Headache¶
Chapter 17 | Part 2: Cardinal Manifestations and Presentation of Diseases
KEY CLINICAL POINTS¶
- Headache is the most common reason for neurologic consultation and causes more global disability than any other neurologic problem
- Primary headaches (migraine, tension-type, cluster) are disorders themselves; secondary headaches are caused by underlying conditions
- Red flag symptoms requiring urgent evaluation include sudden onset, worst headache ever, fever with neck stiffness, abnormal neurologic exam, and onset after age 55
- The trigeminovascular system (trigeminal innervation of intracranial vessels and dura) is the key anatomical substrate for primary headache disorders
- Medication-overuse headache is a common cause of chronic daily headache and requires identification and management of analgesic overuse
1. DEFINITION & OVERVIEW¶
Headache is among the most common reasons patients seek medical attention and is responsible for more disability globally than any other neurologic problem. Diagnosis and management are based on careful clinical evaluation augmented by understanding of the anatomy, physiology, and pharmacology of nervous system pathways mediating various headache syndromes.
Common Causes of Headache¶
| Primary Headache Type | % | Secondary Headache Type | % |
|---|---|---|---|
| Tension-type | 69 | Systemic infection | 63 |
| Migraine | 16 | Head injury | 4 |
| Idiopathic stabbing | 2 | Vascular disorders | 1 |
| Exertional | 1 | Subarachnoid hemorrhage | <1 |
| Cluster | 0.1 | Brain tumor | 0.1 |
1.1 Classification System¶
The International Headache Society (IHS) classification characterizes headache disorders as PRIMARY or SECONDARY: - PRIMARY HEADACHES: Headache and its associated features form the disorder itself (e.g., migraine, tension-type, cluster headache) - SECONDARY HEADACHES: Headaches caused by exogenous disorders (e.g., infection, trauma, vascular disorders, tumors) Primary headache often results in considerable disability and decreased quality of life. Mild secondary headache (e.g., with upper respiratory infections) is common but rarely worrisome. Life-threatening headache is relatively uncommon but requires vigilance for recognition.
2. ANATOMY AND PHYSIOLOGY OF HEADACHE¶
Pain perception in headache may arise from stimulation of peripheral nociceptors (normal physiologic response) or from damage/inappropriate activation of pain-producing pathways in the peripheral or central nervous system. Headache may originate from either or both mechanisms.
2.1 Pain-Producing Cranial Structures¶
STRUCTURES THAT PRODUCE PAIN: - Scalp - Meningeal arteries - Dural sinuses - Falx cerebri - Proximal segments of large pial arteries STRUCTURES THAT DO NOT PRODUCE PAIN: - Ventricular ependyma - Choroid plexus - Pial veins - Most brain parenchyma
2.2 Key Structures in Primary Headache¶
The key structures involved in primary headache include: 1. Large intracranial vessels and dura mater with peripheral terminals of the trigeminal nerve (TRIGEMINOVASCULAR SYSTEM) 2. Caudal portion of trigeminal nucleus extending into dorsal horns of upper cervical spinal cord (C1-C2) receiving input from first and second cervical nerve roots (TRIGEMINOCERVICAL COMPLEX) 3. Rostral pain-processing regions: ventroposteromedial thalamus and cortex 4. Pain-modulatory systems: hypothalamus and brainstem structures that modulate trigeminal nociceptor input and influence vegetative functions
2.3 Cranial Autonomic Symptoms¶
Cranial autonomic symptoms are prominent in trigeminal autonomic cephalalgias (TACs) and often seen in migraine: - Lacrimation - Conjunctival injection - Nasal congestion - Rhinorrhea - Periorbital swelling - Aural fullness - Ptosis These symptoms reflect activation of cranial parasympathetic pathways. Vascular changes in migraine and cluster headache are secondary (driven by autonomic systems), NOT causative. These can be mistaken for cranial sinus inflammation. IMPORTANT: Migraine and primary headache disorders are NOT "vascular headaches" - they do not reliably manifest vascular changes and treatment outcomes cannot be predicted by vascular effects. Migraine is a BRAIN DISORDER.
3. CLINICAL EVALUATION OF ACUTE, NEW-ONSET HEADACHE¶
Patients presenting with new, severe headache have a differential diagnosis quite different from those with recurrent headaches over years. In new-onset severe headache, the probability of finding a potentially serious cause is considerably greater. These patients require prompt evaluation and appropriate treatment.
Headache Symptoms Suggesting Serious Underlying Disorder (Red Flags)¶
| Warning Symptom/Sign |
|---|
| Sudden-onset headache |
| First severe headache |
| Vomiting that precedes headache |
| Subacute worsening over days or weeks |
| Pain induced by bending, lifting, cough |
| Pain that disturbs sleep or presents immediately upon awakening |
| Known systemic illness |
| "Worst" headache ever |
| Onset after age 55 |
| Fever or unexplained systemic signs |
| Abnormal neurologic examination |
| Pain associated with local tenderness (e.g., temporal artery region) |
3.1 Serious Causes to Consider¶
- Meningitis
- Subarachnoid hemorrhage
- Epidural or subdural hematoma
- Glaucoma
- Brain tumor
- Purulent sinusitis
3.2 Essential Evaluation Components¶
NEUROLOGIC EXAMINATION: Essential first step IMAGING: CT or MRI of brain indicated for: - Abnormal neurologic examination - Recent-onset headache history - CT and MRI appear equally sensitive for initial screening LUMBAR PUNCTURE: Required in some circumstances unless benign etiology otherwise established GENERAL EVALUATION: - Cranial arteries by palpation - Cervical spine: passive head movement effects and imaging - Cardiovascular and renal status: blood pressure, urine examination - Eyes: funduscopy, intraocular pressure, refraction - Psychological state: identify comorbidity (depression, anxiety) - not to explain headache but recognize comorbidity
4. SECONDARY HEADACHE DISORDERS¶
Management of secondary headache focuses on diagnosis and treatment of the underlying condition. Secondary headaches may also activate underlying primary headache disorders, complicating management.
4.1 Meningitis¶
CLINICAL FEATURES: - Acute, severe headache - Stiff neck - Fever - Striking accentuation of pain with eye movement DIAGNOSIS: LP is MANDATORY IMPORTANT: Meningitis can be easily mistaken for migraine - cardinal symptoms of pounding headache, photophobia, nausea, and vomiting are frequently present (reflecting underlying biology of some patients).
4.2 Intracranial Hemorrhage¶
SUBARACHNOID HEMORRHAGE: - Acute headache, MAXIMAL in <5 minutes - Severe headache lasting >5 minutes - Stiff neck WITHOUT fever Possible causes: ruptured aneurysm, arteriovenous malformation, intraparenchymal hemorrhage DIAGNOSTIC CONSIDERATIONS: - May present with headache alone - If hemorrhage is small or below foramen magnum, head CT may be NORMAL - LP may be required for definitive diagnosis of subarachnoid hemorrhage
4.3 Brain Tumor¶
EPIDEMIOLOGY: Approximately 30% of brain tumor patients consider headache their chief complaint. Brain tumor is a RARE cause of isolated headache. CLINICAL FEATURES: - Nondescript headache: intermittent, deep, dull aching of moderate intensity - May worsen with exertion or position change - May be associated with nausea and vomiting - Disturbs sleep in ~10% of patients IMPORTANT: This symptom pattern results from MIGRAINE far more often than brain tumor. SPECIFIC PRESENTATIONS: - Vomiting preceding headache by WEEKS: highly characteristic of POSTERIOR FOSSA tumors - Amenorrhea/galactorrhea with headache: suggests prolactin-secreting pituitary adenoma or polycystic ovary syndrome - New headache in patient with known malignancy: suggests cerebral metastases or carcinomatous meningitis - Abrupt headache after bending, lifting, coughing: consider posterior fossa mass, Chiari malformation, or low CSF volume
4.4 Temporal (Giant Cell) Arteritis¶
EPIDEMIOLOGY: - Inflammatory disorder of arteries frequently involving extracranial carotid circulation - Annual incidence: 77 per 100,000 in age ≥ 50 - Average age of onset: 70 years - Women: 65% of cases COMPLICATIONS: - ~50% of untreated patients develop BLINDNESS (ophthalmic artery involvement) - Ischemic optic neuropathy from giant cell arteritis is the MAJOR cause of rapidly developing bilateral blindness in patients >60 years - Glucocorticoid treatment is EFFECTIVE in preventing blindness PRESENTING SYMPTOMS: - Headache (dominant symptom) - Polymyalgia rheumatica - Jaw claudication - Fever - Weight loss - Malaise and muscle aches HEADACHE CHARACTERISTICS: - May be unilateral or bilateral - Temporal location in 50%, but may involve any cranial aspect - Usually gradual onset over hours; occasionally explosive - Quality: dull and boring (infrequently throbbing) with superimposed stabbing pains - Origin perceived as superficial (external to skull) - Scalp tenderness often marked (brushing hair or resting head on pillow may be impossible) - Usually worse at night - Aggravated by cold exposure PHYSICAL FINDINGS: - Reddened, tender nodules - Red streaking of skin over temporal arteries - Tenderness of temporal or occipital arteries DIAGNOSIS: - ESR often elevated but NORMAL ESR does NOT exclude giant cell arteritis - Temporal artery biopsy TREATMENT: - Prednisone 80 mg daily for first 4-6 weeks when clinical suspicion is high - Initiate treatment immediately after biopsy CAUTION: Migraineurs often report headache improvement with prednisone - interpret therapeutic response carefully.
4.5 Glaucoma¶
CLINICAL PRESENTATION: - Prostrating headache - Nausea and vomiting - Often starts with severe eye pain PHYSICAL EXAMINATION: - Red eye - Fixed, moderately dilated pupil
5. PRIMARY HEADACHE DISORDERS¶
Primary headache disorders manifest as headache and associated features occurring in the absence of any exogenous cause. The most common are migraine, tension-type headache, and trigeminal autonomic cephalalgias (TACs), notably cluster headache. Detailed discussion is in Chapter 441.
6. CHRONIC DAILY OR NEAR-DAILY HEADACHE¶
Chronic daily headache (CDH) applies when a patient experiences headache on 15 days or more per month. CDH is NOT a single entity or diagnosis; it encompasses multiple primary and secondary headache syndromes. Population-based estimates suggest approximately 4% of adults have daily or near-daily headache, presenting considerable disability.
Classification of Daily or Near-Daily Headache¶
| Primary (>4 h daily) | Primary (<4 h daily) | Secondary |
|---|---|---|
| Chronic migraine* | Chronic cluster headache** | Posttraumatic/Head injury |
| Chronic tension-type headache* | Chronic paroxysmal hemicrania | Iatrogenic |
| Hemicrania continua* | SUNCT/SUNA | Postinfectious |
| New daily persistent headache* | Hypnic headache | Inflammatory (Giant cell arteritis, Sarcoidosis, Behçet's) |
| Chronic CNS infection | ||
| Medication-overuse headache* |
6.1 Approach to the Patient¶
STEP 1: Diagnose and treat any secondary headache - Can be challenging when underlying cause triggers worsening of a primary headache STEP 2: For primary headache disorders, diagnose headache type to guide therapy PREVENTIVE TREATMENTS: - Tricyclics (amitriptyline or nortriptyline): up to 1 mg/kg - Start low (10-25 mg daily) - Give 12 hours before expected awakening to avoid morning sleepiness - Very useful for CDH from migraine or tension-type headache - Other preventive medications: - Topiramate - Valproate - Propranolol - Flunarizine (not available in US) - Candesartan - CGRP pathway monoclonal antibodies - CGRP receptor antagonists (gepants)
6.2 Management of Medically Intractable Headache¶
NEWER EFFECTIVE THERAPIES: - CGRP pathway monoclonal antibodies (to CGRP or its receptor): effective and well-tolerated in chronic migraine - CGRP receptor antagonists (gepants): licensed for clinical use NON-INVASIVE NEUROMODULATION: - Single-pulse transcranial magnetic stimulation: modulates thalamic processing - Remote electrical neuromodulation: modulates brainstem mechanisms in migraine - Non-invasive vagal nerve stimulation: shows promise in: - Cluster headache - Chronic paroxysmal hemicrania - Hemicrania continua - Possibly SUNA and SUNCT
7. MEDICATION-RELATED AND MEDICATION-OVERUSE HEADACHE¶
Overuse of analgesic medication for headache can: - Aggravate headache frequency - Markedly impair effect of preventive medicines - Induce refractory daily or near-daily headache (medication-overuse headache) A proportion of patients who stop analgesics will experience substantial improvement. However, even after cessation, many patients continue to have headache (though may feel clinically improved, especially if using opioids or barbiturates). Residual symptoms usually represent the underlying primary headache disorder, most commonly migraine.
7.1 Outpatient Management¶
APPROACH 1 - GRADUAL REDUCTION: - Reduce medication dose by 10% every 1-2 weeks - Maintain medication diary for 1-2 months before cessation to identify scope of problem APPROACH 2 - IMMEDIATE CESSATION: - Possible for some patients if no contraindication BOTH APPROACHES: - Naproxen 500 mg BID (if tolerated) helps relieve residual pain during reduction - NSAID overuse is usually NOT a problem when taken once or twice daily with longer half-life - Once analgesic use substantially reduced, introduce preventive medication - Alternative: commence preventive at same time as analgesic reduction (both approaches supported by controlled trial data) COMMON CAUSE OF TREATMENT FAILURE: Using preventive medication while analgesics continue to be used regularly
7.2 Inpatient Management¶
INDICATIONS FOR HOSPITALIZATION: - Failed outpatient withdrawal efforts - Significant medical conditions (diabetes mellitus, epilepsy) complicating outpatient withdrawal PROTOCOL: Day 1: - Complete medication withdrawal (if no contraindication) - Antiemetics and fluids as required - Clonidine for opioid withdrawal symptoms - For acute intolerable pain: Aspirin 1 g IV (not approved in US) - IM chlorpromazine at night (ensure adequate hydration) Days 3-5: - As withdrawn substance effects wear off, initiate IV dihydroergotamine (DHE) - DHE: every 8 hours for 5 consecutive days - DO NOT stop short if headache settles - DHE can induce significant remission allowing preventive treatment establishment ANTIEMETICS WITH DHE: - Serotonin 5-HT3 receptor antagonists: ondansetron or granisetron - Neurokinin receptor antagonist: aprepitant - Domperidone (not available in US): oral or suppository - very helpful - Avoid sedating or side effect-prone antiemetics ALTERNATIVE PROTOCOLS: - 7-10 day course of IV lidocaine - IV divalproex sodium - IV eptinezumab (CGRP antagonist)
8. NEW DAILY PERSISTENT HEADACHE (NDPH)¶
NDPH is a clinically distinct syndrome with important secondary causes. It presents with headache on most or all days, with clear recall of onset moment.
Differential Diagnosis of New Daily Persistent Headache¶
| Primary | Secondary |
|---|---|
| Migrainous-type | Subarachnoid hemorrhage |
| Featureless (tension-type) | Low cerebrospinal fluid (CSF) volume headache |
| Raised CSF pressure headache | |
| Posttraumatic headache* | |
| Chronic meningitis |
8.1 Clinical Presentation¶
- Usually abrupt onset (but may be gradual; up to 3 days evolution proposed as upper limit)
- Patient typically recalls exact day and circumstances of onset
- New, persistent head pain does not remit FIRST PRIORITY: Distinguish primary from secondary causes
- Subarachnoid hemorrhage is most serious secondary cause - must be excluded
8.2 Secondary NDPH - Low CSF Volume Headache¶
CLINICAL FEATURES: - Positional headache: begins when patient sits/stands upright, resolves upon reclining - Occipitofrontal location - Usually dull ache but may be throbbing CHRONIC LOW CSF VOLUME PATTERN: - Headache present from one day to next - Generally NOT present on waking but worsens during day - Recumbency improves headache within minutes - Pain returns within minutes to an hour when upright position resumed CAUSES: - Most common: CSF leak following LP (post-LP headache) - Usually begins within 48 hours, may be delayed up to 12 days - Incidence: 10-30% - Epidural injection - Vigorous Valsalva maneuver (lifting, straining, coughing, clearing eustachian tubes, multiple orgasms) - Spontaneous CSF leaks (diagnosis should be considered even without obvious index event) IMPORTANT: As time passes from index event, postural nature may become less apparent. Cases diagnosed years after index event have been recognized. CSF PRESSURE: Usually 0-50 mm CSF, but pressures as high as 140 mm CSF have been noted with documented leak (symptoms result from low VOLUME, not low pressure) DIFFERENTIAL: Postural orthostatic tachycardia syndrome (POTS) can present similarly
8.3 Diagnosis of Low CSF Volume Headache¶
IMAGING: - Initial study: MRI with gadolinium - Finding: Diffuse meningeal enhancement - so typical that diagnosis is established in appropriate clinical context - Chiari malformations may be noted - posterior fossa decompression surgery is NOT indicated and usually worsens headache ADDITIONAL STUDIES: - Spinal MRI with T2 weighting: may reveal leak - Spinal MRI: may demonstrate spinal meningeal cysts - CT myelography (preferably lateral decubitus digital subtraction): to identify leak source - 111In-DTPA CSF studies: may demonstrate early tracer emptying into bladder or slow tracer progress across brain (rarely employed now)
8.4 Treatment of Low CSF Volume Headache¶
INITIAL TREATMENT: - Bed rest - Caffeinated beverages may provide temporary relief PERSISTENT PAIN: - IV caffeine: 500 mg in 500 mL saline over 2 hours (can be very effective) - Obtain ECG before administration to screen for arrhythmia - Administer at least TWO caffeine infusions before further tests to identify leak - IV caffeine is safe and can be curative, sparing need for further investigations IF IV CAFFEINE UNSUCCESSFUL: - Abdominal binder - Autologous blood patch (if leak identified) - usually curative - For post-LP headache: blood patch at LP site (empirically determined) INTRACTABLE HEADACHE: - Oral theophylline (may take months to be effective) - CSF-venous fistulas require closure
8.5 Raised CSF Pressure Headache¶
IDIOPATHIC INTRACRANIAL HYPERTENSION (Pseudotumor Cerebri): ASSOCIATIONS: - Obesity - Female gender - Pregnancy (occasionally) CLINICAL FEATURES: - Generalized headache present on awakening - Improves as day goes on - Worsens with recumbency - Transient visual obscurations (frequent, may occur when headaches most severe) - Can occur without visual problems (even with normal fundi) DIAGNOSIS: - Straightforward when papilledema present - Must consider even without funduscopic changes - Perform formal visual field testing even without overt ophthalmic involvement EVALUATION: - MRI including MR venogram (initial study) - LP for CSF pressure measurement (if no contraindications) - Measure when patient is symptomatic - Assess response to removal of 20-30 mL CSF - Elevated opening pressure + headache improvement after CSF removal = diagnostic (in absence of fundal changes) ADDITIONAL CONSIDERATIONS: - Partial cerebral venous sinus obstructions found in small number of cases - Persistently raised ICP can trigger chronic migraine syndrome - Other causes of morning/nocturnal headache: obstructive sleep apnea, poorly controlled hypertension TREATMENT: - First-line: Acetazolamide 250-500 mg BID (headache may improve within weeks) - Institute weight loss plan when required - Second-line: Topiramate - Actions: carbonic anhydrase inhibition, weight loss, neuronal membrane stabilization (via phosphorylation pathway effects) - Severely disabled patients unresponsive to medical treatment: - Intracranial pressure monitoring - May require shunting
8.6 Posttraumatic Headache¶
A traumatic event can trigger a headache process lasting months or years. BROAD DEFINITION OF TRAUMA: - Head injury - Infectious episodes (viral meningitis, flu-like illness, parasitic infection) - Carotid dissection - Subarachnoid hemorrhage - Intracranial surgery ASSOCIATED SYMPTOMS: - Dizziness - Vertigo - Impaired memory FINDINGS: - Neurologic examination: typically normal - CT/MRI: usually unrevealing - Consider chronic subdural hematoma (can mimic this disorder) UNDERLYING THEME: Traumatic event involving pain-producing meninges can trigger headache process lasting years.
8.7 Other Causes of NDPH¶
POSTINFECTIOUS NDPH: - One-third of NDPH patients report onset after transient flu-like illness - Features: fever, neck stiffness, photophobia, marked malaise - Evaluation typically reveals no apparent cause - No convincing evidence for persistent Epstein-Barr virus role - Complicating factor: many patients undergo LP during acute illness (consider iatrogenic low CSF volume) - Post-COVID-19 onset of NDPH is now well documented TREATMENT OF NDPH: - Largely empirical, directed at headache phenotype - Options with reported benefit: - Tricyclic antidepressants (amitriptyline) - Anticonvulsants: topiramate, valproate, gabapentin - Candesartan - CGRP pathway blockers (monoclonal antibodies and gepants) - Phenelzine (MAO inhibitor) - in carefully selected patients PROGNOSIS: Headache usually resolves within 3-5 years but can be quite disabling
9. PRIMARY CARE AND HEADACHE MANAGEMENT¶
Most patients with headache will be seen first in a primary care setting. The challenging task is to identify the very few worrisome secondary headaches from the great majority of primary and less dangerous secondary headaches.
9.1 Approach in Primary Care¶
ABSENT WARNING SIGNS: - Treat when diagnosis is established - Investigation should focus on: - Identifying worrisome causes - Helping patient gain confidence if no primary headache diagnosis can be made FOLLOW-UP CARE: - Essential to identify progress against headache complaint - Not all headaches respond to treatment - Worrisome headaches generally will progress and become easier to identify KEY POINT: >90% of patients presenting to primary care with headache complaint will have MIGRAINE
9.2 Indications for Specialist Referral¶
Refer patients who: - Do not have a clear diagnosis - Have a primary headache disorder OTHER than migraine or tension-type headache - Are unresponsive to two or more standard therapies for the considered headache type PRACTICAL CONSIDERATIONS: - Referral threshold determined by: - Experience of primary care physician in headache medicine - Availability of secondary care options
10. KEY POINTS & CLINICAL PEARLS¶
10.1 Diagnostic Pearls¶
- New-onset severe headache has different differential diagnosis than recurrent headache - higher probability of serious cause
- Meningitis can mimic migraine (pounding headache, photophobia, nausea, vomiting) - LP is mandatory with fever and neck stiffness
- Normal head CT does NOT exclude subarachnoid hemorrhage - LP may be required
- Normal ESR does NOT exclude giant cell arteritis
- Diffuse meningeal enhancement on gadolinium MRI is diagnostic of low CSF volume in appropriate context
- Brain tumor is a RARE cause of isolated headache - migraine far more common cause of similar symptoms
- Migraine is the diagnosis in >90% of primary care headache presentations
10.2 Treatment Pearls¶
- Treat secondary headache cause first, but recognize that treatment may be ineffective until underlying primary headache addressed
- Common cause of treatment failure: using preventive medication while analgesics continue regularly
- For giant cell arteritis, start prednisone 80 mg immediately after biopsy when clinical suspicion is high - don't wait for results
- For low CSF volume headache, try at least TWO IV caffeine infusions before invasive investigation for leak
- IV DHE protocol: every 8 hours for 5 consecutive days - don't stop early even if headache resolves
10.3 Pathophysiology Pearls¶
- Migraine is a BRAIN disorder, not a vascular disorder
- Cranial autonomic symptoms in headache are SECONDARY to parasympathetic activation, not causative
- Autonomic symptoms can be mistaken for sinus inflammation leading to inappropriate treatment
- Low CSF volume headache results from low VOLUME, not necessarily low pressure (pressure can be up to 140 mm CSF with documented leak)