What is the best course of action for a 30-year-old female patient with a 7-month history of progressively worsening, severe, chronic headaches localized to the right frontal and orbital area, exacerbated by postural changes, and resistant to multiple oral and intravenous (IV) medications, with a normal computed tomography (CT) scan?

Urgent MRI Brain and Spine with Contrast Required to Rule Out Spontaneous Intracranial Hypotension

This patient requires immediate MRI imaging of the brain and complete spine with contrast to evaluate for spontaneous intracranial hypotension (SIH), which is the most critical diagnosis to exclude given the postural worsening, progressive nature, and medication resistance. 1

Critical Red Flags Present

This presentation contains multiple concerning features that mandate advanced imaging beyond the normal CT:

• Postural worsening (worse when bending over or laying down) is the hallmark of intracranial hypotension 1
• Progressive worsening over 7 months suggests an evolving structural problem 1
• Medication resistance to multiple oral and IV therapies indicates this is not a typical primary headache disorder 1
• Prolonged current episode (>48 hours) with severe intensity 1

Normal CT does not exclude SIH or other serious secondary causes - CT has poor sensitivity for detecting the dural enhancement, brain sagging, and spinal CSF leaks characteristic of intracranial hypotension 1.

Why Spontaneous Intracranial Hypotension Must Be Ruled Out

SIH can precipitate life-threatening complications including cerebral venous thrombosis and intracranial hemorrhage if left undiagnosed 1. The case report literature documents a patient with SIH who developed superior sagittal sinus thrombosis leading to acute intraparenchymal hematoma requiring emergency craniotomy 1. This represents a medical emergency with significant morbidity and mortality risk.

Specific Imaging Protocol Required

MRI brain with IV contrast is essential as the initial brain imaging modality because it demonstrates:

• Diffuse smooth dural enhancement (most sensitive finding) 1
• Brain sagging with descent of brain structures 1
• Subdural fluid collections 1
• Pituitary hyperemia and engorgement 1

MRI complete spine with IV contrast must be performed simultaneously to:

• Identify CSF leak source (epidural fluid collections) 1
• Detect CSF-venous fistulas 1
• Visualize dilated epidural venous plexus 1
• Locate spinal meningeal defects 2

The ACR Appropriateness Criteria (2024) designate MRI brain with IV contrast and MRI complete spine with IV contrast as "usually appropriate" (rating 8-9) for initial imaging of suspected intracranial hypotension with orthostatic headache 1.

Important Clinical Caveat

CSF opening pressure can be normal in patients with SIH - the absence of low CSF pressure should not exclude this diagnosis 1. The diagnosis relies on imaging findings and clinical presentation, not lumbar puncture results alone.

If MRI Confirms SIH

Treatment involves:

• Epidural blood patch (EBP) as first-line therapy for symptomatic relief 1
• Flat positioning for 24 hours post-procedure, then gradual elevation over 48 hours 1
• If two EBPs fail and structural lesion identified, proceed to open surgical repair of the dural defect 1
• Prone Trendelenburg positioning may be used for epidural injection 1

If MRI is Normal

Only after excluding SIH and other secondary causes should you consider this as chronic migraine:

Chronic Migraine Management (If Secondary Causes Excluded)

This patient meets criteria for chronic migraine (>15 headache days/month for >3 months) 1.

Assess for medication overuse headache (MOH) - the resistance to multiple medications and 7-month progression raises concern for MOH, which occurs with frequent acute medication use (>2 days/week) 1.

If MOH present:

• Abrupt withdrawal of overused medications (except opioids, which require tapering) 1
• Warn patient of temporary worsening before improvement 1
• Start prophylactic therapy simultaneously with withdrawal 1

Prophylactic Treatment Options

Topiramate is the only medication with proven efficacy in randomized controlled trials specifically for chronic migraine 1. Start this as first-line prophylaxis.

OnabotulinumtoxinA is FDA-approved specifically for chronic migraine prophylaxis and should be initiated if topiramate fails or is not tolerated 1, 3.

Other options with evidence in episodic migraine (often used off-label for chronic migraine): gabapentin, tizanidine, amitriptyline, valproate 1, 4.

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) are reserved for patients who have failed 2-3 other preventive medications 1.

Referral to Neurology/Headache Specialist

Refer immediately given the severity, chronicity, medication resistance, and need for specialized management 1. Chronic migraine management is challenging and typically requires specialist care 1.