Migraine


Migraine is a neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, light sensitivity and sound sensitivity. Other symptoms may include vomiting, unusual pain, dizziness, and cognitive dysfunction. Some people with migraine experience aura, a period of sensory disturbance at the onset of a migraine attack.
Although primarily considered to be a headache disorder, migraine can be highly varied and is known to present differently from person to person, in both symptoms and severity. Disease burden can range from episodic discrete attacks to chronic disease. Incidence of migraines may increase over time, evolving from episodic migraine to chronic migraine. Overuse of acute pain medications may hasten this process and is a risk factor for developing medication overuse headache.
Migraine is believed to be caused by a combination of genetic, environmental, and neurological factors that influence the behavior of nerve cells, chemical signals and blood vessels within the brain. Migraine attacks are theorized to occur when the brain exceeds an individual sensitivity threshold. Attacks are more likely to occur if stable conditions within the brain are disrupted by changes in hormones, sleep, or stress.
The initial phase of a migraine attack starts 48 hours before the main headache phase, with increasing activity in the hypothalamus and the appearance of early symptoms.
The subsequent pain phase of a migraine attack may be linked to loss of control between the hypothalamus and the limbic system, and increased activity in the pain pathway from the trigeminal nerve to the brainstem. Release of the neuropeptide CGRP increases blood flow and the transmission of pain signals.
Migraineurs display heightened neural sensitivity to stimuli such as light, sound or smell and to pain perception.
Mechanisms that normally enable people to habituate to repeated stimuli may be disrupted in migraineurs.
A migraine management plan often includes lifestyle modifications to cope with migraine triggers and reduce the impact of co-occurring conditions. Non-pharmacological preventive therapies include stress management, improving sleep habits, eating regularly, and some types of exercise. Initial recommended treatment for acute mild to moderate attacks is with over-the-counter medications such as ibuprofen and paracetamol for pain. Triptans are recommended as a first-line therapy for moderate to severe attacks. The approval of CGRP inhibitors is seen as a major advance in migraine treatment. According to the American Headache Society, CGRP therapies are a first-line option for migraine prevention. Anti-nausea medications are used as a second-line treatment for migraine-related nausea. Ergotamines may be used by those experiencing headaches that do not respond to over-the-counter pain medications. Evidence indicates that topiramate reduces the number of monthly migraine days compared with placebo, but its use is associated with higher rates of treatment discontinuation due to adverse effects such as paresthesia and cognitive symptoms. Opioids should not be prescribed, because higher doses of opioids are linked to medication overuse headache and increased risk of progression from episodic to chronic migraines.
Commonly prescribed preventive medications include beta blockers, anticonvulsants, antidepressants, calcium channel blockers, and CGRP inhibitors. Medications inhibit migraine through various mechanisms, such as blocking calcium and sodium channels, activation of the neurotransmitter serotonin, and blocking of CGRP transmission in the network of neurons and blood vessels in the brain's protective layers.
According to the Global Burden of Disease 2021 database approximately 14% of people worldwide are affected by migraine, making it the third most disabling condition affecting the nervous system and one of the most common causes of disability. Beginning at puberty, women experience higher rates than men of incidence, severity of symptoms, and disability related to migraines, in particular to migraine without aura. Occurrence of migraine without aura displays an age-related pattern, beginning around menarche, increasing through the childbearing years, peaking during perimenopause when estrogen levels tend to fluctuate, and tending to decrease following menopause when estrogen levels tend to stabilize. From age 30 to 50, up to 4 times as many women experience migraine attacks as men. Estrogen levels may impact migraine mechanisms of action through blood flow, neurotransmitters, and ion transport across cell membranes.

Signs and symptoms

Migraine typically presents as recurrent, mostly unilateral, pulsating headaches, along with heightened reactivity to light, sound, and other sensory stimuli. The severity of the pain, duration of the headache, and frequency of attacks are variable. Symptoms may last for hours or days, seriously affecting quality of life.
About 30% of people living with migraine experience episodes with aura. Women are more likely than men to experience migraine without aura. Mechanisms in migraine patients with and without aura differ, and it is recommended that these subtypes of migraine be treated separately.
Migraine attacks can be described in terms of four stages or phases, which may not all be experienced. In addition, the period between migraine attacks is sometimes referred to as the interictal phase.
  • The premonitory phase or prodrome, generally defined as the 48 hours preceding the pain phase.
  • Aura, reversible neurological disturbances lasting 5–60 min, generally near onset of the pain phase. These are reported by about 30% of migraineurs.
  • The pain phase, also known as the headache phase.
  • The postdrome, effects following the end of the pain phase of an attack.
A migraine attack lasting longer than 72 hours despite treatment is referred to as status migrainosus. This can lead to complications like dehydration and electrolyte imbalances, and may require emergency room or hospital-level care.
Migraine is associated with neuropsychiatric disorders including major depression, bipolar disorder, anxiety disorders, obsessive–compulsive disorder, and sleep disorders. Shared neurobiological mechanisms may underly multiple conditions. Co-occurrence with specific psychiatric disorders differs for those experiencing migraine with and without aura.

Prodrome phase

The prodrome phase of migraine is generally defined as the 48 hours preceding the pain or aura phases of an attack.
Estimates of the occurrence of premonitory or prodromal symptoms in people with migraine vary widely. Results of a systematic review and metanalysis of studies suggests that around 29% of people with migraine in population-based studies report at least one premonitory symptom, while around 66% of people in clinic populations report premonitory symptoms.
These symptoms may include a wide variety of phenomena, including altered mood, irritability, depression or euphoria, fatigue, craving for certain food, difficulty speaking or reading, yawning, stiff muscles, constipation or diarrhea, and sensitivity to smells or noise. Premonitory symptoms may occur with both migraine without aura and migraine with aura. Neuroimaging indicates that changes in activity in the limbic system and hypothalamus are associated with prodromal symptoms in migraine.

Aura phase

is a transient neurological event that can occur over 5–60 minutes, generally just prior to the onset of headache pain. Symptoms can be visual, sensory or motoric in nature, but visual effects occur most frequently, in as many as 99% of cases of migraine with aura. In rare cases known as persistent aura, aura symptoms may remain after 60 minutes.
Visual disturbances often consist of a scintillating scotoma. These typically start near the center of vision and then spread out to the sides with zigzagging lines, which have been described as looking like fortifications or walls of a castle. Usually, the lines are in black and white, but some people also see colored lines. Some people lose part of their field of vision known as hemianopsia while others experience blurring.
Sensory auras are the second most common type; they occur in 30–40% of people with auras. Often, a feeling of pins-and-needles begins on one side in the hand and arm and spreads to the nose–mouth area on the same side. Numbness usually occurs after the tingling has passed with a loss of position sense. Other symptoms of the aura phase can include speech or language disturbances, world spinning, and, less commonly, motor problems. Motor symptoms indicate that this is a hemiplegic migraine, and weakness often lasts longer than one hour unlike other auras.

Pain phase

Classically the headache is unilateral, throbbing, and moderate to severe in intensity.
The feeling of pulsating pain is not in phase with the pulse. In around 40% of cases, the pain may be bilateral, affecting both sides of the head. The pain usually lasts 4 to 72 hours in adults. Pediatric and adolescent migraines differ from adult presentations, more often involving bilateral headaches with shorter duration.
Pain is frequently accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, sensitivity to smells, fatigue, and irritability. Many prefer a dark and quiet environment, and seek to avoid stimuli to which they are sensitive. Nausea occurs in almost 90% of people, and vomiting occurs in about one-third. Other symptoms may include blurred vision, sino-nasal symptoms such as nasal stuffiness, diarrhea, neck pain, and swelling or tenderness of the scalp. In rare cases of migraine with brainstem aura, neurological symptoms related to the brain stem may affect both sides of the body, including a sense of the world spinning, light-headedness, and confusion.
During the pain phase, motion and physical activity may increase pain. Migraineurs are likely to decrease physical activity during this time. However, the effects of physical activity on migraine are complex, and regular exercise on an on-going basis may have a preventive effect and decrease frequency of migraine attacks.