Secondary Causes of Migraines in a 30-Year-Old Female with Normal CT and MRI
With normal neuroimaging, the focus shifts to identifying non-structural secondary causes including medication overuse headache, hormonal factors (particularly menstrual-related migraine), sleep disorders, and systemic conditions that can trigger or mimic migraine. 1, 2
Key Principle: Normal Imaging Does Not Exclude All Secondary Causes
While normal CT and MRI effectively rule out structural pathology (tumors, vascular malformations, hemorrhage, hydrocephalus), they do not exclude several important secondary headache disorders that require specific evaluation and management. 1, 2
Most Important Secondary Cause to Evaluate: Medication Overuse Headache (MOH)
Medication overuse headache is the most critical secondary cause to identify in patients with apparent chronic migraine and normal imaging. 1
- MOH commonly develops from overuse of acute migraine medications and is often conflated with chronic migraine 1
- This represents a treatable cause that requires specific intervention (medication withdrawal) rather than escalation of preventive therapy 1
- Carefully review frequency of acute medication use through headache calendars 1
Hormonal Factors in Women of Reproductive Age
In a 30-year-old female, menstrual-related migraine is a common secondary pattern requiring specific evaluation and treatment. 1
Menstrual Migraine Considerations:
- Pure menstrual migraine without aura may benefit from perimenstrual preventive treatment 1
- Perimenstrual prophylaxis typically involves daily long-acting NSAID (naproxen) or triptan (frovatriptan or naratriptan) for 5 days, beginning 2 days before expected menstruation 1
- Continuous combined hormonal contraceptives can be considered for pure menstrual migraine without aura 1
- Critical caveat: Combined hormonal contraceptives are absolutely contraindicated in migraine with aura due to increased stroke risk 1
Systemic and Metabolic Causes to Investigate
Blood Work Considerations:
While not explicitly detailed in the guidelines for routine migraine evaluation, certain systemic conditions warrant investigation when clinical suspicion exists:
- Thyroid dysfunction - can trigger or worsen headache patterns 3
- Anemia - may contribute to headache frequency 3
- Inflammatory markers (ESR) - particularly important if any features suggest temporal arteritis, though less likely at age 30 4
Sleep-Related Factors
Headaches that awaken patients from sleep represent a red flag feature, but in the context of normal imaging, consider sleep disorders as secondary contributors. 2, 5, 3
- Sleep apnea can trigger morning headaches 3
- Poor sleep hygiene and sleep deprivation are common migraine triggers 3
Substance-Related Causes
Caffeine:
- Both excessive caffeine intake and caffeine withdrawal can trigger headaches 1
- Caffeine is included in some combination analgesics for migraine treatment but can contribute to MOH 1
Other Substances:
- Alcohol consumption patterns 3
- Dietary triggers (though evidence for specific food triggers is limited) 3
Psychiatric Comorbidities
Depression and anxiety are common comorbid conditions with migraine that can worsen headache patterns and require concurrent treatment. 1, 6
- These represent comorbidities rather than true secondary causes but significantly impact treatment selection 6
- Amitriptyline may be particularly useful when depression coexists with migraine 1, 6
Cervicogenic Headache Consideration
While imaging is normal, cervical spine pathology or cervicogenic headache may mimic migraine:
- Physical examination of the cervical spine and musculature is warranted 3, 7
- This diagnosis requires specific clinical features including neck pain and headache provocation with neck movements 3
Red Flags That Would Warrant Further Investigation Despite Normal Initial Imaging
Even with normal CT/MRI, certain features warrant additional evaluation: 1, 2, 3
- Progressively worsening headache over weeks - may require repeat imaging or CSF analysis 2, 5, 3
- Headache with Valsalva maneuver - consider CSF pressure disorders 2, 5, 3
- Thunderclap onset - if CT negative, lumbar puncture for xanthochromia is mandatory to exclude subarachnoid hemorrhage 5, 7
- Systemic symptoms (fever, weight loss) - warrant infection or malignancy workup 3, 7
Specific Diagnostic Approach for This Patient
Step 1: Detailed Medication History
- Document all acute headache medication use (prescription and over-the-counter) 1
- Use headache calendars to track frequency of medication use 1
- MOH is diagnosed when acute medication is used ≥10 days/month for triptans or ≥15 days/month for simple analgesics 1
Step 2: Menstrual Cycle Correlation
- Track headache timing relative to menstrual cycle for at least 2-3 cycles 1
- Determine if pattern suggests pure menstrual migraine or menstrually-related migraine 1
Step 3: Screen for Comorbidities
- Assess for depression and anxiety 6
- Evaluate sleep quality and sleep disorders 3
- Review cardiovascular risk factors if considering hormonal therapy 1
Step 4: Targeted Laboratory Testing
- Consider thyroid function tests, complete blood count if clinically indicated 3
- ESR only if clinical features suggest inflammatory process 4
Common Pitfalls to Avoid
Do not assume normal imaging means primary migraine without evaluating for MOH - this is the most common treatable secondary cause that requires specific management (medication withdrawal) rather than preventive therapy escalation. 1
Do not prescribe combined hormonal contraceptives without confirming absence of aura - the stroke risk in migraine with aura is absolute contraindication. 1
Do not overlook the diagnostic value of headache calendars - these are essential for identifying medication overuse patterns and menstrual relationships. 1
Do not order repeat neuroimaging without new red flag features - the yield remains extremely low (0.2%) in patients with normal neurological examination and typical migraine features. 2, 4