Hell on earth

Migraine is among the most disabling medical disorders. Every day, 3,000 migraine attacks occur for each million of general population. About fifteen percent of the global population will suffer migraine at some point in their lives. Prime migraine age ranges from twenty to fifty years.

Migraine is the most expensive brain disease for society. (© Brenda Carson - Fotolia.com)

Migraine is the most expensive brain disease for society. (© Brenda Carson – Fotolia.com)

According to the World Health Organisation, migraine is the most expensive brain disease for society due to the major and unpredictable absenteeism it causes. It is also one of the least understood human afflictions. Not much research funds are destined to the investigation of migraine causes and cures. That may be because migraine generally is not a life-threatening disease. Recently, it has been shown though, migraine does contribute to certain brain changes. Migraine sufferers have a substantial bigger risk of suffering a stroke.

Migraine has been around for many centuries already. An early description of the disorder found in Egypt goes back as long as 1500 BC. According to The Oxford Companion to the Mind, migraine is a transient disorder of brain function, which is commonly associated with headache. In fact, migraine has such a clinical heterogeneity that it would be better to talk about migraines.

Artist impression of zig-zag visual disturbance as part of a migraine aura. (© Tehom - Wikipedia)

Artist impression of zig-zag visual disturbance as part of a migraine aura. (© Tehom – Wikipedia)

The headache is severe and pulsating in character. It is accompanied by unilateral pain, nausea or vomiting, sensibility to light, sound, or smell. Recovery follows within hours or can take days.

About one third of migraine sufferers go through an aura, a transient visual, sensory, language, or motor disturbance, which signals the headache will occur soon. In two thirds of the cases, there’s a family history of the condition.

Since three times more women than men suffer from migraine, it was thought to be a disorder of hysterical women. That’s why it took a long time for researchers to take migraine seriously, start investigating its causes and develop therapies for its treatment.

Neurological
For many years, it was thought vascular problems caused migraine. Changes in cerebral blood flow had been registered during migraine attacks. Problems with inappropriately contracting and expanding blood vessels appeared to be the basis of the disorder. New research has made it perfectly clear migraine is a pure neurological syndrome in which the brain is involved primarily and vessel dilatation is an epiphenomenon at most.

Inappropriately contracting and expanding blood vessels were thought to be the basis of migraine. (© Naeblys - Fotolia.com)

Inappropriately contracting and expanding blood vessels in the brain were thought to be the basis of migraine. (© Naeblys – Fotolia.com)

New research methods, like the imaging technique Positron Emission Tomography (PET), made it possible to investigate more thoroughly what goes on in the brain during migraine attacks. This resulted in several plausible neural theories, but there’s no consensus yet about the exact origin and nature of this brain disorder.

One of the theories focuses on the perception of pain. This perception is created by the brain. It is an individual experience and can be different from one moment to the other due to internal or external circumstances. Sensory receptors throughout the body, called nociceptors, when activated, send signals to the brain. This nociceptive stimulus is what makes the brain create the perception of pain.

The brain itself and the skull don’t contain nociceptors and thus are not sensitive to pain. Several areas of the head, like some arteries and veins, and the meninges, do have nociceptors and can sense pain, which is all too clear in headache. Neurons that produce serotonin, one of the chemical messengers in the brain, are part of the pain perception process. During a migraine attack serotonin levels in the brain decrease. Some scientists argue these low serotonin levels in the brain may lead to the process of constriction and dilatation of blood vessels and trigger migraine.

Depression
The best explanation for the migraine process so far is cortical spreading depression (CSD). This brain event was discovered in 1941 by the Brazilian scientist Aristides Leăo, but is only recently linked to migraine. Cortical spreading depression begins with a brief burst of neuronal activity. When a group of neurons become active in unison, they trigger a wave of unusual, intense neuronal activity spreading through an area of the cortex. This hyper excitable phase is followed by a wave of widespread depolarisation, the cortical spreading depression. The neurons are temporarily inhibited and go quiet.

Animation of cortical spreading depression. (© Patrick J. Lynch - Wikipedia)

Animation of cortical spreading depression. (© Patrick J. Lynch – Wikipedia)

The electrical surge of the passing CSD wave causes neurons to release chemically active irritants in the brain. They accumulate at the surface in the meninges where nociceptors are activated and send pain signals to the brain.

CSD frequently begins in the visual cortex or the somatosensory cortex, hence the visual aura or tactile tingling that can be part of a migraine attack. A migraine without aura is probably caused by CSD in areas of the cortex whose activation does not produce any outward symptoms before the onset of the headache.

Functional imaging studies in patients with migraine have demonstrated the occurrence of CSD. Evidence for its relevance to migraine comes from the fact that medications used for migraine prevention have been found to inhibit CSD. The ultimate trigger of CSD is still unknown. It may be a genetic mutation.

Several genes involved in migraine have already been identified, showing that migraine is a complex polygenetic disorder. Migraine sufferers may have a reduced trigger threshold, defined by genetic factors. This means their brain is more excitable and can be over-excited by normal stimuli.

Possible triggers are stress, caffeine withdrawal, certain pharmaceuticals, metabolic changes caused by lack of food or sleep, and hormonal swings. This last factor explains why the number of women in their fertile years suffering from migraine is far larger than the number of men, whereas these numbers are fairly equal before puberty and after menopause.

Evolution
Migraine has a high prevalence across cultures and ethnicities. An interesting question is why the disorder has prevailed during evolution. This may have to do with the excitability of the brain of migraine sufferers. Normally, all brains are equipped with a process called habituation. When we hear a tone or smell an odour for a continuing amount of time, our brain gets used to the sound or the smell and the neurons involved won’t be activated anymore.

The Head Ache, painting by George Cruikshank (1819).

The Head Ache, cartoon by George Cruikshank (1819).

Research has shown, this habituation process isn’t functioning well in people with migraine. They have a continued heightened sensitivity. In the early days of mankind, such a characteristic would have been very useful for instance in persons keeping watch for predators. During a migraine attack, the habituation process normalises, which could mean the brain takes respite from the heightened sensitivity.

Although this excitable brain with heightened sensitivity might sound like a positive thing, it is absolutely no compensation whatsoever for the millions of people all over the world fearing the moment of the next attack. This fear is even greater when you have exhausted all the available medication and nothing works anymore. The only thing you can do is go to bed in a dark room and wait for hours or for days for the crucifying pain to subside.

Image

Lightning strikes © Jürgen Fälchle – Fotolia.com

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