|Classification and external resources|
The pain of a migraine headache can be debilitating.
|eMedicine||neuro/218 neuro/517 emerg/230 neuro/529|
Migraine is a chronic neurological disorder characterized by recurrent moderate to severe headaches often in association with a number of autonomic nervous system symptoms. The word derives from the Greek ἡμικρανία (hemikrania), "pain on one side of the head", from ἡμι- (hemi-), "half", and κρανίον (kranion), "skull".
Typically the headache is unilateral (affecting one half of the head) and pulsating in nature, lasting from 2 to 72 hours. Associated symptoms may include nausea, vomiting, photophobia (increased sensitivity to light), phonophobia (increased sensitivity to sound) and the pain is generally aggravated by physical activity. Up to one-third of people with migraine headaches perceive an aura: a transient visual, sensory, language, or motor disturbance which signals that the headache will soon occur. Occasionally an aura can occur with little or no headache following it.
Migraines are believed to be due to a mixture of environmental and genetic factors. About two-thirds of cases run in families. Fluctuating hormone levels may also play a role, as migraines affect slightly more boys than girls before puberty, but about two to three times more women than men. Propensity for migraines usually decreases during pregnancy. The exact mechanisms of migraine are not known. It is, however, believed to be a neurovascular disorder. The primary theory is related to increased excitability of the cerebral cortex and abnormal control of pain neurons in the trigeminal nucleus of the brainstem.
Initial recommended management is with simple analgesics such as ibuprofen and paracetamol (also known as acetaminophen) for the headache, an antiemetic for the nausea, and the avoidance of triggers. Specific agents such as triptans or ergotamines may be used by those for whom simple analgesics are not effective. Globally, approximately 15% of the population is affected by migraines at some point in life.
- 1 Signs and symptoms
- 2 Cause
- 3 Pathophysiology
- 4 Diagnosis
- 5 Prevention
- 6 Management
- 7 Prognosis
- 8 Epidemiology
- 9 History
- 10 Society and culture
- 11 Research
- 12 References
- 13 External links
Signs and symptoms
Migraines typically present with self-limited, recurrent severe headache associated with autonomic symptoms. About 15-30% of people with migraines experience migraines with an aura and those who have migraines with aura also frequently have migraines without aura. The severity of the pain, duration of the headache, and frequency of attacks is variable. A migraine lasting longer than 72 hours is termed status migrainosus. There are four possible phases to a migraine, although not all the phases are necessarily experienced:
- 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
Prodromal or premonitory symptoms occur in ~60% of those with migraines with an onset of two hours to two days before the start of pain or the aura  These symptoms may include a wide variety of phenomena including: altered mood, irritability, depression or euphoria, fatigue, craving for certain food, stiff muscles (especially in the neck), constipation or diarrhea, and sensitivity to smells or noise. This may occur in those with either migraine with aura or migraine without aura.
An aura is a transient focal neurological phenomenon that occurs before or during the headache. They appear gradually over a number of minutes and generally last fewer than 60 minutes. Symptoms can be visual, sensory or motor in nature and many people experience more than one. 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. Vision 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.) 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 aurae 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.
An aura rarely occurs without a subsequent headache, known as a silent migraine. However, it is difficult to assess the frequency of such cases, because patients who do not experience symptoms severe enough to drive them to seek treatment, may not realise that anything special is happening to them, and pass it off without reporting anything.
Classically the headache is unilateral, throbbing, and moderate to severe in intensity. It usually comes on gradually and is aggravated by physical activity. In more than 40% of cases however the pain may be bilateral, and neck pain is commonly associated. Bilateral pain is particularly common in those who have migraines without an aura. Less commonly pain may occur primarily in the back or top of the head. The pain usually lasts 4 to 72 hours in adults however in young children frequently lasts less than 1 hour. The frequency of attacks is variable, from a few in a lifetime to several a week, with the average being about one a month.
The pain is frequently accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, sensitivity to smells, fatigue and irritability. In a basilar migraine, a migraine with neurological symptoms related to the brain stem or with neurological symptoms on both sides of the body, common effects include: a sense of the world spinning, light-headedness, and confusion. Nausea occurs in almost 90% of people, and vomiting occurs in about one-third. Many thus seek a dark and quiet room. Other symptoms may include: blurred vision, nasal stuffiness, diarrhea, frequent urination, pallor, or sweating. Swelling or tenderness of the scalp may occur as can neck stiffness. Associated symptoms are less common in the elderly.
The effects of migraine may persist for some days after the main headache has ended; this is called the migraine postdrome. 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 patient may feel tired or "hung over" and have head pain, cognitive difficulties, gastrointestinal symptoms, mood changes, and weakness. According to one summary, "Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise."
The underlying causes of migraines are unknown. However, they are believed to be related to a mix of environmental and genetic factors. They run in families in about two-thirds of cases and rarely occur due to a single gene defect. While migraines were once believed to be more common in those of high intelligence, this does not appear to be true. A number of psychological conditions are associated including: depression, anxiety, and bipolar disorder as are many biological events or triggers.
Studies of twins indicate a 34% to 51% genetic influence of likelihood to develop migraine headaches. This genetic relationship is stronger for migraines with aura than for migraines without aura. A number of specific variants of genes increase the risk by a small to moderate amount.
Single gene disorders that result in migraines are rare. One of these is known as familial hemiplegic migraine, a type of migraine with aura, which is inherited in an autosomal dominant fashion. Four genes have been shown to be involved in familial hemiplegic migraine. Three of these genes are involved in ion transport. The fourth is an axonal protein associated with the exocytosis complex. Another genetic disorder associated with migraine is CADASIL syndrome or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Migraines may be induced by triggers, with some reporting it as an influence in a minority of cases and others the majority. Many things have been labeled as triggers, however the strength and significance of these relationships are uncertain. A trigger may be encountered up to 24 hours prior to the onset of symptoms.
Common triggers quoted are stress, hunger, and fatigue (these equally contribute to tension headaches). Migraines are more likely to occur around menstruation. Other hormonal influences, such as menarche, oral contraceptive use, pregnancy, perimenopause, and menopause, also play a role. These hormonal influences seem to play a greater role in migraine without aura. Migraines typically do not occur during the second and third trimesters or following menopause.
Reviews of dietary triggers have found that evidence mostly relies on self-reports and is not rigorous enough to prove or disprove any particular triggers. Regarding specific agents there does not appear to be evidence for an effect of tyramine on migraine and while monosodium glutamate (MSG) is frequently reported as a dietary trigger evidence does not consistently support this.
A review on potential triggers in the indoor and outdoor environment concluded the overall evidence was of poor quality, but nevertheless suggested people with migraines take some preventive measures related to indoor air quality and lighting.
Migraines are believed to be a neurovascular disorder with evidence supporting its mechanisms starting within the brain and then spreading to the blood vessels. Some researchers feel neuronal mechanisms play a greater role, while others feel blood vessels play the key role. Others feel both are likely important. High levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine, are believed to be involved.
Cortical spreading depression or spreading depression of Leão is bursts of neuronal activity followed by a period of inactivity, which is seen in those with migraines with an aura. There are a number of explanations for its occurrence including activation of NMDA receptors leading to calcium entering the cell. After the burst of activity the blood flow to the cerebral cortex in the area affected is decreased for two to six hours. It is believed that when depolarization travels down the underside of the brain, nerves that sense pain in the head and neck are triggered.
The exact mechanism of the head pain which occurs during a migraine is unknown. Some evidence supports a primary role for central nervous system structures (such as the brainstem and diencephalon) while other data support the role peripheral activation (such as via the sensory nerves that surround blood vessels of the head and neck). The potential candidates vessels include: dural arteries, pial arteries and extracranial arteries such as those of the scalp. The role of vasodilatation of the extracranial arteries, in particular, is believed to be significant.
The diagnosis of a migraine is based on signs and symptoms. Imaging tests are occasionally performed to exclude other causes of headaches. It is believed that a substantial number of people with the condition have not been diagnosed.
- 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 half the head);
- "Moderate or severe pain intensity";
- "Aggravation by or causing avoidance of routine physical activity"
- One or more of the following:
If someone experiences two of the following: photophobia, nausea, or inability to work / study for a day the diagnosis is more likely. 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 is 92%. In those with less than three of these symptoms the probability is 17%.
Migraines were first comprehensively classified in 1988. The International Headache Society most recently updated their classification of headaches in 2004. According to this classification migraines are primary headaches along with tension-type headaches and cluster headaches, among others.
Migraines are divided into seven subclasses (some of which include further subdivisions):
- Migraine without aura, or "common migraine", involves migraine headaches that are not accompanied by an aura
- Migraine with aura, or "classic migraine", usually involves migraine headaches accompanied by an aura. Less commonly, an 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 migraines 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.
- 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).
- Retinal migraine involves migraine headaches accompanied by visual disturbances or even temporary blindness in one eye.
- 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 migraines, but where there is not enough evidence to diagnose it as a migraine with certainty (in the presence of concurrent medication overuse).
- Chronic migraine is a complication of migraines, 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.
The diagnosis of abdominal migraines is controversial. Some evidence indicates that recurrent episodes of abdominal pain in the absence of a headache may be a type of migraine or are at least a precursor to migraines. These episodes of pain may or may not follow a migraine like prodrome and typically last minutes to hours. They often occur in those with either a personal or family history of typical migraines. Other syndromes that are believed to be precursors include: cyclical vomiting syndrome and benign paroxysmal vertigo of childhood.
Other conditions that can cause similar symptoms to a migraine headache include: temporal arteritis, cluster headaches, acute glaucoma, meningitis and subarachnoid hemorrhage. Temporal arteritis typically occurs in people over 50 years old and presents with tenderness over the temple, cluster headaches presents with one-sided nose stuffiness, tears and severe pain around the orbits, acute glaucoma is associated with vision problems, meningitis with fevers, and subaracchnoid hemorrhage with a very fast onset. Tension headaches typically occur on both sides, are not pounding, and are less disabling.
Preventive treatments of migraines include: medications, nutritional supplements, lifestyle alterations, and surgery. Prevention is recommended in those who have headaches more than two days a week, cannot tolerate the medications used to treat acute attacks, or those with severe attacks that are not easily controlled.
The goal is to reduce the frequency, painfulness, and/or duration of migraines, and to increase the effectiveness of abortive therapy. Another reason for prevention is to avoid medication overuse headache. This is a common problem and can result in chronic daily headache.
Preventive migraine medications are considered effective if they reduce the frequency or severity of the migraine attacks by at least 50%. Guidelines are fairly consistent in rating topiramate, divalproex/sodium valproate, propranolol, and metoprolol as having the highest level of evidence for first-line use. Recommendations regarding effectiveness varied however for gabapentin. Timolol is also effective for migraine prevention and in reducing migraine attack frequency and severity, while frovatriptan is effective for prevention of menstrual migraine.
Amitriptyline and venlafaxine are probably also effective. Angiotensin inhibition by either angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist may reduce attacks. Botox has been found to be useful in those with chronic migraines but not those with episodic ones.
While acupuncture may be effective, "true" acupuncture is not more efficient than sham acupuncture, a practice where needles are placed randomly. Both have a possibility of being more effective than routine care, with fewer adverse effects than preventative medications. Chiropractic manipulation, physiotherapy, massage and relaxation might be as effective as propranolol or topiramate in the prevention of migraine headaches; however, the research had some problems with methodology. The evidence to support spinal manipulation is poor and insufficient to support its use. There is some tentative evidence of benefit for magnesium, coenzyme Q(10), riboflavin, vitamin B(12), and feverfew, although data is limited and better quality trials must be conducted to reach more definitive conclusions. Of the alternative medicines, butterbur has the best evidence for its use.
Devices and surgery
Medical devices, such as biofeedback and neurostimulators, have some advantages in migraine prevention, mainly when common anti-migraine medications are contraindicated or in case of medication overuse. Biofeedback helps people be conscious of some physiological parameters so as to control them and try to relax and may be efficient for migraine treatment. Neurostimulation uses implantable neurostimulators similar to pacemakers for the treatment of intractable chronic migraines with encouraging results for severe cases. Migraine surgery, which involves decompression of certain nerves around the head and neck, may be an option in certain people who do not improve with medications.
There are three main aspects of treatment: trigger avoidance, acute symptomatic control, and pharmacological prevention. Medications are more effective if used earlier in an attack. The frequent use of medications may result in medication overuse headache, in which the headaches become more severe and more frequent. This may occur with triptans, ergotamines, and analgesics, especially narcotic analgesics. Due to these concerns simple analgesics are recommended to be used less than three days per week at most.
Recommended initial treatment for those with mild to moderate symptoms are simple analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) or the combination of paracetamol, acetylsalicylic acid, and caffeine. A number of NSAIDs have evidence to support their use. Ibuprofen has been found to provide effective pain relief in about half of people and diclofenac has been found effective.
Aspirin can relieve moderate to severe migraine pain, with an effectiveness similar to sumatriptan. Ketorolac is available in an intravenous formulation. Paracetamol (also known as acetaminophen), either alone or in combination with metoclopramide, is another effective treatment with a low risk of adverse effects. In pregnancy, paracetamol and metoclopramide are deemed safe as are NSAIDs until the third trimester.
Triptans such as sumatriptan are effective for both pain and nausea in up to 75% of people. They are the initially recommended treatments for those with moderate to severe pain or those with milder symptoms who do not respond to simple analgesics. The different forms available include oral, injectable, nasal spray, and oral dissolving tablets. In general, all the triptans appear equally effective, with similar side effects. However, individuals may respond better to specific ones. Most side effects are mild, such as flushing; however, rare cases of myocardial ischemia have occurred. They are thus not recommended for people with cardiovascular disease, who have had a stroke, or have migraines that are accompanied by neurological problems. In addition, triptans should be prescribed with caution for those with risk factors for vascular disease. While historically not recommended in those with basilar migraines there is no specific evidence of harm from their use in this population to support this caution. They are not addictive, but may cause medication overuse headaches if used more than 10 days per month.
Ergotamine and dihydroergotamine are older medications still prescribed for migraines, the latter in nasal spray and injectable forms. They appear equally effective to the triptans, are less expensive, and experience adverse effects that typically are benign. In the most debilitating cases, such as those with status migrainosus, they appear to be the most effective treatment option.
Intravenous metoclopramide or intranasal lidocaine are other potential options. Metoclopramide is the recommended treatment for those who present to the emergency department. A single dose of intravenous dexamethasone, when added to standard treatment of a migraine attack, is associated with a 26% decrease in headache recurrence in the following 72 hours. Spinal manipulation for treating an ongoing migraine headache is not supported by evidence. It is recommended that opioids and barbiturates not be used.
Long term prognosis in people with migraines is variable. Most people with migraines have periods of lost productivity due to their disease however typically the condition is fairly benign and is not associated with an increased risk of death. There are four main patterns to the disease: symptoms can resolve completely, symptoms can continue but become gradually less with time, symptoms may continue at the same frequency and severity, or attacks may become worse and more frequent.
Migraines with aura appear to be a risk factor for ischemic stroke doubling the risk. Being a young adult, being female, using hormonal contraception, and smoking further increases this risk. There also appears to be an association with cervical artery dissection. Migraines without aura do not appear to be a factor. The relationship with heart problems is inconclusive with a single study supporting an association. Overall however migraines do not appear to increase the risk of death from stroke or heart disease. Preventative therapy of migraines in those with migraines with auras may prevent associated strokes.
Worldwide, migraines affect nearly 15% or approximately one billion people. It is more common in women at 19% than men at 11%. In the United States, about 6% of men and 18% of women get a migraine in a given year, with a lifetime risk of about 18% and 43% respectively. In Europe, migraines affect 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 yearly. Rates of migraines are slightly lower in Asia and Africa than in Western countries. Chronic migraines occur in approximately 1.4 to 2.2% of the population.
These figures vary substantially with age: migraines most commonly start between 15 and 24 years of age and occur most frequently in those 35 to 45 years of age. In children, about 1.7% of 7 year olds and 3.9% of those between 7 and 15 years have migraines, with the condition being slightly more common in boys before puberty. During adolescence migraines becomes more common among women and this persists for the rest of the lifespan, being two times more common among elderly females than males. In women migraines without aura is more common than migraines with aura, however in men the two types occur with similar frequency.
An early description consistent with migraines is contained in the Ebers papyrus, written around 1500 BCE in ancient Egypt. 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.
A second-century description by Aretaeus of Cappadocia divided headaches into three types: cephalalgia, cephalea, and heterocrania. Galen of Pergamon used the term hemicrania (half-head), from which the word migraine was eventually derived. He also proposed that the pain arose from the meninges and blood vessels of the head. Migraines were 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.
Trepanation, the deliberate drilling of holes into a skull, was practiced as early as 7,000 BCE. While sometimes people survived, many would have died from the procedure due to infection. It was believed to work via "letting evil spirits escape". William Harvey recommended trepanation as a treatment for migraines in the 17th century.
While many treatments for migraines have been attempted, it was not until 1868 that use of a substance which eventually turned out to be effective began. This substance was the fungus ergot from which ergotamine was isolated in 1918. Methysergide was developed in 1959 and the first triptan, sumatriptan, was developed in 1988. During the 20th century with better study design effective preventative measures were found and confirmed.
Society and culture
Migraines are a significant source of both medical costs and lost productivity. It has been estimated that they are the most costly neurological disorder in the European Community, costing more than €27 billion per year. In the United States direct costs have been estimated at 17 billion USD. Nearly a tenth of this cost is due to the cost of triptans. Indirect costs are around 15 Billion USD, of which missed work is the greatest component. In those who do attend work with a migraine effectiveness is decreased by around a third. Negative impacts also frequently occur for a person's family.
Calcitonin gene related peptides (CGRPs) have been found to play a role in the pathogenesis of the pain associated with migraine. CGRP receptor antagonists, such as olcegepant and telcagepant, have been investigated both in vitro and in clinical studies for the treatment of migraine. In 2011, Merck stopped phase III clinical trials for their investigational drug telcagepant. Transcranial magnetic stimulation also shows promise.
- Liddell, Henry George; Scott, Robert. "ἡμικρανία". A Greek-English Lexicon. on Perseus
- Anderson, Kenneth; Anderson, Lois E.; Glanze, Walter D. (1994). Mosby's Medical, Nursing, and Allied Health Dictionary (4 ed.). Mosby. p. 998. ISBN 978-0-8151-6111-0.
- Headache Classification Subcommittee of the International Headache Society (2004). "The International Classification of Headache Disorders: 2nd edition". Cephalalgia 24 (Suppl 1): 9–160. doi:10.1111/j.1468-2982.2004.00653.x. PMID 14979299. as PDF
- Piane, M; Lulli, P; Farinelli, I; Simeoni, S; De Filippis, S; Patacchioli, FR; Martelletti, P (2007 Dec). "Genetics of migraine and pharmacogenomics: some considerations". The journal of headache and pain 8 (6): 334–9. doi:10.1007/s10194-007-0427-2. PMC 2779399. PMID 18058067.
- Bartleson JD, Cutrer FM (May 2010). "Migraine update. Diagnosis and treatment". Minn Med 93 (5): 36–41. PMID 20572569.
- Lay CL, Broner SW (May 2009). "Migraine in women". Neurologic Clinics 27 (2): 503–11. doi:10.1016/j.ncl.2009.01.002. PMID 19289228.
- Stovner LJ, Zwart JA, Hagen K, Terwindt GM, Pascual J (April 2006). "Epidemiology of headache in Europe". European Journal of Neurology 13 (4): 333–45. doi:10.1111/j.1468-1331.2006.01184.x. PMID 16643310.
- Dodick DW, Gargus JJ (August 2008). "Why migraines strike". Sci. Am. 299 (2): 56–63. Bibcode:2008SciAm.299b..56D. doi:10.1038/scientificamerican0808-56. PMID 18666680.
- Bigal, ME; Lipton, RB (2008 Jun). "The prognosis of migraine". Current Opinion in Neurology 21 (3): 301–8. doi:10.1097/WCO.0b013e328300c6f5. PMID 18451714.
- Gutman, Sharon A. (2008). Quick reference neuroscience for rehabilitation professionals : the essential neurologic principles underlying rehabilitation practice (2 ed.). Thorofare, NJ: SLACK. p. 231. ISBN 9781556428005.
- Gilmore, B; Michael, M (2011-02-01). "Treatment of acute migraine headache". American family physician 83 (3): 271–80. PMID 21302868.
- The Headaches, Pg 232-233
- al.], ed. Jes Olesen, ... [et (2006). The headaches. (3 ed.). Philadelphia: Lippincott Williams & Wilkins. p. 512. ISBN 9780781754002.
- Rae-Grant, [edited by] D. Joanne Lynn, Herbert B. Newton, Alexander D. (2004). The 5-minute neurology consult. Philadelphia: Lippincott Williams & Wilkins. p. 26. ISBN 9780683307238.
- Aminoff, Roger P. Simon, David A. Greenberg, Michael J. (2009). Clinical neurology (7 ed.). New York, N.Y: Lange Medical Books/McGraw-Hill. pp. 85–88. ISBN 9780071664332.
- Buzzi, MG; Cologno, D; Formisano, R; Rossi, P (2005 Oct-Dec). "Prodromes and the early phase of the migraine attack: therapeutic relevance". Functional neurology 20 (4): 179–83. PMID 16483458.
- Rossi, P; Ambrosini, A; Buzzi, MG (2005 Oct–Dec). "Prodromes and predictors of migraine attack". Functional neurology 20 (4): 185–91. PMID 16483459.
- Samuels, Allan H. Ropper, Martin A. (2009). Adams and Victor's principles of neurology (9 ed.). New York: McGraw-Hill Medical. pp. Chapter 10. ISBN 9780071499927.
- Tintinalli, Judith E. (2010). Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)). New York: McGraw-Hill Companies. pp. 1116–1117. ISBN 0-07-148480-9.
- The Headaches, pp.407–19
- Tepper, edited by Stewart J. Tepper, Deborah E. (2011-01-01). The Cleveland Clinic manual of headache therapy. New York: Springer. p. 6. ISBN 9781461401780.
- Bigal, ME; Arruda, MA (2010 Jul). "Migraine in the pediatric population – evolving concepts". Headache 50 (7): 1130–43. doi:10.1111/j.1526-4610.2010.01717.x. PMID 20572878.
- al.], ed. Jes Olesen, ... [et (2006). The headaches. (3 ed.). Philadelphia: Lippincott Williams & Wilkins. p. 238. ISBN 9780781754002.
- Dalessio, edited by Stephen D. Silberstein, Richard B. Lipton, Donald J. (2001). Wolff's headache and other head pain (7 ed.). Oxford: Oxford University Press. p. 122. ISBN 9780195135183.
- Kaniecki, RG (2009 Jun). "Basilar-type migraine". Current pain and headache reports 13 (3): 217–20. doi:10.1007/s11916-009-0036-7. PMID 19457282.
- Walton, edited by Robert P. Lisak ... [et al.] ; foreword by John (2009). International neurology : a clinical approach. Chichester, UK: Wiley-Blackwell. p. 670. ISBN 9781405157384.
- contributors, edited by Joel S. Glaser ; with 20 (1999). Neuro-ophthalmology (3 ed.). Philadelphia: Lippincott Williams & Wilkins. p. 555. ISBN 9780781717298.
- Malamut, edited by Joseph I. Sirven, Barbara L. (2008). Clinical neurology of the older adult (2 ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 197. ISBN 9780781769471.
- Kelman L (February 2006). "The postdrome of the acute migraine attack". Cephalalgia 26 (2): 214–20. doi:10.1111/j.1468-2982.2005.01026.x. PMID 16426278.
- Halpern, Audrey L.; Silberstein, Stephen D. (2005). "Ch. 9: The Migraine Attack—A Clinical Description". In Kaplan PW, Fisher RS. Imitators of Epilepsy (2 ed.). New York: Demos Medical. ISBN 1-888799-83-8. NBK7326.
- Robbins MS, Lipton RB (April 2010). "The epidemiology of primary headache disorders". Semin Neurol 30 (2): 107–19. doi:10.1055/s-0030-1249220. PMID 20352581.
- Schürks, M (2012 Jan). "Genetics of migraine in the age of genome-wide association studies". The journal of headache and pain 13 (1): 1–9. doi:10.1007/s10194-011-0399-0. PMC 3253157. PMID 22072275.
- The Headaches, pp. 238–40
- The Headaches, pp. 246–47
- de Vries, B; Frants, RR; Ferrari, MD; van den Maagdenberg, AM (2009 Jul). "Molecular genetics of migraine". Human Genetics 126 (1): 115–32. doi:10.1007/s00439-009-0684-z. PMID 19455354.
- Montagna, P (2008 Sep). "Migraine genetics". Expert Review of Neurotherapeutics 8 (9): 1321–30. doi:10.1586/14737184.108.40.2061. PMID 18759544.
- Ducros, A (2013 Apr 22). "[Genetics of migraine.]". Revue neurologique 169 (5): 360–71. doi:10.1016/j.neurol.2012.11.010. PMID 23618705.
- Levy D, Strassman AM, Burstein R (June 2009). "A critical view on the role of migraine triggers in the genesis of migraine pain". Headache 49 (6): 953–7. doi:10.1111/j.1526-4610.2009.01444.x. PMID 19545256.
- Martin PR (June 2010). "Behavioral management of migraine headache triggers: learning to cope with triggers". Curr Pain Headache Rep 14 (3): 221–7. doi:10.1007/s11916-010-0112-z. PMID 20425190.
- MacGregor, EA (2010-10-01). "Prevention and treatment of menstrual migraine". Drugs 70 (14): 1799–818. doi:10.2165/11538090-000000000-00000. PMID 20836574.
- Lay, CL; Broner, SW (2009 May). "Migraine in women". Neurologic Clinics 27 (2): 503–11. doi:10.1016/j.ncl.2009.01.002. PMID 19289228.
- Rockett, FC; de Oliveira, VR; Castro, K; Chaves, ML; Perla Ada, S; Perry, ID (2012 Jun). "Dietary aspects of migraine trigger factors". Nutrition Reviews 70 (6): 337–56. doi:10.1111/j.1753-4887.2012.00468.x. PMID 22646127.
- Holzhammer J, Wöber C (April 2006). "[Alimentary trigger factors that provoke migraine and tension-type headache]". Schmerz (in German) 20 (2): 151–9. doi:10.1007/s00482-005-0390-2. PMID 15806385.
- Jansen SC, van Dusseldorp M, Bottema KC, Dubois AE (September 2003). "Intolerance to dietary biogenic amines: a review". Annals of Allergy, Asthma & Immunology 91 (3): 233–40; quiz 241–2, 296. doi:10.1016/S1081-1206(10)63523-5. PMID 14533654.
- Sun-Edelstein C, Mauskop A (June 2009). "Foods and supplements in the management of migraine headaches". The Clinical Journal of Pain 25 (5): 446–52. doi:10.1097/AJP.0b013e31819a6f65. PMID 19454881.
- Freeman M (October 2006). "Reconsidering the effects of monosodium glutamate: a literature review". J Am Acad Nurse Pract 18 (10): 482–6. doi:10.1111/j.1745-7599.2006.00160.x. PMID 16999713.
- Friedman DI, De ver Dye T (June 2009). "Migraine and the environment". Headache 49 (6): 941–52. doi:10.1111/j.1526-4610.2009.01443.x. PMID 19545255.
- The Headaches Chp. 29, Pg. 276
- Goadsby, PJ (2009 Jan). "The vascular theory of migraine – a great story wrecked by the facts". Brain : a journal of neurology 132 (Pt 1): 6–7. doi:10.1093/brain/awn321. PMID 19098031.
- Brennan, KC; Charles, A (2010 Jun). "An update on the blood vessel in migraine". Current Opinion in Neurology 23 (3): 266–74. doi:10.1097/WCO.0b013e32833821c1. PMID 20216215.
- Dodick, DW (2008 Apr). "Examining the essence of migraine – is it the blood vessel or the brain? A debate". Headache 48 (4): 661–7. doi:10.1111/j.1526-4610.2008.01079.x. PMID 18377395.
- The Headaches, Chp. 28, pp. 269–72
- Olesen, J; Burstein, R; Ashina, M; Tfelt-Hansen, P (2009 Jul). "Origin of pain in migraine: evidence for peripheral sensitization". Lancet neurology 8 (7): 679–90. doi:10.1016/S1474-4422(09)70090-0. PMID 19539239.
- Akerman, S; Holland, PR; Goadsby, PJ (2011-09-20). "Diencephalic and brainstem mechanisms in migraine". Nature Reviews Neuroscience 12 (10): 570–84. doi:10.1038/nrn3057. PMID 21931334.
- Shevel, E (2011 Mar). "The extracranial vascular theory of migraine – a great story confirmed by the facts". Headache 51 (3): 409–17. doi:10.1111/j.1526-4610.2011.01844.x. PMID 21352215.
- Cousins, G; Hijazze, S; Van de Laar, FA; Fahey, T (2011 Jul–Aug). "Diagnostic accuracy of the ID Migraine: a systematic review and meta-analysis". Headache 51 (7): 1140–8. doi:10.1111/j.1526-4610.2011.01916.x. PMID 21649653.
- Nappi, G (2005 Sep). "Introduction to the new International Classification of Headache Disorders". The journal of headache and pain 6 (4): 203–4. doi:10.1007/s10194-005-0185-y. PMC 3452009. PMID 16362664.
- Negro, A; Rocchietti-March, M; Fiorillo, M; Martelletti, P (2011 Dec). "Chronic migraine: current concepts and ongoing treatments". European review for medical and pharmacological sciences 15 (12): 1401–20. PMID 22288302.
- Davidoff, Robert A. (2002). Migraine : manifestations, pathogenesis, and management (2 ed.). Oxford [u.a.]: Oxford Univ. Press. p. 81. ISBN 9780195137057.
- Russell, G; Abu-Arafeh, I, Symon, DN (2002). "Abdominal migraine: evidence for existence and treatment options". Paediatric drugs 4 (1): 1–8. PMID 11817981.
- Modi S, Lowder DM (January 2006). "Medications for migraine prophylaxis". American Family Physician 73 (1): 72–8. PMID 16417067.
- Diener HC, Limmroth V (August 2004). "Medication-overuse headache: a worldwide problem". Lancet Neurology 3 (8): 475–83. doi:10.1016/S1474-4422(04)00824-5. PMID 15261608.
- Fritsche, Guenther; Diener, Hans-Christoph (2002). "Medication overuse headaches – what is new?". Expert Opinion on Drug Safety 1 (4): 331–8. doi:10.1517/147403220.127.116.111. PMID 12904133.
- Kaniecki R, Lucas S. (2004). "Treatment of primary headache: preventive treatment of migraine". Standards of care for headache diagnosis and treatment. Chicago: National Headache Foundation. pp. 40–52.
- Loder, E; Burch, R; Rizzoli, P (2012 Jun). "The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines". Headache 52 (6): 930–45. doi:10.1111/j.1526-4610.2012.02185.x. PMID 22671714.
- Silberstein, SD; Holland, S; Freitag, F; Dodick, DW; Argoff, C; Ashman, E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society (2012-04-24). "Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology 78 (17): 1337–45. doi:10.1212/WNL.0b013e3182535d20. PMC 3335452. PMID 22529202.
- Shamliyan TA, Choi JY, Ramakrishnan R, Miller JB, Wang SY, Taylor FR et al. (2013). "Preventive pharmacologic treatments for episodic migraine in adults.". J Gen Intern Med 28 (9): 1225–37. doi:10.1007/s11606-013-2433-1. PMC PMC3744311. PMID 23592242.
- Jackson JL, Kuriyama A, Hayashino Y (April 2012). "Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis". JAMA 307 (16): 1736–45. doi:10.1001/jama.2012.505. PMID 22535858.
- Pringsheim T, Davenport W, Mackie G, et al. (Mar 2012). "Canadian Headache Society guideline for migraine prophylaxis". Can J Neurol Sci. 39 (2 Suppl 2): S1–59. PMID 22683887.
- Linde, K; Allais, G; Brinkhaus, B; Manheimer, E; Vickers, A; White, AR (2009). "Acupuncture for migraine prophylaxis". In Linde, Klaus. Cochrane Database of Systematic Reviews (Online) (1): CD001218. doi:10.1002/14651858.CD001218.pub2. PMC 3099267. PMID 19160193.
- Chaibi, Aleksander; Tuchin, Peter J.; Russell, Michael Bjørn (2011). "Manual therapies for migraine: A systematic review". The Journal of Headache and Pain 12 (2): 127–33. doi:10.1007/s10194-011-0296-6. PMC 3072494. PMID 21298314.
- Posadzki, P; Ernst, E (2011 Jun). "Spinal manipulations for the treatment of migraine: a systematic review of randomized clinical trials". Cephalalgia : an international journal of headache 31 (8): 964–70. doi:10.1177/0333102411405226. PMID 21511952.
- Bray, N.N.; Heath, A.A.; Militello, J (May 2013). "Migraine: Burden of disease, treatment, and prevention". Osteopathic Family Physician 5 (3): 116–122. doi:10.1016/j.osfp.2013.01.004.
- Bianchi, A; Salomone, S; Caraci, F; Pizza, V; Bernardini, R; Damato, C (2004). Role of Magnesium, Coenzyme Q10, Riboflavin, and Vitamin B12 in Migraine Prophylaxis. "Vitamins & Hormones Volume 69". Vitamins and hormones. Vitamins & Hormones 69: 297–312. doi:10.1016/S0083-6729(04)69011-X. ISBN 978-0-12-709869-2. PMID 15196887.
- Rios, Juanita; Passe, Megan M. (2004). "Evidence-Based Use of Botanicals, Minerals, and Vitamins in the Prophylactic Treatment of Migraines". Journal of the American Academy of Nurse Practitioners 16 (6): 251–6. doi:10.1111/j.1745-7599.2004.tb00447.x. PMID 15264611.
- Holland, S; Silberstein, SD; Freitag, F; Dodick, DW; Argoff, C; Ashman, E; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache, Society (2012-04-24). "Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology 78 (17): 1346–53. doi:10.1212/WNL.0b013e3182535d0c. PMC 3335449. PMID 22529203.
- Nestoriuc, Yvonne; Martin, Alexandra (2007). "Efficacy of biofeedback for migraine: A meta-analysis". Pain 128 (1–2): 111–27. doi:10.1016/j.pain.2006.09.007. PMID 17084028.
- Nestoriuc, Y; Martin, A; Rief, W; Andrasik, F (2008). "Biofeedback treatment for headache disorders: A comprehensive efficacy review". Applied psychophysiology and biofeedback 33 (3): 125–40. doi:10.1007/s10484-008-9060-3. PMID 18726688.
- Schoenen, J; Allena, M; Magis, D (2010). "Neurostimulation therapy in intractable headaches". Handbook of clinical neurology / edited by P.J. Vinken and G.W. Bruyn. Handbook of Clinical Neurology 97: 443–50. doi:10.1016/S0072-9752(10)97037-1. ISBN 9780444521392. PMID 20816443.
- Reed, KL; Black, SB; Banta Cj, 2nd; Will, KR (2010). "Combined occipital and supraorbital neurostimulation for the treatment of chronic migraine headaches: Initial experience". Cephalalgia 30 (3): 260–71. doi:10.1111/j.1468-2982.2009.01996.x. PMID 19732075.
- Kung, TA; Guyuron, B, Cederna, PS (2011 Jan). "Migraine surgery: a plastic surgery solution for refractory migraine headache". Plastic and reconstructive surgery 127 (1): 181–9. doi:10.1097/PRS.0b013e3181f95a01. PMID 20871488.
- "American Headache Society Five Things Physicians and Patients Should Question". Choosing Wisely. Retrieved 24 November 2013.
- Rabbie R, Derry S, Moore RA, McQuay HJ (2010). "Ibuprofen with or without an antiemetic for acute migraine headaches in adults". In Moore, Maura. Cochrane Database Syst Rev 10 (10): CD008039. doi:10.1002/14651858.CD008039.pub2. PMID 20927770.
- Derry S, Rabbie R, Moore RA (2012). "Diclofenac with or without an antiemetic for acute migraine headaches in adults". In Moore, Maura. Cochrane Database Syst Rev 2: CD008783. doi:10.1002/14651858.CD008783.pub2. PMID 22336852.
- Kirthi V, Derry S, Moore RA, McQuay HJ (2010). "Aspirin with or without an antiemetic for acute migraine headaches in adults". In Moore, Maura. Cochrane Database Syst Rev 4 (4): CD008041. doi:10.1002/14651858.CD008041.pub2. PMID 20393963.
- Derry S, Moore RA, McQuay HJ (2010). "Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults". In Moore, Maura. Cochrane Database Syst Rev 11 (11): CD008040. doi:10.1002/14651858.CD008040.pub2. PMID 21069700.
- Johnston MM, Rapoport AM (August 2010). "Triptans for the management of migraine". Drugs 70 (12): 1505–18. doi:10.2165/11537990-000000000-00000. PMID 20687618.
- "Generic migraine drug could relieve your pain and save you money". Best Buy Drugs. Consumer Reports.
- Tepper Stewart J., S. J.; Tepper, Deborah E. (April 2010). "Breaking the cycle of medication overuse headache". Cleveland Clinic Journal of Medicine 77 (4): 236–42. doi:10.3949/ccjm.77a.09147. PMID 20360117.
- Kelley, NE; Tepper, DE (2012 Jan). "Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium". Headache 52 (1): 114–28. doi:10.1111/j.1526-4610.2011.02062.x. PMID 22211870.
- al.], ed. Jes Olesen, ... [et (2006). The headaches. (3 ed.). Philadelphia: Lippincott Williams & Wilkins. p. 516. ISBN 9780781754002.
- Morren, JA; Galvez-Jimenez, N (2010 Dec). "Where is dihydroergotamine mesylate in the changing landscape of migraine therapy?". Expert opinion on pharmacotherapy 11 (18): 3085–93. doi:10.1517/14656566.2010.533839. PMID 21080856.
- Colman I, Friedman BW, Brown MD et al. (June 2008). "Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence". BMJ 336 (7657): 1359–61. doi:10.1136/bmj.39566.806725.BE. PMC 2427093. PMID 18541610.
- Posadzki, P; Ernst, E (2011 Jun). "Spinal manipulations for the treatment of migraine: a systematic review of randomized clinical trials". Cephalalgia : an international journal of headache 31 (8): 964–70. doi:10.1177/0333102411405226. PMID 21511952.
- Schürks, M; Rist, PM; Shapiro, RE; Kurth, T (2011 Sep). "Migraine and mortality: a systematic review and meta-analysis". Cephalalgia : an international journal of headache 31 (12): 1301–14. doi:10.1177/0333102411415879. PMC 3175288. PMID 21803936.
- Schürks, M; Rist, PM; Bigal, ME; Buring, JE; Lipton, RB; Kurth, T (2009-10-27). "Migraine and cardiovascular disease: systematic review and meta-analysis". BMJ (Clinical research ed.) 339: b3914. doi:10.1136/bmj.b3914. PMC 2768778. PMID 19861375.
- Kurth, T; Chabriat, H; Bousser, MG (2012 Jan). "Migraine and stroke: a complex association with clinical implications". Lancet neurology 11 (1): 92–100. doi:10.1016/S1474-4422(11)70266-6. PMID 22172624.
- Rist, PM; Diener, HC; Kurth, T; Schürks, M (2011 Jun). "Migraine, migraine aura, and cervical artery dissection: a systematic review and meta-analysis". Cephalalgia : an international journal of headache 31 (8): 886–96. doi:10.1177/0333102411401634. PMC 3303220. PMID 21511950.
- Kurth, T (2010 Mar). "The association of migraine with ischemic stroke". Current neurology and neuroscience reports 10 (2): 133–9. doi:10.1007/s11910-010-0098-2. PMID 20425238.
- Weinberger, J (2007 Mar). "Stroke and migraine". Current cardiology reports 9 (1): 13–9. doi:10.1007/s11886-007-0004-y. PMID 17362679.
- Vos, T; Flaxman, AD; Naghavi, M; Lozano, R; Michaud, C; Ezzati, M; Shibuya, K; Salomon, JA et al. (2012 Dec 15). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMID 23245607.
- Wang SJ (2003). "Epidemiology of migraine and other types of headache in Asia". Curr Neurol Neurosci Rep 3 (2): 104–8. doi:10.1007/s11910-003-0060-7. PMID 12583837.
- Natoli, JL; Manack, A; Dean, B; Butler, Q; Turkel, CC; Stovner, L; Lipton, RB (2010 May). "Global prevalence of chronic migraine: a systematic review". Cephalalgia : an international journal of headache 30 (5): 599–609. doi:10.1111/j.1468-2982.2009.01941.x. PMID 19614702.
- Hershey, AD (2010 Feb). "Current approaches to the diagnosis and management of pediatric migraine". Lancet neurology 9 (2): 190–204. doi:10.1016/S1474-4422(09)70303-5. PMID 20129168.
- Nappi, RE; Sances, G; Detaddei, S; Ornati, A; Chiovato, L; Polatti, F (2009 Jun). "Hormonal management of migraine at menopause". Menopause international 15 (2): 82–6. doi:10.1258/mi.2009.009022. PMID 19465675.
- Miller, Neil (2005). Walsh and Hoyt's clinical neuro-ophthalmology. (6 ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. p. 1275. ISBN 9780781748117.
- Borsook, David (2012). The migraine brain : imaging, structure, and function. New York: Oxford University Press. pp. 3–11. ISBN 9780199754564.
- Waldman, [edited by] Steven D. (2011). Pain management (2 ed.). Philadelphia, PA: Elsevier/Saunders. pp. 2122–2124. ISBN 9781437736038.
- Mays, eds. Margaret Cox, Simon (2002). Human osteology : in archaeology and forensic science (Repr. ed.). Cambridge [etc.]: Cambridge University Press. p. 345. ISBN 9780521691468.
- Colen, Chaim (2008). Neurosurgery. Colen Publishing. p. 1. ISBN 9781935345039.
- Daniel, Britt Talley (2010). Migraine. Bloomington, IN: AuthorHouse. p. 101. ISBN 9781449069629.
- Tfelt-Hansen, PC; Koehler, PJ (2011 May). "One hundred years of migraine research: major clinical and scientific observations from 1910 to 2010". Headache 51 (5): 752–78. doi:10.1111/j.1526-4610.2011.01892.x. PMID 21521208.
- Stovner, LJ; Andrée, C; Eurolight Steering, Committee (2008 Jun). "Impact of headache in Europe: a review for the Eurolight project". The journal of headache and pain 9 (3): 139–46. doi:10.1007/s10194-008-0038-6. PMC 2386850. PMID 18418547.
- Mennini, FS; Gitto, L; Martelletti, P (2008 Aug). "Improving care through health economics analyses: cost of illness and headache". The journal of headache and pain 9 (4): 199–206. doi:10.1007/s10194-008-0051-9. PMC 3451939. PMID 18604472.
- Tepper SJ, Stillman MJ (September 2008). "Clinical and preclinical rationale for CGRP-receptor antagonists in the treatment of migraine". Headache 48 (8): 1259–68. doi:10.1111/j.1526-4610.2008.01214.x. PMID 18808506.
- Merck & Co., Inc. (February 28, 2012). "SEC Annual Report, Fiscal Year Ending Dec 31, 2011" (PDF). SEC. p. 65. Retrieved 21 May 2012.
- ClinicalTrials.gov NCT01315847 Position Emission Tomography Study of Brain CGRP Receptors After MK-0974 Administration (MK-0974-067 AM1)
- Olesen, Jes (2006). The headaches. (3 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 9780781754002.