What is the best approach for a diagnostic workup in a 45-year-old male with recurrent headaches and potential underlying conditions such as previous head trauma, hypertension, or family history of headaches?

Diagnostic Workup for Recurrent Headaches in a 45-Year-Old Male

Begin with a focused history targeting red flags and primary headache features, followed by a neurologic examination; neuroimaging is indicated only when red flags are present or the diagnosis remains uncertain after clinical evaluation. 1, 2

Step 1: Screen for Red Flags Requiring Urgent Evaluation

Immediately assess for features demanding emergency neuroimaging or admission: 1, 2, 3

• Thunderclap headache ("worst headache of life") suggesting subarachnoid hemorrhage 1, 2
• New-onset headache after age 50 with scalp tenderness or jaw claudication (giant cell arteritis) 1, 3
• Progressive worsening headache or headache awakening patient from sleep 1, 3
• Headache brought on by Valsalva, cough, or exertion (increased intracranial pressure) 1, 3
• Focal neurological symptoms or signs 1, 2
• Altered consciousness, memory, or personality changes 1, 2
• Neck stiffness or limited neck flexion with unexplained fever (meningitis) 1, 2
• Recent head or neck trauma 1, 3

If any red flag is present, arrange emergency admission and neuroimaging before further evaluation. 2

Step 2: Obtain Detailed Headache Characteristics

Document the following specific features to differentiate primary headache types: 4, 1, 5

Temporal Pattern

• Age at onset: Migraine typically begins at/around puberty 4, 1
• Duration of episodes: Migraine 4-72 hours; cluster 15-180 minutes; tension-type variable 4, 1
• Frequency: Episodic vs ≥15 days/month (chronic migraine) 4, 1

Pain Characteristics

• Location: Unilateral (migraine, cluster) vs bilateral (tension-type) 4, 1
• Quality: Pulsating (migraine) vs pressing/tightening (tension-type) vs severe unilateral (cluster) 4, 1
• Severity: Moderate-to-severe (migraine, cluster) vs mild-to-moderate (tension-type) 4, 1
• Aggravating factors: Routine physical activity worsens migraine but not tension-type 4, 1

Associated Symptoms

• Nausea/vomiting, photophobia, phonophobia (migraine) 4, 1
• Ipsilateral autonomic symptoms (lacrimation, conjunctival injection, nasal congestion, ptosis, miosis) lasting 15-180 minutes (cluster headache) 1
• Visual/hemisensory disturbances lasting 5-60 minutes preceding headache (migraine with aura) 4, 1
• Orthostatic pattern (absent/mild on waking, onset within 2 hours of upright posture, >50% improvement within 2 hours of lying flat) suggests spontaneous intracranial hypotension 1

Step 3: Medication History and Overuse Assessment

Critical pitfall: Medication-overuse headache transforms episodic headaches into chronic daily headaches and requires different management. 1, 6

Document: 1, 6

• Non-opioid analgesics: ≥15 days/month for ≥3 months indicates medication-overuse headache 1
• Triptans, ergots, combination analgesics, or opioids: ≥10 days/month for ≥3 months indicates medication-overuse headache 1
• Include over-the-counter medications and substances obtained from others 6

Step 4: Family History and Comorbidities

• Family history of migraine: Strengthens suspicion of migraine (higher prevalence among first-degree relatives) 4, 1
• Comorbid conditions: Depression, anxiety, substance abuse, chronic musculoskeletal pain syndromes impair treatment effectiveness 6
• Hypertension, previous head trauma: Relevant for secondary headache risk 3

Step 5: Physical and Neurologic Examination

Perform focused examination: 1, 3, 7

• Complete neurologic examination: Abnormal findings warrant neuroimaging 3, 8
• Head and neck examination: Scalp tenderness (giant cell arteritis), neck stiffness (meningitis), limited neck flexion 1, 6
• Fundoscopic examination: Papilledema suggests increased intracranial pressure 8

Step 6: Diagnostic Tools and Screening

Validated Screening Questionnaires

• ID-Migraine questionnaire (3-item): Sensitivity 0.81, specificity 0.75, positive predictive value 0.93 1
• Migraine Screen Questionnaire (5-item): Sensitivity 0.93, specificity 0.81, positive predictive value 0.83 1

Headache Diary

Implement a headache diary to document frequency, duration, character, triggers, accompanying symptoms, and medication use—this reduces recall bias and increases diagnostic accuracy. 1, 5, 6

Step 7: Neuroimaging Indications

Neuroimaging is NOT routinely indicated for recurrent headaches without red flags or abnormal neurologic examination. 3, 9, 8

When to Order Imaging:

• MRI brain with and without contrast: Preferred modality for subacute presentations, suspected tumor/inflammatory process, or when diagnosis remains uncertain after clinical evaluation 1, 3, 8
• Non-contrast CT head: If presenting <6 hours from acute severe headache onset (subarachnoid hemorrhage sensitivity 95% on day 0, declining to 50% at 1 week) 1
• CT head: Acute trauma or abrupt-onset headache 1, 3

MRI reveals more detail than CT and is necessary for imaging the posterior fossa, but is more expensive and less widely available. 8

Step 8: Laboratory Testing (Selective)

Order only when specific secondary causes are suspected: 1

• ESR/CRP: If temporal arteritis suspected (patients >50 years with new-onset headache); note ESR can be normal in 10-36% of giant cell arteritis cases 1
• Morning TSH and free T4: If cold intolerance or lightheadedness present (hypothyroidism) 1
• Thyroid peroxidase (TPO) antibodies: If biochemical hypothyroidism confirmed 1

Step 9: Lumbar Puncture Indications

CSF examination is useful when: 3, 8

• Subarachnoid hemorrhage suspected with negative CT (perform after CT) 8
• Meningitis suspected (fever, neck stiffness) 3
• High or low CSF pressure syndromes (spontaneous intracranial hypotension) 3

Step 10: Referral Criteria

Emergency Admission

Any red flag present or patient unable to self-care without help 1, 2

Urgent Neurology Referral (Within 48 Hours)

Suspected spontaneous intracranial hypotension or patient unable to self-care but has help available 1, 2

Routine Neurology Referral (2-4 Weeks)

• Suspected primary headache disorder with diagnosis uncertain 1
• First-line treatments fail 1
• Headaches difficult to diagnose or worsen despite management 8

Urgent Rheumatology Referral

Suspected giant cell arteritis 1

Common Pitfalls to Avoid

1. Missing medication-overuse headache: Always quantify frequency of acute medication use—this transforms episodic headaches into chronic daily headaches requiring withdrawal before other treatments work 1, 6

2. Ordering unnecessary neuroimaging: Most recurrent headaches are primary headache disorders; imaging is indicated only with red flags or abnormal neurologic examination 3, 9, 8

3. Overlooking giant cell arteritis: ESR can be normal in 10-36% of cases; maintain high suspicion in patients >50 years with new-onset headache and scalp tenderness 1

4. Failing to implement a headache diary: This simple tool dramatically improves diagnostic accuracy and treatment monitoring 1, 5, 6