Overview
Migraine
1. Clinical Overview
Summary
Migraine is a common, chronic, often disabling primary headache disorder characterised by recurrent episodes of moderate-to-severe unilateral throbbing headache, typically accompanied by nausea, vomiting, photophobia, and phonophobia. Attacks last 4-72 hours if untreated. Migraine affects approximately 15% of the global population, with a 3:1 female predominance after puberty. Migraine is classified as Migraine Without Aura (~70-75%) or Migraine With Aura (~25-30%), where the headache is preceded by reversible focal neurological symptoms (Visual, Sensory, Speech). The pathophysiology involves Cortical Spreading Depression (CSD), Trigeminovascular System Activation, and CGRP Release. Acute treatment includes Simple Analgesics (Paracetamol, NSAIDs) and Triptans. Prophylactic treatment is indicated for frequent attacks (≥4/month) and includes Propranolol, Amitriptyline, Topiramate, and Anti-CGRP Monoclonal Antibodies (Erenumab, Fremanezumab, Galcanezumab). Lifestyle factors and trigger avoidance are important adjuncts. [1,2,3]
Clinical Pearls
"POUND": Pulsating, One-day duration (4-72h), Unilateral, Nausea, Disabling. 4/5 = Migraine.
"Aura Before, Not During": Aura precedes headache (Usually 5-60 mins before). Typically visual (Zigzag lines, Scotoma).
"Triptans Work Best Early": Take at first sign of headache. Less effective once headache established.
"Red Flags = Exclude Secondary Causes": Thunderclap, New neuro signs, Fever, Age >50 first headache, Papilloedema → Urgent investigation.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Prevalence | ~15% of adults. ~6% of children. |
| Sex | Female:Male = 3:1 (After puberty). Equal in childhood. |
| Age of Onset | Typically puberty to early adulthood. Peaks 25-55 years. |
| Genetics | Family history common. Polygenic. Familial Hemiplegic Migraine (FHM) = Monogenic. |
Burden
- Leading cause of disability in under-50s (WHO).
- Significant impact on work, School, Relationships, Quality of life.
3. Classification (ICHD-3)
Migraine Types
| Type | Description |
|---|---|
| Migraine Without Aura | ~70-75%. Headache without preceding neurological symptoms. |
| Migraine With Aura | ~25-30%. Headache preceded by reversible focal neurological symptoms (Visual, Sensory, Language). |
| Chronic Migraine | Headache ≥15 days/month for ≥3 months, with ≥8 days having migraine features. |
| Episodic Migraine | less than 15 headache days/month. |
| Hemiplegic Migraine | Aura includes motor weakness. Familial (FHM) or Sporadic. |
| Migraine with Brainstem Aura | Aura symptoms from brainstem (Dysarthria, Vertigo, Tinnitus, Diplopia, Ataxia). |
| Retinal Migraine | Monocular visual symptoms (Rare). |
Diagnostic Criteria (Migraine Without Aura – ICHD-3)
| Criteria |
|---|
| A. ≥5 attacks fulfilling B-D |
| B. Headache lasting 4-72 hours (Untreated) |
| C. At least 2 of: Unilateral, Pulsating, Moderate-Severe, Aggravated by routine activity |
| D. At least 1 of: Nausea/Vomiting, Photophobia AND Phonophobia |
| E. Not better accounted for by another diagnosis |
Aura Characteristics
| Feature | Description |
|---|---|
| Visual (Most Common) | Positive (Zigzag lines, Scintillating scotoma, Fortification spectra). Negative (Scotoma, Hemianopia). Builds over 5-20 mins. |
| Sensory | Paraesthesia (Pins and needles). Numbness. Spreads slowly (Marches). Unilateral face/Arm. |
| Language | Dysphasia. Word-finding difficulty. |
| Motor (Hemiplegic) | Weakness. Rare. Familial or Sporadic. |
| Duration | Each symptom lasts 5-60 mins. Headache follows within 60 mins. |
4. Pathophysiology
Cortical Spreading Depression (CSD)
- Wave of neuronal depolarisation followed by suppression.
- Propagates across cortex at 2-3 mm/min.
- Accounts for Aura (Visual cortex = Visual symptoms).
- Activates trigeminovascular system.
Trigeminovascular System Activation
- CSD or other trigger activates trigeminal afferents innervating meningeal blood vessels.
- Afferents release CGRP (Calcitonin Gene-Related Peptide), Substance P, Neurokinin A.
- Neurogenic Inflammation: Vasodilation, Plasma protein extravasation, Mast cell degranulation.
- Pain signals transmitted via trigeminal nerve to Trigeminal Nucleus Caudalis (TNC) in brainstem.
- Ascending pathways to Thalamus and Cortex = Pain perception.
Key Neurotransmitters
| Molecule | Role |
|---|---|
| CGRP | Key mediator. Vasodilator. Sensitises trigeminal afferents. Target for anti-CGRP therapies. |
| Serotonin (5-HT) | Triptans are 5-HT1B/1D agonists. Cause vasoconstriction and inhibit neuropeptide release. |
| Glutamate | Involved in CSD. |
5. Clinical Presentation
Phases of a Migraine Attack
| Phase | Duration | Features |
|---|---|---|
| Prodrome | Hours to 1-2 days before | Mood changes, Fatigue, Food cravings, Neck stiffness, Yawning, Increased urination. |
| Aura (If present) | 5-60 mins | Visual (Zigzag lines, Scotoma), Sensory (Paraesthesia), Speech. Reversible. |
| Headache | 4-72 hours | Moderate-Severe, Throbbing, Unilateral (May become bilateral), Worsened by activity. Nausea/Vomiting. Photophobia/Phonophobia. Seek dark, Quiet room. |
| Postdrome | Hours to 1-2 days after | "Migraine hangover". Fatigue, Cognitive difficulties, Mood changes, Residual head discomfort. |
Associated Symptoms
| Symptom | Notes |
|---|---|
| Nausea / Vomiting | Very common. May need antiemetics. |
| Photophobia | Sensitivity to light. |
| Phonophobia | Sensitivity to sound. |
| Osmophobia | Sensitivity to smells (Less common). |
| Cutaneous Allodynia | Scalp tenderness. Pain from light touch. |
Red Flags (SNOOP) – Exclude Secondary Causes
| Red Flag | Concerning For |
|---|---|
| Systemic (Fever, Weight loss, Cancer, HIV) | Infection, Malignancy |
| Neurological signs/Symptoms | Tumour, Stroke, Venous thrombosis |
| Onset sudden (Thunderclap) | SAH, CVT, Dissection |
| Onset after 50 years | GCA, Tumour, Secondary causes |
| Pattern change (New, Different, Progressively worsening) | Space-occupying lesion |
| Papilloedema | Raised ICP |
| Positional | Low/High pressure headache |
| Precipitated by Valsalva | Chiari, Posterior fossa lesion |
| Pregnancy / Postpartum | CVT, Pre-eclampsia, Pituitary apoplexy |
6. Investigations
Clinical Diagnosis
- Migraine is a clinical diagnosis. No specific test confirms it.
- Investigations are to exclude secondary causes if Red Flags present.
When to Investigate
| Indication | Investigation |
|---|---|
| Red Flags (SNOOP) | MRI Brain (Preferred) or CT Head. Consider LP if SAH/Meningitis suspected. |
| Thunderclap Headache | CT Head (Urgent). LP if CT negative. CT/MR Angiography. |
| New Neuro Signs | MRI Brain. |
| First Headache >50 | MRI. ESR/CRP (GCA). |
| Atypical Features | MRI to exclude lesion. |
Typical Findings
- Normal Neuroimaging: Expected in primary migraine.
7. Management
Management Algorithm
MIGRAINE DIAGNOSED
(ICHD-3 Criteria, Red Flags Excluded)
↓
ASSESS FREQUENCY AND SEVERITY
┌────────────────┴────────────────┐
ACUTE TREATMENT CONSIDER PROPHYLAXIS
(All Patients) (If ≥4 attacks/month,
Attacks disabling,
Acute meds ineffective/
Overused)
↓
ACUTE TREATMENT
┌──────────────────────────────────────────────────────────┐
│ **STEP 1: Simple Analgesia (Mild-Moderate)** │
│ - Aspirin 900mg OR Ibuprofen 400-600mg OR Paracetamol │
│ 1g │
│ - Add Antiemetic (Metoclopramide 10mg, Prochlorperazine │
│ 10mg) if nausea │
│ - Take EARLY in attack │
│ │
│ **STEP 2: Triptans (Moderate-Severe, Or Step 1 Fails)** │
│ - Sumatriptan 50-100mg PO (Most evidence) │
│ - Rizatriptan 10mg, Zolmitriptan 2.5mg, Eletriptan 40mg │
│ - Sumatriptan 6mg SC (Fast, If vomiting) │
│ - Sumatriptan nasal spray │
│ - Take at onset of HEADACHE (Not aura) │
│ - Can repeat once after 2 hours if partial response │
│ - **Contraindicated in**: IHD, Stroke, Uncontrolled │
│ Hypertension, Hemiplegic/Brainstem aura │
│ │
│ **STEP 3: Combination / Second-Line** │
│ - Triptan + NSAID │
│ - Gepants (Rimegepant, Ubrogepant – CGRP antagonists) │
│ - Ditans (Lasmiditan – 5-HT1F agonist, No │
│ vasoconstriction) │
└──────────────────────────────────────────────────────────┘
↓
PROPHYLACTIC TREATMENT
┌──────────────────────────────────────────────────────────┐
│ **FIRST-LINE ORAL** │
│ - **Propranolol** 40-160mg/day (Beta-blocker) │
│ - **Amitriptyline** 10-50mg nocte (TCA) │
│ - **Topiramate** 50-100mg/day (Antiepileptic) │
│ *Teratogenic – Contraception essential* │
│ - **Candesartan** 8-16mg/day (ARB – Off-label) │
│ │
│ **SECOND-LINE / SPECIALIST** │
│ - **Sodium Valproate** (Teratogenic – Avoid in women of │
│ childbearing potential) │
│ - **Pizotifen** 0.5-1.5mg nocte (Weight gain) │
│ - **Botulinum Toxin A (Botox)** For Chronic Migraine │
│ (≥15 days/month). Specialist. │
│ - **Anti-CGRP Monoclonal Antibodies** │
│ - Erenumab (Aimovig) 70-140mg SC monthly │
│ - Fremanezumab (Ajovy) 225mg SC monthly or 675mg │
│ quarterly │
│ - Galcanezumab (Emgality) 240mg loading then 120mg │
│ monthly │
│ *NICE approved for Chronic Migraine failing ≥3 │
│ prophylactics* │
│ │
│ **TRIAL DURATION**: 2-3 months at adequate dose before │
│ concluding ineffective. │
│ **AIM**: Reduce frequency by ≥50%. │
└──────────────────────────────────────────────────────────┘
↓
LIFESTYLE / NON-PHARMACOLOGICAL
┌──────────────────────────────────────────────────────────┐
│ - **Trigger Avoidance**: Identify and avoid (Stress, │
│ Sleep disturbance, Dehydration, Alcohol, Certain │
│ foods – Variable) │
│ - **Regular Meals, Hydration, Sleep** │
│ - **Exercise**: Regular aerobic exercise may reduce │
│ frequency │
│ - **Headache Diary**: Track attacks, Triggers, Meds │
│ - **Relaxation / Mindfulness / CBT** │
│ - **Avoid Medication Overuse**: >10 days/month Triptans │
│ or >15 days/month Simple analgesics → MOH │
└──────────────────────────────────────────────────────────┘
Medication Overuse Headache (MOH)
| Notes |
|---|
| Chronic daily headache caused by regular overuse of acute headache medication. |
| Triptans ≥10 days/month. Simple analgesics ≥15 days/month. |
| Management: Gradual withdrawal of overused medication. Prophylaxis. |
8. Deep Dive: The CGRP Revolution
Calcitonin Gene-Related Peptide (CGRP) is the holy grail of migraine research.
- The Discovery: During a migraine, CGRP levels in the jugular vein are elevated. Injecting CGRP into a migraineur triggers an attack.
- Mechanism: CGRP is a potent neuropeptide released by the trigeminal nerve. It causes vasodilation and mast cell degranulation (Neurogenic Inflammation).
- The Drugs (The "Mabs" and "Gepants"):
- Monoclonal Antibodies (mAbs): Large molecules. Injectable (SC/IV). Long half-life (Monthly).
- Erenumab: Targets the Receptor.
- Fremanezumab / Galcanezumab: Target the Ligand (Molecule).
- Gepants (Small Molecules): Oral. Short acting.
- Rimegepant: Acute AND Preventive.
- Ubrogepant: Acute.
- Atogepant: Preventive.
- Monoclonal Antibodies (mAbs): Large molecules. Injectable (SC/IV). Long half-life (Monthly).
9. Surgical Atlas: Botox Protocol (PREEMPT)
OnabotulinumtoxinA for Chronic Migraine.
- Indication: ≥15 headache days/month, of which 8 are migraine, for >3 months. Failed 3 oral prophylactics.
- Mechanism: Inhibits release of CGRP and Substance P from nociceptive nerve terminals.
- The Protocol:
- 31 Injections (Total 155 Units).
- 7 Sites:
- Corrugator (Eyebrow): 2 sites.
- Procerus (Between brows): 1 site.
- Frontalis (Forehead): 4 sites.
- Temporalis (Temples): 8 sites (4 per side).
- Occipitalis (Back of head): 6 sites.
- Cervical Paraspinal (Neck): 4 sites.
- Trapezius (Shoulders): 6 sites.
- Frequency: Every 12 weeks.
10. Technical Appendix: ICHD-3 Criteria Details
Migraine with Aura (1.2)
- B. Aura: At least two attacks with aura consisting of visual, sensory, and/or speech/language symptoms, fully reversible, no motor/brainstem/retinal symptoms.
- C. Characteristics: At least 3 of 6:
- Spreads gradually over ≥5 minutes.
- Two or more symptoms occur in succession.
- Each symptom lasts 5-60 minutes.
- At least one symptom is unilateral.
- At least one symptom is positive (scintillations).
- The aura is accompanied, or followed within 60 minutes, by headache.
Status Migrainosus (1.4.1)
- A debilitating migraine attack lasting for more than 72 hours.
- Management: Admission. IV Fluids. IV Antiemetics (Chlorpromazine). IV Dihydroergotamine (DHE) or steroid taper.
11. Rehabilitation: Lifestyle & Triggers
"The Migraine Brain works best with boring routine."
1. The SEEDS of Success
- S - Sleep: Regular wake/sleep times. Avoid lying in at weekends ("Weekend Migraine").
- E - Exercise: Regular aerobic exercise (30 mins, 3x/week) releases endorphins (natural painkillers).
- E - Eat: Prevent hypoglycaemia. Do not skip meals. Regular snacks.
- D - Drink: Hydration is critical. 2-3 Litres water. Limit caffeine (rebound headache).
- S - Stress: Mindfulness, CBT, Relaxation techniques.
2. Common Triggers (The "Trigger Bucket")
Triggers accumulate. One might be fine (e.g. glass of wine), but three together (wine + stress + late night) overflow the bucket.
- Hormonal: Menstruation (Estrogen drop).
- Dietary: Cheese (Tyramine), Chocolate, Citrus, Alcohol (Red wine/Beer), MSG, Aspartame.
- Environmental: Bright lights, Strong smells (Perfume), Weather changes (Barometric pressure).
12. Deep Dive: Medication Overuse Headache (MOH)
The "Painkiller Trap".
- Definition: Headache occurring on ≥15 days/month in a patient with a pre-existing headache disorder, due to regular overuse of acute medication for >3 months.
- Culprits:
- Opioids/Codeine: Highest risk. AVOID in migraine.
- Triptans: Risk if >10 days/month.
- NSAIDs/Paracetamol: Risk if >15 days/month.
- Management:
- Stop Precipitants: Cold turkey vs taper.
- Bridge Therapy: Prednisolone course / Naproxen during withdrawal.
- Start Prophylaxis: Topiramate/Amitriptyline immediately.
- Warn: "It gets worse before it gets better" (Withdrawal headache lasts 1-2 weeks).
8. Complications
| Complication | Notes |
|---|---|
| Chronic Migraine | ≥15 headache days/month. Often associated with MOH. |
| Status Migrainosus | Migraine attack lasting >72 hours. May need hospital admission. IV fluids, Antiemetics, Steroids. |
| Migraine-Related Stroke | Rare. Ischaemic stroke during migraine with aura. |
| Medication Overuse Headache | From frequent acute medication use. |
| Persistent Aura Without Infarction | Aura lasting >1 week without stroke on imaging. |
| Impact on Quality of Life | Work, School, Relationships. |
9. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| Natural History | Chronic but often improves with age. Frequency may decrease post-menopause. |
| Response to Treatment | ~50-70% achieve ≥50% reduction in frequency with prophylaxis. |
| Triggers | Identification and avoidance helps. |
| Menstrual Migraine | May benefit from perimenstrual prophylaxis (Frovatriptan, NSAID). |
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Migraine | NICE CG150 | Acute: Triptan ± NSAID. Prophylaxis: Propranolol, Amitriptyline, Topiramate. Botox for Chronic. Anti-CGRP mAbs for refractory chronic. |
| Headaches | SIGN / BASH | Similar. Headache diary. Lifestyle. |
Key Evidence
- Anti-CGRP mAbs: RCTs show ~50% responder rate for chronic migraine.
- Botox (PREEMPT Trials): Effective for chronic migraine.
11. Patient and Layperson Explanation
What is Migraine?
Migraine is a type of severe headache that comes and goes in attacks. It's much more than just a headache – it often causes nausea, Vomiting, and sensitivity to light and noise.
What are the symptoms?
- Throbbing headache, Often on one side.
- Nausea or Vomiting.
- Sensitivity to Light and Sound.
- Some people get a Warning (Aura) before the headache – like flashing lights or zigzag lines in their vision.
- Attacks last 4-72 hours.
What causes it?
We don't fully understand why, But it involves overactive brain signals and changes in blood vessels and nerves. Triggers include Stress, Lack of sleep, Certain foods, Hormones, and Dehydration.
How is it treated?
- Painkillers: Ibuprofen, Aspirin, Paracetamol – taken early.
- Triptans: Specific migraine tablets that work well if taken at the start of the headache.
- Preventive tablets: If you get frequent migraines, Daily medication can reduce attacks.
- Lifestyle: Regular sleep, Hydration, Avoid triggers.
When should I seek help?
See a doctor if:
- Headaches are frequent or getting worse.
- Painkillers aren't working.
- You have sudden, Severe headache (Worst ever), Weakness, Confusion, Or fever with headache.
12. References
Primary Sources
- National Institute for Health and Care Excellence. Headaches in over 12s (CG150). 2012 (Updated 2021).
- Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (ICHD-3). Cephalalgia. 2018;38(1):1-211.
- Goadsby PJ, et al. Pathophysiology of Migraine. Neurol Clin. 2019;37(4):651-671. PMID: 31563224.
13. Examination Focus
Common Exam Questions
- ICHD Criteria: "What are the diagnostic criteria for Migraine Without Aura?"
- Answer: ≥5 attacks, Duration 4-72h, ≥2 of (Unilateral, Pulsating, Moderate-Severe, Aggravated by activity), ≥1 of (Nausea/Vomiting, Photo+Phonophobia).
- Aura: "What is the most common type of aura?"
- Answer: Visual Aura (Scotoma, Zigzag lines, Fortification spectra).
- Prophylaxis Indication: "When should migraine prophylaxis be considered?"
- Answer: ≥4 attacks per month, Attacks are disabling, Acute treatments ineffective or overused.
- CGRP Drugs: "What is the mechanism of Erenumab?"
- Answer: Monoclonal antibody that blocks the CGRP receptor, Preventing CGRP-mediated trigeminovascular activation.
Viva Points
- POUND Mnemonic: Pulsating, One-day (4-72h), Unilateral, Nausea, Disabling.
- Triptan Contraindications: IHD, Stroke, Uncontrolled HTN, Hemiplegic/Brainstem Aura.
- MOH: Overuse of acute meds leads to chronic daily headache. Withdrawal + Prophylaxis.
- SNOOP Red Flags: Exclude secondary causes before diagnosing primary headache.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.