# Lecture 18: Headache Disorders ## Unit 2.5: Neuroscience --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Describe the classification of headache disorders 2. Explain the pathophysiology and clinical features of migraine 3. Describe tension-type and cluster headaches 4. Identify red flags for secondary headaches 5. Explain the approach to headache diagnosis and evaluation 6. Describe the management of primary headache disorders --- ## Lecture Outline ### I. Headache Classification and Pain-Sensitive Structures Headaches are classified as primary (the headache disorder itself is the diagnosis) or secondary (the headache is a symptom of an underlying condition). Primary headaches include migraine, tension-type headache, and the trigeminal autonomic cephalalgias (such as cluster headache). Secondary headaches have an identifiable cause such as subarachnoid hemorrhage, meningitis, brain tumor, or giant cell arteritis. While primary headaches are far more common, identifying secondary headaches is critical because some represent medical emergencies. Understanding which structures cause head pain is essential. The brain parenchyma itself is not pain-sensitive; neurosurgery can be performed on awake patients without anesthesia to the brain tissue. Pain-sensitive intracranial structures include the dura mater (especially around the dural sinuses and base of the skull), the large blood vessels (both arteries and veins), and cranial nerves V, IX, and X. Extracranial pain-sensitive structures include the scalp and its blood vessels, muscles of the head and neck, the paranasal sinuses, teeth and temporomandibular joint, and the eyes. The International Classification of Headache Disorders (ICHD-3) provides standardized diagnostic criteria for headache disorders. Primary headaches are diagnosed based on clinical features when secondary causes have been excluded. The most common primary headache is tension-type headache, affecting approximately 40% of the population at some point. Migraine affects about 12% of the population and is the leading cause of disability in people under 50 years of age. Trigeminal autonomic cephalalgias including cluster headache are much less common (less than 1%) but cause severe pain and significant disability. Headache classification: Panel 1 - Pie chart showing primary headache prevalence (tension-type 40%, migraine 12%, TACs <1%) and secondary causes. Panel 2 - Anatomical diagram of pain-sensitive intracranial structures: dura mater (highlighted around sinuses and skull base), major arteries (Circle of Willis, meningeal vessels), and cranial nerves V, IX, X. Panel 3 - Extracranial pain-sensitive structures: scalp vessels and muscles, paranasal sinuses, teeth/TMJ, eyes. Panel 4 - ICHD-3 classification tree showing primary headaches (migraine, tension-type, TACs, other) and secondary headache categories. --- ### II. Migraine Pathophysiology Migraine is a complex neurovascular disorder involving both neural and vascular mechanisms. The pathophysiology has evolved from a primarily vascular theory (vasodilation causing pain) to understanding migraine as a brain disorder with secondary vascular changes. Multiple brain regions and neurochemical systems are involved, and the disorder appears to represent a state of altered sensory processing and neuronal hyperexcitability. Cortical spreading depression (CSD) is thought to underlie the migraine aura. CSD is a slowly propagating wave of neuronal and glial depolarization followed by sustained suppression of neural activity. It moves across the cortex at approximately 3 mm per minute, correlating with the gradual march of visual or sensory aura symptoms. CSD also activates trigeminal afferents in the meninges, potentially linking the aura to the subsequent headache phase. The trigeminovascular system is central to migraine pain. Trigeminal nerve fibers innervating the meninges and cerebral blood vessels release vasoactive neuropeptides when activated, particularly calcitonin gene-related peptide (CGRP), substance P, and neurokinin A. CGRP causes potent vasodilation and promotes neurogenic inflammation with plasma protein extravasation and mast cell degranulation. CGRP levels are elevated during migraine attacks and normalize with successful treatment, establishing CGRP as a key target for migraine therapeutics. Central sensitization amplifies pain perception during migraine. After trigeminal activation, second-order neurons in the trigeminal nucleus caudalis become sensitized, responding to previously innocuous stimuli. This explains the cutaneous allodynia (pain from normally non-painful stimuli like light touch or combing hair) experienced by many patients during migraine. The hypothalamus, periaqueductal gray, and brainstem nuclei also show altered activity during migraine, contributing to symptoms beyond pain such as nausea, photophobia, and autonomic disturbances. Migraine pathophysiology: Panel 1 - Cortical spreading depression wave moving across cortex with EEG correlate showing depolarization followed by suppression, and corresponding visual aura progression (scintillating scotoma expanding from center). Panel 2 - Trigeminovascular system diagram showing trigeminal ganglion, meningeal afferents around blood vessels, CGRP release causing vasodilation and neurogenic inflammation with plasma extravasation. Panel 3 - Central sensitization illustration showing trigeminal nucleus caudalis receiving input, with allodynia representation (pain from comb touching scalp). Panel 4 - Brain regions involved in migraine: hypothalamus (premonitory symptoms), PAG (descending modulation), brainstem nuclei (nausea, autonomic features). --- ### III. Migraine Clinical Features Migraine is characterized by recurrent episodes of moderate to severe headache with associated features. The diagnostic criteria for migraine without aura require at least five attacks fulfilling the following: headache duration of 4 to 72 hours (if untreated), at least two of the pain characteristics (unilateral location, pulsating quality, moderate to severe intensity, or aggravation by routine physical activity), and during the headache at least one associated feature (nausea and/or vomiting, or photophobia and phonophobia). Migraine with aura has additional reversible focal neurological symptoms preceding or accompanying the headache. The migraine attack progresses through phases. The prodrome, occurring hours to days before the headache, includes mood changes (irritability, depression, or euphoria), food cravings, yawning, fatigue, neck stiffness, and difficulty concentrating. Approximately 25% of migraine patients experience aura, typically developing over 5 to 20 minutes and lasting less than 60 minutes. Visual aura is most common, presenting as scintillating scotoma (flickering zigzag lines), fortification spectra (jagged lines resembling fortified castle walls), or homonymous visual field defects. Sensory aura produces spreading paresthesias typically affecting the hand and face. The headache phase follows, lasting 4 to 72 hours with the characteristic pain and associated symptoms. The postdrome features fatigue, difficulty concentrating, and mood changes lasting hours to days. Migraine variants include chronic migraine (headache on 15 or more days per month for more than three months, with migraine features on at least 8 days), menstrual migraine (attacks reliably occurring in relation to menstruation), vestibular migraine (vertigo with migraine features), hemiplegic migraine (aura including motor weakness, either sporadic or familial with specific genetic mutations), and migraine with brainstem aura (previously called basilar migraine, with brainstem symptoms such as vertigo, dysarthria, and ataxia). Complications include status migrainosus (attack lasting longer than 72 hours), migrainous infarction (stroke occurring during an aura), and medication overuse headache. Migraine clinical features: Panel 1 - Timeline of migraine phases: prodrome (mood changes, yawning, cravings) → aura if present (visual, sensory) → headache phase (unilateral pulsating pain, nausea, photo/phonophobia) → postdrome (fatigue, cognitive difficulty). Panel 2 - Visual aura progression showing scintillating scotoma with fortification spectra expanding from central vision over 20 minutes. Panel 3 - Sensory aura illustration showing paresthesias spreading from fingertips up the arm and to the face over time. Panel 4 - Migraine diagnostic criteria checklist with the "2 of 4" pain features and "1 of 2" associated features highlighted. --- ### IV. Tension-Type Headache Tension-type headache (TTH) is the most common primary headache, affecting approximately 40% of the population at some point in life. Unlike migraine, which is clearly neurobiological, the pathophysiology of TTH is less well understood and likely involves both peripheral myofascial mechanisms and central sensitization, particularly in the chronic form. The clinical features of tension-type headache distinguish it from migraine. The pain is typically bilateral rather than unilateral, with a pressing or tightening quality (often described as a band around the head) rather than pulsating. The intensity is mild to moderate rather than moderate to severe, and crucially, the headache is not aggravated by routine physical activity such as walking or climbing stairs. Duration ranges from 30 minutes to 7 days. The headache is not accompanied by nausea or vomiting (which would suggest migraine), and at most only one of photophobia or phonophobia is present, not both. Tension-type headache is classified by frequency. Infrequent episodic TTH occurs less than one day per month on average and rarely leads to consultation. Frequent episodic TTH occurs between 1 and 14 days per month. Chronic TTH occurs 15 or more days per month for more than three months and causes significant disability. The chronic form is thought to involve central sensitization and may be more difficult to treat. Peripheral mechanisms include myofascial tenderness of pericranial muscles, which can be assessed by palpation. Patients with TTH often have increased tenderness of temporalis, masseter, frontal, suboccipital, and trapezius muscles. Whether muscle tension is a cause or consequence of the headache remains debated. In chronic TTH, central sensitization with increased general pain sensitivity and decreased pain thresholds suggests CNS changes analogous to those seen in other chronic pain conditions. Tension-type headache: Panel 1 - Illustration of typical TTH character: bilateral "band-like" pressure around the head, patient continuing normal activities (unlike migraine). Panel 2 - Comparison chart of TTH vs migraine: location (bilateral vs unilateral), quality (pressing vs pulsating), severity (mild-moderate vs moderate-severe), activity effect (not aggravated vs aggravated), nausea (absent vs common), both photo AND phonophobia (no vs yes). Panel 3 - TTH classification by frequency: infrequent episodic (<1/month), frequent episodic (1-14/month), chronic (≥15/month). Panel 4 - Pericranial muscle tenderness examination showing palpation points for temporalis, frontal, masseter, and trapezius with typical tender points in TTH patients. --- ### V. Cluster Headache and Trigeminal Autonomic Cephalalgias Cluster headache is the most common trigeminal autonomic cephalalgia (TAC), characterized by severe unilateral periorbital or temporal pain accompanied by ipsilateral autonomic features. It predominantly affects men (male to female ratio of approximately 3:1), typically beginning between ages 20 and 40. The name derives from the tendency for attacks to occur in clusters lasting weeks to months, separated by remission periods of months to years. The attacks are distinctive and unforgettable. The pain is described as excruciating, boring, or stabbing, centered around or behind one eye. Attacks last 15 to 180 minutes (typically 45-90 minutes) and can occur 1 to 8 times daily, often at the same time each day and frequently waking the patient from sleep. Unlike migraine patients who prefer to lie still in a dark room, cluster headache patients are restless and agitated, pacing or rocking. Ipsilateral autonomic features include lacrimation (tearing), conjunctival injection (red eye), nasal congestion or rhinorrhea, forehead sweating, miosis, ptosis, and eyelid edema. Cluster headache occurs in episodic (most common) and chronic forms. Episodic cluster has attack periods (clusters) lasting 7 days to 1 year separated by remission periods of at least 3 months. Chronic cluster has attacks occurring for more than a year without remission or with remissions lasting less than 3 months. The hypothalamus appears central to cluster pathophysiology, explaining the circadian and circannual periodicity; neuroimaging shows hypothalamic activation during attacks. Other trigeminal autonomic cephalalgias share unilateral trigeminal distribution pain with autonomic features but differ in attack duration and frequency. Paroxysmal hemicrania has shorter attacks (2-30 minutes) occurring more frequently (more than 5 per day) and shows absolute response to indomethacin, which is diagnostic. SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (short-lasting unilateral neuralgiform headache attacks with autonomic symptoms) have very brief attacks lasting seconds to minutes. Hemicrania continua is a continuous unilateral headache with autonomic features that also responds completely to indomethacin. Cluster headache and TACs: Panel 1 - Cluster headache clinical presentation showing severe periorbital pain location, patient pacing in distress (not lying still), and ipsilateral autonomic features: red eye (conjunctival injection), tearing (lacrimation), ptosis, miosis, nasal congestion/rhinorrhea, forehead sweating. Panel 2 - Cluster attack pattern diagram showing daily attacks (often nocturnal) occurring during cluster period of weeks-months, followed by remission of months-years. Panel 3 - TAC comparison table: cluster (15-180 min, 1-8/day, oxygen/triptan), paroxysmal hemicrania (2-30 min, >5/day, indomethacin), SUNCT/SUNA (seconds-minutes, many/day, lamotrigine), hemicrania continua (continuous, continuous, indomethacin). Panel 4 - Hypothalamic activation during cluster headache shown on functional imaging with circadian rhythm explanation. --- ### VI. Secondary Headache Red Flags Identifying secondary headaches is critical because some are life-threatening emergencies. The SNOOP4 mnemonic helps remember red flags: Systemic symptoms or illness (fever, weight loss, malignancy, immunocompromised state), Neurological symptoms or signs (focal deficits, altered consciousness, seizures, papilledema), Onset sudden (thunderclap headache reaching maximum intensity within seconds), Older age of onset (new headache beginning after age 50), Pattern change (progressive worsening, new type of headache, or different from previous headaches), Precipitated by Valsalva, exertion, or position, Papilledema, and Pregnancy or postpartum. Thunderclap headache, a severe headache reaching peak intensity within seconds to one minute, requires immediate evaluation for subarachnoid hemorrhage (SAH). SAH presents as the "worst headache of life" with sudden onset, often accompanied by neck stiffness, nausea and vomiting, and altered consciousness. Approximately 12% of patients presenting with thunderclap headache have SAH. CT head is highly sensitive (over 95%) within 6 hours but sensitivity decreases over time; if CT is negative, lumbar puncture is required to look for xanthochromia (yellow discoloration from hemoglobin breakdown). Other causes of thunderclap headache include cerebral venous thrombosis, cervical artery dissection, pituitary apoplexy, and reversible cerebral vasoconstriction syndrome (RCVS). Fever with headache and neck stiffness suggests meningitis, requiring urgent lumbar puncture after appropriate imaging if there are focal signs or altered consciousness. Giant cell (temporal) arteritis must be considered in any patient over 50 with new headache, particularly with jaw claudication, scalp tenderness, visual disturbances, or symptoms of polymyalgia rheumatica; ESR and CRP are typically markedly elevated, and immediate empirical corticosteroid treatment is indicated pending temporal artery biopsy because of the risk of permanent vision loss. Idiopathic intracranial hypertension typically affects young obese women with headache, pulsatile tinnitus, and visual symptoms, with papilledema on examination. Secondary headache red flags: Panel 1 - SNOOP4 mnemonic diagram with each letter expanded and high-risk conditions listed for each category. Panel 2 - Thunderclap headache evaluation algorithm: immediate CT head → if negative, lumbar puncture for xanthochromia and RBCs → if negative, consider CTA/MRV for other vascular causes. Panel 3 - Subarachnoid hemorrhage CT appearance showing blood in basal cisterns and Sylvian fissures with pattern indicating aneurysm location. Panel 4 - Giant cell arteritis features: tender nodular temporal artery, jaw claudication illustration, fundoscopy showing pale swollen disc (anterior ischemic optic neuropathy), and urgent treatment timeline. --- ### VII. Secondary Headaches Subarachnoid hemorrhage (SAH) results from bleeding into the subarachnoid space, most commonly from aneurysm rupture (approximately 85% of cases). The classic presentation is sudden onset of severe headache, though the presentation can be more subtle. A "sentinel headache" from a small warning leak may precede major rupture in up to 40% of patients. Examination may reveal meningismus (neck stiffness from meningeal irritation), altered consciousness, and focal neurological signs depending on aneurysm location. Management includes securing the aneurysm (endovascular coiling or surgical clipping), preventing and treating vasospasm (nimodipine, monitoring with transcranial Doppler), managing hydrocephalus, and supportive care. Delayed cerebral ischemia from vasospasm typically occurs between days 4 and 14. Meningitis presents with headache, fever, and neck stiffness, with the acuity and CSF profile differing by etiology. Bacterial meningitis progresses over hours with high fever, marked meningismus, and rapid deterioration; CSF shows neutrophilic pleocytosis, low glucose, and elevated protein. Viral meningitis develops over days, is generally less severe, and CSF shows lymphocytic pleocytosis with normal glucose. Tuberculous and fungal meningitis have subacute presentations with lymphocytic CSF and low glucose. Giant cell arteritis (GCA) is a vasculitis affecting medium and large arteries, particularly branches of the external carotid. Beyond headache, features include jaw claudication (pain with chewing from masseter ischemia), scalp tenderness (often noticed when brushing hair), visual symptoms (transient visual loss, diplopia, or permanent vision loss from ischemic optic neuropathy), and systemic symptoms of polymyalgia rheumatica in up to 50% of patients. ESR is typically markedly elevated, often above 50-100 mm/hr, and CRP is elevated. Treatment with high-dose corticosteroids should begin immediately upon clinical suspicion, without waiting for biopsy, because vision loss can be prevented if treated early but is usually irreversible once established. Secondary headaches detail: Panel 1 - SAH timeline showing sentinel headache, major rupture with thunderclap, acute management (stabilize, image, secure aneurysm), vasospasm window days 4-14, and long-term monitoring. Panel 2 - Meningitis CSF comparison chart: bacterial (neutrophils, low glucose, high protein, positive culture), viral (lymphocytes, normal glucose, mild protein elevation), TB/fungal (lymphocytes, very low glucose, high protein, slow culture). Panel 3 - GCA clinical features and temporal artery biopsy showing giant cells and intimal thickening with narrowed lumen. Panel 4 - Idiopathic intracranial hypertension: typical patient (young obese woman), papilledema fundoscopic image, MRI showing empty sella and flattened globes, elevated opening pressure on LP. --- ### VIII. Migraine Acute Treatment Acute migraine treatment aims to abort the attack and restore function. Treatment should be taken early, ideally during the prodrome or at headache onset, as efficacy decreases once central sensitization has developed. Treatment selection depends on headache severity, associated symptoms, contraindications, and patient preference. For mild to moderate migraine, simple analgesics are often effective. Options include acetaminophen 1000 mg, aspirin 1000 mg, ibuprofen 400-800 mg, or naproxen 500-1000 mg. Combination products containing caffeine (aspirin-acetaminophen-caffeine) enhance efficacy. Antiemetics such as metoclopramide or prochlorperazine address nausea and may enhance analgesic absorption. Triptans are the mainstay of moderate to severe migraine treatment. They are serotonin 5-HT1B/1D receptor agonists that cause vasoconstriction of meningeal vessels, inhibit CGRP release from trigeminal terminals, and block pain signal transmission. Seven triptans are available with varying pharmacokinetic profiles: sumatriptan (available as oral, nasal spray, and subcutaneous injection), rizatriptan and eletriptan (fast-acting oral), zolmitriptan (oral and nasal), and others with longer duration (naratriptan, frovatriptan). Triptans are contraindicated in patients with cardiovascular disease, uncontrolled hypertension, or history of stroke, and in hemiplegic migraine. They should not be used within 24 hours of ergot derivatives. Newer options include gepants (CGRP receptor antagonists) such as ubrogepant and rimegepant, which are effective without vasoconstriction and thus can be used in patients with cardiovascular contraindications to triptans. Ditans (5-HT1F agonists) such as lasmiditan provide another non-vasoconstrictive option but cause sedation. Emergency department treatment for refractory migraine includes IV antiemetics (prochlorperazine, metoclopramide), ketorolac, IV magnesium, dihydroergotamine (DHE), and dexamethasone to reduce recurrence. Migraine acute treatment: Panel 1 - Treatment selection algorithm by severity: mild-moderate (NSAIDs, acetaminophen ± antiemetic) → moderate-severe (triptans, gepants) → refractory (IV regimens in ED). Panel 2 - Triptan mechanism diagram showing 5-HT1B/1D receptors on meningeal vessels (vasoconstriction) and trigeminal terminals (CGRP inhibition, blocked transmission). Panel 3 - Triptan comparison table showing onset, duration, and available formulations for each. Panel 4 - Gepant mechanism showing CGRP receptor blockade without vasoconstriction, with indication for cardiovascular patients who cannot use triptans. --- ### IX. Migraine Preventive Treatment Preventive treatment is indicated when migraine attacks occur frequently (four or more per month), when attacks cause significant disability despite acute treatment, when acute treatments are contraindicated, ineffective, or overused, or when the patient prefers to reduce attack frequency. The goal is to reduce attack frequency, severity, and duration by at least 50%. Traditional first-line preventive medications include beta-blockers (propranolol 80-240 mg, metoprolol 100-200 mg), antidepressants (amitriptyline 25-150 mg, venlafaxine 75-150 mg), and anticonvulsants (topiramate 50-200 mg, valproate 500-1500 mg). Selection is often based on comorbidities: a patient with hypertension might benefit from a beta-blocker, while one with depression might benefit from amitriptyline or venlafaxine. All require gradual titration and adequate trial duration (2-3 months at target dose) before determining efficacy. CGRP-targeted preventive therapies represent a major advance in migraine prevention. Monoclonal antibodies targeting CGRP itself (fremanezumab, galcanezumab, eptinezumab) or its receptor (erenumab) are administered monthly or quarterly by injection and show approximately 50% reduction in migraine days. They have favorable tolerability with injection site reactions as the main side effect. Gepants (atogepant, rimegepant) are now also approved for prevention as oral daily medications. These CGRP-targeted treatments are particularly valuable for patients who have failed or cannot tolerate traditional preventives. Non-pharmacological approaches are important adjuncts. Lifestyle modifications include regular sleep schedule, regular meals (avoiding fasting), regular aerobic exercise, stress management, and trigger avoidance where identifiable. Behavioral interventions with evidence include biofeedback, cognitive behavioral therapy for headache, and relaxation training. Neuromodulation devices including transcutaneous supraorbital nerve stimulation (Cefaly), single-pulse transcranial magnetic stimulation (SpringTMS), and non-invasive vagus nerve stimulation offer drug-free options with modest efficacy. Migraine prevention: Panel 1 - Indications for preventive treatment: ≥4 attacks/month, significant disability, acute treatment failure/overuse, patient preference. Panel 2 - Traditional preventive medications by class with typical doses, selection considerations based on comorbidities (beta-blocker for hypertension, amitriptyline for insomnia, topiramate for obesity). Panel 3 - CGRP pathway and mechanisms of monoclonal antibodies (targeting CGRP ligand or receptor) vs gepants (small molecule receptor antagonists) with comparison table. Panel 4 - Non-pharmacological approaches: lifestyle (sleep, meals, exercise), behavioral (biofeedback, CBT), neuromodulation devices (Cefaly, SpringTMS) with supporting evidence level. --- ### X. Medication Overuse Headache and Cluster Treatment Medication overuse headache (MOH) is a common cause of chronic daily headache, occurring when acute headache medications are used too frequently. It is defined as headache occurring on 15 or more days per month in a patient with a pre-existing primary headache who has been overusing acute treatment for more than 3 months. The thresholds vary by medication type: triptans, opioids, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on 15 or more days per month. The pathophysiology involves central sensitization and alterations in pain modulation pathways with regular medication exposure. Patients develop a cycle where the headache returns or worsens as the medication wears off, prompting more medication use. The condition is treated by discontinuing the overused medication. This often leads to a temporary worsening of headache for 1-2 weeks (withdrawal headache) before improvement occurs. Bridge therapies during withdrawal include scheduled NSAIDs, a short steroid taper, and antiemetics. Simultaneously starting preventive medication is essential. Patients need education about the condition, close follow-up support, and understanding that relapse occurs in approximately 40% and ongoing management is needed. Cluster headache treatment differs significantly from migraine. Acute treatment options are limited by the rapid onset and short duration of attacks. High-flow oxygen (100% at 12-15 L/min via non-rebreather mask for 15-20 minutes) is highly effective and should be first-line; it aborts attacks in approximately 70% of patients within 15 minutes. Sumatriptan 6 mg subcutaneous injection is rapid and effective; the nasal spray formulation is an alternative. Intranasal lidocaine provides modest relief in some patients. Preventive treatment for cluster headache is essential during cluster periods to reduce attack frequency. Verapamil is first-line (doses often much higher than for cardiac indications, 240-960 mg daily, requiring ECG monitoring). A short course of corticosteroids (prednisone or dexamethasone) can provide rapid suppression as a bridge while verapamil is titrated. Lithium is an alternative or add-on. For refractory cases, options include greater occipital nerve blocks, neurostimulation, and occasionally surgical approaches. Medication overuse headache and cluster treatment: Panel 1 - MOH cycle diagram: headache → medication → temporary relief → medication wears off → rebound headache → more medication; and breaking the cycle with withdrawal and prevention. Panel 2 - MOH treatment approach: education → discontinue overused medication → bridge therapy (NSAIDs, steroids) → start preventive → close follow-up; with typical withdrawal timeline (worse days 1-7, improvement by 2-4 weeks). Panel 3 - Cluster headache acute treatment: oxygen setup showing non-rebreather mask at 12-15 L/min with efficacy timeline, and sumatriptan subcutaneous injection technique. Panel 4 - Cluster preventive treatment ladder: verapamil (first-line, with ECG monitoring note) → short-term steroids (bridge) → lithium (add-on) → GON block, with treatment approach for episodic vs chronic cluster. --- ## Summary - Primary headaches (migraine, tension-type, cluster) are diagnosed clinically; secondary headaches have an underlying cause - Migraine involves cortical spreading depression, trigeminovascular activation, and CGRP release; attacks have prodrome, aura (25%), headache, and postdrome phases - Migraine without aura requires ≥5 attacks with duration 4-72 hours, ≥2 pain features (unilateral, pulsating, moderate-severe, activity-aggravated), and ≥1 associated feature (nausea/vomiting or photophobia and phonophobia) - Tension-type headache is bilateral, pressing, mild-moderate, not activity-aggravated, without nausea, and without both photophobia and phonophobia - Cluster headache is severe unilateral orbital pain with ipsilateral autonomic features (tearing, injection, nasal congestion, ptosis) and restlessness; treat with oxygen and sumatriptan - Red flags (SNOOP4) require investigation: systemic symptoms, neurological signs, sudden onset, older age (>50), pattern change, positional/Valsalva precipitated, papilledema, pregnancy - Thunderclap headache requires SAH exclusion with CT then LP if negative - Acute migraine treatment: NSAIDs for mild; triptans for moderate-severe; gepants if cardiovascular contraindication - Migraine prevention: beta-blockers, antidepressants, anticonvulsants, or CGRP-targeted therapies when ≥4 attacks/month - Medication overuse headache requires withdrawal of overused medication, bridge therapy, and initiation of preventive treatment --- ## Key Terms | Term | Definition | |------|------------| | Migraine aura | Reversible focal neurological symptoms, usually visual, preceding or accompanying headache | | Cortical spreading depression | Wave of neuronal depolarization followed by suppression that underlies aura | | Trigeminal autonomic cephalalgia | Primary headache with autonomic features in trigeminal distribution | | Thunderclap headache | Severe headache reaching maximum intensity within seconds to one minute | | Medication overuse headache | Chronic headache from regular overuse of acute headache medications | | CGRP | Calcitonin gene-related peptide; key mediator released during migraine | | Triptan | 5-HT1B/1D agonist used for acute migraine treatment | | Status migrainosus | Debilitating migraine attack lasting more than 72 hours | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*