Headache, Migraine

Essentials of Diagnosis

• Headache, usually pulsatile, lasting 4 to 72 hours

• Pain typically, but not always, unilateral

• May be accompanied by

  • Nausea

  • Vomiting

  • Photophobia

  • Phonophobia

• Pain is aggravated with routine physical activity

• Classically, an aura of transient neurologic symptoms (typically visual) may precede head pain

• Commonly, head pain occurs with no aura

General Considerations

• Pathophysiology of migraine probably relates to neuronal dysfunction in the trigeminal system resulting in release of vasoactive neuropeptides such as calcitonin gene-related peptide leading to neurogenic inflammation, sensitization, and headache

• Migraine aura is hypothesized to result from cortical spreading depression, a wave of neuronal and glial depolarization that moves slowly across the cerebral cortex corresponding to the clinical symptoms (ie, occipital cortex and visual aura)

Demographics

• Migraine often exhibits a complex, polygenic pattern of inheritance

• Sometimes, an autosomal dominant inheritance pattern is apparent, as in familial hemiplegic migraine (FHM), in which attacks of lateralized weakness represent the aura

Symptoms and Signs

Typical migraine

• May be lateralized or generalized

• May be dull or throbbing

• Sometimes associated with

  • Anorexia, nausea, vomiting

  • Photophobia, phonophobia, osmophobia

  • Cognitive impairment

  • Blurring of vision

• Usually builds up gradually and may last for several hours or longer

• Visual disturbances occur quite commonly and may consist of

  • Field defects

  • Luminous visual hallucinations, such as stars, sparks, unformed light flashes (photopsia), geometric patterns, or zigzags of light

  • Some combination of field defects and luminous hallucinations (scintillating scotomas)

• Migraine with aura may be a risk factor for stroke

• Other focal disturbances

  • Aphasia or numbness

  • Paresthesias

  • Clumsiness

  • Dysarthria

  • Dysequilibrium

  • Weakness in a circumscribed distribution

Common migraine

• Commonly bilateral and periorbital

• Visual disturbances and other focal neurologic deficits do not occur

Basilar artery migraine

• Blindness or disturbances throughout both visual fields are accompanied or followed by

  • Dysarthria

  • Dysequilibrium

  • Tinnitus

  • Perioral and distal paresthesias

• Blindness or visual disturbances sometimes followed by

  • Transient loss or impairment of consciousness or a confusional state

  • This, in turn, is followed by a throbbing (usually occipital) headache, often with nausea and vomiting

Ophthalmoplegic migraine

• Lateralized pain, often about the eye, is accompanied by

  • Nausea

  • Vomiting

  • Diplopia due to transient external ophthalmoplegia

• Due to third nerve palsy, sometimes with accompanying sixth nerve involvement, and may outlast the orbital pain by several days or even weeks

• Ophthalmic division of the fifth nerve has also been affected in some patients

Migraine equivalent

• In rare instances, the neurologic or somatic disturbance accompanying typical migrainous headaches becomes the sole manifestation of an attack without headaches occurring ("migraine equivalent")

Familial hemiplegic migraine (FHM)

• Attacks of lateralized weakness represent aura

Sporadic hemiplegic migraine

• No other family members are affected

Differential Diagnosis

• Other causes of headache

• Cluster headache

• Brain tumor

• Temporal (giant cell) arteritis

• Sinusitis

• Subarachnoid hemorrhage

• Pseudotumor cerebri

• Transient ischemic attack

Imaging Studies

• Changes in brainstem regions involved in sensory modulation may be seen, suggesting that migraine relates to failure of normal sensory processing

Diagnostic Procedures

• Inquire about precipitating and exacerbating factors

• Inquire about family history

Medications

• A simple analgesic (eg, aspirin) taken immediately often provides relief

• However, treatment with extracranial vasoconstrictors or other drugs is sometimes necessary

• Cafergot, a combination of ergotamine tartrate (1 mg) and caffeine (100 mg), is often particularly helpful

  • One or two tablets are taken at the onset of headache or warning symptoms, followed by one tablet every 30 min

  • If necessary, up to six tablets per attack can be taken but no more than 10 tablets per week

  • Ergotamine-containing preparations should be avoided

    • During pregnancy

    • When cardiovascular disease or risk factors are present

    • In patients taking potent CYP 3A4 inhibitors (clarithromycin, telithromycin, itraconazole, ketoconazole, nefazodone, atanazavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir)

• Sumatriptan is a rapidly effective agent for aborting attacks when given subcutaneously by an autoinjection device (4–6 mg once subcutaneously, may repeat once after 2 hours if needed; maximum dose 12 mg/24 h)

• Zolmitriptan is effective for acute treatment

  • Optimal initial oral dose is 5 mg

  • Relief usually occurs within 1 hour

  • May repeat once after 2 hours if needed

  • Maximum dose is 10 mg/24h

  • Can also be taken by nasal spray

    • 5 mg in one nostril once; may repeat once after 2 hours

    • Maximum dose is 10 mg/24h

• Other triptans are available

  • Rizatriptan (5–10 mg orally at onset, may repeat every 2 hours twice (maximum dose 30 mg/24 h)

  • Naratriptan (1–2.5 mg orally at onset, may repeat once after 4 hours (maximum dose 5 mg/24 h)

  • Almotriptan (6.25–12.5 mg orally at onset, may repeat dose once after 2 hours (maximum dose 25 mg/24 h)

  • Eletriptan (20–40 mg orally at onset, may repeat after 2 hours once (maximum dose 80 mg/24 h)

  • Frovatriptan (2.5 mg orally at onset, may repeat after 2 hours once) has longer half-life than eletriptan; helps patients with prolonged attacks (maximum dose 7.5 mg/24 h) or attacks provoked by menstrual periods

• Triptans

  • Should be avoided in pregnancy and in patients with risk factors for stroke

  • Are contraindicated in patients with coronary or peripheral vascular disease

  • May cause nausea or vomiting

• Lasmiditan

  • Dosage: 50–200 mg taken once at headache onset; no more than one dose in 24 hours

  • Lacks the vasoconstrictive properties of triptans

  • Can be given safely to patients with cardiovascular risk factors

  • Side effects: dizziness and somnolence

  • Patients should not drive within 8 hours of administration

• Opioid analgesics are sometimes required when other therapies fail

• Intravenous propofol in subanesthetic doses may help in intractable cases

• When oral medication fails to help due to impaired absorption or vomiting, the following regimens may be used

  • Cafergot given rectally (one-half to one suppository containing 2 mg of ergotamine)

  • Dihydroergotamine mesylate (0.5–1 mg intravenously or 1–2 mg subcutaneously or intramuscularly)

  • Prochlorperazine administered rectally (25 mg suppository) or intravenously or intramuscularly (5–10 mg), or orally (5–10 mg every 6–8 h)

  • Intravenous metoclopramide (10–20 mg) or chlorpromazine (25–50 mg) is useful in the emergency department setting

• Erenumab

  • FDA approved for the preventive treatment of migraine in adults

  • Dosage:

    • 70 mg subcutaneously once a month

    • Some patients may benefit from 140 mg subcutaneously once a month

    • A dose of 140 mg should be administered as 2 consecutive subcutaneous injections of 70 mg each

Therapeutic Procedures

• Management of migraine consists of avoidance of any precipitating factors, together with prophylactic or symptomatic pharmacologic treatment if necessary

• During acute attacks, many patients find it helpful to rest in a quiet, darkened room until symptoms subside

• Transcranial magnetic stimulation

  • Effective in aborting migraine with aura in one sham-controlled trial

  • A handheld device is approved in the United States and European Union but is costly

• Some other neurostimulation techniques look promising, including single-pulse transcranial magnetic stimulation, vagus nerve stimulators, and implantable occipital nerve stimulation, but critical appraisal is necessary

• In chronic migraine (at least 15 days per month with headaches lasting 4 hours per day or longer)

  • Acupuncture is as effective as prophylactic pharmacologic treatment

  • Botulinum toxin type A reduces headache frequency

Complications

• Serotonin syndrome (potentially fatal agitation, confusion, fever, incoordination, vomiting, tachycardia, alterations in blood pressure) may develop when triptans are used with selective serotonin or serotonin/norepinephrine reuptake inhibitors

• Very rarely, the patient may be left with a permanent neurologic deficit following a migrainous attack

Prevention

• Prophylactic treatment may be necessary if migraine headaches occur more frequently than two or three times a month (Table 24–1)

• Several drugs may have to be tried in turn before the headaches are brought under control

• Once a drug has been found to help, it should be continued for several months

• If the patient remains headache free, the dose can then be tapered and the drug eventually withdrawn

• Botulinum toxin type A, injected into specific head and neck muscles, may prevent migraines

• Acupuncture is as effective as prophylactic drug treatment with more rapid pain relief and fewer side effects

• Some neurostimulation techniques look promising, including occipital nerve stimulation