Migraine

Migraine is a primary chronic, headache disorder, that has a strong genetic component and often presents in early-to-mid life. It is characterised by recurrent episodes of unilateral, localised pain that is often associated with nausea and vomiting, photophobia and phonophobia.

They are the second most common type of headache, after tension-type headache. It is a lot more common in females than in males. The first attack often happens in early life (as early as 7 years old). Peak incidence is between 30-39 years old.

Pathophysiology

We still don't fully know why and what happens in a migraine. We do know that it is more likely to happen in individuals with a positive family history/ genetic predispositions. About 70% of individuals have a family history of migraine.

Let’s look at some of the factors involved:

1. Genetics

Seeing as individuals with a family history are more likely to experience migraines, there seems to be a clear genetic component to the disease aetiology.

2. Neuronal hyperexcitability

When migraines occur, there seems to be abnormalities in the activity of the brain especially in migraines with aura. There is a wave of sustained depolarisation followed by a period of neuronal inhibition. This is known as cortical spreading depression (CSD) and is responsible for the aura symptoms perceived.

3. Vascular changes

There was previously the theory that migraines were the result of vasodilation within the brain. This was known as the vascular theory of migraine and has subsequently been discredited. It now seems as though the vascular changes seen in migraine are due to neuronal mechanisms. The changes in blood flow and vasodilation do seem to have a role in the headache phase of migraines.

4. Neurotransmitters

Neurtotransmitters suc has serotonin, dopamine, calcitonin gene-related peptide (CGRP) are all involved in migraine pathophysiology. Serotonin levels drop during an attack and this may contribute to the vascular changes seen within the cranial blood vessels. It may also be involved with sensitisation of the afferent fibres in the meninges which leads to pain sensitisation.

5. Trigeminovascular system activation

The trigeminovascular system is a neural pathway primarily involving the trigeminal nerve (CNV)and associated blood vessels that plays a pivotal role in pain perception, particularly related to migraines and headaches. Activation of this system can lead to the release of inflammatory mediators, sensitizing nerve fibres and contributing to the sensation of pain.

6. Neuroinflammation

Evidence shows that inflammation of the brain and the perivascular regions are involved in migraines.

7. Sensory processing abnormalities - individuals suffering from migraines experience altered perception and sensitivity to light, sound and smells during an attack.

Migraine is considered a neurovascular disorder, meaning that it is neurological events that precede and initiate the headache.

Pathophysiology of migraine headache:

CSD causes release of excitatory mediators & amino acids, resulting in activation of nociceptors in the adjacent dura and blood vessels, leading in turn to activation of the trigeminal sensory nucleus. How these neurons are triggered in migraine without aura is unknown, but one hypothesis is that cortical spreading depression in migraine without aura occurs in 'silent' areas of the brain that do not produce recognisable symptoms of aura.

When activated, the trigeminal neurons release neuropeptides including calcitonin gene-related peptide (CGRP), substance P, and bradykinin. They cause dilation of meningeal blood vessels, leakage of plasma proteins into surrounding tissue, platelet activation, and sensitisation of peripheral nociceptors. This peripheral sensitisation results in increased nociceptive inputs into the trigeminal ganglion, and ultimately in central sensitisation by relaying the pain signal into the trigeminocervical complex (TCC). This results in non-painful stimuli being interpreted as painful.

Note that whilst the vasodilation of meningeal vessels was prevously thought to be a primary cause of migraine, it is now known to be an epiphenomenon (a by-product of migraine).

Pathophysiology of aura:

Aura is a neurological phenomenon that occurs due to neuronal dysfunction. It is characterized by a wave of neuronal excitation that spreads throughout the cortex, followed by a period of decreased neuronal activity and eventual neuronal recovery - this is CSD. During CSD, there is a wave of sustained depolarization in the brain, which is followed by a period of neuronal inhibition. This wave of excitation and subsequent depression is responsible for the aura symptoms experienced by individuals with migraines. It is important to note that aura is a distinct phase that occurs before the onset of a migraine headache.

Potential triggers of migraine include:

😷 Presentation

We will discuss the symptoms that are present throughout the 4 stages of migraine. It is also important to note that all 4 stages do not necessarily happen in all patients.

1. Prodromal/premonitory phase - this is a phase of vague symptoms that can occur as early as 24 hours before the migraine attack, such as:
• Excessive yawning
• Difficulties with reading or writing
• Sudden hunger or lack of appetite
• Mood changes
2. Aura - this phase consists of focal neurological symptoms that develop gradually, that usually persist up to one hour. The most common type of aura is visual, but can also have other sensory or language disturbance symptoms. It is only experienced by 25% of migraineurs.

Typical aura:

• ⭐️ Visual disturbances - such as scintillating scotoma, central scotoma blurred vision, flashing lights, fortification spectra, distorted colour perception
• Sensory deficits - such as paraesthesia (pins and needles), numbness, altered sensations.
• Aphasia
• Absence of motor symptoms

Atypical aura:

• Motor symptoms - such as paresis (and this includes cranial nerve palsies).
• Dizziness
• Aura >1 hour



3. Migraine headache/attack - this typically happens within 1 hour of resolution of aura symptoms.
• Localisation:
• Typically unilateral (possibly switching sides), but bilateral headache is possible.
• Especially frontal, frontotemporal, retro-orbital.
• Duration: usually 4–24 hours (rarely over 72 hours). Resolution phase is marked by deep sleep.
• Course: progression of pulsating, throbbing, or pounding pain.
• Exacerbated by physical activity
• Accompanying symptoms include photophobia, phonophobia, nausea, vomiting.
4. Postdromal/migraine hangover - lasts up to 24 hours after the spontaneous resolution of the pain, patients may experience:
• Malaise
• Fatigue
• Anorexia/food cravings

🔍 Investigations

⭐️ Migraine is a clinical diagnosis, based on the history and physical examination. We do need to rule out secondary headaches (to infection, haemorrhage, tumours, etc) by looking for red flags.

• Neuroimaging is not needed for patients with headaches consistent with migraine who have a normal neurological examination, with no atypical features or red flags present.

🧰 Management