Jaclyn Laine, DO

Ann Pakalnis, MD

DESCRIPTION

Migraine is an episodic primary headache disorder characterized by at least 5 episodes lasting 4–72 hours. Patients experience throbbing, moderate-to-severe pain which may be unilateral in location. Complaints of nausea, vomiting, photophobia, and phonophobia are common. Migraine aura manifests as characteristic reversible, focal neurologic symptoms. This will gradually develop from 5 to 20 minutes, but should last less than 1 hour.

• Migraine classification according to the International Headache Society IHS ICHD-II includes these migraine variants:
  • Migraine without aura
  • Migraine with aura
    • Typical aura with migraine
    • Typical aura with non-migraine headache
    • Typical aura without headache
    • Familial/sporadic hemiplegic migraine
    • Basilar migraine
  • Retinal migraine
  • Chronic migraine headache ≥15 days/month, no medication overuse
  • Medication overuse occurring in migraine:
    • Headache present ≥15 days/month
    • Regular overuse for >3 months

EPIDEMIOLOGY

Incidence

• 20–29-year-old population most at risk to develop migraine.
• Occurs more often in males prior to puberty, more common in females after menarche.

Prevalence

• Occurs in 12% of the US population affecting 17% women and 6% of men.
• The World Health Organization (WHO) estimates a worldwide prevalence of current migraine of 10% and a lifetime prevalence of 14%.
• Female-to-male ratio 2.8:1 at puberty and 3.5:1 at 40 years old.
• Lower among African Americans and Asian Americans than whites.

RISK FACTORS

Migraine family history, highest risk if first-degree relative with migraine with aura.

Pregnancy Considerations

• Migraine improves for half of women during pregnancy.
• Low estradiol levels trigger migraine during menstruation and high levels may be protective during pregnancy.
• Migraine during pregnancy increases the risk of stroke, thrombosis, and other vascular diseases.

Genetics

• Migraine develops from a combination of polygenic and environmental factors.
• Hemiplegic migraine—50% sporadic.
• Familial hemiplegic migraine (FHM1) – autosomal dominant mapped to the CACNA1 gene coding for voltage-gated P/Q calcium channel on chromosome 19.
• FHM2 is associated with the gene ATP1A2 on chromosome 1 encoding for the alpha 2 subunit of the Na⁺/K⁺ pump.

GENERAL PREVENTION

Maintain a regular sleep schedule, avoid triggers, do not skip meals, maintain adequate hydration, regular exercise.

PATHOPHYSIOLOGY

• Migraine is a neurovascular headache, involving a cortical spreading depression of activity in migraine with aura. There is an abnormal afferent activation of the trigeminocervical complex on dural blood vessels, associated with vasodilation and pain signal.
• Serotonin receptors (5HT) in the trigeminal sensory neurons aid regulating neuropeptide release, producing neurogenic inflammation and secondary vessel dilation.

ETIOLOGY

Combination of genetic predisposition and environmental factors contributes to development.

COMMONLY ASSOCIATED CONDITIONS

Depression, anxiety, ischemic stroke, irritable bowel syndrome, epilepsy, hypertension.

HISTORY

To distinguish migraine from other headache disorders consider:

• Gradual onset throbbing pain, more often unilateral although bilateral location is common
• Associated nausea, vomiting, lightheadedness, and blurred vision
• Photophobia, phonophobia and pain aggravated by activity
• Spreading sensory/motor symptoms between locations on body over minutes

PHYSICAL EXAM

Normal neurologic and fundus exam.

DIAGNOSTIC TESTS AND INTERPRETATION

Lab

Initial Lab Tests

No specific tests are indicated routinely.

Follow-Up & Special Considerations

Additional testing may be needed to exclude secondary headache disorders.

Imaging

Initial Approach

Imaging is not needed in patients with non-focal exam, with characteristic symptoms and normal exam (4)[B].

Follow-Up & Special Considerations

• Brain imaging is recommended:
  • Change in headache pattern (4)[C]
  • Abnormal or changed neurologic exam (4)[B]
  • Atypical aura or duration longer than 60 minutes (4)[C]
• White-matter abnormalities are more common in migraineurs. Subclinical posterior circulation infarcts are more common in migraine with aura.

Diagnostic Procedures/Other

Lumbar puncture to measure opening pressure and exclude vascular, inflammatory, and infectious etiologies.

Pathological Findings

No abnormal findings.

DIFFERENTIAL DIAGNOSIS

Tension-type headache, cluster headache, temporomandibular joint dysfunction, trigeminal neuralgia, vasculitis, tumor, infection, idiopathic intracranial hypertension, arteriovenous malformation, arterial dissection, venous sinus thrombosis.

MEDICATION

First Line

Abortive

NSAIDs

• Naproxen sodium 1,100 mg/day, effective in menstrual migraine (4)[A]
• Ibuprofen (4)[A]

Combination analgesics

• ASA, caffeine, acetaminophen (4)[A]

Triptans

• Sumatriptan 50 mg, 100 mg oral, nasal spray, subcutaneous injection (4)[A]
• Rizatriptan, zolmitriptan, faster acting
• Naratriptan, frovatriptan, longer half life
• Treximet^® (sumatriptan 85 mg/naproxen 500 mg) (4)[A], triptans contraindicated in vascular disease, basilar and hemiplegic migraine

Prophylaxis

Antiepileptics

• Divalproex 500–1,500 mg/day, weight gain, hair loss, tremor, liver dysfunction (4)[A]
• Topiramate 50–200 mg/day, mental slowness, paresthesias, kidney stones (4)[C]

Antihypertensives

• Propranolol 80–240 mg/day, use caution with depression and asthma (3)[A]
• Timolol 20–30 mg/day (3)[A]

Tricyclic antidepressants

• Amitriptyline 30–150 mg/day, can cause arrhythmia, drowsiness, anticholinergic effects (3)[A]
• Nortriptyline, better tolerated than amitriptyline (3)[C]

Second Line

Abortive

Combination treatment

• Butalbital/ASA/caffeine/codeine, caution with overuse and rebound (4)[B]

Ergot derivatives

• Ergotamine/caffeine (3)[B]
• Dihydroergotamine, nasal spray, contraindicated in peripheral or coronary artery disease and uncontrolled hypertension (3)[A]

Prophylaxis

Calcium channel blockers

• Verapamil 240 mg/day, constipation (3)[B]

Selective serotonin reuptake inhibitor

• Fluoxetine 20–40 mg/day, insomnia, fatigue, tremor (3)[B]

Other

• Cyproheptadine, used more in pediatric migraine, can cause weight gain (3)[C]
• Butterbur 100–150 mg/day, reflux and burping

Nausea associated with migraine

• Prochlorperazine (2)[B]
• Chlorpromazine (2)[B]

Treatment in pregnancy

Acute attack:

• Acetaminophen (preg B) (4)[B]
• Prochlorperazine (preg C) (4)[B]
• Prednisone (preg B) refractory cases (4)[B]

Prophylaxis: Reserved for refractory cases

• Magnesium (preg B) 400–600 mg/day (3)[B]
• Riboflavin (vitamin B2) (preg B) up to 400 mg/day (3)[B]
• Propranolol (preg C) <160 mg/day

ADDITIONAL TREATMENT

General Measures

Indications for prophylaxis: 4 or more headaches per month, abortive therapy fails or used more than twice per week, headache lasting more than 24 hours, symptoms causing significant disability.

Issues for Referral

Neurosurgery for possible surgical intervention and neuro-ophthalmology for concerning visual field testing or fundus exam.

Additional Therapies

Cognitive behavioral therapy, physical therapy, relaxation therapy.

COMPLEMENTARY AND ALTERNATIVE THERAPIES

Biofeedback, massage, acupuncture.

SURGERY/OTHER PROCEDURES

Onabotulinum toxin (Botox type A) – FDA-approved treatment for chronic migraine.

IN-PATIENT CONSIDERATIONS

Initial Stabilization

Ensure patient environment is quiet, dark, with little disruption.

Admission Criteria

Intractable headache that fails to respond to appropriate outpatient or emergency department measures, failed outpatient detoxification, effective treatment of dehydration due to intractable vomiting (1)[C].

Nursing

Education for: Dietary management, stress management, exercise programs.

Discharge Criteria

Significant improvement of pain level and associated nausea and vomiting, detoxification, and transition to alternative prophylaxis.

FOLLOW-UP RECOMMENDATIONS

Patients should keep a headache journal for accurate account of headaches.

DIET

• Adequate hydration, avoid triggers: Chocolate, alcohol, aspartame, monosodium glutamate, and tyramine-containing foods.
• Caffeine: Wean off one cup per week for chronic migraineurs.

PATIENT EDUCATION

Appropriate timing in self-administered abortive treatment, reinforcing lifestyle changes.

PROGNOSIS

Migraine is a chronic condition, but frequency and severity decreases with age.

COMPLICATIONS

• Migrainous infarction may occur as a serious complication of migraine. This risk is highest in patients with migraine with aura, are female, smokers, and with estrogen use.
• Status migrainous, persistent aura without infarction, migraine-triggered seizure.

• Sheftell FD, Bigal ME. Medication overuse headache. Headache continuum. Philadelphia, PA: Lippincott Williams, and Wilkins, 2006;2(6):153–169.
• Silberstein SD, Olesen J, Bousser M-G, et al. The international classification of headache disorders. 2nd ed. Cephalalgia 2004;24(suppl 1):1–160.

ICD9

• 346.00 Migraine with aura, without mention of intractable migraine without mention of status migrainosus
• 346.10 Migraine without aura, without mention of intractable migraine without mention of status migrainosus
• 346.90 Migraine, unspecified, without mention of intractable migraine without mention of status migrainosus

• Migraine is a neurovascular headache and development depends on both environmental and genetic factors.
• Ensure that secondary headache causes are ruled out.
• Treatment relies on changes in lifestyle, diet, and individualized abortive and prophylactic drug choices.

1. Freitag FG, Lake A, Lipton R, et al. Inpatient treatment of headache: an evidence based assessment. Headache 2004;44(4):342–360.
2. Matchar DB, Young WB, Rosenberg JH, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. US Headache Consortium. 2000. www.aan.com/professionals/practice/pdfs/gl0087.pdf.
3. Ramadan NM, Silberstein SD, Freitag FG, et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. US Headache Consortium. 2000. www.aan.com/professionals/practice/pdfs/gl0090.pdf.
4. Silberstein SD. Practice parameter: evidence based guideline for migraine headache: report of Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754.