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Migraine

By

Stephen D. Silberstein

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Aug 2021| Content last modified Aug 2021
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Topic Resources

Migraine is an episodic primary headache disorder. Symptoms typically last 4 to 72 hours and may be severe. Pain is often unilateral, throbbing, worse with exertion, and accompanied by symptoms such as nausea and sensitivity to light, sound, or odors. Auras occur in about 25% of patients, usually just before but sometimes after the headache. Diagnosis is clinical. Treatment is with triptans, dihydroergotamine, antiemetics, and analgesics. Preventive regimens include lifestyle modifications (eg, of sleeping habits or diet) and drugs (eg, beta-blockers, amitriptyline, topiramate, divalproex, monoclonal antibodies).

Epidemiology of Migraine

Migraine is the most common cause of recurrent moderate to severe headache; 1-year prevalence is 18% for women and 6% for men in the US. Migraine most commonly begins during puberty or young adulthood, waxing and waning in frequency and severity over the ensuing years; it often diminishes after age 50. Studies show familial aggregation of migraine.

Pathophysiology of Migraine

Migraine is thought to be a neurovascular pain syndrome with altered central neuronal processing (activation of brain stem nuclei, cortical hyperexcitability, and spreading cortical depression) and involvement of the trigeminovascular system (triggering neuropeptide release, which causes painful inflammation in cranial vessels and the dura mater).

Many potential migraine triggers have been identified; they include the following:

  • Drinking red wine

  • Skipping meals

  • Excessive afferent stimuli (eg, flashing lights, strong odors)

  • Weather changes

  • Sleep deprivation

  • Stress

  • Hormonal factors, particularly menstruation

  • Certain foods

Food triggers vary from person to person.

Fluctuating estrogen levels are a potent migraine trigger. Many women have onset of migraine at menarche, severe attacks during menstruation (menstrual migraine), and worsening during menopause. For most women, migraines remit during pregnancy (but sometimes they worsen during the 1st or 2nd trimester); they worsen after childbirth, when estrogen levels decrease rapidly.

Oral contraceptives and other hormone therapy occasionally trigger or worsen migraine and have been associated with stroke in women who have migraine with aura.

Familial hemiplegic migraine, a rare subtype of migraine, is associated with genetic defects on chromosomes 1, 2, and 19. The role of genes in the more common forms of migraine is under study. In some families, the migraine phenotype varies considerably, causing primarily headache in some family members, vertigo in others, and hemiplegia or an aura in others. This finding suggests that migraine may actually be a more generalized disorder and not just a headache disorder.

Symptoms and Signs of Migraine

Often, a prodrome (a sensation that a migraine is beginning) heralds attacks. The prodrome may include mood changes, neck pain, food cravings, loss of appetite, nausea, or a combination.

An aura precedes attacks in about 25% of patients. Auras are temporary neurologic disturbances that can affect sensation, balance, muscle coordination, speech, or vision; they last minutes to an hour. The aura may persist after headache onset. Most commonly, auras involve visual symptoms (fortification spectra—eg, binocular flashes, arcs of scintillating lights, bright zigzags, scotomata). Paresthesias and numbness (typically starting in one hand and marching to the ipsilateral arm and face), speech disturbances, and transient brain stem dysfunction (causing, for example, ataxia, confusion, or even obtundation) are less common than visual auras. Some patients have an aura with little or no headache.

Headache varies from moderate to severe, and attacks last from 4 hours to several days, typically resolving with sleep. The pain is often unilateral but may be bilateral, most often in a frontotemporal distribution, and is typically described as pulsating or throbbing.

Migraine is more than a headache. Associated symptoms such as nausea (and occasionally vomiting), photophobia, sonophobia, and osmophobia are prominent. Patients report difficulty concentrating during attacks. Routine physical activity usually aggravates migraine headache; this effect, plus the photophobia and sonophobia, encourages most patients to lie in a dark, quiet room during attacks. Severe attacks can be incapacitating, disrupting family and work life.

Attacks vary significantly in frequency and severity. Many patients have several types of headache, including milder attacks without nausea or photophobia; they may resemble tension-type headache Tension-Type Headache Tension-type headache causes mild generalized pain (usually viselike) without the incapacity, nausea, or photophobia associated with migraine. (See also Approach to the Patient With Headache... read more but are a forme fruste of migraine.

Chronic migraine

Patients with episodic migraine can develop chronic migraine. These patients have headaches 15 days/month. This headache disorder used to be called combination or mixed headache because it had features of migraine and tension-type headache. These headaches often develop in patients who overuse drugs for acute treatment of headaches.

Other symptoms

Other, rare forms of migraine can cause other symptoms:

  • Basilar artery migraine causes combinations of vertigo, ataxia, visual field loss, sensory disturbances, focal weakness, and altered level of consciousness.

  • Hemiplegic migraine, which may be sporadic or familial, causes unilateral weakness.

Diagnosis of Migraine

  • Clinical evaluation

Red flag findings that suggest an alternate diagnosis (even in patients known to have migraine) include the following:

Patients with characteristic symptoms and no red flag findings do not require testing. Patients with red flag findings often require testing Testing Headache is pain in any part of the head, including the scalp, face (including the orbitotemporal area), and interior of the head. Headache is one of the most common reasons patients seek medical... read more , including MRI and sometimes lumbar puncture.

Common diagnostic errors include the following:

  • Not realizing that migraine often causes bilateral pain and is not always described as throbbing

  • Misdiagnosing migraine as sinus headache or eye strain because autonomic and visual symptoms of migraine are absent

  • Assuming that any headache in patients known to have migraine represents another migraine attack (a thunderclap headache or a change in the previous headache pattern may indicate a new, potentially serious disorder)

  • Mistaking migraine with aura for a transient ischemic attack, especially when the aura occurs without headache, in older people

  • Diagnosing a thunderclap headache as migraine because a triptan relieves it (a triptan can also relieve a headache due to subarachnoid hemorrhage)

Several unusual disorders can mimic migraine with aura:

Prognosis of Migraine

For some patients, migraine is an infrequent, tolerable inconvenience. For others, it is a devastating disorder resulting in frequent periods of incapacity, loss of productivity, and severely impaired quality of life.

Treatment of Migraine

  • Elimination of obvious triggers

  • Relaxation techniques,yoga, or behavioral interventions

  • For mild headaches, acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs)

  • For acute attacks, triptans, lasmiditan, gepants, or dihydroergotamine plus a dopamine antagonist antiemetic

  • Neuromodulatory devices for acute treatment and prevention

A thorough explanation of the disorder helps patients understand that although migraine cannot be cured, it can be controlled, enabling them to better participate in treatment.

Patients are urged to keep a written headache diary to document the number and timing of attacks, possible triggers, and response to treatment. Identified triggers are eliminated when possible. However, elimination of triggers can be overdone.

Clinicians sometimes recommend behavioral interventions (biofeedback, stress management, psychotherapy) to manage migraine, especially when stress is a major trigger or when analgesics are being overused.

Yoga can reduce headache frequency and intensity; it enhances vagal tone and decreases sympathetic drive, thus improving cardiac autonomic balance. Relaxation techniques can reduce sympathetic nervous system activity, ease muscle tension, and alter brain wave activity.

Acute attacks

NSAIDs or acetaminophen is used to treat mild to moderate migraine attacks.

If these drugs are ineffective, clinicians should consider using triptans or dihydroergotamine. A good response to dihydroergotamine or a triptan should not be interpreted as diagnostic for migraine because these drugs may relieve headache due to subarachnoid hemorrhage or other structural abnormalities.

If mild attacks worsen or if attacks are severe from the onset, triptans or dihydroergotamine can be used. When nausea is prominent, combining a triptan with an antiemetic at the onset of attacks is effective.

Triptans are selective serotonin 1B,1D receptor agonists. They are not analgesic per se but specifically block the release of neuropeptides that trigger migraine pain. Triptans are most effective when taken at the onset of attacks. They are available in oral, intranasal, and subcutaneous forms (see table Drugs for Migraine and Cluster Headaches Drugs for Cluster Headaches Cluster headaches cause excruciating, unilateral periorbital or temporal pain, with ipsilateral autonomic symptoms (ptosis, lacrimation, rhinorrhea, nasal congestion). Diagnosis is clinical... read more ); subcutaneous forms are more effective but have more adverse effects. Overuse of triptans can also lead to medication overuse headache Medication Overuse Headache Medication overuse headache is a chronic headache that occurs > 15 days/month in patients who regularly overuse headache drugs for > 3 months. It usually develops in people with migraine or... read more . Triptans and dihydroergotamine can cause coronary artery constriction and are thus contraindicated in patients with coronary artery disease or uncontrolled hypertension; these drugs must be used with caution in older patients and in patients with vascular risk factors. Ubrogepant and rimegepant, which are gepants (small-molecule calcitonin gene–related peptide [CGRP] receptor antagonists), are alternatives.

Lasmiditan (a new selective serotonin [5-HT] 1F receptor agonist) or a gepant, such as ubrogepant or rimegepant, can be used when triptans or dihydroergotamine are contraindicated because of cardiovascular disorders. Lasmiditan, which has a much greater affinity for serotonin 1F receptors than for 1B receptors, has no cardiovascular contraindications. (Triptans cause vasoconstriction by activating 5-HT1B receptors.) As of this time, gepants have no cardiovascular precautions or contraindications and have no serious cardiovascular and gastrointestinal effects.

An antiemetic (eg, metoclopramide, prochlorperazine) alone may be used to relieve mild or moderate attacks. Prochlorperazine suppositories (25 mg) or tablets (10 mg) are an option for patients who cannot tolerate triptans and other vasoconstrictors.

Strong evidence supports use of neuromodulatory devices for acute attacks and prevention of migraine headaches.

Intractable attacks

IV fluids (eg, 1 to 2 L of 0.9% normal saline solution) can help relieve headache and increase a sense of well-being, especially in patients who are dehydrated from vomiting.

IV dihydroergotamine with a dopamine antagonist antiemetic (eg, metoclopramide 10 mg IV, prochlorperazine 5 to 10 mg IV) helps abort very severe, persistent attacks. Dihydroergotamine is also available in a subcutaneous form and as a nasal spray. A pulmonary-delivery formulation is being developed.

Opioids should be used as a last resort (rescue drug) for severe headache when other measures are ineffective.

Chronic migraines

The same drugs used to prevent episodic migraine, including monoclonal antibodies that block CGRP, are used to treat chronic migraine. Also, supporting evidence is strong for onabotulinumtoxinA and, topiramate.

Evidence supports use of neurostimulation for acute treatment and prevention of chronic migraine headaches. Noninvasive options include supraorbital stimulation, vagus nerve stimulation, and single-pulse transcranial magnetic stimulation and remote electrical stimulation.

Table
icon

Neuromodulatory treatments

Neuromodulatory treatments, which affect brain activity through electrical currents or magnetic fields, can be noninvasive, using commercially available devices. They can also be used to treat attacks and to prevent them.

Noninvasive transcranial magnetic stimulation, using a handheld device applied to the back of the head may relieve acute migraine (3 Treatment references Migraine is an episodic primary headache disorder. Symptoms typically last 4 to 72 hours and may be severe. Pain is often unilateral, throbbing, worse with exertion, and accompanied by symptoms... read more ). A device that uses an armband to deliver a nonpainful electrical skin stimulus (called remote electrical neuromodulation) can relieve acute migraine pain. A handheld device that delivers noninvasive vagus nerve stimulation Vagus nerve stimulation A seizure is an abnormal, unregulated electrical discharge that occurs within the brain’s cortical gray matter and transiently interrupts normal brain function. A seizure typically causes altered... read more is also effective.

Trigeminal nerve stimulation, with a device applied to the forehead, can be used in patients who are ≥ 18 to treat acute migraine attacks (with or without an aura) or to reduce the frequency of attacks in some patients.

Noninvasive neuromodulatory devices have no significant adverse effects. Invasive treatments tend to be available only at specialized centers and have greater risks than noninvasive treatments.

Treatment references

  • 1. Marmura MJ, Silberstein SD, Schwedt TJ: The acute treatment of migraine in adults: The American Headache Society evidence assessment of migraine pharmacotherapies. Headache 55 (1):3–20, 2015.

  • 2. Miller S, Sinclair AJ, Davies B, Matharu M: Neurostimulation in the treatment of primary headaches. Pract Neurol 16 (5):362–375, 2016. doi: 10.1136/practneurol-2015-001298

  • 3. 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 9:373–380, 2010. doi: 10.1016/S1474-4422(10)70054-5

Prevention of Migraine

Daily preventive therapy is warranted when frequent migraines interfere with activity despite acute treatment. Some experts consider onabotulinumtoxinA the drug of choice.

For patients who use analgesics frequently (eg, > 2 days/week), particularly those with medication overuse headache, preventive drugs (see table Drugs for Migraine and Cluster Headaches Drugs for Cluster Headaches Cluster headaches cause excruciating, unilateral periorbital or temporal pain, with ipsilateral autonomic symptoms (ptosis, lacrimation, rhinorrhea, nasal congestion). Diagnosis is clinical... read more ) should be combined with a program for stopping overused analgesics. Choice of drug can be guided by coexisting disorders, as for the following:

  • A bedtime dose of amitriptyline for patients with insomnia

  • A beta-blocker for patients with anxiety or coronary artery disease

  • Topiramate, which can induce weight loss, for obese patients or for patients who wish to avoid weight gain

  • A monoclonal antibody (eg, erenumab, fremanezumab, galcanezumab) if other drugs are ineffective

  • Gepants can be used for acute attacks (ubrogepant, rimegepant) and prevention (atogepant, rimegepant) of migraine

Monoclonal antibodies that are used to prevent migraines block the activation of calcitonin gene-related peptide (CGRP), which can precipitate migraines (1 Treatment references Migraine is an episodic primary headache disorder. Symptoms typically last 4 to 72 hours and may be severe. Pain is often unilateral, throbbing, worse with exertion, and accompanied by symptoms... read more ).

Neuromodulatory treatments can also help. Transcutaneous supraorbital nerve stimulation, using a device applied to the forehead, can reduce the frequency of migraines (2 Treatment references Migraine is an episodic primary headache disorder. Symptoms typically last 4 to 72 hours and may be severe. Pain is often unilateral, throbbing, worse with exertion, and accompanied by symptoms... read more ). Transcranial magnetic stimulation, using by a device applied to the back of the skull, is indicated for the acute and prophylactic treatment of migraine headache in adolescents (≥ 12) and adults.

Treatment references

  • 1. Jain S, Silberstein SD: Invited commentary on preventive anti-migraine therapy (PAMT). Curr Treat Options Neurol 21 (4):14, 2019. doi:10.1007/s11940-019-0555-4.

  • 2. Schoenen J, Vandersmissen B, Jeangette S, et al: Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial. Neurol 80 (8):697–704, 2013. doi: https://doi.org/10.1212/WNL.0b013e3182825055

Key Points

  • Migraine is a common primary headache disorder.

  • Symptoms can include throbbing unilateral or bilateral pain, nausea, sensitivity to sensory stimuli (eg, light, sounds, smells), nonspecific prodromal symptoms, and temporary neurologic symptoms that precede headache (auras).

  • Diagnose migraine based on clinical findings; if patients have red flag findings, imaging and other tests are often needed.

  • Involve patients in their care, including avoiding triggers and using biofeedback, stress management, and psychotherapy as appropriate.

  • Treat most headaches with analgesics, IV dihydroergotamine, or triptans.

  • If attacks are frequent and interfere with activities, use preventive therapy (eg, monoclonal antibodies that block calcitonin gene-related peptide [CGRP], amitriptyline, a beta-blocker, a gepant, topiramate, divalproex), onabotulinumtoxinA, or sometimes neuromodulatory treatments.

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