Tell me Differential diagnosis for Headache

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Differential Diagnosis of Headache

Headache is one of the most common clinical complaints. Causes are broadly divided into primary (no underlying structural cause) and secondary (caused by another condition).

I. PRIMARY HEADACHES

These are diagnoses of intrinsic headache disorders — no underlying disease causing them.

Type	Key Features	Duration	Associated Symptoms
Migraine	Unilateral or bilateral; throbbing; moderate–severe; worsens with activity; family history common; more frequent in women	Hours to days	Photophobia, phonophobia, nausea/vomiting; may have aura (visual, sensory, motor)
Tension-type headache	Bilateral band-like pressure; mild–moderate; improves with activity; most common headache type (75% of people experience it)	Hours to days	No nausea/vomiting; minimal light or sound sensitivity (not both)
Cluster headache	Severe, unilateral; steady boring pain behind one eye; 4× more common in men; episodic clusters over weeks then remission for months	30–90 minutes	Ipsilateral: tearing, eye redness, ptosis, miosis, nasal congestion, flushing
Paroxysmal hemicrania	Unilateral facial pain; more frequent in women	Minutes	Ipsilateral autonomic features; responds to indomethacin
Hemicrania continua	Continuous unilateral headache with episodic stabbing pains; more in women	Continuous	Ipsilateral autonomic features; responds to indomethacin
SUNCT (Short-lasting Unilateral Neuralgiform headache with Conjunctival injection and Tearing)	Unilateral orbital/eye pain; more common in men	Seconds to 240 seconds	Conjunctival injection, tearing

II. SECONDARY HEADACHES

A. Increased Intracranial Pressure (ICP)

Trauma (post-traumatic headache)
Intracranial hemorrhage — subarachnoid (classically "thunderclap," worst headache of life), subdural, epidural
Intracranial tumor / neoplasm — worse in morning, worsened by Valsalva
Hydrocephalus
Idiopathic intracranial hypertension (pseudotumor cerebri) — obese young women; papilledema; pulsatile tinnitus
Brain abscess / epidural abscess
Cerebral edema
Arachnoid cyst

B. Decreased ICP

Post–lumbar puncture headache
VP shunt placement
CSF leak (spontaneous or post-procedural) — positional (worse upright, better supine)

C. Cerebrovascular

Cerebral infarct (ischemic stroke)
Carotid or vertebral artery dissection — neck pain + Horner's syndrome; young patients
Venous sinus thrombosis — progressive headache; may have papilledema or seizures
Reversible cerebral vasoconstriction syndrome (RCVS) — recurrent thunderclap headaches
Vasculitis (including giant cell arteritis — temporal tenderness, jaw claudication, ESR elevation in elderly)
Hypertension — severe hypertension (hypertensive urgency/emergency)
Arteriovenous malformation (AVM)

D. Infectious / Inflammatory

Meningitis (bacterial, viral, fungal, TB) — fever, neck stiffness, photophobia, Kernig's/Brudzinski's signs
Encephalitis
Sinusitis — frontal/facial pressure; worse on bending forward
Systemic infection (influenza, COVID-19, etc.)

E. Referred / Structural

Eyes: glaucoma (acute angle-closure — periorbital pain, red eye, halos), refractive errors, uveitis
Ears: otitis media, mastoiditis
Teeth/jaw: dental abscess, temporomandibular joint (TMJ) dysfunction
Cervical spine: cervicogenic headache — occipital/neck origin, referred to head
Scalp: referred pain from scalp lesions

F. Post-ictal Headache

Follows a seizure; usually resolves within hours

G. Toxic / Metabolic

Medication or drug exposure: stimulants, steroids, drugs of abuse, nitrates, sildenafil, CCBs
Carbon monoxide poisoning — diffuse headache, cherry-red skin, CO exposure history
Caffeine withdrawal — temporal or diffuse; resolves with caffeine

H. Analgesic/Medication Overuse

Medication overuse headache (analgesic rebound) — chronic daily headache from frequent use of abortive analgesics (>10–15 days/month)

I. Sleep & Respiratory

Sleep deprivation
Obstructive sleep apnea — morning headaches, daytime somnolence

J. Psychiatric

Depression, anxiety, conversion disorder, malingering, acute stress, mood disorders

III. Special Consideration: Acute vs. Recurrent/Chronic

Red Flag Headaches ("SNOOP" mnemonic) — Warrant urgent workup:

Flag	Concern
Systemic symptoms (fever, weight loss)	Infection, malignancy
Neurologic deficits	Mass lesion, stroke, abscess
Onset sudden/thunderclap	Subarachnoid hemorrhage, RCVS
Older age (>50, new headache)	Giant cell arteritis, tumor
Progressive / postural / papilledema	Raised ICP
Preceding trauma	Epidural/subdural hematoma

IV. Distinguishing Primary Headache Types at a Glance

Location:
  Unilateral + autonomic features → Cluster / TAC
  Bilateral band-like             → Tension-type
  Unilateral throbbing + nausea   → Migraine
  Unilateral + responds to Indo   → Paroxysmal hemicrania / Hemicrania continua

Onset:
  Thunderclap (peak <60 sec)      → SAH until proven otherwise

Timing:
  Minutes (30–90)                 → Cluster headache
  Hours to days                   → Migraine, Tension
  Continuous                      → Hemicrania continua, Medication overuse

Sources:

The Harriet Lane Handbook (23rd ed.), Boxes 20.7–20.8
Goldman-Cecil Medicine (International Ed.), Table 367-3
Neuroanatomy through Clinical Cases (3rd ed.), Table 5.2

Management of primary headache

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Management of Primary Headache

Primary headaches covered: Migraine, Tension-type, Cluster headache, and Trigeminal Autonomic Cephalgias (TACs).

1. MIGRAINE

A. Non-Pharmacologic Management

Identify and avoid triggers: alcohol, caffeine/caffeine withdrawal, oral contraceptives, hormonal changes, strong scents, nitrate-containing foods, aged cheese, chocolate, fasting, stress, weather changes
Regular sleep schedule and exercise
Stress management and relaxation techniques
Rest in a dark, quiet room during mild attacks
Physical therapy

B. Acute (Abortive) Treatment

Therapy is stratified by attack severity:

Mild–Moderate Attacks

Drug	Dose	Notes
NSAIDs — Ibuprofen	400–800 mg	First-line for mild attacks
NSAIDs — Naproxen	500–550 mg	Also used for menstrual migraine
Aspirin + Metoclopramide	Aspirin 900 mg + metoclopramide 10 mg	Effective combination
Acetaminophen + Isometheptene + Dichloralphenazone (Midrin)	2 caps at onset, then 1/hr PRN; max 5/12hr	Dizziness, liver toxicity
Ketorolac (IV/IM)	15–30 mg IM/IV q6h	Parenteral option

Moderate–Severe Attacks (Migraine-Specific Therapy)

Triptans (5-HT₁B/D agonists) — First-line migraine-specific agents:

Triptan	Route	Dose	Max/day
Sumatriptan	SC, nasal, oral	6 mg SC; 5–20 mg nasal	12 mg SC; 40 mg oral
Zolmitriptan	Oral, nasal, ODT	2.5–5 mg	10 mg
Rizatriptan	Oral, ODT	5–10 mg	30 mg
Naratriptan	Oral	1–2.5 mg	5 mg
Eletriptan	Oral	20–40 mg	80 mg
Almotriptan	Oral	2.5 mg	7.5 mg
Frovatriptan	Oral	2.5 mg	7.5 mg

⚠️ Contraindications for triptans: Coronary artery disease, uncontrolled hypertension, hemiplegic migraine, stroke history, basilar migraine, pregnancy (relative)

Ditans (5-HT₁F agonists) — e.g., Lasmiditan — cardiovascular-safe alternative to triptans

CGRP antagonists (gepants) — e.g., Ubrogepant, Rimegepant — newer acute agents, no vasoconstriction

Ergot derivatives:

Drug	Route	Dose	Notes
Ergotamine + Caffeine (Cafergot)	Oral	2 tabs at onset; max 6/attack, 10/week	Nausea, vasoconstriction, avoid in pregnancy
Dihydroergotamine (DHE-45)	IV/IM/SC	1 mg q1h; max 2 mg IV, 3 mg IM/SC	Useful for status migrainosus
Dihydroergotamine (Migranal)	Nasal	0.5 mg/spray each nostril	Repeat in 15 min

Antiemetics (adjuncts):

Prochlorperazine, Metoclopramide, Promethazine — treat nausea AND have direct anti-migraine properties
Domperidone — useful for nausea

IV rescue therapy (ED / status migrainosus):

IV prochlorperazine or metoclopramide + diphenhydramine
IV valproate sodium
IV DHE
Dexamethasone (prevents recurrence)

C. Preventive (Prophylactic) Treatment

Indicated when:

≥4 attacks/month
Attacks lasting >12 hours and causing significant disability
Poor response or contraindications to abortive therapy
Specific subtypes: hemiplegic migraine, migraine with prolonged aura

Drug Class	Agents	Dose	Side Effects	Special Indications
β-Blockers	Propranolol, Nadolol, Timolol	Propranolol 20–80 mg/day (titrate up)	Lethargy, depression	Migraine + hypertension; avoid in asthma
Ca²⁺ Channel Blockers	Verapamil, Amlodipine	Verapamil 120–480 mg/day	Hypotension	Migraine + hypertension
Anticonvulsants	Topiramate, Valproate, Lamotrigine	Topiramate 25–100 mg/day	Weight loss/gain, cognitive effects	Also for epilepsy comorbidity
TCAs	Amitriptyline, Nortriptyline, Imipramine	Low dose (10–75 mg QHS)	Sedation, anticholinergic	Migraine + depression/poor sleep, tension-type
NSAIDs	Naproxen, Ibuprofen	Naproxen 200–600 mg/day	GI upset	Menstrual migraine
CGRP monoclonal antibodies	Erenumab, Fremanezumab, Galcanezumab, Eptinezumab	Monthly or quarterly injection	Well-tolerated	Chronic migraine, medication overuse

2. TENSION-TYPE HEADACHE

Acute Treatment

Drug	Notes
NSAIDs (ibuprofen 400 mg, naproxen 500 mg, aspirin 500–1000 mg)	First-line
Acetaminophen (500–1000 mg)	Alternative first-line
Combination analgesics (aspirin + caffeine + acetaminophen)	More effective than monotherapy

⚠️ Avoid opioids and frequent analgesic use → risk of medication overuse headache (>10–15 days/month)

Preventive Treatment

Drug	Notes
Amitriptyline 10–75 mg QHS	First-line prophylaxis for chronic tension-type headache
Mirtazapine, Venlafaxine	Second-line
NSAIDs (long-term)	Use with GI protection

Non-Pharmacologic

Muscle relaxation techniques (biofeedback, progressive muscle relaxation)
Cognitive-behavioral therapy (especially if depression-associated)
Physical therapy, massage, acupuncture
Stress reduction; regular sleep

3. CLUSTER HEADACHE

Acute (Abortive) Treatment

Drug	Dose	Notes
100% Oxygen (inhaled)	7–12 L/min via non-rebreather mask for 15 min	Most effective; fast-acting, no side effects
Sumatriptan SC	6 mg SC	Fastest-onset triptan; most effective
Sumatriptan nasal spray	20 mg	Alternative to SC
Zolmitriptan nasal spray	5–10 mg	Alternative
DHE (IM/SC/nasal)	1 mg	Effective parenteral option
Lidocaine nasal drops	1 mL of 10% solution	Ipsilateral nostril; second-line

Preventive Treatment

Drug	Dose	Notes
Verapamil	240–960 mg/day	Drug of choice for cluster prevention
Lithium	300 mg TID	Especially for chronic cluster
Corticosteroids (prednisone)	60–80 mg/day tapered	Transitional therapy to bridge until verapamil takes effect
Ergotamine (at bedtime)	1–2 mg	When attacks are nocturnal and predictable
Topiramate, Valproate	Variable	Second-line
Melatonin	10 mg at night	Adjunct

Interventional (Refractory)

Occipital nerve block
Sphenopalatine ganglion stimulation
Deep brain stimulation (posterior hypothalamus) — highly specialized

4. TRIGEMINAL AUTONOMIC CEPHALGIAS (TACs)

Paroxysmal Hemicrania & Hemicrania Continua

Indomethacin 25–50 mg TID — pathognomonic response; complete response confirms diagnosis
Indomethacin + gastroprotection (PPI) due to GI side effects

SUNCT/SUNA

Lamotrigine — first-line
Carbamazepine, gabapentin — alternatives
Lidocaine IV for acute attacks

Summary Table: First-Line Treatments at a Glance

Headache Type	Acute Treatment	Prophylaxis
Migraine (mild)	NSAIDs, acetaminophen	β-blockers, topiramate, CGRP mAbs
Migraine (moderate–severe)	Triptans, gepants, ditans	Amitriptyline, valproate
Tension-type	NSAIDs, acetaminophen	Amitriptyline
Cluster	100% O₂, sumatriptan SC	Verapamil
Paroxysmal hemicrania	Indomethacin	Indomethacin
Hemicrania continua	Indomethacin	Indomethacin

Sources:

Textbook of Family Medicine (9th ed.), Chapter 41
Goldman-Cecil Medicine (International Ed.), Tables 367-3 & 367-4
Neuroanatomy through Clinical Cases (3rd ed.), Chapter 5

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