Aetiology

Good-quality evidence supports the view that the brain in people who experience migraine is hyperexcitable to a variety of stimuli. Results from neurophysiological studies are, however, ambiguous. It may be more appropriate to view migraine as a disorder of excitability that is characterised by deficient regulation of the cortical excitatory–inhibitory balance.[13][14]

Migraine has a strong genetic component. Genes associated with migraine increase or alter neuronal excitability through a variety of mechanisms.[15][16]

Pathophysiology

Migraine is a neurovascular disorder, in which neurological events precede and initiate headache.

The headache of migraine results from neurogenic inflammation of first-division trigeminal sensory neurons that innervate the large vessels and meninges of the brain. This causes a change in the way that pain is processed by the brain.[17] Increased neuronal activity can be demonstrated in areas of the brainstem during migraine, and this persists even when the headache is relieved by triptans. It is not known whether this brainstem activation reflects the cause of migraine (the so-called brainstem generator) or signifies activation of endogenous pain-control systems.[18]

When activated, the trigeminal neurons release substances that cause dilation of meningeal blood vessels, leakage of plasma proteins into surrounding tissue, and platelet activation. Peptides including calcitonin gene-related peptide, substance P, and bradykinin are released, resulting in sensitisation of peripheral nociceptors. This peripheral sensitisation results in increased nociceptive inputs into the trigeminal sensory nucleus, and ultimately in central sensitisation, so that non-painful stimuli (for example, light touch) are interpreted as pain.[19][20][21]​ Calcitonin gene-related peptide has a key role in pain transmission and in migraine.[22][23][24]

Aura is caused by neuronal dysfunction.[25] A wave of neuronal excitation spreads anteriorly in the cortex, at a rate of 3-5 mm/minute (which correlates temporally with the reported rate of change in visual symptoms). This is followed by a prolonged period of decreased neuronal activity, and finally neuronal recovery. Cortical depression causes release of excitatory amino acids and other mediators of excitation, resulting in activation of nociceptors in adjacent dura and blood vessels, leading in turn to activation of the trigeminal sensory nucleus.[21] 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.[26]

Classification

International classification of headache disorders, 3rd edition (ICHD-3)[3]

  • 1.1 Migraine without aura: recurrent headache disorder manifesting in attacks lasting 4 to 72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea and/or photophobia and phonophobia.

  • 1.2 Migraine with aura: recurrent attacks, lasting minutes, of unilateral fully reversible visual, sensory, or other central nervous system symptoms that usually develop gradually and are usually followed by headache and associated migraine symptoms

    • 1.2.1 Migraine with typical aura: migraine with aura, in which aura consists of visual and/or sensory and/or speech/language symptoms, but no motor weakness, and is characterised by gradual development, duration of each symptom no longer than 1 hour, a mix of positive and negative features, and complete reversibility

      • 1.2.1.1 Typical aura with headache

      • 1.2.1.2 Typical aura without headache

    • 1.2.2 Migraine with brainstem aura: migraine with aura symptoms clearly originating from the brainstem, but no motor weakness

    • 1.2.3 Hemiplegic migraine: migraine with aura including motor weakness

      • 1.2.3.1 Familial hemiplegic migraine (FHM)

        • 1.2.3.1.1 Familial hemiplegic migraine type 1 (FHM1)

        • 1.2.3.1.2 Familial hemiplegic migraine type 2 (FHM2)

        • 1.2.3.1.3 Familial hemiplegic migraine type 3 (FHM3)

        • 1.2.3.1.4 Familial hemiplegic migraine, other loci

      • 1.2.3.2 Sporadic hemiplegic migraine (SHM)

    • 1.2.4 Retinal migraine: repeated attacks of monocular visual disturbance, including scintillations, scotomata, or blindness, associated with migraine headache.

  • 1.3 Chronic migraine: headache occurring on 15 or more days/month for more than 3 months, which, on at least 8 days/month, has the features of migraine headache.

  • 1.4 Complications of migraine

    • 1.4.1 Status migrainosus: a debilitating migraine attack lasting for more than 72 hours

    • 1.4.2 Persistent aura without infarction: aura symptoms persisting for 1 week or more without evidence of infarction on neuroimaging

    • 1.4.3 Migrainous infarction: one or more migraine aura symptoms occurring in association with an ischaemic brain lesion in the appropriate territory demonstrated by neuroimaging, with onset during the course of a typical migraine with aura attack

    • 1.4.4 Migraine aura-triggered seizure: a seizure triggered by an attack of migraine with aura.

  • 1.5 Probable migraine: migraine-like attacks missing one of the features required to fulfil all criteria for a type or subtype of migraine coded above, and not fulfilling criteria for another headache disorder

    • 1.5.1 Probable migraine without aura

    • 1.5.2 Probable migraine with aura.

  • 1.6 Episodic syndromes that may be associated with migraine

    • 1.6.1 Recurrent gastrointestinal disturbance

      • 1.6.1.1 Cyclical vomiting syndrome

      • 1.6.1.2 Abdominal migraine

    • 1.6.2 Benign paroxysmal vertigo

    • 1.6.3 Benign paroxysmal torticollis.

Use of this content is subject to our disclaimer