Trigeminal autonomic cephalalgias

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

TACs reflect activation of trigeminal pain pathways and cranial parasympathetic outflow, producing unilateral orbital, supraorbital or temporal pain with a red watering eye, rhinorrhoea, nasal blockage, eyelid oedema, facial sweating, ear fullness, miosis or ptosis. The autonomic sign must be interpreted with attack timing: unilateral tearing can accompany migraine, and persistent eye redness can be ocular disease. Record exact untreated duration with a stopwatch where possible, daily frequency, pain-free intervals, background pain, triggers and restlessness. Examine pupils, ocular movements, acuity, fields and cranial nerves during and between attacks. A fixed deficit or autonomic sign outside attacks weakens a straightforward primary diagnosis.

The syndromes occupy different temporal scales. Cluster headache attacks last 15–180 minutes and occur from every other day to eight times daily in bouts. Paroxysmal hemicrania lasts 2–30 minutes, often more than five times daily, and remits completely with therapeutic indometacin. SUNCT and SUNA attacks are brief unilateral neuralgiform pains lasting 1–600 seconds and occurring at least daily during active periods; attacks may be single stabs, series or saw-tooth patterns. SUNCT specifies both conjunctival injection and lacrimation, while SUNA does not meet that combination. Hemicrania continua produces persistent side-locked pain beyond 3 months with exacerbations, autonomic symptoms or agitation, and an absolute indometacin response. These criteria prevent 'cluster variant' from becoming a catch-all.

Specialist confirmation matters because treatment and secondary mimics differ. MRI brain with attention to the pituitary and posterior fossa, and vascular or orbital imaging when indicated, may reveal a lesion capable of reproducing the syndrome. Paroxysmal hemicrania and hemicrania continua require a supervised adequate indometacin trial; rapid complete response supports diagnosis, while partial relief at an inadequate dose does not. Gastroprotection and renal, gastrointestinal and cardiovascular risk must be managed. SUNCT or SUNA is difficult to treat acutely because attacks are so short; lamotrigine is a commonly used specialist preventive, titrated slowly because of rash risk, with intravenous lidocaine reserved for selected severe transitional care in monitored specialist settings. Cluster-specific oxygen, triptans and verapamil should not be automatically transferred to every TAC.

Key points

Trigeminal autonomic cephalalgias combine strictly unilateral trigeminal-distribution pain with ipsilateral cranial autonomic activation or attack-related restlessness.
Duration and frequency are the quickest discriminator: cluster lasts 15–180 minutes, paroxysmal hemicrania 2–30 minutes, and SUNCT or SUNA usually seconds to minutes.
Paroxysmal hemicrania usually occurs more than five times daily and responds absolutely to adequate indometacin, making a supervised trial diagnostically important.
SUNCT requires both ipsilateral conjunctival injection and tearing; SUNA has only one or neither of those two signs, although other cranial autonomic features occur.
Hemicrania continua is continuous unilateral headache for over 3 months with exacerbations and an absolute response to indometacin, rather than a series of pain-free attacks.
Short-lasting attacks can be triggered by touch or chewing and resemble trigeminal neuralgia, but prominent autonomic signs, longer refractory behaviour and attack pattern help distinction.
Obtain headache-neurology input and specialist-directed MRI for a new TAC phenotype because pituitary, posterior-fossa, orbital and vascular lesions can imitate a primary syndrome.
Do not group all TACs under cluster treatment: oxygen and sumatriptan, indometacin and lamotrigine belong to different syndrome-specific pathways.
An indometacin test needs gastrointestinal, renal, cardiovascular and interaction assessment plus gastroprotection; casual low-dose exposure cannot exclude an indometacin-responsive headache.

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

Primary trigeminal autonomic disease

Cluster headache, paroxysmal hemicrania, SUNCT, SUNA and hemicrania continua are primary disorders of cranial pain and autonomic networks.

Hypothalamic and circadian susceptibility

Disordered central timing is especially relevant to cluster headache and helps explain predictable daily attacks and bouts.

Secondary structural mimic

Pituitary, posterior-fossa, orbital and vascular lesions can generate a TAC-like phenotype, particularly at new or atypical presentation.

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

1
Trigeminal afferent activation
First-division trigeminal pain pathways generate severe strictly unilateral orbital, temporal or facial pain during each attack.
2
Cranial parasympathetic reflex
Trigeminal input activates parasympathetic outflow, producing tearing, conjunctival injection, nasal symptoms and eyelid change on the pain side.
3
Central pattern generation
Hypothalamic and brainstem networks determine distinctive attack duration, frequency, continuous background and restlessness across TAC subtypes.
4
Syndrome-specific modulation
Marked indometacin responsiveness in selected TACs reflects a distinct biological treatment response that also assists specialist classification.

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

Paroxysmal hemicrania

Strictly unilateral 2–30-minute attacks occurring many times daily with autonomic signs and complete indometacin response define the characteristic pattern.

SUNCT phenotype

Unilateral neuralgiform attacks lasting seconds to minutes with both conjunctival injection and tearing suggest short-lasting unilateral neuralgiform headache with conjunctival injection and tearing.

SUNA phenotype

Very brief unilateral neuralgiform attacks with cranial autonomic activation but without the required combination of both red eye and tearing fit SUNA after mimics are excluded.

Hemicrania continua

Continuous side-locked headache for more than 3 months with superimposed exacerbations and an absolute indometacin response is distinct from recurrent pain-free attacks.

Trigeminal neuralgia overlap

Stimulus-triggered electric-shock pain lasting fractions of a second to 2 minutes suggests trigeminal neuralgia, although short TACs can also be triggered and need expert separation.

Secondary TAC clueRed flag

Abnormal ocular movements, field loss, endocrine symptoms, persistent Horner syndrome, bilateral or changing signs, late atypical onset or incomplete syndrome raises concern for structural disease.

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
High-resolution attack diaryFirst step
Why
Capture untreated duration in seconds or minutes, attack number, continuous background pain, triggers and exact autonomic signs.
Interpretation and limitations
Temporal scale separates cluster, paroxysmal hemicrania and SUNCT or SUNA; continuous baseline pain redirects assessment towards hemicrania continua.
02
Cranial nerve and ophthalmic examination
Why
Document whether autonomic findings are transient and detect orbital, cavernous-sinus or brainstem abnormality.
Interpretation and limitations
Fixed pupil asymmetry, ophthalmoplegia, reduced acuity, field loss or sensory deficit should prompt urgent targeted imaging and specialist assessment.
03
MRI brain with pituitary-focused views
Why
Exclude structural causes that can reproduce a trigeminal-autonomic presentation in a new or atypical case.
Interpretation and limitations
Interpret small pituitary findings in endocrine and phenotypic context; add vascular or orbital sequences when the history points beyond the sellar region.
04
Supervised indometacin trial
Why
Test the defining treatment response of paroxysmal hemicrania or hemicrania continua using an adequate specialist regimen.
Interpretation and limitations
Complete response at therapeutic exposure supports the diagnosis; partial response, early discontinuation or low dosing is not a definitive negative test.
05
Renal, blood-pressure and gastrointestinal risk assessment
Why
Determine whether an indometacin trial can be undertaken safely and what monitoring or protection is required.
Interpretation and limitations
Renal impairment, ulceration, anticoagulation, heart failure or high cardiovascular risk may require an alternative diagnostic strategy and specialist advice.

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

Migraine

Longer attacks with nausea, sensory sensitivity and preference for stillness favour migraine, though cranial autonomic symptoms can occur.

Trigeminal neuralgia

Electric shocks triggered by touch or chewing with a refractory interval favour neuralgia; prominent autonomic signs and longer attacks support a TAC.

Orbital or sinus disease

Persistent eye signs, fever, proptosis or local structural abnormality indicates ocular, orbital or sinus pathology rather than a primary TAC.

Vascular or pituitary lesion

New headache with neurological, endocrine or visual-field findings requires specialist imaging for dissection, aneurysm or sellar disease.

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

01ClassificationLet time structure the differentialFirst stepSevere side-locked orbital or temporal pain occurs with cranial autonomic symptoms.

1Record untreated duration precisely, daily frequency, background pain, bout-remission pattern, triggers, restlessness and which autonomic signs occur on the pain side.
2Map minutes-to-hours attacks towards cluster, 2–30-minute high-frequency attacks towards paroxysmal hemicrania, seconds-to-minutes attacks towards SUNCT or SUNA, and continuous pain towards hemicrania continua.
3Examine eye, pupils and cranial nerves between attacks and screen for vascular, pituitary, orbital and posterior-fossa warning features.
4Refer for headache-neurology confirmation and appropriate imaging before committing to prolonged syndrome-specific therapy.

02Indometacin phenotypeConfirm an indometacin-responsive syndromeParoxysmal hemicrania or hemicrania continua is strongly suspected.

1Review ulcer, renal, cardiovascular, anticoagulant, pregnancy and NSAID-sensitivity risks and obtain baseline measures under the specialist protocol.
2Provide gastroprotection and undertake an adequate supervised oral or parenteral indometacin test with contemporaneous attack recording.
3AlternativeTreat complete response as part of the diagnostic criterion, while reconsidering dose, adherence and alternative diagnosis after an incomplete result.
4If confirmed, find the lowest effective maintenance exposure and monitor NSAID toxicity, seeking alternatives when harm outweighs benefit.

03Very short attacksManage SUNCT or SUNA through specialist careFrequent seconds-to-minutes neuralgiform attacks with ipsilateral autonomic activation are established.

1Distinguish from trigeminal neuralgia using autonomic profile, refractory behaviour, distribution and expert review, while completing MRI assessment for secondary causes.
2Discuss lamotrigine or another specialist preventive, introducing it slowly and providing clear rash and systemic-hypersensitivity advice.
3For a severe sustained attack burden, consider monitored transitional therapy such as intravenous lidocaine only in an experienced inpatient setting.
4Use diary frequency and disability to guide titration, avoiding ineffective cluster or ordinary analgesic regimens simply because all TACs are unilateral.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

An absolute response is diagnostically defining and therapeutically effective for paroxysmal hemicrania and hemicrania continua.

Indometacin diagnostic and preventive trial

Use a headache-specialist titration to an adequate therapeutic exposure, then reduce to the lowest dose that maintains complete control if diagnosis is confirmed.

High gastrointestinal, renal, cardiovascular and bleeding toxicity requires risk assessment, gastroprotection and monitoring; avoid casual unsupervised trials or combination with other NSAIDs.

A commonly preferred preventive for SUNCT or SUNA when the diagnosis and structural assessment are established.

Lamotrigine

Start at the specialist low dose and titrate slowly over weeks using the current BNF schedule and interaction-specific adjustments.

Stop and seek urgent assessment for rash or systemic hypersensitivity; valproate greatly changes titration, and abrupt escalation increases severe cutaneous-reaction risk.

Can provide transitional suppression of very frequent SUNCT or SUNA attacks while a slower preventive is introduced.

Intravenous lidocaine

Use only a specialist weight-based monitored infusion protocol in hospital for selected severe short-lasting neuralgiform attack states.

Requires continuous cardiac and neurological monitoring because arrhythmia, hypotension, seizures and systemic toxicity can occur; it is not community rescue treatment.

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

Severe distress and mood deterioration

Frequent excruciating attacks can cause panic, depressed mood and profound distress, especially when diagnosis and effective rescue are delayed.

Sleep and occupational disruption

Repeated daily or nocturnal attacks impair sleep, concentration, driving and ability to work during active bouts.

Misclassification and ineffective treatment

Grouping all TACs as cluster headache exposes patients to unsuitable treatment while withholding therapy appropriate for the correct subtype.

Medicine and procedure harm

Indometacin, triptans, preventives and invasive procedures carry gastrointestinal, renal, cardiovascular, conduction and neurological risks during treatment.

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

Count attacks using a fine-resolution diary that distinguishes seconds, minutes and continuous background pain; coarse daily headache counts lose the diagnostic signal.
During indometacin treatment monitor gastrointestinal symptoms, blood pressure, renal function, oedema and bleeding risk at intervals matched to age and comorbidity.
During lamotrigine titration review rash, fever, mucosal symptoms, lymphadenopathy, mood and adherence, acting urgently on possible hypersensitivity.
Repeat ocular and neurological assessment if autonomic signs persist between attacks or new sensory, visual, endocrine or cranial-nerve features appear.
Measure disability, sleep interruption and mental-health burden as well as attack number, because hundreds of brief attacks can be profoundly disabling.

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

Chronometry is a test

Untreated attack duration functions almost like a bedside investigation: seconds, tens of minutes, hours and continuous pain lead to different TAC diagnoses.

Indometacin response is binary

The classical syndromes require complete prevention at adequate exposure. Merely feeling somewhat better after an NSAID is not the defining response.

Autonomic does not mean sinus

Nasal blockage, discharge and eye watering during unilateral pain reflect cranial autonomic activation and commonly lead to unnecessary antibiotics or sinus procedures.

Triggers do not settle identity

Touch can provoke both SUNCT or SUNA and trigeminal neuralgia, so duration, autonomic combination, refractory period and imaging remain important.

Secondary can look perfect

Pituitary or posterior-fossa lesions may produce convincing TAC phenotypes; new presentations deserve specialist structural assessment even when criteria appear tidy.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every unilateral headache with tearing cluster headache without measuring attack duration, frequency and continuous background pain.
02
Diagnosing paroxysmal hemicrania after partial benefit from a small over-the-counter NSAID dose rather than an adequate supervised indometacin trial.
03
Prescribing indometacin without checking renal, gastrointestinal, cardiovascular, anticoagulant and pregnancy risk or arranging gastroprotection.
04
Treating SUNCT or SUNA with repeated ordinary analgesics that cannot act within a seconds-long attack and may create medication overuse.
05
Escalating lamotrigine rapidly or ignoring a rash, particularly when an interacting drug has altered the safe titration schedule.
06
Omitting imaging and interval neurological examination because the attack satisfies a primary TAC checklist.