Clinical Approach to Headache
Comprehensive Practical Framework1. Symptom Overview
Understanding the clinical significance and classification of Headache
Headache is among the most common symptoms encountered in clinical practice, affecting approximately 50% of the global adult population at least once per year. It accounts for roughly 2-4% of all emergency department visits and is the fourth leading cause of disability worldwide according to the Global Burden of Disease Study. Approximately 15% of the population experiences migraine, while tension-type headache affects up to 80% of adults at some point in their lives. Despite its prevalence, headache remains frequently under-diagnosed and under-treated, with significant impact on quality of life and economic productivity.
Definition
Headache is defined as pain located anywhere in the region of the head or upper neck. It arises from activation of pain-sensitive structures including the meninges, blood vessels, muscles, periosteum, and cranial nerves. Notably, the brain parenchyma itself lacks pain receptors and cannot generate pain directly. The International Classification of Headache Disorders (ICHD-3) divides headaches into primary disorders (where headache itself is the disease) and secondary disorders (where headache is a symptom of another condition).
Classification by Duration
| Category | Duration | Common Causes | Clinical Significance |
|---|---|---|---|
| Acute (New-Onset) | First episode or less than 4 weeks | Viral illness, subarachnoid hemorrhage, meningitis, first migraine, hypertensive emergency | Requires careful evaluation to exclude secondary causes; “first or worst” headache is a red flag |
| Subacute | 4 weeks to 3 months | Intracranial mass, subdural hematoma, giant cell arteritis, medication overuse headache | Progressive pattern suggests evolving pathology; warrants imaging if features change |
| Chronic | Greater than 3 months | Chronic migraine, chronic tension-type headache, medication overuse headache, new daily persistent headache | Primary headache disorders predominate; focus on identifying triggers and preventing medication overuse |
Classification by Etiology: Primary versus Secondary
Primary Headache Disorders
Headache is the disease itself, with no underlying structural or systemic cause. These represent approximately 90% of all headaches.
- Migraine — with or without aura
- Tension-type headache — episodic or chronic
- Trigeminal autonomic cephalalgias — including cluster headache
- Other primary headaches — cough headache, exertional headache, sex-related headache
Secondary Headache Disorders
Headache is a symptom of an identifiable underlying cause. These represent approximately 10% but include life-threatening conditions.
- Vascular — subarachnoid hemorrhage, stroke, arterial dissection
- Infectious — meningitis, encephalitis, sinusitis
- Structural — mass lesion, hydrocephalus, Chiari malformation
- Metabolic/Toxic — carbon monoxide, hypoxia, medication overuse
Classification by Character
| Quality | Description | Typical Associations |
|---|---|---|
| Throbbing/Pulsating | Pain that beats in rhythm with the pulse | Migraine, vascular headaches, fever-associated headache |
| Pressing/Tightening | Band-like pressure, non-pulsating | Tension-type headache, cervicogenic headache |
| Sharp/Stabbing | Brief, intense, ice-pick like jabs | Primary stabbing headache, trigeminal neuralgia, cluster headache |
| Burning | Constant burning sensation | Neuropathic pain, occipital neuralgia, post-herpetic neuralgia |
| Explosive/Thunderclap | Maximal intensity within seconds to one minute | Subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, pituitary apoplexy — always a red flag |
Classification by Pattern and Timing
| Pattern | Description | Suggests |
|---|---|---|
| Morning predominance | Headache present on waking, improves through day | Raised intracranial pressure, sleep apnea, medication overuse, hypertension |
| Evening predominance | Builds through the day, worst in evening | Tension-type headache, eye strain, cervicogenic headache |
| Nocturnal awakening | Wakes patient from sleep at consistent times | Cluster headache (often 1-2 hours after sleep onset), hypnic headache, raised intracranial pressure |
| Positional | Worse when lying down or standing up | Lying down worse: raised intracranial pressure; Standing worse: intracranial hypotension (CSF leak) |
| Exertional | Triggered by physical exertion, coughing, straining | Primary exertional headache, but must exclude subarachnoid hemorrhage and Chiari malformation |
| Menstrual | Occurs predictably with menstrual cycle | Menstrual migraine (typically perimenstrual, days -2 to +3) |
Classification by Location
| Location | Typical Causes | Clinical Notes |
|---|---|---|
| Unilateral | Migraine, cluster headache, trigeminal neuralgia, hemicrania continua | Strictly unilateral without side shift suggests trigeminal autonomic cephalalgia |
| Bilateral | Tension-type headache, medication overuse, systemic illness | Most common pattern for tension-type headache |
| Frontal | Tension-type, sinusitis, frontal sinus disease | True sinus headache is overdiagnosed; most “sinus headaches” are migraine |
| Occipital/Posterior | Cervicogenic headache, occipital neuralgia, posterior fossa lesion | Check for neck stiffness and range of motion |
| Periorbital/Retro-orbital | Cluster headache, migraine, acute glaucoma, cavernous sinus pathology | Associated autonomic features (tearing, rhinorrhea) suggest cluster headache |
Key Concept: The “Big Four” Primary Headaches
Four primary headache disorders account for the vast majority of headache presentations:
- Migraine — approximately 15% of population; episodic, often unilateral, pulsating, with nausea and photophobia
- Tension-type headache — approximately 40% lifetime prevalence; bilateral, pressing, mild-to-moderate intensity
- Medication overuse headache — affects 1-2% of population; daily or near-daily headache in patients using acute medications more than 10-15 days per month
- Cluster headache — approximately 0.1% of population; strictly unilateral, severe, with autonomic features, occurring in clusters
Together with secondary causes, a systematic approach to these entities allows accurate diagnosis in the majority of patients.
2. Pathophysiology and Mechanisms
Understanding the underlying mechanisms of Headache
Understanding headache pathophysiology is essential for rational diagnosis and treatment. The brain parenchyma itself is insensitive to pain; headache arises from activation of pain-sensitive structures including the meninges (particularly the dura mater), cerebral blood vessels, cranial nerves (especially the trigeminal nerve), upper cervical nerve roots, and pericranial muscles. The trigeminovascular system plays a central role in most primary headache disorders, while secondary headaches result from direct activation of nociceptors by inflammation, traction, compression, or vascular disturbance.
Pain-Sensitive Structures of the Head
| Structure | Innervation | Clinical Relevance |
|---|---|---|
| Dura mater and dural sinuses | Trigeminal nerve (V1 primarily), upper cervical roots | Traction or inflammation causes referred pain to frontal and vertex regions |
| Cerebral arteries (proximal) | Trigeminal nerve afferents | Vasodilation and neurogenic inflammation central to migraine |
| Meningeal arteries | Trigeminal nerve (middle meningeal artery via V3) | Epidural hematoma causes severe ipsilateral headache |
| Pericranial muscles | Trigeminal motor, facial nerve, cervical roots | Muscle tension contributes to tension-type headache |
| Extracranial arteries | Trigeminal and cervical afferents | Temporal artery inflammation in giant cell arteritis |
| Upper cervical structures (C1-C3) | Upper cervical nerve roots | Convergence with trigeminal nucleus explains referred pain patterns |
The Trigeminovascular System
| Component | Structure | Function |
|---|---|---|
| Peripheral Receptors | Trigeminal nerve endings around meningeal vessels | Detect mechanical, chemical, and inflammatory stimuli; release calcitonin gene-related peptide (CGRP) |
| Afferent Pathway | Trigeminal nerve (primarily V1 ophthalmic division) | Transmit pain signals from intracranial structures to brainstem |
| First Relay | Trigeminal nucleus caudalis (in medulla) | Receives convergent input from trigeminal and upper cervical afferents; explains referred pain patterns |
| Second Relay | Thalamus (ventral posteromedial nucleus) | Relays pain to cortical areas; modulated by descending pathways |
| Cortical Processing | Somatosensory cortex, insular cortex, anterior cingulate | Conscious perception of pain; emotional and autonomic responses |
| Modulation Centers | Periaqueductal gray, rostral ventromedial medulla | Descending pain modulation; dysfunction may contribute to chronic headache |
How Different Conditions Cause Headache
| Condition | Mechanism | Treatment Implication |
|---|---|---|
| Migraine | Cortical spreading depression triggers trigeminal activation; neurogenic inflammation and CGRP release cause vasodilation and sensitization; hypothalamic and brainstem nuclei modulate attack threshold | Triptans block CGRP release and cause vasoconstriction; CGRP monoclonal antibodies prevent attacks; preventive medications raise attack threshold |
| Tension-type headache | Peripheral myofascial nociception from pericranial muscles; central sensitization in chronic form; stress and postural factors contribute | NSAIDs for acute episodes; tricyclic antidepressants for prevention address central sensitization; physical therapy addresses peripheral factors |
| Cluster headache | Hypothalamic activation (circadian pacemaker) triggers trigeminal-autonomic reflex; parasympathetic outflow causes autonomic features; trigeminal activation causes pain | High-flow oxygen aborts attacks via hypothalamic and vasoconstrictor effects; verapamil prevents by modulating hypothalamic activity; triptans effective acutely |
| Medication overuse headache | Frequent analgesic or triptan use causes receptor down-regulation, increased cortical excitability, and impaired descending pain modulation; creates cycle of headache and medication use | Withdrawal of overused medication is essential; bridge therapy during withdrawal; preventive medication started simultaneously |
| Subarachnoid hemorrhage | Blood in subarachnoid space directly irritates meninges; rapid rise in intracranial pressure stretches pain-sensitive structures; vasospasm may cause secondary ischemia | Neurosurgical intervention to secure aneurysm; nimodipine for vasospasm prevention; emergency management of raised intracranial pressure |
| Meningitis | Infection causes meningeal inflammation; inflammatory mediators activate trigeminal nociceptors; raised intracranial pressure from edema and impaired cerebrospinal fluid absorption | Empiric antibiotics immediately; dexamethasone reduces inflammation and improves outcomes in bacterial meningitis |
| Intracranial hypertension | Elevated pressure causes traction on dura and vessels; distortion of pain-sensitive structures; papilledema results from impaired axoplasmic flow | Treat underlying cause; acetazolamide reduces cerebrospinal fluid production; therapeutic lumbar puncture provides temporary relief |
| Intracranial hypotension (cerebrospinal fluid leak) | Low cerebrospinal fluid volume causes brain sag; traction on meninges and vessels when upright; compensatory venous engorgement | Conservative measures (bed rest, hydration, caffeine); epidural blood patch seals dural tear if conservative measures fail |
| Giant cell arteritis | Granulomatous inflammation of medium and large arteries; temporal artery involvement causes scalp tenderness; ophthalmic artery involvement risks blindness | High-dose corticosteroids started immediately (do not wait for biopsy); prevents irreversible vision loss |
| Cervicogenic headache | Upper cervical pathology (facet joints, discs, muscles) activates C1-C3 afferents that converge with trigeminal nucleus; pain referred to head | Physical therapy, nerve blocks; treating cervical source addresses referred head pain |
Key Neurotransmitters and Mediators
Calcitonin Gene-Related Peptide (CGRP)
Location: Trigeminal ganglion neurons and their terminals
Role: Potent vasodilator; promotes neurogenic inflammation; levels elevated during migraine attacks
Clinical relevance: CGRP receptor antagonists (gepants) and monoclonal antibodies against CGRP or its receptor are effective migraine treatments
Serotonin (5-HT)
Location: Brainstem raphe nuclei; peripheral receptors on vessels
Role: Modulates trigeminovascular transmission; 5-HT1B/1D receptor activation inhibits CGRP release and causes vasoconstriction
Clinical relevance: Triptans are 5-HT1B/1D agonists; low serotonin states may predispose to migraine
Dopamine
Location: Hypothalamus, brainstem nuclei
Role: Hypersensitivity may explain premonitory symptoms (yawning, nausea, mood changes); modulates hypothalamic function
Clinical relevance: Dopamine antagonists (metoclopramide, prochlorperazine) effective for acute migraine and associated nausea
Glutamate
Location: Excitatory synapses throughout pain pathways
Role: Primary excitatory neurotransmitter; cortical spreading depression involves glutamate wave; central sensitization mediated by NMDA receptors
Clinical relevance: Topiramate and valproate (preventive medications) have anti-glutamatergic effects
Nitric Oxide
Location: Vascular endothelium, neurons
Role: Potent vasodilator; nitric oxide donors trigger migraine attacks in susceptible individuals; role in maintaining chronic pain
Clinical relevance: Explains why nitroglycerin triggers headache; potential target for future therapies
Substance P
Location: Trigeminal neurons, released with CGRP
Role: Promotes neurogenic inflammation; increases vascular permeability; involved in pain transmission
Clinical relevance: Contributes to peripheral sensitization; target of some experimental therapies
Cortical Spreading Depression and Migraine Aura
Understanding Cortical Spreading Depression
Cortical spreading depression (CSD) is a slowly propagating wave of neuronal and glial depolarization that spreads across the cortex at approximately 3-5 millimeters per minute. This explains the gradual spread of visual aura symptoms over 20-30 minutes (corresponding to movement across the visual cortex).
Sequence of Events:
- Initial neuronal hyperexcitability and depolarization
- Release of potassium, glutamate, and ATP into extracellular space
- Wave of depolarization spreads across cortex
- Followed by prolonged neuronal suppression
- Activation of trigeminal afferents in meninges triggers headache phase
Central Sensitization in Chronic Headache
Why Chronic Headache Becomes Harder to Treat
Repeated activation of pain pathways leads to central sensitization — a state of heightened excitability in central pain neurons. This manifests clinically as:
- Allodynia — pain from normally non-painful stimuli (e.g., combing hair, wearing glasses during migraine)
- Hyperalgesia — exaggerated pain response to painful stimuli
- Expansion of receptive fields — pain felt over larger area than initially
- Reduced descending inhibition — impaired ability to suppress pain signals
Central sensitization explains why chronic headache disorders are more difficult to treat than episodic forms and why preventive therapy is essential.
Often Overlooked Mechanism: The Trigeminocervical Complex
The trigeminal nucleus caudalis extends into the upper cervical spinal cord, where it receives convergent input from both trigeminal afferents (supplying the head) and cervical afferents (C1-C3, supplying the upper neck). This trigeminocervical complex explains several important clinical observations:
- Why cervical spine pathology causes referred pain to the head (cervicogenic headache)
- Why migraine pain often extends into the neck
- Why occipital nerve blocks can be effective for migraine
- Why posture and neck position affect headache
This anatomical convergence means that examining the cervical spine is important in all headache patients, not just those with obvious neck symptoms.
3. History Taking
A comprehensive approach to eliciting the Headache history
Red Flags — Require Urgent Evaluation
- Thunderclap onset — maximal intensity within seconds to one minute suggests subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, or pituitary apoplexy
- “First or worst” headache — new headache type or worst headache of life requires urgent evaluation
- Progressive worsening over days to weeks — suggests mass lesion, subdural hematoma, or chronic meningitis
- Fever with headache — consider meningitis, encephalitis, or intracranial abscess
- New headache in immunocompromised patient — opportunistic infection or malignancy
- Papilledema or focal neurological signs — suggests raised intracranial pressure or structural lesion
- New headache after age 50 — consider giant cell arteritis, malignancy, or subdural hematoma
- Headache triggered by Valsalva, cough, or exertion — must exclude subarachnoid hemorrhage and Chiari malformation
- Positional component — worse lying down suggests raised intracranial pressure; worse standing suggests intracranial hypotension
- Associated with altered consciousness, seizures, or personality change — suggests serious intracranial pathology
Systematic History: The “HEADACHE” Approach
Use the mnemonic “HEADACHE” to ensure comprehensive history taking:
- H — How did it start?: Sudden thunderclap versus gradual onset; what were you doing when it began?
- E — Evolution and duration: How long does each episode last? How has the pattern changed over time?
- A — Associated symptoms: Nausea, vomiting, photophobia, phonophobia, visual changes, autonomic features, fever, neck stiffness?
- D — Description and location: What does it feel like (throbbing, pressing, stabbing)? Where exactly is the pain? Does it spread?
- A — Aggravating and alleviating factors: What makes it worse (light, noise, movement, cough)? What helps (dark room, sleep, medication)?
- C — Chronology and frequency: How often do headaches occur? Any pattern (time of day, menstrual, seasonal)?
- H — History (past medical, medications, family): Previous headaches? Medications including over-the-counter? Family history of headache?
- E — Effect on life: Impact on work, relationships, daily activities? Disability assessment
Targeted Questions by Suspected Cause
| Suspected Cause | Key Features | Ask This Question |
|---|---|---|
| Migraine | Unilateral, pulsating, moderate-to-severe, nausea, photo/phonophobia, worsened by activity | “Do you need to lie down in a dark, quiet room during attacks? Does the pain throb with your heartbeat?” |
| Tension-type headache | Bilateral, pressing/tightening, mild-to-moderate, no nausea or vomiting | “Does the headache feel like a tight band around your head? Can you continue your normal activities during the headache?” |
| Cluster headache | Strictly unilateral, periorbital, severe, restlessness, autonomic features (tearing, rhinorrhea, ptosis) | “During attacks, do you feel restless and need to pace around? Does your eye water or become red on the painful side?” |
| Medication overuse headache | Daily or near-daily headache, regular use of acute medications more than 10-15 days per month | “How many days per month do you take painkillers or triptans for headache? Do you take medication to prevent a headache from starting?” |
| Subarachnoid hemorrhage | Thunderclap onset, “worst headache of life,” may have neck stiffness, altered consciousness | “Did this headache reach its maximum intensity within seconds? Is this the worst headache you have ever experienced?” |
| Meningitis | Fever, neck stiffness, photophobia, rash (meningococcal), altered mental status | “Do you have a fever? Does bending your neck forward make the headache worse? Have you noticed any rash?” |
| Giant cell arteritis | Age over 50, temporal tenderness, jaw claudication, visual symptoms, polymyalgia symptoms | “Is your scalp tender when you brush your hair or rest your head on a pillow? Does your jaw ache when chewing?” |
| Intracranial hypertension | Worse lying down and in morning, visual obscurations, pulsatile tinnitus, papilledema | “Is the headache worse when you wake up in the morning? Do you notice brief episodes where your vision goes grey or dark?” |
| Intracranial hypotension (cerebrospinal fluid leak) | Worse when upright, improves lying down, often follows lumbar puncture or trauma | “Does the headache get much better within 15-30 minutes of lying flat? Did you have a lumbar puncture or spinal procedure recently?” |
| Cervicogenic headache | Unilateral, starts in neck and spreads to head, reduced neck range of motion, triggered by neck movement | “Does the headache start in your neck and spread to your head? Does turning your neck make the headache worse?” |
| Trigeminal neuralgia | Brief electric shock-like pain, triggered by light touch, chewing, or talking | “Is the pain like an electric shock? Is it triggered by touching your face, eating, or brushing your teeth?” |
Asking About Aura Symptoms
Characterizing Visual and Sensory Symptoms
Migraine aura has specific features that distinguish it from other causes of neurological symptoms:
- Timing: “Do the visual symptoms occur before the headache starts, or during it?”
- Duration: “How long do the visual symptoms last?” (Typical aura: 5-60 minutes)
- Spread: “Do the symptoms gradually spread or expand over time?” (Cortical spreading depression causes gradual spread over 20-30 minutes)
- Character: “Do you see flashing lights, zigzag lines, or blind spots?” (Scintillating scotoma is characteristic)
- Sensory symptoms: “Do you get tingling that spreads from your hand up your arm to your face?” (Cheiro-oral distribution)
- Recovery: “Do all symptoms resolve completely?” (Full recovery expected with typical aura)
Red flag: Sudden onset, persistent symptoms, or motor weakness require urgent evaluation to exclude stroke or other structural causes.
Medication and Social History
Medications That Cause or Worsen Headache
- Nitrates (nitroglycerin, isosorbide) — vasodilation causes immediate headache; can trigger migraine
- Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) — similar mechanism to nitrates
- Calcium channel blockers (nifedipine, amlodipine) — vasodilation, though verapamil prevents cluster headache
- Proton pump inhibitors — associated with headache in some patients
- Hormonal contraceptives — may worsen or improve migraine; assess pattern
- Overused acute medications — simple analgesics more than 15 days/month, triptans or combination analgesics more than 10 days/month
- Withdrawal from caffeine, opioids, or ergots — rebound headache
- Dipyridamole — vasodilator, common cause of headache
Social and Occupational History
- Caffeine intake: Both excess consumption and withdrawal can trigger headache; quantify daily intake
- Alcohol: Red wine commonly triggers migraine; alcohol excess causes next-day headache; cluster headache triggered during cluster periods
- Sleep patterns: Both too little and too much sleep trigger migraine; sleep apnea causes morning headache
- Occupation: Screen time (eye strain), posture (cervicogenic), shift work (sleep disruption), exposure to fumes or chemicals
- Stress: Major life events, work stress, anxiety, depression — both trigger and perpetuate headache
- Diet: Meal skipping, dehydration, specific food triggers (aged cheese, processed meats, MSG in susceptible individuals)
- Carbon monoxide exposure: Faulty heating, enclosed spaces — headache with drowsiness affecting multiple household members
Family History
Relevance of Family History in Headache
- Migraine — strong genetic component; 70-90% of patients have first-degree relative with migraine
- Cluster headache — 5-20 times increased risk in first-degree relatives
- Familial hemiplegic migraine — autosomal dominant; ask about family members with migraine plus weakness
- Intracranial aneurysm — screen if two or more first-degree relatives affected
- CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) — family history of early stroke and dementia with migraine
The Value of a Headache Diary
A prospective headache diary is invaluable for accurate diagnosis and management. Ask patients to record:
- Date and time of headache onset and resolution
- Pain intensity (0-10 scale)
- Location and character of pain
- Associated symptoms
- Potential triggers (food, sleep, stress, menstrual cycle)
- Medications taken and response
- Impact on activities
A diary kept for at least 4 weeks often reveals patterns not apparent from history alone and accurately quantifies medication use (patients often underestimate).
4. Physical Examination
A systematic head-to-toe approach for Headache
Systematic Framework: The headache examination serves two purposes: (1) to identify red flags suggesting secondary causes requiring urgent investigation, and (2) to find positive signs supporting specific diagnoses. Use a “General → Vital Signs → Head and Neck → Neurological” approach for complete evaluation.
General Inspection
- Appearance and behavior: Restlessness and pacing suggest cluster headache; preference for stillness and dark room suggests migraine; confusion or drowsiness suggests serious intracranial pathology
- Facial expression: Grimacing, eye closure, hand holding head — assess pain severity
- Autonomic features: Unilateral lacrimation, conjunctival injection, rhinorrhea, ptosis, miosis — suggests trigeminal autonomic cephalalgia
- Skin: Petechial or purpuric rash (meningococcemia); café-au-lait spots (neurofibromatosis with possible intracranial tumors)
- Habitus: Obesity — associated with idiopathic intracranial hypertension; weight loss — consider malignancy
Vital Signs
| Vital Sign | What to Look For | Clinical Significance |
|---|---|---|
| Temperature | Fever (greater than 38°C) | Suggests infection — meningitis, encephalitis, sinusitis, systemic infection; also consider drug-induced fever |
| Blood Pressure | Severe hypertension (greater than 180/120 mmHg) | Hypertensive emergency can cause headache; however, mild-moderate hypertension rarely causes headache — look for other causes |
| Heart Rate | Tachycardia or bradycardia | Tachycardia with fever suggests infection; bradycardia with hypertension (Cushing response) suggests raised intracranial pressure |
| Respiratory Rate | Abnormal pattern | Irregular breathing may indicate brainstem dysfunction; hyperventilation associated with anxiety-related headache |
| Oxygen Saturation | Hypoxia | Hypoxia causes headache; consider carbon monoxide poisoning (co-oximetry needed as standard pulse oximetry may be falsely normal) |
Head and Neck Examination
Scalp and Skull
- Temporal arteries: Palpate bilaterally for tenderness, thickening, reduced or absent pulsation — suggests giant cell arteritis
- Scalp tenderness: Localized tenderness over temporal arteries (giant cell arteritis); diffuse tenderness to light touch (allodynia in migraine)
- Pericranial muscle tenderness: Palpate temporalis, frontalis, suboccipital, and trapezius muscles — tenderness supports tension-type headache
- Trauma signs: Bruising, lacerations, Battle’s sign (mastoid bruising), raccoon eyes (periorbital bruising) — suggest head injury
- Surgical scars: Previous craniotomy or shunt suggests secondary causes
Eyes
| Finding | How to Assess | Significance |
|---|---|---|
| Pupil asymmetry | Compare size in dim and bright light | Unilateral dilation with ptosis — third nerve palsy (posterior communicating artery aneurysm); miosis with ptosis — Horner syndrome (carotid dissection, cluster headache) |
| Conjunctival injection | Direct inspection | Unilateral with lacrimation — cluster headache or other trigeminal autonomic cephalalgia; bilateral — consider acute glaucoma |
| Visual acuity | Snellen chart or bedside reading | Reduced acuity — consider giant cell arteritis (ischemic optic neuropathy), papilledema, or primary eye pathology |
| Visual fields | Confrontation testing | Defects suggest intracranial pathology (pituitary tumor, occipital lesion); transient obscurations suggest raised intracranial pressure |
| Eye movements | Follow finger in H pattern | Diplopia or restriction — cranial nerve palsy, orbital or cavernous sinus pathology, raised intracranial pressure (sixth nerve) |
Fundoscopy
Fundoscopy Is Essential in Headache Assessment
Papilledema (optic disc swelling due to raised intracranial pressure) is a critical finding that changes management:
- Features: Blurred disc margins (starting nasally), loss of spontaneous venous pulsation, disc hyperemia, engorged veins, eventual disc elevation and hemorrhages
- Significance: Indicates raised intracranial pressure — contraindication to lumbar puncture until imaging excludes mass lesion
- Causes: Intracranial mass, idiopathic intracranial hypertension, cerebral venous thrombosis, meningitis
Subhyaloid hemorrhage (blood between retina and vitreous) strongly suggests subarachnoid hemorrhage.
Ears, Nose, and Throat
- Ears: Otoscopy for middle ear infection, mastoiditis; pressing the tragus or pulling the pinna (pain suggests otitis externa)
- Sinuses: Tenderness over frontal and maxillary sinuses; however, most “sinus headaches” are actually migraine
- Nasal examination: Purulent discharge suggests sinusitis; unilateral clear rhinorrhea may be cerebrospinal fluid leak
- Oropharynx: Dental pathology can cause referred headache; temporomandibular joint tenderness and reduced opening
Neck Examination
- Meningism: Neck stiffness on passive flexion (not rotation) — indicates meningeal irritation from infection or blood
- Range of motion: Restricted and painful movement suggests cervicogenic cause; test flexion, extension, rotation, lateral flexion
- Cervical spine tenderness: Palpate spinous processes, facet joints, paraspinal muscles
- Occipital nerves: Tenderness at greater occipital nerve (midway between mastoid and occipital protuberance) — occipital neuralgia or referred from migraine
- Lymph nodes: Enlarged nodes may indicate infection or malignancy
- Carotid bruit: May indicate stenosis or dissection (though dissection may have no bruit)
Neurological Examination
Mental Status
- Level of consciousness: Glasgow Coma Scale; drowsiness or confusion suggests serious pathology
- Orientation: Time, place, person
- Attention and concentration: Serial sevens, months backward
- Memory: New learning and recall
- Language: Dysphasia suggests dominant hemisphere involvement
Cranial Nerves
| Cranial Nerve | Test | Significance if Abnormal |
|---|---|---|
| II (Optic) | Visual acuity, fields, fundoscopy, pupillary responses | Papilledema, visual field defects, optic neuropathy (giant cell arteritis) |
| III, IV, VI (Oculomotor, Trochlear, Abducens) | Eye movements, pupils, ptosis | Third nerve palsy with pupil involvement — posterior communicating artery aneurysm; sixth nerve palsy — raised intracranial pressure (false localizing) |
| V (Trigeminal) | Facial sensation, corneal reflex, jaw strength | Sensory loss in trigeminal neuralgia or cavernous sinus lesion; corneal reflex loss important sign |
| VII (Facial) | Facial movements, taste | Facial weakness — may accompany cluster headache (rare); consider brainstem or cerebellopontine angle lesion |
| VIII (Vestibulocochlear) | Hearing, vestibular function | Hearing loss with headache — consider acoustic neuroma; vertigo with headache — vestibular migraine, posterior fossa lesion |
| IX, X, XI, XII (Lower cranial nerves) | Palate, gag, sternocleidomastoid, trapezius, tongue | Lower cranial nerve palsies suggest skull base pathology |
Motor and Sensory Examination
- Tone: Increased tone suggests upper motor neuron lesion
- Power: Test major muscle groups; focal weakness requires investigation
- Reflexes: Asymmetry or hyperreflexia suggests structural lesion; upgoing plantars (Babinski sign) indicate upper motor neuron lesion
- Sensation: Test light touch, pinprick in all limbs; hemisensory loss suggests thalamic or cortical lesion
- Coordination: Finger-nose, heel-shin testing; cerebellar signs suggest posterior fossa pathology
Gait and Balance
- Observe gait: Ataxia suggests cerebellar involvement; hemiparetic gait indicates motor pathway lesion
- Romberg test: Positive with proprioceptive or vestibular dysfunction
- Tandem gait: Sensitive for subtle cerebellar dysfunction
Special Tests for Meningeal Irritation
Neck Stiffness
Technique: Passively flex the neck while patient is supine
Positive finding: Resistance and pain with neck flexion (but rotation preserved)
Significance: Meningeal irritation from infection or subarachnoid hemorrhage
Kernig Sign
Technique: Flex hip to 90°, then attempt to extend the knee
Positive finding: Pain and resistance to knee extension
Significance: Meningeal irritation; sensitivity approximately 5%, specificity greater than 95%
Brudzinski Sign
Technique: Passively flex the neck while patient supine
Positive finding: Involuntary flexion of hips and knees
Significance: Meningeal irritation; low sensitivity, high specificity
Sensitivity of Meningeal Signs
Classic meningeal signs have low sensitivity (approximately 5-30%) but high specificity. Absence of neck stiffness does not exclude meningitis, especially in elderly, immunocompromised, or very young patients. If clinical suspicion is high, proceed with lumbar puncture regardless of examination findings.
Expected Findings by Etiology
| Condition | General Appearance | Key Examination Findings | Red Flags |
|---|---|---|---|
| Migraine | Prefers to lie still, may avoid light | Usually normal between attacks; during attack may have cutaneous allodynia | Focal neurological signs persisting beyond aura |
| Tension-type headache | Often continues activities | Pericranial muscle tenderness; otherwise normal | Neurological signs unexpected |
| Cluster headache | Agitated, restless, pacing | Ipsilateral lacrimation, conjunctival injection, rhinorrhea, ptosis, miosis, facial sweating | Persistent Horner syndrome between attacks |
| Subarachnoid hemorrhage | May be drowsy or agitated | Neck stiffness (may take hours to develop), altered consciousness, focal signs, subhyaloid hemorrhage | Any abnormal neurological sign |
| Meningitis | Ill-appearing, photophobic | Fever, neck stiffness, positive Kernig/Brudzinski (variable), petechial rash (meningococcal) | Altered mental status, seizures, rash |
| Giant cell arteritis | May appear well | Tender, thickened temporal arteries with reduced pulsation; scalp tenderness; jaw claudication history | Visual loss or transient visual symptoms |
| Raised intracranial pressure | May be drowsy | Papilledema, sixth nerve palsy, visual field defects, focal signs depending on cause | Papilledema, decreasing consciousness |
| Intracranial hypotension | Prefers to lie flat | Orthostatic headache; may have low-pressure papillopathy, sixth nerve palsy, subdural collections | Neurological signs, subdural hematoma |
| Cervicogenic headache | Often has neck posture abnormality | Reduced cervical range of motion, tenderness of cervical structures, pain reproduced by neck movement | Myelopathic signs |
Important Teaching Point
Normal examination is common! The majority of patients with headache — including migraine, tension-type headache, medication overuse headache, and many secondary causes — have completely normal physical examinations between attacks. A normal examination does not exclude serious pathology; it must be interpreted in the context of the history.
Conversely, the examination becomes crucial for:
- Identifying red flags that mandate urgent investigation (papilledema, focal signs, meningism)
- Supporting specific diagnoses (autonomic features in cluster headache, temporal artery abnormality in giant cell arteritis)
- Establishing a baseline for monitoring
5. Differential Diagnosis
Systematic approach organized by probability and clinical features
The differential diagnosis of headache is broad, but a systematic approach based on temporal pattern (acute versus chronic), associated features, and red flags allows efficient narrowing. Primary headache disorders account for approximately 90% of presentations, but the clinician must remain vigilant for the 10% that represent secondary causes, some of which are life-threatening.
Acute Headache (New-Onset or First Presentation)
| Probability | Condition | Key Features | Red Flags |
|---|---|---|---|
| COMMON (approximately 70%) | Primary headache (first migraine or tension-type) | Features typical of migraine or tension-type; no red flags; may have family history | None — diagnosis of exclusion in acute setting |
| COMMON | Systemic viral illness | Fever, myalgia, upper respiratory symptoms; diffuse headache; resolves with illness | Neck stiffness, rash, altered mental status |
| LESS COMMON (approximately 20%) | Sinusitis (acute bacterial) | Facial pain/pressure, purulent nasal discharge, fever; pain worse on bending forward | Periorbital swelling, visual changes, altered consciousness (suggests intracranial extension) |
| LESS COMMON | Hypertensive emergency | Blood pressure typically greater than 180/120 mmHg with end-organ damage; diffuse headache | Encephalopathy, visual changes, chest pain, acute kidney injury |
| UNCOMMON BUT SERIOUS (approximately 10%) | Subarachnoid hemorrhage | Thunderclap onset; “worst headache of life”; may have neck stiffness, vomiting, altered consciousness | Thunderclap onset, meningism, focal signs, decreased consciousness |
| UNCOMMON BUT SERIOUS | Bacterial meningitis | Fever, neck stiffness, photophobia, altered mental status; rapid progression | Fever, meningism, rash, altered consciousness, seizures |
| UNCOMMON BUT SERIOUS | Viral encephalitis | Headache with altered behavior, confusion, seizures, fever; may have focal signs | Altered mental status, personality change, seizures, focal signs |
| UNCOMMON BUT SERIOUS | Cerebral venous thrombosis | Progressive headache over days; may have focal signs, seizures; risk factors include oral contraceptives, pregnancy, thrombophilia | Progressive headache, seizures, focal signs, papilledema |
| UNCOMMON BUT SERIOUS | Arterial dissection (carotid or vertebral) | Unilateral head/neck pain, often following minor trauma; may have Horner syndrome, stroke symptoms | Horner syndrome, neck pain, stroke symptoms in young patient |
| UNCOMMON BUT SERIOUS | Acute angle-closure glaucoma | Severe eye pain, headache, nausea, visual halos; mid-dilated fixed pupil, red eye | Eye pain with visual loss, fixed mid-dilated pupil |
| UNCOMMON BUT SERIOUS | Carbon monoxide poisoning | Headache, nausea, confusion; multiple household members affected; winter months, faulty heating | Altered consciousness, multiple affected individuals, winter presentation |
Chronic Headache (Greater Than 3 Months Duration)
Step-by-Step Approach to Chronic Headache:
- Step 1: Exclude medication overuse headache — ask about frequency of acute medication use (more than 10-15 days per month)
- Step 2: Identify primary headache type — migraine, tension-type, or trigeminal autonomic cephalalgia based on features
- Step 3: Consider secondary causes if red flags present or atypical features — imaging and further investigation
- Step 4: Assess for multiple overlapping headache types — common in chronic presentations
| Probability | Condition | Approximate Frequency | Key Distinguishing Features |
|---|---|---|---|
| COMMON | Chronic migraine | Approximately 2% of population | Headache 15 or more days per month for more than 3 months; at least 8 days with migraine features; often evolved from episodic migraine |
| COMMON | Chronic tension-type headache | Approximately 2-3% of population | Headache 15 or more days per month; bilateral, pressing, mild-to-moderate; no nausea or vomiting; may have mild photophobia or phonophobia (not both) |
| COMMON | Medication overuse headache | 1-2% of population; up to 50% of chronic daily headache | Headache 15 or more days per month; regular overuse of acute medication more than 10-15 days per month for more than 3 months; often superimposed on migraine or tension-type |
| LESS COMMON | New daily persistent headache | Rare; less than 1% | Daily headache from onset; patient can pinpoint exact day it began; often follows viral illness; may have migraine or tension-type features |
| LESS COMMON | Hemicrania continua | Rare | Continuous strictly unilateral headache; mild-to-moderate baseline with exacerbations; autonomic features during exacerbations; absolute response to indomethacin |
| LESS COMMON | Cervicogenic headache | Approximately 2-4% of chronic headache | Unilateral, starting in neck and radiating to head; reduced cervical range of motion; triggered by neck movement or posture |
| LESS COMMON | Idiopathic intracranial hypertension | 1-2 per 100,000; higher in obese women of childbearing age | Daily headache, worse lying down, visual obscurations, pulsatile tinnitus, papilledema; typically young obese women |
| UNCOMMON BUT SERIOUS | Intracranial mass (tumor, abscess) | Less than 1% of chronic headache | Progressive headache; worse in morning; associated focal signs, seizures, personality change; papilledema |
| UNCOMMON BUT SERIOUS | Chronic subdural hematoma | More common in elderly, anticoagulated patients | Progressive headache, confusion, focal signs; may have history of minor trauma weeks earlier (or no recalled trauma) |
| UNCOMMON BUT SERIOUS | Giant cell arteritis | Approximately 20 per 100,000 in those over 50 | New headache in patient over 50; scalp or temporal tenderness; jaw claudication; visual symptoms; elevated inflammatory markers |
Trigeminal Autonomic Cephalalgias
| Condition | Attack Duration | Attack Frequency | Key Features | Treatment Response |
|---|---|---|---|---|
| Cluster headache | 15-180 minutes | 1-8 per day during cluster period | Strictly unilateral, severe, periorbital; restlessness; ipsilateral autonomic features; circadian pattern; male predominance | Oxygen, sumatriptan; verapamil for prevention |
| Paroxysmal hemicrania | 2-30 minutes | More than 5 per day | Strictly unilateral, severe; autonomic features; more frequent but shorter than cluster | Absolute response to indomethacin (diagnostic) |
| Short-lasting unilateral neuralgiform headache attacks (SUNCT/SUNA) | 1-600 seconds | 3-200 per day | Very brief, stabbing; prominent autonomic features; may be triggered by touch | Lamotrigine, topiramate; refractory to most treatments |
| Hemicrania continua | Continuous | Constant baseline with exacerbations | Strictly unilateral, continuous; mild-to-moderate baseline; autonomic features during exacerbations | Absolute response to indomethacin (diagnostic) |
Anatomical Approach to Secondary Headache
Intracranial — Vascular
Subarachnoid hemorrhage
Intracerebral hemorrhage
Ischemic stroke (less common cause of headache)
Cerebral venous thrombosis
Arterial dissection (carotid, vertebral)
Reversible cerebral vasoconstriction syndrome
Pituitary apoplexy
Intracranial — Non-Vascular
Intracranial hypertension (idiopathic or secondary)
Intracranial hypotension (cerebrospinal fluid leak)
Mass lesion (tumor, abscess)
Hydrocephalus
Chiari malformation
Meningitis, encephalitis
Subdural or epidural hematoma
Extracranial — Head and Neck
Giant cell arteritis
Cervicogenic headache
Temporomandibular joint dysfunction
Acute sinusitis
Acute glaucoma
Dental pathology
Occipital neuralgia
Trigeminal neuralgia
Systemic Causes
Systemic infection with fever
Hypertensive emergency
Hypoxia, hypercapnia
Carbon monoxide poisoning
Medication-induced or substance-related
Metabolic (hypoglycemia, dialysis headache)
Pre-eclampsia/eclampsia
Anemia (severe)
Drug-Induced and Substance-Related Headache
| Drug or Substance | Mechanism | Characteristics | Time Course |
|---|---|---|---|
| Nitrates (nitroglycerin, isosorbide) | Nitric oxide-mediated vasodilation | Immediate throbbing headache; may trigger delayed migraine in susceptible individuals | Minutes after administration; resolves within hours |
| Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) | Vasodilation via nitric oxide pathway | Diffuse headache; dose-related | Hours; may persist with long-acting agents |
| Dipyridamole | Vasodilation, adenosine potentiation | Very common; throbbing headache | Often improves with continued use over 1-2 weeks |
| Calcium channel blockers (dihydropyridines) | Vasodilation | Throbbing headache, flushing | May improve with dose reduction or switching agents |
| Proton pump inhibitors | Uncertain; possibly magnesium depletion | Diffuse headache in some patients | May develop after weeks of use |
| Hormone therapy (estrogen) | Hormonal fluctuation; may improve or worsen migraine | May trigger migraine or alter pattern | Variable; often cyclic with hormone withdrawal |
| Caffeine withdrawal | Adenosine receptor upregulation during chronic use; withdrawal causes vasodilation | Bilateral throbbing headache, fatigue | 12-24 hours after last caffeine; peaks at 1-2 days; resolves in 2-9 days |
| Alcohol (hangover) | Dehydration, vasodilation, toxic metabolites | Bilateral throbbing, nausea | Hours after consumption; resolves within 24 hours |
| Carbon monoxide | Tissue hypoxia, direct toxic effect | Diffuse headache, nausea, confusion; multiple household members affected | Progressive with exposure; resolves with removal from source and oxygen |
| Analgesic/triptan overuse (medication overuse headache) | Central sensitization, receptor changes, impaired pain modulation | Daily or near-daily headache; acute medications more than 10-15 days per month | Develops over months; resolves weeks after withdrawal |
Quick Reference: “If You See This, Think This”
| Clinical Clue | Think This First | Next Step |
|---|---|---|
| Thunderclap headache (maximal in seconds) | Subarachnoid hemorrhage until proven otherwise | CT head immediately; lumbar puncture if CT negative |
| Headache with fever and neck stiffness | Meningitis | Blood cultures, empiric antibiotics, lumbar puncture |
| New headache over age 50 with scalp tenderness | Giant cell arteritis | Urgent ESR/CRP; start steroids if high suspicion; temporal artery biopsy |
| Unilateral headache with ipsilateral eye watering and restlessness | Cluster headache | High-flow oxygen, subcutaneous sumatriptan for acute attack |
| Daily headache in patient taking painkillers most days | Medication overuse headache | Withdrawal of overused medication; start preventive therapy |
| Positional headache worse when upright | Intracranial hypotension (cerebrospinal fluid leak) | MRI brain with contrast; may need CT myelogram |
| Positional headache worse when lying down | Raised intracranial pressure | Urgent imaging; fundoscopy for papilledema |
| Headache with papilledema in obese young woman | Idiopathic intracranial hypertension | MRI/MRV to exclude venous thrombosis; lumbar puncture for opening pressure |
| Headache following neck trauma or manipulation | Cervical artery dissection | CT or MR angiography of head and neck |
| Severe eye pain with fixed mid-dilated pupil | Acute angle-closure glaucoma | Emergency ophthalmology referral |
| Headache with confusion affecting multiple household members | Carbon monoxide poisoning | Remove from environment; check carboxyhemoglobin; high-flow oxygen |
| Strictly unilateral continuous headache responding to indomethacin | Hemicrania continua or paroxysmal hemicrania | Indomethacin trial (diagnostic and therapeutic) |
6. Diagnostic Investigations
A stepwise, cost-effective approach guided by clinical suspicion
Investigation of headache should be guided by clinical features. The majority of primary headache disorders (migraine, tension-type headache, cluster headache) are diagnosed clinically without investigation. Investigations are indicated when red flags are present, the clinical picture is atypical, or there is a change in an established headache pattern.
Indications for Investigation
- Red flags present — thunderclap onset, fever, neurological signs, papilledema, altered consciousness
- New headache in patient over 50 — exclude giant cell arteritis and secondary causes
- Change in established headache pattern — significant change in frequency, severity, or character
- Atypical features — features not fitting recognized primary headache patterns
- Treatment failure — inadequate response to appropriate treatment for presumed diagnosis
- Immunocompromised patient — lower threshold for investigation
- Patient anxiety — investigation may be reasonable for reassurance if clinical suspicion low
Baseline Investigations When Indicated
| Investigation | Purpose | What to Look For | Practical Points |
|---|---|---|---|
| Full blood count | Screen for infection, anemia, malignancy | Leukocytosis (infection); anemia (may contribute to headache); thrombocytosis (consider giant cell arteritis) | Part of routine workup; non-specific but may guide further testing |
| Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) | Inflammatory markers; essential if giant cell arteritis suspected | ESR typically greater than 50 mm/hour in giant cell arteritis; CRP usually elevated; both may be normal in 5% of cases | Order urgently if giant cell arteritis suspected; do not delay treatment waiting for results if clinical suspicion high |
| Basic metabolic panel | Electrolytes, renal function, glucose | Hypoglycemia, hyponatremia, uremia — all can cause headache | Routine; particularly important if altered mental status |
| Thyroid function tests | Thyroid dysfunction can cause or exacerbate headache | Hypothyroidism or hyperthyroidism | Consider in chronic headache workup; not urgent |
| Carboxyhemoglobin level | Carbon monoxide poisoning | Elevated carboxyhemoglobin (greater than 3% non-smokers, greater than 10% smokers) | Requires arterial or venous blood gas with co-oximetry; pulse oximetry not reliable |
Neuroimaging
CT Head Without Contrast
Indications
- Thunderclap headache — first-line to detect subarachnoid hemorrhage (sensitivity greater than 95% if within 6 hours, decreases with time)
- Suspected intracranial hemorrhage
- Head trauma with headache
- Acute focal neurological signs
- Initial screen when urgent imaging needed and MRI not immediately available
Limitations
- Less sensitive than MRI for posterior fossa, pituitary, and white matter lesions
- Sensitivity for subarachnoid hemorrhage decreases after 6-12 hours
- May miss small tumors, arteriovenous malformations, or early infarcts
- Does not visualize vascular pathology (requires CT angiography)
MRI Brain
Indications
- Suspected mass lesion, tumor, or posterior fossa pathology
- Pituitary pathology (pituitary apoplexy, adenoma)
- White matter disease (multiple sclerosis, small vessel disease)
- Intracranial hypotension (pachymeningeal enhancement, brain sag)
- Cerebral venous thrombosis (MRI with MR venography)
- Chiari malformation
- Normal CT but high clinical suspicion for structural cause
Specific Sequences
- T1 with gadolinium: Enhancing lesions, meningeal disease, pituitary
- T2/FLAIR: White matter lesions, edema
- DWI: Acute infarction
- GRE/SWI: Blood products, microhemorrhages
- MRA: Arterial pathology (aneurysm, dissection, vasoconstriction)
- MRV: Venous thrombosis
CT/MR Angiography
| Indication | Modality | What to Look For |
|---|---|---|
| Suspected aneurysm (after subarachnoid hemorrhage) | CT angiography (first-line) or MR angiography | Aneurysm location, size, morphology; may need catheter angiography if CTA negative |
| Arterial dissection | CT angiography or MR angiography with fat-suppressed T1 | Intramural hematoma, luminal stenosis, pseudoaneurysm; include cervical vessels |
| Reversible cerebral vasoconstriction syndrome | CT angiography or MR angiography; may need repeat imaging | Multifocal segmental vasoconstriction of cerebral arteries; may be normal early |
| Cerebral venous thrombosis | MR venography (preferred) or CT venography | Filling defect in dural sinus or cortical vein; absent flow signal |
Lumbar Puncture
When to Perform Lumbar Puncture
- Suspected meningitis or encephalitis — urgent; do not delay for imaging unless focal signs or papilledema
- Suspected subarachnoid hemorrhage with negative CT — essential if CT negative and clinical suspicion persists; look for xanthochromia (appears 12 hours after bleed)
- Suspected idiopathic intracranial hypertension — measure opening pressure (greater than 25 cm H2O diagnostic in appropriate context); therapeutic effect from cerebrospinal fluid removal
- Suspected intracranial hypotension — typically low or unmeasurable opening pressure; may show elevated protein
- Suspected carcinomatous meningitis — cerebrospinal fluid cytology
Contraindications: Imaging first if focal signs, papilledema, altered consciousness, or immunocompromised to exclude mass lesion. Coagulopathy is a relative contraindication.
Cerebrospinal Fluid Analysis
| Parameter | Normal Values | Abnormal Findings and Significance |
|---|---|---|
| Opening pressure | 10-20 cm H2O (up to 25 cm H2O) | Elevated: intracranial hypertension, meningitis, venous thrombosis. Low: intracranial hypotension |
| Appearance | Clear and colorless | Turbid: infection. Xanthochromia (yellow): subarachnoid hemorrhage (appears 12 hours after bleed, persists 2 weeks) |
| White blood cells | Less than 5 cells per microliter | Neutrophils: bacterial meningitis. Lymphocytes: viral, tuberculous, or fungal meningitis |
| Protein | 15-45 mg/dL | Elevated: infection, hemorrhage, malignancy, Guillain-Barré syndrome |
| Glucose | Greater than 60% of serum glucose | Low: bacterial, tuberculous, or fungal meningitis; carcinomatous meningitis |
| Red blood cells | None (or traumatic tap) | Elevated with xanthochromia: subarachnoid hemorrhage. Elevated without xanthochromia: traumatic tap |
Targeted Investigations by Suspected Etiology
If Suspecting Giant Cell Arteritis
First-Line Tests
- ESR: Typically greater than 50 mm/hour; very high values (greater than 100 mm/hour) strongly suggestive
- CRP: Usually elevated; may be more sensitive than ESR
- Platelet count: Often elevated (reactive thrombocytosis)
- Full blood count: Normocytic anemia common
Confirmatory Tests
- Temporal artery biopsy: Gold standard; should be performed within 2 weeks of starting steroids; may be negative due to skip lesions (bilateral biopsy increases yield)
- Temporal artery ultrasound: “Halo sign” (hypoechoic ring around vessel); operator-dependent; increasingly used as first-line in experienced centers
- PET-CT or MRA: May show large vessel involvement
If Suspecting Subarachnoid Hemorrhage
First-Line Tests
- CT head without contrast: Sensitivity greater than 95% within 6 hours; decreases to approximately 85% at 24 hours; approximately 50% at 1 week
- CT angiography: Perform immediately if CT shows blood to identify aneurysm source
If CT Negative
- Lumbar puncture: Perform if CT negative and clinical suspicion persists; wait at least 6-12 hours from headache onset for xanthochromia to develop
- Xanthochromia: Spectrophotometry preferred over visual inspection; bilirubin indicates breakdown of hemoglobin confirming true hemorrhage versus traumatic tap
If Suspecting Idiopathic Intracranial Hypertension
First-Line Tests
- MRI brain with MR venography: Exclude mass lesion and venous thrombosis; may show empty sella, flattened posterior globe, distended optic nerve sheaths
- Fundoscopy: Document papilledema; grade severity
Confirmatory Tests
- Lumbar puncture: Opening pressure greater than 25 cm H2O in lateral decubitus position (diagnostic criterion); cerebrospinal fluid composition normal
- Visual field testing: Perimetry to document and monitor visual field loss (enlarged blind spot, peripheral constriction)
- Optical coherence tomography: Quantifies optic disc swelling; useful for monitoring
If Suspecting Intracranial Hypotension
First-Line Tests
- MRI brain with gadolinium: Diffuse pachymeningeal enhancement, brain sagging, subdural collections, pituitary engorgement
- Lumbar puncture: Low or unmeasurable opening pressure (though may be normal if intermittent leak); may show elevated protein
Localization of Leak
- MRI spine: May show extradural cerebrospinal fluid collection
- CT myelography: Gold standard for leak localization; requires lumbar injection of contrast
- Radioisotope cisternography: Alternative for leak detection
Empiric Treatment Trials as Diagnostic Tools
When Response to Treatment Confirms Diagnosis
In some headache disorders, response to specific treatment is a diagnostic criterion:
- Indomethacin trial (hemicrania continua, paroxysmal hemicrania): Start indomethacin 25 mg three times daily, increase to 50-75 mg three times daily. Complete resolution of headache within days confirms diagnosis. Use gastroprotection.
- High-flow oxygen (cluster headache): 100% oxygen at 12-15 liters per minute via non-rebreather mask for 15-20 minutes. Rapid relief (within 15 minutes) supports cluster headache diagnosis.
- Triptan trial (migraine): Response to triptans supports migraine diagnosis, though not specific.
- Occipital nerve block (cervicogenic headache, occipital neuralgia): Temporary relief following local anesthetic injection supports diagnosis and predicts response to further intervention.
- Proton pump inhibitor trial: If reflux-related headache suspected (rare), 8-week high-dose proton pump inhibitor trial.
Summary: Investigation by Clinical Scenario
| Clinical Scenario | First-Line Investigation | Second-Line if Needed |
|---|---|---|
| Thunderclap headache | CT head immediately, then CT angiography if blood present | Lumbar puncture if CT negative (xanthochromia) |
| Headache with fever and meningism | Blood cultures, lumbar puncture (unless contraindicated) | CT head before lumbar puncture if focal signs or reduced consciousness |
| New headache over age 50 | ESR, CRP, full blood count; CT or MRI brain | Temporal artery biopsy or ultrasound if giant cell arteritis suspected |
| Headache with papilledema | MRI brain with MR venography | Lumbar puncture for opening pressure (after excluding mass) |
| Positional headache (worse upright) | MRI brain with gadolinium | CT myelography for leak localization |
| Headache after head or neck trauma | CT head; CT angiography of head and neck | MRI if CT normal but symptoms persist |
| Chronic daily headache with medication overuse | Clinical diagnosis; imaging only if atypical features | MRI if treatment failure or red flags develop |
| Typical migraine or tension-type headache | No routine investigation needed | MRI if atypical features, treatment failure, or patient anxiety |
7. Pattern Recognition and Clinical Decision-Making
Practical algorithms and decision pathways
Step 1: Is This Urgent?
| Clinical Scenario | Urgency Level | Immediate Action |
|---|---|---|
| Thunderclap headache (maximal intensity within seconds to one minute) | EMERGENT | CT head immediately; if negative, lumbar puncture for xanthochromia; CT angiography if blood found |
| Headache with fever, neck stiffness, altered mental status | EMERGENT | Blood cultures, empiric antibiotics (do not delay), lumbar puncture when safe; dexamethasone |
| Headache with focal neurological deficit | EMERGENT | CT head immediately; consider stroke, mass lesion, or hemorrhage; neurology consultation |
| Headache with papilledema | EMERGENT | Urgent MRI/MRV to exclude mass and venous thrombosis; do not perform lumbar puncture until imaging complete |
| Headache with decreased level of consciousness | EMERGENT | ABC assessment, CT head, consider intubation if GCS declining; treat for raised intracranial pressure if suspected |
| New headache in patient over 50 with scalp tenderness or visual symptoms | URGENT | ESR/CRP urgently; start high-dose corticosteroids same day if giant cell arteritis suspected (do not wait for biopsy) |
| Severe cluster headache attack | URGENT | High-flow oxygen 12-15 L/min via non-rebreather; subcutaneous sumatriptan 6 mg if oxygen unavailable or ineffective |
| Headache with unilateral Horner syndrome after neck trauma | URGENT | CT or MR angiography of head and neck to exclude carotid dissection |
| Severe acute migraine with significant distress | URGENT | Parenteral treatment: IV metoclopramide plus IV NSAID (ketorolac) or subcutaneous sumatriptan; consider IV fluids |
| Chronic headache without red flags, established pattern | ROUTINE | Comprehensive history; assess for medication overuse; consider preventive therapy; outpatient follow-up |
| Typical episodic migraine or tension-type headache | ROUTINE | Confirm diagnosis clinically; acute treatment optimization; preventive therapy if frequent; headache diary |
Step 2: Classify by Temporal Pattern
Acute/New-Onset
Duration: First episode or less than 4 weeks
Priority: Exclude secondary causes
Proceed to Algorithm A
Episodic Recurrent
Duration: Recurrent discrete episodes with pain-free intervals
Priority: Identify primary headache type
Proceed to Algorithm B
Chronic Daily
Duration: Headache 15 or more days per month for more than 3 months
Priority: Assess for medication overuse
Proceed to Algorithm C
Step 3: Follow the Appropriate Algorithm
Algorithm A: Acute/New-Onset Headache
| Clinical Scenario | Most Likely Diagnosis | Action |
|---|---|---|
| Thunderclap onset, worst headache ever | Subarachnoid hemorrhage until proven otherwise | Emergency CT head → CT angiography if positive → lumbar puncture if CT negative |
| Fever, neck stiffness, photophobia | Meningitis | Blood cultures → empiric antibiotics immediately → lumbar puncture → adjust antibiotics based on results |
| Unilateral throbbing with nausea, photo/phonophobia, family history | First migraine presentation | Clinical diagnosis if typical features, no red flags → acute treatment → consider MRI if atypical |
| Bilateral pressing headache with viral symptoms | Systemic viral illness | Symptomatic treatment → reassess if worsening or not resolving with illness |
| Headache with blood pressure greater than 180/120 and end-organ symptoms | Hypertensive emergency | Controlled blood pressure reduction → CT head if neurological symptoms → treat end-organ damage |
| Severe unilateral headache with ipsilateral autonomic features, restlessness | Cluster headache (first presentation) | High-flow oxygen for acute attack → MRI to exclude secondary cause → start verapamil if cluster confirmed |
| Headache following head/neck trauma with Horner syndrome | Cervical artery dissection | CT or MR angiography of head and neck → anticoagulation or antiplatelet per findings |
Algorithm B: Episodic Recurrent Headache
| Clinical Scenario | Most Likely Diagnosis | Action |
|---|---|---|
| Unilateral, pulsating, moderate-to-severe, nausea, photo/phonophobia, worsened by activity, lasts 4-72 hours | Migraine without aura | Confirm ICHD-3 criteria → optimize acute treatment (triptans, NSAIDs) → preventive therapy if 4 or more days per month |
| Same as above, preceded by visual symptoms (scintillations, scotoma) lasting 5-60 minutes | Migraine with aura | Same as above → counsel regarding aura symptoms → consider contraception implications (estrogen contraindicated in migraine with aura) |
| Bilateral, pressing/tightening, mild-to-moderate, no nausea/vomiting, not worsened by activity | Episodic tension-type headache | Simple analgesics for acute attacks → limit use to avoid medication overuse → stress management, physical therapy |
| Strictly unilateral, severe periorbital pain, 15-180 minutes, 1-8 attacks per day, ipsilateral autonomic features, restlessness | Cluster headache | Acute: oxygen or sumatriptan → preventive: verapamil during cluster period → consider MRI to exclude secondary causes |
| Strictly unilateral, 2-30 minute attacks, more than 5 per day, autonomic features | Paroxysmal hemicrania | Indomethacin trial (diagnostic) → complete response confirms diagnosis → continue indomethacin with gastroprotection |
| Headache triggered by coughing, straining, or exertion | Primary cough headache or primary exertional headache (but must exclude secondary causes) | MRI brain to exclude Chiari malformation and other structural causes → if normal, trial of indomethacin |
Algorithm C: Chronic Daily Headache
| Clinical Scenario | Most Likely Diagnosis | Action |
|---|---|---|
| Daily headache in patient taking acute medications more than 10-15 days per month | Medication overuse headache | Withdrawal of overused medications (may need bridge therapy) → start preventive therapy simultaneously → expect temporary worsening |
| Headache 15 or more days per month, at least 8 days with migraine features, evolved from episodic migraine | Chronic migraine | Rule out medication overuse → preventive therapy (topiramate, propranolol, amitriptyline, or CGRP monoclonal antibodies) → consider botulinum toxin |
| Headache 15 or more days per month, bilateral pressing, mild-to-moderate, no migraine features | Chronic tension-type headache | Amitriptyline for prevention → physical therapy → address stress, sleep, and lifestyle factors |
| Daily headache from onset with exact recall of start date, often after viral illness | New daily persistent headache | MRI to exclude secondary cause → treat based on phenotype (migraine-like or tension-like) → often refractory |
| Continuous strictly unilateral headache with exacerbations and autonomic features | Hemicrania continua | Indomethacin trial → complete response confirms diagnosis → MRI to exclude secondary cause |
| Daily headache worse in morning, visual obscurations, pulsatile tinnitus, obese young woman | Idiopathic intracranial hypertension | MRI/MRV → lumbar puncture for opening pressure → acetazolamide → weight loss → ophthalmology monitoring |
“What Do I Do If…” Decision Reference
| Clinical Situation | Immediate Action | Next Step |
|---|---|---|
| CT is negative but I still suspect subarachnoid hemorrhage | Perform lumbar puncture (wait 6-12 hours from onset if possible) | Look for xanthochromia (spectrophotometry); if positive, CT angiography to find source |
| Patient over 50 with new headache and elevated ESR | Start prednisolone 40-60 mg daily immediately | Arrange temporal artery biopsy within 2 weeks; do not wait for biopsy to start treatment |
| Migraine is not responding to triptans | Ensure adequate dose, early treatment, and correct formulation | Try different triptan; consider combination with NSAID; rule out medication overuse; consider CGRP antagonists |
| Patient is overusing analgesics | Explain medication overuse headache; plan withdrawal | Stop overused medication (abrupt or tapered); start preventive therapy; bridge with limited use of different drug class |
| Patient has migraine with aura and wants contraception | Avoid combined hormonal contraceptives (estrogen) | Recommend progestogen-only methods, copper IUD, or barrier methods; migraine with aura plus estrogen increases stroke risk |
| I suspect cluster headache but patient is not in an attack | Detailed history to confirm cluster features; prescribe oxygen and sumatriptan | MRI brain to exclude secondary causes; start verapamil if in cluster period; refer to headache specialist |
| Patient has chronic daily headache and no clear diagnosis | Assess for medication overuse first; detailed diary for 4 weeks | MRI if not already done; identify predominant phenotype; trial of appropriate preventive therapy; consider indomethacin trial if strictly unilateral |
| Headache is worse when patient stands up | Consider intracranial hypotension (cerebrospinal fluid leak) | MRI brain with gadolinium → if characteristic findings, conservative management first; epidural blood patch if refractory |
| Headache is worse when patient lies down | Consider raised intracranial pressure | Fundoscopy for papilledema; urgent MRI/MRV; lumbar puncture for opening pressure after imaging |
| Patient presents with first seizure and headache | Emergency CT head | Consider cerebral venous thrombosis (especially if papilledema), mass lesion, encephalitis; MRI/MRV; lumbar puncture if infection suspected |
Troubleshooting Refractory Headache
When Treatment Is Not Working, Ask These Questions
- Is the diagnosis correct? — Review history; consider alternative diagnoses; reassess for secondary causes
- Is there medication overuse? — This is the most common reason for treatment failure; carefully quantify acute medication use
- Was preventive treatment adequate? — Appropriate drug, adequate dose, sufficient duration (at least 8-12 weeks at target dose)?
- Was adherence good? — Many patients stop preventive medications due to side effects or lack of immediate benefit
- Are there multiple overlapping headache types? — Common to have migraine plus tension-type plus medication overuse
- Are there perpetuating factors? — Sleep disorders, caffeine, stress, depression, anxiety, musculoskeletal issues
- Has something changed? — New secondary cause superimposed on primary headache disorder
- Would specialist referral help? — Headache specialist, pain clinic, multidisciplinary team
When to Refer to a Specialist
Urgent Referral
- Suspected giant cell arteritis — ophthalmology and rheumatology
- Papilledema with visual symptoms — ophthalmology and neurology
- Trigeminal autonomic cephalalgia not responding to first-line treatment
- New daily persistent headache (often refractory)
- Intracranial hypotension requiring blood patch
Routine Referral
- Chronic migraine failing multiple preventive treatments
- Consideration for botulinum toxin or CGRP monoclonal antibodies
- Diagnostic uncertainty after initial workup
- Medication overuse headache with failed withdrawal attempts
- Significant psychiatric comorbidity affecting headache management
8. Clinical Pearls and Pitfalls
Practical wisdom — learn from successes and avoid common mistakes
Must-Know Clinical Pearls
Thunderclap headache is subarachnoid hemorrhage until proven otherwise: Even with a normal CT, lumbar puncture is mandatory if clinical suspicion persists. CT sensitivity drops from greater than 95% at 6 hours to approximately 50% at one week.
Medication overuse is the most common cause of chronic daily headache: Always quantify acute medication use. Using analgesics or triptans more than 10-15 days per month transforms episodic headache into daily headache.
Most “sinus headaches” are actually migraine: Studies show that up to 90% of self-diagnosed sinus headaches meet criteria for migraine. True bacterial sinusitis usually has purulent discharge and fever.
Giant cell arteritis can cause irreversible blindness within hours: In any patient over 50 with new headache, scalp tenderness, jaw claudication, or visual symptoms, start high-dose corticosteroids immediately — do not wait for biopsy or inflammatory markers.
Cluster headache patients are restless; migraine patients prefer stillness: This behavioral difference is highly discriminating. Cluster headache patients pace, rock, or bang their head; migraine patients lie down in a dark, quiet room.
Response to indomethacin is diagnostic for certain headaches: Complete resolution with indomethacin confirms hemicrania continua or paroxysmal hemicrania. This is both diagnostic and therapeutic — trial it when considering these diagnoses.
A normal neurological examination does not exclude serious pathology: Subarachnoid hemorrhage, meningitis, and early mass lesions may present with completely normal examination. The history drives the investigation.
Positional headache is a valuable clue: Worse lying down suggests raised intracranial pressure; worse standing suggests intracranial hypotension. This simple question can dramatically change the differential.
Critical Pitfalls to Avoid
Accepting a normal CT as excluding subarachnoid hemorrhage: CT sensitivity decreases with time. If the clinical picture suggests subarachnoid hemorrhage and CT is negative, lumbar puncture is mandatory — xanthochromia may be the only evidence.
Waiting for biopsy results before treating suspected giant cell arteritis: Vision loss can occur within hours. Start corticosteroids immediately if clinical suspicion is high. Biopsy remains positive for at least 2 weeks after starting steroids.
Attributing new headache in an older patient to “tension”: New-onset headache after age 50 requires investigation. Consider giant cell arteritis, mass lesion, subdural hematoma, and medication-related causes before diagnosing primary headache.
Prescribing frequent acute medications without addressing overuse: Providing ongoing prescriptions for analgesics or triptans without monitoring frequency perpetuates medication overuse headache. Always quantify and counsel.
Stopping preventive medications too early: Most preventive medications take 8-12 weeks at target dose to show full effect. Stopping after 2-4 weeks due to “no improvement” is premature.
Missing meningeal signs in elderly or immunocompromised patients: Classic signs of meningism are often absent in these populations. Have a low threshold for lumbar puncture if meningitis is suspected clinically.
Prescribing combined hormonal contraceptives to women with migraine with aura: This significantly increases stroke risk. Migraine with aura is a contraindication to estrogen-containing contraceptives.
Performing lumbar puncture without imaging when papilledema or focal signs are present: This risks herniation if there is a mass lesion. Always image first when there are signs suggesting raised intracranial pressure or focal pathology.
Key Takeaways
- Primary headache disorders (migraine, tension-type, cluster) account for approximately 90% of headache presentations, but always consider and exclude secondary causes when red flags are present.
- Thunderclap headache (maximal intensity within seconds) requires emergency investigation for subarachnoid hemorrhage regardless of examination findings.
- New headache in patients over 50 should prompt consideration of giant cell arteritis, malignancy, and subdural hematoma — do not assume a primary headache disorder.
- Medication overuse headache is under-recognized and is the most common cause of chronic daily headache that fails to respond to treatment.
- The clinical history is the most important diagnostic tool — most primary headaches are diagnosed clinically without investigation.
- Physical examination in primary headache is often normal; its main value is detecting red flags that indicate secondary causes.
- Fundoscopy should be performed in all patients with new, severe, or progressive headache to detect papilledema.
- Positional features are diagnostically valuable: worse lying down suggests raised intracranial pressure; worse standing suggests intracranial hypotension.
- Cluster headache is distinguished by restlessness during attacks and ipsilateral autonomic features — high-flow oxygen is first-line acute treatment.
- Response to indomethacin is diagnostic for paroxysmal hemicrania and hemicrania continua — trial it when these diagnoses are considered.
- Prevention is key in frequent headache — patients having 4 or more migraine days per month benefit from preventive therapy rather than relying on acute treatment alone.
- Always consider multiple overlapping diagnoses — it is common to have migraine plus tension-type headache plus medication overuse in the same patient.
Quick Reference Algorithm
Systematic Approach to Headache:
- Assess urgency: Are there red flags requiring emergency investigation? (thunderclap onset, fever with meningism, focal neurological signs, papilledema, altered consciousness)
- Classify temporally: Is this acute/new-onset, episodic recurrent, or chronic daily headache?
- Take targeted history: Use the “HEADACHE” mnemonic; ask about positional features, medication use, and autonomic symptoms
- Perform focused examination: Vital signs, fundoscopy, cranial nerves, meningeal signs, temporal arteries in patients over 50
- Investigate appropriately: Based on clinical suspicion — remember most primary headaches need no investigation
- Make a specific diagnosis: Apply ICHD-3 criteria; consider secondary causes if atypical features
- Address medication overuse: If present, this must be addressed before other treatments will be effective
- Initiate appropriate treatment: Acute treatment for attacks; preventive therapy if frequent; lifestyle modification
- Plan follow-up: Use headache diary; reassess diagnosis if treatment fails; adjust management accordingly