Migraine Headache Clinical Presentation
- Author: Jasvinder Chawla, MD, MBA; Chief Editor: Helmi L Lutsep, MD more...
Migraine attacks commonly occur when the migraineur is awake, although an attack may have already started by the time the individual wakes. Less commonly, it may awaken the patient at night.
The typical migraine headache is throbbing or pulsatile. However, more than 50% of people who suffer from migraines report nonthrobbing pain at some time during the attack.
The headache is initially unilateral and localized in the frontotemporal and ocular area, but pain can be felt anywhere around the head or neck. The pain typically builds up over a period of 1-2 hours, progressing posteriorly and becoming diffuse.
The headache typically lasts from 4-72 hours. Among females, more than two thirds of patients report attacks lasting longer than 24 hours.
Pain intensity is moderate to severe and intensifies with movement or physical activity. Many patients prefer to lie quietly in a dark room. The pain usually subsides gradually within a day and after a period of sleep. Most patients report feeling tired and weak after the attack.
Nausea and vomiting usually occur later in the attack in about 80% and 50% of patients, respectively, along with anorexia and food intolerance. Some patients have been noted to be pale and clammy, especially if nausea develops. Photophobia and/or phonophobia also commonly are associated with the headache. Lightheadedness is frequent. See Migraine-Associated Vertigo for more information on migraine-related vestibulopathy.
Other neurologic symptoms that may be observed include the following:
Hemiparesis (this symptom defines hemiplegic migraine)
Paresthesias or numbness
About 60% of people who experience migraines report premonitory symptoms that occur hours to days before headache onset. Although the prodromal features vary, they tend to be consistent for a given individual and may include the following:
Heightened sensitivity to light, sound, and odors
Lethargy or uncontrollable yawning
Mental and mood changes (eg, depression, anger, euphoria)
Excessive thirst and polyuria
Constipation or diarrhea
These symptoms may be difficult to diagnose as part of the migraine complex if they occur in isolation from the headache or if they are mild. The prodrome of migraine has yet to receive significant investigational attention.
The migraine aura is a complex of neurologic symptoms that may precede or accompany the headache phase or may occur in isolation. It usually develops over 5-20 minutes and lasts less than 60 minutes. The aura can be visual, sensory, or motor or any combination of these.
Auras most commonly consist of visual symptoms, which may be negative or positive. Negative symptoms (see the images below) include negative scotomata or negative visual phenomena, such as the following:
Homonymous hemianopic or quadrantic field defects
Altitudinal visual defects
Complete blindnessMigraine headache. Frank visual field loss can also occur associated with migraine. This example shows loss of the entire right visual field as described by a person who experiences migraines.Migraine headache. Example of a central scotoma as described by a person who experiences migraines. Note the visual loss in the center of vision.
The most common positive visual phenomenon is the scintillating scotoma. This consists of an arc or band of absent vision with a shimmering or glittering zigzag border. The disturbance begins in the paracentral area, and gradually enlarges and moves across the hemifield, eventually breaking up and resolving. It is often combined with photopsias (uniform flashes of light) or visual hallucinations, which may take various shapes (see the images below).
Scintillating scotoma occurs prior to the headache phase of an attack and is pathognomonic of a classic migraine. It is sometimes called a "fortification spectrum," because the serrated edges of the hallucinated "C" resemble a "fortified town with bastions around it."
Heat waves, fractured vision, macropsia, micropsia, and achromatopsia are other visual symptoms that may occur.
Paresthesias, occurring in 40% of cases, constitute the next most common aura; they are often cheiro-oral, with numbness starting in the hand, migrating to the arm, and then jumping to involve the face, lips, and tongue. As with visual auras, positive symptoms typically are followed by negative symptoms; paresthesias may be followed by numbness.
Sensory aura rarely occurs in isolation and usually follows visual aura. The rate of spread of sensory aura is helpful in distinguishing it from transient ischemic attack (TIA) or a sensory seizure. Just as a visual aura spreads across the visual field slowly, paresthesias may take 10-20 minutes to spread, which is slower than the spread of sensory symptoms of TIA.
Motor symptoms may occur in 18% of patients and usually are associated with sensory symptoms. Motor symptoms often are described as a sense of heaviness of the limbs before a headache but without any true weakness.
Speech and language disturbances have been reported in 17-20% of patients. These disturbances are commonly associated with upper extremity heaviness or weakness.
Course and diagnostic significance
The migrainous aura generally resolves within a few minutes and then is followed by a latent period before the onset of headache. However, some patients report merging of the aura with the headache.
Whether migraine with and without aura (prevalences, 36% and 55%, respectively) represent 2 distinct processes remains debatable; however, the similarities of the prodrome, headache, and resolution phases of the attacks, as well as the similarity in therapeutic response and the fact that 9% of patients experience both, suggest that they are the same entity.
When an aura is not followed by a headache, it is called a migraine equivalent or acephalic migraine. This is reported most commonly in patients older than 40 years who have a history of recurrent headache.
Scintillating scotoma has been considered to be diagnostic of migraine even in the absence of a headache; however, paresthesias, weakness, and other transient neurologic symptoms are not. In the absence of a prior history of recurrent headache and first occurrence after age 45 years, TIA should be considered and investigated fully.
Postdromal symptoms may persist for 24 hours after the headache and can include the following:
Tired, “washed out,” or irritable feeling
Unusually refreshed or euphoric feeling
Muscle weakness or myalgias
Anorexia or food cravings
A history of migraine triggers may be elicited. Common triggers include the following:
Hormonal changes (eg, those resulting from menstruation, ovulation, oral contraceptives, or hormone replacement)
Lack of exercise 
Medications (eg, nitroglycerin, histamine, reserpine, hydralazine, ranitidine, estrogen)
Approximately 70% of patients have a first-degree relative with a history of migraine. The risk of migraine is increased 4-fold in relatives of people who have migraine with aura. Migraine headache generally shows a multifactorial inheritance pattern, but the specific nature of the genetic influence is not yet completely understood.
Simple questionnaires, such as the Migraine Disability Assessment Scale (MIDAS), can be used to quantify the extent of disability on the first visit. These questionnaires can also be used for follow-up evaluations.
Although a thorough screening neurologic examination is essential, the results will be normal in most patients with headache. Evidence of autonomic nervous system involvement can be helpful, although most patients with migraine exhibit few or no findings. Serial neurologic examinations are recommended.
Possible findings during a migraine include the following:
Cranial/cervical muscle tenderness
Horner syndrome (ie, relative miosis with 1-2 mm of ptosis on the same side as the headache)
Hemisensory or hemiparetic neurologic deficits (ie, complicated migraine)
Adie-type pupil (ie, poor light reactivity, with near dissociation to light)
Pertinent physical examination findings that suggest a headache diagnosis other than migraine include the following:
Dim scotoma lasting a few seconds to several minutes (ie, amaurosis)
Temporal artery tenderness in the elderly
Increased lethargy (unrelated to medication use)
Mental status changes
Physical examination findings suggesting a more serious cause of headache include systemic symptoms (eg, myalgia, fever, malaise, weight loss, scalp tenderness, jaw claudication) and focal neurologic abnormalities or confusion, seizures, or any impairment of level of consciousness. On the other hand, focal neurologic findings that occur with the headache and persist temporarily after the pain resolves suggest a migraine variant, as follows:
Unilateral paralysis or weakness - Hemiplegic migraine
Aphasia, syncope, and balance problems - Basilar-type migraines
Third nerve palsy, with ocular muscle paralysis and ptosis, including or sparing the pupillary response - Ophthalmoplegic migraine
Ophthalmic migraines cause a visual disturbance (usually lateral field deficit). This variant is more common in children, with the abnormal motor findings lasting hours to days after the headache.
The diagnosis of migraine is based on the history. According to diagnostic criteria established by the International Headache Society, patients must have had at least 5 headache attacks that lasted 4-72 hours (untreated or unsuccessfully treated) and the headache must have had at least 2 of the following characteristics :
Moderate or severe pain intensity
Aggravation by or causing avoidance of routine physical activity (eg, walking, climbing stairs)
In addition, during the headache the patient must have had at least 1 of the following:
Nausea and/or vomiting
Photophobia and phonophobia
Finally, these features must not be attributable to another disorder. (See the chart below.)
The International Headache Society defines aura as reversible focal neurologic symptoms that usually develop gradually over 5-20 minutes and last for less than 60 minutes. Headache with the features of migraine without aura usually follows the aura symptoms. Less commonly, the headache lacks migrainous features or is completely absent.
Migraine variants include the following:
Childhood periodic syndromes
Late-life migrainous accompaniments
See the Medscape Reference article Childhood Migraine Variants for more information on these topics.
Childhood periodic syndromes
Childhood periodic syndromes evolve into migraine in adulthood. These syndromes include cyclic vomiting, abdominal migraine, and benign paroxysmal vertigo of childhood.
In cyclic vomiting, the child has at least 5 attacks of intense nausea and vomiting ranging from 1 hour to 5 days. Abdominal migraine consists of episodic midline abdominal pain lasting 1-72 hours with at least 2 of 4 other symptoms (ie, nausea, vomiting, anorexia, and/or pallor). Benign paroxysmal vertigo of childhood involves recurrent attacks of vertigo, often associated with vomiting or nystagmus.
See Migraine in Children for more information on these topics.
Late-life migrainous accompaniments
In elderly persons, a stereotypical series of prodromelike symptoms may entirely replace the migrainous episode; this is termed late-life migrainous accompaniments. If the headache is always on one side, a structural lesion needs to be excluded using imaging studies.
Eliciting a history of recurrent typical attacks and determining the provoking agent are important because a secondary headache can mimic migraine. A new headache, even if it appears typical on the basis of its history, should always suggest a broad differential diagnosis and the possibility of a secondary headache.
Basilar-type and hemiplegic migraine
Patients with basilar-type migraine can present without headaches but with basilar-type symptoms, such as the following:
Tingling of extremities
Hemiplegic migraine is a very rare migraine variant in which headaches are associated with temporary, unilateral hemiparesis or hemiplegia, at times accompanied by ipsilateral numbness or tingling, with or without a speech disturbance. The focal neurologic deficit may precede or accompany the headache, which is usually less dramatic than the motor deficit. Other migraine symptoms may variably be present. Patients may also experience disturbance of consciousness, and (rarely) coma
Ophthalmoplegic and retinal migraine
Ophthalmoplegic migraine is characterized by transient palsies of the extraocular muscle with dilated pupils and eye pain. This migraine variant has been reclassified by the International Headache Society as a neuralgia and is thought to be caused by idiopathic inflammatory neuritis. In the acute phase, enhancement of the cisternal segment of the third cranial nerve occurs.
Rarely, patients develop retinal and optic nerve involvement during or before a migraine headache and present with visual disturbance, papilledema, and retinal hemorrhages affecting 1 eye. This variant is called retinal migraine or ocular migraine.
The International Headache Society criteria for retinal migraine are at least 2 attacks of fully reversible, monocular visual phenomena, positive and/or negative (eg, scintillations, scotomata, or blindness). These are to be confirmed by examination during an attack or (after proper instruction) by the patient's drawing of a monocular field defect during an attack. In addition, migraine without aura must begin during the visual symptoms or follow them within 60 minutes.
The patient must have a normal ophthalmologic examination between attacks. Other causes of transient, monocular blindness must be excluded with appropriate investigations.
Status migrainosus and chronic migraine
Status migrainosus occurs when the migraine attack persists for more than 72 hours. It may result in complications such as dehydration.
Chronic migraine is defined as migraine headache that occurs for more than 15 days a month for greater than 3 months. Most patients with chronic migraine have a history of migraine headaches that started at a young age. Associated symptoms of nausea, vomiting, photophobia, and phonophobia may be less frequent.
Comorbidities of Migraine
Migraine is associated with the following:
Epilepsy (eg, benign rolandic epilepsy, benign childhood epilepsy)
Hereditary hemorrhagic telangiectasia
Hereditary essential tremor
Hereditary cerebral amyloid angiopathy
Ischemic stroke (migraine with aura is a risk factor, with an odds ratio of 6)
Posttraumatic stress disorder
Epilepsy increases the relative risk of migraine by 2.4. A Danish study found that migraine occurs in 20-30% of patients with several medical conditions, including kidney stone, psoriasis, rheumatoid arthritis, and fibromyalgia. Migraine with aura had more comorbidities than migraine without aura.
According to one study, a history of asthma may predict chronic migraine in individuals who have episodic migraine. Results show that study participants with asthma had a greater than twofold risk for progression to chronic migraine compared with those without asthma. The highest risk was found among those with the greatest number of respiratory symptoms.
Complications of Migraine
Complications of migraine include the following:
Migrainous infarction (stroke with migraine)
Persistent aura (eg, 30-60 minutes) without infarction
Ischemic stroke may occur as a rare, but serious, complication of migraine. In migraines with aura, hemorrhagic stroke is also a possible, but rare, complication. Risk factors for stroke include the following:
Migraine with aura
Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988. 8 Suppl 7:1-96. [Medline].
Hughes S. Choosing Wisely: 5 Headache Interventions Discouraged. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814816. Accessed: November 25, 2013.
Loder E, Weizenbaum E, Frishberg B, Silberstein S; the American Headache Society Choosing Wisely Task Force. Choosing Wisely in Headache Medicine: The American Headache Society's List of Five Things Physicians and Patients Should Question. Headache. Available at http://onlinelibrary.wiley.com/doi/10.1111/head.12233/abstract. Accessed: November 25, 2013.
[Guideline] Matchar DB, Young WB, Rosenberg JA, et al. Evidence-based guidelines for migraine headache in the primary care setting: Pharmacological management of acute attacks. American Academy of Neurology. Accessed February 10, 2011. [Full Text].
Silberstein SD, Freitag FG. Preventative treatment of migraine. Neurology. 2003. 60(7):S38-44.
Anderson P. New Screening Tool for Chronic Migraine. Medscape Medical News. Available at http://www.medscape.com/viewarticle/831261. Accessed: September 8, 2014.
[Guideline] The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004. 24 Suppl 1:9-160. [Medline].
Anderson P. New Headache Classification System Published. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/807334. Accessed: July 15, 2013.
[Guideline] Solomon GD, Cady RK, Klapper JA, Ryan RE Jr. Standards of care for treating headache in primary care practice. National Headache Foundation. Cleve Clin J Med. 1997 Jul-Aug. 64(7):373-83. [Medline].
[Guideline] Ducharme J. Canadian Association of Emergency Physicians Guidelines for the acute management of migraine headache. J Emerg Med. 1999 Jan-Feb. 17(1):137-44. [Medline].
Perciaccante A. Migraine is characterized by a cardiac autonomic dysfunction. Headache. 2008 Jun. 48(6):973. [Medline].
May A, Goadsby PJ. The trigeminovascular system in humans: pathophysiologic implications for primary headache syndromes of the neural influences on the cerebral circulation. J Cereb Blood Flow Metab. 1999 Feb. 19(2):115-27. [Medline].
Cutrer FM, Charles A. The neurogenic basis of migraine. Headache. 2008 Oct. 48(9):1411-4. [Medline].
Waeber C, Moskowitz MA. Therapeutic implications of central and peripheral neurologic mechanisms in migraine. Neurology. 2003 Oct 28. 61(8 Suppl 4):S9-20. [Medline].
Welch KM. Contemporary concepts of migraine pathogenesis. Neurology. 2003 Oct 28. 61(8 Suppl 4):S2-8. [Medline].
Hauge AW, Asghar MS, Schytz HW, Christensen K, Olesen J. Effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. Lancet Neurol. 2009 Aug. 8(8):718-23. [Medline].
Moulton EA, Burstein R, Tully S, Hargreaves R, Becerra L, Borsook D. Interictal dysfunction of a brainstem descending modulatory center in migraine patients. PLoS One. 2008. 3(11):e3799. [Medline]. [Full Text].
Richter F, Lehmenkühler A. [Cortical spreading depression (CSD): a neurophysiological correlate of migraine aura]. Schmerz. 2008 Oct. 22(5):544-6, 548-50. [Medline].
Martins-Oliveira A, Speciali JG, Dach F, Marcaccini AM, Gonçalves FM, Gerlach RF, et al. Different circulating metalloproteinases profiles in women with migraine with and without aura. Clin Chim Acta. 2009 Oct. 408(1-2):60-4. [Medline].
Imamura K, Takeshima T, Fusayasu E, Nakashima K. Increased plasma matrix metalloproteinase-9 levels in migraineurs. Headache. 2008 Jan. 48(1):135-9. [Medline].
Piilgaard H, Lauritzen M. Persistent increase in oxygen consumption and impaired neurovascular coupling after spreading depression in rat neocortex. J Cereb Blood Flow Metab. 2009 Sep. 29(9):1517-27. [Medline].
Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH. An association between migraine and cutaneous allodynia. Ann Neurol. 2000 May. 47(5):614-24. [Medline].
Peroutka SJ. Dopamine and migraine. Neurology. 1997 Sep. 49(3):650-6. [Medline].
Sun-Edelstein C, Mauskop A. Role of magnesium in the pathogenesis and treatment of migraine. Expert Rev Neurother. 2009 Mar. 9(3):369-79. [Medline].
Napoli R, Guardasole V, Zarra E, Matarazzo M, D'Anna C, Saccà F, et al. Vascular smooth muscle cell dysfunction in patients with migraine. Neurology. 2009 Jun 16. 72(24):2111-4. [Medline].
Gruber HJ, Bernecker C, Lechner A, Weiss S, Wallner-Blazek M, Meinitzer A, et al. Increased nitric oxide stress is associated with migraine. Cephalalgia. 2010 Apr. 30(4):486-92. [Medline].
Tietjen GE, Herial NA, White L, Utley C, Kosmyna JM, Khuder SA. Migraine and biomarkers of endothelial activation in young women. Stroke. 2009 Sep. 40(9):2977-82. [Medline].
Hamed SA. The vascular risk associations with migraine: relation to migraine susceptibility and progression. Atherosclerosis. 2009 Jul. 205(1):15-22. [Medline].
Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology. 2008 Nov 25. 71(22):1821-8. [Medline].
Kors EE, Haan J, Ferrari MD. Genetics of primary headaches. Curr Opin Neurol. 1999 Jun. 12(3):249-54. [Medline].
Barbas NR, Schuyler EA. Heredity, genes, and headache. Semin Neurol. 2006 Nov. 26(5):507-14. [Medline].
Chasman DI, Schürks M, Anttila V, de Vries B, Schminke U, Launer LJ, et al. Genome-wide association study reveals three susceptibility loci for common migraine in the general population. Nat Genet. 2011 Jun 12. 43(7):695-8. [Medline]. [Full Text].
Anttila V, Stefansson H, Kallela M, Todt U, Terwindt GM, Calafato MS, et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet. 2010 Oct. 42(10):869-73. [Medline]. [Full Text].
Ligthart L, de Vries B, Smith AV, Ikram MA, Amin N, Hottenga JJ, et al. Meta-analysis of genome-wide association for migraine in six population-based European cohorts. Eur J Hum Genet. 2011 Aug. 19(8):901-7. [Medline]. [Full Text].
Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 1996 Nov 1. 87(3):543-52. [Medline].
Thomsen LL, Kirchmann M, Bjornsson A, Stefansson H, Jensen RM, Fasquel AC, et al. The genetic spectrum of a population-based sample of familial hemiplegic migraine. Brain. 2007 Feb. 130:346-56. [Medline].
Ferrari MD. Heritability of migraine. Neurology. 2003. 60(7):S15-20.
De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L, et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003 Feb. 33(2):192-6. [Medline].
Kahlig KM, Rhodes TH, Pusch M, Freilinger T, Pereira-Monteiro JM, Ferrari MD, et al. Divergent sodium channel defects in familial hemiplegic migraine. Proc Natl Acad Sci U S A. 2008 Jul 15. 105(28):9799-804. [Medline]. [Full Text].
Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S, et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet. 2005 Jul 30-Aug 5. 366(9483):371-7. [Medline].
Opherk C, Peters N, Herzog J, Luedtke R, Dichgans M. Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004 Nov. 127:2533-9. [Medline].
Richards A, van den Maagdenberg AM, Jen JC, Kavanagh D, Bertram P, Spitzer D, et al. C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet. 2007 Sep. 39(9):1068-70. [Medline].
Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006 Apr 6. 354(14):1489-96. [Medline].
Stam AH, Haan J, van den Maagdenberg AM, Ferrari MD, Terwindt GM. Migraine and genetic and acquired vasculopathies. Cephalalgia. 2009 Sep. 29(9):1006-17. [Medline].
MacGregor EA. Menstrual migraine. Curr Opin Neurol. 2008 Jun. 21(3):309-15. [Medline].
Allais G, Gabellari IC, De Lorenzo C, Mana O, Benedetto C. Oral contraceptives in migraine. Expert Rev Neurother. 2009 Mar. 9(3):381-93. [Medline].
Wöber C, Brannath W, Schmidt K, Kapitan M, Rudel E, Wessely P, et al. Prospective analysis of factors related to migraine attacks: the PAMINA study. Cephalalgia. 2007 Apr. 27(4):304-14. [Medline].
Klein E, Spencer D. Migraine frequency and risk of cardiovascular disease in women. Neurology. 2009 Aug 25. 73(8):e42-3. [Medline].
Woodward M. Migraine and the risk of coronary heart disease and ischemic stroke in women. Womens Health (Lond Engl). 2009 Jan. 5(1):69-77. [Medline].
Scher AI, Gudmundsson LS, Sigurdsson S, Ghambaryan A, Aspelund T, Eiriksdottir G, et al. Migraine headache in middle age and late-life brain infarcts. JAMA. 2009 Jun 24. 301(24):2563-70. [Medline].
Kurth T, Winter AC, Eliassen AH, Dushkes R, Mukamal KJ, Rimm EB, et al. Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ. 2016 May 31. 353:i2610. [Medline].
Kruit MC, Launer LJ, Overbosch J, van Buchem MA, Ferrari MD. Iron accumulation in deep brain nuclei in migraine: a population-based magnetic resonance imaging study. Cephalalgia. 2009 Mar. 29(3):351-9. [Medline].
Welch KM. Iron in the migraine brain; a resilient hypothesis. Cephalalgia. 2009 Mar. 29(3):283-5. [Medline].
Nguyen RH, Ford S, Calhoun AH, Holden JK, Gracely RH, Tommerdahl M. Neurosensory assessments of migraine. Brain Res. 2013 Jan 5. [Medline].
Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002 Mar 26. 58(6):885-94. [Medline].
Stewart WF, Linet MS, Celentano DD, Van Natta M, Ziegler D. Age- and sex-specific incidence rates of migraine with and without visual aura. Am J Epidemiol. 1991 Nov 15. 134(10):1111-20. [Medline].
Hsu LC, Wang SJ, Fuh JL. Prevalence and impact of migrainous vertigo in mid-life women: a community-based study. Cephalalgia. 2011 Jan. 31(1):77-83. [Medline].
Burton WN, Landy SH, Downs KE, Runken MC. The impact of migraine and the effect of migraine treatment on workplace productivity in the United States and suggestions for future research. Mayo Clin Proc. 2009 May. 84(5):436-45. [Medline]. [Full Text].
Bille B. Migraine in childhood and its prognosis. Cephalalgia. 1981 Jun. 1(2):71-5. [Medline].
Milhaud D, Bogousslavsky J, van Melle G, Liot P. Ischemic stroke and active migraine. Neurology. 2001 Nov 27. 57(10):1805-11. [Medline].
Kruit MC, Launer LJ, Ferrari MD, van Buchem MA. Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study. Brain. 2005 Sep. 128:2068-77. [Medline].
Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ. Cardiovascular risk factors and migraine: the GEM population-based study. Neurology. 2005 Feb 22. 64(4):614-20. [Medline].
Bigal ME, Kurth T, Santanello N, Buse D, Golden W, Robbins M, et al. Migraine and cardiovascular disease: a population-based study. Neurology. 2010 Feb 23. 74(8):628-35. [Medline].
Gudmundsson LS, Scher AI, Aspelund T, Eliasson JH, Johannsson M, Thorgeirsson G, et al. Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study. BMJ. 2010 Aug 24. 341:c3966. [Medline]. [Full Text].
International Headache Society. IHS Classification ICHD-II: Migraine. Available at http://ihs-classification.org/en/02_klassifikation/02_teil1/01.00.00_migraine.html. Accessed: March 27, 2013.
Le H, Tfelt-Hansen P, Russell MB, Skytthe A, Kyvik KO, Olesen J. Co-morbidity of migraine with somatic disease in a large population-based study. Cephalalgia. 2011 Jan. 31(1):43-64. [Medline].
Martin VT, Fanning KM, Serrano D, Buse DC, Reed ML, Lipton RB. Asthma is a risk factor for new onset chronic migraine: Results from the American migraine prevalence and prevention study. Headache. 2015 Nov 19. [Medline].
Loder E. Migraine with aura and increased risk of ischaemic stroke. BMJ. 2009 Oct 27. 339:b4380. [Medline].
Harling DW, Peatfield RC, Van Hille PT, Abbott RJ. Thunderclap headache: is it migraine?. Cephalalgia. 1989 Jun. 9(2):87-90. [Medline].
Forsyth PA, Posner JB. Headaches in patients with brain tumors: a study of 111 patients. Neurology. 1993 Sep. 43(9):1678-83. [Medline].
Anderson P. Neuropeptide May Be Biomarker for Chronic Migraine. Medscape Medical News. Aug 27 2013. [Full Text].
Cernuda-Morollón E, Larrosa D, Ramón C, et al. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology. 2013 Aug 23. [Medline].
Silberstein SD, Edvinsson L. Is CGRP a marker for chronic migraine?. Neurology. 2013 Aug 28. [Medline].
Wilper A, Woolhandler S, Himmelstein D, Nardin R. Impact of insurance status on migraine care in the United States: a population-based study. Neurology. 2010 Apr 13. 74(15):1178-83. [Medline].
Detsky ME, McDonald DR, Baerlocher MO, Tomlinson GA, McCrory DC, Booth CM. Does this patient with headache have a migraine or need neuroimaging?. JAMA. 2006 Sep 13. 296(10):1274-83. [Medline].
Sahai-Srivastava S, Desai P, Zheng L. Analysis of headache management in a busy emergency room in the United States. Headache. 2008 Jun. 48(6):931-8. [Medline].
Tornabene SV, Deutsch R, Davis DP, Chan TC, Vilke GM. Evaluating the use and timing of opioids for the treatment of migraine headaches in the emergency department. J Emerg Med. 2009 May. 36(4):333-7. [Medline].
Friedman BW, Solorzano C, Esses D, Xia S, Hochberg M, Dua N, et al. Treating headache recurrence after emergency department discharge: a randomized controlled trial of naproxen versus sumatriptan. Ann Emerg Med. 2010 Jul. 56(1):7-17. [Medline]. [Full Text].
Kelman L. Women's issues of migraine in tertiary care. Headache. 2004 Jan. 44(1):2-7. [Medline].
US Food and Drug Administration. FDA allows marketing of first device to relieve migraine headache pain [press release]. December 13, 2013. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm378608.htm. Accessed: December 23, 2013.
Jeffrey S. FDA approves first device to treat migraine pain. Medscape Medical News. December 13, 2013. [Full Text].
Lipton RB, Dodick DW, Silberstein SD, et al. Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial. Lancet Neurol. 2010 Apr. 9(4):373-80. [Medline].
eNeura Therapeutics. Clinical trials -- study: migraine with aura. Available at http://www.eneura.com/clinical_trials.html. Accessed: January 28, 2014.
Holroyd KA, Cottrell CK, O'Donnell FJ, Cordingley GE, Drew JB, Carlson BW, et al. Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ. 2010 Sep 29. 341:c4871. [Medline]. [Full Text].
Derry S, Moore RA, McQuay HJ. Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults. Cochrane Database Syst Rev. 2010 Nov 10. CD008040. [Medline].
Matchar DB. Acute management of migraine: highlights of the US Headache Consortium. Neurology. 60(7):S21-3.
Friedman BW, Mulvey L, Esses D, et al. Metoclopramide for acute migraine: a dose-finding randomized clinical trial. Ann Emerg Med. 2011 May. 57(5):475-482.e1. [Medline].
Taggart E, Doran S, Kokotillo A, Campbell S, Villa-Roel C, Rowe BH. Ketorolac in the treatment of acute migraine: a systematic review. Headache. 2013 Feb. 53(2):277-87. [Medline].
[Guideline] American Academy of Neurology. Practice parameter: appropriate use of ergotamine tartrate and dihydroergotamine in the treatment of migraine and status migrainosus (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1995 Mar. 45(3 Pt 1):585-7. [Medline].
Dowson AJ, Mathew NT, Pascual J. Review of clinical trials using early acute intervention with oral triptans for migraine management. Int J Clin Pract. 2006 Jun. 60(6):698-706. [Medline].
Barclay L. FDA Approves Transdermal Patch for Migraine. Available at http://www.medscape.com/viewarticle/777871. Accessed: January 29, 2013.
Cady RK, McAllister PJ, Spierings EL, Messina J, Carothers J, Djupesland PG, et al. A randomized, double-blind, placebo-controlled study of breath powered nasal delivery of sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study). Headache. 2015 Jan. 55 (1):88-100. [Medline].
Anderson, P. FDA Okays Onzetra Xsail Intranasal Migraine Medication. Medscape Medical News. Available at http://www.medscape.com/viewarticle/857970. January 29, 2016; Accessed: February 3, 2016.
Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4. 297(13):1443-54. [Medline].
Kostic MA, Gutierrez FJ, Rieg TS, Moore TS, Gendron RT. A prospective, randomized trial of intravenous prochlorperazine versus subcutaneous sumatriptan in acute migraine therapy in the emergency department. Ann Emerg Med. 2010 Jul. 56(1):1-6. [Medline].
Belotti EA, Taddeo I, Ragazzi M, Pifferini R, Simonetti GD, Bianchetti MG, et al. Chronic impact of topiramate on acid-base balance and potassium in childhood. Eur J Paediatr Neurol. 2010 Sep. 14(5):445-8. [Medline].
Misra UK, Kalita J, Bhoi SK. Allodynia in Migraine: Clinical Observation and Role of Prophylactic Therapy. Clin J Pain. 2013 Jan 16. [Medline].
[Guideline] Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E. 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. 2012 Apr 24. 78(17):1346-53. [Medline]. [Full Text].
Krymchantowski AV, Jevoux C, Moreira PF. An open pilot study assessing the benefits of quetiapine for the prevention of migraine refractory to the combination of atenolol, nortriptyline, and flunarizine. Pain Med. 2010 Jan. 11(1):48-52. [Medline].
Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004 Feb 25. 291(8):965-73. [Medline].
Mathew NT, Rapoport A, Saper J, Magnus L, Klapper J, Ramadan N, et al. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001 Feb. 41(2):119-28. [Medline].
Jeffrey S. FDA Okays First Drug for Migraine Prevention in Adolescents. Medscape Medical News. Mar 28 2014. [Full Text].
Topamax (topiramate) prescribing information [package insert]. Titusville, NJ.: Janssen Pharmaceuticals, Inc., Titusville, NJ. March 2014. 2014. Available at [Full Text].
Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003 Jan 1. 289(1):65-9. [Medline].
Schrader H, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study. BMJ. 2001 Jan 6. 322(7277):19-22. [Medline]. [Full Text].
Conway S, Delplanche C, Crowder J, Rothrock J. Botox therapy for refractory chronic migraine. Headache. 2005 Apr. 45(4):355-7. [Medline].
Schulte-Mattler WJ, Martinez-Castrillo JC. Botulinum toxin therapy of migraine and tension-type headache: comparing different botulinum toxin preparations. Eur J Neurol. 2006 Feb. 13 Suppl 1:51-4. [Medline].
Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010 Jun. 50(6):921-36. [Medline].
[Guideline] Simpson David M., Hallett Mark, Ashman Eric J., et al. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. April 18, 2016. [Full Text].
Jeffrey S. FDA Approves First Device to Prevent Migraine. Medscape Medical News. Available at http://www.medscape.com/viewarticle/821810. Accessed: March 17, 2014.
Edwards KR, Norton J, Behnke M. Comparison of intravenous valproate versus intramuscular dihydroergotamine and metoclopramide for acute treatment of migraine headache. Headache. 2001 Nov-Dec. 41(10):976-80. [Medline].
Alstadhaug KB, Odeh F, Salvesen R, Bekkelund SI. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology. 2010 Oct 26. 75(17):1527-32. [Medline].
De Leo V, Scolaro V, Musacchio MC, Di Sabatino A, Morgante G, Cianci A. Combined oral contraceptives in women with menstrual migraine without aura. Fertil Steril. 2011 Oct. 96(4):917-20. [Medline].
von Peter S, Ting W, Scrivani S, Korkin E, Okvat H, Gross M, et al. Survey on the use of complementary and alternative medicine among patients with headache syndromes. Cephalalgia. 2002 Jun. 22(5):395-400. [Medline].
Lipton RB, Göbel H, Einhäupl KM, Wilks K, Mauskop A. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004 Dec 28. 63(12):2240-4. [Medline].
Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology. 1998 Feb. 50(2):466-70. [Medline].
Sándor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005 Feb 22. 64(4):713-5. [Medline].
Slater SK, Nelson TD, Kabbouche MA, LeCates SL, Horn P, Segers A, et al. A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia. 2011 Jun. 31(8):897-905. [Medline].
Ferrari MD, Odink J, Tapparelli C, Van Kempen GM, Pennings EJ, Bruyn GW. Serotonin metabolism in migraine. Neurology. 1989 Sep. 39(9):1239-42. [Medline].
Arnadottir TS, Sigurdardottir AK. Is craniosacral therapy effective for migraine? Tested with HIT-6 Questionnaire. Complement Ther Clin Pract. 2013 Feb. 19(1):11-4. [Medline].
John PJ, Sharma N, Sharma CM, Kankane A. Effectiveness of yoga therapy in the treatment of migraine without aura: a randomized controlled trial. Headache. 2007 May. 47(5):654-61. [Medline].
Linde K, Vickers A, Hondras M, ter Riet G, Thormählen J, Berman B, et al. Systematic reviews of complementary therapies - an annotated bibliography. Part 1: acupuncture. BMC Complement Altern Med. 2001. 1:3. [Medline]. [Full Text].
Walker JE. QEEG-guided neurofeedback for recurrent migraine headaches. Clin EEG Neurosci. 2011 Jan. 42(1):59-61. [Medline].
Nestoriuc Y, Martin A. Efficacy of biofeedback for migraine: a meta-analysis. Pain. 2007 Mar. 128(1-2):111-27. [Medline].
Rosenzweig S, Greeson JM, Reibel DK, Green JS, Jasser SA, Beasley D. Mindfulness-based stress reduction for chronic pain conditions: variation in treatment outcomes and role of home meditation practice. J Psychosom Res. 2010 Jan. 68(1):29-36. [Medline].
Dirnberger F, Becker K. Surgical treatment of migraine headaches by corrugator muscle resection. Plast Reconstr Surg. 2004 Sep 1. 114(3):652-7; discussion 658-9. [Medline].
Rockett FC, de Oliveira VR, Castro K, Chaves ML, Perla Ada S, Perry ID. Dietary aspects of migraine trigger factors. Nutr Rev. 2012 Jun. 70(6):337-56. [Medline].
Tepper SJ. Complementary and alternative treatments for childhood headaches. Curr Pain Headache Rep. 2008 Oct. 12(5):379-83. [Medline].
Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia. 2011 Oct. 31(14):1428-38. [Medline]. [Full Text].
Busch V, Gaul C. Exercise in migraine therapy--is there any evidence for efficacy? A critical review. Headache. 2008 Jun. 48(6):890-9. [Medline].
Durham PL, Garrett FG. Neurological mechanisms of migraine: potential of the gap-junction modulator tonabersat in prevention of migraine. Cephalalgia. 2009 Nov. 29 Suppl 2:1-6. [Medline].
Farinelli I, De Filippis S, Coloprisco G, Missori S, Martelletti P. Future drugs for migraine. Intern Emerg Med. 2009 Oct. 4(5):367-73. [Medline].
[Guideline] Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, et al. 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. 2012 Apr 24. 78 (17):1337-45. [Medline].
[Guideline] Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E, et al. 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. 2012 Apr 24. 78 (17):1346-53. [Medline].
Orr SL, Friedman BW, Christie S, Minen MT, Bamford C, Kelley NE, et al. Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache. 2016 Jun. 56 (6):911-40. [Medline].
[Guideline] Silberstein S. The Management of Adults With Acute Migraine in the Emergency Department. Headache. 2016 Jun. 56 (6):907-8. [Medline].
Imitrex (sumatriptan succinate) injection. Prescribing Information. GlaxoSmithKline. February 2010. [Full Text].
Imitrex (sumatriptan succinate) tablets. Prescribing Information. GlaxoSmithKline. February 2010. [Full Text].
Imitrex (sumatriptan) Nasal Spray. Prescribing Information. GlaxoSmithKline. February 2010. [Full Text].
Leonardi M, Mathers C. Global burden of migraine in the Year 2000: summary of methods and data sources. World Health Organization. Available at http://www.who.int/healthinfo/statistics/bod_migraine.pdf. Accessed: March 27, 2013.
Lowry F. Chronic Migraine Responds to OnabotulinumtoxinA. Medscape Medical News. Available at http://www.medscape.com/viewarticle/825002. Accessed: May 19, 2014.
Minson CT, Green DJ. Measures of vascular reactivity: prognostic crystal ball or Pandora's box?. J Appl Physiol. 2008 Aug. 105(2):398-9. [Medline].
[Guideline] Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E. 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. 2012 Apr 24. 78(17):1337-45. [Medline]. [Full Text].
|Ergotamine||Sumatriptan (SC,NS)||Dopamine antagonists|
|DHE=Dihydroergotamine; NSAIDs=nonsteroidal anti-inflammatory drugs|
|First line||High efficacy||Beta blockers
|MAOIs = monoamine oxidase inhibitors|
|Depression||Tricyclic antidepressants, SSRIs|
|Underweight||Tricyclic antidepressants (nortriptyline, protriptyline)|
|Epilepsy||Valproic acid, topiramate|
|SSRIs = selective serotonin reuptake inhibitors|