What is the differential diagnosis, red‑flag assessment, and initial treatment for a patient presenting with a headache at the base of the skull?

Headache at the Base of the Skull: Differential Diagnosis, Red Flags, and Initial Management

Immediate Red Flag Assessment

The first priority is to exclude life-threatening secondary causes through targeted red flag screening, focusing on thunderclap onset, fever, focal neurological deficits, and orthostatic pattern. 1

Critical Red Flags Requiring Urgent Investigation:

• Thunderclap headache (sudden, severe onset) – suggests subarachnoid hemorrhage or cerebral venous thrombosis 1
• Unexplained fever – raises concern for meningitis or other infectious etiologies 1
• Focal neurological symptoms (weakness, sensory changes, sixth nerve palsy) – indicates possible structural lesion or intracranial pathology 1, 2
• Impaired memory or altered consciousness – suggests serious intracranial process 1
• Recent head trauma – must be evaluated for subdural hematoma or other traumatic injury 1

Orthostatic Pattern Assessment (Critical for SIH):

Ask two specific questions to identify spontaneous intracranial hypotension (SIH): "Is the headache absent or mild upon waking?" and "Does it worsen significantly within 2 hours of standing and improve >50% within 2 hours of lying flat?" 1, 2

• True orthostatic headache has consistent timing of onset and offset with position changes 1
• Brief (2-second) visual darkening or intermittent 10-15 minute headaches that respond to simple analgesics do not meet SIH criteria 2
• Normal CSF opening pressure does NOT exclude SIH – clinical presentation and imaging findings are more reliable than measured pressure 2

Differential Diagnosis for Occipital/Skull Base Headache

Primary Headache Disorders:

Cervicogenic Headache (most common for fixed occipital pain):

• Unilateral, fixed side-locked pain starting in the neck and radiating to frontal/temporal regions 3, 4, 5
• Provoked by cervical movement or sustained neck positions, not by upright posture alone 1, 3, 5
• Reduced cervical range of motion and myofascial tenderness on examination 1, 3, 5
• Digital pressure over upper nuchal trigger points reproduces the pain pattern 4, 5
• History of whiplash injury is common 4, 5

Migraine with Occipital Location:

• Pain worsened by physical movement rather than posture 1
• Accompanied by nausea, photophobia, phonophobia 1
• May have aura or vertigo (not tinnitus or hearing loss) 1
• Bilateral or alternating sides more common than fixed unilateral 1

Tension-Type Headache:

• Bilateral pressing or tightening quality 1
• Mild to moderate intensity, not aggravated by routine physical activity 1
• Lacks accompanying symptoms of migraine 1

Occipital Neuralgia:

• Paroxysmal lancinating pain in the distribution of greater, lesser, or third occipital nerves 6
• Pain restricted to the nerve distribution, not radiating to frontal regions 4, 6
• Distinct from cervicogenic headache by its sharp, shooting quality 6

Secondary Headache Disorders:

Spontaneous Intracranial Hypotension (SIH):

• Orthostatic headache as defined above, with eye pain and pulsatile tinnitus 1, 2
• Predisposing factors: connective tissue disorders (Ehlers-Danlos, Marfan), joint hypermobility, spinal osteophytes, disc herniation 1, 2
• Cerebral venous thrombosis occurs in ~2% of SIH cases 2

Postural Orthostatic Tachycardia Syndrome (PoTS):

• Perform active standing test: measure supine heart rate/blood pressure, then at 1,3,5, and 10 minutes standing 1, 2
• Diagnosis requires heart rate increase >30 beats/minute in adults 1, 2
• Negative standing test does not exclude PoTS if clinical suspicion remains high 1, 2

Orthostatic Hypotension:

• Standing test shows systolic BP drop >20 mmHg or diastolic drop >10 mmHg 1, 2
• Headache improves with lying flat but lacks other SIH features 1

Skull Base Lesions (rare but important):

• Meningiomas: headache with visual disturbances from optic apparatus compression 7
• Leiomyomas/angioleiomyomas: extremely rare, headache most common symptom, average tumor size 2.75 cm 1, 8
• Pituitary adenomas: sellar/suprasellar location with visual field defects 7

Initial Diagnostic Workup

Clinical Examination:

Perform targeted neurological examination including:

• Cervical range of motion and myofascial palpation for trigger points 1, 3, 5
• Assessment for sixth nerve palsy, neck stiffness, focal deficits 2
• Fundoscopic examination if visual symptoms present 7
• Active standing test with vital signs at specified intervals 1, 2
• Evaluation for joint hypermobility and skin extensibility (connective tissue disorder screening) 1, 2

Imaging Indications:

Order MRI brain with IV contrast AND complete spine MRI with fluid-sensitive sequences if:

• Confirmed orthostatic pattern meeting SIH criteria 1, 2
• Any red flag features present 1
• Progressive visual disturbances suggesting skull base lesion 7

MRI findings in SIH include:

• Diffuse pachymeningeal enhancement, venous sinus engorgement, midbrain descent, pituitary enlargement 2
• Epidural fluid collections or CSF-venous fistula on spine imaging 2
• Note: ~20% of active CSF leaks have normal brain MRI – negative imaging does not exclude SIH with high clinical suspicion 2

CT or MR venography if:

• Concern for cerebral venous thrombosis (rare SIH complication) 2

Initial Treatment Approach

For Cervicogenic Headache (Most Likely if No Red Flags):

• Physical therapy targeting cervical dysfunction 3, 4, 5
• NSAIDs or acetaminophen for acute pain 3
• Consider greater occipital nerve block with anesthetic ± corticosteroid for diagnostic confirmation and therapeutic benefit 3, 4, 6
• Refractory cases may benefit from botulinum toxin type A injections 3

For Confirmed SIH:

• Early epidural blood patch (EBP) is first-line treatment and should be performed as soon as possible after diagnosis 2
• Non-targeted EBP is appropriate initially; myelography reserved for failed cases 2
• Refer to neurology within 2-4 weeks if ambulatory and self-caring, within 48 hours if unable to self-care with help, or emergency admission if unable to self-care without help 1, 2

For Migraine or Tension-Type Headache:

• Standard acute and preventive migraine therapies per established protocols 1
• Headache diary to document frequency, triggers, and medication use 1

Common Pitfalls to Avoid

• Do not exclude SIH based on normal CSF opening pressure – CSF hypovolemia, not pressure, is the problem 2
• Do not diagnose cervicogenic headache based solely on occipital location – must have provocation by cervical movement and reduced neck mobility 1, 3, 4
• Do not assume nerve blocks are diagnostic for cervicogenic headache alone – they are also effective in migraine and can produce false positives 6
• Do not delay imaging if red flags present – thunderclap onset, fever, or focal deficits require urgent investigation 1
• Do not miss deep skull involvement – always assess whether a palpable mass involves bone, requiring neurosurgical evaluation 8