Nervous System & Special Senses

Cluster headache: acute and preventive management

Clinical Overview and When to Suspect Cluster Headache

— Episodic CH (ECH) ~85%: bouts ("clusters") of weeks–months separated by remissions ≥3 months.

— Chronic CH (CCH) ~15%: attacks recurring >1 year without remission or with remissions <3 months.

Board pearl: Pain that is strictly unilateral, side-locked, with ipsilateral autonomic features AND motor restlessness in a middle-aged smoker is cluster headache until proven otherwise — order an MRI brain with pituitary views on the first work-up to exclude secondary causes (pituitary lesions, cavernous sinus pathology, vertebral dissection).

Definition: Cluster headache (CH) is a primary trigeminal autonomic cephalalgia (TAC) defined by attacks of severe, strictly unilateral periorbital or temporal pain lasting 15–180 minutes, occurring 1–8 times daily, with ipsilateral cranial autonomic features and/or a sense of restlessness/agitation.

Epidemiology: Prevalence ~0.1%. Male:female ~3:1 (narrowing in recent cohorts). Onset typically 20s–40s. Strong association with tobacco use (~65–80% smokers or former smokers).

Pathophysiology: Activation of the trigeminovascular system and ipsilateral parasympathetic outflow via the superior salivatory nucleus → cranial autonomic signs. Hypothalamic (posterior/inferior) involvement explains circadian and circannual rhythmicity — attacks often strike at the same hour nightly, frequently 1–2 hours after sleep onset (REM-related).

Two clinical forms:

When to suspect on Step 3: Middle-aged man, awakens from sleep with excruciating retro-orbital pain, paces/rocks (vs. migraine patient who lies still), with lacrimation, ptosis, miosis, rhinorrhea, conjunctival injection on the painful side. Often describes pain as "hot poker in the eye" or "10/10, worst of life."

Common triggers during a bout: alcohol (highly specific), nitroglycerin, histamine, strong odors, altitude, naps.

Presentation Patterns and Key History

— Location: orbital, supraorbital, or temporal — always unilateral and side-locked within a bout; ~15% switch sides between bouts.

— Quality: boring, stabbing, "ice pick," "hot poker"; intensity peaks within 5–10 minutes.

— Duration: untreated 15–180 minutes (avg 45–90 min).

— Frequency: 1 every other day up to 8/day during a bout.

— Circadian: attacks at near-identical clock times, classically nocturnal awakening 1–2 hrs after sleep onset.

— Circannual: bouts often recur in spring and fall, with seasonal change in photoperiod.

— Bouts last 6–12 weeks in ECH, followed by months–years of remission.

— Conjunctival injection, lacrimation

— Nasal congestion, rhinorrhea

— Eyelid edema

— Forehead/facial sweating or flushing

— Partial Horner (ptosis, miosis) — may persist between attacks in chronic disease

— Sense of restlessness or agitation (alternative to autonomic features)

— Alcohol within 30–60 min (avoid entirely during bout)

— Nitroglycerin, sildenafil

— Histamine, strong perfumes, solvents

— Naps, high altitude

— Late onset (>50), persistent neuro deficit, papilledema, side-shift within attack, fever, thunderclap pattern, "first or worst."

Key distinction: Migraine = unilateral or bilateral, 4–72 hours, photo/phonophobia, wants quiet/dark, lies still. Cluster = strictly unilateral, 15–180 min, autonomic features, restless and pacing. Trigeminal neuralgia = brief electric shocks (seconds) triggered by cutaneous stimuli, no autonomic features. Paroxysmal hemicrania = shorter (2–30 min), more frequent (>5/day), absolutely indomethacin-responsive.

Attack character:

Temporal signature (high-yield):

Associated autonomic features (ipsilateral, ≥1 required by ICHD-3):

Behavioral signature: Patient paces, rocks, bangs head, may self-harm. Migraine patients prefer dark, still room — opposite behavior.

Triggers during a bout (not between bouts):

Red flags warranting urgent imaging:

Physical Exam Findings and Bedside Assessment

— Agitated, pacing, rocking, may strike head against wall — pathognomonic restlessness.

— Tachycardia, transient hypertension from sympathetic surge; bradycardia can occur with severe vagal response.

— Conjunctival injection and lacrimation.

— Ptosis and miosis (partial Horner syndrome) — postganglionic sympathetic dysfunction; may become permanent in chronic CH.

— Nasal congestion, rhinorrhea, eyelid edema, forehead sweating.

— Facial flushing or pallor; periorbital tenderness.

— Should be otherwise normal. Cranial nerves II–XII intact, no motor/sensory deficits, no papilledema.

— Any focal deficit, papilledema, fever, neck stiffness, or asymmetric pupils beyond Horner pattern → secondary headache work-up.

— Check anisocoria in light vs dark to confirm Horner (smaller pupil fails to dilate in dark).

— Fundoscopy to exclude papilledema (IIH, mass).

— Palpate temporal arteries in patients ≥50 to exclude GCA.

— Auscultate carotids; check for carotid tenderness suggesting dissection (especially with neck pain, recent trauma, or unilateral Horner with pain).

— Document BP, HR, SpO₂ — relevant for triptan/oxygen safety.

— Cardiovascular history is essential before prescribing triptans (CAD, uncontrolled HTN, prior MI/stroke are contraindications).

— Tobacco use in >70%; document pack-years.

— Cocaine and methamphetamine can mimic or trigger CH-like attacks.

Step 3 management: Before giving a triptan or high-flow oxygen for a first presumed cluster attack, screen for contraindications at the bedside: ask about chest pain, prior MI, stroke, uncontrolled HTN, pregnancy, and ergot use within 24 hours. Document a baseline neuro exam — any focal deficit mandates non-contrast head CT followed by MRI/MRA before empiric abortive therapy.

General appearance during an attack:

Cranial/facial exam (ipsilateral to pain):

Neurologic exam (between and during attacks):

Targeted bedside maneuvers:

Vital signs and systemic check:

Smoking and substance history:

Diagnostic Workup — Initial Evaluation and Imaging

— MRI brain with and without contrast, including pituitary and cavernous sinus views and MRA of head/neck.

— Up to 3–5% of "cluster-like" headaches harbor a structural lesion: pituitary adenoma, meningioma, AVM, cavernous sinus pathology, carotid/vertebral dissection, Chiari I.

— Order MRA if any Horner syndrome with neck pain → exclude carotid dissection (medical emergency).

— ESR/CRP if age ≥50 or temporal tenderness → giant cell arteritis.

— TSH, prolactin, IGF-1, cortisol, LH/FSH if pituitary enlargement on MRI or features of endocrinopathy.

— Toxicology screen if substance-induced suspected.

— Pregnancy test in women of childbearing age (alters drug choices).

— ECG before triptans/verapamil — verapamil prolongs PR; baseline PR and QRS critical.

— BP and cardiovascular risk profile — relevant for triptans and ergots.

— Pulse oximetry baseline if planning home O₂ therapy.

— Screen for obstructive sleep apnea — comorbid in 30–80% of CH patients; consider polysomnography especially if nocturnal attacks dominate or BMI/snoring suggest OSA.

Board pearl: The single most-tested first-line investigation for a new diagnosis of cluster headache is MRI brain with pituitary and cavernous sinus protocols, not CT. CT misses pituitary microadenomas and posterior fossa lesions that mimic CH. Order MRI even when the clinical picture is "classic" — secondary mimics are too consequential to skip.

Diagnosis is clinical (ICHD-3 criteria): ≥5 attacks of severe unilateral orbital/supraorbital/temporal pain lasting 15–180 min, with ≥1 ipsilateral autonomic feature OR restlessness, frequency 1 every other day to 8/day, not better explained by another disorder.

Mandatory imaging on first presentation:

Laboratory testing — none routinely diagnostic, but tailored:

Other initial assessments:

Sleep history:

Diagnostic Workup — Advanced and Confirmatory Studies

— MRA or CTA head and neck: dissection, aneurysm (especially posterior communicating artery — can present with ipsilateral painful third nerve palsy mimicking CH), AVM.

— MRV if features of intracranial hypertension or sinus thrombosis (papilledema, postural pain).

— Dedicated pituitary MRI with dynamic contrast: prolactinoma, GH-secreting adenomas often present with cluster-like pain.

— Paroxysmal hemicrania and hemicrania continua respond completely to indomethacin 25–75 mg TID within 1–2 days.

— True cluster headache does not consistently respond — this is a diagnostic discriminator.

— Always co-prescribe PPI and warn about GI/renal effects.

— Morning cortisol, ACTH, prolactin, IGF-1, TSH/free T4, LH/FSH, testosterone/estradiol.

— Not routine. Indicated only when secondary causes (meningitis, SAH with normal imaging, IIH) are suspected.

— Patient-recorded log of attack timing, duration, triggers, response to abortives — critical for monitoring and titrating preventives.

Key distinction: Paroxysmal hemicrania is the great mimic: similar location, autonomic features, but attacks are shorter (2–30 min), more frequent (>5/day), and absolutely responsive to indomethacin. If a presumed cluster patient responds completely to indomethacin, revise the diagnosis — the chronic treatment paradigm changes entirely.

When the picture is atypical (side-shift within attack, age >50 at onset, persistent neuro deficit, indomethacin-responsive features), pursue:

Indomethacin trial to distinguish from indomethacin-responsive TACs:

Polysomnography: consider if nocturnal predominance, witnessed apneas, daytime somnolence, or refractory disease. Treating coexistent OSA can reduce attack burden.

Endocrine workup (if pituitary lesion or suspicion):

Autonomic testing is rarely needed clinically; pharmacologic pupil testing (cocaine, hydroxyamphetamine) can localize Horner if etiology unclear.

Lumbar puncture:

Headache diary:

Management Logic and Treatment Framework

— Abortive (acute) therapy for each attack

— Transitional (bridging) therapy to suppress attacks while preventives are titrated

— Preventive therapy taken throughout the bout (ECH) or chronically (CCH)

— Start all three simultaneously at first presentation during a bout — do not wait.

— Educate on strict alcohol abstinence during a bout, smoking cessation, sleep hygiene.

— Avoid nitrates/sildenafil during bouts if possible.

— First-line: high-flow 100% oxygen 12–15 L/min via non-rebreather × 15–20 min, sitting forward.

— First-line: subcutaneous sumatriptan 6 mg (max 2 doses/24 h) OR intranasal zolmitriptan 5–10 mg / sumatriptan 20 mg.

— Second-line: intranasal lidocaine 4–10%, intranasal/SC dihydroergotamine.

— Avoid oral triptans (onset too slow for attack duration).

— Prednisone 60–100 mg/day × 5 days, taper over 2–3 weeks, OR

— Occipital nerve block (greater occipital, ipsilateral): methylprednisolone + lidocaine — Level A evidence, lasts 2–4 weeks.

— First-line: verapamil 240–960 mg/day, titrated with serial ECGs.

— Alternatives: lithium, topiramate, galcanezumab (FDA-approved for ECH), melatonin 10 mg qHS.

Step 3 management: When a known cluster patient calls during a new bout, initiate all three tiers at the same visit: prescribe SC sumatriptan + home O₂ (abortive), start prednisone taper or do occipital block (transitional), and begin verapamil titration with baseline ECG (preventive). Do not stage these sequentially — bouts are too disabling.

Three-pronged approach to cluster headache:

General principles:

Abortive therapy hierarchy (must work within 15 min — oral routes too slow):

Transitional therapy (rapid suppression while verapamil titrates):

Preventive therapy:

Refractory disease: neuromodulation (sphenopalatine ganglion stimulation, occipital nerve stimulation, vagus nerve stimulator — gammaCore is FDA-cleared).

Pharmacotherapy — Abortive and Acute Therapy in Depth

— 100% O₂ at 12–15 L/min via non-rebreather mask × 15–20 min, seated leaning forward.

— Aborts ~70% of attacks within 15 min. No systemic side effects, repeatable.

— Arrange home O₂ through DME provider; document medical necessity (insurance often denies — appeal with diagnosis code G44.0).

— Caution in severe COPD (theoretical hypercapnia, but short duration usually safe).

— Onset 10–15 min; relief in ~75% by 15 min.

— Max 2 injections/24 h, separated by ≥1 hour.

— Contraindications: ischemic heart disease, prior MI/stroke, uncontrolled HTN, peripheral vascular disease, hemiplegic/basilar migraine, pregnancy, ergot use within 24 h, MAOI within 2 weeks.

— Zolmitriptan 5–10 mg IN or sumatriptan 20 mg IN — slower than SC but useful when SC not tolerated.

— IN 2 mg, SC/IM 1 mg, or IV 0.5–1 mg q8h (inpatient bridge for refractory bouts).

— Cannot combine with triptans within 24 h.

— Contraindicated in CAD, PVD, uncontrolled HTN, pregnancy, sepsis, hepatic/renal failure, recent ergot use.

Board pearl: In a cluster patient with CAD or uncontrolled HTN, the first-line abortive becomes high-flow oxygen (no vasoactive effect); add octreotide 100 mcg SC or intranasal lidocaine as backup. Never give SC sumatriptan or DHE in this setting — vignettes testing this routinely include a 55-year-old smoker with prior MI.

High-flow oxygen (Level A):

Subcutaneous sumatriptan 6 mg (Level A):

Intranasal triptans:

Avoid oral triptans — onset 30–60 min exceeds typical attack duration.

Intranasal lidocaine 4–10% 1 mL into ipsilateral nostril, head tilted back and toward affected side — modest efficacy, useful adjunct.

Dihydroergotamine (DHE):

Octreotide 100 mcg SC: alternative when triptans contraindicated (e.g., CAD).

Avoid opioids — ineffective, promote medication-overuse headache and tolerance; this is a quality measure.

Noninvasive vagal nerve stimulation (gammaCore): FDA-cleared for acute episodic CH; useful when pharmacotherapy contraindicated.

Pharmacotherapy — Preventive, Transitional, and Neuromodulation

— Start 80 mg TID; increase by 80 mg every 10–14 days; usual effective dose 240–480 mg/day, may reach 960 mg/day in refractory cases.

— ECG before each dose escalation above 240 mg: monitor for PR prolongation (>0.22 s), heart block, bradycardia (<50).

— Side effects: constipation, peripheral edema, gingival hyperplasia, bradycardia. Avoid in heart block, severe LV dysfunction.

— Target level 0.6–0.8 mEq/L; monitor TSH, creatinine, and lithium level every 3–6 months.

— Narrow therapeutic window; avoid with NSAIDs, ACEi, thiazides.

— Oral prednisone 60–100 mg/day × 5 days, then taper by 10 mg every 2–3 days. Limit cumulative steroid exposure; avoid recurrent courses.

— Greater occipital nerve block (ipsilateral): triamcinolone or methylprednisolone with lidocaine — Level A; preferred over repeated oral steroids.

— IV methylprednisolone or DHE protocol for inpatient refractory bouts.

— Sphenopalatine ganglion stimulator (Pulsante)

— Occipital nerve stimulation

— Noninvasive vagal nerve stimulation (gammaCore) — both acute and preventive use.

— Hypothalamic deep brain stimulation — last resort.

Step 3 management: Before titrating verapamil >240 mg/day, obtain a baseline ECG, then repeat ECG with each 80 mg increment and again 10 days after stable dose. Dose-related AV block can be silent — many board questions hinge on recognizing PR prolongation as the reason to stop up-titration.

Verapamil — first-line preventive (Level A):

Lithium 600–900 mg/day (especially CCH):

Topiramate 50–200 mg/day: useful adjunct; watch for paresthesias, cognitive slowing, nephrolithiasis, teratogenicity (cleft palate).

Galcanezumab 300 mg SC monthly: anti-CGRP mAb, FDA-approved for episodic CH only (not chronic). First dose loading injection.

Melatonin 10 mg qHS — adjunct, especially for nocturnal attacks; very safe.

Civamide, valproate, gabapentin, baclofen: third-line options.

Transitional therapy (bridge while verapamil titrates over 2–3 weeks):

Neuromodulation / surgical for refractory CCH:

Special Populations — Elderly, Renal, and Hepatic Impairment

— New-onset CH after age 50 is uncommon — actively investigate secondary causes: GCA (check ESR/CRP), pituitary tumor, cervical artery dissection, intracranial mass.

— Higher prevalence of CAD/HTN — many become triptan-ineligible. Default acute therapy: high-flow oxygen ± octreotide ± intranasal lidocaine.

— Verapamil: start lower (40–80 mg TID), titrate slowly; watch for AV block, constipation, falls from bradycardia.

— Lithium: reduce dose 25–50%; renal clearance declines with age; check creatinine and TSH q3 months.

— Steroid bridges: monitor glucose (steroid-induced hyperglycemia), BP, mood; consider bone protection if recurrent courses.

— Lithium: avoid if CrCl <30; dose-adjust and monitor levels closely if 30–60. Hold during dehydration or NSAID use.

— Topiramate: reduce dose 50% if CrCl <70; risk of metabolic acidosis and nephrolithiasis.

— Triptans: sumatriptan SC generally safe in mild–moderate CKD; avoid in severe.

— Gabapentin: dose by CrCl.

— Verapamil: hepatic metabolism — no renal adjustment, but caution if comorbid HF.

— Verapamil: reduce dose 50–70% in cirrhosis; monitor closely.

— Triptans: contraindicated in severe hepatic impairment.

— Valproate, topiramate: hepatotoxicity risk — check LFTs at baseline and periodically.

— DHE: contraindicated in significant hepatic impairment.

— Verapamil + simvastatin → rhabdomyolysis risk (limit simva to 10 mg).

— Verapamil + digoxin → digoxin level ↑.

— Lithium + ACEi/ARB/thiazide/NSAID → lithium toxicity.

— Triptans + SSRIs/SNRIs → serotonin syndrome (low absolute risk; counsel but don't withhold).

Board pearl: A 65-year-old with new "cluster-like" headaches and a transient Horner syndrome with neck pain requires urgent CTA or MRA of the neck to exclude carotid artery dissection — do not treat as primary cluster headache until vascular imaging is clear.

Elderly patients (≥60):

Renal impairment:

Hepatic impairment:

Polypharmacy considerations:

Special Populations — Pregnancy, Lactation, and Pediatrics

— Cluster headache often improves during pregnancy, but bouts can occur or persist.

— Avoid: triptans (generally avoided; sumatriptan has most data and is preferred only if necessary), ergots and DHE (absolute contraindication — uterotonic, vasoconstrictive), valproate (NTDs), topiramate (cleft palate, low birth weight), lithium (Ebstein anomaly, esp. first trimester).

— First-line abortive: high-flow 100% oxygen — no fetal risk; preferred therapy in pregnancy.

— Intranasal lidocaine acceptable.

— Preventive: verapamil is the preferred preventive in pregnancy (Category C, but most experience). Prednisone short bursts can be used cautiously, especially after first trimester.

— Occipital nerve blocks with lidocaine ± low-dose steroid are safe and effective.

— Sumatriptan SC compatible (low milk transfer); pump-and-discard not routinely required but some advise 8–12 h interval.

— Verapamil compatible.

— Lithium generally avoided; ergots contraindicated (suppress lactation, ergot toxicity in infant).

— Rare but described. Diagnosis requires exclusion of secondary causes — MRI mandatory.

— Same abortive principles: oxygen first-line; SC sumatriptan if needed (off-label).

— Preventive: verapamil with cardiology input; topiramate, melatonin.

— Counsel on contraception before initiating topiramate (reduces OCP efficacy, teratogenic) or valproate.

— Discuss pregnancy planning; transition to oxygen-based abortive and verapamil-based prevention before conception.

Step 3 management: For a pregnant patient with active cluster bout, arrange home high-flow oxygen as primary abortive, perform an ipsilateral greater occipital nerve block as transitional therapy, and start verapamil with serial ECGs as preventive. Counsel against alcohol, document shared decision-making, and coordinate with obstetrics.

Pregnancy:

Lactation:

Pediatric and adolescent CH:

Women of reproductive age:

Complications and Adverse Outcomes

— Suicidality: CH carries the moniker "suicide headache" — lifetime suicidal ideation up to 55%, attempts ~2–25%. Screen every visit with PHQ-9 and direct questioning.

— Major depression and anxiety: prevalent comorbidities; treat aggressively.

— Sleep deprivation: nocturnal attacks cause chronic insomnia; screen for OSA.

— Loss of productivity, job loss, financial strain: document for disability paperwork.

— Substance use disorder: alcohol avoidance during bouts; opioid misuse from inappropriate prescribing.

— Verapamil: AV block, bradycardia, constipation, peripheral edema, gingival hyperplasia, heart failure exacerbation. Annual ECG while on chronic therapy.

— Lithium: tremor, hypothyroidism, nephrogenic DI, CKD with long-term use, toxicity (ataxia, confusion, seizures) with dehydration, NSAIDs, ACEi.

— Triptans/DHE: chest tightness, coronary vasospasm, MI (rare), serotonin syndrome with SSRIs.

— Steroids: hyperglycemia, hypertension, mood lability, osteoporosis, AVN of femoral head (cumulative risk — limit total exposure).

— Topiramate: paresthesias, cognitive slowing, weight loss, nephrolithiasis, metabolic acidosis, acute angle-closure glaucoma, oligohidrosis, teratogenicity.

— Galcanezumab: injection-site reactions, constipation, rare hypersensitivity.

— High-flow O₂: fire hazard at home (no smoking near tanks), nasal dryness.

— Overuse of triptans (≥10 days/month for ≥3 months) can transform headache pattern. Less common in pure CH than migraine, but possible with daily triptan use during bouts.

Board pearl: Suicide screening is mandatory in every cluster headache visit. A vignette describing a young man with refractory cluster headache and "hopeless" statements is signaling acute suicide risk assessment — answer is direct safety questioning and psychiatric referral, not just headache medication adjustment.

Disease-related complications:

Treatment-related adverse effects:

Medication overuse headache (MOH):

Permanent Horner syndrome in long-standing chronic CH.

When to Escalate — Inpatient, Consult, and ICU Triage

— Status clusteralgicus: continuous or near-continuous attacks unresponsive to standard abortive and transitional therapy.

— Suicidal ideation with plan or intent → psychiatric admission, 1:1 sitter, safety plan.

— First-presentation atypical features: focal neuro deficit, papilledema, fever, age >50, suspected dissection or SAH → ED evaluation with urgent imaging.

— Cardiac instability from verapamil: symptomatic bradycardia, second/third-degree AV block, syncope → cardiology, telemetry, possible pacemaker evaluation.

— Lithium toxicity: confusion, ataxia, tremor → ED, hold lithium, IV fluids, level, possible hemodialysis if level >4 or symptomatic >2.5.

— IV dihydroergotamine (Raskin protocol): 0.5–1 mg IV q8h × 3 days with antiemetic pretreatment (metoclopramide); telemetry; contraindicated with recent triptan, CAD, pregnancy.

— IV methylprednisolone 250–500 mg/day × 3 days.

— Continuous occipital nerve block or repeated regional blocks.

— Consider noninvasive vagal nerve stimulation as adjunct.

— Neurology / headache specialist: refractory, chronic, or diagnostic uncertainty.

— Cardiology: high-dose verapamil with conduction changes.

— Psychiatry: depression, suicidality, substance use.

— Pain medicine / interventional: SPG block or stimulator candidacy.

— Neurosurgery: deep brain stimulation candidates for medically refractory CCH.

— Document home oxygen prescription, abortive plan, preventive titration schedule, and follow-up date.

— Provide a written action plan with abortive instructions and ED criteria.

CCS pearl: For a patient admitted in status clusteralgicus, the order set is: continuous pulse ox and telemetry, IV access, antiemetic, IV DHE 0.5 mg test dose then 1 mg q8h × 72 h, ipsilateral greater occipital nerve block, initiate verapamil with baseline ECG, neurology consult, psychiatry consult for suicide risk, home O₂ setup before discharge.

Outpatient management is the norm for most cluster patients. Escalate when:

Inpatient bridging protocols for refractory bouts:

Consultations:

Care transitions:

Key Differentials — Other Trigeminal Autonomic Cephalalgias

— Unilateral orbital/temporal pain, autonomic features (like CH).

— Shorter attacks (2–30 min), more frequent (>5/day, often 10–30).

— Absolute response to indomethacin (25–75 mg TID) — diagnostic.

— Female predominance; chronic form more common.

— Continuous unilateral pain with superimposed exacerbations.

— Mild autonomic features; restlessness during exacerbations.

— Indomethacin-responsive — diagnostic.

— Very brief attacks (1–600 seconds), very frequent (3–200/day).

— Stab-like, often cutaneous triggers (like trigeminal neuralgia) but with autonomic features.

— Treatment: lamotrigine (first-line), topiramate, gabapentin; IV lidocaine for status.

— Mandatory MRI — high rate of posterior fossa or pituitary lesions.

— Brief (seconds) electric-shock pain in V2/V3 distribution.

— Triggered by cutaneous stimuli (chewing, brushing teeth, wind).

— No autonomic features (key distinction).

— First-line: carbamazepine; second-line oxcarbazepine, lamotrigine, baclofen.

— MRI to rule out MS (especially if bilateral or age <40), vascular loop.

— Single or salvo of stabs lasting seconds, no autonomic features.

— Responsive to indomethacin.

Key distinction: Within the TAC family, the discriminator is attack duration and frequency: CH = 15–180 min, 1–8/day; PH = 2–30 min, >5/day, indomethacin-responsive; SUNCT/SUNA = seconds, dozens to hundreds/day; hemicrania continua = continuous baseline pain. Memorize this duration ladder — Step 3 frequently tests it.

Paroxysmal hemicrania (PH):

Hemicrania continua:

SUNCT / SUNA (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing / with cranial Autonomic symptoms):

Trigeminal neuralgia (TN):

Primary stabbing headache ("ice-pick"):

Key Differentials — Secondary and Other-Category Headaches

— 4–72 hours, unilateral or bilateral, pulsating, photo/phonophobia, nausea/vomiting.

— Patient prefers dark, still room — opposite of cluster restlessness.

— Treatment: triptans, NSAIDs, anti-CGRP for prevention.

— Thunderclap onset, "worst headache of life," peak in seconds, neck stiffness, possible focal deficits or LOC.

— Non-contrast CT, LP if CT negative >6 h, CTA.

— Unilateral head/neck pain with Horner syndrome (carotid) or posterior neck/occipital pain (vertebral); preceded by trauma or chiropractic manipulation.

— May cause TIA/stroke. CTA or MRA neck.

— Treat with antithrombotic therapy.

— Sudden severe retro-orbital headache, visual field defect, ophthalmoplegia, endocrine collapse.

— MRI pituitary; emergency endocrine and neurosurgical evaluation.

— Temporal headache, jaw claudication, scalp tenderness, visual changes, polymyalgia rheumatica.

— ESR/CRP elevated; start high-dose prednisone immediately; temporal artery biopsy within 1–2 weeks.

— Severe unilateral eye pain with mid-dilated, non-reactive pupil, halos, nausea, hard globe. Ophtho emergency.

— Unilateral periorbital pain, proptosis, chemosis, ophthalmoplegia (CN III, IV, VI), fever. MRV; anticoagulation.

— Localized infection signs differentiate.

Board pearl: New-onset "cluster-like" headache in a patient >50 with jaw claudication and visual changes is giant cell arteritis — start prednisone 60 mg/day immediately and arrange temporal artery biopsy within 1–2 weeks; do not wait for biopsy to treat (vision loss risk).

Migraine without aura:

Subarachnoid hemorrhage (SAH):

Carotid or vertebral artery dissection:

Pituitary apoplexy or adenoma:

Giant cell arteritis (GCA) (age ≥50):

Acute angle-closure glaucoma:

Cavernous sinus thrombosis:

Sinusitis, dental abscess, herpes zoster ophthalmicus:

Medication overuse headache, hypnic headache (elderly, awakens from sleep, no autonomic features, treated with caffeine/lithium at bedtime).

Discharge Planning and Long-Term Management

— Abortive at home: SC sumatriptan autoinjector (2/day max), home oxygen concentrator + nonrebreather (insurance-approved DME), intranasal zolmitriptan as backup.

— Preventive throughout bout: verapamil titrated to effective dose; continue ~2 weeks beyond bout cessation, then taper.

— Transitional: prednisone burst at bout onset OR occipital nerve block; avoid frequent repeat steroid bursts (cumulative toxicity).

— Continuous verapamil ± lithium ± galcanezumab (off-label for CCH); consider neuromodulation referral after failure of 2–3 preventives.

— Smoking cessation: high priority. Offer nicotine replacement, varenicline, bupropion; emphasize cardiovascular benefit beyond headache.

— Alcohol abstinence during bouts; usually tolerated between bouts.

— Avoid nitroglycerin, sildenafil/tadalafil during bouts when possible.

— Sleep hygiene; treat coexisting OSA.

— Caution with high altitude exposure; consider prophylactic O₂ or acetazolamide.

— Verapamil: ECG at baseline, with each up-titration ≥240 mg, then annually; BP, HR each visit.

— Lithium: level, TSH, BUN/creatinine every 3–6 months.

— Topiramate: electrolytes (bicarb), renal function periodically.

— Galcanezumab: clinical response; track attack diary.

— Standard adult immunizations; influenza yearly; pneumococcal if on chronic steroids.

— DEXA scan if cumulative steroid exposure >3 months.

Step 3 management: At discharge from a cluster bout admission, provide a written action plan, ensure home oxygen delivery is arranged before discharge (call DME), prescribe SC sumatriptan autoinjector, document smoking cessation counseling and pharmacotherapy offer, and schedule neurology follow-up within 2–4 weeks.

Bout-based plan for episodic CH:

Chronic CH (CCH):

Lifestyle and trigger control:

Monitoring while on preventives:

Vaccinations and preventive health:

Follow-Up, Monitoring, and Patient Counseling

— Within 2–4 weeks of starting preventive therapy: assess attack frequency, side effects, ECG (verapamil titration).

— Every 4–6 weeks until bout resolves or preventive is at effective steady-state.

— Every 3–6 months during remission for ECH; every 3 months for CCH.

— More frequent visits during steroid taper or lithium initiation.

— Document date/time, duration, intensity, autonomic features, triggers, abortive used, response. Bring to each visit.

— Set realistic expectations: preventives reduce frequency/intensity, rarely eliminate.

— Strict alcohol avoidance during bouts — even small amounts trigger attacks.

— Smoking cessation: enroll in quitline (1-800-QUIT-NOW), offer pharmacotherapy.

— Safety of home oxygen: no smoking, no flames, secure tanks.

— Triptan limits: ≤2 SC injections per 24 hours; recognize chest tightness as common (not always cardiac) but report severe symptoms.

— Recognize medication overuse: if using triptans >10 days/month chronically, discuss with neurologist.

— Refer to Clusterbusters or similar patient support communities.

— Mental health follow-up given high comorbidity and suicide risk.

— Family education to recognize attacks and avoid mistaking restlessness for substance intoxication.

— Provide documentation for FMLA, ADA accommodations during bouts (flexible scheduling, dark room access).

— Counsel patients not to drive during an attack — pain and triptan-related drowsiness impair driving.

CCS pearl: At every follow-up visit, order/document: PHQ-9, headache diary review, attack frequency, BP/HR, side-effect review, ECG if on verapamil ≥240 mg or recent up-titration, smoking status with counseling, and next follow-up scheduled before patient leaves.

Follow-up cadence:

Headache diary (paper or smartphone app):

Counseling points:

Psychosocial support:

Disability and work accommodations:

Driving safety:

Ethical, Legal, and Patient Safety Considerations

— High suicide rate in CH; routine PHQ-9 and explicit safety screening are standard of care. Document risk level, plan/intent, access to means, and disposition.

— If imminent risk: emergency psychiatric evaluation, possible involuntary hold under state statute. Communicate with family per safety exception to HIPAA.

— Galcanezumab for chronic CH, lithium long-term, deep brain stimulation, sphenopalatine ganglion stimulators — discuss FDA status, alternatives, risks (suicide ideation reported with some CGRP agents), and document.

— Verapamil doses >480 mg/day exceed standard cardiac indications — explain rationale and ECG monitoring plan; document shared decision-making.

— Avoid opioids for cluster headache — ineffective, addictive, promote MOH. Document refusal to prescribe with rationale; offer evidence-based alternatives.

— Check state PDMP if prior opioid use; coordinate care if patient is doctor-shopping.

— Mandatory counseling: no smoking near oxygen (combustion risk, house fires), secure tanks upright, distance from open flame/heat. Document fire safety education.

— Insurance coverage: many denials — appeals with literature citations are part of advocacy.

— Counsel about not driving during attacks or after SC sumatriptan; many states require physician reporting only for impaired drivers (varies by jurisdiction — know your state).

— Bout flares after PCP/specialist handoffs; ensure medication reconciliation of preventives and abortives at every transition. Verapamil refills must not lapse — abrupt discontinuation can rebound.

— Counsel reproductive-age patients about teratogenic preventives (topiramate, valproate, lithium) and need for reliable contraception.

Step 3 management: When a cluster patient demands opioids "because nothing else works," the correct approach is empathic refusal, education that opioids worsen outcomes, offer SC sumatriptan + home O₂ + occipital nerve block, screen for suicide risk and depression, check PDMP, and document the shared decision-making conversation thoroughly.

Suicide risk and duty to act:

Informed consent for off-label and emerging therapies:

Controlled substance stewardship:

Home oxygen safety:

Driving and occupational safety:

Transitions of care risk:

Pregnancy planning:

High-Yield Associations and Rapid-Fire Facts

Board pearl: If a stem mentions "awakens from sleep at the same time each night" + unilateral red, tearing eye + patient is pacing, the diagnosis is cluster headache. First step: 100% oxygen 12 L/min via non-rebreather; long-term preventive: verapamil with serial ECGs.

Demographics: Male:female ~3:1; onset 20s–40s; tobacco use in 65–80%.

Pain location: strictly unilateral, side-locked within a bout; orbital/temporal.

Duration: 15–180 minutes untreated; 1–8 per day.

Circadian and circannual rhythmicity — implicates posterior hypothalamus.

Behavior: restless, paces (opposite of migraine).

Ipsilateral autonomic signs: lacrimation, conjunctival injection, ptosis, miosis, rhinorrhea, nasal congestion, eyelid edema, forehead sweating.

Triggers during bout: alcohol (high specificity), nitroglycerin, histamine, sildenafil.

First-line abortive: 100% O₂ 12–15 L/min via NRB × 15 min + SC sumatriptan 6 mg.

Avoid: oral triptans (too slow), opioids (ineffective, addictive).

First-line preventive: verapamil (start 240 mg, titrate to 480–960 mg with ECG monitoring).

Transitional bridge: oral prednisone taper OR greater occipital nerve block.

Second-line preventives: lithium (especially CCH), topiramate, galcanezumab (ECH only), melatonin 10 mg qHS.

Mandatory test on first diagnosis: MRI brain with pituitary protocol + MRA.

Indomethacin response → think paroxysmal hemicrania or hemicrania continua, NOT cluster.

Comorbidities: depression, anxiety, suicidality, OSA, tobacco/alcohol use disorders.

Verapamil monitoring: serial ECGs for PR prolongation/AV block.

Lithium target: 0.6–0.8 mEq/L; monitor TSH and creatinine.

Pregnancy preferred regimen: oxygen + verapamil + occipital nerve block.

Refractory chronic CH: SPG stimulator, occipital nerve stimulation, gammaCore VNS.

"Suicide headache" — universally screen for suicidality.

Permanent Horner syndrome can develop in long-standing CCH.

Galcanezumab: FDA-approved only for episodic CH (300 mg monthly).

ICHD-3 criterion: ≥5 attacks meeting definition; not better explained by another disorder.

Board Question Stem Patterns

— 35-year-old male smoker awakens at 2 AM with excruciating left retro-orbital pain, pacing the bedroom; left eye is red, tearing, drooping eyelid, runny nostril. Episode resolves in 60 min. Has had similar attacks daily for 2 weeks each spring.

— Answer: Cluster headache. Next step: MRI brain. Acute: O₂ + SC sumatriptan.

— Same patient now in ED during attack. He has well-controlled hypertension and no cardiac disease.

— Answer: 100% O₂ 12–15 L/min via non-rebreather for 15 min ± SC sumatriptan 6 mg.

— Cluster patient with prior MI and stents presents in attack.

— Answer: Oxygen first; avoid triptans/DHE; consider octreotide SC or intranasal lidocaine.

— Patient with recurrent cluster bouts each fall — what to start at onset of next bout?

— Answer: Verapamil with baseline ECG, titrate up; prednisone bridge or occipital nerve block while verapamil reaches effective dose.

— On verapamil 480 mg/day, follow-up ECG shows PR 0.24 s.

— Answer: Do not increase; reduce dose; reassess in 1–2 weeks.

— Patient with unilateral periorbital attacks lasting 10 min, 15 times/day, with autonomic signs — completely resolves on indomethacin.

— Answer: Paroxysmal hemicrania, not cluster.

— 68-year-old with new "cluster-like" unilateral temporal pain, jaw claudication, ESR 90.

— Answer: Start prednisone 60 mg, biopsy.

— Pregnant patient with active bout.

— Answer: Home oxygen + occipital nerve block + verapamil; avoid triptans/ergots/topiramate.

— Cluster patient says "I can't take this anymore" — next step is direct suicide risk assessment.

Key distinction: Step 3 stems often probe management sequencing: identify cluster → image (MRI) → start abortive (O₂ + SC triptan) → bridge (steroid/nerve block) → preventive (verapamil with ECGs) → counsel on smoking, alcohol, and home oxygen safety → screen for depression/suicide → schedule follow-up.

Classic stem 1 — Recognition:

Classic stem 2 — Abortive choice:

Classic stem 3 — Triptan contraindication:

Classic stem 4 — Preventive choice:

Classic stem 5 — Verapamil monitoring:

Classic stem 6 — Indomethacin discriminator:

Classic stem 7 — GCA mimic:

Classic stem 8 — Pregnancy:

Classic stem 9 — Suicide screen:

One-Line Recap

Cluster headache is a strictly unilateral, side-locked, 15–180-minute trigeminal autonomic cephalalgia with circadian rhythm and motor restlessness, treated acutely with 100% high-flow oxygen and subcutaneous sumatriptan, bridged with prednisone or occipital nerve block, and prevented with ECG-monitored verapamil — with mandatory MRI to exclude secondary causes and universal screening for suicidality.

Board pearl: If the patient is pacing, has ipsilateral lacrimation and ptosis, and the attack lasts under 3 hours, give oxygen and SC sumatriptan first, image with MRI, and start verapamil with an ECG — that single sequence answers most Step 3 cluster headache questions.

Recognize: middle-aged male smoker, unilateral retro-orbital pain, ipsilateral lacrimation/ptosis/miosis/rhinorrhea, paces during attack, attacks at same nightly hour for weeks at a time.

First-line abortive: 100% O₂ 12–15 L/min via NRB × 15 min + SC sumatriptan 6 mg (max 2/24 h). Avoid oral triptans and opioids.

Transitional bridge: oral prednisone burst with taper OR ipsilateral greater occipital nerve block (preferred to avoid repeated steroid courses).

First-line preventive: verapamil starting 240 mg/day, titrated to 480–960 mg with serial ECGs at each up-titration (watch PR interval and AV block). Alternatives: lithium (especially chronic CH), topiramate, galcanezumab (episodic CH), melatonin.

Mandatory work-up: MRI brain with pituitary and cavernous sinus protocol + MRA at first diagnosis to exclude pituitary tumor, dissection, AVM.

Pregnancy: oxygen + occipital nerve block + verapamil; avoid triptans, ergots, topiramate, valproate, lithium.

Universal screening: suicidality ("suicide headache"), OSA, depression/anxiety, tobacco use — offer cessation pharmacotherapy at every visit.

Refractory CCH: noninvasive vagal nerve stimulation (gammaCore), sphenopalatine ganglion stimulator, occipital nerve stimulation, hypothalamic DBS as last resort.