Radiation-Induced Brachial Plexopathy

Radiation induced brachial plexopathy is damage to the brachial plexus from radiotherapy to the breast, axilla, supraclavicular fossa or lung apex. It causes progressive sensory loss, weakness and pain of the arm and may follow a latency of many years.

Epidemiology. Risk rises with total dose (over about 60 Gy), large fraction size, and concurrent chemotherapy. Modern techniques have lowered the incidence to about 1 to 2% or less.

Forms. Early transient plexopathy appears within months and resolves. Delayed progressive plexopathy appears after a median of 1 to 4 years and can appear up to 30 years later.

Pattern. The upper trunk (C5 and C6) is commonly affected. Early pain is mild and paraesthesia is common, unlike tumour infiltration.

Outcome. Progression is usual. Many patients lose useful arm function.

Pathophysiology.

Radiation causes microvascular damage and fibrosis of the tissue around the plexus, with nerve compression and ischaemia. Axonal loss and demyelination follow.

Fibrosis can entrap the plexus within the thoracic outlet.

• Arm and hand paraesthesia and numbness, then weakness, with shoulder girdle and arm wasting.
• Reduced reflexes and arm lymphoedema in some.
• Pain, usually moderate; severe pain develops in a minority.

Red flags.

• Severe early pain, lower trunk pattern or Horner syndrome (tumour recurrence).
• Rapid worsening, or new spinal cord signs.

• Treatment history with dose and fields.
• Electromyography and nerve conduction studies: axonal loss with myokymic discharges, which favour radiation injury.
• MRI of the brachial plexus: diffuse T2 hyperintensity without a discrete mass; PET-CT or CT to exclude recurrence.
• Biopsy only when a mass or atypical findings exist.

Differential diagnosis. Tumour infiltration of the plexus, cervical radiculopathy, Parsonage-Turner syndrome, thoracic outlet syndrome, Pancoast tumour, post-surgical neuropathy, lymphoedema related pain.

• No treatment reverses the injury. Treat any recurrence separately.
• Physiotherapy, occupational therapy, splints, support of the arm to prevent shoulder subluxation, and lymphoedema care.
• 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.
• Duloxetine orally 30 mg once daily for 1 week, then 60 mg once daily. Maximum 120 mg daily, with little added benefit over 60 mg. Review at 4 to 6 weeks and stop if no benefit; withdraw slowly. Monitor blood pressure, sodium, mood and bleeding. Avoid when creatinine clearance is under 30 mL/min, in hepatic impairment, with monoamine oxidase inhibitors and with other serotonergic drugs.
• Pentoxifylline with vitamin E has been used for fibrosis, with weak evidence: pentoxifylline 400 mg orally three times daily with food for at least 6 months. Maximum 1.2 g daily. Monitor for bleeding and indigestion. Reduce to 400 mg twice daily when creatinine clearance is under 30 mL/min.
• Surgical neurolysis with a vascularised flap in selected patients, in specialist centres.

Monitoring. Neurological examination and function review every 3 to 6 months; imaging when symptoms change.

Referral and escalation. Neurology and pain clinic; oncology to exclude recurrence; rehabilitation and hand therapy.