What are the potential causes and management options for a 30-year-old female with intractable migraines lasting 5 days, worsening with positional changes, and unresponsive to oral or intravenous (IV) medications, with a normal computed tomography (CT) scan?

Intractable Migraine with Positional Worsening: Differential Diagnosis and Management

Critical Red Flag Assessment

This clinical presentation—5 days of intractable headache worsening with lying down/bending over despite normal CT—raises serious concern for elevated intracranial pressure from a mass lesion, idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST), or subdural hematoma that CT may have missed. 1

Immediate Diagnostic Priorities

• Obtain MRI with venography immediately to rule out CVST, posterior fossa mass, or other structural lesions that CT can miss, as CT has limited sensitivity for these conditions 1
• Perform lumbar puncture with opening pressure measurement if MRI is negative, as IIH (pseudotumor cerebri) is common in women of childbearing age and presents with positional headache worsening when supine 1
• The positional component (worse lying down/bending over) is atypical for primary migraine and strongly suggests increased intracranial pressure rather than typical migraine pathophysiology 1

Secondary Headache Considerations

High-Risk Features Present in This Case

• Duration >72 hours (status migrainosus threshold) with treatment failure indicates either refractory primary headache or undiagnosed secondary cause 2
• Positional worsening is a red flag that mandates investigation beyond CT, as this pattern suggests intracranial pressure abnormalities 1
• Failure to respond to both oral and IV medications is unusual for typical migraine and raises concern for alternative diagnosis 3

Most Likely Secondary Causes Given This Presentation

• Idiopathic intracranial hypertension (pseudotumor cerebri): Most common in women of childbearing age, presents with positional headache worse when supine, and requires LP with opening pressure >25 cm H2O for diagnosis 1
• Cerebral venous sinus thrombosis: Can present with progressive headache over days, positional features, and normal initial CT in 20-30% of cases; requires MR venography for diagnosis 1
• Posterior fossa mass or Chiari malformation: Positional worsening with Valsalva/bending suggests posterior fossa pathology that CT may miss 1

If Secondary Causes Are Excluded: Refractory Migraine Management

Immediate IV Treatment Protocol

Administer IV metoclopramide 10 mg plus IV ketorolac 30 mg as first-line combination therapy, which provides the highest efficacy for severe refractory migraine while avoiding opioids that cause dependency and rebound headaches 3, 4

• Add IV magnesium sulfate 2 grams over 15 minutes, which has evidence for refractory migraine in the emergency setting 3
• Consider IV dihydroergotamine (DHE) 0.5-1 mg if the above combination fails, as DHE has good evidence for status migrainosus 3
• Avoid opioids completely, as they lead to medication-overuse headache, dependency, and loss of efficacy over time 3, 4

Medication-Overuse Headache Assessment

• Determine frequency of acute medication use over the past 3 months, as using triptans ≥10 days/month or NSAIDs ≥15 days/month causes medication-overuse headache (MOH) that presents as daily intractable headache 3, 2
• If MOH is present, discontinue all acute medications and initiate preventive therapy immediately, as continued acute medication use perpetuates the cycle 3

Transition to Preventive Therapy

Initiate preventive therapy immediately for this patient, as intractable migraine lasting 5 days with treatment failure meets criteria for preventive therapy (≥2 attacks per month producing disability ≥3 days) 3, 5

• First-line options include propranolol 80-240 mg/day, topiramate 50-200 mg/day, or amitriptyline 30-150 mg/day, all with documented high efficacy 3, 5
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) should be considered if oral preventives fail or are contraindicated, with efficacy assessed after 3-6 months 3
• Preventive therapy requires 2-3 months for oral agents to show full effect, so set realistic expectations 3

Critical Pitfalls to Avoid

• Do not attribute positional worsening to typical migraine without excluding secondary causes, as this pattern demands investigation for elevated intracranial pressure 1
• Do not escalate acute medication frequency in response to treatment failure, as this creates medication-overuse headache; instead transition to preventive therapy 3
• Do not use opioids for refractory migraine, as they worsen outcomes through dependency, rebound headaches, and transformation to chronic daily headache 3, 4
• Do not rely on CT alone to exclude serious pathology when red flags are present; MRI with venography and LP with opening pressure are required 1