A migraine is a neurologic disorder typically lasting 4-72 hours, with concomitant phonophobia/photophobia, nausea, and vomiting. Migraines are a primary headache disorder and can be subcategorized based on whether aura is or is not present. Aura can separately be defined as a singular or constellation of precedent symptomatology including but not limited to focal neurological dysfunction, fatigue, neck pain, and/or repetitive yawning.
Criteria for Migraine without aura diagnosis as per the International Classification of Headache Disorders (ICHD-3):
- At least five attacks fulfilling criteria B-D
- Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated).
- Headache has at least two of the following:
- Unilateral location
- Pulsating quality
- Moderate or severe pain intensity
- Aggravation by or causing avoidance of routine physical activity
- During the headache, at least one of following occurs:
- Nausea and/or vomiting
- Photophobia and phonophobia
- Not better accounted for by another ICHD-3 diagnosis.1
ICHD-3 outlines diagnostic criteria for the additional types and subtypes of Migraine, with Migraine with aura being the other major type.
The true etiology of migraine headache is not fully understood, but is thought to involve neuronal hyperexcitability and activation of the trigeminovascular pathway.2 Some theories are discussed below. Molecular genetics is an area of current research exploring potential familial and hereditary associations in migraine risk.
The Global Burden of Disease Survey 2019 designates headache disorders as the 3rd leading cause of years lived with disability (YLD) worldwide, with the majority of headaches classified as migraine.3,32,33
Migraine is a highly prevalent medical condition, affecting 1 out of 7 Americans annually.
Female to Male ratio of 2:1.
There appears to be a disproportionate distribution in vulnerable populations (unemployed, low socioeconomic status, and uninsured).4
Nonmodifiable Risk Factors: age, gender, socioeconomic status, head injury.
Modifiable Risk Factors: obesity, medication overuse, stress, caffeine, sleep, attack frequency5
Vascular Risk Factors: increased levels of C reactive protein, interleukins, tumor necrosis factor-alpha, cerebrovascular accident, coronary heart disease, increased body weight, hypertension, hypercholesterolemia, insulin resistance, and elevated homocysteine.6
In a 2007 prospective analysis by Wöber et. al., menstruation as a risk factor was shown to have the greatest impact on occurrence and persistence of migraine headaches.7
Neurovascular theory: This theory held that vasoconstriction and vasodilation was the causative agent in migraine. A later attempt to better explain the pain and aura aspects of migraine, unanswered by the neurovascular theory, produced the neurogenic inflammation theory. This added that the trigeminovascular system, which innervates cranial meningeal blood vessels, may be irritated and thus release neuropeptides and several other inflammatory agents leading to eventual edema, inflammation, and pain.
Cortical spreading depression: This is described as a propagating disruption of ionic gradients across the cerebral cortex. Consensus among researchers appears to be that cortical spreading depression is the cause of visual aura in migraine. However, it is unclear whether it is the direct cause of pain in migraine sufferers.8
Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)
Life time course of migraine headache is extremely varied, with a percentage of patients transitioning from an episodic migraine pattern (<15 headache d/mo) to a chronic migraine pattern (≥15 headache d/mo).9
Specific Secondary or Associated Conditions and Complications
Active migraine with aura is associated with an increased risk for major cardiovascular disease in men and women.10,11
Migraine is associated with an increased risk for developing myocardial infarction in men.11
Migraine with aura in midlife is associated with cerebellar infarct-like lesions on magnetic resonance imaging (MRI) in later life, particularly in women.12
Essentials of Assessment
Onset: What age did they start? During menstrual period? Do they appear when you’re awake or asleep?
Location: Unilateral? Diffuse? Always in the same place? Pain extending to the neck?
Duration: Typically, can last anywhere between 4 to 72 hours
Frequency: How often do they occur? How many days per week/month?
Intensity: Moderate to severe?
Associated symptoms: Nausea, vomiting, photophobia, phonophobia? Less commonly: lightheadedness, paresthesias, confusion.
Aggravating or precipitating factors: Menstruation? Environmental triggers? Physical activity? Sleep disturbances? Stress? Bruxism?
Alleviating factors: Dark, quiet room? Sleep?
Diet/Nutrition: Food triggers? Caffeine intake; ETOH use.
Past medical history: Traumatic brain injury/concussion? Stroke?
Recent procedures: i.e., lumbar puncture, rhinoscopy, tooth extraction
Aura: gradual onset. visual symptoms are most common, but can include motor and sensory findings. Examples:
- Scintillating scotoma – pathognomonic of migraine.
- Visual field deficits
- Tunnel vision
- Speech disturbance
Prodrome: can occur days before onset. Examples: constipation/diarrhea, photophobia, irritability, malaise, depression, food craving, exhilaration, fluid retention, and anxiety.
Red flags of headaches as emergencies include:
- First headache of its kind.
- Most severe headache that patient has ever had.
- Headache represents a distinct change in the usual recurrent pattern.
- Sudden onset of headache may indicate rupture of aneurysms/arteriovenous malformation (AVM) and bleeding from mass.
- Worsening with Valsalva raises concern for increased intracranial pressure from mass or bleeding.
- Concurrent systemic complaint may be associated with brain abscess, meningitis, arteritis, or collagen vascular disease.
- Physical exam should be normal between episodes.
- Check vitals – elevated BP could be manifestation of end organ damage. Fever as sign of active infection/inflammation.
- It is necessary to rule out other more serious illnesses if any of the following are present: fever, hypertension (but may occur due to pain), weight loss, jaw claudication, and bradycardia.
Head, eye, ear, nose, and throat examination: check fundi and ears for signs of head trauma. Papilledema raises concern of increased intracranial pressure from a more serious problem. During an acute attack, patient may have Horner’s syndrome or injected conjunctivae.
Temporomandibular joint dysfunction (TMJ): crepitus/clicking/maltracking with opening/closing of mouth.
- Check for stiff neck as a sign of meningeal irritation – Brudziński’s sign
- A negative Spurling’s maneuver does not rule out radicular involvement.
- Cranial Nerve testing, Motor/Sensory exam, DTR’s, Babinski, finger to nose testing, mental status.
- Focal findings, confusion, or seizure may indicate other more serious neurologic problems such as mass lesions, AVM, and collagen vascular disease.
Migraine headaches may lead to a reduced ability to function at work and in the home, participate in academic pursuits, or interact in social and leisure activities.13 It is important for physicians to understand the scope of this disorder, including its associated medical, psychological and functional impact, in order to choose the appropriate therapeutic intervention.14
As stated in American Headache Society’s 2020 systematic review and evidence based guideline, neuroimaging is not typically recommended for patients with migraine who have normal neurologic exam and are without atypical features or red flag signs/symptoms (Grade A recommendation).
However, neuroimaging may be considered for presumed migraine in the following circumstances (Grade C recommendation):
- Change in clinical features
- Increasing frequency or severity
- First or worst migraine
- Posttraumatic headache
- Unusual, prolonged, or persistent aura
- Aura without headache
- Migraine with brainstem aura, confusion, or motor manifestations (hemiplegic migraine)
- Late-life migraine accompaniments
- Side-locked headache15
Supplemental Assessment Tools
- Migraine Disability Assessment Questionnaire (MIDAS)
- Migraine Severity Scale
- Migraine Disability Inventory
- Migraine Specific Questionnaire
- Headache Impact Test- 6 (HIT- 6)
- Headache Impact Questionnaire
- Headache Disability Inventory
Early Predictions of Outcomes
The Headache Impact Test-6 is an assessment tool to measure the impact of migraine headaches on the lives of each patient. Risk factors pertaining to a greater severity of impact include: higher MSS scores, higher average headache pain severity, and depression.16
Although controversy exists as to the correlation between environmental influence and migraines, some potential triggers include: stress, diet and nutrition (including preservatives, caffeine, nitrites, and artificial sweeteners), medications, sleep disturbance, and history of head trauma.17
Social Role and Social Support System
- More than 85% of women and 82% of men with severe migraine had some headache-related disability.
- Men required 3.8 bed rest days per year, whereas women required 5.6 bed rest days per year.
- The loss of productive time from migraine in the US workforce is more than $13 billion per year, most of which is in the form of reduced productivity while at work.18
Rehabilitation Management and Treatments
Goals in Treatment of Acute Migraine:
- Treat attacks rapidly.
- Restore patient’s ability to function.
- Optimize patient’s self-care.
- Minimize use of rescue medications.
- Minimize adverse events.
Treatment Strategy for Migraine Headache Should Be Divided into Abortive and Preventative Therapies.
According to the US Headache Consortium, recommended medications for abortive therapy include Acetaminophen/Aspirin/Caffeine, Aspirin, Ibuprofen, and Naproxen Sodium. Migraine specific medications including Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan are recommended if the migraine is severe and unresponsive to the above medications. Also to be considered are DHE, DHE/antiemetic, Prochlorperazine, and Butorphanol for those who cannot tolerate a PO medication. 19
In accordance with the American Academy of Neurology’s 2012 evidence based treatment guidelines, the following medications had Level A evidence (Established as predictive for a condition in a specified population) for reduction of frequency and severity of migraines, as well as for prevention of attack: Antiepileptics including: Divalproex Sodium, Sodium Valproate, Topiramate; Beta-blockers including: Metoprolol, Propranolol, and Timolol. Frovatriptan was additionally found to be effective (Level A) for prevention of menstrual migraine in the female population.20
In considering NSAIDs and alternative medications for prevention of migraine in adults, the American Academy of Neurology’s 2012 guidelines recommend Petasites (Butterbur) as the only Level A treatment effective for migraine prevention and reduction of frequency and severity of migraine attacks. Level B recommendations [probably effective (1 Class I or 2 Class II studies)] include Fenoprofen, Ibuprofen, Ketoprofen, Naproxen, Naproxen sodium, MIG-99 (feverfew), Magnesium, Riboflavin, and subcutaneous histamine.21
Botulinum Toxin A injection: The findings from 2 large 24-week multicenter randomized controlled trials (PREEMPT 1 AND PREEMPT 2) suggest that Botulinum Toxin type A is effective for the treatment of chronic migraine.22,23 FDA approved its use in 2010 for patients with intractable, chronic migraine that has failed to respond to at least 3 conventional preventive medications. The 2016 American Academy of Neurology Practice Guidelines recommend that Botulinum Toxin A be offered as treatment option for chronic migraine sufferers to increase the number of “headache-free” days (Level A) and reduce headache impact on quality of life (Level B).24
Novel targets have emerged and represent progress in the available abortive and preventive pharmacologic migraine treatments. CGRP monocolonal antibodies (mAbs), with their first FDA approval in 2018, are used for the preventive treatment of migraine headaches.29 CGRP receptor antagonists (gepants), with their first FDA approval in 2019, are used for the acute treatment of migraine attacks and are being studied for their benefit in prevention.30 5-HT1F receptor agonists (ditans), with their first FDA approval in 2020, are used for the acute treatment of migraine attacks.31
The first FDA approved device for the treatment of migraine pain gained approval in 2013.25 Examples of noninvasive neuromodulation devices with FDA clearance include transcutaneous supraorbital neurostimulaton (tSNS), single-pulse transcranial magnetic stimulation (sTMS), non-invasive vagus nerve stimulaton (nVNS), and remote electrical neuromodulation (REN).27,28
More research is being conducted to establish an evidence base for nonpharmacologic treatment options. Some of these options include lifestyle modifications, integrative health interventions (acupuncture, relaxation therapy, stress management), behavioral health approaches (cognitive behavioral therapy, biofeedback, mindfulness based stress reduction), exercise based approaches, non-invasive and invasive neuromodulation, and interventional procedures.
At Different Disease Stages
The American Migraine Prevalence and Prevention Study recommends treatment if:
- 6 or more headache days per month
- 4 or more headache days with impairment
- 3 or more headache days with severe impairment
Still, prophylaxis may be considered even when those exact criteria are not met dependent on individual circumstances. 26
Coordination of Care
If clinical findings warrant, consultation to neurology or neurosurgery should be considered.
- Advancements in therapeutic targets has led to promising new treatments for migraine headaches, including CGRP monocolonal antibodies (mAbs), CGRP receptor antagonists (gepants), and 5HT1F receptor agonists (ditans).
- The FDA approved the first noninvasive neuromodulation device for prevention of migraine headaches in 2013. Since that time, multiple devices have gained clearance, including devices to treat migraine in adults and adolescents.
Physicians should remember to rule out red flag issues that requires emergent management such as subdural hematoma, subarachnoid hemorrhage, AVM, brain mass, infection, meningitis, arteritis, and collagen vascular disease.
Remember that in cases of refractory migraine, rehabilitation measures for pain control such as use of ice and relaxation, biofeedback, stress management, avoidance of aggravating factors, and patient education is important.
Cutting Edge/ Emerging and Unique Concepts and Practice
Genetic studies are highlighting specific gene targets for potential areas of treatment. Although preliminary research is promising, a larger evidence base is necessary.
Gaps in the Evidence- Based Knowledge
Debate remains on the precise cause of pain during a migraine as well as the true etiology of the condition. Genetic studies have provided a complicated picture with many implicated genes, but significant research is required to better understand the migraine process.
- Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211.
- Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015;35(17):6619-6629.
- GBD (2019) Diseases and injuries collaborators (2020) global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet 396:1204–1222
- Burch RC, Loder S, Loder E, Smitherman TA. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache: The Journal of Head and Face Pain. 2015;55(1):21-34.
- Smitherman T, Rebecca B, Huma S, and Loder, E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: A review of statistics from national surveillance studies. Headache: The Journal of Head and Face Pain. 2013: 53.3; 427-36.
- Hamed, SA. The vascular risk associations with migraine: Relation to migraine susceptibility and progression. Atherosclerosis 2009: 205.1; 15-22.
- Wöber C, Brannath W, Schmidt K, Kapitan M, Rudel E, Wessely P, and Wöber-Bingöl Ç. Prospective analysis of factors related to migraine attacks: The PAMINA Study. Cephalalgia 2007:27.4; 304-14.
- Gasparini C, Sutherland H, and Griffiths L. Studies on the pathophysiology and genetic basis of migraine. CG Current Genomics 2013: 14.5; 300-15.
- Lucchesi C, Baldacci F, Cafalli M, Dini E, Giampietri L, Siciliano G, and Gori S. Fatigue, sleep–wake pattern, depressive and anxiety symptoms and body-mass index: analysis in a sample of episodic and chronic migraine patients. Neurological Sciences Neurol Sci
- Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006; 296: 283-291.
- Gudmundsson LS, Scher AI, Aspelund T, et al. Migraine with aura and risk of cardiovascular and all cause mortality in men and women: prospective cohort study. BMJ. 2010; 341: c3966.
- Scher, Ann I., et al. Migraine headache in middle age and late-life brain infarcts. Jama 2009: 301.24; 2563-2570.
- Brandes, Jan Lewis. Migraine and functional impairment. CNS drugs 2009: 23.12; 1039-1045.
- Weatherall, Mark W. The diagnosis and treatment of chronic migraine. Therapeutic advances in chronic disease 2015: 2040622315579627.
- Evans RW, Burch RC, Frishberg BM, et al. Neuroimaging for migraine: the american headache society systematic review and evidence‐based guideline. Headache: The Journal of Head and Face Pain. 2020;60(2):318-336.
- Buse D, Manack A, Serrano D, et al. Headache impact of chronic and episodic migraine: results from the American Migraine Prevalence and Prevention study. Headache: The Journal of Head and Face Pain 2012;52(1):3-17.
- Hoffmann J, Recober A. Migraine and triggers: post hoc ergo propter hoc? Curr Pain Headache Rep. 2013;17(10):370.
- 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; 84: 436-445.
- Snow, Vincenza. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Annals of Internal Medicine Ann Intern Med 2002: 137.10; 840.
- Silberstein, S. D., 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: 78.17; 1337-1345.
- Holland S, Silberstein SD, Freitag F, 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;78(17):1346-1353.
- Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010; 30: 793-803.
- Diener HC, Dodick DW, Aurora SK, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010; 30: 804-814.
- Simpson, David M. et al. Practice guideline update summary: Botulinum Neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the guideline development subcommittee of the American Academy of Neurology. Neurology 2016: published ahead of print April 18, 2016 http://dx.doi.org/10.1212%2FWNL.0000000000002560
- Jeffrey S. FDA approves first device to treat migraine pain. Medscape Medical News. Published: December 13, 2013. Available at http://www.medscape.com/viewarticle/817831 Accessed: April 11, 2016.
- Estemalik E, Tepper S. Preventive treatment in migraine and the new US guidelines. Neuropsychiatr Dis Treat. 2013;9:709-720.
- Rapoport AM, Edvinsson L. Some aspects on the pathophysiology of migraine and a review of device therapies for migraine and cluster headache. Neurol Sci. 2019;40(S1):75-80.
- Halker Singh RB, Ailani J, Robbins MS. Neuromodulation for the acute and preventive therapy of migraine and cluster headache. Headache: The Journal of Head and Face Pain. 2019;59(S2):33-49.
- Dyer O. US approves first monoclonal antibody to prevent migraines. BMJ. Published online May 18, 2018:k2228.
- Tepper D. Gepants. Headache: The Journal of Head and Face Pain. 2020;60(5):1037-1039.
- Lasmiditan, first oral serotonin 5-ht1f receptor agonist or ditan, available for prescription. American Headache Society. Published: February 1, 2020. Available at https://americanheadachesociety.org/news/lasmiditan-prescription/
- Institute for Health Metrics and Evaluation (2020) Available at: http://www.healthdata.org/results/gbd_summaries/2019/headache-disorders-level-3-cause
- Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z. Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain. 2020;21(1):137, s10194-020-01208-0.
Original Version of the Topic
Yi-Wen Pu, MD, Amruta Ashtekar, MD. Migraine Headaches. 11/11/2011
Previous Revision(s) of the Topic
Jason Georgekutty, Bruno Subbarao, DO, Blessen C. Eapen, MD. Migraine Headaches. 9/15/2016
Udai Nanda, DO
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