Clinical Approach to Headache

Comprehensive Practical Framework

1
Symptom Overview
Overview
2
Pathophysiology
Mechanism
3
History Taking
History
4
Physical Examination
Examination
5
Differential Diagnosis
Differential
6
Investigations
Workup
7
Clinical Decision-Making
Algorithm
8
Pearls and Pitfalls
Summary

1. Symptom Overview

Understanding the clinical significance and classification of Headache

Headache is one of the most common symptoms encountered in clinical practice, affecting approximately 50% of the global population annually. It accounts for roughly 4% of all emergency department visits and is the fourth leading cause of visits to outpatient clinics. The lifetime prevalence of headache exceeds 90%, with tension-type headache affecting 30-78% of adults and migraine affecting 12-15% of the population. Despite its ubiquity, headache remains a diagnostic challenge because it can represent anything from benign primary disorders to life-threatening emergencies.

Definition

Headache is defined as pain located anywhere in the region of the head, including the face, temples, and upper cervical area. It arises from activation of pain-sensitive structures within the cranium (meninges, blood vessels, cranial nerves) or extracranial tissues (muscles, fascia, periosteum, skin, blood vessels). The brain parenchyma itself is insensate and does not generate pain.

The Fundamental Division: Primary vs Secondary Headache

Primary Headache Disorders

Definition: Headache is the disease itself; no underlying structural, metabolic, or systemic cause.

Prevalence: Account for over 90% of all headaches.

Examples: Migraine, tension-type headache, cluster headache, other trigeminal autonomic cephalalgias.

Clinical significance: Diagnosis based on clinical criteria; investigations typically normal.

Secondary Headache Disorders

Definition: Headache is a symptom of an identifiable underlying condition.

Prevalence: Account for less than 10% of headaches but carry higher morbidity and mortality.

Examples: Subarachnoid hemorrhage, meningitis, brain tumor, giant cell arteritis, idiopathic intracranial hypertension.

Clinical significance: Requires identification and treatment of the underlying cause.

Classification by Duration and Temporal Pattern

Category	Duration	Common Causes	Clinical Significance
Hyperacute (Thunderclap)	Peaks within seconds to 1 minute	Subarachnoid hemorrhage, cerebral venous thrombosis, arterial dissection, reversible cerebral vasoconstriction syndrome, pituitary apoplexy	Medical emergency until proven otherwise; requires immediate investigation
Acute	Less than 4 weeks	Viral illness, sinusitis, first migraine attack, medication-related, intracranial infection, hypertensive emergency	New-onset headache requires careful evaluation to exclude secondary causes
Subacute	4 weeks to 3 months	Evolving intracranial mass, subdural hematoma, giant cell arteritis, idiopathic intracranial hypertension, medication overuse	Progressive or changing headache pattern warrants investigation
Chronic	Greater than 3 months	Chronic migraine, chronic tension-type headache, new daily persistent headache, medication overuse headache, hemicrania continua	Focus on identifying headache type, triggers, and medication overuse

Classification by Character and Quality

Character	Description	Typical Associations
Pulsating/Throbbing	Rhythmic pain corresponding with heartbeat	Migraine, fever-related headache, hangover, arteriovenous malformation
Pressing/Tightening	Band-like or vice-like pressure sensation	Tension-type headache, cervicogenic headache, medication overuse headache
Stabbing/Piercing	Brief, sharp, ice-pick like jabs	Primary stabbing headache, trigeminal neuralgia, cluster headache
Burning	Hot, searing quality	Neuropathic pain, occipital neuralgia, post-herpetic neuralgia
Explosive	Sudden, severe, “worst headache of life”	Subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, thunderclap headache
Deep/Boring	Constant, deep-seated ache	Cluster headache, hemicrania continua, intracranial mass

Classification by Location

Unilateral

Strictly unilateral: Cluster headache, paroxysmal hemicrania, hemicrania continua, trigeminal neuralgia

Usually unilateral: Migraine (60% unilateral), cervicogenic headache

Bilateral

Holocephalic: Tension-type headache, meningitis, subarachnoid hemorrhage, idiopathic intracranial hypertension

Bifrontal: Frontal sinusitis, tension-type headache

Localized

Periorbital: Cluster headache, acute glaucoma, optic neuritis

Temporal: Giant cell arteritis, temporomandibular joint dysfunction

Occipital: Cervicogenic, occipital neuralgia, posterior fossa lesions

Classification by Pattern and Timing

Pattern	Description	Suggests
Early morning headache	Present upon waking, may improve with upright position	Raised intracranial pressure, sleep apnea, medication overuse, carbon monoxide exposure
Nocturnal awakening	Awakens patient from sleep at consistent times	Cluster headache (alarm clock headache), hypnic headache, raised intracranial pressure
End-of-day worsening	Builds throughout the day, worst in evening	Tension-type headache, eye strain, cervicogenic headache
Positional	Changes with body position	Worse upright: low cerebrospinal fluid pressure; Worse supine: raised intracranial pressure
Exertional	Triggered by physical exertion, Valsalva, cough, or sexual activity	Primary exertional headache, or secondary to Chiari malformation, intracranial lesion
Episodic clustering	Multiple attacks daily over weeks, then remission for months	Cluster headache, paroxysmal hemicrania
Menstrual association	Occurs predictably with menstrual cycle	Menstrual migraine (typically perimenstrual, days -2 to +3)

Key Concept: The “Big Five” Primary Headaches

Five primary headache disorders account for the vast majority of headache presentations:

Tension-type headache — most common (lifetime prevalence 30-78%)
Migraine without aura — second most common (12% prevalence)
Migraine with aura — subset of migraine (4-5% prevalence)
Cluster headache — rare but distinctive (0.1% prevalence)
Medication overuse headache — iatrogenic, increasingly common (1-2% prevalence)

Global Impact of Headache Disorders

Migraine alone is ranked as the second leading cause of years lived with disability worldwide. Headache disorders collectively represent the third highest cause of disability globally. The economic burden includes direct healthcare costs, lost productivity, and reduced quality of life. Despite this, headache disorders remain underdiagnosed and undertreated, with fewer than 50% of migraine sufferers receiving an accurate diagnosis.

2. Pathophysiology and Mechanisms

Understanding the underlying mechanisms of Headache

Understanding headache pathophysiology is essential for rational diagnosis and treatment. The brain parenchyma itself lacks pain receptors, so headache arises from activation of pain-sensitive structures: the meninges, blood vessels, cranial nerves (particularly the trigeminal nerve), and extracranial tissues including muscles, fascia, and periosteum. The trigeminovascular system serves as the final common pathway for most headache disorders.

Pain-Sensitive Structures of the Head

Structure	Innervation	Clinical Relevance
Dura mater and venous sinuses	Trigeminal nerve (cranial nerve V, ophthalmic division primarily)	Referred pain to frontal region; activated in migraine, meningitis, intracranial hypotension
Cerebral arteries (proximal)	Trigeminal nerve	Distension, inflammation, or spasm causes headache; key in migraine and subarachnoid hemorrhage
Cranial nerves V, VII, IX, X	Direct nociceptive fibers	Neuralgias produce characteristic stabbing pain in nerve distribution
Upper cervical nerve roots (C1-C3)	Cervical spinal nerves	Cervicogenic headache; convergence with trigeminal nucleus explains referred pain to head
Scalp muscles and fascia	Trigeminal nerve, cervical nerves	Tension-type headache; pericranial muscle tenderness
Periosteum of skull	Trigeminal nerve, cervical nerves	Trauma, bone lesions, Paget disease
Extracranial arteries	Trigeminal nerve	Giant cell arteritis affects temporal, occipital arteries
Paranasal sinuses	Trigeminal nerve (V1, V2)	Sinusitis causes referred pain; often misdiagnosed when actually migraine
Eyes and orbits	Trigeminal nerve (V1)	Acute glaucoma, optic neuritis; cluster headache periorbital location

The Trigeminovascular System

The trigeminovascular system is central to the pathophysiology of primary headache disorders, particularly migraine and cluster headache. It consists of sensory nerve fibers from the trigeminal ganglion that innervate cerebral blood vessels and meninges.

Component	Structure	Function
Peripheral afferents	Trigeminal nerve fibers surrounding meningeal vessels	Detect noxious stimuli; release vasoactive neuropeptides (calcitonin gene-related peptide, substance P)
First-order neurons	Trigeminal ganglion	Cell bodies of trigeminal sensory neurons
Second-order neurons	Trigeminal nucleus caudalis (in brainstem/upper cervical cord)	Receives convergent input from trigeminal and upper cervical afferents; explains referred pain patterns
Third-order neurons	Thalamus (ventral posteromedial nucleus)	Relay to cortex for conscious pain perception
Cortical processing	Somatosensory cortex, insular cortex, anterior cingulate	Pain perception, emotional response, autonomic responses

Migraine Pathophysiology

Migraine is now understood as a complex neurovascular disorder involving cortical, subcortical, and brainstem mechanisms rather than a purely vascular phenomenon.

Cortical Spreading Depression

Mechanism: Wave of neuronal depolarization followed by suppression that spreads across the cortex at 3-5 mm/minute.

Clinical correlation: Corresponds to the spreading visual and sensory symptoms of migraine aura.

Downstream effects: Activates trigeminal afferents in the meninges, triggering the headache phase.

Trigeminal Activation

Mechanism: Release of calcitonin gene-related peptide (CGRP) from trigeminal nerve endings.

Effects: Vasodilation, neurogenic inflammation, mast cell degranulation, plasma protein extravasation.

Therapeutic target: CGRP antagonists and monoclonal antibodies are effective migraine treatments.

Phase	Mechanism	Clinical Features
Prodrome (hours to days before)	Hypothalamic activation; dopaminergic and serotoninergic changes	Yawning, food cravings, mood changes, neck stiffness, fatigue
Aura (5-60 minutes)	Cortical spreading depression	Visual phenomena (scintillating scotoma), sensory symptoms, speech disturbance
Headache (4-72 hours)	Trigeminovascular activation; central sensitization	Unilateral throbbing pain, photophobia, phonophobia, nausea, cutaneous allodynia
Postdrome (hours to days after)	Recovery phase; residual cortical dysfunction	Fatigue, cognitive difficulties, mood changes

Tension-Type Headache Pathophysiology

Peripheral Mechanisms

Pericranial muscle tenderness: Increased tenderness on palpation of head and neck muscles
Myofascial trigger points: Localized areas of muscle hyperirritability
Sustained muscle contraction: Leads to local ischemia and sensitization

Central Mechanisms

Central sensitization: Enhanced excitability of second-order neurons in trigeminal nucleus
Impaired supraspinal modulation: Reduced descending inhibition of pain pathways
Chronification: Repeated peripheral input leads to persistent central changes

Cluster Headache and Trigeminal Autonomic Cephalalgias

Cluster headache involves activation of both the trigeminovascular system and the trigeminal-autonomic reflex, with a central role for the hypothalamus.

Component	Mechanism	Clinical Manifestation
Hypothalamic activation	Posterior hypothalamus acts as pacemaker; explains circadian and circannual periodicity	Attacks occur at same time daily; seasonal clustering
Trigeminal activation	First division trigeminal nerve activation causes severe pain	Excruciating unilateral periorbital/temporal pain
Parasympathetic activation	Trigeminal-autonomic reflex via superior salivatory nucleus	Lacrimation, conjunctival injection, nasal congestion, rhinorrhea
Sympathetic dysfunction	Impaired sympathetic outflow (possibly from cavernous sinus involvement)	Ptosis, miosis (partial Horner syndrome)

Mechanisms of Secondary Headaches

Condition	Mechanism	Clinical Implication
Subarachnoid hemorrhage	Blood irritates meninges; sudden stretch of arterial wall; raised intracranial pressure	Thunderclap onset; meningism develops over hours; always investigate sudden severe headache
Meningitis	Inflammation of meninges activates trigeminal afferents; raised intracranial pressure	Fever, meningism, photophobia; may mimic severe migraine initially
Raised intracranial pressure	Traction on pain-sensitive dura, blood vessels, and cranial nerves	Worse supine, morning headache, Valsalva worsening, papilledema
Low cerebrospinal fluid pressure	Brain sags, causing traction on meninges and bridging veins	Postural headache: severe when upright, relieved when supine
Giant cell arteritis	Granulomatous inflammation of medium and large arteries	Temporal artery tenderness, jaw claudication, visual loss risk; urgent steroids needed
Cervicogenic headache	Upper cervical afferents converge with trigeminal nucleus caudalis	Pain referred from neck to head; triggered by neck movement or posture
Medication overuse headache	Central sensitization from frequent analgesic use; altered pain modulation	Headache paradoxically worsens with increasing analgesic use; requires withdrawal

Central Sensitization and Chronification

Central sensitization is a key mechanism in the transformation from episodic to chronic headache disorders. Understanding this process is crucial for prevention and management.

Central Sensitization: A state of hyperexcitability in the central nervous system that amplifies pain signals and can maintain pain even after the initial trigger has resolved.

Clinical manifestation: Cutaneous allodynia (pain from normally non-painful stimuli, such as brushing hair or wearing glasses)
Risk factors for chronification: High attack frequency, medication overuse, obesity, depression, stressful life events
Treatment implication: Early and effective treatment of acute attacks may prevent central sensitization

Often Overlooked Mechanism

Trigeminocervical convergence: The trigeminal nucleus caudalis extends into the upper cervical spinal cord (C1-C3), where it receives convergent input from both trigeminal and cervical afferents. This anatomical arrangement explains why neck pain commonly accompanies primary headache disorders and why cervical pathology can cause headache referred to the head. It also explains the effectiveness of occipital nerve blocks in some headache disorders. Always examine the cervical spine in headache patients.

Key Neurotransmitters and Therapeutic Targets

Calcitonin gene-related peptide (CGRP): Potent vasodilator; key mediator of migraine; target of gepants and monoclonal antibodies
Serotonin (5-HT): Receptor subtypes 5-HT1B/1D are targets of triptans; 5-HT1F is target of ditans
Substance P: Promotes neurogenic inflammation; co-released with CGRP from trigeminal afferents
Nitric oxide: Potent vasodilator; may trigger migraine; glyceryl trinitrate can provoke attacks
Glutamate: Excitatory neurotransmitter; elevated in migraine; may contribute to cortical spreading depression

3. History Taking

A comprehensive approach to eliciting the Headache history

Red Flags — Require Urgent Evaluation

Thunderclap onset — Subarachnoid hemorrhage, reversible cerebral vasoconstriction syndrome, arterial dissection, pituitary apoplexy
New headache after age 50 — Giant cell arteritis, intracranial mass, subdural hematoma
Progressive worsening over weeks — Intracranial mass, chronic subdural hematoma, idiopathic intracranial hypertension
Systemic symptoms (fever, weight loss, night sweats) — Infection, malignancy, giant cell arteritis
Neurological symptoms or signs — Intracranial lesion, stroke, venous thrombosis

Papilledema — Raised intracranial pressure (requires urgent imaging)
Positional component — Raised intracranial pressure (worse supine) or low cerebrospinal fluid pressure (worse upright)
Triggered by Valsalva, cough, or exertion — Chiari malformation, intracranial lesion (requires imaging first presentation)
Immunocompromised state — Opportunistic infection, lymphoma
History of malignancy — Metastatic disease, carcinomatous meningitis
Pregnancy or postpartum — Pre-eclampsia, cerebral venous thrombosis, reversible cerebral vasoconstriction syndrome

Recognizing Secondary Headache: The “SNOOP” Criteria

The “SNOOP” mnemonic helps identify red flags suggesting secondary headache:

S — Systemic symptoms (fever, weight loss) or Secondary risk factors (HIV, malignancy, immunosuppression)
N — Neurological symptoms or signs (confusion, weakness, visual changes, papilledema)
O — Onset sudden (thunderclap headache reaching maximum intensity within seconds to minutes)
O — Older age at onset (new headache beginning after age 50 years)
P — Pattern change (progressive headache, change in established headache pattern, positional features, precipitated by Valsalva)

Systematic History: The “HEADACHE” Approach

Use the mnemonic “HEADACHE” to ensure comprehensive history taking:

H — How did it start?: Onset (sudden vs gradual), first occurrence or recurrent, any precipitating event
E — Experience of pain: Quality (throbbing, pressing, stabbing), severity (0-10 scale), location and radiation
A — Associated symptoms: Nausea, vomiting, photophobia, phonophobia, aura, autonomic features, fever, neck stiffness
D — Duration and frequency: Length of individual attacks, frequency per week/month, total headache days per month
A — Aggravating and alleviating factors: Position, activity, Valsalva, sleep, medications, caffeine
C — Current and past treatments: What has been tried, what helped, medication frequency (overuse?)
H — History (medical, family, social): Previous headaches, comorbidities, family history of migraine, occupation, stress
E — Effect on life: Impact on work, relationships, mood, sleep, disability assessment

Targeted Questions by Suspected Cause

Suspected Cause	Key Features	Ask This Question
Migraine	Unilateral, pulsating, moderate-severe, nausea, photophobia, phonophobia, disability	“Does light or noise bother you during the headache? Do you need to lie down in a dark room?”
Tension-type headache	Bilateral, pressing/tightening, mild-moderate, no nausea, no significant photophobia	“Does the headache feel like a tight band around your head? Can you continue your normal activities?”
Cluster headache	Strictly unilateral, severe periorbital pain, autonomic features, restlessness, circadian pattern	“Do you get a blocked or runny nose, or watery red eye on the same side? Do you feel restless and pace around during attacks?”
Medication overuse headache	Daily or near-daily headache, regular analgesic use, headache returns when medication wears off	“How many days per week do you take painkillers or triptans? Do you wake up with headache that improves after taking medication?”
Subarachnoid hemorrhage	Thunderclap onset, “worst headache of life,” meningism, loss of consciousness	“Did this headache reach its maximum intensity within seconds? Is this the worst headache you have ever experienced?”
Giant cell arteritis	Age over 50, new headache, scalp tenderness, jaw claudication, visual symptoms, polymyalgia	“Does your jaw ache when you chew? Is your scalp tender when you brush your hair? Have you had any visual changes?”
Raised intracranial pressure	Worse in morning, worse supine, worse with Valsalva, visual obscurations, pulsatile tinnitus	“Is the headache worse when you wake up or when lying flat? Does coughing or straining make it worse? Do you have brief episodes of vision going grey?”
Low cerebrospinal fluid pressure	Postural (worse upright, better lying down), may follow lumbar puncture or trauma	“Is the headache much worse when you stand up and better when you lie down? Have you had a recent lumbar puncture or epidural?”
Cervicogenic headache	Unilateral, starts in neck, precipitated by neck movement or sustained posture	“Does the headache start in your neck and spread to your head? Does turning your head trigger the pain?”
Trigeminal neuralgia	Brief electric shock-like pain, triggered by light touch, chewing, talking; refractory periods	“Is the pain like an electric shock lasting only seconds? Is it triggered by touching your face, chewing, or talking?”

Characterizing Migraine Aura

Key Questions for Aura

Aura is a fully reversible focal neurological symptom that typically develops gradually over 5-20 minutes and lasts less than 60 minutes. Ask specifically:

Visual aura (most common, 90%): “Do you see flashing lights, zigzag lines, or have blind spots before the headache?”
Sensory aura: “Do you get tingling or numbness that spreads gradually across your hand or face?”
Speech aura: “Do you have difficulty finding words or speaking clearly before the headache?”
Timing: “How long do these symptoms last? Do they come before, during, or separate from the headache?”
Gradual spread: “Do the visual or sensory symptoms spread gradually, or do they appear all at once?” (Gradual spread suggests aura; sudden onset suggests stroke)

Medication and Substance History

Medications That Cause or Worsen Headache

Nitrates — Vasodilation causes throbbing headache
Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) — Vasodilation
Calcium channel blockers — Vasodilation
Hormone replacement therapy / oral contraceptives — May trigger or worsen migraine
Proton pump inhibitors — Reported association with headache
Overused analgesics — Paracetamol, NSAIDs, opioids, triptans, combination analgesics
Withdrawal from — Caffeine, opioids, estrogen

Substances and Lifestyle Factors

Caffeine: Both excess intake and withdrawal can trigger headache
Alcohol: Red wine and other triggers in migraine; cluster headache triggered during cluster periods
Recreational drugs: Cocaine, amphetamines can cause severe headache (and stroke)
Sleep: Both deprivation and oversleeping trigger migraine
Fasting: Skipped meals trigger migraine
Stress: Common trigger; also “let-down” headache after stress resolves
Carbon monoxide exposure: Bilateral headache, multiple household members affected

Identifying Medication Overuse

Medication Type	Threshold for Overuse	Key Points
Simple analgesics (paracetamol, aspirin, NSAIDs)	≥15 days per month for ≥3 months	Most common cause of medication overuse headache
Triptans	≥10 days per month for ≥3 months	May cause medication overuse headache more rapidly than simple analgesics
Opioids	≥10 days per month for ≥3 months	Particularly problematic; associated with poor outcomes
Combination analgesics (e.g., paracetamol + codeine + caffeine)	≥10 days per month for ≥3 months	Multiple components increase overuse risk
Ergotamine	≥10 days per month for ≥3 months	Rarely used now but historically significant

Social and Occupational History

Occupational Considerations

Screen time: Prolonged computer use, eye strain
Posture: Desk work, cervicogenic triggers
Shift work: Sleep disruption triggers migraine
Chemical exposure: Solvents, carbon monoxide
Noise exposure: May exacerbate or trigger headache
Physical labor: Exertional headache considerations

Psychosocial Assessment

Depression and anxiety: Bidirectional relationship with chronic headache
Sleep disorders: Insomnia, sleep apnea associated with morning headache
Life stressors: Work, relationships, finances
Domestic situation: Consider intimate partner violence if injuries
Impact assessment: Days missed from work, reduced productivity
Coping strategies: What does the patient do during attacks?

Family History

Why Family History Matters

Migraine: Over 70% of migraine patients have a first-degree relative with migraine. A positive family history strongly supports the diagnosis.

Cluster headache: First-degree relatives have 14-39 times increased risk.

Intracranial aneurysm: Family history of subarachnoid hemorrhage or known aneurysm increases risk; screening may be indicated.

Ask specifically: “Does anyone in your family have bad headaches or migraines? Has anyone had a brain hemorrhage or aneurysm?”

4. Physical Examination

A systematic head-to-toe approach for Headache

Systematic Framework: Use the “General → Vital Signs → Head and Neck → Neurological → Fundoscopy” approach for complete examination of patients presenting with headache. The goals are to: (1) identify signs of secondary headache, (2) detect neurological deficits, and (3) look for features supporting primary headache diagnosis.

General Inspection

Level of consciousness: Altered consciousness suggests serious pathology (infection, hemorrhage, raised intracranial pressure)
Appearance: Distress level, pallor, diaphoresis, photophobia (wearing sunglasses, avoiding light)
Behavior during attack: Lying still (migraine) versus pacing/restless (cluster headache)
Ptosis: May indicate Horner syndrome (cluster headache, carotid dissection) or third nerve palsy
Facial asymmetry: May suggest stroke or mass lesion
Skin: Rash (meningococcal disease), café-au-lait spots (neurofibromatosis)
Cushingoid features: Consider idiopathic intracranial hypertension

Vital Signs

Vital Sign	What to Look For	Clinical Significance
Temperature	Fever (>38°C)	Meningitis, encephalitis, brain abscess, sinusitis, systemic infection; also giant cell arteritis
Blood pressure	Severe hypertension (>180/120 mmHg)	Hypertensive emergency can cause headache; also check for pre-eclampsia in pregnancy
Heart rate	Bradycardia with hypertension (Cushing reflex)	Suggests raised intracranial pressure with impending herniation
Respiratory rate	Irregular breathing patterns	May indicate brainstem dysfunction or raised intracranial pressure
Oxygen saturation	Hypoxia	Consider carbon monoxide poisoning if unexplained (check carboxyhemoglobin)

Head and Face Examination

Scalp and Skull

Temporal arteries: Tenderness, thickening, reduced pulsation, nodularity (giant cell arteritis)
Scalp tenderness: Localized (giant cell arteritis, referred pain) or diffuse (tension-type headache, cutaneous allodynia in migraine)
Pericranial muscle tenderness: Palpate temporalis, frontalis, masseter, pterygoids, sternocleidomastoid, trapezius
Skull tenderness: Over sinuses (sinusitis), localized bony lesion
Trigger points: Greater occipital nerve at nuchal line

Face and Sinuses

Sinus tenderness: Frontal and maxillary percussion/pressure
Temporomandibular joint: Tenderness, clicking, reduced opening (temporomandibular dysfunction)
Facial sensation: Test all three trigeminal divisions
Trigger zones: Light touch triggering pain suggests trigeminal neuralgia
Autonomic features: Conjunctival injection, lacrimation, nasal congestion, eyelid edema (cluster headache)

Eye Examination

Finding	How to Assess	Clinical Significance
Visual acuity	Snellen chart or near vision card	Reduced acuity suggests optic nerve involvement (giant cell arteritis, idiopathic intracranial hypertension, optic neuritis)
Visual fields	Confrontation testing	Field defects suggest intracranial lesion; enlarged blind spot in idiopathic intracranial hypertension
Pupil responses	Direct and consensual light reflex, accommodation	Third nerve palsy (aneurysm): dilated pupil, ptosis. Horner syndrome (dissection, cluster): miosis, ptosis
Eye movements	Test in all directions; ask about diplopia	Sixth nerve palsy often earliest sign of raised intracranial pressure; painful ophthalmoplegia suggests cavernous sinus
Conjunctival injection	Inspect for redness	Ipsilateral injection in cluster headache; bilateral in acute glaucoma
Intraocular pressure	Tonometry if available; hard globe on palpation	Elevated in acute angle-closure glaucoma (ocular emergency)

Fundoscopic Examination

Critical Importance of Fundoscopy

Fundoscopy should be performed in all patients presenting with new or changed headache. It is the only non-invasive method to directly visualize signs of raised intracranial pressure.

Papilledema: Blurred disc margins, loss of venous pulsations, elevated disc, hemorrhages — indicates raised intracranial pressure; requires urgent imaging
Subhyaloid hemorrhage: Crescent-shaped hemorrhage between retina and vitreous — strongly suggests subarachnoid hemorrhage
Optic atrophy: Pale disc — previous optic nerve damage
Absent venous pulsations: Early sign of raised intracranial pressure (though absent in 10% of normal individuals)

Neck Examination

Meningism Assessment

Neck stiffness: Resistance to passive neck flexion (chin to chest)
Kernig sign: Pain on knee extension with hip flexed
Brudzinski sign: Involuntary hip/knee flexion when neck is flexed
Interpretation: Meningism suggests meningitis or subarachnoid hemorrhage; may be absent early or in elderly/immunocompromised

Cervical Spine Assessment

Range of motion: Flexion, extension, rotation, lateral flexion
Tenderness: Paraspinal muscles, facet joints, greater occipital nerve
Provocation: Does neck movement reproduce or worsen headache? (cervicogenic headache)
Carotid tenderness: May suggest carotid dissection (handle gently)

Neurological Examination

Cranial Nerves

Cranial Nerve	Test	Relevant Findings
I (Olfactory)	Smell identification	Anosmia may occur with frontal lobe lesions, post-traumatic
II (Optic)	Acuity, fields, fundoscopy, pupil afferent	See eye examination above; critical in headache assessment
III, IV, VI (Oculomotor, Trochlear, Abducens)	Eye movements, pupil size, ptosis	Third nerve palsy with dilated pupil: posterior communicating artery aneurysm until proven otherwise
V (Trigeminal)	Facial sensation, corneal reflex, jaw power	Sensory loss suggests trigeminal nerve lesion; trigger points in trigeminal neuralgia
VII (Facial)	Facial movements	Weakness may indicate brainstem or cortical lesion
VIII (Vestibulocochlear)	Hearing, balance, nystagmus	Hearing loss with headache: acoustic neuroma, meningitis
IX, X, XI, XII	Palate, voice, sternocleidomastoid, tongue	Lower cranial nerve palsies suggest posterior fossa or skull base pathology

Motor, Sensory, and Coordination

Motor examination: Tone, power (all limbs), pronator drift — asymmetry suggests structural lesion
Reflexes: Deep tendon reflexes, plantar responses — asymmetry or upgoing plantars suggest upper motor neuron lesion
Sensory examination: Light touch, pinprick, proprioception — sensory level suggests spinal cord involvement
Coordination: Finger-nose, heel-shin, gait — ataxia suggests cerebellar or posterior fossa pathology
Gait: Observe walking, tandem gait, Romberg test

Expected Findings by Etiology

Condition	General / Vitals	Head and Neck	Neurological
Migraine	Photophobic, lying still in dark; normal vitals	Cutaneous allodynia; pericranial tenderness	Usually normal; may have mild focal signs during aura (resolves)
Tension-type headache	Able to continue activities; normal vitals	Pericranial muscle tenderness	Normal
Cluster headache	Agitated, pacing; normal vitals	Ipsilateral: ptosis, miosis, lacrimation, conjunctival injection, rhinorrhea, facial sweating	Normal (partial Horner may persist between attacks)
Subarachnoid hemorrhage	May be drowsy; hypertension common	Neck stiffness (may take hours to develop); subhyaloid hemorrhage	May have focal deficits; reduced consciousness
Meningitis	Fever; may appear unwell	Neck stiffness, Kernig and Brudzinski signs; rash in meningococcal disease	May be normal or have reduced consciousness, focal signs
Giant cell arteritis	Low-grade fever; weight loss	Temporal artery: tender, thickened, non-pulsatile; scalp tenderness	May have visual loss (emergency); jaw claudication on history
Idiopathic intracranial hypertension	Often obese female; normal vitals	Papilledema; pulsatile tinnitus on history	Enlarged blind spots; sixth nerve palsy possible
Intracranial mass	Variable; may have weight loss	Papilledema if raised intracranial pressure	Focal neurological deficits depending on location
Carotid or vertebral dissection	May follow trauma; normal vitals	Horner syndrome (carotid); neck tenderness	May have stroke symptoms (hemispheric or posterior circulation)

Important Teaching Point

Normal examination is common! The vast majority of headache patients, particularly those with primary headache disorders (migraine, tension-type headache, cluster headache), will have an entirely normal physical examination between attacks. A normal examination does not exclude significant pathology — the history remains paramount. Key exceptions:

Cluster headache may show residual partial Horner syndrome
Migraine during attack may show cutaneous allodynia
Chronic tension-type headache typically shows pericranial muscle tenderness

However: Always perform fundoscopy. Papilledema is often the only abnormal sign in idiopathic intracranial hypertension and early intracranial masses.

Examination During a Cluster Headache Attack

Witnessing the Attack is Diagnostic

If possible, examine a patient during a cluster headache attack (or review photos/videos). The combination of severe unilateral pain with ipsilateral autonomic features is virtually pathognomonic:

Severe agitation, inability to lie still, pacing
Ipsilateral conjunctival injection and/or lacrimation
Ipsilateral nasal congestion and/or rhinorrhea
Ipsilateral eyelid edema
Ipsilateral forehead and facial sweating
Ipsilateral miosis and/or ptosis

5. Differential Diagnosis

Systematic approach organized by probability and clinical features

Step-by-Step Approach to Headache Diagnosis:

Step 1: Exclude secondary causes — Look for red flags (SNOOP criteria), perform examination including fundoscopy
Step 2: If secondary cause suspected — Investigate urgently based on clinical suspicion
Step 3: If no red flags — Apply diagnostic criteria for primary headache disorders
Step 4: Consider medication overuse — If headache ≥15 days/month and regular analgesic use
Step 5: Assess for comorbidities — Depression, anxiety, sleep disorders often coexist

Acute Headache (New Onset, Less Than 4 Weeks)

Probability	Condition	Key Features	Red Flags
COMMON (approximately 70%)	Viral illness / systemic infection	Fever, malaise, myalgia, rhinorrhea, bilateral headache	High fever with neck stiffness, rash, altered consciousness
COMMON	First migraine attack	Unilateral, pulsating, nausea, photophobia, phonophobia, disability	Thunderclap onset, worst headache ever, neurological signs persisting beyond aura
COMMON	Tension-type headache	Bilateral, pressing, mild-moderate, no nausea, able to function	Progressive worsening, focal neurological signs
LESS COMMON (approximately 20%)	Acute sinusitis	Facial pain/pressure, purulent nasal discharge, fever, worse bending forward	Periorbital swelling, visual changes, altered consciousness (suggests complications)
LESS COMMON	Medication-induced headache	Temporal relationship with new medication (nitrates, PDE5 inhibitors, calcium channel blockers)	Persistent after stopping medication
LESS COMMON	Post-traumatic headache	Onset within 7 days of head injury, variable character	Progressive worsening, neurological deterioration, vomiting (subdural/epidural hematoma)
UNCOMMON BUT SERIOUS (approximately 10%)	Subarachnoid hemorrhage	Thunderclap onset, “worst headache of life,” meningism, may have focal signs	Always investigate thunderclap headache
UNCOMMON BUT SERIOUS	Bacterial meningitis	Fever, headache, neck stiffness, photophobia, altered consciousness, rash	Medical emergency — immediate antibiotics
UNCOMMON BUT SERIOUS	Cerebral venous thrombosis	Subacute onset, may be thunderclap, headache with seizures or focal signs, pregnancy/postpartum	Papilledema, focal deficits, seizures
UNCOMMON BUT SERIOUS	Arterial dissection (carotid or vertebral)	Unilateral head/neck pain, Horner syndrome, may follow minor trauma or manipulation	Stroke symptoms (dissection can cause stroke)
UNCOMMON BUT SERIOUS	Hypertensive emergency	Severe hypertension (>180/120), headache, visual changes, chest pain, confusion	End-organ damage — urgent BP control needed
UNCOMMON BUT SERIOUS	Acute angle-closure glaucoma	Severe periorbital pain, red eye, fixed mid-dilated pupil, visual halos, hard globe	Vision loss if untreated — ophthalmology emergency

Thunderclap Headache — A Medical Emergency

Causes of Thunderclap Headache (Pain Maximal Within 1 Minute)

Thunderclap headache requires urgent investigation. While primary thunderclap headache exists, it is a diagnosis of exclusion.

Subarachnoid hemorrhage — Most important to exclude
Intracerebral hemorrhage
Cerebral venous thrombosis
Arterial dissection (carotid or vertebral)
Pituitary apoplexy

Reversible cerebral vasoconstriction syndrome
Hypertensive crisis
Spontaneous intracranial hypotension
Colloid cyst of third ventricle
Primary thunderclap headache (diagnosis of exclusion)

Chronic Headache (Greater Than 3 Months)

Approach to Chronic Daily Headache (≥15 days/month):

Step 1: Exclude secondary causes — New daily persistent headache requires investigation
Step 2: Assess for medication overuse — Present in up to 50% of chronic daily headache
Step 3: Classify the primary headache type — Chronic migraine vs chronic tension-type vs others
Step 4: Consider hemicrania continua — Responds specifically to indomethacin

Probability	Condition	Approximate Frequency	Key Distinguishing Features
COMMON	Chronic migraine	2% of population	≥15 headache days/month, ≥8 with migraine features, for >3 months; often medication overuse component
COMMON	Chronic tension-type headache	2-3% of population	≥15 days/month, bilateral pressing, mild-moderate, no significant nausea/vomiting
COMMON	Medication overuse headache	1-2% of population	≥15 days/month in patient with pre-existing headache disorder; regular overuse of acute medications
LESS COMMON	New daily persistent headache	Rare	Daily from onset, patient can pinpoint exact date of onset, no prior headache history
LESS COMMON	Hemicrania continua	Rare	Strictly unilateral continuous headache, autonomic features, complete response to indomethacin
LESS COMMON	Cervicogenic headache	2-4% of population	Unilateral, starts in neck, triggered by neck movement, reduced cervical range of motion
UNCOMMON — EXCLUDE	Idiopathic intracranial hypertension	1-2 per 100,000	Obese female, papilledema, visual obscurations, pulsatile tinnitus, sixth nerve palsy
UNCOMMON — EXCLUDE	Chronic subdural hematoma	Variable	Elderly, anticoagulation, history of fall (may be minor/forgotten), progressive, fluctuating cognition
UNCOMMON — EXCLUDE	Intracranial mass	Variable	Progressive headache, focal neurological signs, papilledema, seizures, personality change

Primary Headache Disorders: Diagnostic Features

Feature	Migraine	Tension-Type	Cluster
Location	Unilateral (60%) or bilateral	Bilateral	Strictly unilateral (orbital/supraorbital/temporal)
Quality	Pulsating/throbbing	Pressing/tightening (band-like)	Stabbing/boring
Intensity	Moderate to severe	Mild to moderate	Severe to very severe
Duration	4-72 hours	30 minutes to 7 days	15-180 minutes
Frequency	Variable; chronic if ≥15 days/month	Variable; chronic if ≥15 days/month	1-8 attacks/day during cluster period
Aggravated by activity	Yes — routine physical activity worsens	No	No — restlessness/pacing during attack
Nausea/Vomiting	Common (≥1 required)	Absent (mild nausea may occur)	May occur
Photophobia/Phonophobia	Yes (≥1 required)	One or neither (not both)	May occur (often ipsilateral)
Autonomic features	Usually absent	Absent	Ipsilateral (lacrimation, rhinorrhea, ptosis, miosis, etc.)
Aura	In 25-30% (migraine with aura)	Absent	Absent
Behavior during attack	Lies still in dark, quiet room	Continues activities	Agitated, pacing, restless

Anatomical Approach to Secondary Headache

Intracranial — Vascular

Subarachnoid hemorrhage

Intracerebral hemorrhage

Cerebral venous thrombosis

Arterial dissection

Reversible cerebral vasoconstriction syndrome

Giant cell arteritis

Intracranial — Non-Vascular

Raised intracranial pressure (tumor, idiopathic intracranial hypertension)

Low cerebrospinal fluid pressure

Meningitis / Encephalitis

Brain abscess

Subdural / Epidural hematoma

Chiari malformation

Head and Neck Structures

Acute sinusitis

Acute glaucoma

Temporomandibular joint dysfunction

Cervicogenic headache

Occipital neuralgia

Dental pathology

Systemic Causes

Systemic infection with fever

Hypertensive emergency

Hypoxia / Hypercapnia

Carbon monoxide poisoning

Pre-eclampsia / Eclampsia

Medication-induced

Drug-Induced Headache

Drug or Drug Class	Mechanism	Characteristics	Time to Resolution After Stopping
Nitrates (glyceryl trinitrate, isosorbide)	Nitric oxide-mediated vasodilation	Immediate throbbing headache; may trigger migraine in susceptible individuals	Minutes to hours (immediate headache); may trigger prolonged migraine
Phosphodiesterase-5 inhibitors (sildenafil, tadalafil)	Vasodilation via increased cyclic GMP	Bilateral throbbing headache, facial flushing	Hours (correlates with drug half-life)
Calcium channel blockers (nifedipine, amlodipine)	Vasodilation	Often at treatment initiation; may improve with continued use	Days to weeks
Dipyridamole	Vasodilation, increased adenosine	Very common (up to 40%); often limits tolerability	Days
Proton pump inhibitors	Unknown	Reported association; mechanism unclear	Variable
Hormonal contraceptives / HRT	Estrogen effects on trigeminovascular system	May trigger migraine, especially during hormone-free interval	Cycles to months
Caffeine withdrawal	Rebound vasodilation after chronic vasoconstriction	Bilateral throbbing, begins 12-24 hours after last caffeine	2-9 days
Opioid withdrawal	Central sensitization, autonomic dysregulation	Part of withdrawal syndrome with other features	Days to weeks
Analgesic overuse (paracetamol, NSAIDs, triptans, opioids)	Central sensitization, altered pain modulation	Daily or near-daily headache; headache recurs as medication wears off	2-12 weeks after withdrawal (often worsens initially)

Headache in Special Populations

Age Over 50 Years

Giant cell arteritis — New headache, jaw claudication, visual symptoms, scalp tenderness, polymyalgia rheumatica
Intracranial mass — Primary brain tumor or metastases
Chronic subdural hematoma — Often forgotten minor trauma
Trigeminal neuralgia — Peak incidence 50-70 years
Hypnic headache — “Alarm clock headache,” occurs only during sleep, age >50

Pregnancy and Postpartum

Pre-eclampsia/Eclampsia — Hypertension, proteinuria, headache a warning sign
Cerebral venous thrombosis — Hypercoagulable state of pregnancy
Reversible cerebral vasoconstriction syndrome — Especially postpartum
Pituitary apoplexy — Pituitary enlarges in pregnancy
Post-dural puncture headache — After epidural/spinal anesthesia
Migraine — Often improves in pregnancy, may worsen postpartum

Quick Reference: “If You See This, Think This”

Clinical Clue	Think This First	Next Step
Thunderclap onset (maximal in seconds)	Subarachnoid hemorrhage	CT head immediately → LP if CT negative
Fever + headache + neck stiffness	Bacterial meningitis	Blood cultures → antibiotics → LP
New headache age >50 + jaw claudication	Giant cell arteritis	Urgent ESR/CRP → start steroids → temporal artery biopsy
Unilateral + autonomic features + restlessness	Cluster headache	Trial of high-flow oxygen or sumatriptan
Worse when upright, better lying down	Low cerebrospinal fluid pressure	MRI brain with gadolinium
Worse when lying down, morning headache	Raised intracranial pressure	Fundoscopy → CT/MRI brain → LP if no mass
Papilledema in obese female	Idiopathic intracranial hypertension	MRI + MRV → LP with opening pressure
Headache + Horner syndrome + neck pain	Carotid or vertebral dissection	CT angiography or MR angiography neck
Daily headache + analgesics ≥10-15 days/month	Medication overuse headache	Medication withdrawal + preventive therapy
Unilateral, continuous + autonomic features	Hemicrania continua	Indomethacin trial (diagnostic and therapeutic)
Brief electric shock pain triggered by touch	Trigeminal neuralgia	MRI brain to exclude secondary causes
Multiple household members with headache	Carbon monoxide poisoning	Remove from environment → carboxyhemoglobin level

6. Diagnostic Investigations

A stepwise, cost-effective approach guided by clinical suspicion

Key Principle: Primary headache disorders are clinical diagnoses. Investigations are performed to exclude secondary causes when red flags are present, not to confirm primary headache.

Indications for Investigation:

Any red flag present (SNOOP criteria)
Abnormal neurological examination
Papilledema on fundoscopy
New-onset headache in patient >50 years
Change in established headache pattern
Headache not fitting primary headache criteria
Treatment-refractory headache (consider if diagnosis correct)

Baseline Investigations When Secondary Cause Suspected

Investigation	Purpose	What to Look For	Practical Points
Full blood count	Screen for infection, anemia, malignancy	Elevated white cells (infection), low hemoglobin (anemia causing headache), thrombocytosis (giant cell arteritis)	Non-specific but useful baseline
Erythrocyte sedimentation rate (ESR)	Screen for giant cell arteritis	Typically >50 mm/hr in giant cell arteritis (often >100); normal does not exclude	Order in all patients >50 with new headache
C-reactive protein (CRP)	Inflammation marker; complements ESR	Elevated in infection, giant cell arteritis, other inflammatory conditions	More specific than ESR; rises and falls faster
Urea and electrolytes	Renal function, electrolyte abnormalities	Hyponatremia can cause headache; baseline before contrast imaging	Required before contrast CT/MRI
Glucose	Hypoglycemia, diabetes	Hypoglycemia causes headache; diabetes increases stroke risk	Include in baseline workup
Thyroid function	Thyroid disorders	Both hypo- and hyperthyroidism associated with headache	Consider in chronic headache workup

Neuroimaging

CT Head (Non-Contrast)

Indications

Thunderclap headache (first-line to detect subarachnoid hemorrhage)
Suspected acute intracranial hemorrhage
Head trauma
Acute focal neurological deficit
Altered consciousness
Before lumbar puncture if signs of raised intracranial pressure

Strengths and Limitations

Strengths: Fast, widely available, excellent for acute blood, bone
Sensitivity for subarachnoid hemorrhage: 98% within 6 hours, drops to 93% at 24 hours, 50% at 1 week
Limitations: Radiation exposure; poor for posterior fossa, small lesions, venous thrombosis

MRI Brain

Indications

New daily persistent headache
Suspected intracranial mass
Suspected low cerebrospinal fluid pressure
Suspected cerebral venous thrombosis (with MR venography)
Trigeminal neuralgia (exclude secondary causes)
Pituitary pathology suspected
Posterior fossa symptoms
CT negative but clinical suspicion remains high

Key Sequences

T1-weighted: Anatomy, subacute blood (bright)
T2-weighted: Edema, white matter lesions
FLAIR: Periventricular lesions, subarachnoid blood
Diffusion-weighted (DWI): Acute stroke, abscess
Gadolinium enhancement: Tumors, meningeal enhancement, pachymeningeal enhancement in low CSF pressure
MR venography (MRV): Cerebral venous thrombosis
MR angiography (MRA): Aneurysm, dissection

CT Angiography (CTA) / MR Angiography (MRA)

Indication	Preferred Modality	What to Look For
Suspected aneurysm	CTA (more sensitive for small aneurysms) or MRA	Saccular outpouching, typically at Circle of Willis
Suspected arterial dissection	CTA or MRA (with fat-saturated T1 for intramural hematoma)	Luminal narrowing, intimal flap, intramural hematoma
Reversible cerebral vasoconstriction syndrome	CTA or MRA	Multifocal segmental narrowing (“string of beads”); may be normal early
Cerebral venous thrombosis	CT venography or MR venography	Absent flow in venous sinuses; “empty delta sign” on contrast CT

Lumbar Puncture

Before Lumbar Puncture

CT head required before LP if:

Focal neurological signs
Papilledema
Altered consciousness
Immunocompromised state
History of CNS disease
New-onset seizures

Do not delay antibiotics for suspected bacterial meningitis — give empiric treatment, then LP when safe.

Indication	Key CSF Findings	Interpretation
Subarachnoid hemorrhage (CT negative)	Xanthochromia (yellow discoloration), elevated red cells that do not clear	Xanthochromia takes 12 hours to develop; LP should be done 6-12 hours after onset if CT negative
Bacterial meningitis	High white cells (>1000, neutrophil predominant), high protein, low glucose (<40% serum)	Send for Gram stain, culture, PCR
Viral meningitis	Moderate white cells (10-500, lymphocyte predominant), mildly elevated protein, normal glucose	Send viral PCR panel
Idiopathic intracranial hypertension	Elevated opening pressure (>25 cmH2O), normal composition	Therapeutic as well as diagnostic; symptoms may improve after LP
Low CSF pressure	Low opening pressure (<6 cmH2O); may be normal	MRI findings (pachymeningeal enhancement, brain sagging) often more helpful
Carcinomatous meningitis	Elevated protein, low glucose, lymphocytosis; cytology may show malignant cells	May need repeated LPs for cytology; sensitivity ~50% per LP

Targeted Investigations by Suspected Etiology

If Suspecting Giant Cell Arteritis

First-Line Tests

ESR: Typically >50 mm/hr; often >100 mm/hr
CRP: Elevated; more specific 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; skip lesions occur so need adequate length (>1 cm)
Temporal artery ultrasound: “Halo sign” (hypoechoic ring around vessel); operator dependent
Do not delay steroids while awaiting biopsy if clinical suspicion high

If Suspecting Subarachnoid Hemorrhage

Investigation Pathway for Thunderclap Headache:

CT head (non-contrast): Sensitivity 98% within 6 hours, 93% at 24 hours
If CT negative and <14 days from onset: Lumbar puncture at least 6-12 hours after onset (for xanthochromia to develop)
If SAH confirmed or CT/LP inconclusive: CT angiography to identify aneurysm
If no aneurysm found: Consider MRI/MRA, repeat angiography, or catheter angiography

If Suspecting Idiopathic Intracranial Hypertension

Diagnostic Criteria

Papilledema present
Normal neurological examination (except sixth nerve palsy allowed)
Normal brain imaging (MRI preferred; may show empty sella, optic nerve sheath distension)
Normal CSF composition
Elevated opening pressure (>25 cmH2O in adults)

Additional Tests

MRI brain with gadolinium: Exclude mass, venous thrombosis
MR venography: Exclude cerebral venous thrombosis (can mimic idiopathic intracranial hypertension)
Visual field testing: Baseline and monitoring (enlarged blind spots, peripheral constriction)
Optical coherence tomography: Quantify optic nerve head swelling

If Suspecting Cerebral Venous Thrombosis

Investigation	Findings	Notes
CT head	“Cord sign” (hyperdense thrombosed vein); “empty delta sign” (contrast CT); may show hemorrhagic infarct	May be normal; low sensitivity (30%)
CT venography	Filling defect in venous sinuses	Good first-line if CVT suspected
MRI + MR venography	Absent flow signal in affected sinus; parenchymal changes	Most sensitive and specific
D-dimer	Often elevated	Normal D-dimer does not exclude CVT

Empiric Treatment Trials as Diagnostic Tools

Therapeutic Trials in Headache Diagnosis

Some headache disorders are diagnosed by their response to specific treatments:

Indomethacin-responsive headaches: Complete response to indomethacin is diagnostic for hemicrania continua and paroxysmal hemicrania. Start 25 mg three times daily, increase to 50-75 mg three times daily. Response usually within 1-2 weeks.
Cluster headache: Response to high-flow oxygen (12-15 L/min via non-rebreather mask) or subcutaneous sumatriptan supports diagnosis.
Medication overuse headache: Improvement after withdrawal of overused medications (often after initial worsening) confirms the diagnosis.
Occipital neuralgia: Response to greater occipital nerve block supports diagnosis.

Other Investigations

Investigation	Indication	What It Shows
Carboxyhemoglobin level	Suspected carbon monoxide poisoning (multiple household members with headache)	>3% in non-smokers, >10% in smokers suggests exposure
Electroencephalogram (EEG)	Suspected seizures with post-ictal headache; encephalitis	Epileptiform activity, encephalopathic changes
Sleep study (polysomnography)	Suspected sleep apnea (morning headaches, snoring, daytime somnolence)	Apnea-hypopnea index indicating sleep apnea severity
Intraocular pressure measurement	Suspected acute angle-closure glaucoma	Elevated pressure (>21 mmHg; often much higher in acute closure)
Sinus CT	Suspected complicated sinusitis (not routine for “sinus headache”)	Opacification, air-fluid levels, bone erosion
Cervical spine imaging	Suspected cervicogenic headache with neurological features	Degenerative changes, disc pathology (correlation with symptoms needed)

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 within seconds to 1 minute)	EMERGENT	CT head immediately → LP if CT negative → CTA if SAH confirmed
Headache + fever + neck stiffness + altered consciousness	EMERGENT	Blood cultures → empiric antibiotics immediately → CT → LP
Headache + focal neurological deficit + altered consciousness	EMERGENT	CT head → consider stroke pathway, hemorrhage, mass lesion
Headache + papilledema	EMERGENT	CT/MRI brain urgently → LP if no mass (measure opening pressure)
New headache age >50 + jaw claudication or visual symptoms	URGENT	ESR/CRP → start high-dose steroids same day → temporal artery biopsy within 2 weeks
Severe unilateral headache + Horner syndrome + neck pain	URGENT	CTA or MRA neck → carotid/vertebral dissection workup
Severe periorbital headache + red eye + fixed dilated pupil	URGENT	Check intraocular pressure → acute angle-closure glaucoma → ophthalmology emergency
Postural headache (worse upright) after LP or epidural	URGENT	Conservative measures → epidural blood patch if persistent >48 hours
New progressive headache over weeks with no red flags	SEMI-URGENT	MRI brain within 2 weeks → neurology referral if abnormal or diagnostic uncertainty
Recurrent episodic headache fitting primary headache criteria	ROUTINE	Clinical diagnosis → trial of appropriate acute and preventive therapy

Step 2: Classify by Presentation Type

Acute Single Episode

Key question: Is this a dangerous secondary cause?

Proceed to Algorithm A

Recurrent Episodic

Key question: Which primary headache disorder?

Proceed to Algorithm B

Chronic Daily

Key question: Is there medication overuse?

Proceed to Algorithm C

Step 3: Follow the Appropriate Algorithm

Algorithm A: Acute Single Episode Headache

Clinical Scenario	Most Likely Diagnosis	Action
Thunderclap onset, worst headache ever	Subarachnoid hemorrhage until proven otherwise	CT head → LP if negative → CTA
Fever + headache + neck stiffness	Meningitis	Empiric antibiotics → CT if indicated → LP
Headache + focal neurology + sudden onset	Stroke (ischemic or hemorrhagic)	CT head → stroke pathway
Unilateral headache + ipsilateral autonomic features + agitation	Cluster headache (first attack)	High-flow oxygen or sumatriptan → MRI to exclude secondary cause
Headache + viral prodrome + no red flags	Viral illness-associated headache	Supportive care; reassess if worsening or prolonged
Typical migraine features, no red flags, positive family history	First migraine attack	Clinical diagnosis; trial of acute migraine therapy

Algorithm B: Recurrent Episodic Headache

Clinical Scenario	Most Likely Diagnosis	Action
Unilateral, pulsating, moderate-severe, nausea, photo/phonophobia, 4-72 hours, aggravated by activity	Migraine without aura	Clinical diagnosis; acute therapy (triptan, NSAID) + consider preventive if ≥4 days/month
Above features preceded by visual/sensory aura lasting 5-60 minutes	Migraine with aura	Clinical diagnosis; avoid estrogen-containing contraceptives; same treatment approach
Bilateral, pressing, mild-moderate, no nausea, no significant photo/phonophobia, can continue activities	Episodic tension-type headache	Simple analgesics; address triggers (stress, posture); preventive if frequent
Strictly unilateral severe periorbital pain, 15-180 min, 1-8/day, with autonomic features, restless	Cluster headache	Acute: oxygen, sumatriptan; Preventive: verapamil; MRI to exclude secondary
Strictly unilateral, 2-30 min attacks, >5/day, autonomic features, responds to indomethacin	Paroxysmal hemicrania	Indomethacin trial (diagnostic and therapeutic)
Brief electric shock-like pain in trigeminal distribution, triggered by light touch	Trigeminal neuralgia	MRI brain → carbamazepine or oxcarbazepine

Algorithm C: Chronic Daily Headache (≥15 days/month)

Clinical Scenario	Most Likely Diagnosis	Action
Chronic headache + analgesic use ≥10-15 days/month	Medication overuse headache	Withdraw overused medication + bridge therapy + start preventive
≥15 days/month, ≥8 with migraine features, <4 hours untreated	Chronic migraine (± medication overuse)	Address medication overuse if present; preventive therapy (topiramate, amitriptyline, CGRP antibodies)
≥15 days/month, bilateral pressing, no migraine features	Chronic tension-type headache	Amitriptyline; address triggers; physiotherapy
Daily from onset, patient recalls exact date it started	New daily persistent headache	MRI brain → may be refractory; trial preventives
Strictly unilateral, continuous, mild-moderate with exacerbations, autonomic features	Hemicrania continua	Indomethacin trial (complete response is diagnostic)
Chronic headache + papilledema + obese female	Idiopathic intracranial hypertension	MRI + MRV → LP with opening pressure → acetazolamide, weight loss

“What Do I Do If…” Decision Reference

Clinical Situation	Immediate Action	Next Step
CT negative for SAH but clinical suspicion high	Perform LP (wait 6-12 hours from onset for xanthochromia)	If LP also negative and >2 weeks from onset, consider other causes of thunderclap headache
ESR/CRP elevated but patient not convinced to start steroids	Explain risk of permanent visual loss (15-20% if untreated)	Start steroids immediately; arrange temporal artery biopsy within 2 weeks
Patient using painkillers daily and headache worsening	Explain medication overuse headache; plan withdrawal	Abrupt withdrawal (preferred for most) or gradual taper; bridge with preventive; warn of initial worsening
Migraine not responding to triptans	Check timing (take early), dose, formulation (try different triptan or route)	Consider gepant or ditan; assess for medication overuse; optimize preventive therapy
Cluster headache patient in acute attack in emergency department	High-flow oxygen 12-15 L/min via non-rebreather OR subcutaneous sumatriptan 6 mg	Initiate preventive (verapamil); short-term bridge with prednisolone; refer to headache specialist
Unilateral continuous headache not responding to usual treatments	Consider hemicrania continua; trial of indomethacin 25 mg three times daily	Increase to 50-75 mg three times daily; complete response confirms diagnosis
Post-LP headache not improving after 48 hours	Continue conservative measures (fluids, caffeine, bed rest)	If persistent or severe, refer for epidural blood patch
Patient with migraine with aura requesting combined oral contraceptive	Contraindicated due to increased stroke risk	Offer progestogen-only methods, IUD, or non-hormonal contraception
Pregnant patient with new severe headache	Check BP (pre-eclampsia?); neurological examination; fundoscopy	Low threshold for imaging; consider cerebral venous thrombosis, reversible cerebral vasoconstriction syndrome, pituitary apoplexy

When to Start Preventive Therapy

Consider Preventive Therapy If:

≥4 headache days per month affecting function
Acute medications ineffective or contraindicated
Overuse of acute medications (or risk of)
Patient preference for fewer attacks
Presence of hemiplegic migraine or brainstem aura (prolonged aura)
Significant disability despite acute treatment

Troubleshooting Refractory Headache

Ask These Questions When Headache Does Not Respond to Treatment

Is the diagnosis correct? Reconsider differential; consider secondary causes
Is there medication overuse? Present in up to 50% of chronic daily headache
Was the treatment adequate? Correct dose, duration (8-12 weeks for preventives), correct timing (acute meds taken early)
Are there comorbidities? Depression, anxiety, sleep disorders often coexist and require treatment
Are there perpetuating factors? Stress, poor sleep hygiene, caffeine, triggers not addressed
Is there more than one headache type? Patients may have migraine AND tension-type headache
Has hemicrania continua been excluded? Trial of indomethacin
Should this patient be referred to a headache specialist? Consider if refractory after adequate trials

8. Clinical Pearls and Pitfalls

Practical wisdom — learn from successes and avoid common mistakes

Must-Know Clinical Pearls

The history is everything: Over 90% of headache diagnoses are made from history alone. A thorough, systematic history is more valuable than any investigation.

Thunderclap headache is subarachnoid hemorrhage until proven otherwise: A negative CT does not exclude SAH — perform LP if clinical suspicion persists. CT sensitivity drops from 98% at 6 hours to 50% at 1 week.

Always examine the fundi: Papilledema may be the only sign of raised intracranial pressure. It takes 30 seconds and can be life-saving. Make fundoscopy a routine part of every headache examination.

New headache after age 50 = giant cell arteritis until proven otherwise: Check ESR and CRP, and if clinical suspicion exists, start steroids the same day. Do not wait for biopsy — permanent visual loss can occur within hours.

Medication overuse is everywhere: Up to 50% of patients with chronic daily headache have medication overuse. Always ask about analgesic frequency — the headache will not improve until overuse is addressed.

Behavior during attack is diagnostic: Migraine patients lie still in a dark room. Cluster headache patients pace, rock, and cannot stay still. This single observation can clinch the diagnosis.

Indomethacin response is diagnostic: Complete resolution with indomethacin confirms hemicrania continua or paroxysmal hemicrania. Always consider a therapeutic trial in unilateral continuous headache.

“Sinus headache” is usually migraine: Studies show that up to 90% of self-diagnosed or physician-diagnosed “sinus headache” actually meets criteria for migraine. Nasal congestion can be a migraine symptom (autonomic activation).

Critical Pitfalls to Avoid

Assuming CT rules out SAH: A negative CT only has high sensitivity in the first 6 hours. If thunderclap headache occurred >6 hours ago and CT is negative, LP is mandatory. Many SAH are missed by stopping at a negative CT.

Missing giant cell arteritis: Do not dismiss new headache in the elderly as “tension headache.” Always check ESR/CRP. A normal ESR does not exclude giant cell arteritis (10-20% have normal ESR).

Prescribing opioids for primary headache: Opioids are ineffective for migraine and cluster headache, promote medication overuse headache, and worsen long-term outcomes. They should almost never be used for primary headache disorders.

Not asking about medication frequency: Patients often do not volunteer how often they take painkillers. You must ask specifically: “How many days per week do you take any painkiller for headache?”

Giving up on preventive therapy too soon: Most preventives take 8-12 weeks at adequate dose to show benefit. Patients and clinicians often abandon effective treatments prematurely.

Attributing headache to “cervical spondylosis” on imaging: Degenerative changes are ubiquitous in adults and rarely explain headache. Do not anchor on incidental imaging findings.

Missing meningitis because neck stiffness is absent: Neck stiffness may be absent early in meningitis, in the elderly, and in immunocompromised patients. A high index of suspicion is required.

Forgetting to ask about pregnancy: Pregnancy changes the differential dramatically. Pre-eclampsia, cerebral venous thrombosis, and reversible cerebral vasoconstriction syndrome must be considered. Many usual medications are contraindicated.

Key Takeaways

Primary headache disorders (migraine, tension-type, cluster) account for >90% of headaches but are clinical diagnoses — investigations are performed to exclude secondary causes when red flags are present.
The SNOOP criteria (Systemic symptoms, Neurological signs, Onset sudden, Older age, Pattern change) identify red flags requiring investigation.
Thunderclap headache (maximal within seconds) is a medical emergency. CT head followed by LP (if CT negative) is the standard workup for suspected subarachnoid hemorrhage.
Giant cell arteritis must be considered in any patient >50 years with new headache. Start steroids immediately if suspected — do not wait for biopsy.
Medication overuse headache affects up to 50% of patients with chronic daily headache. Improvement requires withdrawal of the overused medication.
Normal physical examination does not exclude serious pathology. History is paramount, and fundoscopy should be performed in all new or changed headaches.
The three most common primary headaches can be distinguished by: location (bilateral vs unilateral), behavior during attack (still vs agitated), and associated features (nausea/photophobia vs autonomic features).
Preventive therapy should be considered when headaches occur ≥4 days per month, acute treatments are ineffective, or medication overuse is a risk.
When headache is refractory, reconsider the diagnosis, look for medication overuse, and ensure treatment was adequate before concluding treatment has failed.
Hemicrania continua and paroxysmal hemicrania are diagnosed by their complete response to indomethacin — always consider a therapeutic trial in unilateral headaches that do not fit typical patterns.

Quick Reference Algorithm

Systematic Approach to Headache:

Identify emergencies: Thunderclap? Fever + meningism? Focal deficits? Papilledema? → Investigate and treat urgently
Screen for red flags: Apply SNOOP criteria. If any present → targeted investigation based on clinical suspicion
Examine the patient: Vital signs, fundoscopy, neurological examination. Look for signs of secondary causes
Classify by pattern: Acute single episode, recurrent episodic, or chronic daily? → Follow appropriate algorithm
Apply diagnostic criteria: Does the headache fit migraine, tension-type, cluster, or another primary disorder?
Assess for medication overuse: If ≥15 headache days/month, ask about analgesic frequency. Address overuse if present
Initiate appropriate therapy: Acute treatment for attacks; preventive therapy if indicated
Review and reassess: Follow up to assess response, adjust treatment, and reconsider diagnosis if not improving