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 United States (1). 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.

Evidence suggests that migraine may frequently develop after mild traumatic brain injury (2, 3).

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 [eg, CGRP], which causes painful inflammation in cranial vessels and the dura mater).

Many potential migraine triggers have been identified; they include the following (1):

• 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.

Head trauma, neck pain, or temporomandibular joint dysfunction sometimes triggers or exacerbates migraine.

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 worsen during the first or second 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 (2). 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.

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 (eg, causing 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 that may resemble tension-type headache but are a forme fruste of migraine.

• History and physical examination

Diagnosis of migraine is based on characteristic symptoms and a normal physical examination, which includes a thorough neurologic examination.

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

• Pain that reaches peak intensity within a few seconds or less (thunderclap headache)

• Onset after age 50

• Headaches that increase in intensity or frequency for weeks or longer

• History of cancer (brain metastases) or an immunosuppressive disorder (eg, HIV infection)

• Fever, meningismus, altered mental status, or a combination

• Persistent focal neurologic deficits

• Papilledema

• A clear change in an established headache pattern

Patients with characteristic symptoms and no red flag findings do not require testing. Patients with red flag findings often require testing, 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 adults

• 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:

• Dissection of the carotid or vertebral artery

• Cerebral vasculitis

• Moyamoya disease

• CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)

• MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome

Migraine treatment may include the following approaches (1, 2):

• 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 (small-molecule calcitonin gene–related peptide [CGRP] receptor antagonists), or dihydroergotamine plus adopamine 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, triggers are often overdiagnosed and should be avoided in moderation; elimination of all possible triggers can be excessive and lead to unnecessary life restrictions.

Choice of medications used to treat acute migraine headache is based on frequency, duration, and severity of attacks. Analgesics, antiemetics, triptans, lasmiditan, gepants, or dihydroergotamine may be used (3). If patients wish to avoid medications or if medications have been ineffective, neuromodulatory treatments can sometimes be used for acute attacks and/or prevention.

Patients who frequently (eg, > 2 days/week) use medications to treat their acute migraine attacks (particularly analgesics that contain butalbital, triptans, ergotamine, or opioids) should be treated with preventive migraine drugs combined with a program for stopping overused analgesics.

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.

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. In a study from a U.S. database (the National Hospital Ambulatory Medical Care Survey and the National Health Interview Survey), migraine was the fifth most common reason for an emergency department visit and 40 percent of adults with migraine were unemployed and economically disadvantaged (1).

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 should be combined with a program for stopping overused analgesics. Choice of medication 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 patients with obesity or for patients who wish to avoid weight gain

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

• Gepants can be used for migraine prevention (atogepant, rimegepant)

Monoclonal antibodies and gepants that are used to prevent migraines block the activation of calcitonin gene-related peptide (CGRP), which can precipitate migraines (1).

Neuromodulatory treatments can also help. Transcutaneous supraorbital nerve stimulation, using a device applied to the forehead, can reduce the frequency of migraines (2). Transcranial magnetic stimulation, using 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.