How to manage headaches in patients with light chain amyloidosis?

Management of Headaches in Patients with Light Chain Amyloidosis

For patients with light chain amyloidosis experiencing headaches, treatment should focus on standard migraine management protocols while carefully considering medication side effects that may worsen amyloidosis-related symptoms. 1

Diagnostic Approach

First, determine the headache type using ICHD-3 criteria:

• Migraine without aura: Recurrent headaches lasting 4-72 hours with at least two of: unilateral location, pulsating quality, moderate/severe intensity, aggravation by physical activity; plus nausea/vomiting and/or photophobia/phonophobia 1
• Migraine with aura: Visual, sensory, speech/language, motor, brainstem, or retinal symptoms that spread gradually over ≥5 minutes and last 5-60 minutes 1
• Chronic migraine: Headaches ≥15 days/month for >3 months with migraine features on ≥8 days/month 1
• Medication-overuse headache: Headaches ≥15 days/month with regular overuse of acute headache medications 1

Treatment Algorithm

First-line medications for acute headache management:

• Ondansetron: 4-8 mg every 4-8 hours (preferred antiemetic as it has fewer cardiac side effects) 1
• NSAIDs: Consider with caution in patients with preserved renal function

Avoid or use with extreme caution:

• Metoclopramide: Risk of extrapyramidal side effects, QT prolongation, and hyperprolactinemia 1
• Triptans: May worsen cardiac symptoms in patients with cardiac amyloidosis
• Ergot derivatives: Contraindicated due to vasoconstrictive properties

Preventive treatment options:

For patients requiring preventive therapy, consider:

• Beta-blockers: Use with caution and close monitoring in patients with cardiac amyloidosis
• Topiramate: Starting at low doses (25 mg daily) and titrating slowly
• CGRP monoclonal antibodies: Consider in patients with normal renal function

Special Considerations

Cardiac involvement:

• Patients with cardiac amyloidosis require careful medication selection to avoid worsening cardiac symptoms
• Avoid medications that can prolong QT interval or cause hypotension
• Monitor for medication side effects that may mimic amyloidosis progression 1

Renal involvement:

• Adjust medication doses based on renal function
• Avoid nephrotoxic medications in patients with renal amyloidosis

Autonomic neuropathy:

• Consider that headaches may be related to dysautonomia rather than primary headache disorders
• Monitor for orthostatic hypotension which may worsen headache symptoms

Treatment of Underlying Disease

• Treat the underlying plasma cell dyscrasia to prevent progression of amyloidosis 2
• First-line therapy with daratumumab, bortezomib, cyclophosphamide, and dexamethasone has shown the best outcomes 2
• For eligible patients, consider autologous stem cell transplantation 3

When to Refer

Consider neurology referral for:

• Headaches not responding to first-line treatments
• Unusual headache presentations
• Rapid worsening of headache symptoms

Consider hematology/oncology referral for:

• Optimization of amyloidosis treatment
• Management of treatment-related side effects

Pitfalls to Avoid

• Don't miss medication-induced headaches: Many medications used to treat amyloidosis can cause headaches as a side effect 1
• Don't overlook cardiac involvement: Headaches may be a symptom of cardiac dysfunction in amyloidosis
• Don't use medications that may worsen organ dysfunction: Carefully review all medications for potential impact on affected organs
• Don't delay treatment of the underlying amyloidosis: Early and effective treatment of the plasma cell dyscrasia is essential for improving outcomes 2