Headache red flags and secondary headache investigation

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Secondary-headache assessment is a risk-stratification exercise rather than a memorised acronym. Characterise onset to maximum intensity, first versus recurrent occurrence, progression, posture, Valsalva or exertional provocation, sleep interruption, trauma and relation to pregnancy. Ask about fever, rash, weight loss, cancer, immune compromise, anticoagulants, recent procedures, carbon monoxide exposure and vasoactive substances. Define eye pain, visual obscurations, diplopia, jaw claudication, neck pain and focal or cognitive symptoms. Medication history should include nitrates, phosphodiesterase inhibitors, hormonal treatments and analgesic frequency. Examination needs observations, mental state, neck stiffness, pupils, eye and temporal-artery assessment when relevant, fundoscopy and a reproducible neurological record. Red flags change urgency and the diagnostic question; they do not all mandate the same scan.

Thunderclap headache is treated as subarachnoid haemorrhage until adequately assessed, but differential diagnoses include reversible cerebral vasoconstriction syndrome, cervical artery dissection, cerebral venous sinus thrombosis, pituitary apoplexy and posterior reversible encephalopathy. NICE NG228 recommends urgent non-contrast CT. When CT is performed within 6 hours of onset and reported by a radiologist as showing no subarachnoid haemorrhage, routine lumbar puncture should not be offered; seek specialist advice and consider alternatives. If CT is later than 6 hours and negative, consider lumbar puncture, waiting at least 12 hours after symptom onset for bilirubin assessment. A positive CT proceeds to urgent vascular imaging and specialist discussion. The exact local radiology and laboratory pathway matters.

Subacute secondary patterns demand different pathways. Fever, neck stiffness, altered cognition or a non-blanching rash raises meningitis or encephalitis; obtain cultures and give time-critical antimicrobials under the local protocol without allowing imaging to create avoidable delay. Papilloedema suggests raised intracranial pressure and requires urgent neuroimaging, usually including venous imaging when cerebral venous sinus thrombosis is plausible, before a properly measured lumbar puncture when safe. New headache over 50 with visual or ischaemic symptoms suggests giant cell arteritis and needs immediate steroids plus same-working-day specialist coordination. Painful red eye with halos and vomiting suggests angle-closure glaucoma. In pregnancy and the puerperium, pre-eclampsia, venous thrombosis, dissection and pituitary disease lower the imaging threshold. Choose CT, MRI, angiography, venography, eye review or cerebrospinal-fluid analysis to answer the suspected mechanism.

Key points

First ask how quickly pain reached maximum intensity: instantaneous or within minutes is a thunderclap phenotype and must be investigated for subarachnoid haemorrhage and vascular alternatives.
A new progressive headache with fever, immunosuppression, malignancy, pregnancy, recent trauma, cognitive change, focal signs or papilloedema has a lower threshold for urgent investigation.
Measure blood pressure and temperature, perform fundoscopy where competent, assess visual acuity and fields, and document a full neurological examination including cognition and gait.
For suspected subarachnoid haemorrhage arrange immediate non-contrast CT head; the role and timing of lumbar puncture depend on scan timing, interpretation and the NICE pathway.
Do not perform lumbar puncture before resolving contraindications such as signs of raised intracranial pressure, focal mass effect, cardiorespiratory instability or a bleeding risk.
Jaw or tongue claudication, scalp tenderness, visual symptoms and polymyalgic features in an older adult suggest giant cell arteritis; inflammatory markers cannot safely overrule a strong phenotype.
Normal neuroimaging does not make every secondary cause disappear: cerebral venous sinus thrombosis, dissection, meningitis, pituitary apoplexy and pressure disorders need targeted tests.
A familiar primary headache can coexist with a new secondary disorder; compare the current episode with the person's established pattern instead of relying only on a previous migraine label.
Avoid routine imaging solely for reassurance when migraine or tension-type headache is clinically secure and no secondary features are present, because incidental findings can create harm.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Vascular emergencies

Subarachnoid or intracerebral haemorrhage, cervical dissection, cerebral venous thrombosis, ischaemic stroke and reversible vasoconstriction can present with new severe or thunderclap headache.

Infection and inflammation

Meningitis, encephalitis, giant-cell arteritis and systemic inflammatory disease cause headache with fever, meningism, visual, cognitive or constitutional features.

Pressure and structural disease

Tumour, hydrocephalus, abscess, idiopathic intracranial hypertension and cerebrospinal-fluid leak alter pressure or distort pain-sensitive structures, usually with contextual neurological clues.

Pregnancy, ocular and systemic causes

Hypertensive pregnancy disorders, acute glaucoma, severe hypertension, hypoxia, carbon-monoxide exposure and metabolic illness require targeted physiological and specialty assessment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Pain-sensitive structure activation
Disease irritates meninges, cerebral vessels, cranial nerves, venous sinuses or extracranial tissues, as brain parenchyma itself is relatively insensitive to pain.
2
Mechanical or inflammatory signalling
Pressure change, vessel-wall stretch, blood, infection or cytokines activate trigeminovascular and upper-cervical nociceptive pathways and produce secondary headache.
3
Neurological dysfunction
When the causal process also impairs perfusion, raises intracranial pressure or inflames brain tissue, focal deficits, seizures, visual loss or altered consciousness accompany pain.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Thunderclap phenotypeRed flag

Pain reaching maximal severity instantly or within a few minutes, particularly during exertion or sexual activity, needs urgent vascular assessment even when examination later normalises.

Raised intracranial pressureRed flag

Papilloedema, transient visual obscurations, pulsatile tinnitus, diplopia, progressive morning headache or vomiting suggests pressure pathology; a sixth-nerve palsy can be a false localising sign.

Central nervous system infectionRed flag

Fever, meningism, rash, photophobia, seizure, behavioural change or reduced consciousness should trigger immediate sepsis and meningitis or encephalitis pathways, recognising that the complete cluster may be absent.

Giant cell arteritisRed flag

New headache with scalp tenderness, jaw or tongue claudication, visual disturbance, constitutional features or polymyalgia in an older person threatens irreversible sight and requires immediate action.

Cervical artery dissectionRed flag

New unilateral head or neck pain with partial Horner syndrome, pulsatile tinnitus, cranial-nerve symptoms or delayed cerebral ischaemia warrants urgent arterial imaging and stroke expertise.

Pregnancy-associated secondary headacheRed flag

Severe new or changing headache during pregnancy or after birth, especially with hypertension, proteinuria, seizure, focal signs or thrombosis risk, must not be dismissed as ordinary migraine.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Immediate non-contrast CT headFirst step
Why
Detect acute subarachnoid or other intracranial haemorrhage and major mass effect in an emergency presentation.
Interpretation and limitations
Sensitivity for subarachnoid blood is highest early; apply the NICE timing pathway and radiologist interpretation rather than treating every negative scan identically.
02
Lumbar puncture with opening pressure
Why
Analyse cerebrospinal fluid for infection, haemorrhage or pressure disorder after safety assessment and appropriate imaging.
Interpretation and limitations
The required studies depend on the question; for CT-negative suspected subarachnoid haemorrhage after 6 hours, wait at least 12 hours from onset for bilirubin analysis.
03
MRI brain with targeted vascular imaging
Why
Assess parenchymal, pituitary, venous or arterial disease not adequately answered by an unenhanced CT.
Interpretation and limitations
Request MRV or CTV for suspected venous thrombosis and CTA or MRA for arterial pathology; a generic MRI request may omit the sequence needed.
04
Fundoscopy and formal ophthalmic assessment
Why
Identify papilloedema, threatened vision, optic neuropathy or an ocular cause of headache.
Interpretation and limitations
Uncertain disc swelling should prompt urgent competent review rather than a false negative; record acuity, pupils and fields as well as disc appearance.
05
FBC, CRP and ESR
Why
Support assessment for inflammation, infection, anaemia or thrombocytosis when giant cell arteritis or systemic disease is suspected.
Interpretation and limitations
Raised inflammatory markers support but do not establish giant cell arteritis, and normal values do not safely exclude a compelling ischaemic clinical presentation.
06
Pregnancy, blood pressure and urine protein assessment
Why
Detect pregnancy-specific risk and pre-eclampsia in a person with new severe headache.
Interpretation and limitations
Hypertension, proteinuria, abnormal liver or platelet results, visual symptoms or seizure needs immediate obstetric assessment; normal blood pressure does not exclude venous thrombosis.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Migraine

Recurrent episodic headache with nausea, light or sound sensitivity and a stable pattern favours migraine, but a changed phenotype or focal deficit requires reassessment.

Tension-type headache

Bilateral mild-to-moderate pressure without vomiting or activity aggravation supports tension-type headache when examination and context show no secondary concern.

Cluster headache or another TAC

Strictly unilateral short attacks with ipsilateral autonomic signs and restlessness suggest a trigeminal autonomic cephalalgia rather than a diffuse secondary process.

Medication-overuse headache

Frequent headache with regular acute-medicine exposure supports overuse, but this diagnosis should not suppress investigation of a new red-flag feature.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First minutesTriage the dangerous phenotypeFirst stepA person presents with a new, severe or substantially changed headache.

1Stabilise ABCDE, check glucose, temperature and blood pressure, establish exact onset-to-peak time and identify seizure, focal deficit, meningism, visual threat or impaired consciousness.
2Activate the relevant emergency pathway for thunderclap headache, sepsis, pregnancy-related hypertension, acute eye disease, carbon monoxide exposure or intracranial pressure signs.
3Obtain focused exposure, medicine and risk history while arranging the correct immediate imaging or specialist examination, avoiding routine primary-headache treatment as a diagnostic trial.
4Reassess symptoms and neurology after initial analgesia because improvement does not exclude haemorrhage, dissection, infection or raised pressure.

02ThunderclapFollow the subarachnoid haemorrhage sequenceHeadache reached maximum intensity within minutes and no benign explanation is secure.

1Arrange immediate non-contrast CT head and document onset time, scan time and whether the report was issued by a radiologist.
2If CT shows subarachnoid haemorrhage, seek urgent neurosurgical or neurovascular advice and proceed to vascular imaging within the local network.
3AlternativeIf CT within 6 hours is negative, do not routinely offer lumbar puncture under NICE guidance; obtain specialist advice and investigate plausible alternative vascular causes.
4If a scan performed more than 6 hours after onset is negative, consider lumbar puncture at least 12 hours after onset, following local bilirubin and safety procedures.

03Progressive headacheMatch the test to the mechanismSymptoms evolve over days or weeks, or context suggests pressure, inflammation, cancer or thrombosis.

1Examine discs, vision, cognition and focal neurology, and review cancer, immune, pregnancy, thrombosis, trauma and systemic inflammatory risk.
2Select contrast MRI, venography, arterial imaging, ophthalmology, inflammatory tests or infection studies according to the leading mechanism rather than ordering an unqualified scan.
3DefinitiveTreat time-critical suspected giant cell arteritis or infection before definitive confirmation when delay would threaten sight or life, while collecting useful samples promptly.
4Safety-net with explicit return triggers and ensure every abnormality, pending report and referral has named ownership and a defined timescale.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Reduces risk of further cranial ischaemia while rapid diagnostic confirmation and specialist assessment are arranged.

Prednisolone for suspected giant cell arteritis

Start an urgent high-dose regimen, commonly 40–60 mg orally daily, under the current local giant-cell-arteritis pathway.

Do not delay treatment for blood tests or imaging when suspicion is strong; visual symptoms require same-day ophthalmic or rheumatology advice and may need intravenous therapy.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Missed time-critical disease

Failure to recognise haemorrhage, infection, arteritis, venous thrombosis or mass effect can lead to stroke, blindness, herniation or death.

Unsafe lumbar puncture

Puncture in the presence of mass effect, severe instability or bleeding risk can precipitate neurological deterioration or serious haemorrhagic complications.

Incidental-imaging harm

Indiscriminate scanning of secure primary headache can reveal unrelated abnormalities, generating anxiety, invasive follow-up and diagnostic distraction.

Persistent pain and disability

Delayed diagnosis or poorly explained uncertainty can drive medication overuse, sleep loss, work absence and repeated emergency attendance.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Repeat neurological observations, consciousness, pupils and headache trajectory in any patient retained for acute investigation; document change rather than a single normal examination.
Track visual acuity, fields and disc findings when raised pressure, giant cell arteritis or ocular pathology is possible, escalating any deterioration immediately.
Record onset, CT and lumbar-puncture times accurately because interpretation of suspected subarachnoid haemorrhage depends on chronology.
Review outstanding imaging, cerebrospinal-fluid cultures and inflammatory results through a reliable handover system, not solely through patient-initiated follow-up.
After an emergency cause is excluded, revisit phenotype and analgesic use so that a primary headache is treated deliberately rather than by repeated unscheduled attendance.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Peak time beats adjectives

Patients use 'sudden' variably. Asking how many seconds or minutes elapsed before maximal pain is more discriminating for a thunderclap mechanism.

The test follows the theory

Unenhanced CT, venography, angiography and pituitary MRI answer different questions; a normal study cannot exclude a disease it was not designed to show.

Papilloedema changes sequencing

Suspected raised intracranial pressure generally requires urgent imaging before lumbar puncture, followed by a properly measured opening pressure only when the procedure is safe.

Relief is not exclusion

Secondary headaches may improve with analgesia or antiemetics. Response to treatment should never replace assessment of onset, context and objective neurological signs.

A previous label can anchor

Someone with migraine can still develop haemorrhage, meningitis or venous thrombosis; the useful question is whether this episode matches the established pattern exactly.

11Common pitfallsFrequent interpretation and management errors.

01
Writing 'no red flags' without documenting onset to peak, systemic context, fundoscopy or the key neurological findings that justify that conclusion.
02
Performing lumbar puncture reflexively after every negative early CT rather than applying the NICE subarachnoid-haemorrhage timing pathway.
03
Allowing CT or lumbar puncture to delay time-critical antibiotics, antivirals or corticosteroids when the clinical emergency already requires treatment.
04
Requesting routine brain imaging for a secure primary-headache phenotype solely to reassure, without discussing incidental findings and downstream harm.
05
Treating normal inflammatory markers as definitive exclusion of giant cell arteritis when cranial ischaemic symptoms are compelling.
06
Assuming papilloedema is absent after an unskilled or technically limited examination instead of arranging urgent competent assessment.