Headache
Headache is a painful sensation in any region of the head, ranging from sharp to dull, that may arise from primary neurological dysfunction or secondary to an underlying systemic or structural condition.
Headache (cephalalgia) — from Greek kephalē (head) + algos (pain) — is pain or discomfort felt over the head or face [1][2].
- It is the most common type of pain experienced by humans [1][2].
- It causes considerable worry but rarely represents sinister disease [1][2] — roughly 90% of headaches presenting to primary care are benign primary headaches.
- The clinical challenge is to efficiently identify the dangerous minority (~10%) who harbour a serious secondary cause.
Key concept: The brain parenchyma itself has NO pain receptors. Headache arises from stimulation of nociceptors in pain-sensitive structures around the brain — vessels, meninges, scalp, orbit, sinuses and ears. Understanding which structures are pain-sensitive is the foundation for understanding every headache syndrome.
Epidemiology
- Tension-type headache (TTH) is the most frequent cause of headache globally [1][2], with a lifetime prevalence of 70% in males and 90% in females [3].
- Migraine affects roughly 15% of women and 6% of men worldwide [3].
- Cluster headache is uncommon: 0.1% lifetime risk, M:F = 4.3:1 [4].
- Medication-overuse headache (MOH) affects ~1–2% of the general population but up to 50% of chronic headache referrals.
- Stroke (a secondary cause of headache) is the 2nd–3rd leading cause of death in China and Hong Kong [6].
- Hypertension prevalence ~20% in HK [7] — relevant because malignant hypertension (BP ≥ 220/120 + Grade 3–4 fundal changes) can present with severe headache and is a medical emergency [8].
- Drugs that may cause headache: alcohol, analgesics (rebound), caffeine, antihypertensives (several), COCP, corticosteroids, NSAIDs (esp. indomethacin), vasodilators esp. nitrates, sildenafil [9].
- Hypertension is an uncommon cause of headache — a point often over-estimated by students [9].
- A patient > 55 years presenting with unaccustomed headache probably has an organic cause [9].
- Giant cell arteritis (GCA) — the commonest primary vasculitis — has an incidence of ~20/100k/year in those > 50 years, F:M = 2:1, and rarely occurs before age 50 [10].
- Idiopathic intracranial hypertension (IIH) tends to occur in obese women of child-bearing age, incidence 1–2/100k/year [5].
Anatomy and Pain-Sensitive Structures
Understanding headache requires knowing what can actually hurt inside and outside the skull.
| Structure | Innervation | Clinical Relevance |
|---|---|---|
| Venous sinuses (superior sagittal, transverse, sigmoid) | CN V (ophthalmic division V1), upper cervical nerves | Cerebral venous sinus thrombosis → headache |
| Cortical veins | CN V | Cerebral venous infarction |
| Basal arteries (circle of Willis, proximal segments) | CN V, IX, X | SAH → thunderclap headache because blood irritates these arterial walls |
| Dura mater (especially basal dura) | CN V (V1 = anterior fossa & tentorium; V2/V3 = middle fossa); C1–C3 = posterior fossa dura | Mass effect, meningitis, intracranial hypotension |
The brain parenchyma itself and the ependymal lining of ventricles are NOT pain-sensitive. A slowly growing tumour can become massive before headache develops — headache only occurs when it stretches the dura, displaces vessels, or raises ICP.
- Scalp: vessels (superficial temporal artery — palpated in GCA) and muscles (frontalis, temporalis, occipitalis — spasm in TTH)
- Orbit: globe, extraocular muscles, periorbita (acute glaucoma headache)
- Cavities: oral (dental), nasal, paranasal sinuses (sinusitis)
- Ear: external and middle ear (otitis)
The dura in different cranial fossae is innervated by different nerves:
- Anterior cranial fossa: V1 (ophthalmic) → referred pain to forehead/eye
- Middle cranial fossa: V2/V3 (maxillary/mandibular) → referred pain to temple/cheek
- Posterior cranial fossa: C1–C3 (upper cervical) → referred pain to occiput/neck
This is why a posterior fossa tumour causes occipital headache, while a frontal mass causes frontal headache.
Meningeal arteries:
- The middle meningeal artery (MMA) runs through the foramen spinosum and along the inner skull table of the temporal bone. Temporal bone fracture → MMA laceration → epidural haematoma (EDH) [11][12].
- EDH bleeds are arterial (85%), explaining why they progress rapidly (the "lucid interval" — patient initially compensates, then deteriorates as arterial bleeding accumulates).
Bridging veins:
- Drain from cerebral cortex across the subdural space to the dural venous sinuses.
- Stretched in cerebral atrophy (elderly, alcoholics) → vulnerable to shearing during acceleration/deceleration → subdural haematoma (SDH) [11][12].
- SDH bleeds are venous (majority), explaining their slower accumulation and chronic presentations.
Circle of Willis:
- Berry aneurysms form at bifurcation points (particularly anterior communicating artery, posterior communicating artery, MCA bifurcation).
- Rupture → subarachnoid haemorrhage (SAH) with blood in the basal cisterns irritating pain-sensitive basal arteries → thunderclap headache [13][14].
Risk Factors
| Risk Factor | Mechanism |
|---|---|
| Family history (especially migraine — +ve in 70%) | Genetic predisposition to cortical hyperexcitability and trigeminovascular activation [3] |
| Female sex | Oestrogen fluctuations trigger migraine (perimenstrual, OCP-related); IIH more common in women [3][5] |
| Stress, anxiety, depression | Drives chronic muscular tension and central sensitisation → TTH [3] |
| Obesity | Major risk factor for IIH (mechanism: ↑intra-abdominal pressure → ↑intrathoracic pressure → ↑central venous pressure → ↓CSF reabsorption) [5] |
| Dietary triggers | Alcohol, chocolate, tyramine-containing foods (dairy), starvation, caffeine [15] |
| Hormonal factors | Premenstrual or related to OCP (fluctuation in oestrogen) [15] |
| Medication overuse | Analgesics > 15 days/month or triptans/ergotamine > 10 days/month → MOH [15] |
| Risk Factor | Associated Condition |
|---|---|
| Hypertension | Hypertensive encephalopathy, ICH, malignant HTN [7][8] |
| Anticoagulation / coagulopathy | ICH, SDH, EDH [11][14] |
| Age > 50 | GCA, cerebral tumour, SDH [9][10] |
| Cerebral atrophy (elderly, chronic alcoholism) | SDH (stretched bridging veins) [11] |
| Immunodeficiency | Intracranial abscess, fungal meningitis, CNS lymphoma |
| Pregnancy / OCP / COC use | Cerebral venous thrombosis (F > M), IIH, eclampsia [5][13] |
| Drugs: OCP, tetracycline, nalidixic acid, vitamin A, systemic steroid withdrawal | IIH [5] |
| Smoking | Stroke (dose-response); cluster headache |
| Recent head trauma | EDH, SDH, SAH, post-concussion syndrome [11][12] |
Pathophysiology
Headache results from pressure, traction, displacement, or inflammation of nociceptors in pain-sensitive structures of the head.
These nociceptors are found on:
- Blood vessels (intracranial and extracranial)
- Meninges (particularly the dura)
- Muscles and periosteum of the scalp
- Cranial nerves (especially V, IX, X) and upper cervical nerve roots (C1–C3)
The signal travels via:
- Trigeminal nerve (CN V) for pain above the tentorium cerebelli (forehead, temples, vertex)
- Upper cervical nerves (C1–C3) for pain from the posterior fossa and occiput
- The trigeminocervical complex in the upper spinal cord is where these converge — this is why neck stiffness and occipital pain so commonly accompany headache
Pathophysiology by Headache Type
- Incompletely understood but thought to be muscular in origin
- Likely represents a misinterpretation of sensory afferents from epicranial muscles as pain — peripheral sensitization of myofascial nociceptors + central sensitization
- Associated with stress, anxiety, and underlying depression
- Chronic TTH involves central sensitization — the brain's pain-processing system becomes "turned up," so normal muscle signals are perceived as painful
The pathophysiology of migraine is a multi-step process:
- Cortical spreading depression (CSD): a wave of neuronal and glial depolarization that spreads across the cortex at 3–5mm/min. This explains the visual aura — the wave crosses the occipital cortex, producing a scintillating scotoma that "marches" across the visual field over ~20 minutes.
- Trigeminovascular activation: CSD activates trigeminal afferents on meningeal blood vessels → release of CGRP (calcitonin gene-related peptide) → vasodilation + neurogenic inflammation → throbbing pain.
- CGRP is the key mediator — this is why CGRP antagonists (e.g., erenumab, fremanezumab, galcanezumab) are effective prophylactics [15].
- Central sensitization explains photophobia, phonophobia, nausea (activation of brainstem nuclei including the nucleus tractus solitarius for vomiting).
- Pathophysiology: unknown, associated with abnormal hypothalamic or thalamic activity and paroxysmal discharges of central trigeminal and parasympathetic pathways [4]
- The hypothalamus is the "biological clock" of the body — this explains the clockwork regularity of attacks (same time daily) and the seasonal clustering.
- Activation of the trigeminal-autonomic reflex → parasympathetic outflow via CN VII → lacrimation, nasal congestion, conjunctival injection
- Sympathetic dysfunction (due to carotid periarteriolar inflammation) → transient Horner's syndrome (~30–50%) [4]
- ICP is determined by the Monro-Kellie doctrine: Brain + Blood + CSF = constant volume within the rigid skull
- If any one component increases (tumour, haemorrhage, hydrocephalus, cerebral oedema), the others must decrease or ICP rises
- ↑ICP → traction on pain-sensitive dura and basal vessels → headache
- Classic features: headache worse in the morning (because recumbency ↑venous return to brain → ↑ICP), worse with coughing/straining/bending (↑intrathoracic pressure → ↑jugular venous pressure → ↑ICP), associated with nausea/vomiting (pressure on area postrema in floor of 4th ventricle)
- Papilloedema: ↑ICP → transmitted along subarachnoid space of optic nerve sheath → "tourniquet" effect on optic nerve → ↓axoplasmic outflow from optic disc → axonal swelling = disc oedema [16]
- 85% due to ruptured cerebral aneurysm (berry aneurysm) among non-traumatic causes
- Blood at high pressure enters the subarachnoid space → directly irritates nociceptors on basal arteries and meninges → sudden-onset "thunderclap" / worst headache ever [13]
- Blood in CSF → meningeal irritation → neck stiffness, photophobia
- Subsequent vasospasm (peak days 4–14) due to blood breakdown products irritating arterial walls → delayed cerebral ischaemia
- Cause: CSF leak (post-LP, spontaneous arachnoid tear)
- Pathophysiology: brain no longer floats in CSF → traction on anchoring/supporting structures (dura, bridging veins, cranial nerves) [5]
- Classic feature: orthostatic headache that promptly resolves upon lying down — when upright, gravity pulls the brain down, increasing traction; when supine, the brain is supported again
- Granulomatous inflammation of medium-large arteries (especially superficial temporal artery)
- Intimal thickening + inflammatory infiltrate → luminal narrowing → ischaemia of supplied tissues
- Temporal headache: inflamed, swollen temporal artery wall stretches periarteriolar nociceptors
- Jaw claudication: ischaemia of the masseter muscle (supplied by branches of the external carotid) during chewing
- AAION (anterior arteritic ischaemic optic neuropathy): posterior ciliary artery occlusion → optic nerve head infarction → sudden visual loss
- Infection → inflammatory exudate in subarachnoid space → direct stimulation of meningeal nociceptors → headache
- Inflammation of meninges → reflex protective muscle spasm → neck stiffness (Kernig's and Brudzinski's signs)
Classification
The ICHD-3 is the gold-standard classification:
Part 1: Primary Headaches
- Migraine
- Tension-type headache
- Trigeminal autonomic cephalalgias (TACs) — cluster headache, paroxysmal hemicrania, SUNCT/SUNA, hemicrania continua
- Other primary headaches (cough headache, exercise headache, sexual headache, thunderclap headache, cold-stimulus headache, etc.)
Part 2: Secondary Headaches 5. Headache attributed to trauma or injury to the head and/or neck 6. Headache attributed to cranial or cervical vascular disorder (SAH, ICH, dissection, GCA, CVST) 7. Headache attributed to non-vascular intracranial disorder (↑ICP, ↓ICP, neoplasm) 8. Headache attributed to a substance or its withdrawal (MOH, nitrate headache, caffeine withdrawal) 9. Headache attributed to infection (meningitis, encephalitis, abscess) 10. Headache attributed to disorder of homeostasis (hypoxia, hypertension, hypothyroidism) 11. Headache attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth, or other facial/cervical structure 12. Headache attributed to psychiatric disorder
Part 3: Painful Cranial Neuropathies and Other Facial Pains 13. Trigeminal neuralgia, glossopharyngeal neuralgia, occipital neuralgia 14. Other headache disorders
| Pattern | Examples | Key Feature |
|---|---|---|
| Sudden onset (seconds) | SAH, ICH, cerebral venous thrombosis, pituitary apoplexy, arterial dissection | Thunderclap — must rule out SAH |
| Acute (hours–days) | Meningitis, acute glaucoma, first migraine, sinusitis, acute respiratory infection | Febrile illness, focal signs, eye pain |
| Subacute (days–weeks) | GCA, IIH, subdural haematoma, cerebral tumour | Progressive, new in elderly |
| Chronic/recurrent | TTH, migraine, cluster headache, MOH | Pattern recognition key |
Acute: respiratory infection Chronic: tension-type headache, combination headache, migraine, transformed migraine
- Cardiovascular: subarachnoid haemorrhage, intracranial haemorrhage, carotid or vertebral artery dissection, temporal arteritis, cerebral venous thrombosis
- Neoplasia: cerebral tumour, pituitary tumour
- Infection: meningitis (esp. fungal), encephalitis, intracranial abscess
- Haematoma: extradural/subdural
- Glaucoma
- Benign intracranial hypertension
Important
'Combination headaches', which can last for days, have a mix of components such as tension, depression, vascular headache and drug dependence [9]. Don't force every headache into a single diagnostic box — many patients have overlapping features.
Etiology (Focus on Hong Kong)
| Etiology | Prevalence | Notes |
|---|---|---|
| Tension-type headache | Most frequent cause [1][2] | Lifetime prevalence 70% M, 90% F |
| Migraine | 2nd most common | 15% F, 6% M globally; family Hx +ve in 70% |
| Cluster headache | Uncommon (0.1%) | Predominantly male smokers |
| MOH (medication overuse headache) | 1–2% general population | Gradual ↑headache frequency and drug consumption, change in headache characteristics [15] |
Secondary Headaches (~10%)
| Cause | Key Pathophysiology | HK Relevance |
|---|---|---|
| SAH | Ruptured berry aneurysm (85% of spontaneous SAH) → blood in subarachnoid space → meningeal irritation [13][14] | Acute neurosurgical emergency; mortality 50% at 1 month [6] |
| Intracerebral haemorrhage (ICH) | Hypertensive arteriopathy (MC — rupture of Charcot-Bouchard microaneurysms in deep perforating arteries); cerebral amyloid angiopathy (CAA) for lobar ICH [14] | Common sites: pons, cerebellum, putamen, thalamus [14]; high HTN prevalence in HK |
| Epidural haematoma (EDH) | Head trauma (most common) → MMA laceration → arterial bleed between skull and dura [11][12] | RTA, falls, assaults; lucid interval is classic |
| Subdural haematoma (SDH) | Head trauma (most common) → bridging vein tear → venous bleed between dura and arachnoid [11][12] | Elderly with atrophy, chronic alcoholism — both common in HK |
| Carotid/vertebral artery dissection | Intimal tear → intramural haematoma → vessel narrowing/occlusion; can be spontaneous or post-trauma | Young stroke — important in HK ED presentations |
| Cerebral venous sinus thrombosis (CVST) | Venous outflow obstruction → ↑ICP, venous infarction [13] | F > M; pregnancy, COC use; 1% of stroke |
| GCA | Granulomatous arteritis → vessel wall inflammation + luminal narrowing [10] | Commonest primary vasculitis; rare in Chinese populations but must not be missed |
| Malignant hypertension | BP ≥ 220/120 + fibrinoid necrosis of small vessels → encephalopathy [8] | Severe headache, vomiting, visual disturbances, transient paralyses, convulsions, stupor and coma [8] |
| Cause | Pathophysiology |
|---|---|
| Cerebral tumour | Mass effect → ↑ICP → traction on dura/vessels |
| Pituitary tumour | Local symptoms: headache, VF defects, CN palsies, hypopituitarism [17]; headache from stretching of diaphragma sellae |
| Skull base tumour | Anterior fossa: anosmia, Foster-Kennedy syndrome; Middle fossa: CN III–VI involvement; Posterior fossa: hydrocephalus [18] |
| Cause | Pathophysiology |
|---|---|
| Bacterial meningitis | Inflammation of leptomeninges → meningeal nociceptor stimulation |
| Fungal meningitis | Especially in immunocompromised [9]; insidious onset |
| Encephalitis | Parenchymal inflammation + ↑ICP |
| Intracranial abscess | Mass effect + surrounding oedema + meningeal irritation |
| Cause | Notes |
|---|---|
| Acute glaucoma | Sudden ↑intraocular pressure → pain in/around eye, may be perceived as headache |
| Sinusitis | Mucosal inflammation + ↑pressure in sinus cavity |
| Cervicogenic headache | Referred pain from C1–C3 facet joints or muscles |
| Post-concussion syndrome | Persistent headache after head injury; multifactorial |
Think Structured
Is the cause something that should not be missed? Use Murtagh's framework: Cardiovascular → Neoplasia → Infection → Haematoma → Glaucoma → Benign intracranial hypertension [9]. Screen for these "can't miss" diagnoses before attributing to a benign primary headache.
Clinical Features
Symptoms — With Pathophysiological Basis
The key to headache diagnosis is a thorough pain analysis — a full description of the pain including a pain analysis should be obtained, especially associated symptoms. It is useful to get the patient to prepare a diary with a grid plotting the relative pain intensity with time of day. Family history, psychosocial history and drug history [9].
| Symptom | Pathophysiological Basis |
|---|---|
| Bilateral, generalized but often radiates forwards from occipital region | Epicranial muscle tension → nociceptor activation in temporalis, frontalis, occipitalis |
| Generalized band-like tightness | Sustained contraction of pericranial muscles creating circumferential pressure sensation |
| Lasting for hours to weeks, recur often | Peripheral and central sensitization maintain chronic pain |
| No associated symptoms (no photophobia/phonophobia) | Unlike migraine, there is no significant trigeminovascular activation or brainstem sensitization [3] |
| Patient can carry on with activities | Pain is mild-moderate; no central sensitization severe enough to impair function |
| May be worse in later part of the day | Muscle tension accumulates over the day with sustained posture/stress [1][2][3] |
| Can be associated with anxiety/depression | Shared central serotonergic dysregulation; depression lowers pain thresholds [1][2][3] |
| Symptom | Pathophysiological Basis |
|---|---|
| Unilateral throbbing/pulsating headache | Trigeminovascular activation → meningeal vessel vasodilation → pulsatile arterial pain transmitted with each heartbeat |
| Aura (20% of migraineurs): scintillating scotoma, fortification spectra, paraesthesia, rarely motor | Cortical spreading depression: wave of neuronal depolarization across cortex → transient visual/sensory/motor dysfunction; visual cortex is most commonly affected |
| Nausea and vomiting | Activation of nucleus tractus solitarius in medulla (vomiting centre) via trigeminal afferents |
| Photophobia and phonophobia | Central sensitization in trigeminal nucleus caudalis → enhanced sensitivity to visual and auditory stimuli |
| Duration 4–72 hours | Self-limiting trigeminovascular inflammatory cascade |
| Aggravated by routine physical activity | Movement ↑intracranial pulsation → ↑mechanical stimulation of sensitized meningeal nociceptors |
| Prodrome (hours before): yawning, mood change, food cravings | Hypothalamic and limbic activation preceding CSD |
| Postdrome: fatigue, cognitive difficulty | Residual neuronal exhaustion after CSD |
| Precipitants: dietary (alcohol, chocolate, tyramine, starvation, caffeine), hormonal (premenstrual, OCP), emotional (stress, anger), change in sleep, smoking, weather [15] | Various triggers lower the threshold for CSD initiation in genetically susceptible individuals |
| Symptom | Pathophysiological Basis |
|---|---|
| Extreme unilateral periorbital piercing/throbbing pain | Trigeminovascular activation centred on V1 (ophthalmic) territory |
| Unilateral autonomic features: lacrimation, nasal congestion, conjunctival injection, ↑sweating | Trigeminal-autonomic reflex: trigeminal afferent activation → parasympathetic efferent outflow via CN VII (greater superficial petrosal nerve → pterygopalatine ganglion) → vasodilation of lacrimal/nasal glands |
| ± Transient Horner's syndrome (~30–50%) | Pericarotid sympathetic plexus inflammation/compression → sympathetic dysfunction → miosis, ptosis, ± anhidrosis [4] |
| Agitation during attacks | So severe that patients pace, rock, bang head — cf. migraine where patients lie still in dark room |
| Periodicity: identical headache beginning at same hour daily | Hypothalamic "clock" dysfunction — the suprachiasmatic nucleus drives circadian rhythms; hypothalamic hyperactivation seen on functional imaging [4] |
| Clustering: 6–12 weeks of daily attacks then months of remission | Seasonal variation in hypothalamic activity |
| Duration 15–180min, 1–8 episodes/day | Brief but intense trigeminal-autonomic discharges |
| Precipitants: alcohol, glyceryl trinitrate (GTN) | Vasodilators provoke attacks during cluster periods (can be used as a diagnostic test) [4] |
| Symptom | Pathophysiological Basis |
|---|---|
| Headache worse in morning | Recumbency during sleep → ↑venous return to brain → ↑intracranial blood volume → ↑ICP |
| Worse with coughing, straining, bending | ↑intrathoracic/intra-abdominal pressure → ↑jugular venous pressure → impaired venous drainage → ↑ICP |
| Nausea and vomiting (may be projectile) | Direct pressure on area postrema (chemoreceptor trigger zone) in floor of 4th ventricle |
| Transient visual obscurations (TVOs) | Fleeting monocular visual disturbance that clears completely within seconds — transient fluctuations in optic nerve head perfusion due to ICP fluctuations [16] |
| Binocular horizontal diplopia | CN VI has the longest intracranial course → vulnerable to stretch with ↑ICP → false localizing sign → lateral rectus palsy → incomitant esotropia [16] |
| Pulsatile tinnitus | Transmitted intracranial pulsations through CSF to cochlear apparatus [5] |
| Progressive personality change, cognitive decline | Frontal lobe compression by mass |
| Symptom | Pathophysiological Basis |
|---|---|
| Sudden onset, severe "thunderclap" / worst headache ever had | Acute ↑↑ICP + direct meningeal nociceptor irritation by subarachnoid blood [13] |
| Brief loss of consciousness | Transient global cerebral hypoperfusion from acute ↑ICP |
| Meningism: neck stiffness, photophobia, nausea/vomiting | Blood breakdown products irritate meninges → reflex protective paravertebral muscle spasm [13] |
| Seizures | Cortical irritation by subarachnoid blood |
| Symptom | Pathophysiological Basis |
|---|---|
| Headache | Mass effect → traction on dura and vessels |
| Nausea and vomiting | ↑ICP → pressure on vomiting centre |
| Drowsiness/confusion | ↑ICP → ↓cerebral perfusion → diffuse cortical dysfunction |
| Aphasia/ataxia | Focal cortical/cerebellar compression depending on haematoma location |
| Seizure | Direct cortical irritation by blood products |
| EDH "lucid interval" | Initial concussion → brief LOC → recovery as compensatory mechanisms cope → deterioration as arterial bleeding overwhelms compliance |
| Chronic SDH — insidious progressive confusion in elderly | Slow venous bleeding → gradual accumulation → progressive mass effect over weeks–months |
| Symptom | Pathophysiological Basis |
|---|---|
| New temporal headache (2/3) | Inflammation of temporal artery wall → periarteriolar nociceptor stimulation [10] |
| Jaw claudication (1/2) | Ischaemia of masseter muscle due to inflamed/narrowed maxillary artery branches [10] |
| Amaurosis fugax → permanent visual loss (15–20%) | Posterior ciliary artery inflammation → optic nerve head ischaemia (AAION) [10] |
| Constitutional symptoms: fever (50%), fatigue, weight loss | Systemic inflammatory response; IL-6 mediated |
| ± PMR symptoms (40–50%): proximal polyarthralgia and myalgia | Shared disease process affecting proximal limb girdle musculature [10] |
| Symptom | Pathophysiological Basis |
|---|---|
| Orthostatic headache that promptly ↓↓ upon lying down | Brain no longer floats in CSF → traction on anchoring/supporting structures when upright [5] |
| Neck pain/stiffness | Traction on cervical meninges |
| Nausea/vomiting, tinnitus, altered hearing, horizontal diplopia | Traction on cranial nerves and brainstem structures [5] |
| Symptom | Pathophysiological Basis |
|---|---|
| Gradual ↑headache frequency and drug consumption | Chronic analgesic use → downregulation of endogenous pain inhibition pathways → rebound pain when drug wears off → escalating consumption [15] |
| Change in headache characteristics | Transformation from episodic migraine/TTH to chronic daily headache |
| Large amounts of caffeine-containing beverages | Caffeine withdrawal → cerebral vasodilation → headache [15] |
Key examination: Use the basic tools of trade: thermometer, sphygmomanometer, pen torch, diagnostic set with ophthalmoscope and stethoscope [9].
Areas to examine [9]:
- Inspect the head, temporal arteries and eyes
- Palpate temporal arteries, facial and neck muscles, cervical spine, sinuses, teeth and TMJs
- Look for signs of meningeal irritation and papilloedema
- A mental state examination is advisable
- Perform a basic neurological examination
| Sign | Found In | Pathophysiological Basis |
|---|---|---|
| Papilloedema (swollen optic disc, blurred margins, absent spontaneous venous pulsation) | ↑ICP (tumour, IIH, CVST, ICH) | ↑ICP transmitted along optic nerve sheath → ↓axoplasmic flow → disc swelling [16] |
| Neck stiffness / meningism (Kernig's, Brudzinski's signs) | SAH, meningitis | Meningeal irritation → reflex paravertebral muscle spasm to splint inflamed meninges |
| Focal neurological deficit (hemiparesis, aphasia, visual field defect) | Stroke, tumour, abscess | Localizing sign indicating structural lesion in corresponding brain region |
| CN palsy | EDH/SDH (CN III uncal herniation), tumour, raised ICP | CN III: uncal herniation → ipsilateral pupil dilation; CN VI: ↑ICP → false localizing sign [11] |
| Ipsilateral dilated pupil (anisocoria) | Uncal herniation with compression of CN III [11] | Parasympathetic fibres run on outside of CN III → first to be compressed → loss of pupillary constriction → mydriasis |
| Contralateral hemiparesis | Direct compression of cortex by haematoma [11] | Motor cortex or corticospinal tract compression on same side as lesion → contralateral weakness |
| Ipsilateral hemiparesis ("false localizing sign") | Lateral displacement of midbrain by mass effect → contralateral cerebral peduncle compressed against free edge of tentorium [11] | Known as Kernohan's notch phenomenon |
| Cushing's reflex: Hypertension + Bradycardia + Respiratory depression/irregularity | Severely ↑ICP (imminent herniation) | ↑ICP → brainstem ischaemia → sympathetic surge (hypertension) → baroreceptor reflex (bradycardia) → medullary respiratory centre compression (irregular breathing) [11] |
| Temporal artery: prominent, tender, non-pulsatile | GCA | Inflamed vessel wall → thickened, tender to palpation; thrombosis → loss of pulsation [10] |
| Scalp tenderness | GCA | Scalp artery ischaemia from temporal artery inflammation [10] |
| Fundus: chalky white, swollen optic disc with haemorrhage | GCA (AAION) | Posterior ciliary artery occlusion → optic nerve head infarction [10] |
| Horner's syndrome (miosis, ptosis, anhidrosis) | Cluster headache, carotid dissection | Sympathetic chain disruption — in cluster: pericarotid inflammation; in dissection: intramural haematoma compresses sympathetic fibres running along ICA [4] |
| Fever | Meningitis, encephalitis, abscess, GCA | Pyrogens (infective or inflammatory) act on hypothalamic thermoregulatory centre |
| Hypertensive retinopathy (copper/silver wiring, AV nicking, flame haemorrhages, hard exudates, cotton-wool spots, papilloedema) | Malignant hypertension | Fibrinoid necrosis → endothelial damage → leakage → haemorrhages and exudates; endothelial dysfunction → retinal ischaemia → cotton wool spots; papilloedema from hypertensive encephalopathy [19] |
| Decreased pulse/discrepant BP/bruits | GCA with large vessel involvement [10] | Vasculitis of aortic branches → stenosis → flow murmur and reduced distal perfusion |
| Scalp/forehead laceration, battle sign, raccoon eyes, CSF rhinorrhoea/otorrhoea | Skull base fracture (risk of EDH/SDH) | Direct trauma signs indicating high-energy injury |
Cushing's Reflex — A Late and Ominous Sign
Cushing's reflex (hypertension + bradycardia + irregular respirations) indicates critically raised ICP with impending brainstem herniation. If you see this, the patient needs immediate neurosurgical assessment. Do NOT wait for imaging — stabilize and call neurosurgery.
The mnemonic SNOOP4 is widely used for headache red flags:
| Letter | Red Flag | Concern |
|---|---|---|
| S | Systemic symptoms (fever, weight loss) or disease (immunocompromised, cancer) | Meningitis, abscess, metastases, GCA |
| N | Neurological deficit or dysfunction | Tumour, stroke, abscess |
| O | Onset sudden (thunderclap) | SAH, ICH, dissection, CVST, pituitary apoplexy |
| O | Onset after age 50 (new headache) | GCA, tumour, SDH |
| P | Pattern change or progressive headache | Tumour, MOH, CVST |
| P | Positional headache | IIH (worse lying down), intracranial hypotension (worse standing) |
| P | Precipitated by Valsalva | Posterior fossa lesion, Chiari malformation |
| P | Papilloedema | ↑ICP from any cause |
High Yield Summary
Definition: Headache = pain/discomfort over head or face; most common pain experienced; brain parenchyma has no nociceptors — pain arises from vessels, dura, scalp, orbit, sinuses, ears.
Classification: Primary (~90%: TTH, migraine, cluster) vs Secondary (~10%: vascular, neoplastic, infective, CSF pressure disorders).
Pathophysiology:
- TTH: muscular — misinterpretation of epicranial muscle afferents as pain; a/w stress, anxiety, depression
- Migraine: cortical spreading depression → trigeminovascular activation → CGRP release → meningeal vasodilation + neurogenic inflammation
- Cluster: hypothalamic dysfunction → trigeminal-autonomic reflex → unilateral pain + autonomic features
- ↑ICP: Monro-Kellie doctrine; headache from traction on dura/vessels; worse AM and with Valsalva
- SAH: blood in subarachnoid space → meningeal nociceptor irritation → thunderclap headache
Key clinical discriminators:
- TTH: bilateral, band-like, no associated symptoms, can carry on activities
- Migraine: unilateral, throbbing, ± aura, photophobia/phonophobia/nausea, debilitating
- Cluster: unilateral periorbital, extreme severity, autonomic features, clockwork regularity, agitation
- SAH: sudden-onset worst-ever headache, meningism, LOC
- GCA: new temporal headache in > 50yo, jaw claudication, visual symptoms, tender temporal artery
- IIH: headache + TVOs + papilloedema in obese young woman
- Intracranial hypotension: orthostatic headache relieved by lying down
Red flags: SNOOP4. Any thunderclap headache = SAH until proven otherwise.
Murtagh's serious disorders not to be missed: SAH, ICH, dissection, GCA, CVST, tumour, meningitis, encephalitis, abscess, EDH/SDH, glaucoma, IIH.
Active Recall - Headache (Part 1)
[1] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.4.1 Headache) [2] Senior notes: Ryan Ho Neurology.pdf (Section 2.1 Approach to Headache) [3] Senior notes: Ryan Ho Neurology.pdf (Section 2.2.1 Tension-type Headache; Section 2.2.2 Migraine) [4] Senior notes: Ryan Ho Neurology.pdf (Section 2.2.3 Cluster Headache and TACs) [5] Senior notes: Ryan Ho Neurology.pdf (Section 4 Miscellaneous ICP-related Disorders — IIH and Intracranial Hypotension) [6] Senior notes: Ryan Ho Neurology.pdf (Section 3.2 Cerebrovascular Diseases) [7] Senior notes: Ryan Ho Cardiology.pdf (Section 3.6 Hypertension, p175) [8] Senior notes: Ryan Ho Cardiology.pdf (Section Malignant Hypertension, p182) [9] Lecture slides: murtagh merge.pdf (p58–60, Headache) [10] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.6.1 GCA and PMR) [11] Senior notes: felixlai.md (Sections II–V: EDH and SDH Etiology, Pathogenesis, Clinical Manifestation) [12] Senior notes: Ryan Ho Radiology.pdf (p20, EDH and SAH imaging) [13] Senior notes: maxim.md (Section 5.2 Cerebrovascular disease — SAH, CVST) [14] Senior notes: maxim.md (Intracerebral haemorrhage) [15] Senior notes: Ryan Ho Neurology.pdf (Migraine Treatment and MOH, p63) [16] Senior notes: Ryan Ho Opthalmology.pdf (Papilloedema, p90) [17] Senior notes: Ryan Ho Endocrine.pdf (Section 5.2.3 Acromegaly — local symptoms) [18] Senior notes: maxim.md (Skull base tumours table) [19] Senior notes: Ryan Ho Opthalmology.pdf (Hypertensive retinopathy pathophysiology, p72)
Differential Diagnosis of Headache
The differential diagnosis of headache is one of the broadest in medicine. The clinical approach is to first stratify by tempo (sudden / acute / subacute / chronic), then systematically consider primary versus secondary causes, and finally use clinical features to narrow the list. The overriding goal is always: can I safely attribute this headache to a benign primary cause, or must I investigate for something life-threatening?
Organising Framework — Murtagh's Diagnostic Strategy
John Murtagh's framework is an excellent bedside structure. It forces you to think beyond the obvious [9].
| Tempo | Most Likely Cause |
|---|---|
| Acute | Respiratory infection |
| Chronic | Tension-type headache, combination headache, migraine, transformed migraine |
Why respiratory infection for acute? Upper respiratory tract infections produce headache via mucosal congestion in the paranasal sinuses → ↑sinus cavity pressure → stimulation of V1/V2 nociceptors in sinus mucosa. This is the headache you get with every common cold.
| Category | Conditions |
|---|---|
| Cardiovascular | Subarachnoid haemorrhage, intracranial haemorrhage, carotid or vertebral artery dissection, temporal arteritis, cerebral venous thrombosis |
| Neoplasia | Cerebral tumour, pituitary tumour |
| Infection | Meningitis (esp. fungal), encephalitis, intracranial abscess |
| Haematoma | Extradural / subdural |
| Other | Glaucoma, benign intracranial hypertension |
- Cervical spondylosis / dysfunction
- Dental disorders
- Refractive errors of eye
- Sinusitis
- Ophthalmic herpes zoster (pre-eruption) — pain precedes the rash by days; if you don't think of it, you'll miss it until vesicles appear in V1 territory
- Exertional headache
- Hypoglycaemia
- Post-traumatic headache (e.g. post-concussion)
- Post-spinal procedure (e.g. epidural, lumbar puncture)
- Sleep apnoea — morning headaches from nocturnal hypercapnia → cerebral vasodilation → ↑ICP
- Rarities: Paget disease, post-sexual intercourse, cluster headache, Cushing syndrome, Conn syndrome, Addison disease, dysautonomic cephalgia
Exertional and Sexual Headache — Don't Forget SAH
Headaches associated with specific activities: sudden severe headache with exertion, especially sexual activity, lasting < 10–15 minutes. The critical differential is subarachnoid haemorrhage (which can also occur during coitus) [2]. Always investigate the first episode of thunderclap headache during exertion/sex — you cannot assume it is benign until SAH has been excluded.
- Depression — chronic daily headache may be the presenting complaint of underlying depressive illness
- Diabetes — hypoglycaemia can present as headache; diabetic ketoacidosis causes headache from cerebral oedema
- Drugs (see list) — alcohol, analgesics (rebound), caffeine, antihypertensives, COCP, corticosteroids, NSAIDs (esp. indomethacin), vasodilators esp. nitrates, sildenafil [9]
- Anaemia — severe anaemia → compensatory ↑cerebral blood flow → vessel distension → headache
- Thyroid disorder and other endocrine (Cushing, Conn, Addison) — hypothyroidism a/w headache via ↑CSF pressure; phaeochromocytoma: classic triad of paroxysmal headache, sweating, palpitations [20]
- Spinal dysfunction (cervicogenic)
- UTI — systemic infection → febrile headache
Quite likely if there is an underlying psychogenic disorder [9]. Always consider whether the headache is the patient's "ticket" to discuss stress, anxiety, depression, domestic violence, or substance abuse.
Differential Diagnosis by Temporal Profile
This is the most practical way to approach headache in an exam or at the bedside. The table below integrates multiple sources [1][2][3][21].
| D/dx | Distinguishing Features | Why These Features Occur |
|---|---|---|
| Sinusitis | Preceding 'cold', nasal discharge [3][21] | Mucosal inflammation + sinus obstruction → ↑pressure in closed sinus cavity → V1/V2 nociceptor activation |
| Migraine | Visual/neurological aura, nausea, vomiting [3][21]; unilateral, throbbing, 4–72h, debilitating | Cortical spreading depression → trigeminovascular activation → CGRP release → neurogenic inflammation |
| Cluster headache | Lacrimation, rhinorrhoea [3][21]; severe periorbital, 15–180min, same time daily, agitation | Hypothalamic activation → trigeminal-autonomic reflex |
| Glaucoma | 'Misting' of vision, 'haloes' around objects [3][21]; severe eye pain, red eye, fixed mid-dilated pupil, rock-hard globe | Acute ↑intraocular pressure → corneal oedema (haloes) + direct stimulation of ciliary/trigeminal nociceptors |
| Arterial dissection (carotid) | Unilateral pain, Horner's syndrome [3][21]; ipsilateral neck pain, may have TIA/stroke | Intimal tear → intramural haematoma stretches vessel wall nociceptors; haematoma compresses pericarotid sympathetic → Horner's |
| Arterial dissection (vertebral) | Symptoms of cerebral ischaemia [3][21]; occipital/posterior neck pain | Vertebral artery supplies posterior circulation → dissection → posterior stroke risk |
| Retrobulbar neuritis | Loss of vision (unilateral) [3][21]; pain on eye movement | Inflammation of posterior optic nerve → pain from traction on inflamed nerve sheath by extraocular muscles [22] |
| Post-traumatic | Following head injury [3][21] | Direct trauma to pain-sensitive structures ± evolving intracranial haematoma |
| Drugs/toxins | On vasodilator drugs [3][21] | Vasodilation → ↑pulsatile stretch of intracranial arterial nociceptors |
| Haemorrhage (SAH, ICH) | Instantaneous onset, vomiting, neck stiffness, impaired conscious level [3][21] | SAH: blood in subarachnoid space → meningeal irritation; ICH: rapid mass effect → traction on dura/vessels |
| Infection (meningitis, encephalitis) | As above but more gradual onset with pyrexia [3][21] | Infectious exudate in subarachnoid space → meningeal nociceptor stimulation + systemic inflammatory response → fever |
| Hydrocephalus | Impaired conscious levels, leg weakness, impaired upward gaze [3][21] | Acute CSF outflow obstruction → rapid ↑ICP → traction on dura; upward gaze palsy from pressure on tectal plate (Parinaud's) |
| Pituitary apoplexy | Sudden excruciating headache, diplopia (CN III), hypopituitarism (esp. adrenal crisis) [17] | Acute haemorrhage into pituitary → rapid stretching of diaphragma sellae (dural fold) → headache; lateral extension compresses CN III in cavernous sinus |
| Hypertensive crisis | Severe headache, vomiting, visual disturbances, transient paralyses, convulsions [8] | Acute ↑↑BP → failure of cerebral autoregulation → cerebral oedema → ↑ICP |
| Cerebral venous sinus thrombosis | ↑ICP (headache, papilloedema, ↓GCS), seizure, focal neurological deficit [13] | Venous outflow obstruction → ↑venous pressure → ↑ICP + venous infarction |
| D/dx | Distinguishing Features | Why These Features Occur |
|---|---|---|
| Infection (subacute/chronic meningitis, e.g. TB; cerebral abscess) | Impaired conscious level, pyrexia, neck stiffness, focal neurological signs [3][21] | Chronic granulomatous basal meningitis (TB) → basal cistern exudate → CN palsies (esp. II, VI), hydrocephalus [23]; abscess → focal mass effect + surrounding oedema |
| Intracranial tumour | Vomiting, papilloedema, impaired conscious level + focal neurological signs [3][21] | Growing mass → ↑ICP → traction on dura/vessels → headache; focal signs reflect location of tumour |
| Chronic subdural haematoma | As above (vomiting, papilloedema, ↓conscious level, focal signs) [3][21] | Slow venous bleeding from torn bridging veins → gradually expanding collection → progressive mass effect over weeks [11] |
| Hydrocephalus | Impaired conscious levels, leg weakness, impaired upward gaze [3][21] | Progressive CSF accumulation → ventriculomegaly → compression of periventricular white matter |
| Idiopathic intracranial hypertension (IIH) | Papilloedema, visual obscurations, CN6 palsy [3][5][21] | ↑ICP without mass lesion; obese young woman; mechanism: ↓CSF reabsorption + ↑CSF outflow resistance |
| Temporal arteritis (GCA) | Thickened, tender scalp arteries [3][10][21]; new headache > 50yo, jaw claudication, visual symptoms, ↑↑ESR | Granulomatous arteritis of superficial temporal artery → vessel wall inflammation → nociceptor stimulation; luminal narrowing → ischaemia (jaw claudication, AAION) |
| Intracranial hypotension | Worse on standing [3][5][21]; orthostatic headache that promptly resolves when supine | CSF leak → ↓CSF volume → brain sags → traction on dura, bridging veins, CN [5] |
| D/dx | Distinguishing Features | Why These Features Occur |
|---|---|---|
| Tension-type headache | Anxiety, depression [3][21]; bilateral band-like, no associated symptoms, can carry on with activities | Chronic muscular tension + central sensitization in pericranial muscles |
| Transformed migraine | Previous history of episodic migraine [3][21]; gradual ↑frequency over months–years | Repeated trigeminovascular activation → central sensitization → chronification; often MOH contributes |
| Medication overuse headache (MOH) | Regular analgesic > 15 days a month [3][21]; headache worsens despite ↑medication | Chronic analgesic use → downregulation of endogenous pain-inhibitory pathways → rebound headache when drug wears off |
| Ocular 'eye strain' | Impaired visual acuity [3][21] | Uncorrected refractive error → sustained contraction of ciliary and extraocular muscles → frontal headache |
| Cervical spondylosis (referred) | Commonly over occipital region; neck stiffness/pain [2] | Degenerative cervical spine disease → nociceptor activation of C1–C3 nerve roots → referred pain to occiput (trigeminocervical convergence) |
This is a high-yield comparison that comes up repeatedly in exams [2][3].
| Feature | Migraine | Tension-type | Cluster |
|---|---|---|---|
| Onset | Gradual onset, crescendo | Gradual onset, wax-and-wane | Rapid onset |
| Triggers | Premenstrual, stress, exercise | Emotions, stress | Alcohol, GTN; periodicity and clustering |
| Quality | Unilateral pulsating, moderate-severe, debilitating (↑by movement) | Bilateral band-like tightness | Severe unilateral periorbital deep, piercing pain; restlessness |
| Duration | 4–72h | 30min–7d | 15min–3h |
| Associated | Nausea/vomiting, photophobia, phonophobia; preceded by aura | None | Ipsilateral autonomic features (lacrimation, nasal congestion, conjunctival injection, Horner's) |
| Behaviour during attack | Lies still in dark, quiet room | Can carry on with activities | Paces, rocks, restless — cannot keep still |
Mnemonic for migraine = POUND: Pounding, lasting 4–72 hOurs, Unilateral, Nausea/vomiting, Debilitating [2].
This is the approach to use when something doesn't feel right [2][3].
| Red Flag | Differential to Consider | Why |
|---|---|---|
| Systemic upset (constitutional symptoms, fever, cancer, immunodeficiency) | CNS infections, neoplastic (lymphoma/metastasis), vasculitis [3] | Systemic inflammation or immunosuppression → ↑risk of opportunistic CNS infection, haematogenous spread of tumour, or systemic vasculitis |
| Neurological symptoms (confusion, focal symptoms, LOC, seizures, meningism) | Intracranial pathologies (vascular, neoplastic, infection) [3] | Focal neurological deficit implies structural lesion disrupting specific neural pathways |
| Onset is new and sudden | Temporal arteritis if new onset > 60yo [3]; Sudden onset: Primary — crash migraine, cluster, benign exertional/orgasmic; Secondary vascular — unruptured saccular aneurysm, SAH, ICA dissection, CVST, hypertensive crises; Secondary non-vascular — intermittent hydrocephalus, benign intracranial HTN, pituitary apoplexy, infections, acute mountain sickness, acute optic neuritis, acute glaucoma [3] | Sudden onset implies a "vascular" mechanism (rupture, occlusion, dissection) until proven otherwise |
| Other associating symptoms | Trauma → intracranial haematoma; Worse when supine + vomiting + ↑with exertion/cough → ↑ICP; Meningococcemic rash → DIC from systemic N. meningitidis; Visual symptoms → glaucoma [3] | Each associated symptom narrows the differential by pointing to a specific pain-generating mechanism |
| Progression or persistence despite treatment | Evolving secondary cause or MOH | Primary headaches should respond to appropriate treatment; failure suggests misdiagnosis or medication overuse |
Special Differential Considerations
A thunderclap headache (peak intensity within 60 seconds) has a broad secondary differential [2][3]:
| Cause | Key Differentiating Feature |
|---|---|
| SAH (most dangerous) | Meningism, LOC, blood on CT or xanthochromia on LP |
| ICH | Focal neurological deficit, hypertension |
| CVST | Seizures, papilloedema, young woman on OCP/pregnant |
| Arterial dissection | Neck/face pain, Horner's, TIA symptoms |
| Pituitary apoplexy | Sudden headache + diplopia (CN III) + hypopituitarism [17] |
| Reversible cerebral vasoconstriction syndrome (RCVS) | Recurrent thunderclap headaches over days, triggered by exertion/Valsalva/sex, segmental vasoconstriction on angiography |
| Hypertensive crisis | BP > 180/120 + target organ damage [8] |
| Primary thunderclap headache | Diagnosis of exclusion after all secondary causes ruled out |
SAH Rule
Every thunderclap headache is SAH until proven otherwise. A normal CT brain within 6 hours has > 98% sensitivity for SAH, but after 6 hours sensitivity drops rapidly — you MUST do an LP if CT is negative and clinical suspicion remains. Look for xanthochromia (yellow CSF from bilirubin, present 12h–12d after bleed) [13].
A patient > 55 years presenting with unaccustomed headache probably has an organic cause [9]. The differential shifts:
- GCA (must exclude — visual loss is preventable with steroids)
- Chronic SDH (elderly with atrophy; may have trivial/forgotten trauma)
- Cerebral tumour (primary or metastatic)
- Cervical spondylosis
- Medication-related (polypharmacy common)
Several endocrine conditions present with headache as a prominent symptom [9][17][20]:
| Condition | Mechanism of Headache |
|---|---|
| Phaeochromocytoma | Paroxysmal catecholamine surges → acute ↑BP → headache; classic triad: paroxysmal headache, sweating, palpitations [20] |
| Pituitary adenoma | Mass effect stretching diaphragma sellae → headache; + VF defects, CN palsies, hypopituitarism [17] |
| Acromegaly | Pituitary adenoma local effects (headache, VF defects) + GH excess → soft tissue/bone overgrowth [17] |
| Cushing syndrome | Cortisol excess → ↑BP → headache; + IIH association [9] |
| Conn syndrome | Aldosterone excess → ↑BP → headache [9] |
| Addison disease | Cortisol deficiency → headache (mechanism unclear; possibly ↑vasopressin/↓cortisol modulation of nociception) [9] |
| Hypoglycaemia | ↓glucose → cerebral energy crisis → compensatory cerebral vasodilation → headache [9] |
| Category | Conditions |
|---|---|
| Primary | TTH, migraine (± aura), cluster headache, paroxysmal hemicrania, SUNCT, hemicrania continua, primary exertional/cough/sexual/thunderclap headache |
| Vascular | SAH, ICH, EDH, SDH, carotid/vertebral dissection, CVST, GCA, malignant HTN, RCVS |
| Neoplastic | Cerebral tumour (primary/metastatic), pituitary adenoma/apoplexy, skull base tumour |
| Infective | Bacterial/viral/TB/fungal meningitis, encephalitis, cerebral abscess |
| CSF pressure | IIH (↑ICP), intracranial hypotension (↓ICP), hydrocephalus |
| Structural | Cervical spondylosis, Chiari malformation |
| Ocular | Acute angle-closure glaucoma, refractive error, optic neuritis |
| ENT/Dental | Sinusitis, otitis, dental infection, TMJ dysfunction |
| Cranial neuralgia | Trigeminal neuralgia, glossopharyngeal neuralgia, occipital neuralgia, post-herpetic neuralgia, herpes zoster (pre-eruption) |
| Medication/substance | MOH, nitrate headache, caffeine withdrawal, COCP, alcohol |
| Endocrine/metabolic | Phaeochromocytoma, hypoglycaemia, hypothyroidism, Cushing/Conn/Addison, OSA (CO₂ retention) |
| Systemic | URTI, anaemia, carbon monoxide poisoning, altitude sickness |
| Psychiatric | Depression, anxiety, somatisation |
| Trauma | Post-concussion syndrome, post-spinal procedure headache |
| Other rare | Paget disease, spontaneous CSF leak, reversible posterior leucoencephalopathy syndrome |
High Yield Summary — Differential Diagnosis of Headache
- Always stratify by tempo: sudden (think vascular emergency) → acute → subacute → chronic.
- Murtagh's probability diagnosis: acute = URTI; chronic = TTH, combination headache, migraine, transformed migraine.
- Serious disorders not to be missed: SAH, ICH, dissection, GCA, CVST, tumour, meningitis, EDH/SDH, glaucoma, IIH.
- Primary headache differentiation: Migraine = POUND (Pounding, 4-72 hOurs, Unilateral, Nausea, Debilitating); TTH = bilateral band, no associated symptoms; Cluster = unilateral periorbital + autonomic features + clockwork periodicity + agitation.
- Thunderclap headache = SAH until proven otherwise (CT → LP if CT normal).
- New headache in > 55yo = likely organic (GCA, tumour, SDH).
- Don't forget masquerades: depression, drugs, anaemia, thyroid, diabetes (hypoglycaemia), phaeochromocytoma.
- Pitfalls: cervical spondylosis, dental disease, refractive error, pre-eruption herpes zoster, sleep apnoea, post-LP headache.
Active Recall - Differential Diagnosis of Headache
References
[1] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.4.1 Headache) [2] Senior notes: Ryan Ho Neurology.pdf (Section 2.1 Approach to Headache, pp. 56–58) [3] Senior notes: Ryan Ho Neurology.pdf (D/dx table pp. 57–58, 60; Primary headache differentiation p. 58) [5] Senior notes: Ryan Ho Neurology.pdf (Section 4 Miscellaneous ICP-related Disorders — IIH and Intracranial Hypotension, p. 158) [8] Senior notes: Ryan Ho Cardiology.pdf (Section Malignant Hypertension, p. 182) [9] Lecture slides: murtagh merge.pdf (pp. 58–60, Headache — Probability diagnosis, Serious disorders, Pitfalls, Masquerades) [10] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.6.1 GCA and PMR, p. 95) [11] Senior notes: felixlai.md (Sections II–V: EDH and SDH Etiology, Pathogenesis, Clinical Manifestation) [13] Senior notes: maxim.md (Section 5.2 Cerebrovascular disease — SAH, CVST) [17] Senior notes: Ryan Ho Endocrine.pdf (Pituitary adenoma p. 107, Pituitary apoplexy p. 107, Acromegaly p. 111) [20] Senior notes: maxim.md (Phaeochromocytoma); Senior notes: Ryan Ho Endocrine.pdf (Phaeochromocytoma p. 66) [21] Senior notes: Ryan Ho Neurology.pdf (D/dx table by temporal course, p. 60) [22] Senior notes: Ryan Ho Opthalmology.pdf (Optic neuritis, p. 92) [23] Senior notes: Ryan Ho Respiratory.pdf (TB meningitis, p. 79)
Diagnostic Criteria for Primary Headache Syndromes
The International Classification of Headache Disorders, 3rd edition (ICHD-3, 2018) provides the gold-standard diagnostic criteria for all headache types. Primary headaches are clinical diagnoses — there is no blood test or imaging study that "confirms" them. The criteria exist to ensure diagnostic consistency and, crucially, to ensure that secondary causes have been appropriately considered.
TTH is divided into episodic (infrequent or frequent) and chronic forms.
Episodic TTH (the most common):
- At least 10 episodes of headache occurring on < 15 days/month for ≥ 3 months
- Lasting 30 minutes to 7 days
- At least 2 of the following 4 characteristics:
- Bilateral location
- Pressing / tightening (non-pulsating) quality — "band-like"
- Mild or moderate intensity
- Not aggravated by routine physical activity (walking, climbing stairs)
- Both of the following:
- No nausea or vomiting
- No more than one of photophobia or phonophobia
- Not better accounted for by another ICHD-3 diagnosis
Why these criteria work from first principles: TTH arises from pericranial muscle tension, NOT trigeminovascular activation. So there is no pulsating quality (no vascular component), no worsening with physical activity (no meningeal sensitization), and no nausea/photophobia/phonophobia (no brainstem sensitization). These "negative" features distinguish it from migraine.
Chronic TTH: ≥ 15 days/month for > 3 months. Mild nausea is permitted but not moderate/severe nausea or vomiting.
B. Migraine — ICHD-3 Criteria [3][4]
Migraine patient defined as: ≥ 2 attacks with aura OR ≥ 5 attacks without aura [4].
- At least 5 attacks fulfilling criteria 2–4
- Headache attacks lasting 4–72 hours (untreated or unsuccessfully treated)
- Headache has at least 2 of the following 4:
- Unilateral location
- Pulsating quality
- Moderate or severe pain intensity
- Aggravation by or causing avoidance of routine physical activity
- During headache, at least 1 of the following:
- Nausea and/or vomiting
- Photophobia AND phonophobia
- Not better accounted for by another ICHD-3 diagnosis
Mnemonic: POUND — Pulsating, 4–72 hOurs, Unilateral, Nausea, Debilitating [2].
- At least 2 attacks fulfilling criteria 2 and 3
- One or more fully reversible aura symptoms:
- Visual (most common — 99%), sensory (31%), speech/language (18%), motor (6%), brainstem, retinal
- At least 3 of the following 6:
- ≥ 1 aura symptom spreads gradually over ≥ 5 minutes
- ≥ 2 aura symptoms occur in succession
- Each individual aura symptom lasts 5–60 minutes
- ≥ 1 aura symptom is unilateral
- ≥ 1 aura symptom is positive (scintillations, pins and needles)
- Aura accompanied or followed within 60 minutes by headache
- Not better accounted for by another ICHD-3 diagnosis
Why must aura spread gradually? Cortical spreading depression (CSD) propagates at 3–5 mm/min across the cortex. This slow march produces a visual aura that "builds" over minutes — unlike a vascular event (stroke/TIA) where onset is maximal within seconds. If a patient describes instantaneous onset of visual symptoms, think vascular, not migraine.
- At least 5 attacks fulfilling criteria 2–4
- Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 minutes (untreated)
- Either or both of the following:
- At least 1 ipsilateral autonomic sign: conjunctival injection/lacrimation, nasal congestion/rhinorrhoea, eyelid oedema, forehead/facial sweating, miosis/ptosis (Horner's)
- A sense of restlessness or agitation
- Occurring with a frequency between one every other day and 8 per day
- Not better accounted for by another ICHD-3 diagnosis
Key distinguisher from migraine: cluster headache patients are restless and agitated (pacing, rocking); migraine patients lie still in a dark room. This reflects the different underlying neurobiology — in cluster headache, hypothalamic activation produces an "arousal" state, whereas in migraine, central sensitization makes all stimulation painful.
Diagnosis requires ≥ 3 of the following 5 criteria:
| Criterion | Rationale |
|---|---|
| 1. Age of onset ≥ 50 years | GCA virtually never occurs < 50yo — the granulomatous process targets age-degenerated arterial walls |
| 2. New headache | New-onset or new-type headache in a previously headache-free elderly patient |
| 3. Temporal artery abnormality on clinical examination | Tender, thickened, or reduced pulsation reflects vessel wall inflammation and possible thrombosis |
| 4. Elevated ESR ( > 50 mm/h) | Systemic inflammation; IL-6 mediated acute phase response |
| 5. Abnormal findings on biopsy of temporal artery | Panarteritis with granulomatous inflammation, giant cells, intimal thickening, fragmentation of internal elastic lamina [10][24] |
Start Steroids Before Biopsy!
Treatment is started upon presumed clinical diagnosis even despite negative initial investigations [10]. Biopsy should be performed within 1–2 weeks but must NOT delay corticosteroids — delay risks permanent blindness from AAION. Biopsy remains positive for at least 2 weeks after steroid initiation because granulomatous inflammation resolves slowly.
- Signs and symptoms of ↑ICP (headache, papilloedema, TVOs, CN6 palsy, pulsatile tinnitus)
- No localizing neurological signs (except CN6 palsy — a false localizing sign)
- Normal brain parenchyma on neuroimaging with:
- Small or normal ventricles ('slit' ventricles)
- Enlarged sella filled with CSF (empty sella sign)
- ± MRV to rule out secondary ↑ICP due to CVST [5]
- LP: ↑ opening pressure ( > 25 cmH₂O in adults) but normal CSF constituents [5]
- No other identifiable cause of ↑ICP
Why MR venography is essential: CVST can perfectly mimic IIH (headache + papilloedema + ↑ICP with "normal" brain parenchyma). The ONLY way to distinguish them is to look at the venous sinuses. Always order MRV before labelling someone with IIH.
Investigation Modalities — Key Findings and Interpretations
Key history [9]:
- A full description of the pain including a pain analysis should be obtained, especially associated symptoms
- It is useful to get the patient to prepare a diary with a grid plotting the relative pain intensity with time of day
- Family history, psychosocial history and drug history
Key examination [9]:
- Use the basic tools of trade: thermometer, sphygmomanometer, pen torch, diagnostic set with ophthalmoscope and stethoscope
- Inspect the head, temporal arteries and eyes
- Areas to palpate include the temporal arteries, the facial and neck muscles, the cervical spine and sinusitis, teeth and TMJs
- Look for signs of meningeal irritation and papilloedema
- A mental state examination is advisable
- Perform a basic neurological examination
A thorough history and focused neurological examination will correctly classify ~95% of headache presentations. Investigations are reserved for red-flag features or diagnostic uncertainty.
| Test | When to Order | Key Findings | Interpretation |
|---|---|---|---|
| FBE (Full Blood Examination) [9] | Baseline screening; suspected infection, anaemia, haematological malignancy | ↑WCC → infection; ↓Hb → anaemia; ↑platelets → reactive thrombocytosis (GCA) or essential thrombocythaemia | Anaemia itself can cause headache (↑cerebral blood flow for O₂ delivery compensation) |
| ESR / CRP [9][10][24] | Suspected GCA, infection, vasculitis | GCA: characteristically very high ESR (reaching 100 mm/h) with ↑CRP [10]; NcNc anaemia, reactive thrombocytosis | ESR > 50 is one of the ACR criteria for GCA; CRP rises and falls faster than ESR → useful for monitoring treatment response |
| Glucose | Suspected hypoglycaemia, DM | ↓glucose → hypoglycaemia headache; ↑glucose → DM (risk factor for stroke) | Hypoglycaemia causes headache via compensatory cerebral vasodilation |
| Coagulation screen (PT/aPTT/INR) | On anticoagulation, suspected coagulopathy, pre-LP | Prolonged → ↑bleeding risk; must correct before LP | Coagulopathy predisposes to ICH and SDH [14] |
| TFT | Suspected hypothyroidism | ↑TSH, ↓fT4 → hypothyroidism | Hypothyroidism a/w headache (possibly via ↑CSF pressure) |
| 24h urine fractionated metanephrines / plasma metanephrines | Suspected phaeochromocytoma (paroxysmal headache + sweating + palpitations + HTN) | 24h urine fractionated metanephrines: Sens 98% Spec 98% [20] | Elevated metanephrines confirm catecholamine-secreting tumour |
3. Neuroimaging
This is the workhorse investigation for secondary headache.
When: First-line imaging for acute headache [12]. Specifically:
- Thunderclap headache [12]
- Red flags: new-onset, Hx of CA/immunodeficiency, coagulopathy or on anticoagulation, with mental status changes, with meningitic features, with focal neurology, progressive deterioration [12]
- Head trauma with indications (Canadian CT Head Rule or New Orleans Criteria) [27]
Why CT first? CT is fast (~1 minute scan time), widely available, excellent at detecting acute blood (which appears hyperdense/white) and bony pathology. It is the most time-efficient way to answer the critical question: "Is there blood?"
| Condition | CT Findings | Why It Looks That Way |
|---|---|---|
| SAH | Hyperdensity in basal cisterns around circle of Willis (65%) or Sylvian fissure (30%) [13] | Fresh blood is hyperdense due to high protein content of haemoglobin; blood pools in dependent cisterns by gravity |
| ICH | Hyperdense lesion within brain parenchyma; common sites: pons, cerebellum, putamen, thalamus (hypertensive) or lobar (CAA) [14] | Acute blood = hyperdense; oedema surrounding = hypodense; attenuation changes with time: acute = hyperdense → subacute = isodense → chronic = hypodense [26] |
| EDH | Biconvex (lentiform) extra-axial hyperdensity that does not cross sutures [12][25] | Arterial blood strips dura from inner skull table; extent limited by suture attachments because dura (endosteal layer) crosses through sutures; shape is biconvex because high-pressure arterial blood pushes the dura inward |
| SDH | Crescent-shaped extra-axial collection that crosses sutures but not the midline falx | Venous blood spreads freely in the subdural space (no dural attachments to sutures); crescent-shaped because it conforms to brain surface; acute = hyperdense, subacute = isodense (the dangerous "invisible" SDH), chronic = hypodense |
| Hydrocephalus | Dilated ventricles ± periventricular hypodensity (transependymal CSF seepage) | CSF accumulation distends ventricles; pressure forces CSF across ependyma into periventricular white matter |
| Mass lesion | Hypodense/isodense/mixed density lesion ± surrounding oedema ± midline shift | Tumour tissue may be of varying density; oedema is vasogenic (from BBB disruption) → hypodense |
Sensitivity of CT for SAH is time-dependent:
- Within 6 hours: > 98% (nearly 100% with modern scanners) — if CT is truly negative at < 6h, some guidelines now allow discharge without LP in low-risk patients
- At 12 hours: ~93%
- At 24 hours: ~86%
- At 1 week: ~50%
- After 2 weeks: may be completely normal
This is why LP remains essential when CT is negative but clinical suspicion for SAH persists — especially if presentation > 6h from onset.
When: Suspected intracranial infection, tumour, inflammatory lesion, vascular pathologies.
| Condition | Findings | Interpretation |
|---|---|---|
| Brain abscess | Ring-enhancing lesion with surrounding oedema | Contrast enhancement indicates BBB disruption; ring = capsule wall of abscess which is highly vascularized |
| Tumour | Normal brain tissue does not enhance (due to BBB). Enhancement indicates: (1) outside BBB (e.g. meningioma — homogeneously enhancing) or (2) disruption of BBB (e.g. high-grade tumours, inflammation) [28] | Low-grade tumours may not enhance; high-grade gliomas and metastases typically show avid ring or heterogeneous enhancement |
| CTA | Opacified vessels showing aneurysm, dissection, stenosis, or thrombus | CT angiography: use of rapid injection of large IV bolus of contrast to opacify vessels [26]; identifies aneurysm location for SAH surgical planning |
When: MRI is a problem-solving tool — used for clinically stable patients when CT is non-diagnostic or when greater soft tissue detail is needed.
MRI is more sensitive than CT except in acute haemorrhage, bony lesions, and calcific lesions [12].
| Sequence | What It Shows Best | Clinical Use in Headache |
|---|---|---|
| T1-weighted | Anatomy (CSF = dark, fat = bright). T1 + gadolinium contrast: enhancing lesions | Tumour delineation, meningeal enhancement (meningitis, leptomeningeal carcinomatosis, intracranial hypotension) |
| T2-weighted / FLAIR | Oedema, gliosis, demyelination (bright). CSF is bright on T2, dark on FLAIR | White matter lesions, MS plaques, vasogenic oedema around tumours |
| DWI (Diffusion-Weighted Imaging) | Restricted diffusion = bright on DWI, dark on ADC | Early ischaemic stroke (within minutes!) [29] — DWI is the most sensitive early indicator; also bright in abscess (restricted diffusion of pus) |
| SWI / GRE | Microbleeds, old blood products (dark "blooming") | Cerebral amyloid angiopathy (lobar microbleeds), chronic hypertensive microbleeds (deep), cavernomas |
| MRV (MR venography) | Venous sinus patency | CVST: filling defect in venous sinus; empty delta sign (superior sagittal sinus involvement) [13]; essential to exclude before diagnosing IIH [5] |
| MRA | Arterial anatomy without iodinated contrast | Aneurysm detection, arterial dissection (intramural haematoma), stenosis |
MRI in intracranial hypotension [5]:
- Diffuse pachymeningeal enhancement (due to ↑blood volume as compensatory mechanism via Monro-Kellie doctrine)
- Dilated veins, sagging brain (brain "droops" from loss of CSF buoyancy)
- ± pocket of CSF at site of leakage
MRI in IIH [5]:
- Normal brain parenchyma with small/normal ventricles ('slit' ventricles)
- Enlarged sella filled with CSF (empty sella sign)
- Flattening of posterior globe, distension of optic nerve sheaths
Comparison: CT vs MRI in stroke [26][29]:
| Feature | CT | MRI |
|---|---|---|
| Radiation | Yes | No |
| Examination time | ~1 minute | ~20 minutes |
| Availability | Good | Fair |
| Sensitivity for infarct | Poor (especially < 24h; ~48% < 1 day) | Good (DWI positive within minutes) |
| Sensitivity for haemorrhage | Good | Good (SWI/GRE) |
Why is CT poor for early infarct? Cytotoxic oedema in early ischaemia causes only subtle density changes — mild hypodensity with loss of grey-white junction. These changes take hours to become apparent on CT. MRI DWI detects restricted water diffusion from cellular swelling within minutes.
LP is performed when you need to analyze CSF directly. Always do CT before LP if raised ICP is suspected — LP in the presence of a mass lesion risks transtentorial herniation (removing CSF from below creates a pressure gradient that "sucks" brain tissue downward through the tentorium).
| Indication in Headache | Key CSF Findings | Interpretation |
|---|---|---|
| SAH (CT-negative) | Bloody CSF, xanthochromia (12h to 12d), persistent ↑RBC > 100,000, ↑protein [13] | Xanthochromia = yellow discoloration from bilirubin (formed by in-vivo breakdown of haemoglobin in CSF — takes ≥ 12h). This distinguishes true SAH from traumatic tap (where RBC count drops between tubes and there is no xanthochromia) |
| Meningitis / encephalitis | ↑WCC (neutrophilic in bacterial, lymphocytic in viral/TB), ↑protein, ↓glucose (bacterial/TB), +ve culture/PCR | Bacterial: turbid, WCC > 1000, protein > 1g/L, glucose < 40% serum. TB: ↑OP 18–30cmH₂O, ↑protein 1–5g/L, ↓glucose < 2.5mmol/L, lymphocytic pleocytosis 100–500/μL, AFB smear Sens 30–60% [23] |
| IIH | ↑ opening pressure ( > 25 cmH₂O) but normal constituents [5] | Confirms ↑ICP; normal protein, glucose and cells exclude infection and malignancy |
| Intracranial hypotension | ↓ opening pressure ( < 6 cmH₂O) | Low pressure confirms CSF leak |
| Carcinomatous meningitis | ↑protein, ↓glucose, lymphocytic pleocytosis, +ve cytology for malignant cells | CSF cytology has ~50% sensitivity on first sample → repeat if suspicious |
LP timing for SAH: Must wait ≥ 12 hours after symptom onset before performing LP for SAH workup. This allows enough time for bilirubin to form (xanthochromia), which is the distinguishing feature from a traumatic tap.
| Modality | Indication | Key Findings |
|---|---|---|
| CTA (CT Angiography) | SAH (identify aneurysm), suspected dissection, suspected CVST | Aneurysm seen as contrast-filled outpouching at arterial bifurcation; dissection shows intimal flap or tapered occlusion; CVST shows filling defect |
| MRA (MR Angiography) | Non-invasive alternative to CTA; aneurysm screening, dissection | Intramural haematoma in dissection appears as crescent-shaped bright signal on T1 fat-sat |
| DSA (Digital Subtraction Angiography) | Gold standard for cerebral aneurysms; when CTA/MRA equivocal | Definitive identification of aneurysm morphology and vascular anatomy for surgical planning. Now mainly therapeutic rather than purely diagnostic (coiling of aneurysms) [26] |
| Colour Doppler USG of head and neck | Suspected GCA when biopsy not immediately available; carotid stenosis | Halo sign in GCA — hypoechoic ring around temporal artery representing vessel wall oedema |
- When: Suspected GCA (new headache in > 50yo + ↑ESR + temporal artery abnormalities)
- What it shows: Panarteritis with mixed infiltrates with fragmentation of intima and necrosis of media ± giant cells [10]
- Pitfall: May be falsely negative due to patchy ("skip") inflammation — a 2cm or longer biopsy segment is recommended; contralateral biopsy if first is negative but suspicion remains high
- Timing: Should be done within 1–2 weeks of starting steroids (histological changes persist for at least 2–4 weeks after steroid initiation)
| Finding | Technique | Significance |
|---|---|---|
| Papilloedema | Fundoscopy with direct ophthalmoscope — swollen disc with blurred edges, dilated superficial capillaries, NO spontaneous venous pulsation of CRV [16] | Indicates ↑ICP → immediate CT/MRI to r/o SOL and hydrocephalus → LP if imaging normal |
| Visual fields (VF) | Confrontation VF, formal perimetry | Enlarged blind spot (acute papilloedema), bitemporal hemianopia (pituitary adenoma compressing chiasm [17]), altitudinal defect (AAION [10]) |
| Intraocular pressure (IOP) | Tonometry | ↑IOP > 21mmHg → acute angle-closure glaucoma |
| RAPD (Relative Afferent Pupillary Defect) | Swinging flashlight test | Present in optic neuritis (the affected eye has ↓pupillary constriction when light swung to it); absent in papilloedema (bilateral equal involvement) |
| Suspected Diagnosis | Key Investigations | Findings |
|---|---|---|
| SAH | CT brain → LP (if CT -ve) → CTA/MRA → DSA [13] | CT: hyperdensity in basal cisterns; LP: xanthochromia; CTA/DSA: aneurysm |
| ICH | Urgent NCCT brain [14]; vascular imaging if non-hypertensive aetiology suspected (no HT, age < 40–45, atypical location, CT abnormality) [14] | CT: parenchymal hyperdensity ± IVH/hydrocephalus ± mass effect |
| EDH | CT brain [11][25] | Biconvex hyperdensity not crossing sutures ± skull fracture |
| SDH | CT brain [11][25] | Crescent hyperdensity (acute) or hypodensity (chronic) crossing sutures |
| Meningitis | CT brain → LP (CSF analysis, Gram stain, culture, PCR) [21][23] | Turbid CSF, ↑WCC, ↑protein, ↓glucose, +organism |
| CVST | CT brain (can be normal!) → MRI brain + MR venogram [13] | Empty delta sign on contrast CT; filling defect on MRV |
| GCA | Urgent ESR/CRP, FBE → temporal artery biopsy [10][24] | Very high ESR; biopsy: granulomatous arteritis ± giant cells |
| IIH | MRI brain (normal parenchyma, slit ventricles, empty sella) + MRV (r/o CVST) → LP (↑OP, normal CSF) [5] | Diagnosis of exclusion after CVST ruled out |
| Intracranial hypotension | Contrast MRI brain [5]; ± CSF flow study/MR myelogram | Diffuse pachymeningeal enhancement, dilated veins, sagging brain |
| Pituitary adenoma/apoplexy | Contrast MRI (modality of choice) [17]; pituitary hormone profile; visual field assessment | MRI: sellar mass ± haemorrhage; hormone panel: hyper- or hypo-secretion |
| Cerebral tumour | CT brain ± contrast → MRI with contrast [28] | Mass lesion ± oedema ± enhancement ± midline shift |
| Dissection (carotid/vertebral) | Vascular imaging: Doppler, MR or CT angiogram [21] | CTA: intimal flap, tapered occlusion; MRI T1 fat-sat: crescent intramural haematoma |
| Sinusitis | Imaging of nasal sinuses (CT sinuses) [21] | Mucosal thickening, air-fluid levels, opacification of sinuses |
High Yield — Investigation Priorities for Headache
- Most headaches need NO investigations — primary headaches (TTH, migraine, cluster) are clinical diagnoses based on ICHD-3 criteria.
- Key investigations to consider: FBE, ESR/CRP, selective radiography (skull XR, sinus XR, CT scan or MRI scan) [9].
- Thunderclap headache: urgent NCCT → LP (if CT -ve, at ≥ 12h) → CTA/DSA.
- CT is king in acute setting: fast, detects blood and fractures. MRI is the problem-solver for subacute/chronic.
- Never LP without CT first if raised ICP suspected — risk of herniation.
- GCA: start steroids → then biopsy. Do not delay treatment for histology.
- IIH: MRI + MRV (to exclude CVST) → LP for opening pressure. Diagnosis of exclusion.
- EDH vs SDH on CT: Biconvex (lentiform), doesn't cross sutures = EDH; Crescent, crosses sutures = SDH.
Active Recall - Diagnosis of Headache
[1] Senior notes: Ryan Ho Fundamentals.pdf (Section 3.4.1 Headache) [2] Senior notes: Ryan Ho Neurology.pdf (Section 2.1 Approach to Headache, pp. 56–58) [3] Senior notes: Ryan Ho Neurology.pdf (D/dx table pp. 57–58, 60; Primary headache differentiation p. 58) [4] Senior notes: Ryan Ho Neurology.pdf (Section 2.2 Primary Headache Syndromes — TTH p. 61, Migraine pp. 61–63, Cluster p. 64) [5] Senior notes: Ryan Ho Neurology.pdf (Section 4 IIH and Intracranial Hypotension, p. 158) [9] Lecture slides: murtagh merge.pdf (pp. 58–60, Headache — Key history, Key examination, Key investigations, Diagnostic tips) [10] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.6.1 GCA and PMR, p. 95) [11] Senior notes: felixlai.md (Sections II–V: EDH and SDH) [12] Senior notes: Ryan Ho Radiology.pdf (Section 2.2 Choice of Modality, p. 17) [13] Senior notes: maxim.md (Section 5.2 SAH and CVST) [14] Senior notes: maxim.md (Intracerebral haemorrhage) [16] Senior notes: Ryan Ho Opthalmology.pdf (Papilloedema, p. 90) [17] Senior notes: Ryan Ho Endocrine.pdf (Pituitary tumour pp. 106–107) [20] Senior notes: Ryan Ho Endocrine.pdf (Phaeochromocytoma p. 66) [21] Senior notes: Ryan Ho Neurology.pdf (Investigation table by cause, p. 60) [23] Senior notes: Ryan Ho Respiratory.pdf (Diagnosis of TBM, p. 79) [24] Senior notes: Ryan Ho Neurology.pdf (GCA diagnostic criteria, p. 65) [25] Senior notes: Ryan Ho Radiology.pdf (EDH and SAH imaging, p. 20) [26] Senior notes: Ryan Ho Diagnostic Radiology.pdf (CT in stroke pp. 40–43) [27] Senior notes: felixlai.md (Canadian CT Head Rule and New Orleans Criteria, p. 1661) [28] Senior notes: Ryan Ho Neurology.pdf (Brain tumour investigations, p. 162) [29] Senior notes: Ryan Ho Diagnostic Radiology.pdf (MRI in acute stroke, p. 50)
The management of headache follows the same logical structure as any condition: identify the cause → treat the cause → relieve symptoms → prevent recurrence. The critical first branch is always: Is this a primary headache or a secondary headache? If secondary, you treat the underlying pathology. If primary, you use a combination of trigger avoidance, abortive therapy, and prophylactic therapy [2][30].
Management: simple or specific analgesics depending on pathology [2][30]:
- Avoidance of triggers
- Preventive (prophylactic) Tx: regular Rx, indicated if frequent or disabling attacks
- Symptomatic (abortive) Tx: for acute attacks
Indications for referral [2][30]:
- Features of potentially serious disease (SNOOP)
- Refractory to appropriate Rx
- Problems with drug treatment, e.g. comorbid disease, medication abuse
- Possibility of psychiatric disease
Management of Primary Headaches
A. Tension-Type Headache (TTH) [4][30]
The key goal is to prevent TTH from becoming chronic [4]. Once chronic, it becomes much harder to treat and overlaps significantly with MOH.
| Drug | Mechanism | Notes |
|---|---|---|
| Paracetamol [4][30] | Central COX inhibition + serotonergic descending pain pathway modulation; exact mechanism debated | First-line for mild-moderate episodes; safe if < 15 days/month use |
| NSAIDs (e.g. ibuprofen, naproxen) or COX-2 inhibitors [4][30] | Inhibit cyclooxygenase → ↓prostaglandin synthesis → ↓peripheral and central sensitization | Effective; GI side effects limit chronic use; avoid if peptic ulcer disease, renal impairment, aspirin-exacerbated respiratory disease |
| Combination analgesics (e.g. paracetamol + caffeine) | Caffeine enhances analgesic absorption and has intrinsic mild analgesic effect via adenosine receptor antagonism → cerebral vasoconstriction | Risk of MOH if used frequently — caffeine withdrawal itself causes headache |
Avoid Opioids and Barbiturates
Opioids and barbiturate-containing analgesics should NOT be used for TTH. They carry high addiction potential, rapidly induce medication overuse headache, and do not address the underlying muscular/central sensitization mechanism.
| Modality | Mechanism | Indication |
|---|---|---|
| REASSURANCE [4] — most important | Patients often fear brain tumour or stroke; explaining the benign nature reduces anxiety → breaks the stress-tension-headache cycle | All patients with TTH |
| Amitriptyline [4][30] | Tricyclic antidepressant ("ami" = friend, "trip" = three [tricyclic]): blocks serotonin and noradrenaline reuptake → enhances descending pain inhibition pathways; also has direct analgesic effect independent of antidepressant action | Chronic TTH (≥ 15 days/month); start at low dose (10–25mg nocte), titrate up |
| Behavioural therapy [4] — stress management, relaxation therapy, EMG biofeedback | Directly addresses the muscular tension component; reduces central sensitization through stress reduction | Chronic TTH, especially if a/w significant psychological stressors |
| Avoidance of likely precipitants [4] | Removes the trigger for muscle tension | All patients |
B. Migraine [4][15][30]
Triggers to identify and modify:
- Dietary: alcohol, chocolate, tyramine-containing foods (e.g. dairy products), starvation, caffeine
- Hormonal: often premenstrual or related to OCP (fluctuation in oestrogen)
- Emotional: stress, anger, excitement
- Others: change in sleep, irregular meals, certain drugs, smoking, fluorescent lights, weather
Why trigger avoidance works from first principles: Each trigger independently lowers the threshold for cortical spreading depression (CSD) in a genetically susceptible brain. Removing triggers keeps the brain below the CSD threshold → fewer attacks.
Step 2: Abortive (Acute) Treatment [15][30]
The principle is stratified care — match treatment intensity to attack severity.
| Drug | Mechanism | Key Points |
|---|---|---|
| Aspirin, paracetamol, NSAIDs [15][30] | COX inhibition → ↓prostaglandin-mediated peripheral and central sensitization; aspirin also has anti-platelet and anti-inflammatory effects on meningeal vessels | Should be taken early in the attack before central sensitization develops (the "window of opportunity"); if taken too late, oral absorption is impaired by gastric stasis |
| D2-blocker antiemetics: metoclopramide, domperidone [15][30] | D2 receptor antagonism in chemoreceptor trigger zone → ↓nausea/vomiting; ALSO prokinetic → ↑gastric emptying → ↑absorption of oral analgesics; ALSO intrinsic anti-headache effect (unclear mechanism, possibly via central dopamine pathway modulation) | Give as adjunct to simple analgesics; domperidone preferred over metoclopramide in young patients (lower risk of extrapyramidal side effects because domperidone does not cross BBB well) |
| Drug | Mechanism | Examples | Side Effects | Contraindications |
|---|---|---|---|---|
| Triptans — treatment of choice for severe headache [15] | 5HT₁B/₁D agonist → (1) vasoconstriction of dilated meningeal vessels, (2) peripheral neuronal inhibition on trigeminal terminals, (3) ↓CN V neurotransmission in trigeminal nucleus caudalis [15] | Sumatriptan (oral, subcutaneous, nasal), naratriptan (PO), zolmitriptan (PO) [15] | Dizziness, somnolence, asthenia, nausea; chest tightness (usually benign "triptan sensation" but concerning in CAD patients) [15] | IHD, stroke, CAD, uncontrolled HTN [15] — because vasoconstriction can worsen coronary/cerebral ischaemia |
| Ergotamine [15] | 5HT₁ agonist → vasoconstriction, ↓trigeminal neurotransmission [15]; also acts on dopamine and adrenergic receptors (hence more side effects than triptans) | Ergotamine (PO, PR), dihydroergotamine (IV, IN) | Vascular events (sustained generalized vasoconstriction), high risk of overuse syndrome and rebound headache [15]; nausea, peripheral vasospasm (Raynaud-like) | IHD, thyrotoxic heart disease, PVD, uncontrolled HTN [15]; pregnancy (oxytocic effect) |
Why triptans are preferred over ergotamine: Triptans are selective 5HT₁B/₁D agonists — they only constrict the specific meningeal vessels involved in migraine. Ergotamine is a "dirty drug" that hits multiple receptor types → widespread vasoconstriction → more side effects and higher risk of MOH. Modern practice reserves ergotamine for refractory cases.
| Drug | Mechanism | Key Points |
|---|---|---|
| Rimegepant, ubrogepant | Small molecule CGRP receptor antagonist → blocks the final common mediator of trigeminovascular pain without vasoconstriction | No cardiovascular contraindications (unlike triptans) — safe in patients with IHD/CAD; can also be used for prophylaxis (rimegepant every other day); approved since 2019–2020 |
Indications for prophylaxis [15]:
- Attacks weekly or > 2 times a month
- Attacks less often but very prolonged and debilitating
| Drug Class | Examples | Mechanism | Notes |
|---|---|---|---|
| Antihypertensives | β-blockers (propranolol, metoprolol), CCB (flunarizine) [15][30] | β-blockers: ↓sympathetic tone → modulates cortical excitability and trigeminovascular reactivity; exact mechanism uncertain; CCB: ↓cortical spreading depression propagation | Propranolol is the most evidence-based β-blocker; C/I in asthma (β₂ blockade → bronchospasm), bradycardia, heart block |
| Antidepressants | Amitriptyline, venlafaxine [15][30] | Amitriptyline: TCA → ↑serotonin and noradrenaline in descending pain inhibition pathways; also blocks sodium channels (direct analgesic); Venlafaxine: SNRI → similar mechanism | Amitriptyline is the most versatile prophylactic — also covers coexisting TTH and depression; sedating → give nocte; C/I in cardiac arrhythmias (QT prolongation) |
| Anticonvulsants | Topiramate, valproate [15][30] | Topiramate: blocks voltage-gated Na channels + enhances GABA + inhibits glutamate + carbonic anhydrase inhibition; Valproate: enhances GABA, modulates ion channels | Topiramate: causes weight loss (useful in obese patients, also beneficial if comorbid IIH), cognitive dulling ("dopamax"), nephrolithiasis, paraesthesia; C/I in pregnancy (teratogenic). Valproate: C/I in women of childbearing age (highly teratogenic — neural tube defects) |
| CGRP monoclonal antibodies | Erenumab, fremanezumab, galcanezumab [15] | Monoclonal antibodies targeting CGRP or its receptor → block the final common mediator of migraine pain; "erenumab" = anti-CGRP receptor, "fremanezumab"/"galcanezumab" = anti-CGRP ligand | New drugs approved since 2018 [15]; monthly SC injection; well tolerated; no hepatotoxicity, no CNS side effects (large molecules don't cross BBB); expensive |
| Others | Pizotifen (5HT₂ blocker) [15]; Botox injections around head and neck every 12 weeks (if refractory) [15] | Pizotifen: blocks 5HT₂C receptors → ↓vascular reactivity; weight gain is major limitation. Botox (onabotulinumtoxinA): ↓release of CGRP and substance P from trigeminal terminals; also ↓peripheral muscle tension | Botox is specifically licensed for chronic migraine (≥ 15 headache days/month for ≥ 3 months); pizotifen rarely used now due to weight gain and sedation |
| Prophylactic NSAIDs | Naproxen, mefenamic acid | COX inhibition → ↓prostaglandin-mediated sensitization | Specifically for menstrual or orgasmic migraine [15] — started 2 days before expected menses and continued through the period |
C. Cluster Headache [6][30]
Cluster headache management is divided into acute attack treatment and prophylaxis during cluster periods.
| Treatment | Mechanism | Key Points |
|---|---|---|
| Subcutaneous sumatriptan [6][30] — 1st line | 5HT₁B/₁D agonist → rapid vasoconstriction of dilated meningeal vessels + ↓trigeminal neurotransmission | SC route is critical — oral triptans are too slow for the brief, intense attacks of cluster headache (attack may last only 15–45 min, but oral absorption takes 30+ min); onset of SC sumatriptan ~10 min |
| 100% O₂ at 15 L/min [6][30] — 1st line | Mechanism debated: likely causes vasoconstriction of meningeal vessels + modulates parasympathetic outflow from pterygopalatine ganglion + may inhibit trigeminal nociceptive firing | Via non-rebreather mask for ≥ 15 min; safe, no drug interactions, can be used in patients with CVD (unlike triptans); patients should be upright and leaning slightly forward |
| Intranasal lidocaine [6][30] | Local anaesthetic blocks signal transmission in sphenopalatine ganglion (located behind middle turbinate in nasal cavity); the ganglion is a relay station for the trigeminal-autonomic reflex | Administered ipsilaterally — the head is tilted back and rotated 30° toward the affected side to allow lidocaine to reach the sphenopalatine fossa |
| PO ergotamine or IV dihydroergotamine [6] | 5HT₁ agonist → vasoconstriction + ↓trigeminal neurotransmission | Reserved for refractory cases; same contraindications as for migraine |
Prophylaxis should be started during cluster periods [6]:
| Drug | Mechanism | Key Points |
|---|---|---|
| Verapamil [6][30] — 1st line for long-lasting cluster periods | L-type calcium channel blocker → ↓hypothalamic neuronal excitability (the "clock" driving cluster periodicity) + ↓vascular smooth muscle tone | Requires ECG monitoring before and after dose titration (risk of heart block — PR prolongation); doses used in cluster headache (240–960mg/day) are much higher than for cardiovascular indications |
| Short course oral corticosteroids [6][30] — for shorter-lasting cluster periods | ↓neurogenic inflammation via multiple anti-inflammatory pathways; rapidly effective (often within 24–48h) | Typically prednisolone 60–80mg/day tapered over 2–3 weeks; used as a "bridge" while verapamil is titrated up; cannot be used long-term (Cushingoid effects, osteoporosis, adrenal suppression) |
| Topiramate, methysergide [6] | Topiramate: as for migraine; Methysergide: 5HT₂ antagonist → ↓vascular reactivity; must have a 1-month drug holiday every 6 months to prevent retroperitoneal/cardiac fibrosis | Second-line agents |
| Lithium [6][30] — if severe debilitating clusters | Modulates circadian rhythm via effects on hypothalamic circadian pacemaker neurons (suprachiasmatic nucleus); also modulates serotonergic and dopaminergic transmission | Requires monitoring of serum level, TFT, RFT [6]; narrow therapeutic index (0.6–1.2 mmol/L); toxicity causes tremor, ataxia, renal impairment, hypothyroidism |
| Gabapentin [6] | Binds α2δ subunit of voltage-gated calcium channels → ↓excitatory neurotransmitter release | Third-line; generally well-tolerated; sedation is main side effect |
Medication overuse (analgesic) headache [15]:
- Can complicate any kind of headache syndrome but especially a/w migraine and TTH
- Characterized by: gradual ↑headache frequency and drug consumption, change in headache characteristics
- Ultimately take analgesics and large amounts of caffeine-containing beverages
Diagnostic threshold (ICHD-3):
- Simple analgesics ≥ 15 days/month for > 3 months
- Triptans, ergotamine, opioids, or combination analgesics ≥ 10 days/month for > 3 months
Management Approach
| Step | Action | Rationale |
|---|---|---|
| 1. Education | Explain the paradox: the medication meant to relieve headache is perpetuating it | Patient understanding is essential for compliance with withdrawal |
| 2. Withdrawal of offending analgesic | Abrupt withdrawal if simple analgesics or triptans; gradual taper if opioids or barbiturates (to avoid withdrawal seizures) | Removing the drug allows endogenous pain-inhibition pathways to recover; expect a transient worsening ("rebound") lasting 2–10 days |
| 3. Bridge therapy during withdrawal | Naproxen 500mg BD for 2–4 weeks (different class from the overused drug); or short course prednisolone; adequate hydration | Provides analgesia during the difficult withdrawal period without perpetuating the MOH cycle |
| 4. Start appropriate prophylaxis | Begin prophylactic medication for the underlying primary headache (e.g. topiramate, amitriptyline, CGRP mAb for migraine) | Prophylaxis reduces attack frequency → reduces the "need" for acute analgesics → prevents relapse into MOH |
| 5. Follow-up and headache diary | Limit acute medication to < 2 days/week; regular review | Ongoing monitoring prevents relapse; diary identifies remaining triggers |
MOH — The Vicious Cycle
Frequent analgesic use → downregulation of endogenous opioid and serotonin pathways → ↓pain threshold → headache recurs sooner → patient takes MORE analgesics → further downregulation. Breaking this cycle requires withdrawing the offending drug AND simultaneously starting prophylaxis so the patient can tolerate the withdrawal period.
Management of Secondary Headaches
| Phase | Management | Rationale |
|---|---|---|
| Resuscitation | ABC, stabilize airway, IV access, monitor GCS | Airway at risk if ↓consciousness |
| Secure the aneurysm | Endovascular coiling (preferred) or surgical clipping — within 24–72h of diagnosis | Prevents catastrophic re-bleeding (4% risk in first 24h, 20% in first 2 weeks); coiling involves threading a catheter from the femoral artery and packing the aneurysm with platinum coils; clipping involves craniotomy and placing a metal clip across the aneurysm neck |
| Prevent vasospasm | Nimodipine 60mg PO q4h for 21 days (dihydropyridine CCB) | Nimodipine crosses the BBB and ↓calcium influx into vascular smooth muscle → ↓cerebral vasospasm; the only intervention proven to ↓delayed cerebral ischaemia (DCI) in SAH. NOT for BP lowering — the effect is neuroprotective |
| Prevent re-bleeding | Bed rest, analgesia, stool softeners (avoid straining), target SBP < 160 before aneurysm secured | ↓transmural pressure across aneurysm wall; straining → ↑intrathoracic pressure → ↑ICP → ↑risk of re-bleed |
| Manage hydrocephalus | External ventricular drain (EVD) if acute obstructive hydrocephalus; VP shunt if chronic | Blood products block CSF reabsorption at arachnoid granulations → communicating hydrocephalus; or blood in ventricles obstructs foramina |
| Monitor for DCI | Daily neurological examination, transcranial Doppler (↑MCA velocities > 120cm/s suggest vasospasm), CT perfusion if deterioration | DCI peaks days 4–14 post-bleed |
| Triple-H therapy (historical) | Hypertension, hypervolaemia, haemodilution → now largely replaced by euvolaemia and induced hypertension if DCI suspected | Maintaining cerebral perfusion through the vasospastic segment; hypervolaemia actually increases complications so current practice favours euvolaemia |
| Intervention | Details | Rationale |
|---|---|---|
| Resuscitation | ABC; watch out for cervical spine injury [14]; NPOEM, IV fluids, monitor vitals + neuro-obs [14] | Haemorrhagic stroke often follows trauma or occurs with severe HTN |
| Blood pressure control | IV labetalol [14]; treat if SBP > 150 (unless evidence of increased ICP); target SBP < 140, but avoid rapid BP reduction [14] | ↓BP reduces ongoing bleeding and haematoma expansion, but excessive ↓BP risks ischaemia in the penumbra around the haematoma. Labetalol is ideal: combined α₁ + β blockade → smooth ↓BP without reflex tachycardia |
| Reversal of anticoagulation | Warfarin → IV vitamin K + 4-factor PCC; DOACs → specific reversal agents (idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors); antiplatelet → platelet transfusion (controversial) [14] | Coagulopathy promotes haematoma expansion; rapid reversal limits secondary injury |
| Acute hydrocephalus | Burr hole + EVD [14] | Intraventricular extension of blood → obstructive hydrocephalus → ↑ICP → EVD provides immediate CSF drainage |
| Surgical evacuation | Consider for superficial lobar ICH with ↓GCS, cerebellar haemorrhage > 3cm, or signs of brainstem compression | Cerebellar haemorrhage is a neurosurgical emergency — posterior fossa is a small, enclosed space → rapid brainstem compression |
| Condition | Management | Why |
|---|---|---|
| Acute EDH | Emergency craniotomy + haematoma evacuation | Arterial bleed → rapid expansion → uncal herniation within hours if untreated |
| Acute SDH | Craniotomy + evacuation if ≥ 10mm thickness or midline shift ≥ 5mm or GCS deterioration | Large acute SDH causes significant mass effect |
| Chronic SDH | Burr hole drainage (1 or 2 holes) + subdural drain | Chronic SDH is liquefied (venous blood has broken down) → easily drained through small holes; craniotomy usually unnecessary |
| Small/asymptomatic SDH | Conservative: observation with serial imaging | Small collections may reabsorb spontaneously; surgery carries its own risks |
| Step | Action | Details |
|---|---|---|
| Immediate | Urgent high-dose systemic corticosteroids: prednisolone 1–2 mg/kg/day [10] or 60mg/day [24] | Treatment is started upon presumed clinical diagnosis even despite negative initial Ix [10]; urgent Tx prevents blindness and brainstem stroke and ↓headache [24] |
| If visual symptoms already present | Parenteral high-dose steroids [24] (IV methylprednisolone 1g/day for 3 days → oral) | Intravenous route achieves faster therapeutic levels; visual loss may still be irreversible but treats the fellow eye |
| Steroid taper | Gradual ↓dosage to maintenance level according to ESR level [24]; typically over 1–2 years [10] | Too-rapid taper → relapse; monitor ESR/CRP to guide tapering |
| Steroid-sparing agents | Tocilizumab (anti-IL6), methotrexate upon relapsing disease [10] | IL-6 drives the acute-phase response in GCA; tocilizumab (GiACTA trial) allows faster steroid taper and ↓relapse rate |
| Prognosis | Usually dramatic response to steroid (complete resolution of S/S ≤ 48–72h of treatment) [10] | If no response to steroids within 48–72h → reconsider the diagnosis |
25% at risk of severe permanent vision loss [5] — this drives the urgency of treatment.
| Treatment | Mechanism | Details |
|---|---|---|
| Dietary changes to ↓weight [5][16] | Obesity → ↑intra-abdominal pressure → ↑central venous pressure → ↓CSF reabsorption; weight loss reverses this chain | Even 5–10% weight loss can dramatically ↓ICP; bariatric surgery considered if BMI very high |
| Carbonic anhydrase inhibitor (1st-line): acetazolamide (Diamox), topiramate [5][16] | Acetazolamide inhibits carbonic anhydrase in choroid plexus → ↓CSF production (choroid plexus produces ~500mL CSF/day; blocking CA can ↓production by ~50%) | Typical dose: acetazolamide 250mg BD → titrate up to 1–2g/day; side effects: paraesthesia (acral), metabolic acidosis, nephrolithiasis, taste disturbance. Topiramate has dual benefit: CA inhibition + appetite suppression (weight loss) |
| ± Diuretics, e.g. furosemide (if refractory) [5][16] | ↓CSF production via uncertain mechanism (possibly ↓Na/K transport at choroid plexus) | Second-line add-on therapy |
| Short-course corticosteroids, e.g. prednisolone [5] | Anti-inflammatory → may ↓CSF outflow resistance; but can cause weight gain → paradoxically worsen IIH long-term | Used only as a bridge (e.g. while waiting for acetazolamide to take effect or before surgery); NOT for long-term use |
| Serial LPs to ↓ICP [5] | Directly removes CSF → immediate ↓ICP → symptom relief | Temporary measure; useful in acute setting or pregnancy when drugs are limited |
| Optic nerve fenestration (ONSF) [5][16] | Surgical slits cut in the optic nerve sheath → creates a "safety valve" allowing CSF to drain away from the optic nerve → ↓pressure on optic nerve | Specifically for progressive visual loss; protects vision but may not relieve headache |
| CSF shunting [5][16] (lumboperitoneal shunt) | Diverts CSF from lumbar thecal sac to peritoneal cavity → continuous CSF drainage → sustained ↓ICP | For refractory cases with both headache and visual loss; complications include shunt obstruction, over-drainage, infection |
| Venous sinus stenting | Stents placed in stenotic transverse sinuses → improves venous outflow → ↓ICP | Emerging treatment for selected patients with documented venous sinus stenosis on MRV; increasingly used in refractory IIH |
| Treatment | Details | Rationale |
|---|---|---|
| Anticoagulation: LMWH (acute) → warfarin or dabigatran for 3 months (chronic) [13] | LMWH (e.g. enoxaparin) → immediate anticoagulation; transition to oral anticoagulant for maintenance | Even in the presence of haemorrhagic venous infarction, anticoagulation is indicated — the haemorrhage is a consequence of venous congestion, and the treatment is to relieve the venous obstruction; anticoagulation prevents thrombus propagation and allows the body's fibrinolytic system to resolve the existing clot |
| Endovascular thrombolysis in selected patients [13] | Direct catheter-based lysis of thrombus | For severe/deteriorating cases despite anticoagulation |
| ICP management [13] | Acetazolamide, head elevation, ± EVD if acute hydrocephalus | Venous outflow obstruction → ↑ICP; same principles as IIH |
| Treat seizures [13] | Antiepileptic drugs (levetiracetam preferred) | Seizures occur in up to 40% of CVST; cortical venous infarction is epileptogenic |
Hypertensive emergency: BP > 180/120 + worsening/new TOD [8]:
| Phase | BP Target | Agent |
|---|---|---|
| 1st hour | ≤ 25% ↓BP [8] | IV labetalol, IV nicardipine, or IV sodium nitroprusside (ICU with IABP monitoring) |
| Next 2–6 hours | To 160/110 [8] | Continue IV infusion, titrate carefully |
| Next 24–48 hours | Cautiously to normal [8] | Transition to oral agents |
Aim SBP < 140 in 1st hour and < 120 in aortic dissection for those with compelling indications for acute BP control [8].
Why Not Drop BP Too Fast?
Cerebral autoregulation in chronic hypertensives is "reset" to higher pressures. The autoregulatory curve shifts right — meaning the brain can only maintain perfusion above a certain (higher than normal) MAP. If you drop BP too rapidly, you fall below the autoregulatory threshold → cerebral hypoperfusion → watershed infarction. The ≤ 25% rule in the first hour is designed to lower BP enough to stop target organ damage without causing ischaemic injury.
| Type | Treatment | Key Points |
|---|---|---|
| Bacterial | Empirical IV ceftriaxone 2g q12h + ampicillin (if Listeria risk — age > 50, immunosuppressed) + dexamethasone (before or with first antibiotic dose) | Dexamethasone ↓inflammatory response → ↓cerebral oedema → improved outcomes (proven for S. pneumoniae); must be given before/with antibiotics, not after |
| TB | RIPE regimen (rifampicin + isoniazid + pyrazinamide + ethambutol) × 2 months → RI × 10 months (total 12 months) + adjunctive dexamethasone | TB meningitis treatment is longer than pulmonary TB; dexamethasone ↓mortality in TB meningitis |
| Viral | Supportive; IV aciclovir if HSV suspected (do NOT wait for PCR results) | HSV encephalitis has 70% mortality if untreated → empirical treatment is life-saving |
| Treatment | Mechanism | Details |
|---|---|---|
| Conservative | Flat bed rest, hydration, caffeine (adenosine receptor antagonist → cerebral vasoconstriction → ↑ICP slightly) | Most post-LP headaches resolve spontaneously within 1–2 weeks |
| Epidural blood patch | Patient's own blood (15–20mL) injected into epidural space at or near the site of the dural puncture → clot seals the leak + mass effect of blood ↑epidural pressure → ↑CSF pressure | Gold standard for post-LP headache; ~90% success rate with single patch; may need repeat if recurrent |
| Surgical dural repair | Direct suture or patching of identified dural tear | For refractory spontaneous intracranial hypotension with identified leak site on MR myelography |
| Drug | Major Contraindications | Why |
|---|---|---|
| Triptans | IHD, stroke, CAD, uncontrolled HTN [15] | Vasoconstriction worsens coronary/cerebral ischaemia |
| Ergotamine | IHD, thyrotoxic heart disease, PVD, uncontrolled HTN [15]; pregnancy | Sustained generalized vasoconstriction; oxytocic |
| Propranolol | Asthma, COPD, bradycardia, heart block, Raynaud's | β₂ blockade → bronchospasm; β₁ blockade → ↓HR |
| Valproate | Women of childbearing age (teratogenic — NTDs), hepatic disease | Highly teratogenic; hepatotoxic |
| Topiramate | Pregnancy, nephrolithiasis, metabolic acidosis | Teratogenic (cleft palate); CA inhibition → acidosis/stones |
| Verapamil (high-dose for cluster) | Heart block, severe LV dysfunction | ↓AV conduction → requires ECG monitoring |
| Lithium | Renal impairment, thyroid disease, pregnancy | Narrow therapeutic index; nephrotoxic, causes hypothyroidism, Ebstein's anomaly in fetus |
| Amitriptyline | Cardiac arrhythmia (long QT), recent MI, urinary retention, narrow-angle glaucoma | Anticholinergic effects; QT prolongation → torsades |
| Acetazolamide | Severe hepatic/renal impairment, sulfonamide allergy, hypokalemia | ↓K⁺ (CA inhibition → bicarbonaturia → K⁺ loss); cross-reactivity with sulfonamide allergy |
High Yield Summary — Management of Headache
Primary headaches — three pillars: (1) Trigger avoidance, (2) Abortive treatment, (3) Prophylactic treatment.
TTH: Abortive = paracetamol/NSAIDs. Prophylactic = REASSURANCE (most important!) + amitriptyline + behavioural therapy.
Migraine: Mild → paracetamol/NSAIDs + antiemetic. Severe → triptans (5HT₁ agonist; C/I in IHD/stroke/CAD). Prophylaxis (if ≥ 2/month or disabling) → propranolol, amitriptyline, topiramate, or CGRP monoclonal antibodies.
Cluster: Acute → SC sumatriptan OR 100% O₂ 15L/min. Prophylaxis → verapamil (1st line, needs ECG monitoring), short-course steroids (bridge), lithium (severe).
MOH: Withdraw offending drug + bridge therapy (naproxen or short-course prednisolone) + start appropriate prophylaxis.
SAH: Secure aneurysm (coil or clip) + nimodipine 21 days + manage hydrocephalus.
ICH: BP control (IV labetalol, target SBP < 140) + reverse anticoagulation + EVD if hydrocephalus.
GCA: Urgent prednisolone 60mg (or IV methylprednisolone if visual loss) → slow taper over 1–2 years ± tocilizumab.
IIH: Weight loss + acetazolamide (1st line) ± surgery (ONSF, shunt) if progressive visual loss.
CVST: Anticoagulation (even if haemorrhagic infarct!) + ICP management.
Hypertensive emergency: ≤ 25% ↓BP in 1st hour → 160/110 over next 2–6h → normal over 24–48h.
Active Recall - Management of Headache
[2] Senior notes: Ryan Ho Neurology.pdf (Section 2.1 Approach to Headache, management summary p. 59) [4] Senior notes: Ryan Ho Neurology.pdf (Section 2.2.1 TTH treatment p. 61) [5] Senior notes: Ryan Ho Neurology.pdf (Section 4 IIH and Intracranial Hypotension, p. 158) [6] Senior notes: Ryan Ho Neurology.pdf (Section 2.2.3 Cluster Headache management, p. 64) [8] Senior notes: Ryan Ho Cardiology.pdf (Section Malignant Hypertension and hypertensive emergency, p. 182) [9] Lecture slides: murtagh merge.pdf (pp. 58–60, Headache) [10] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.6.1 GCA and PMR, p. 95) [11] Senior notes: felixlai.md (Sections II–V: EDH and SDH) [13] Senior notes: maxim.md (Section 5.2 SAH and CVST management) [14] Senior notes: maxim.md (Intracerebral haemorrhage management) [15] Senior notes: Ryan Ho Neurology.pdf (Section 2.2.2 Migraine treatment pp. 63; MOH p. 63) [16] Senior notes: Ryan Ho Opthalmology.pdf (Papilloedema and IIH management, p. 90) [24] Senior notes: Ryan Ho Neurology.pdf (Section 2.3 GCA treatment, p. 65) [30] Senior notes: Ryan Ho Fundamentals.pdf (Headache management summary table, p. 314)
Complications in the headache domain fall into two broad buckets:
- Complications of the primary headache disorders themselves — these are consequences of the headache disease process running unchecked, or of its treatment going wrong.
- Complications of the serious secondary causes of headache — these are the sequelae of SAH, ICH, meningitis, GCA, IIH, etc. Understanding them is essential because preventing and recognising these complications drives much of acute headache management.
I. Complications of Primary Headache Disorders
Migraine is not simply a "benign" headache — chronic or severe migraine can lead to well-defined complications recognised by the ICHD-3.
| Complication | Definition | Pathophysiology | Clinical Significance |
|---|---|---|---|
| Chronic migraine | ≥ 15 headache days/month for > 3 months without medication overuse [4] | Repeated trigeminovascular activation → progressive central sensitization of the trigeminal nucleus caudalis → ↓pain threshold → headaches become self-perpetuating even without external triggers | Major burden on quality of life; often coexists with MOH; requires prophylactic treatment (CGRP mAb, botox, topiramate) |
| Status migrainosus | Debilitating migraine attack lasting > 72 hours [4] | Prolonged trigeminovascular activation that fails to self-terminate; often triggered by medication overuse, hormonal changes, or emotional stress | Medical emergency — risk of dehydration from protracted vomiting; may require IV fluids, IV metoclopramide, IV dexamethasone, and parenteral triptans or dihydroergotamine |
| Persistent aura without infarction | Aura symptoms lasting > 1 week [4] without evidence of infarction on imaging | Cortical spreading depression fails to resolve → persistent cortical dysfunction; mechanism poorly understood | Must image (MRI with DWI) to exclude infarction; reassurance if imaging normal; may persist for months |
| Migrainous infarction | Aura symptoms lasting > 1 hour + ischaemic infarct confirmed on CT/MRI [4] | CSD → prolonged cortical oligaemia → if blood flow drops below the infarction threshold, irreversible ischaemia occurs; there is a small but documented ↑risk of stroke during/after a migrainous attack [4] | Treat as acute ischaemic stroke; thrombolysis if within window; long-term — risk factor modification, consider discontinuing OCP (oestrogen-containing contraceptives compound the risk) |
| Migraine-triggered seizure | Epileptic seizure occurring during or ≤ 1 hour of aura [4] | CSD wave is a massive wave of neuronal depolarization — if it reaches sufficient intensity, it can trigger epileptiform discharges; the cortex is transiently hyperexcitable during CSD | Anticonvulsant therapy if recurrent; distinguished from seizure with post-ictal headache (which is the reverse temporal relationship) |
Why are migraineurs at ↑risk of stroke? Several mechanisms are proposed: (1) CSD can reduce cortical perfusion below the ischaemic threshold; (2) migraine-associated endothelial dysfunction promotes thrombosis; (3) patent foramen ovale (PFO) — more prevalent in migraineurs with aura — allows paradoxical embolism; (4) oestrogen-containing OCP further ↑thrombotic risk. This is why migraine with aura + OCP + smoking is a dangerous triad for stroke risk.
MOH is the most common complication of all primary headache treatment. It deserves emphasis because it is largely iatrogenic and preventable.
- Can complicate any kind of headache syndrome but especially a/w migraine and TTH [15]
- Characterized by: gradual ↑headache frequency and drug consumption, change in headache characteristics [15]
- Mechanism: chronic analgesic use → downregulation of endogenous opioid and serotonin pain-inhibition pathways → ↓pain threshold → rebound headache when drug wears off → patient takes MORE drug → vicious cycle
- Ergotamine has high risk of overuse syndrome and rebound headache [15]
- Prevention: limit acute medication to < 2 days/week; start prophylaxis early if attacks are frequent
- Episodic TTH can evolve into chronic TTH (≥ 15 days/month for > 3 months) if not managed
- Central sensitization becomes established → headache becomes self-sustaining
- Often overlaps with MOH and depression — creating a "triple comorbidity" that is difficult to treat
- Suicide risk: cluster headache is sometimes called "suicide headache" because of the unbearable severity; patients during cluster periods are at genuinely elevated risk of self-harm
- Chronic cluster headache: ~10–15% of patients develop chronic cluster (attacks recur > 1 year without remission > 1 month) — much harder to treat; may require lithium or occipital nerve stimulation
- Horner's syndrome may become permanent after repeated cluster periods due to cumulative sympathetic damage in the pericarotid plexus
II. Complications of Secondary Causes of Headache
SAH has the highest complication burden of any headache-associated emergency. The 50% mortality at 1 month [6] reflects the severity of these complications.
| Complication | Timing | Mechanism | Management |
|---|---|---|---|
| Re-bleeding | Highest in first 24h (3–4%), then 1–2% per day in first month [31] | Unsecured aneurysm with thin-walled fundus at rupture point → systemic BP fluctuations → re-rupture; aneurysmal rupture is associated with a mortality of 70% [31] | Aneurysm repair (clip or coil) within 24–72 hours [31]; bed rest, stool softeners, BP control before securing |
| Cerebral vasospasm and delayed cerebral ischaemia (DCI) | Days 4–14 (peak day 7) | Blood breakdown products (oxyhaemoglobin, bilirubin oxidation products) in the subarachnoid space → direct smooth muscle contraction + endothelial dysfunction + inflammation → segmental arterial narrowing → ↓cerebral perfusion | Nimodipine 60mg q4h PO × 21 days (prevents DCI, not vasospasm per se); euvolaemia; induced hypertension if DCI occurs; IA vasodilators or balloon angioplasty for refractory vasospasm |
| Hydrocephalus | Acute (hours–days) or chronic (weeks–months) | Acute: blood clot in 4th ventricle or cerebral aqueduct → obstructive hydrocephalus; Chronic: blood products impair CSF reabsorption at arachnoid granulations → communicating hydrocephalus [31][32] | Acute: EVD (external ventricular drain) [31]; Chronic: VP shunt |
| Seizures [31][32] | Acute or delayed | Cortical irritation by subarachnoid blood; cortical ischaemia from vasospasm → epileptogenic focus | Prophylactic anticonvulsant if SAH [32]; early IV phenytoin or levetiracetam if seizure occurs |
| Cerebral oedema [31] | Hours–days | Global cerebral ischaemia from acute ↑ICP + vasospasm → cytotoxic oedema; BBB disruption → vasogenic oedema | Head elevation 30°, osmotherapy (IV mannitol), avoid hyperthermia, consider decompressive craniectomy if refractory |
| Herniation [31] | Hours–days | Expanding haematoma or severe oedema → brain displacement through tentorial or foramen magnum openings | Emergency neurosurgery; osmotherapy as temporising measure |
| Hyponatraemia | Days 3–14 | Cerebral salt wasting (CSW — inappropriate natriuresis from ANP/BNP release) or SIADH → ↓serum Na | Distinguish CSW (hypovolaemic) from SIADH (euvolaemic): CSW requires saline replacement; SIADH requires fluid restriction. Hyponatraemia can worsen cerebral oedema |
| Cardiac complications | Acute | Sympathetic surge from hypothalamic dysfunction → catecholamine storm → myocardial stunning ("neurogenic stunned myocardium"), arrhythmias, troponin rise, ECG changes (deep T-wave inversions, prolonged QT) | Continuous cardiac monitoring; usually self-limiting; distinguish from ACS |
| Complication | Mechanism | Notes |
|---|---|---|
| Haematoma expansion | Ongoing bleeding in the first 6–24h; more likely if on anticoagulants, large initial volume, "spot sign" on CTA (active contrast extravasation) | Drives early neurological deterioration; aggressive BP control (SBP < 140) and anticoagulation reversal reduce expansion |
| ↑ICP and herniation | Mass effect of haematoma + surrounding oedema → Monro-Kellie exceeded → herniation | Head elevation 30°; IV mannitol (osmotic diuretic) is the treatment of choice to lower ICP; corticosteroids should NOT be administered — dexamethasone does NOT improve outcome but increases complication rate, primarily infection [31] |
| Intraventricular haemorrhage (IVH) | Haematoma ruptures into ventricle → obstructive hydrocephalus | Burr hole + EVD [14]; consider intraventricular tPA to accelerate clot lysis |
| Seizures | Cortical irritation by blood products; more common in lobar ICH (cortical location) than deep ICH | Prophylactic use of anticonvulsants is NOT recommended; treat clinical seizures and electrographic seizures on EEG [31][32] |
Steroids in ICH — A Common Exam Trap
Corticosteroids should NOT be administered in patients with elevated ICP in intracerebral haemorrhage. Dexamethasone does NOT improve outcome but increases complication rate, primarily infection [31]. This is different from tumour-related oedema where steroids ARE helpful (because tumour oedema is vasogenic and steroid-responsive, while ICH oedema is predominantly cytotoxic).
| Complication | Mechanism | Key Points |
|---|---|---|
| Uncal herniation → ipsilateral CN III palsy → ipsilateral dilated pupil | Expanding supratentorial mass → medial temporal lobe (uncus) herniates over tentorial edge → compresses CN III | Parasympathetic fibres on surface of CN III are compressed first → loss of pupillary constriction → fixed, dilated pupil; a neurosurgical emergency |
| Contralateral OR ipsilateral hemiparesis | Contralateral: direct cortical compression. Ipsilateral ("false localizing sign"): lateral displacement of midbrain compresses contralateral cerebral peduncle against free edge of tentorium (Kernohan's notch) [11] | Presence of ipsilateral weakness can be misleading about the side of the lesion — always correlate with imaging |
| Cushing's reflex | Hypertension + bradycardia + respiratory depression/irregularity [11] — ↑ICP → brainstem ischaemia → sympathetic surge + baroreceptor reflex + respiratory centre compression | Terminal sign of impending brainstem herniation; demands immediate neurosurgical intervention |
| Chronic SDH → recurrent haematoma | After burr-hole drainage, the subdural space has a neovascular membrane → fragile new vessels can re-bleed → recurrence in ~5–30% | Serial imaging post-drainage; some centres leave subdural drains for 24–48h to reduce recurrence |
| Overshunting in CSF shunts (if shunt placed for secondary hydrocephalus) | Postural headache (worsened with standing, relieved lying down); can lead to subdural haematoma (stretching of bridging veins) [33] | Paradoxically, treating one complication (hydrocephalus) can create another (SDH from over-drainage) |
Mainly occurs in pyogenic and chronic meningitis [34]:
| Complication | Mechanism | Clinical Significance |
|---|---|---|
| Hydrocephalus → ↑ICP [34][35] | Basal meningeal adhesions due to incomplete organization of inflammatory exudates → block CSF reabsorption (communicating) or obstruct foramina (obstructive) | Hydrocephalus in 80% of TB meningitis [35]; requires EVD or VP shunt; a major cause of morbidity |
| CN palsies (III, IV, VI most common; VIII involvement tends to persist) [34] | Basal meningeal inflammation and scarring → CN entrapment at the skull base | CN VIII involvement → sensorineural hearing loss (may be permanent); CN VI → diplopia |
| Arteritis / thrombophlebitis → cerebral infarction [34][35] | Inflammatory exudate surrounds basal arteries → vasculitis → thrombosis → infarction; stroke observed in 26% of TBM [35] | Can cause devastating focal neurological deficit; often presents as unexpected deterioration during treatment |
| Parenchymal damage | Direct neuronal injury from infection + inflammatory mediators + ischaemia | Neurological sequelae: intellectual impairment, mental retardation or cerebral palsy (especially in paediatric pyogenic meningitis) [34] |
| Seizures | Occur in 10% of acute bacterial meningitis; ~5% develop epilepsy [34] | Cortical irritation from inflammation and ischaemia |
| Spread of infection | Locally → cerebritis, cerebral abscess, subdural effusion/empyema; systemically → arthritis, infective endocarditis [34] | Abscess is a surgical emergency if mass effect significant |
| SIADH → hyponatraemia [34][35] | Meningeal inflammation stimulates ADH release → water retention → dilutional hyponatraemia; also cerebral salt wasting (CSWS) in TBM [35] | Hyponatraemia worsens cerebral oedema; must distinguish SIADH (fluid restrict) from CSWS (salt replace) |
| Visual loss (TBM) | Optochiasmic arachnoiditis (encasement of optic nerve and chiasma by thick TB exudates), dilated 3rd ventricle compressing optic chiasma, ↑ICP, endarteritis of optic nerve and chiasmal vessels [35] | Affects ~25% of TBM patients; often irreversible |
| Sensorineural hearing loss | Labyrinthitis (spread of infection through cochlear aqueduct) or CN VIII vasculitis | Permanent hearing loss is a major sequela of bacterial meningitis, particularly pneumococcal and meningococcal |
| Complication | Mechanism | Key Points |
|---|---|---|
| Permanent visual loss (15–20%) [10] | AAION: posterior ciliary artery occlusion → optic nerve head infarction | Once established, visual loss is irreversible; the fellow eye is at risk (up to 50% within days if untreated) — this is why steroids must be started immediately |
| Stroke | Basilar artery or vertebral artery thrombosis from granulomatous inflammation → posterior circulation infarct | Less common than visual loss but devastating |
| Aortic aneurysm / dissection [10] | Large vessel involvement — granulomatous inflammation weakens aortic wall → aneurysmal dilation or intimal disruption | Thoracic aortic aneurysm risk ↑17× in GCA; requires long-term surveillance imaging |
| Large artery stenosis / occlusion / ectasia [10] | Transmural inflammation → intimal hyperplasia → luminal narrowing in subclavian, axillary, carotid arteries | Presents as claudication of upper limbs, discrepant BP, absent pulses |
| Steroid-related complications (iatrogenic) | Long-term high-dose prednisolone → osteoporosis, diabetes, cataracts, infections, adrenal suppression, Cushingoid features, peptic ulcer | Steroid-sparing agents (tocilizumab) are used specifically to minimise this burden; bone protection (bisphosphonates + calcium/vitamin D) started with steroid initiation |
| Complication | Mechanism | Key Points |
|---|---|---|
| Severe permanent vision loss (25% at risk) [5] | Chronic papilloedema → progressive optic nerve damage — sustained ↑ICP → chronic ischaemia and axonal loss at the optic nerve head [16] | Visual prognosis: chronic papilloedema can cause permanent optic nerve damage! [16]; visual fields must be monitored regularly |
| VF constriction | Progressive loss of peripheral vision from chronic papilloedema → concentric VF loss | Often insidious — the patient may not notice until severe; formal perimetry (Humphrey VF) at every follow-up |
| CN6 palsy | False localizing sign from ↑ICP → CN6 stretched over petrous temporal bone | Horizontal diplopia; reversible with ICP reduction |
| Headache chronification | Persistent ↑ICP → chronic daily headache refractory to simple analgesics | May develop MOH as patients escalate medication; must address the underlying ICP |
| Complication | Mechanism | Key Points |
|---|---|---|
| Venous haemorrhagic infarction | Venous outflow obstruction → ↑venous pressure → capillary rupture → haemorrhagic transformation of venous infarct | Unlike arterial infarcts, venous infarcts often have a haemorrhagic component from the outset; seizures much more common in venous infarcts (up to 40%) than in arterial infarcts [36] |
| Seizures (up to 40%) [13][36] | Cortical irritation from venous congestion, oedema, and haemorrhage | Levetiracetam preferred (fewer drug interactions than phenytoin); prophylactic AEDs controversial |
| ↑ICP | Impaired CSF drainage (venous sinuses are the site of CSF reabsorption at arachnoid granulations) | Papilloedema, headache, visual loss; managed with acetazolamide ± serial LP |
| Chronic dural sinus stenosis | Residual thrombus → fibrosis → permanent narrowing of venous sinuses | Can lead to persistent ↑ICP mimicking IIH; may require venous sinus stenting |
| Complication | Mechanism | Key Points |
|---|---|---|
| ↑ICP → oedema, herniation | Mass effect + vasogenic oedema (BBB disruption by tumour) → Monro-Kellie exceeded | Dexamethasone IS effective here (unlike ICH) — it ↓vasogenic oedema by stabilising BBB; surgical decompression if refractory |
| Epilepsy | Affects 50–80% primary tumours and 10–20% secondary tumours [37]; always supratentorial | Focal seizures (simple, complex, with secondary generalisation); anticonvulsants necessary; levetiracetam preferred (fewer interactions with chemotherapy) |
| Focal neurological deficit | Neuronal destruction + pressure effect + oedema | Location-specific; may improve with steroids (oedema component) |
| Pituitary apoplexy (in pituitary adenoma) | Sudden haemorrhage into the adenoma → rapid expansion within the confined sella turcica [17] | Sudden excruciating headache + diplopia (CN III) + hypopituitarism (especially adrenal crisis → life-threatening if cortisol not replaced); needs steroid cover + urgent surgical decompression |
| Cranial irradiation complications [37] | Acute: reactive swelling → worsening of prior neurological symptoms (pre-treat with steroids); Chronic: radionecrosis (1–3 years post-RT), neurocognitive deficits, vasculopathy, hypopituitarism (up to 80%), secondary brain tumours | Radionecrosis mimics tumour recurrence on MRI → distinguish by lack of clearly defined T2W lesion and high oedema-to-enhancement ratio; treated symptomatically with steroids |
I. Stroke-Related Complications (Ischaemic and Haemorrhagic) [31][32]
These are relevant because stroke is a major secondary cause of headache.
- Seizures — cortical irritation by ischaemia or blood; prophylactic use of anticonvulsants is NOT recommended for ischaemic or haemorrhagic stroke [31][32]; treat only if clinical seizures occur
- Cerebral oedema → ↑ICP → herniation — peaks days 2–5 post-stroke; managed by head elevation, osmotherapy, decompressive craniectomy for malignant MCA syndrome or massive cerebellar infarct [14]
- Haemorrhagic transformation of ischaemic infarct — particularly after thrombolysis (5–7% symptomatic ICH with IV alteplase [31]); managed by stopping tPA + cryoprecipitate + antifibrinolytics (tranexamic acid or aminocaproic acid)
| Complication | Mechanism | Prevention/Management |
|---|---|---|
| Aspiration pneumonia | Dysphagia from brainstem/cortical stroke → aspiration of oral secretions/food | Speech therapist assessment before oral feeding; NGT if unsafe swallow |
| DVT / PE | Immobilization → venous stasis (Virchow's triad) | SC unfractionated/LMW heparin in immobilized patients (ischaemic); intermittent pneumatic compression starting day of admission (haemorrhagic) [31][32]; aspirin if anticoagulants contraindicated |
| UTI | Indwelling catheter → ascending infection; neurogenic bladder from cortical/brainstem lesions | Intermittent catheterisation preferred; avoid prolonged indwelling catheter; measure post-void residual [32] |
| Pressure sores | Immobility → sustained pressure on skin → tissue necrosis | Frequent turning, pressure-relieving mattresses, nutritional optimisation [32] |
| Post-stroke depression | Prevalence 29% [31]; multifactorial — neurochemical changes (disrupted monoamine pathways), psychological reaction to disability, social isolation | Structured depression screening recommended; treat with antidepressants in absence of contraindications [31]; SSRIs preferred (fewer anticholinergic side effects than TCAs) |
| Dehydration / malnutrition | ↓oral intake from dysphagia + ↓consciousness | Early NGT or PEG feeding if prolonged dysphagia expected |
| Contractures / frozen shoulder | Prolonged immobility → joint capsule shortening | Early physiotherapy and occupational therapy [32]; positioning of weak limbs |
Relevant because hydrocephalus is a complication of many headache-causing conditions (SAH, meningitis, tumour, IIH).
| Complication | Details | Mechanism |
|---|---|---|
| Shunt blockage (most common) | 80% proximal block, 10% valve, 10% distal block; causes: choroid plexus, brain parenchyma, protein, tumour cells [33] | Tissue debris obstructs the narrow lumen of the ventricular catheter |
| Shunt infection (most serious) | Pathogens: S. epidermidis, S. aureus; S/S: fever, lethargy, meningism, signs of raised ICP [33] | Biofilm formation on shunt catheter by skin commensals introduced at surgery |
| Overshunting | Postural headache (worsened with standing/sitting, relieved lying down); can lead to subdural haematoma (stretching of bridging veins) [33] | Excessive CSF drainage → intracranial hypotension → brain sags → bridging veins tear → SDH |
| Distal catheter complications | Inguinal hernia, perforated abdominal viscus/peritonitis, intraperitoneal CSF-filled pseudocyst, tumour seeding [33] | Peritoneal end of VP shunt can irritate or perforate bowel; CSF collection can form loculated pseudocysts |
High Yield Summary — Complications of Headache and Its Causes
Primary headache complications:
- Migraine: chronic migraine, status migrainosus, migrainous infarction, persistent aura without infarction, migraine-triggered seizure.
- MOH: the most common iatrogenic complication of headache treatment; limit acute analgesics to < 2 days/week.
- Cluster: suicide risk, chronic cluster, permanent Horner's syndrome.
SAH complications: re-bleeding (secure aneurysm within 24–72h), vasospasm/DCI (days 4–14; nimodipine × 21 days), hydrocephalus (EVD/VP shunt), seizures, hyponatraemia (SIADH vs CSW), cardiac stunning.
ICH complications: haematoma expansion, ↑ICP/herniation (mannitol; NOT steroids!), IVH → hydrocephalus, seizures.
Meningitis complications: hydrocephalus (especially TBM — 80%), CN palsies, cerebral infarction from arteritis, parenchymal damage, seizures, SIADH, hearing loss, visual loss.
GCA complications: permanent visual loss (15–20% — AAION), stroke, aortic aneurysm, steroid side effects.
IIH complications: permanent visual loss (25% at risk), VF constriction, CN6 palsy.
CVST complications: haemorrhagic venous infarction, seizures (up to 40%), persistent ↑ICP.
Shunt complications: blockage (MC), infection (most serious — S. epidermidis, S. aureus), overshunting → SDH.
Active Recall - Complications of Headache
[4] Senior notes: Ryan Ho Neurology.pdf (Section 2.2.2 Migraine complications, p. 62) [5] Senior notes: Ryan Ho Neurology.pdf (Section 4 IIH, p. 158) [6] Senior notes: Ryan Ho Neurology.pdf (Section 3.2 Cerebrovascular Diseases — SAH mortality, p. 74) [10] Senior notes: Ryan Ho Rheumatology.pdf (Section 3.6.1 GCA and PMR, p. 95) [11] Senior notes: felixlai.md (Sections IV–V: EDH and SDH clinical manifestation) [13] Senior notes: maxim.md (Section 5.2 SAH and CVST) [14] Senior notes: maxim.md (Intracerebral haemorrhage management) [15] Senior notes: Ryan Ho Neurology.pdf (MOH, p. 63) [16] Senior notes: Ryan Ho Opthalmology.pdf (Papilloedema and IIH, p. 90) [17] Senior notes: Ryan Ho Endocrine.pdf (Pituitary apoplexy, p. 107) [31] Senior notes: felixlai.md (Stroke complications pp. 1701–1710; SAH treatment and complications pp. 1707–1708; ICH complications p. 1704) [32] Senior notes: Ryan Ho Neurology.pdf (Stroke complications and prevention pp. 80–82) [33] Senior notes: maxim.md (CSF shunt complications, p. 769) [34] Senior notes: Ryan Ho Neurology.pdf (Meningitis complications p. 145) [35] Senior notes: Ryan Ho Respiratory.pdf (TB meningitis complications, p. 79) [36] Senior notes: Ryan Ho Neurology.pdf (CVST complications, p. 89) [37] Senior notes: Ryan Ho Neurology.pdf (Brain tumour complications and cranial irradiation, pp. 162–164)
High Yield Summary
Definition: Headache = pain/discomfort over head or face; most common pain experienced; brain parenchyma has no nociceptors — pain arises from vessels, dura, scalp, orbit, sinuses, ears.
Classification: Primary (~90%: TTH, migraine, cluster) vs Secondary (~10%: vascular, neoplastic, infective, CSF pressure disorders).
Pathophysiology:
- TTH: muscular — misinterpretation of epicranial muscle afferents as pain; a/w stress, anxiety, depression
- Migraine: cortical spreading depression → trigeminovascular activation → CGRP release → meningeal vasodilation + neurogenic inflammation
- Cluster: hypothalamic dysfunction → trigeminal-autonomic reflex → unilateral pain + autonomic features
- ↑ICP: Monro-Kellie doctrine; headache from traction on dura/vessels; worse AM and with Valsalva
- SAH: blood in subarachnoid space → meningeal nociceptor irritation → thunderclap headache
Key clinical discriminators:
- TTH: bilateral, band-like, no associated symptoms, can carry on activities
- Migraine: unilateral, throbbing, ± aura, photophobia/phonophobia/nausea, debilitating
- Cluster: unilateral periorbital, extreme severity, autonomic features, clockwork regularity, agitation
- SAH: sudden-onset worst-ever headache, meningism, LOC
- GCA: new temporal headache in > 50yo, jaw claudication, visual symptoms, tender temporal artery
- IIH: headache + TVOs + papilloedema in obese young woman
- Intracranial hypotension: orthostatic headache relieved by lying down
Red flags: SNOOP4. Any thunderclap headache = SAH until proven otherwise.
Murtagh's serious disorders not to be missed: SAH, ICH, dissection, GCA, CVST, tumour, meningitis, encephalitis, abscess, EDH/SDH, glaucoma, IIH.
High Yield Summary — Differential Diagnosis of Headache
- Always stratify by tempo: sudden (think vascular emergency) → acute → subacute → chronic.
- Murtagh's probability diagnosis: acute = URTI; chronic = TTH, combination headache, migraine, transformed migraine.
- Serious disorders not to be missed: SAH, ICH, dissection, GCA, CVST, tumour, meningitis, EDH/SDH, glaucoma, IIH.
- Primary headache differentiation: Migraine = POUND (Pounding, 4-72 hOurs, Unilateral, Nausea, Debilitating); TTH = bilateral band, no associated symptoms; Cluster = unilateral periorbital + autonomic features + clockwork periodicity + agitation.
- Thunderclap headache = SAH until proven otherwise (CT → LP if CT normal).
- New headache in > 55yo = likely organic (GCA, tumour, SDH).
- Don't forget masquerades: depression, drugs, anaemia, thyroid, diabetes (hypoglycaemia), phaeochromocytoma.
- Pitfalls: cervical spondylosis, dental disease, refractive error, pre-eruption herpes zoster, sleep apnoea, post-LP headache.
High Yield — Investigation Priorities for Headache
- Most headaches need NO investigations — primary headaches (TTH, migraine, cluster) are clinical diagnoses based on ICHD-3 criteria.
- Key investigations to consider: FBE, ESR/CRP, selective radiography (skull XR, sinus XR, CT scan or MRI scan) [9].
- Thunderclap headache: urgent NCCT → LP (if CT -ve, at ≥ 12h) → CTA/DSA.
- CT is king in acute setting: fast, detects blood and fractures. MRI is the problem-solver for subacute/chronic.
- Never LP without CT first if raised ICP suspected — risk of herniation.
- GCA: start steroids → then biopsy. Do not delay treatment for histology.
- IIH: MRI + MRV (to exclude CVST) → LP for opening pressure. Diagnosis of exclusion.
- EDH vs SDH on CT: Biconvex (lentiform), doesn't cross sutures = EDH; Crescent, crosses sutures = SDH.
High Yield Summary — Management of Headache
Primary headaches — three pillars: (1) Trigger avoidance, (2) Abortive treatment, (3) Prophylactic treatment.
TTH: Abortive = paracetamol/NSAIDs. Prophylactic = REASSURANCE (most important!) + amitriptyline + behavioural therapy.
Migraine: Mild → paracetamol/NSAIDs + antiemetic. Severe → triptans (5HT₁ agonist; C/I in IHD/stroke/CAD). Prophylaxis (if ≥ 2/month or disabling) → propranolol, amitriptyline, topiramate, or CGRP monoclonal antibodies.
Cluster: Acute → SC sumatriptan OR 100% O₂ 15L/min. Prophylaxis → verapamil (1st line, needs ECG monitoring), short-course steroids (bridge), lithium (severe).
MOH: Withdraw offending drug + bridge therapy (naproxen or short-course prednisolone) + start appropriate prophylaxis.
SAH: Secure aneurysm (coil or clip) + nimodipine 21 days + manage hydrocephalus.
ICH: BP control (IV labetalol, target SBP < 140) + reverse anticoagulation + EVD if hydrocephalus.
GCA: Urgent prednisolone 60mg (or IV methylprednisolone if visual loss) → slow taper over 1–2 years ± tocilizumab.
IIH: Weight loss + acetazolamide (1st line) ± surgery (ONSF, shunt) if progressive visual loss.
CVST: Anticoagulation (even if haemorrhagic infarct!) + ICP management.
Hypertensive emergency: ≤ 25% ↓BP in 1st hour → 160/110 over next 2–6h → normal over 24–48h.
High Yield Summary — Complications of Headache and Its Causes
Primary headache complications:
- Migraine: chronic migraine, status migrainosus, migrainous infarction, persistent aura without infarction, migraine-triggered seizure.
- MOH: the most common iatrogenic complication of headache treatment; limit acute analgesics to < 2 days/week.
- Cluster: suicide risk, chronic cluster, permanent Horner's syndrome.
SAH complications: re-bleeding (secure aneurysm within 24–72h), vasospasm/DCI (days 4–14; nimodipine × 21 days), hydrocephalus (EVD/VP shunt), seizures, hyponatraemia (SIADH vs CSW), cardiac stunning.
ICH complications: haematoma expansion, ↑ICP/herniation (mannitol; NOT steroids!), IVH → hydrocephalus, seizures.
Meningitis complications: hydrocephalus (especially TBM — 80%), CN palsies, cerebral infarction from arteritis, parenchymal damage, seizures, SIADH, hearing loss, visual loss.
GCA complications: permanent visual loss (15–20% — AAION), stroke, aortic aneurysm, steroid side effects.
IIH complications: permanent visual loss (25% at risk), VF constriction, CN6 palsy.
CVST complications: haemorrhagic venous infarction, seizures (up to 40%), persistent ↑ICP.
Shunt complications: blockage (MC), infection (most serious — S. epidermidis, S. aureus), overshunting → SDH.
Hand/wrist/elbow Pain
Hand, wrist, or elbow pain is a clinical presentation of discomfort in the upper extremity that may arise from musculoskeletal, neurological, or inflammatory conditions such as carpal tunnel syndrome, tendinopathy, arthritis, or epicondylitis.
Knee Pain
Knee pain is a common musculoskeletal complaint arising from injury, overuse, or degenerative, inflammatory, or infectious processes affecting the bones, cartilage, ligaments, tendons, or bursae of the knee joint.