Migraine

Migraine (Template:IPA-cen, Template:IPA-cen)<ref>Template:Cite LPD</ref><ref>Template:Cite EPD</ref> is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity.<ref name="Pescador_Ruschel_2024">Template:Cite book</ref><ref name="Cephalalgia_2018">Template:Cite journal</ref> Other characterizing symptoms may include vomiting, cognitive dysfunction, allodynia, and dizziness.<ref name="Pescador_Ruschel_2024" /> Exacerbation or worsening of headache symptoms during physical activity is another distinguishing feature.<ref>Template:Cite journal</ref>

Up to one-third of people with migraine experience aura, a premonitory period of sensory disturbance widely accepted to be caused by cortical spreading depression at the onset of a migraine attack.<ref name="Cephalalgia_2018" /> Although primarily considered to be a headache disorder, migraine is highly heterogenous in its clinical presentation and is better thought of as a spectrum disease rather than a distinct clinical entity.<ref name="Katsarava_2012">Template:Cite journal</ref> Disease burden can range from episodic discrete attacks to chronic disease.<ref name="Katsarava_2012" /><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Migraine is believed to be caused by a mixture of environmental and genetic factors that influence the excitation and inhibition of nerve cells in the brain.<ref name=Lulli2007>Template:Cite journal</ref> The accepted hypothesis suggests that multiple primary neuronal impairments lead to a series of intracranial and extracranial changes, triggering a physiological cascade that leads to migraine symptomatology.<ref>Template:Cite journal</ref>

Initial recommended treatment for acute attacks is with over-the-counter analgesics (pain medication) such as ibuprofen and paracetamol (acetaminophen) for headache, antiemetics (anti-nausea medication) for nausea, and the avoidance of migraine triggers.<ref name=Gilmore2011>Template:Cite journal</ref> Specific medications such as triptans, ergotamines, or calcitonin gene-related peptide receptor antagonist (CGRP) inhibitors may be used in those experiencing headaches that do not respond to the over-the-counter pain medications.<ref>Template:Cite journal</ref> For people who experience four or more attacks per month, or could otherwise benefit from prevention, prophylactic medication is recommended.<ref>Template:Cite journal</ref> Commonly prescribed prophylactic medications include beta blockers like propranolol, anticonvulsants like sodium valproate, antidepressants like amitriptyline, and other off-label classes of medications.<ref name="NBK507873">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Preventive medications inhibit migraine pathophysiology through various mechanisms, such as blocking calcium and sodium channels, blocking gap junctions, and inhibiting matrix metalloproteinases, among other mechanisms.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Non-pharmacological preventive therapies include nutritional supplementation, dietary interventions, sleep improvement, and aerobic exercise.<ref>Template:Cite journal</ref> In 2018, the first medication (Erenumab) of a new class of drugs specifically designed for migraine prevention called calcitonin gene-related peptide receptor antagonists (CGRPs) was approved by the FDA.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> As of July 2023, the FDA has approved eight drugs that act on the CGRP system for use in the treatment of migraine.<ref>Template:Cite book</ref>

Globally, approximately 15% of people are affected by migraine.<ref name=LancetEpi2012>Template:Cite journal</ref> In the Global Burden of Disease Study, conducted in 2010, migraine ranked as the third-most prevalent disorder in the world.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It most often starts at puberty and is worst during middle age.<ref name=WHO2012>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Template:As of, it is one of the most common causes of disability.<ref>Template:Cite journal</ref>

Signs and symptoms

Migraine typically presents with self-limited, recurrent severe headache associated with autonomic symptoms.<ref name="Bart10">Template:Cite journal</ref><ref name="Prognosis2008">Template:Cite journal</ref> About 15–30% of people living with migraine experience episodes with aura,<ref name=Gilmore2011/><ref>Template:Cite book</ref> and they also frequently experience episodes without aura.<ref name = "Olesen_2006" /> The severity of the pain, duration of the headache, and frequency of attacks are variable.<ref name=Bart10/> A migraine attack lasting longer than 72 hours is termed status migrainosus.<ref>Template:Cite book</ref> There are four possible phases to a migraine attack, although not all the phases are necessarily experienced:<ref name="ICHD2004">Template:Cite journal</ref>

• The prodrome, which occurs hours or days before the headache
• The aura, which immediately precedes the headache
• The pain phase, also known as headache phase
• The postdrome, the effects experienced following the end of a migraine attack

Migraine is associated with major depression, bipolar disorder, anxiety disorders, and obsessive–compulsive disorder. These psychiatric disorders are approximately 2–5 times more common in people without aura, and 3–10 times more common in people with aura.<ref name=Baskin06>Template:Cite journal</ref>

Prodrome phase

Prodromal or premonitory symptoms occur in about 60% of those with migraine,<ref name="Amin2009">Template:Cite book</ref><ref name=Five2004>Template:Cite book</ref> with an onset that can range from two hours to two days before the start of pain or the aura.<ref name=Buzzi2005>Template:Cite journal</ref> These symptoms may include a wide variety of phenomena,<ref>Template:Cite journal</ref> including altered mood, irritability, depression or euphoria, fatigue, craving for certain food(s), stiff muscles (especially in the neck), constipation or diarrhea, and sensitivity to smells or noise.<ref name=Five2004/> This may occur in those with either migraine with aura or migraine without aura.<ref name=Sam2009>Template:Cite book</ref> Neuroimaging indicates the limbic system and hypothalamus as the origin of prodromal symptoms in migraine.<ref>Template:Cite journal</ref>

Aura phase

Enhancements reminiscent of a zigzag fort structure	Negative scotoma, loss of awareness of local structures
Positive scotoma, local perception of additional structures	Mostly one-sided loss of perception

Aura is a transient focal neurological phenomenon that occurs before or during the headache.<ref name=Amin2009/> Aura appears gradually over a number of minutes (usually 5–60) and generally lasts less than 60 minutes.<ref name=Tint2010/><ref name="Ashina">Template:Cite journal</ref> Symptoms can be visual, sensory or motoric in nature, and many people experience more than one.<ref name = "Cutrer_2006" /> Visual effects occur most frequently: they occur in up to 99% of cases and in more than 50% of cases are not accompanied by sensory or motor effects.<ref name = "Cutrer_2006" /> If any symptom remains after 60 minutes, the state is known as persistent aura.<ref>Template:Cite journal</ref>

Visual disturbances often consist of a scintillating scotoma (an area of partial alteration in the field of vision which flickers and may interfere with a person's ability to read or drive).<ref name=Amin2009/> 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.<ref name = "Cutrer_2006" /> Usually the lines are in black and white but some people also see colored lines.<ref name = "Cutrer_2006" /> Some people lose part of their field of vision known as hemianopsia while others experience blurring.<ref name = "Cutrer_2006" />

Sensory aura are the second most common type; they occur in 30–40% of people with auras.<ref name = "Cutrer_2006" /> 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.<ref name = "Cutrer_2006" /> Numbness usually occurs after the tingling has passed with a loss of position sense.<ref name = "Cutrer_2006" /> Other symptoms of the aura phase can include speech or language disturbances, world spinning, and less commonly motor problems.<ref name = "Cutrer_2006" /> Motor symptoms indicate that this is a hemiplegic migraine, and weakness often lasts longer than one hour unlike other auras.<ref name = "Cutrer_2006" /> Auditory hallucinations or delusions have also been described.<ref>Template:Cite book</ref>

Pain phase

Classically the headache is unilateral, throbbing, and moderate to severe in intensity.<ref name=Tint2010>Template:Cite book</ref> It usually comes on gradually<ref name=Tint2010/> and is aggravated by physical activity during a migraine attack.<ref name=ICHD2004/> However, the effects of physical activity on migraine are complex, and some researchers have concluded that, while exercise can trigger migraine attacks, regular exercise may have a prophylactic effect and decrease frequency of attacks.<ref name="The association between migraine an">Template:Cite journal</ref> The feeling of pulsating pain is not in phase with the pulse.<ref name="pathos">Template:Cite journal</ref> In more than 40% of cases, however, the pain may be bilateral (both sides of the head), and neck pain is commonly associated with it.<ref>Template:Cite book</ref> Bilateral pain is particularly common in those who have migraine without aura.<ref name=Amin2009/> Less commonly pain may occur primarily in the back or top of the head.<ref name=Amin2009/> The pain usually lasts 4 to 72 hours in adults;<ref name=Tint2010/> however, in young children frequently lasts less than 1 hour.<ref name=Bigal2010>Template:Cite journal</ref> The frequency of attacks is variable, from a few in a lifetime to several a week, with the average being about one a month.<ref name = "Rasmussen_2006">Template:Cite book</ref><ref>Template:Cite book</ref>

The pain is frequently accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, sensitivity to smells, fatigue, and irritability.<ref name=Amin2009/> Many thus seek a dark and quiet room.<ref name=Walton2009/> In a basilar migraine, a migraine with neurological symptoms related to the brain stem or with neurological symptoms on both sides of the body,<ref name=Basil2009>Template:Cite journal</ref> common effects include a sense of the world spinning, light-headedness, and confusion.<ref name=Amin2009/> Nausea occurs in almost 90% of people, and vomiting occurs in about one-third.<ref name=Walton2009>Template:Cite book</ref> Other symptoms may include blurred vision, nasal stuffiness, diarrhea, frequent urination, pallor, or sweating.<ref name=Joel1999>Template:Cite book</ref> Swelling or tenderness of the scalp may occur as can neck stiffness.<ref name=Joel1999/> Associated symptoms are less common in the elderly.<ref name=ElderlyBook2008/>

Silent migraine

Sometimes, aura occurs without a subsequent headache.<ref name = "Cutrer_2006">Template:Cite book</ref> This is known in modern classification as a typical aura without headache, or acephalgic migraine in previous classification, or commonly as a silent migraine.<ref name="americanmigrainefoundation.org-Robblee-2019-Silent-Guide">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="jmedicalcaserep-Yusheng-2015-aura-w/o-headache">Template:Cite journal</ref> However, silent migraine can still produce debilitating symptoms, with visual disturbance, vision loss in half of both eyes, alterations in color perception, and other sensory problems, like sensitivity to light, sound, and odors.<ref name="medicalnewstoday-Leonard-2018-Silent-migraine">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It can last from 15 to 30 minutes, usually no longer than 60 minutes, and it can recur or appear as an isolated event.<ref name="jmedicalcaserep-Yusheng-2015-aura-w/o-headache"/>

Postdrome

The migraine postdrome could be defined as that constellation of symptoms occurring once the acute headache has settled.<ref>Template:Cite journal</ref> Many report a sore feeling in the area where the migraine was, and some report impaired thinking for a few days after the headache has passed. The person may feel tired or "hung over" and have head pain, cognitive difficulties, gastrointestinal symptoms, mood changes, and weakness.<ref name="pmid16426278">Template:Cite journal</ref> According to one summary, "Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise."<ref>Template:Cite book</ref>Template:Unreliable medical source

Cause

The underlying cause of migraine is unknown.<ref name=Rob10>Template:Cite journal</ref> However, it is believed to be related to a mix of environmental and genetic factors.<ref name=Lulli2007/> Migraine runs in families in about two-thirds of cases<ref name=Bart10/> and rarely occur due to a single gene defect.<ref name="Schurk2012"/> While migraine attacks were once believed to be more common in those of high intelligence, this does not appear to be true.<ref name = "Rasmussen_2006" /> A number of psychological conditions are associated, including depression, anxiety, and bipolar disorder.<ref name=HA26>The Headaches, pp. 246–247</ref>

File:Gray786.png

Intracranial cavernous sinus: a potential site where dilation of cerebral vessels can compress multiple cranial nerves.

Success of the surgical migraine treatment by decompression of extracranial sensory nerves adjacent to vessels<ref>Template:Cite journal</ref> suggests that people with migraine may have anatomical predisposition for neurovascular compression<ref>Template:Cite journal</ref> that may be caused by both intracranial and extracranial vasodilation due to migraine triggers.<ref>Template:Cite journal</ref> This, along with the existence of numerous cranial neural interconnections,<ref>Template:Cite journal</ref> may explain the multiple cranial nerve involvement and consequent diversity of migraine symptoms.<ref>Template:Cite journal</ref>

Genetics

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Studies of twins indicate a 34–51% genetic influence on the likelihood of developing migraine.<ref name="Lulli2007" /> This genetic relationship is stronger for migraine with aura than for migraine without aura.<ref name="Olesen_2006" /> It is clear from family and populations studies that migraine is a complex disorder, where numerous genetic risk variants exist, and where each variant increases the risk of migraine marginally.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> It is also known that having several of these risk variants increases the risk by a small to moderate amount.<ref name="Schurk2012" />

Single gene disorders that result in migraine are rare.<ref name=Schurk2012>Template:Cite journal</ref> One of these is known as familial hemiplegic migraine, a type of migraine with aura, which is inherited in an autosomal dominant fashion.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Four genes have been shown to be involved in familial hemiplegic migraine.<ref name=Ducros2013>Template:Cite journal</ref> Three of these genes are involved in ion transport.<ref name=Ducros2013/> The fourth is the axonal protein PRRT2, associated with the exocytosis complex.<ref name=Ducros2013/> Another genetic disorder associated with migraine is CADASIL syndrome or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.<ref name=Amin2009/> One meta-analysis found a protective effect from angiotensin converting enzyme polymorphisms on migraine.<ref>Template:Cite journal</ref> The TRPM8 gene, which codes for a cation channel, has been linked to migraine.<ref>Template:Cite journal</ref>

The common forms migraine are polygenetic, where common variants of numerous genes contributes to the predisposition for migraine. These genes can be placed in three categories increasing the risk of migraine in general, specifically migraine with aura, or migraine without aura.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Three of these genes, CALCA, CALCB, and HTR1F are already target for migraine specific treatments. Five genes are specific risk to migraine with aura, PALMD, ABO, LRRK2, CACNA1A and PRRT2, and 13 genes are specific to migraine without aura. Using the accumulated genetic risk of the common variations, into a so-called polygenetic risk, it is possible to assess e.g. the treatment response to triptans.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Triggers

Migraine may be induced by triggers, with some reporting it as an influence in a minority of cases<ref name=Bart10/> and others the majority.<ref name=Trigger09/> Many things such as fatigue, certain foods, alcohol, and weather have been labeled as triggers; however, the strength and significance of these relationships are uncertain.<ref name=Trigger09>Template:Cite journal</ref><ref>Template:Cite journal</ref> Most people with migraine report experiencing triggers.<ref>Template:Cite journal</ref> Symptoms may start up to 24 hours after a trigger.<ref name=Bart10/>

Also, evidence shows a strong association between migraine and the quality of sleep, particularly poor subjective quality of sleep. The relationship seems to be bidirectional, as migraine frequency increases with low quality of sleep yet the underlying mechanism of this correlation remains poorly understood.<ref>Template:Cite journal</ref>

Physiological aspects

Common triggers quoted are stress, hunger, and fatigue (these equally contribute to tension headaches).<ref name=Trigger09/> Psychological stress has been reported as a factor by 50–80% of people.<ref name=Rad2013>Template:Cite journal</ref> Migraine has also been associated with post-traumatic stress disorder and abuse.<ref>Template:Cite journal</ref> Migraine episodes are more likely to occur around menstruation.<ref name="Rad2013"/> Other hormonal influences, such as menarche, oral contraceptive use, pregnancy, perimenopause, and menopause, also play a role.<ref name=Chai2014>Template:Cite journal</ref> These hormonal influences seem to play a greater role in migraine without aura.<ref name = "Rasmussen_2006" /> Migraine episodes typically do not occur during the second and third trimesters of pregnancy, or following menopause.<ref name=Amin2009/>

Dietary aspects

Between 12% and 60% of people report foods as triggers.<ref name=Finocchi>Template:Cite journal</ref><ref>Template:Cite journal</ref>

There are many reports<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite book</ref><ref>Template:Cite journal</ref> that tyramine – which is naturally present in chocolate, alcoholic beverages, most cheeses, processed meats, and other foods – can trigger migraine symptoms in some individuals. Monosodium glutamate (MSG) has been reported as a trigger for migraine,<ref>Template:Cite journal</ref> but a systematic review concluded that "a causal relationship between MSG and headache has not been proven... It would seem premature to conclude that the MSG present in food causes headache".<ref>Template:Cite journal</ref>

Environmental aspects

Migraines may be triggered by weather changes, including changes in temperature and barometric pressure.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

A 2009 review on potential triggers in the indoor and outdoor environment previously concluded that while there were insufficient studies to confirm environmental factors as causing migraine, "migraineurs worldwide consistently report similar environmental triggers ... such as barometric pressure change, bright sunlight, flickering lights, air quality and odors".<ref name="Fri2009">Template:Cite journal</ref>

Pathophysiology

File:Cortical spreading depression.gif

Animation of cortical spreading depression

Migraine is believed to be primarily a neurological disorder,<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> while others believe it to be a neurovascular disorder with blood vessels playing the key role, although evidence does not support this completely.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Others believe both are likely important.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref name="Neurovascular contributions to migr">Template:Cite journal</ref><ref>Template:Cite journal</ref> One theory is related to increased excitability of the cerebral cortex and abnormal control of pain neurons in the trigeminal nucleus of the brainstem.<ref>Template:Cite journal</ref>

Sensitization of trigeminal pathways is a key pathophysiological phenomenon in migraine. It is debatable whether sensitization starts in the periphery or in the brain.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Aura

Cortical spreading depression, or spreading depression according to Leão, is a burst of neuronal activity followed by a period of inactivity, which is seen in those with migraine with aura.<ref name=HA28>The Headaches, Chp. 28, pp. 269–72</ref> There are a number of explanations for its occurrence, including activation of NMDA receptors leading to calcium entering the cell.<ref name=HA28/> After the burst of activity, the blood flow to the cerebral cortex in the area affected is decreased for two to six hours.<ref name=HA28/> It is believed that when depolarization travels down the underside of the brain, nerves that sense pain in the head and neck are triggered.<ref name=HA28/>

Pain

The exact mechanism of the head pain which occurs during a migraine episode is unknown.<ref name=Olesen2009>Template:Cite journal</ref> Some evidence supports a primary role for central nervous system structures (such as the brainstem and diencephalon),<ref>Template:Cite journal</ref> while other data support the role of peripheral activation (such as via the sensory nerves that surround blood vessels of the head and neck).<ref name=Olesen2009/> The potential candidate vessels include dural arteries, pial arteries and extracranial arteries such as those of the scalp.<ref name=Olesen2009/> The role of vasodilatation of the extracranial arteries, in particular, is believed to be significant.<ref>Template:Cite journal</ref>

Neuromodulators

Adenosine, a neuromodulator, may be involved.<ref name=Burn2015/> Released after the progressive cleavage of adenosine triphosphate (ATP), adenosine acts on adenosine receptors to put the body and brain in a low activity state by dilating blood vessels and slowing the heart rate, such as before and during the early stages of sleep. Adenosine levels have been found to be high during migraine attacks.<ref name=Burn2015>Template:Cite book</ref><ref>Template:Cite book</ref> Caffeine's role as an inhibitor of adenosine may explain its effect in reducing migraine.<ref>Template:Cite journal</ref> Low levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine (5-HT), are also believed to be involved.<ref>Template:Cite journal</ref>

Calcitonin gene-related peptides (CGRPs) have been found to play a role in the pathogenesis of the pain associated with migraine, as levels of it become elevated during an attack.<ref name=Gilmore2011/><ref name=pathos/>

Diagnosis

The diagnosis of a migraine is based on signs and symptoms.<ref name=Bart10/> Neuroimaging tests are not necessary to diagnose migraine, but may be used to find other causes of headaches in those whose examination and history do not confirm a migraine diagnosis.<ref name="AHSfive">

• Template:Cite journal
• Template:Cite journal
• Template:Cite journal</ref> It is believed that a substantial number of people with the condition remain undiagnosed.<ref name=Bart10/>

The diagnosis of migraine without aura, according to the International Headache Society, can be made according the "5, 4, 3, 2, 1 criteria", which is as follows:<ref name=ICHD2004/>

• Five or more attacks – for migraine with aura, two attacks are sufficient for diagnosis.
• Four hours to three days in duration
• Two or more of the following:
  • Unilateral (affecting one side of the head)
  • Pulsating
  • Moderate or severe pain intensity
  • Worsened by or causing avoidance of routine physical activity
• One or more of the following:
  • Nausea and/or vomiting
  • Sensitivity to both light (photophobia) and sound (phonophobia)

If someone experiences two of the following: photophobia, nausea, or inability to work or study for a day, the diagnosis is more likely.<ref>Template:Cite journal</ref> In those with four out of five of the following: pulsating headache, duration of 4–72 hours, pain on one side of the head, nausea, or symptoms that interfere with the person's life, the probability that this is a migraine attack is 92%.<ref name=Gilmore2011/> In those with fewer than three of these symptoms, the probability is 17%.<ref name=Gilmore2011/>

Classification

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Migraine was first comprehensively classified in 1988.<ref name="Olesen_2006">Template:Cite book</ref>

The International Headache Society updated their classification of headaches in 2004.<ref name=ICHD2004/> A third version was published in 2018.<ref>Template:Cite journal</ref> According to this classification, migraine is a primary headache disorder along with tension-type headaches and cluster headaches, among others.<ref>Template:Cite journal</ref>

Migraine is divided into six subclasses (some of which include further subdivisions):<ref>Template:Cite journal</ref>

• Migraine without aura, or "common migraine", involves migraine headaches that are not accompanied by aura.
• Migraine with aura, or "classic migraine", usually involves migraine headaches accompanied by aura. Less commonly, aura can occur without a headache, or with a nonmigraine headache. Two other varieties are familial hemiplegic migraine and sporadic hemiplegic migraine, in which a person has migraine with aura and with accompanying motor weakness. If a close relative has had the same condition, it is called "familial", otherwise it is called "sporadic". Another variety is basilar-type migraine, where a headache and aura are accompanied by difficulty speaking, world spinning, ringing in ears, or a number of other brainstem-related symptoms, but not motor weakness. This type was initially believed to be due to spasms of the basilar artery, the artery that supplies the brainstem. Now that this mechanism is not believed to be primary, the symptomatic term migraine with brainstem aura (MBA) is preferred.<ref name=Basil2009/> Retinal migraine (which is distinct from visual or optical migraine) involves migraine headaches accompanied by visual disturbances or even temporary blindness in one eye.
• Childhood periodic syndromes that are commonly precursors of migraine include cyclical vomiting (occasional intense periods of vomiting), abdominal migraine (abdominal pain, usually accompanied by nausea), and benign paroxysmal vertigo of childhood (occasional attacks of vertigo).
• Complications of migraine describe migraine headaches and/or auras that are unusually long or unusually frequent, or associated with a seizure or brain lesion.
• Probable migraine describes conditions that have some characteristics of migraine, but where there is not enough evidence to diagnose it as migraine with certainty (in the presence of concurrent medication overuse).
• Chronic migraine is a complication of migraine, and is a headache that fulfills diagnostic criteria for migraine headache and occurs for a greater time interval. Specifically, greater or equal to 15 days/month for longer than 3 months.<ref>Template:Cite journal</ref>

Abdominal migraine

The diagnosis of abdominal migraine is controversial.<ref name=Abdo2002>Template:Cite book</ref> Some evidence indicates that recurrent episodes of abdominal pain in the absence of a headache may be a type of migraine<ref name=Abdo2002/><ref>Template:Cite journal</ref> or are at least a precursor to migraine attacks.<ref name = "Olesen_2006" /> These episodes of pain may or may not follow a migraine-like prodrome and typically last minutes to hours.<ref name=Abdo2002/> They often occur in those with either a personal or family history of typical migraine.<ref name=Abdo2002/> Other syndromes that are believed to be precursors include cyclical vomiting syndrome and benign paroxysmal vertigo of childhood.<ref name = "Olesen_2006" />

Differential diagnosis

Other conditions that can cause similar symptoms to a migraine headache include temporal arteritis, cluster headaches, acute glaucoma, meningitis and subarachnoid hemorrhage.<ref name=Gilmore2011/> Temporal arteritis typically occurs in people over 50 years old and presents with tenderness over the temple, cluster headache presents with one-sided nose stuffiness, tears and severe pain around the orbits, acute glaucoma is associated with vision problems, meningitis with fevers, and subarachnoid hemorrhage with a very fast onset.<ref name=Gilmore2011/> Tension headaches typically occur on both sides, are not pounding, and are less disabling.<ref name=Gilmore2011/>

Those with stable headaches that meet criteria for migraine should not receive neuroimaging to look for other intracranial disease.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> This requires that other concerning findings such as papilledema (swelling of the optic disc) are not present. People with migraine are not at an increased risk of having another cause for severe headaches.Template:Citation needed

Management

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Management of migraine includes prevention of migraine attacks and rescue treatment. There are three main aspects of treatment: trigger avoidance, acute (abortive), and preventive (prophylactic) control.<ref>Template:Cite journal</ref>

Modern approaches to migraine management emphasize personalized care that considers individual patient needs. Lifestyle modifications, such as managing triggers and addressing comorbidities, form the foundation of treatment. Behavioral techniques and supplements like magnesium and riboflavin can serve as supportive options for some individuals.<ref>Jenkins, B. Migraine management. Australian Prescriber. 2020; 43(5):148–151. https://doi.org/10.18773/austprescr.2020.047</ref> Behavioral techniques that have been utilized in the treatment of migraines include Cognitive Behavioral Therapy (CBT), relaxation training, biofeedback, Acceptance and Commitment Therapy (ACT), as well as mindfulness-based therapies.<ref name = "Treadwell_2024" /> A 2024 systematic literature review and meta analysis found evidence that treatments such as CBT, relaxation training, ACT, and mindfulness-based therapies can reduce migraine frequency both on their own and in combination with other treatment options.<ref name = "Treadwell_2024">Template:Cite report</ref> In addition, it was found that relaxation therapy aided in the lessening of migraine frequency when compared to education by itself.<ref name = "Treadwell_2024" /> Similarly for children and adolescents, CBT and biofeedback strategies have shown effective in a decrease of frequency and intensity of migraines. These techniques often include relaxation methods and promotion of long-term management without medication side effects which is emphasized for younger individuals.<ref name = "Treadwell_2024" /> Acute treatments, including NSAIDs and triptans, are most effective when administered early in an attack, while preventive medications are recommended for those experiencing frequent or severe migraines. Proven preventive options include beta blockers, topiramate, and CGRP inhibitors like erenumab and galcanezumab, which have demonstrated significant efficacy in clinical studies.<ref name="pmid32802591">Template:Cite journal</ref> The European Consensus Statement provides a framework for diagnosis and management, emphasizing the importance of accurate assessment, patient education, and consistent adherence to prescribed treatments. Innovative therapies of oral medications used to treat migraine symptoms, such as gepants and ditans, are emerging as alternatives for patients who cannot use traditional options.<ref name="pmid34145431">Template:Cite journal</ref>

A 2024 systematic review and network meta analysis compared the effectiveness of medications for acute migraine attacks in adults. It found that triptans were the most effective class of drugs followed by non-steroidal anti-inflammatories. Gepants were less effective than non-steroidal anti-inflammatory drugs.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Calcitonin Gene Related Peptide (CGRP)

Calcitonin gene-related peptide (CGRP) is a neuropeptide implicated in the pathophysiology of migraines. It is predominantly found in the trigeminal ganglion and central nervous system pathways associated with migraine mechanisms.<ref>Template:Cite journal</ref> During migraine attacks, elevated levels of CGRP are detected, leading to vasodilation of cerebral and dural blood vessels and the release of inflammatory mediators from mast cells. These actions contribute to the transmission of nociceptive signals, culminating in migraine pain. Targeting CGRP has emerged as a promising therapeutic strategy for migraine management.Template:Med cn

Prognosis

"Migraine exists on a continuum of different attack frequencies and associated levels of disability."<ref>Template:Cite journal</ref> For those with occasional, episodic migraine, a "proper combination of drugs for prevention and treatment of migraine attacks" can limit the disease's impact on patients' personal and professional lives.<ref name="NINDS">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> But fewer than half of people with migraine seek medical care and more than half go undiagnosed and undertreated.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> "Responsive prevention and treatment of migraine is incredibly important" because evidence shows "an increased sensitivity after each successive attack, eventually leading to chronic daily migraine in some individuals."<ref name="NINDS" /> Repeated migraine results in "reorganization of brain circuitry", causing "profound functional as well as structural changes in the brain."<ref name="Brennan_2018">Template:Cite journal</ref> "One of the most important problems in clinical migraine is the progression from an intermittent, self-limited inconvenience to a life-changing disorder of chronic pain, sensory amplification, and autonomic and affective disruption. This progression, sometimes termed chronification in the migraine literature, is common, affecting 3% of migraineurs in a given year, such that 8% of migraineurs have chronic migraine in any given year." Brain imagery reveals that the electrophysiological changes seen during an attack become permanent in people with chronic migraine; "thus, from an electrophysiological point of view, chronic migraine indeed resembles a never-ending migraine attack."<ref name="Brennan_2018" /> Severe migraine ranks in the highest category of disability, according to the World Health Organization, which uses objective metrics to determine disability burden for the authoritative annual Global Burden of Disease report. The report classifies severe migraine alongside severe depression, active psychosis, quadriplegia, and terminal-stage cancer.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Migraine with aura appears to be a risk factor for ischemic stroke<ref name=Stroke2009>Template:Cite journal</ref> doubling the risk.<ref>Template:Cite journal</ref> Being a young adult, being female, using hormonal birth control, and smoking further increases this risk.<ref name=Stroke2009/> There also appears to be an association with cervical artery dissection.<ref>Template:Cite journal</ref> Migraine without aura does not appear to be a factor.<ref name=Kurth2010>Template:Cite journal</ref> The relationship with heart problems is inconclusive with a single study supporting an association.<ref name=Stroke2009/> Migraine does not appear to increase the risk of death from stroke or heart disease.<ref name="Death2011">Template:Cite journal</ref> Preventative therapy of migraine in those with migraine with aura may prevent associated strokes.<ref>Template:Cite journal</ref> People with migraine, particularly women, may develop higher than average numbers of white matter brain lesions of unclear significance.<ref>Template:Cite journal</ref>

Epidemiology

File:Chalmer 2023.jpg

Percent of women and men who have experienced migraine with or without aura within the last 3 months

Migraine is common, with around 33% of women and 18% of men affected at some point in their lifetime.<ref name=Ferrari2022>Template:Cite journal</ref> Onset can be at any age, but prevalence rises sharply around puberty, and remains high before declining after age 50.<ref name=Ferrari2022/> Before puberty, boys and girls are equally impacted, with around 5% of children experiencing migraine attacks. From puberty onwards, women experience migraine attacks at greater rates than men. From age 30 to 50, up to 4 times as many women experience migraine attacks as men.,<ref name=Ferrari2022/> this is most pronounced in migraine without aura.<ref>Template:Cite journal</ref>

Worldwide, migraine affects nearly 15% or approximately one billion people.<ref name=LancetEpi2012/> In the United States, about 6% of men and 18% of women experience a migraine attack in a given year, with a lifetime risk of about 18% and 43% respectively.<ref name=Bart10/> In Europe, migraine affects 12–28% of people at some point in their lives with about 6–15% of adult men and 14–35% of adult women getting at least one attack yearly.<ref name="Stovner2007">Template:Cite journal</ref> Rates of migraine are slightly lower in Asia and Africa than in Western countries.<ref name = "Rasmussen_2006" /><ref name=AsiaEpi2003>Template:Cite journal</ref> Chronic migraine occurs in approximately 1.4–2.2% of the population.<ref>Template:Cite journal</ref>

During perimenopause symptoms often get worse before decreasing in severity.<ref name="Pol2009">Template:Cite journal</ref> While symptoms resolve in about two-thirds of the elderly, in 3–10% they persist.<ref name="ElderlyBook2008">Template:Cite book</ref>

History

File:Cruikshank - The Head Ache.png

The Head Ache, George Cruikshank (1819)

An early description consistent with migraine is contained in the Ebers Papyrus, written around 1500 BCE in ancient Egypt.<ref name=Miller2005>Template:Cite book</ref>

The word migraine is from the Greek ἡμικρᾱνίᾱ (hēmikrāníā), 'pain in half of the head',<ref>{{#invoke:citation/CS1|citation |CitationClass=web }} on Perseus</ref> from ἡμι- (hēmi-), 'half' and κρᾱνίον (krāníon), 'skull'.<ref>Template:Cite book</ref> Template:TOC limit

In 200 BCE, writings from the Hippocratic school of medicine described the visual aura that can precede the headache and a partial relief occurring through vomiting.<ref name=Borsook2012>Template:Cite book</ref>

A second-century description by Aretaeus of Cappadocia divided headaches into three types: cephalalgia, cephalea, and heterocrania.<ref name=Waldman2011>Template:Cite book</ref> Galen of Pergamon used the term hemicrania (half-head), from which the word migraine was eventually derived.<ref name=Waldman2011/> He proposed that the pain arose from the meninges and blood vessels of the head.<ref name=Borsook2012/> Migraine was first divided into the two now used types – migraine with aura (migraine ophthalmique) and migraine without aura (migraine vulgaire) in 1887 by Louis Hyacinthe Thomas, a French librarian.<ref name=Borsook2012/> The mystical visions of Hildegard von Bingen, which she described as "reflections of the living light", are consistent with the visual aura experienced during migraine attacks.<ref name="Distillations">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

File:Trepanated skull of a woman-P4140363-black.jpg

A trepanated skull, from the Neolithic. The perimeter of the hole in the skull is rounded off by ingrowth of new bony tissue, indicating that the person survived the operation.

Trepanation, the deliberate drilling of holes into a skull, was practiced as early as 7,000 BCE.<ref name=Miller2005/> While sometimes people survived, many would have died from the procedure due to infection.<ref>Template:Cite book</ref> It was believed to work via "letting evil spirits escape".<ref>Template:Cite book</ref> William Harvey recommended trepanation as a treatment for migraine in the 17th century.<ref>Template:Cite book</ref> The association between trepanation and headaches in ancient history may simply be a myth or unfounded speculation that originated several centuries later. In 1913, the world-famous American physician William Osler misinterpreted the French anthropologist and physician Paul Broca's words about a set of Neolithic children's skulls that he had found during the 1870s. These skulls presented no evident signs of fractures that could justify this complex surgery for mere medical reasons. Trepanation was probably born of superstitions, to remove "confined demons" inside the head, or to create healing or fortune talismans with the bone fragments removed from the skulls of the patients. However, Osler wanted to make Broca's theory more palatable to his modern audiences, and explained that trepanation procedures were used for mild conditions such as "infantile convulsions headache and various cerebral diseases believed to be caused by confined demons."<ref>Template:Cite book</ref>

While many treatments for migraine have been attempted, it was not until 1868 that use of a substance which eventually turned out to be effective began.<ref name=Borsook2012/> This substance was the fungus ergot from which ergotamine was isolated in 1918<ref name=Hanson2011>Template:Cite journal</ref> and first used to treat migraine in 1925.<ref>Template:Cite journal</ref> Methysergide was developed in 1959 and the first triptan, sumatriptan, was developed in 1988.<ref name=Hanson2011/> During the 20th century with better study-design, effective preventive measures were found and confirmed.<ref name=Borsook2012/>

Society and culture

Migraine is a significant source of both medical costs and lost productivity. It has been estimated that migraine is the most costly neurological disorder in the European Community, costing more than €27 billion per year.<ref name=EU2008>Template:Cite journal</ref> In the United States, direct costs have been estimated at $17 billion, while indirect costs – such as missed or decreased ability to work – is estimated at $15 billion.<ref name=EcoUSA2008>Template:Cite journal</ref> Nearly a tenth of the direct cost is due to the cost of triptans.<ref name=EcoUSA2008/> In those who do attend work during a migraine attack, effectiveness is decreased by around a third.<ref name=EU2008/> Negative impacts also frequently occur for a person's family.<ref name=EU2008/>

Research

Prevention mechanisms

Transcranial magnetic stimulation shows promise,<ref name="Gilmore2011" /><ref>Template:Cite journal</ref> as does transcutaneous supraorbital nerve stimulation.<ref>Template:Cite journal</ref> There is preliminary evidence that a ketogenic diet may help prevent episodic and long-term migraine.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

Sex dependency

Statistical data indicates that women may be more prone to having migraine, showing migraine incidence three times higher among women than men.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> The Society for Women's Health Research has also mentioned hormonal influences, mainly estrogen, as having a considerable role in provoking migraine pain. Studies and research related to the sex dependencies of migraine are ongoing, and conclusions have yet to be achieved.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

See also

• Cluster headache
• Tension headache
• Trigeminal neuralgia

Further reading

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External links

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