Migraine · Grey Matter

Migraine is a common brain disorder of recurring attacks of headache, usually throbbing and one-sided and made worse by light, sound and movement, that last from hours to a few days; in about a third of people who have it, some attacks begin with an aura.

Migraine. Migraine is a common brain disorder of recurring attacks of headache, usually throbbing and one-sided and made worse by light, sound and movement, that last from hours to a few days; in about a third of people who have it, some attacks begin with an aura.

The aura is a reversible neurological symptom that builds over minutes and lasts up to about an hour, most often visual: a flickering zigzag or bright arc that drifts slowly across the visual field and leaves a blind patch behind it. Its slow, steady march across the visual map of the cortex is the main evidence that it is produced by cortical spreading depression in the occipital lobe. Tingling that spreads over a hand and the face, or trouble finding words, are less common forms of the same process in other cortical areas.

The headache comes from a different system. The meninges and their large blood vessels are innervated by sensory fibres of the trigeminal nerve, mostly from its first (ophthalmic, V1) division; when these trigeminovascular fibres are activated they release peptides such as CGRP, the coverings become sensitised, and pain signals pass through the brainstem and the thalamus to the cortex. How an attack starts is still studied: changes in the hypothalamus and brainstem hours before the pain, and spreading depression activating the trigeminal fibres in animal models, are the two most discussed threads.

Most attacks have no aura. The trigeminovascular pathway is common to both forms, so the headache does not depend on spreading depression; drugs that block CGRP or its receptor treat attacks with and without aura.

An attack can have phases: warning signs hours before, aura, headache and a recovery phase, and not every attack shows all of them.

Between attacks, studies often find a brain that habituates less to repeated stimuli. Whether that reflects a cortex that is more excitable, and how it connects to the start of an attack, is an open question.

Questions: How can a wave in the cortex lead to a headache, if the brain itself feels no pain? The pain comes from the meninges and their blood vessels, which are innervated by sensory fibres of the trigeminal nerve, mostly its ophthalmic (V1) division. In animal models, the potassium, glutamate and other substances released by spreading depression reach these trigeminovascular fibres and activate them; the fibres release peptides such as CGRP, the meninges become sensitised, and the signal passes through the brainstem and thalamus to the cortex as throbbing pain. Spreading depression is therefore a plausible trigger for attacks with aura. Most attacks have no aura, however, and they share the same trigeminovascular pain pathway, so how those attacks begin is still studied. What counts as a migraine aura, and how long does it last? A migraine aura is a fully reversible neurological symptom (visual, sensory, speech or, rarely, motor) that develops gradually and is followed by or comes with the headache. By the international classification, at least one symptom spreads gradually over five minutes or more, each symptom lasts five to sixty minutes, at least one is on one side, and several may follow one another. More than 90 % of auras are visual, typically a flickering zigzag or bright arc that expands and leaves a blind patch, and an aura can also occur without any headache after it. Why does blocking CGRP prevent migraine attacks? CGRP is the main peptide released by activated trigeminal pain fibres in the meninges, where it widens blood vessels and sensitises the tissue and the nerve pathway that carries the pain. Its levels rise during attacks, and giving it to people with migraine provokes migraine-like headaches, which identified it as a cause along the pain pathway. Antibodies that bind CGRP or its receptor (the first, erenumab, was approved in the United States in 2018) and small-molecule receptor blockers interrupt that step, reducing attacks with and without aura, because the trigeminovascular pathway is common to both.