ESSENTIALS OF DIAGNOSIS
Headache, usually pulsatile, lasting 4–72 hours.
Pain is typically, but not always, unilateral.
Nausea, vomiting, photophobia, and phonophobia are common accompaniments.
Pain is aggravated with routine physical activity.
An aura of transient neurologic symptoms (commonly visual) may precede head pain.
Commonly, head pain occurs with no aura.
The 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). 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.
Typical migrainous headache is a lateralized throbbing headache that occurs episodically following its onset in adolescence or early adult life. In many cases, the headaches do not conform to this pattern, although their associated features and response to antimigrainous preparations nevertheless suggest a similar basis. In this broader sense, migrainous headaches may be lateralized or generalized, may be dull or throbbing, and are sometimes associated with anorexia, nausea, vomiting, photophobia, phonophobia, osmophobia, cognitive impairment, and blurring of vision. They usually build up gradually and last several hours or longer. Focal disturbances of neurologic function (migraine aura) may precede or accompany the headaches. Visual disturbances occur commonly and may consist of field defects (scotoma); of luminous visual hallucinations such as stars, sparks, unformed light flashes (photopsia), geometric patterns, or zigzags of light; or of some combination of field defects and luminous hallucinations (scintillating scotomas). Other focal disturbances such as aphasia or numbness, paresthesias, clumsiness, dysarthria, dysequilibrium, or weakness in a circumscribed distribution may also occur.
In rare instances, the neurologic or somatic disturbance accompanying typical migrainous headaches becomes the sole manifestation of an attack (“migraine equivalent”). Very rarely, the patient may be left with a permanent neurologic deficit following a migrainous attack, and migraine with aura may be a risk factor for stroke.
Patients often give a family history of migraine. Attacks may be triggered by emotional or physical stress, lack or excess of sleep, missed meals, specific foods (eg, chocolate), alcoholic beverages, bright lights, loud noise, menstruation, or use of oral contraceptives.
An uncommon variant is basilar artery migraine, in which blindness or visual disturbances throughout both visual fields are accompanied or followed by dysarthria, dysequilibrium, tinnitus, and perioral and distal paresthesias and are sometimes followed by transient loss or impairment of consciousness or by a confusional state. This, in turn, is followed by a throbbing (usually occipital) headache, often with nausea and vomiting.
In ophthalmoplegic migraine, lateralized pain—often about the eye—is accompanied by nausea, vomiting, and diplopia due to transient external ophthalmoplegia. The ophthalmoplegia is due to third nerve palsy, sometimes with accompanying sixth nerve involvement, and may outlast the orbital pain by several days or even weeks. The ophthalmic division of the fifth nerve has also been affected in some patients. Ophthalmoplegic migraine is rare and a diagnosis of exclusion; more common causes of a painful ophthalmoplegia are internal carotid artery aneurysms and diabetes.
Management of migraine consists of avoidance of any precipitating factors, together with prophylactic or symptomatic pharmacologic treatment if necessary.
During acute attacks, rest in a quiet, darkened room may be helpful until symptoms subside. A simple analgesic (eg, aspirin, acetaminophen, ibuprofen, or naproxen) taken immediately often provides relief, but prescription medication is sometimes necessary. To prevent medication overuse, use of simple analgesics should be limited to 15 days or less per month, and combination analgesics should be limited to no more than 10 days per month.
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 minutes, if necessary, up to six tablets per attack and no more than 10 days per month. Cafergot given rectally (one-half to one suppository containing 2 mg of ergotamine) or dihydroergotamine mesylate (0.5–1 mg intravenously or 1–2 mg subcutaneously or intramuscularly) may be useful when vomiting precludes use of oral medications. Ergotamine-containing preparations should be avoided during pregnancy, in patients with cardiovascular disease or its risk factors, and in patients taking potent CYP 3A4 inhibitors.
Triptans are 5-HT1b/1d receptor agonists that inhibit release of vasoactive neuropeptides. 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). Nasal and oral preparations are available but may be less effective due to slower absorption. Zolmitriptan is available in oral and nasal formulations. The dose is 5 mg orally or in one nostril once; this may be repeated once after 2 hours. The maximum dose for both formulations is 10 mg/24 h. Other triptans are available, including 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]); frovatriptan (2.5 mg orally at onset, may repeat after 2 hours once [maximum dose 7.5 mg/24]); and eletriptan (20–40 mg orally at onset; may repeat after 2 hours once [maximum dose 80 mg/24 h]). Eletriptan is useful for immediate therapy and frovatriptan, which has a longer half-life, may be worthwhile for patients with prolonged attacks or attacks provoked by menstrual periods. Patients often experience greater benefit when the triptan is combined with naproxen (500 mg orally).
Triptans may cause nausea and vomiting. They should probably be avoided in women who are pregnant, and in patients with hemiplegic or basilar migraine, a history of stroke or transient ischemic attack (TIA), or uncontrolled hypertension. In patients whose hypertension is controlled, triptans are commonly used safely, although caution is advised. Triptans are contraindicated in patients with coronary or peripheral vascular disease and Prinzmetal angina.
Lasmiditan (50–200 mg taken once at headache onset; no more than one dose in 24 hours) is a 5-HT1F receptor agonist approved for use in the United States that lacks the vasoconstrictive properties of triptans and can be given safely to patients with cardiovascular risk factors. Dizziness and somnolence are common side effects, and patients should not drive within 8 hours of administration.
Prochlorperazine is effective and may be administered rectally (25 mg suppository), intravenously or intramuscularly (5–10 mg), or orally (5–10 mg). Intravenous metoclopramide (10–20 mg) or chlorpromazine (25–50 mg) is also particularly useful in the emergency department setting. Various butalbital-containing combination oral analgesics risk overuse and dependence and should only be used as a last resort. Opioid analgesics should be avoided because of high rates of rebound headache and the tendency to develop medication overuse headache.
Sham-controlled trials show that single-pulse transcranial magnetic stimulation aborts migraine with aura, and noninvasive vagus nerve stimulation, transcutaneous trigeminal nerve stimulation, and remote electrical stimulation applied to the upper arm abort migraine with or without aura. Transcranial magnetic stimulation is contraindicated in patients with epilepsy.
Preventive treatment may be necessary if migraine headaches occur more frequently than two or three times a month or significant disability is associated with attacks. Avoidance of triggers and maintenance of homeostasis with regular sleep, meals, and hydration should not be neglected; a headache diary may be useful to identify triggers. Some more common agents used for prophylaxis are listed in Table 24–1. The medication chosen first will vary with the individual patient, depending on factors such as comorbid obesity, depression, anxiety, hypertension, and patient preference. Several medications may have to be tried in turn before headaches are brought under control. Once a medication has been found to help, it should be continued for several months. If the patient remains headache-free, the dose may be tapered and the medication eventually withdrawn. Transcutaneous supraorbital neurostimulation reduced the number of migraine days per month in a sham-controlled randomized trial and is approved in the United States. 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, and botulinum toxin type A reduces headache frequency. Certain neurostimulation techniques look promising as preventive treatment as well as having a role in treatment of acute attacks. These include single-pulse transcranial magnetic stimulation, vagus nerve stimulators, and implantable occipital nerve stimulation, but critical appraisal is necessary.
Table 24–1.Pharmacologic prophylaxis of migraine (listed in alphabetical order within classes). ||Download (.pdf) Table 24–1. Pharmacologic prophylaxis of migraine (listed in alphabetical order within classes).
|Medication ||Usual Adult Oral Daily Dose ||Selected Side Effects and Comments |
|Topiramate ||100 mg (divided twice daily) ||Somnolence, nausea, dyspepsia, irritability, dizziness, ataxia, nystagmus, diplopia, glaucoma, renal calculi, weight loss, hypohidrosis, hyperthermia. |
|Valproic acid2,3 ||500–1000 mg (divided twice daily) ||Nausea, vomiting, diarrhea, drowsiness, alopecia, weight gain, hepatotoxicity, thrombocytopenia, tremor, pancreatitis. |
|Candesartan3 ||8–32 mg once daily ||Dizziness, cough, diarrhea, fatigue. |
|Guanfacine ||1 mg once daily ||Dry mouth, somnolence, dizziness, constipation, erectile dysfunction. |
|Propranolol4 ||80–240 mg (divided twice to four times daily) ||Fatigue, dizziness, hypotension, bradycardia, depression, insomnia, nausea, vomiting, constipation. |
|Verapamil5 ||120–240 mg (divided three times daily) ||Headache, hypotension, flushing, edema, constipation. May aggravate atrioventricular nodal heart block and heart failure. |
|Amitriptyline7 ||10–150 mg at bedtime ||Sedation, dry mouth, constipation, weight gain, blurred vision, edema, hypotension, urinary retention. |
|Venlafaxine ||37.5–150 mg extended release once daily ||Nausea, somnolence, dry mouth, dizziness, diaphoresis, sexual dysfunction, anxiety, weight loss. |
|Monoclonal antibodies against calcitonin gene–related peptide |
|Erenumab ||70–140 mg subcutaneously once monthly ||Injection site reactions, constipation, muscle cramps, antibody development. |
|Fremanezumab ||225 mg subcutaneously once monthly ||Injection site reactions, antibody development. |
|Galcanezumab ||120 mg subcutaneously daily × 2 doses, followed by 120 mg monthly ||Injection site reactions, antibody development. |
|Acupuncture || ||More rapid pain relief and fewer side effects than pharmacologic treatment. |
|Botulinum toxin A ||Intramuscular injection ||Injection site reaction, hypersensitivity, muscle weakness. |
|Riboflavin ||400 mg once daily ||Yellow-orange discoloration of urine. |
|Transcutaneous supraorbital neurostimulation ||20 minutes daily ||Transient paresthesia at site of stimulation. |