Migraine Headaches

Author(s): Jason Georgekutty, Bruno Subbarao, DO, Blessen C. Eapen, MD

Originally published:11/11/2011

Last updated:09/15/2016



A migraine is a chronic neurologic disorder typically lasting 4-72 hours, with concomitant phono/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 diagnosis as per the International Classification of Headache Disorders (ICDH3):

  1. At least five attacks fulfilling criteria B-
  2. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated).
  3. Headache has at least two of the following:
    1. Unilateral location.
    2. Pulsating quality.
    3. Moderate or severe pain intensity
    4. Aggravation by or causing avoidance of routine physical activity
  4. During the headache at least one of following occurs:
    1. Nausea and/or vomiting.
    2. Photophobia and phonophobia.
  5. Not attributed to another d.1


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 2013 designates Migraine Headaches as the 6th leading cause of years lived with disability (YLD) worldwide.3

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


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



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


Intensity: Moderate to severe?

Associated symptoms: Nausea, vomiting, photophobia, phonophobia? Less commonly: lightheadedness, parasthesias, 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.

Family History


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:

  1. Scintillating scotoma – pathognomonic of migraine.
  2. Visual field deficits
  3. Tunnel vision
  4. Parasthesias
  5. 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:

  1. First headache of its kind.
  2. Most severe headache that patient has ever had.
  3. Headache represents a distinct change in the usual recurrent pattern.
    1. Sudden onset of headache may indicate rupture of aneurysms/arteriovenous malformation (AVM) and bleeding from mass.
    2. Worsening with Valsalva raises concern for increased intracranial pressure from mass or bleeding.
    3. Concurrent systemic complaint may be associated with brain abscess, meningitis, arteritis, or collagen vascular disease.

Physical Examination

General physical:

  1. Physical exam should be normal between episodes.
  2. Check vitals – elevated BP could be manifestation of end organ damage.  Fever as sign of active infection/inflammation.
  3. 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.


  1. Check for stiff neck as a sign of meningeal irritation – Brudziński’s sign
  2. A negative Spurling’s maneuver does not rule out radicular involvement.


  1. Cranial Nerve testing, Motor/Sensory exam, DTR’s, Babinski, finger to nose testing, mental status.
  2. Focal findings, confusion, or seizure may indicate other more serious neurologic problems such as mass lesions, AVM, and collagen vascular disease.

Functional Assessment

Migraine headaches may lead to a reduced ability to work at home, participate in academic, 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


Neuroimaging is not typically recommended for patients with migraine and normal neurologic exam.

However, obtain imaging if:

  1. On clinical findings there is suspicion of a tumor: ex. Papilledema, focal neurological signs, or previous history of cancer
  2. There is any change in the usual migraine symptoms: ex: most severe headache, increased frequency, presence of fever, seizures, persistence without relief
  3. New onset in: greater than 50-year-old population, severely immunocompromised patient15

Supplemental Assessment Tools

  1. Migraine Disability Assessment Questionnaire (MIDAS)
  2. Migraine Severity Scale
  3. Migraine Disability Inventory
  4. Migraine Specific Questionnaire
  5. Headache Impact Test- 6 (HIT- 6)
  6. Headache Impact Questionnaire
  7. 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 depression16


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

  1. More than 85% of women and 82% of men with severe migraine had some headache-related disability.
  2. Men required 3.8 bed rest days per year, whereas women required 5.6 bed rest days per year.
  3. 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


Goals in Treatment of Acute Migraine:

  1. Treat attacks rapidly.
  2. Restore patient’s ability to function.
  3. Optimize patient’s self-care.
  4. Minimize use of rescue medications.
  5. 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

Nonpharmacologic Treatments

The Cerena Transcranial Magnetic Stimulator is the first device approved by the FDA to treat migraine pain in patients diagnosed with migraine with aura, and who are older than 18 years of age.25

Although more research is required to establish an evidence base for other nonpharmacological treatment options, cold packs, acupuncture, occipital nerve stimulator, sphenopalatine ganglion neurostimulation, biofeedback, cognitive-behavioral therapy, and relaxation techniques could be considered.

At Different Disease Stages

The American Migraine Prevalence and Prevention Study recommends treatment if:

  1. 6 or more headache days per month
  2. 4 or more headache days with impairment
  3. 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.

Emerging Interventions

  1. Acupuncture as a safe alternative treatment27
  2. Sphenopalatine ganglion neurostimulation as a treatment modality28,29
  3. The FDA approved the first device for prevention of migraine headaches in 2014.  It is a transcutaneous electrical stimulation device that stimulates the trigeminal nerve. It is indicated for patients 18 years of age and older.30

Practice “Pearls

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 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.


  1. Headache Classification Committee of the International Headache Society (IHS.) The International Classification of Headache Disorders, (beta version). Cephalalgia 2013:33.9; 629-808.
  2. Burstein, Rami, Rodrigo Noseda, and David Borsook. Migraine: multiple processes, complex pathophysiology. The Journal of Neuroscience 2015:35.17; 6619-6629.
  3. Vos, Theo, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet 2015:386.9995; 743-800.
  4. Burch, Rebecca C., et al. 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.
  5. 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.
  6. Hamed, SA. The vascular risk associations with migraine: Relation to migraine susceptibility and progression. Atherosclerosis 2009: 205.1; 15-22.
  7. 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.
  8. Gasparini C, Sutherland H, and Griffiths L. Studies on the pathophysiology and genetic basis of migraine. CG Current Genomics 2013: 14.5; 300-15.
  9. 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
  10. 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.
  11. 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.
  12. Scher, Ann I., et al. Migraine headache in middle age and late-life brain infarcts. Jama 2009: 301.24; 2563-2570.
  13. Brandes, Jan Lewis. Migraine and functional impairment. CNS drugs 2009: 23.12; 1039-1045.
  14. Weatherall, Mark W. The diagnosis and treatment of chronic migraine. Therapeutic advances in chronic disease 2015: 2040622315579627.
  15. 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.
  16. Buse, Dawn, Aubrey Manack, Daniel Serrano, Michael Reed, Sepideh Varon, Catherine Turkel, and Richard Lipton. 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.
  17. Hoffmann, Jan, and Ana Recober. Migraine and triggers: Post hoc ergo propter hoc? Current Pain and Headache Reports 2013: 17.10.
  18. 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.
  19. 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.
  20. 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.
  21. Holland, Silberstein, 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.
  22. 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.
  23. 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.
  24. 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).
  25. 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.
  26. Estemalik, Emad, and Tepper. Preventive treatment in migraine and the new US Guidelines. NDT Neuropsychiatric Disease and Treatment 2013: 709.
  27. Silva, Arnaldo Neves Da. Acupuncture for migraine prevention. Headache: The Journal of Head and Face Pain 2015: 55.3; 470-73.
  28. Khan, S, Schoenen J, and Ashina M. Sphenopalatine ganglion neuromodulation in migraine: What is the rationale? Cephalalgia 2013: 34.5; 382-91.
  29. Cady R, Joel S, Kent D, and Manley HR. A double-blind, placebo-controlled study of repetitive transnasal sphenopalatine ganglion blockade with Tx360 ® as acute treatment for chronic migraine. Headache: The Journal of Head and Face Pain 2014: 55.1; 101-16.
  30. Jeffrey S. FDA approves first device to prevent migraine. Medscape Medical News. Published March 11, 2014. Available at http://www.medscape.com/viewarticle/821810. Accessed: April 11, 2016.

Original Version of the Topic:

Yi-Wen Pu, MD, Amruta Ashtekar, MD. Migraine Headaches. Publication Date: 2011/11/11.

Author Disclosure

Jason Georgekutty, MD
Nothing to Disclose

Bruno Subbarao, DO
Nothing to Disclose

Blessen C. Eapen, MD
Nothing to Disclose

Related Articles