What is the recommended diagnostic work‑up and acute management for a patient presenting with a sudden, severe thunderclap headache?

Thunderclap Headache: Diagnostic Work-Up and Acute Management

Immediately obtain a noncontrast head CT on a high-quality scanner interpreted by a board-certified neuroradiologist, as this is 98.7% sensitive for detecting subarachnoid hemorrhage (SAH) when performed within 6 hours of headache onset and can exclude SAH without further testing in this time window. 1

Initial Diagnostic Approach

Immediate CT Imaging

• Perform noncontrast head CT immediately as the cornerstone diagnostic test, with 98% sensitivity and 99% specificity for acute SAH 1, 2
• If CT is performed within 6 hours of symptom onset and is negative, SAH is essentially excluded and no lumbar puncture is required in patients without new neurological deficits 1, 3
• CT sensitivity declines rapidly after 6 hours: 93% at 24 hours and 57-85% at 6 days, making timing critical 1

Risk Stratification Using Ottawa SAH Rule

Apply the Ottawa SAH Rule to determine need for additional testing if CT is negative or unavailable. Any patient meeting one or more of these criteria requires further workup 1:

• Age ≥40 years
• Neck pain or stiffness
• Witnessed loss of consciousness
• Onset during exertion
• Thunderclap headache (instantly peaking pain)
• Limited neck flexion on examination

The Ottawa SAH Rule has 100% sensitivity but only 15.3% specificity, meaning it effectively screens out low-risk patients 1

Lumbar Puncture Protocol

When to Perform LP

• Mandatory if CT is negative or nondiagnostic AND symptom onset was >6 hours ago 1
• Mandatory if CT is negative but patient meets Ottawa SAH Rule criteria 1
• Must be performed at least 6-12 hours after symptom onset to allow xanthochromia development 1

LP Interpretation

• Visual inspection for xanthochromia has 93% sensitivity and 95% specificity for detecting ruptured aneurysms 4
• Spectrophotometric analysis for xanthochromia demonstrates 100% sensitivity and 95.2% specificity 1
• Red blood cell count, white blood cell count, and bilirubin detection are critical components 1

Advanced Vascular Imaging

CT Angiography

• CTA is a reasonable alternative to LP after negative CT if clinical suspicion remains high, with 97.2% sensitivity for cerebrovascular pathology 1, 3
• CTA has >95% sensitivity for aneurysms ≥3mm but only 61% sensitivity for aneurysms <3mm 1, 5
• CTA is faster and safer than conventional angiography and should be obtained if SAH is identified on initial CT 1

MRI/MRA Considerations

• If both CT and LP are negative, obtain brain MRI with susceptibility-weighted imaging (SWI) and vascular imaging (CTA or MRA) to evaluate for reversible cerebral vasoconstriction syndrome (RCVS), arterial dissection, cerebral venous thrombosis, and other vascular pathology 5, 6
• FLAIR and SWI/GRE sequences are most sensitive for SAH on MRI, with sensitivity ranging from 50-94% in acute SAH 1
• MRA has 85-100% sensitivity for aneurysms ≥5mm but drops to 56% for aneurysms <5mm 1

Digital Subtraction Angiography

• DSA with 3-dimensional rotational angiography is indicated when SAH is confirmed to detect aneurysm and plan treatment 1
• DSA is more sensitive than CTA/MRA for small vessel disease and arterial dissection 1

Critical Differential Diagnoses to Exclude

Life-Threatening Vascular Causes

• Aneurysmal SAH accounts for 10-25% of thunderclap headaches with 27-44% mortality and is described by 80% of alert patients as "worst headache of my life" 1, 5, 7
• Cervical artery dissection presents with thunderclap headache in up to 20% of cases and may be associated with Horner syndrome 5, 2, 7
• Cerebral venous sinus thrombosis can mimic SAH, particularly involving superior sagittal or lateral sinuses 5, 2
• Reversible cerebral vasoconstriction syndrome (RCVS) has become the second most common etiology of thunderclap headache and requires vascular imaging for diagnosis 6, 3

Other Critical Causes

• Spontaneous intracranial hypotension presents as thunderclap headache followed by orthostatic headache 5
• Intracranial infection (meningitis/encephalitis) can present with thunderclap headache, particularly with fever and altered mental status 5, 2
• Intracerebral hemorrhage associated with aneurysms or vascular malformations 5
• Pituitary apoplexy 6

Acute Management Priorities

Blood Pressure Management

• Between symptom onset and aneurysm obliteration, control blood pressure with a titratable agent to balance the risk of rebleeding against maintaining cerebral perfusion pressure 1

Preventing Rebleeding

• The risk of early aneurysm rebleeding is high and associated with very poor outcomes, making urgent evaluation and treatment mandatory 1
• Surgical clipping or endovascular coiling should be performed as early as feasible to reduce rebleeding risk 1
• Rebleeding increases odds 10-fold with sentinel headache, and up to 12% of patients die before receiving medical attention 1

Neuroprotection

• Oral nimodipine should be administered to all patients with confirmed aneurysmal SAH to improve neurological outcomes 1

Transfer Considerations

• **Low-volume hospitals (<10 aSAH cases per year) should consider early transfer** to high-volume centers (>35 aSAH cases per year) with experienced cerebrovascular surgeons, endovascular specialists, and multidisciplinary neuro-intensive care 1

Critical Pitfalls to Avoid

Timing Errors

• Never rely on CT alone after 6 hours from symptom onset, as sensitivity drops significantly and LP becomes mandatory when clinical suspicion remains high 1, 5
• Never perform LP before 6 hours from symptom onset, as xanthochromia may not have developed yet 1

Diagnostic Failures

• Failure to obtain noncontrast head CT is the most common diagnostic error, leading to misdiagnosis rates of 12% in recent studies (down from 64% before 1985) 1
• Misdiagnosis is associated with nearly 4-fold higher likelihood of death or disability at 1 year in patients with minimal neurological deficit 1, 5
• Do not skip LP based on negative CT in high-risk presentations, as this is the leading cause of missed SAH 5

Atypical Presentations

• Atypical presentations such as primary neck pain, syncope, seizure, or new focal neurological deficit still warrant full imaging workup, as standard algorithms may not apply 1
• Sentinel or warning headaches occur in 10-43% of patients within 2-8 weeks before major rupture and may be milder but last several days 1

Special Population Considerations

Familial Risk

• Patients with first-degree relatives with aneurysms or vascular abnormalities require neuroimaging even with atypical presentations, as these conditions are familial 1, 5
• Autosomal dominant polycystic kidney disease (ADPKD) increases risk for intracranial aneurysms, and these patients should be educated to recognize thunderclap headache as requiring immediate medical attention 5

Pediatric Patients

• Thunderclap headaches are rare in children, and evidence is based mainly on adult experience 1
• In children, MRI is more sensitive than CT for acute infarction when arterial dissection is suspected 1
• Girls using oral contraceptives are at increased risk for venous sinus thrombosis 1