Medical School · Year 3 · Neurology · includes a quiz and discussion video

Seminar 03: Headache Disorders

Year 3: Neurology Clerkship

Learning Objectives

By the end of this seminar, students will be able to:

1. Classify primary and secondary headache disorders
2. Diagnose and treat migraine with and without aura
3. Recognize tension-type and cluster headaches
4. Identify red flags for secondary headache
5. Apply acute and preventive headache management
6. Evaluate thunderclap and other emergent headaches

Seminar Outline

I. Approach to Headache

Headache represents one of the most common presenting complaints in clinical practice, requiring systematic evaluation to distinguish benign primary headache disorders from potentially life-threatening secondary causes. Primary headaches including migraine, tension-type headache, and the trigeminal autonomic cephalalgias are conditions where the headache itself constitutes the disorder, without an underlying structural or metabolic cause. Secondary headaches arise from identifiable pathology such as subarachnoid hemorrhage, meningitis, brain tumors, temporal arteritis, and medication overuse. The clinical challenge lies in efficiently identifying patients who require urgent investigation while avoiding unnecessary testing in the vast majority with primary headache disorders.

Thorough history taking provides the foundation for headache diagnosis, as examination and testing are often unrevealing in primary headache disorders. The onset of headache, whether sudden or gradual, and when symptoms first began are essential to establish. Location, whether unilateral or bilateral, frontal, temporal, or occipital, provides diagnostic clues. The character of pain, whether throbbing, pressure-like, or stabbing, helps distinguish headache types. Severity rated on a numeric scale and duration of individual attacks guide classification. Associated symptoms including nausea, photophobia, phonophobia, autonomic features, and focal neurological symptoms must be explored. Identifying triggers such as stress, foods, sleep patterns, and hormonal changes aids diagnosis and management.

The SNOOP mnemonic captures essential red flags that should prompt urgent evaluation and imaging. Systemic symptoms including fever, weight loss, or signs of malignancy suggest secondary causes requiring investigation. Neurological symptoms or signs including focal weakness, visual changes, or altered mental status indicate structural pathology. Onset that is sudden, reaching maximum intensity within seconds to minutes, defines thunderclap headache and mandates evaluation for subarachnoid hemorrhage. Older age of onset, particularly new headache in patients over 50, raises concern for giant cell arteritis and mass lesions. Pattern change in a patient with established headache, progressive worsening, or positional features should trigger reassessment. Additional concerning features include prior cancer, immunocompromised status, and pregnancy.

Imaging is indicated when red flags are present, when the headache pattern is atypical for primary headache, or when there is diagnostic uncertainty. Non-contrast CT is appropriate for suspected subarachnoid hemorrhage, with lumbar puncture indicated if CT is negative but clinical suspicion remains. MRI with and without contrast is preferred for evaluating possible mass lesions, inflammatory conditions, and posterior fossa pathology. First or worst headache presentations warrant consideration of imaging, though the decision depends on clinical context and associated features. Change in headache pattern in a patient with established primary headache disorder may prompt imaging to exclude superimposed secondary pathology, particularly if the change is unexplained.

<image>Panel A: Primary versus secondary headache classification with examples of each category and prevalence. Panel B: Comprehensive headache history elements including onset, location, character, severity, duration, and associated symptoms. Panel C: SNOOP red flags mnemonic with clinical significance and appropriate next steps for each flag. Panel D: Imaging decision algorithm based on clinical features and suspected etiology.</image>

II. Migraine

Migraine affects approximately 12 percent of the general population and represents the second leading cause of disability worldwide. The disorder demonstrates a striking female predominance, with women affected three times more frequently than men, likely related to hormonal influences. Onset typically occurs before age 30, with many patients experiencing their first migraine in childhood or adolescence. Genetic factors play a significant role, with positive family history present in the majority of affected individuals. Beyond the substantial personal burden of episodic disability, migraine imposes enormous economic costs through lost productivity and healthcare utilization.

The International Headache Society diagnostic criteria for migraine without aura require at least five attacks meeting specific characteristics. Each attack lasts between 4 and 72 hours when untreated or unsuccessfully treated. The headache must have at least two of four typical features: unilateral location, pulsating quality, moderate to severe intensity, and aggravation by routine physical activity. Additionally, during the headache, at least one of two accompanying symptom complexes must occur: nausea and/or vomiting, or photophobia and phonophobia together. The symptoms should not be attributable to another disorder, which requires consideration of secondary causes when atypical features are present.

Migraine with aura occurs in approximately one-quarter of migraine patients and adds reversible focal neurological symptoms to the clinical picture. Visual aura is most common, manifesting as scintillating scotoma with flickering zigzag lines expanding across the visual field, or as fortification spectra resembling the walls of a medieval castle. Sensory aura produces tingling or numbness typically starting in the hand and spreading over minutes to involve the arm and face. Language aura causes word-finding difficulty or dysarthria. Motor aura, seen in the rare hemiplegic migraine, produces weakness. Aura symptoms characteristically spread or march over 5 to 60 minutes, distinguishing them from the sudden onset of vascular events, and are followed within 60 minutes by headache.

Migraine proceeds through distinct phases that inform both recognition and treatment. The prodrome occurs hours to days before the headache and includes mood changes, food cravings, fatigue, neck stiffness, and frequent yawning. Recognition of prodromal symptoms allows early treatment. The aura phase, when present, precedes or accompanies headache onset. The headache phase brings the characteristic throbbing, unilateral pain with associated symptoms, typically lasting 4 to 72 hours. The postdrome follows headache resolution and manifests as fatigue, cognitive difficulty, and depressed mood that may persist for hours to days. Understanding these phases helps patients and clinicians identify migraine at various stages.

<image>Panel A: Migraine epidemiology showing prevalence by age and sex with disability ranking and economic burden. Panel B: Diagnostic criteria flowchart for migraine without aura with required features and exclusion considerations. Panel C: Migraine aura types illustrated including visual, sensory, language, and motor manifestations with typical spread patterns. Panel D: Four phases of migraine showing prodrome, aura, headache, and postdrome with characteristic symptoms and time course.</image>

III. Migraine Acute Treatment

First-line treatment for mild to moderate migraine attacks centers on nonsteroidal anti-inflammatory drugs and simple analgesics taken early in the attack. Ibuprofen at doses of 400 to 800 mg provides effective relief for many patients and should be taken at the first sign of migraine rather than waiting for full attack development. Naproxen at 500 to 750 mg offers longer duration of action that may prevent headache recurrence. Acetaminophen at 1000 mg provides an alternative when NSAIDs are contraindicated due to gastrointestinal or cardiovascular concerns. Aspirin at 900 to 1000 mg is effective and inexpensive. These medications are most effective when combined with rest in a dark, quiet environment and adequate hydration.

Triptans represent the gold standard for moderate to severe migraine and for mild attacks unresponsive to simple analgesics. These serotonin 5-HT1B/1D receptor agonists abort migraine by causing vasoconstriction of dilated cranial vessels and inhibiting trigeminal nerve activity. Sumatriptan is available in oral, subcutaneous, and nasal formulations, with subcutaneous administration offering the fastest onset but highest side effect burden. Rizatriptan and eletriptan are generally considered among the most effective oral triptans. Zolmitriptan nasal spray provides an alternative for patients with nausea. Contraindications to triptans include coronary artery disease, uncontrolled hypertension, prior stroke, and hemiplegic or basilar migraine due to the vasoconstrictive mechanism.

Newer acute treatments have expanded options for patients who cannot use or do not respond to triptans. Gepants are small molecule calcitonin gene-related peptide receptor antagonists that abort migraine without vasoconstriction, making them safe in cardiovascular disease. Ubrogepant and rimegepant are available as oral formulations, with rimegepant also approved for prevention with alternate-day dosing. Ditans, represented by lasmiditan, are selective 5-HT1F receptor agonists that do not cause vasoconstriction and are safe in cardiovascular disease, though they cause significant central nervous system effects including sedation and driving impairment. Dihydroergotamine remains useful for refractory cases, particularly in the emergency department or as home nasal spray.

Treatment principles maximize efficacy while minimizing the risk of medication overuse headache. Early treatment when migraine is mild produces better outcomes than waiting for severe pain, as peripheral and central sensitization progress as attacks continue. Adequate dosing is essential, as subtherapeutic doses often fail. Route of administration matters, with subcutaneous or nasal formulations preferable when nausea and vomiting are prominent. Antiemetics such as metoclopramide and prochlorperazine serve dual purposes by relieving nausea and having independent antimigraine effects. Patients should limit triptan use to fewer than 10 days per month and analgesic use to fewer than 15 days to prevent medication overuse headache. Opioids should be avoided as they are less effective than migraine-specific treatments and increase chronification risk.

<image>Panel A: First-line acute treatments including NSAIDs and acetaminophen with dosing and timing recommendations. Panel B: Triptan comparison showing available formulations, onset of action, and selection based on patient characteristics. Panel C: Novel acute treatments including gepants and ditans with mechanisms, cardiovascular safety profiles, and clinical roles. Panel D: Treatment principles emphasizing early dosing, route selection, frequency limits, and medication overuse prevention.</image>

IV. Migraine Prevention

Preventive therapy should be considered when migraine significantly impacts quality of life despite optimal acute treatment. Traditional indications include four or more headache days per month, significant disability with attacks, failure or contraindications to acute treatments, and risk of medication overuse headache. Special circumstances favoring prevention include hemiplegic migraine, prolonged aura, brainstem aura, and migrainous infarction due to their higher risk of permanent neurological injury. Prevention aims to reduce attack frequency by at least 50 percent, decrease attack severity and duration, improve response to acute treatment, and enhance quality of life.

First-line preventive medications include beta-blockers, antiepileptics, and tricyclic antidepressants, each with distinct advantages and disadvantages. Propranolol at 40 to 240 mg daily is well-established but contraindicated in asthma and may cause fatigue and exercise intolerance. Topiramate at 25 to 100 mg daily provides modest weight loss in many patients but causes cognitive impairment, paresthesias, and teratogenicity. Amitriptyline at 10 to 75 mg at bedtime is advantageous when insomnia or depression coexist but causes sedation, weight gain, and anticholinergic effects. Valproate at 500 to 1500 mg daily is highly effective but teratogenic with a neural tube defect risk that absolutely precludes use in women of childbearing potential.

Calcitonin gene-related peptide pathway monoclonal antibodies have transformed migraine prevention with superior efficacy and tolerability compared to traditional preventives. Erenumab targets the CGRP receptor, while fremanezumab, galcanezumab, and eptinezumab target the CGRP ligand itself. These medications are administered subcutaneously monthly or quarterly, with eptinezumab given intravenously every three months. Benefits include no titration requirement, minimal drug interactions, no daily dosing, and generally excellent tolerability with injection site reactions and constipation being the main adverse effects. Cost and insurance coverage remain barriers for many patients, though efficacy in treatment-resistant patients justifies pursuit of prior authorization.

Additional preventive options address specific patient populations and comorbidities. Venlafaxine provides migraine prevention in patients with comorbid depression. Candesartan is effective in patients requiring blood pressure control. Botulinum toxin A is FDA-approved for chronic migraine, defined as 15 or more headache days per month for at least 3 months, with injections at 31 sites across the head and neck every 12 weeks. Neuromodulation devices including Cefaly for supraorbital stimulation, SpringTMS for single-pulse transcranial magnetic stimulation, and gammaCore for non-invasive vagus nerve stimulation offer drug-free alternatives. Supplements including magnesium, riboflavin, and coenzyme Q10 provide modest benefit with excellent safety.

<image>Panel A: Indications for preventive therapy including frequency thresholds, disability measures, and special circumstances. Panel B: Traditional preventive medications showing propranolol, topiramate, amitriptyline, and valproate with dosing, benefits, and key adverse effects. Panel C: CGRP pathway antibodies comparing erenumab, fremanezumab, galcanezumab, and eptinezumab with targets, dosing schedules, and tolerability. Panel D: Alternative preventive approaches including botulinum toxin injection sites, neuromodulation devices, and supplement options.</image>

V. Tension-Type Headache

Tension-type headache represents the most common primary headache disorder, affecting approximately 40 percent of the population at some point in their lives. Unlike migraine, the sex distribution is approximately equal or shows only slight female predominance. Attacks can occur at any age, though prevalence peaks in middle adulthood. Triggers include stress, fatigue, poor posture, and musculoskeletal tension. While individual attacks are typically less disabling than migraine, the high frequency in some patients creates substantial cumulative burden.

The diagnostic criteria for tension-type headache emphasize what is absent as much as what is present, distinguishing it from migraine. Episodes last from 30 minutes to 7 days. The pain has at least two of four characteristics: bilateral location, pressing or tightening quality rather than pulsating, mild to moderate intensity, and lack of aggravation by routine physical activity. Unlike migraine, there is no nausea, and at most one of photophobia or phonophobia may be present, but not both. These negative features help avoid misdiagnosis of mild migraine as tension-type headache.

Classification of tension-type headache by frequency guides treatment approach. Infrequent episodic tension-type headache occurs less than one day per month on average and typically requires no intervention beyond reassurance and occasional simple analgesics. Frequent episodic tension-type headache occurs 1 to 14 days per month and may warrant more systematic management. Chronic tension-type headache occurs 15 or more days per month for at least 3 months and often requires preventive treatment. The distinction between chronic tension-type headache and chronic migraine can be challenging, and the two conditions may coexist or evolve between phenotypes.

Treatment of tension-type headache emphasizes lifestyle modification and judicious use of medications. Acute treatment with NSAIDs or acetaminophen is appropriate for episodic attacks, with care to avoid medication overuse by limiting use to fewer than 15 days per month. Opioids and barbiturate-containing compounds should be avoided due to poor efficacy and high risk of medication overuse headache. Preventive treatment for chronic tension-type headache typically begins with amitriptyline at low doses, gradually titrated for effect. Non-pharmacological approaches including stress management, physical therapy, sleep hygiene, and cognitive behavioral therapy are particularly valuable and should be integrated with medication management when indicated.

<image>Panel A: Tension-type headache epidemiology showing high prevalence, age distribution, and contrast with migraine demographics. Panel B: Diagnostic criteria emphasizing bilateral pressing pain, mild-moderate intensity, no aggravation by activity, and absence of migraine features. Panel C: Frequency-based classification with infrequent episodic, frequent episodic, and chronic subtypes with treatment implications. Panel D: Treatment approach for acute and preventive management with emphasis on analgesic limits and non-pharmacological strategies.</image>

VI. Trigeminal Autonomic Cephalalgias

Cluster headache is the most common and most severe of the trigeminal autonomic cephalalgias, characterized by excruciating unilateral pain with prominent ipsilateral autonomic features. The pain is centered in the orbital, supraorbital, or temporal region and is described as burning, boring, or stabbing. Individual attacks last 15 to 180 minutes and may occur one to eight times daily during cluster periods. Unlike migraine patients who seek rest and dark, quiet environments, cluster headache patients characteristically pace, rock, or exhibit psychomotor agitation during attacks. Ipsilateral autonomic features include lacrimation, conjunctival injection, nasal congestion or rhinorrhea, eyelid edema, forehead sweating, and miosis or ptosis. Cluster periods typically last weeks to months, followed by remission periods in the episodic form.

Acute treatment of cluster headache requires rapidly acting interventions given the short duration of attacks. High-flow oxygen at 12 to 15 liters per minute delivered by non-rebreather mask aborts the majority of attacks within 15 minutes and is well-tolerated without significant adverse effects. Subcutaneous sumatriptan at 6 mg provides the fastest pharmacological relief, though intranasal sumatriptan or zolmitriptan are alternatives when injection is impractical. Oral triptans are generally too slow for this indication. Intranasal lidocaine directed at the sphenopalatine ganglion provides adjunctive benefit. Emergency department treatment may require parenteral medications including dihydroergotamine.

Preventive treatment aims to suppress attacks throughout the cluster period. Verapamil is the first-line preventive agent, initiated at 80 mg three times daily and titrated to efficacy, with doses sometimes exceeding 400 mg daily. Electrocardiogram monitoring for PR prolongation is required at higher doses. Transitional therapy with a prednisone taper, typically starting at 60 to 80 mg daily and tapering over 2 to 3 weeks, provides rapid suppression while verapamil is titrated. Greater occipital nerve block with local anesthetic and corticosteroid offers rapid relief lasting weeks. Lithium and topiramate serve as alternatives when verapamil is ineffective or contraindicated. Alcohol is a potent trigger during cluster periods and should be strictly avoided.

Other trigeminal autonomic cephalalgias differ from cluster headache primarily in attack duration and frequency. Paroxysmal hemicrania produces attacks lasting 2 to 30 minutes but occurring more than five times daily, with complete response to indomethacin being diagnostically required. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, known as SUNCT, produces attacks lasting only seconds with many episodes daily, responding best to lamotrigine. Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, known as SUNA, is similar but without the full conjunctival injection and tearing. Hemicrania continua is a continuous unilateral headache with superimposed exacerbations and autonomic features, showing absolute response to indomethacin that is diagnostically required.

<image>Panel A: Cluster headache characteristics including pain quality and location, autonomic features, attack duration, and restless behavior. Panel B: Acute cluster treatment with high-flow oxygen setup, sumatriptan administration, and response timeline. Panel C: Preventive cluster treatment showing verapamil titration, prednisone transitional therapy, and greater occipital nerve block technique. Panel D: Comparison of trigeminal autonomic cephalalgias showing cluster, paroxysmal hemicrania, SUNCT, and hemicrania continua with distinguishing features.</image>

VII. Medication Overuse Headache

Medication overuse headache represents one of the most important and potentially reversible causes of chronic daily headache, affecting approximately 1 to 2 percent of the general population. The diagnostic criteria require headache occurring 15 or more days per month for more than 3 months in a patient with a preexisting primary headache disorder who regularly overuses acute headache medication. Different medication classes have different thresholds, with triptans, opioids, and combination analgesics carrying higher risk at 10 or more days of use per month, while simple analgesics pose risk at 15 or more days monthly. The condition reflects a maladaptive cycle where progressively more medication provides progressively less relief.

Risk factors for developing medication overuse headache extend beyond simple frequency of medication use. An underlying primary headache disorder, typically migraine or tension-type headache, provides the substrate upon which overuse develops. The type of medication matters significantly, with opioids and butalbital-containing compounds carrying the highest risk and NSAIDs the lowest. Psychological comorbidities including anxiety and depression increase vulnerability, as does a family history of substance abuse. Certain personality traits including external locus of control and catastrophizing also confer risk. Recognition of these factors allows identification of patients requiring closer monitoring.

The pathophysiology of medication overuse headache involves central sensitization, development of tolerance, and neuroplastic changes that perpetuate the cycle. Repeated medication exposure leads to progressive downregulation of serotonin receptors and other pain-modulating systems. The brain's pain matrix becomes sensitized, lowering the threshold for headache initiation. Withdrawal of the overused medication produces rebound headache that drives further medication use. Functional imaging studies demonstrate changes in brain structure and function that partially normalize with successful treatment. Understanding these mechanisms informs the treatment approach.

Treatment of medication overuse headache requires medication withdrawal, which may be accomplished through several strategies. Patient education is essential, as understanding the paradox of medication causing headache motivates adherence to the treatment plan. For triptans and NSAIDs, abrupt discontinuation is generally preferred, with a bridge therapy such as longer-acting NSAIDs, corticosteroids, or dihydroergotamine to manage the withdrawal phase. For opioids and barbiturates, gradual tapering is safer due to physiological dependence. Preventive medication should be initiated or optimized simultaneously, as prevention reduces the substrate of frequent headaches that drove overuse. Close follow-up during the withdrawal phase provides support and monitors for complications. The prognosis is favorable, with 50 to 70 percent of patients showing sustained improvement after successful withdrawal.

<image>Panel A: Medication overuse headache diagnostic criteria showing headache frequency threshold, duration, and medication-specific day limits. Panel B: Risk factors including medication types, psychiatric comorbidities, and personality factors that increase susceptibility. Panel C: Pathophysiology illustration showing central sensitization, receptor downregulation, and rebound headache cycle. Panel D: Treatment approach with withdrawal strategies by medication class, bridge therapy options, and preventive medication initiation.</image>

VIII. Secondary Headaches

Giant cell arteritis, also known as temporal arteritis, represents a medical emergency requiring immediate recognition and treatment to prevent irreversible blindness. This large vessel vasculitis occurs almost exclusively in patients over 50 years of age, with incidence increasing with advancing age. Symptoms include new-onset headache often localized to the temporal region, jaw claudication that is highly specific, scalp tenderness, and systemic symptoms of fatigue and weight loss. The dreaded complication is anterior ischemic optic neuropathy from involvement of the posterior ciliary arteries, presenting as sudden painless monocular vision loss. Laboratory findings include elevated erythrocyte sedimentation rate and C-reactive protein, though normal values do not exclude the diagnosis. Temporal artery biopsy confirms the diagnosis but should not delay treatment, as high-dose prednisone must be initiated immediately when clinical suspicion is present.

Idiopathic intracranial hypertension, formerly known as pseudotumor cerebri, typically affects young obese women and presents with headache, transient visual obscurations, and pulsatile tinnitus. The headache is often worse with Valsalva maneuvers or changes in position and may have features of elevated intracranial pressure including morning predominance and nausea. Fundoscopic examination reveals papilledema, which can progress to visual field loss and blindness if untreated. Lumbar puncture demonstrates elevated opening pressure exceeding 25 cm H2O with normal cerebrospinal fluid composition, and imaging shows no ventricular enlargement or mass lesion. Treatment centers on weight loss, which is highly effective, and acetazolamide for medical management. Refractory cases may require cerebrospinal fluid diversion procedures including ventriculoperitoneal or lumboperitoneal shunting or optic nerve sheath fenestration for visual preservation.

Spontaneous intracranial hypotension results from cerebrospinal fluid leak, most commonly at the level of the thoracic or cervical spine. The hallmark is orthostatic headache that is severe in the upright position and relieved by recumbency, though chronic cases may lose this postural component. Additional symptoms may include nausea, neck stiffness, and cranial nerve palsies from brain sagging. MRI with gadolinium shows characteristic pachymeningeal enhancement, brain sagging with descent of the cerebellar tonsils, and subdural fluid collections or hygromas. Initial treatment is conservative with bed rest, hydration, and caffeine. Epidural blood patch, where autologous blood is injected into the epidural space to seal the leak, is highly effective for cases not responding to conservative measures. Localization of the leak site with CT myelography may be necessary for targeted treatment.

Cerebral venous thrombosis presents with headache in the majority of cases, often accompanied by seizures and focal neurological deficits. Risk factors include oral contraceptive use, pregnancy and the peripartum period, hypercoagulable states, and local infection or trauma. The headache is typically progressive and may have features of elevated intracranial pressure. Diagnosis requires a high index of suspicion, as the presentation is variable and may mimic other conditions. MR venography or CT venography demonstrates absence of flow in affected sinuses. Treatment with anticoagulation is indicated even when hemorrhagic venous infarction is present, as the hemorrhage results from venous congestion rather than arterial rupture. Prognosis is generally favorable with appropriate treatment.

<image>Panel A: Giant cell arteritis clinical features including age, headache, jaw claudication, and vision loss with ESR/CRP and temporal artery biopsy findings. Panel B: Idiopathic intracranial hypertension demographics, symptoms, papilledema appearance, and treatment ladder from weight loss to shunting. Panel C: Spontaneous intracranial hypotension orthostatic headache pattern, MRI findings of sagging brain and pachymeningeal enhancement, and epidural blood patch procedure. Panel D: Cerebral venous thrombosis risk factors, clinical presentation, MRV/CTV appearance, and anticoagulation rationale.</image>

IX. Thunderclap Headache

Thunderclap headache is defined by its temporal profile: a severe headache that reaches maximum intensity within one minute of onset, often described as instantaneous. This pattern mandates emergency evaluation because it may represent subarachnoid hemorrhage, a life-threatening condition where early diagnosis dramatically affects outcome. The approach to thunderclap headache is driven by the principle that subarachnoid hemorrhage must be excluded before any other diagnosis can be entertained, regardless of how typical the presentation may seem for a benign cause.

The differential diagnosis of thunderclap headache extends well beyond subarachnoid hemorrhage, though SAH remains the most critical to exclude. Cerebral venous thrombosis can present with thunderclap onset and requires venography for diagnosis. Arterial dissection of the carotid or vertebral arteries may cause sudden severe headache, often with neck pain and sometimes with Horner syndrome. Pituitary apoplexy from hemorrhage into a pituitary adenoma produces thunderclap headache with visual field deficits and ophthalmoplegia from chiasmal and cavernous sinus involvement. Reversible cerebral vasoconstriction syndrome presents with recurrent thunderclap headaches. Hypertensive emergency with marked blood pressure elevation can cause severe sudden headache. Primary thunderclap headache is a diagnosis of exclusion made only after thorough investigation has excluded all dangerous etiologies.

Evaluation of thunderclap headache follows a structured protocol designed to maximize sensitivity for subarachnoid hemorrhage. Non-contrast CT of the head is the first test and detects subarachnoid blood in approximately 95 percent of cases when performed within 6 hours of headache onset. Sensitivity declines substantially after 6 hours as blood is cleared and diluted by cerebrospinal fluid. When CT is negative but clinical suspicion persists, lumbar puncture is mandatory to exclude subarachnoid hemorrhage. Xanthochromia, the yellowish discoloration of cerebrospinal fluid supernatant from bilirubin, distinguishes true subarachnoid hemorrhage from traumatic tap and requires spectrophotometry for reliable detection. CT angiography or MR angiography evaluates for aneurysm, dissection, and venous thrombosis. MRI may demonstrate parenchymal lesions not visible on CT.

Reversible cerebral vasoconstriction syndrome deserves particular attention as an increasingly recognized cause of thunderclap headache. The syndrome is characterized by recurrent thunderclap headaches over days to weeks, often triggered by sexual activity, exertion, Valsalva maneuver, or emotional stress. Vasoconstrictive substances including sympathomimetics, triptans, and selective serotonin reuptake inhibitors, as well as the postpartum state, are associated triggers. Cerebral angiography or CT angiography demonstrates multifocal segmental vasoconstriction that reverses spontaneously over 1 to 3 months. Despite the typically benign course, complications including posterior reversible encephalopathy syndrome, ischemic stroke, and convexity subarachnoid hemorrhage can occur. Management includes removal of precipitating factors and calcium channel blockers for symptom control.

<image>Panel A: Thunderclap headache definition with time-intensity curve and clinical urgency emphasizing SAH exclusion. Panel B: Differential diagnosis including SAH, CVT, dissection, pituitary apoplexy, RCVS, and hypertensive emergency with distinguishing features. Panel C: Evaluation protocol showing CT timing, sensitivity decline, LP indications, xanthochromia interpretation, and vascular imaging. Panel D: RCVS features including trigger factors, recurrent thunderclap pattern, angiographic findings, potential complications, and management.</image>

X. Special Populations

Headache management in pregnancy requires careful consideration of both efficacy and fetal safety across trimesters. Migraine often improves during pregnancy, particularly during the second and third trimesters, due to stable high estrogen levels. When treatment is required, acetaminophen is the safest analgesic throughout pregnancy. NSAIDs may be used in the second trimester but should be avoided in the first trimester due to potential teratogenicity and in the third trimester due to risk of premature ductus arteriosus closure. Triptans are generally avoided, particularly in the first trimester, though registry data are somewhat reassuring. Red flags in pregnant patients include the standard secondary headache warnings plus additional concerns for preeclampsia and cerebral venous thrombosis, both of which have increased incidence during pregnancy. Preventive options include propranolol at low doses and magnesium supplementation. Valproate is absolutely contraindicated.

Pediatric headache, particularly migraine, differs in presentation from adult migraine in several important ways. Headache duration may be shorter, meeting criteria at only 1 to 2 hours rather than the 4-hour minimum for adults. Location is more commonly bilateral rather than unilateral. Pallor and abdominal symptoms may be prominent. Childhood periodic syndromes including cyclic vomiting syndrome, abdominal migraine, and benign paroxysmal vertigo are migraine precursors that may evolve into typical migraine with advancing age. Treatment emphasizes behavioral approaches, adequate sleep, regular meals, and hydration, with ibuprofen and acetaminophen as first-line acute treatments. Triptans are approved for adolescents and have been used in younger children. The same red flags for secondary headache apply, with particularly high concern for posterior fossa tumors in young children presenting with morning headache, vomiting, and cerebellar signs.

Elderly patients presenting with new headache require heightened vigilance for secondary causes. Giant cell arteritis should be considered in any patient over 50 with new headache, and erythrocyte sedimentation rate and C-reactive protein should be checked with a low threshold for temporal artery biopsy. Secondary headaches from mass lesions, subdural hematoma, and medication side effects are more common than in younger populations. When primary headache treatment is indicated, medications should be started at lower doses with slower titration given altered pharmacokinetics and increased sensitivity to adverse effects. Drug interactions warrant careful review, as polypharmacy is common. Hypnic headache is a rare primary headache disorder specific to the elderly, presenting as dull headache that awakens the patient from sleep at a consistent time nightly, responding well to caffeine before bed or lithium.

Post-traumatic headache develops within 7 days of head injury and may persist for months to years. The headache phenotype often resembles migraine or tension-type headache and should be treated according to the phenotype. Acute post-traumatic headache resolves within 3 months, while persistent post-traumatic headache continues beyond this point. Co-occurring symptoms are common and include cognitive complaints, mood symptoms, dizziness, and sleep disturbance, collectively termed post-concussion syndrome. Management addresses the headache itself with standard approaches while also managing associated symptoms. Prognosis is generally favorable, with most patients improving over months, though a minority develop chronic headache.

<image>Panel A: Pregnancy headache management showing medication safety by trimester, red flags including preeclampsia and CVT, and preventive options. Panel B: Pediatric migraine differences from adults including shorter duration, bilateral location, and childhood periodic syndromes as precursors. Panel C: Elderly headache approach emphasizing GCA concern, secondary cause vigilance, careful medication selection, and hypnic headache characteristics. Panel D: Post-traumatic headache definition, phenotype-based treatment approach, associated post-concussion symptoms, and recovery trajectory.</image>

Summary

• Primary headaches including migraine, tension-type, and cluster headaches are diagnosed clinically, while secondary headaches arise from underlying pathology requiring specific treatment
• The SNOOP mnemonic captures red flags: systemic symptoms, neurological signs, sudden onset, older onset, and pattern change or progression
• Migraine diagnostic criteria require five attacks lasting 4-72 hours with specific pain characteristics plus nausea/vomiting or photophobia and phonophobia
• Acute migraine treatment progresses from NSAIDs for mild attacks to triptans for moderate-severe, with gepants and ditans as alternatives when triptans are contraindicated
• Migraine prevention is indicated for 4 or more headache days monthly, with options including propranolol, topiramate, amitriptyline, and CGRP monoclonal antibodies
• Tension-type headache is distinguished from migraine by bilateral pressing pain, mild-moderate intensity, no activity aggravation, and absence of nausea
• Cluster headache causes severe unilateral orbital pain with autonomic features, treated acutely with oxygen and sumatriptan and preventively with verapamil
• Medication overuse headache occurs with more than 10 triptan or opioid days monthly or 15 analgesic days, treated by withdrawal with bridging
• Giant cell arteritis in patients over 50 with new headache requires immediate high-dose steroids to prevent blindness
• Thunderclap headache mandates CT followed by lumbar puncture if negative to exclude subarachnoid hemorrhage

Key Terms

This content is subject to the MIT License. © 2024–2026 Hibbert School of Medicine.

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