Migraine is a neurological disorder that is typically defined as recurring attacks of moderate to severe headaches and accompanying symptoms (particularly neurological and sensory symptoms). Migraine may be a primary condition, or it may be caused by another health condition (secondary). Migraine headaches are usually one-sided (unilateral) but can affect both sides. Migraine affects approximately 15% of people at some stage during their lives and most commonly affects those aged between 30 and 40.

Types of Migraine

Depending on how often and how long migraine attacks occur, migraine is defined as either:

  • Episodic / intermittent – acute migraine attacks that occur 0 to 14 days per month; or,
  • Chronic – migraine attacks occurring on 15 or more days per month, for at least 3 months.

Further classification of migraine depends on whether sensory symptoms, known as aura, are experienced or not:

  • Migraine with aura – previously known as classical or complicated migraine;
  • Migraine without aura – the most common type of migraine.

Auras are discussed in the next section.

Migraine Phases & Symptoms

Migraine is more than just a headache. It is a series of changing symptoms, not just pain, that have different mechanisms and that occur in phases. The phases and their symptoms vary depending on the type of migraine and differ between individuals. The four possible phases of a migraine attack are known as prodrome, aura, migraine headache and postdrome.

Migraine Phases by JoanDragonfly (Flickr)

Prodrome

Most people with migraine will experience a pre-migraine attack phase, during which early symptoms / signs of a migraine occur before any headache. This phase can act as a warning. Prodrome symptoms may occur hours or even days before a migraine attack. Symptoms include:

  • Yawning / fatigue
  • Irritability
  • Changes in mood
  • Food cravings
  • Sensitivity to light
  • Nausea
  • Increased urination

Auras

Auras are disturbances to the senses that may occur before a migraine headache in people who experience “migraine with aura”. Some people experience auras even without headache – this is known as silent migraine.

The most common auras are visual, but also include auditory auras and other sensations, such as the following:

Visual Auditory Other
  • Blind spots (scotoma)
  • Flashing lights
  • Glittering lights
  • Zig-zag lines
  • Partial loss of vision
  • Kaleidoscope effect
  • Difficulty focusing
  • Distorted vision
  • Tunnel vision
  • Hearing voices
  • Hearing distortion
  • Hearing loss
  • Ringing or buzzing (tinnitus)
  • Confusion or difficulty concentrating
  • Sudden anxiety
  • Problems with speech / language
  • Numbness
  • Tingling / pins-and-needles
  • Muscle weakness
  • Sense of dissociation

Examples of visual auras:

Migraine Headache

Most migraine attacks involve a headache phase. The pain is usually moderate to severe, but can be mild or even absent (i.e. silent migraine). Over 50% of migraine headaches are one-sided. Common features of migraine headache and other accompanying symptoms include the following:

Headache Features Other Symptoms
  • Commonly one-sided (60%)
  • Throbbing (50%)
  • Worsened by physical activity or head movement (90%)
  • Accompanying neck pain (75%)
  • Sinus pain or pressure (40%)
  • Light sensitivity (photophobia, 94%)
  • Sound sensitivity (phonophobia, 91%)
  • Dizziness (72%)
  • Nausea (50%)
  • Vomiting (33%)
  • Vertigo

Postdrome

Many migraineurs will experience a “hangover” phase at the end of a migraine attack. How long it lasts for will vary from person to person. Typical symptoms include:

  • Fatigue
  • Dizziness
  • Trouble concentrating
  • Sensitivity to light

What Causes Migraine?

Image by JoanDragonfly [CC BY-SA 2.0 (https://www.flickr.com/photos/joandragonfly/26221134888)]

Triggers

Things that can bring on a migraine are known as triggers. Common triggers include:

  • Intense light, sounds and/or smells
  • Stress or anxiety
  • Poor diet or specific foods
  • Skipped meals
  • Dehydration
  • Caffeine
  • Alcohol
  • Poor sleep or change in sleep cycle
  • Hormonal changes (e.g. menstruation or menopause)

Health Conditions & Risk Factors

Migraine may be a primary condition, or it may be a secondary condition – meaning it is caused by another medical condition. Chronic migraine is considered a primary condition, however certain conditions can increase the risk. Conditions that may be associated with migraine or are risk factors include:

  • Stroke, heart disease or vascular (blood vessel) disorders
  • Head trauma / injury
  • Obesity or metabolic syndrome
  • Depression
  • Neuralgia (nerve pain disorder)

Biological Mechanisms

Many migraine triggers or medical conditions associated with migraine cause imbalances in the body’s normal biology (e.g. change in hormone levels, sleep disturbances, change in diet). These imbalances cause specific areas of the brain to be activated. These areas of the brain may be responsible for controlling biological processes or pathways that have been linked to prodrome symptoms or migraine headache, for example: pain processing and signalling, changes in brain blood flow, processing of light, sound and smell signals.

Genetics have also been heavily implicated in migraine, with most migraines (especially migraine with aura) appearing to run in families.

Migraine auras specifically are said to be caused by “cortical spreading depression”. This is a pathophysiological (disease-related) event in the brain that may be described as a slowly moving wave of altered brain cell activity. This is also associated with changes in brain blood flow (known as cortical spreading ischemia) which is likely related to migraine headache.

Subtypes of Migraine

Migraines naturally vary considerably between individuals, particularly in terms of symptoms experienced. There are, however, certain sets of symptoms and factors that can indicate a specific migraine subtype / diagnosis, such as the following:

  • Hemiplegic migraine – a rare form of migraine involving temporary weakness, or even paralysis, of one side of the body;
  • Silent migraine – migraine with auras, but no headache;
  • Migraine with brainstem aura (basilar migraine) – a rare form of migraine involving symptoms such as imbalance, fainting, vision impairment, difficulty speaking, etc;
  • Vestibular migraine – migraine dominated by dizziness, vertigo and/or imbalance, often without headache;
  • Menstrual migraine – migraine attacks linked to a woman’s menstrual cycle;
  • Retinal migraine (ophthalmic migraine) – eye-related migraine dominated by visual disturbances, such as temporary loss of vision, and often occurring in one eye only.

Current Treatment Options

Medications

Prevention (Prophylaxis)

Preventative treatments (prophylactic agents) are recommended for people who experience at least 2 migraines per month. They rarely completely stop migraines, but they should reduce how often they occur, how long they last and how severe they are. There are many prophylactic agents for migraine, they include:

  • Anticonvulsants (anti-seizure drugs) – e.g. topiramate, sodium valproate;
  • Beta-blockers (anti-hypertensives) – e.g. propranolol, metoprolol, timolol;
  • Antidepressants – e.g. amitriptyline, venlafaxine;
  • Others – e.g. botulinum toxin type A (for chronic migraine).

Acute Treatment

Medications for acute treatment of migraine are best when taken early when the pain is mild. It is important to find the most effective medication, or combination of medications, and the right dose, as overuse or ineffective treatments can worsen migraine and increase the risk of chronic migraine. Contraindications also need to be considered (e.g. triptans may not be safe in patients with vascular risk factors). Acute treatments include:

  • Simple analgesics – e.g. aspirin, paracetamol, ibuprofen, naproxen, diclofenac;
  • Triptans – e.g. sumatriptan, almotriptan, elitriptan, frovatriptan, zolmitriptan.

Neuromodulation

There is a small amount of evidence that some forms of neuromodulation / neurostimulation may help migraine when other treatments fail. More studies are needed. Neuromodulation therapies include:

  • Occipital nerve stimulation (ONS) – a surgically implanted device that stimulates the nerves at the back of the head;
  • Transcutaneous vagal nerve stimulation (tVNS) – a noninvasive handheld device that stimulates the vagus nerve at the side of the neck;
  • Transcranial magnetic stimulation (TMS) – a noninvasive device that is held against the back of the head. It generates a magnetic field that is thought to suppress migraine related brain activity and help prevent migraine.

New & Emerging Treatments

Recent developments in migraine treatment or prevention have focused on a specific biological target. Calcitonin gene-related peptide (CGRP) is a neurotransmitter that is released during a migraine. Several drugs targeting CGRP or its receptor protein have recently been approved or are close to receiving approval. These include monoclonal antibodies (mABs – laboratory-made proteins that bind specifically to CGRP or its receptor) for migraine prevention; and a CGRP receptor antagonist (receptor blocker) for acute migraine treatment:

Drug Type Route of Administration Status
Erenumab CGRP receptor mAB Injection Approved
Fremanezumab CGRP mAB Injection Approved
Galcanezumab CGRP mAB Injection Approved
Eptinezumab CGRP mAB Intravenous infusion Early clinical trials
Ubrogepant CGRP receptor antagonist Oral Completed clinical trials

Clinical Trials:


References & Resources:

Websites:

  1. Headache Australia: https://headacheaustralia.org.au/
  2. Pain Australia: https://www.painaustralia.org.au
  3. The Migraine Trust: https://www.migrainetrust.org/
  4. “Managing Migraine”. NPS MedicineWise 2017 (accessed 16/10/2018): https://www.nps.org.au/medical-info/consumer-info/managing-migraine
  5. “Migraine” [fact sheet]. International Association for the Study of Pain 2011; available via: http://www.iasp-pain.org/Advocacy/Content.aspx?ItemNumber=1093
  6. “Migraine”. myVMC 2003; last updated 24 May 2018 (accessed on 16/10/2018): https://www.myvmc.com/diseases/migraine/
  7. “Migraine – ICHD-3 The International Classification of Headache Disorders 3rd edition”. International Headache Society 2018 (accessed 05/11/2018): https://www.ichd-3.org/1-migraine
  8. “The Timeline of a Migraine Attack”. American Migraine Foundation 2018 (accessed 5/11/2018): https://americanmigrainefoundation.org/understanding-migraine/timeline-migraine-attack/

Journal Articles:

  1. Bohm PE, et al. “Migraine Headache: Updates and Future Developments”. Mayo Clinic Proceedings 2018; 93(11): 1648-1653. https://www.mayoclinicproceedings.org/article/S0025-6196(18)30710-9/fulltext (Free)
  2. Charles A. “The pathophysiology of migraine: implications for clinical management”. Lancet Neurology 2018; 17(2): 174-182. https://www.ncbi.nlm.nih.gov/pubmed/29229375
  3. Diener HC, et al. “Chronic migraine—classification, characteristics and treatment”. Nature Review. Neurology 2012; 8(3): 162-171. https://www.ncbi.nlm.nih.gov/pubmed/22331030
  4. Dodick DW. “Migraine”. Lancet 2018; 391: 1315-1330. https://www.ncbi.nlm.nih.gov/pubmed/29523342
  5. May A & Schulte LH. “Chronic migraine: risk factors, mechanisms and treatment”. Nature Reviews. Neurology 2016; 12(8): 455-464. https://www.ncbi.nlm.nih.gov/pubmed/27389092
  6. Puledda F, et al. “An update on migraine: current understanding and future directions”. Journal of Neurology 2017; 264(9): 2031-2039. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587613/ (Free)
  7. Silberstein SD. “Current management: migraine headache”. CNS spectrums 2017; 22(S1): 1-13. https://www.ncbi.nlm.nih.gov/pubmed/29350125
  8. Stark RJ & Stark CD. “Migraine prophylaxis”. The Medical Journal of Australia 2008; 189(5): 283-288. https://www.mja.com.au/journal/2008/189/5/migraine-prophylaxis (Free)
  9. Weatherall MW. “The diagnosis and treatment of chronic migraine”. Therapeutic Advances in Chronic Disease 2015; 6(3): 115-123. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416971/ (Free)
  10. Yalın OÖ, et al. “Phenotypic features of chronic migraine”. The Journal of Headache and Pain 2016; 17: 26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791410/ (Free)

Images:

  1. Phases of migraine image by JoanDragonfly [CC BY-SA 2.0 (https://www.flickr.com/photos/joandragonfly/39384099324)].
  2. Migraine triggers image by JoanDragonfly [CC BY-SA 2.0 (https://www.flickr.com/photos/joandragonfly/26221134888)].