss of pain sensation
• loss of temperature sensation
• altered balance
• bowel and/or bladder incontinence
• Brown-Sequard syndrome.

Investigations and diagnosis

Before diagnosing TRM and CPRM, it is essential to rule out other aetiologies, such as tumour progression or development of new metastases leading to spinal cord compression. Patients should be given a thorough neurological examination and receive an MRI scan for comprehensive assessment. Increased spinal cord metabolic activity and positive positron emission tomography (PET) imaging have been described in association with Lhermitte sign.^r However, there are no investigations to conclusively diagnose TRM.

Grading

Table 1. CTCAE grading for myelitis.^r

Common Terminology Criteria for Adverse Events opens in a new tab or window (CTCAE) v5.0, 27 November, 2017

Treatment

TRM

No treatment approach has demonstrated clear benefits, and since TRM typically resolves gradually on its own, it generally does not need specific management.

CPRM

No treatment approach has been shown to be beneficial, there is some limited evidence for considering the following:

• high dose steroids
• anticoagulants
• hyperbaric oxygen therapy
• referral to an occupational therapist/physiotherapist to maximise function.^r

Educate the patient:

• to immediately report any progression of neurological symptoms
• on preventing injuries that may occur due to neurological or sensory deficits.

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