Managing Migraine: Are You Up to Date?

Emerg Med 38(11):20-32, 2006

Our understanding of migraine headaches continues to evolve. Here’s the latest on the pathophysiology, evaluation, and acute treatment of this condition, which is frequently seen in emergency departments.

By David E. J. Bazzo, MD, and Geneen T. Gin, MD

A migraine is a constellation of symptoms, with headache typically being the most dominant and disabling. Migraine headaches affect 28 million Americans, approximately 18% of women and 6% of men. More than two thirds of migraineurs seek headache evaluation and treatment—many in emergency departments. Such patients pose both diagnostic and therapeutic challenges for their providers. Over the past 20 years, great advances in neuroimaging and a better understanding of migraine pathophysiology have given rise to the introduction of migraine-specific therapy.

This article will review migraine pathophysiology, diagnosis, and treatment. It will familiarize emergency physicians with indications for neuroimaging and acute migraine therapy.

NEUROVASCULAR EVENT

In the past, migraine was thought to be a vascular headache. The symptomatic aura was presumed to be caused by vasoconstriction, with headache resulting from reflexive vasodilation of the large cranial blood vessels. Neuroimaging studies, however, reveal that the migraine headache begins while the large vessels are still constricted, suggesting that it is a neurovascular phenomenon. Migraine symptoms stem from a miscommunication between the cerebral neurons that regulate pain reception and those that control vascular dilation and constriction.

The headache is believed to arise out of a complex interaction between cranial blood vessels, trigeminal innervation of these vessels and the meninges, and trigeminal reflex connections with cranial parasympathetic outflow. A wave of glial and neuronal depolarization moving across the cerebral cortex, known as cortical spreading depression, presumably triggers trigeminal activation, which is key to migraine development. In response, vasoactive peptides, such as substance P and calcitonin gene-related peptide, are released. The pain and the subsequent migraine result from vasodilation and inflammatory changes in the meninges.

four Phases of Migraine

The classic migraine consists of four phases: the prodrome, aura, mild headache, and moderate to severe headache. Not all migraineurs experience the four phases, however, and phases may vary from episode to episode even for a single patient.

The prodrome is characterized by diverse symptoms: fatigue, anxiety, mood changes, food cravings, nasal congestion, yawning, cold hands, and cognitive dysfunction. Up to 80% of migraineurs can identify the prodrome, which results from abnormal central neurologic impulses that precede the onset of the headache itself. Patients able to identify a prodrome may abort a migraine by taking prophylactic non-steroidal anti- inflammatory drugs (NSAIDs).

Auras follow the prodrome and precede the headache. They can last from 5 to 60 minutes and may be characterized by visual scotoma (sparkling lights or squiggly lines), partial loss of vision, or other brain involvement such as partial weakness, acute sense of smell, disequilibrium, or even altered consciousness.

The mild headache that follows the aura tends to be diffuse without significant associated symptoms. It may last anywhere from minutes to hours.

The moderate to severe headache phase is characterized by a throbbing head pain that is associated with nausea and sensory sensitivity. Typically, it is worsened by movement. Symptoms can last from 4 to 72 hours, with the average duration being 24 hours.

PRIMARY VERSUS SECONDARY HEADACHES

Headache diagnosis begins with classification. The classification system published by the International Headache Society (IHS) in 1988 and revised in 2004 first differentiates primary from secondary headaches. Primary headaches, which include tension, cluster, and migraine headaches, are benign and comprise the majority of headaches seen in most emergency departments. Secondary headaches are caused by an underlying disease or condition, such as infection, mass, or trauma.

The history and physical are important tools in distinguishing primary from secondary headaches and identifying red flags associated with the latter. The practitioner needs to consider headache history, symptoms, onset, location, quality of pain, medical problems, current drug use, and recent trauma. Any red flags associated with secondary headaches can be recalled easily with the mnemonic SNOOP.

Considerations in Taking a Patient History Headache history first headache worst headache headache frequency differences from past headaches Symptoms prior to onset during headache Onset sudden gradual ongoing Symptoms prior to onset during headache Location radiating localized diffuse Quality of pain soft tissue injury throbbing dull aching pressing sharp Medical problems past current Current drug use prescribed medications nonprescription medications recreational drugs herbal supplements Recent trauma medical procedure dental procedure injury

SNOOP Mnemonic for Red Flags Associated with Secondary Headaches Systemic symptoms or disease Neurologic signs or symptoms Onset sudden Onset before age 5 or after age 50 Pattern changes from prior headaches

Physical examination of the patient presenting with headache focuses on abnormalities identified in the history and includes a complete neurologic examination. In addition to assessing vital signs, cardiovascular function, and respiratory status, the physician performs fundoscopy and evaluates papillary response, mental status, level of consciousness, meningeal and cerebellar function, cranial nerves, muscle strength and tone, coordination, sensation, and deep tendon reflexes.

TWO DIAGNOSTIC APPROACHES

Traditionally, migraine diagnosis focuses on the frequency and intensity of such symptoms as nausea, photophobia, and aura. Based on IHS criteria for migraine, this approach is limited in that it allows many cases of migraine to be overlooked.

International Headache Society Criteria for Migraine Headache episodic recurrent lasting 4 to 72 hours with TWO of the following pain qualities: -unilateral -throbbing -worsened with motion or activity -moderate to severe intensity and ONE of the following symptoms: -nausea -vomiting -photophobia -phonophobia

For example, the classic migraine is said to be unilateral and accompanied by pulsatile, throbbing pain as well as nausea and vomiting. In fact, while most migraineurs experience some nausea, only 30% report vomiting. Pain is reportedly bilateral in 41% of migraines and nonpulsatile in 50% of migraines. Although aura is thought to be the hallmark of migraine headaches, only about 20% of migraineurs experience aura.

An alternative diagnostic approach is based on symptom pattern and impact. Several screening tools are available to help emergency physicians diagnose migraines on these grounds, including the ID Migraine, Migraine Dis-ability Assess-ment (MIDAS), Headache Impact 6 (HIT-6), and Brief Headache Screen (BHS).

ID Migraine. This three-item screening tool has been found to be valid and reliable in identifying migraineurs. The presence of two out of the three symptoms included in this questionnaire (disability, photophobia, and nausea) is 93% predictive of migraine in emergency departments.

MIDAS. Through the use of five questions, MIDAS enables the physician to determine the amount of time headache has taken the patient away from work, school, household upkeep, leisure time, and social activities over the past three months and, on that basis, to assess its impact on quality of life. The MIDAS questionnaire could be used reliably in an emergency department to hasten migraine treatment. (MIDAS is available online at: www.midas-migraine.net/edu/question/Default.asp.)

HIT-6. A six-item questionnaire, HIT-6 addresses headache severity, impact on daily activities, related disability (the need to lie down), related fatigue, resulting frustration or irritation, and impact on ability to concentrate. It has demonstrated accuracy for migraine diagnosis in 89% of patients with headache. (HIT-6 is available online at: www.headachetest.com/HIT6/PDFS/English.pdf.)

BHS. Not only does the BHS screen for migraine and other headache syndromes, but for drug rebound headache as well. Different versions of the BHS, containing anywhere from three to six questions, have been created, but the version adopted by the American Academy of Neurology includes four questions.

American Academy of Neurology Brief Headache Screen How often do you get severe headaches (that is, headaches that make it difficult to function without treatment?) How often do you get other (milder) headaches? How often do you take headache relievers or pain pills? Has there been any recent change in your headaches?

In one validation study, the first question, which establishes the presence of disabling headache, correctly identified 93% of patients with episodic migraine and 78% of patients with chronic migraine. Fewer than 2% of migraineurs were not identified by this criterion. Any severe episodic headache, therefore, should be considered a migraine.

The second and third questions in the BHS, which inquire about the frequency of milder headaches and the use of analgesics, are useful in identifying patients who overuse medication (for example, those who use acute, abortive headache medications more than three times a week) and those who have daily headaches. The fourth question, which deals with recent changes in headache pattern, may reveal secondary causes of headache. A patient with a stable pattern for six months or more usually has a primary headache disorder.

The presence of symptoms with menstruation, in association with certain foods or environmental factors, improvement with sleep, family history of migraines, and history of motion sickness, vertigo, and osmophobia are reassuring for the diagnosis of a primary migraine.

challenging Differential diagnosis

Diagnosing migraine headaches can be challenging. For starters, no single set of criteria is considered confirmatory. Further complicating matters, migraine and the other types of headache included in the differential diagnosis have overlapping symptoms. There are, however, some key distinctions.

Cluster headache. Occurring in only 0.2% of the population, the cluster headache is the least prevalent primary headache. It can be distinguished from the migraine and tension headache by its circadian and circannual nature and by its short duration of symptoms. Patients with cluster headaches experience severe and rapid onset of unilateral, orbital pain accompanied by ipsilateral nasal congestion, rhinorrhea, conjunctival erythema, ptosis, and miosis. Affected patients are agitated and restless, often pacing around the room, in contrast to patients with migraine, who frequently need to lie still in a dark room.

Tension headache. Tension headaches, experienced by 74% of the population, are the most prevalent primary headache. The percentage of patients who seek medical attention for tension headache, however, is disproportionately small because the level of disability is low and the majority of affected individuals treat the headache with over-the-counter medications.

Classically, tension head-aches are characterized by bilateral pressing or tightening of the neck and head, mild to moderate pain without associated nausea or worsening of symptoms with movement, and either photophobia or phonophobia but not both. Different-iating migraine from tension headache can be difficult because 41% of individuals meeting the IHS criteria for migraine report bilateral pain, 75% report neck pain, and 92% of those with neck pain experience it during the head-ache phase of migraine. It has been postulated that any recurrent headache should be considered a migraine until proven otherwise.

Sinus headache. Although sinus headache is not classified as a primary headache, a migraine may be misdiagnosed as such. The IHS criteria for sinus headache include presence of fever, purulent nasal drainage, and acute sinusitis. Nevertheless, the simple presence of rhinorrhea, nasal congestion, sinus pain, or watery eyes in patients with headache often prompts the misdiagnosis of sinus headache. What may be overlooked is that inflamed sinuses produce an exudate that exerts pressure on the trigeminal nerve. In fact, in a study of 2291 patients with self-described "sinus headache," 80% met IHS criteria for migraine. In the absence of fever or purulent drainage, it is important to keep migraine in the differential diagnosis of patients with recurrent headaches whether or not nasal or ocular symptoms are present.

Neuroimaging and Diagnostic studies

In 2000, the U.S. Headache Consortium developed evidence-based recommendations for the use of diagnostic imaging. The consortium operated under the general principle that imaging should be considered only if findings will change headache management, the patient is at elevated risk for a significant neurologic abnormality, or the patient requires reassurance.

Applying this principle to an extensive literature review, the consortium recommended that neuroimaging be considered in patients presenting with nonacute headache and an unexplained abnormal finding on neurologic examination (grade B) or such red flag symptoms as a headache that awakens the individual from sleep, onset after age 50, or progressive headache (grade C). They proposed that neuroimaging is not indicated in patients with typical migraine symptoms and a normal neurologic examination and is unlikely to demonstrate structural abnormalities in patients with tension headaches. In terms of the relative sensitivity of computerized tomography (CT) versus magnetic resonance imaging, they found insufficient data to recommend one over the other.

Lumbar puncture is useful in assessing cerebrospinal fluid (CSF) for glucose and protein content, abnormal pressure, and the presence of bacteria or blood. For example, if subarachnoid hemorrhage is suspected and a CT scan is negative for bleeding, lumbar puncture could be performed to determine whether the CSF contains blood. Cerebrospinal fluid can also be evaluated for xanthrochromia, which will be present for one week after the initial hemorrhage. Headaches caused by idiopathic hypertension, hemorrhage, abscess, tumor, or other space-occupying lesion will be accompanied by an elevated CSF pressure (above 200 mm H2O). Headaches caused by CSF leakage, as can occur with trauma (including epidural anesthesia or lumbar puncture), have a low CSF pressure (below 90 mm H₂O).

best approach to Treatment

The goals of migraine therapy focus on relieving pain and restoring function while avoiding adverse effects. There are various strategies for selecting and sequencing migraine medication. In step care, for example, the patient initially receives the safest medication. If after two or three attempts the treatment fails, the patient progresses to a migraine-specific medication.

U.S. Headache Consortium Goals of Migraine Therapy freedom from pain within 2 hours of using abortive medication once pain free, no headache recurrence for at least 24 hours no adverse drug effects return to full function within 4 hours of dosing

This approach to treatment offers little in the initial phases to patients with marked symptoms and disability. The results of ineffective early treatment are multiple patient visits and frustration and ultimately the potential for termination of care.

In stratified care, the initial treatment choice is based on the severity of symptoms and the level of disability the patient is experiencing. Patients with minimal symptoms and disability are given the safest, least expensive medications, whereas those whose symptoms and disability are significant receive migraine-specific medications.

The U.S. Headache Consortium supports stratified care for migraine. Its treatment guideline calls for patient education and involvement, use of migraine-specific agents in patients who fail to respond to NSAIDs or over-the-counter analgesics, use of a nonoral route of administration in patients with nausea or vomiting, and prophylactic therapy to prevent medication overuse.

Nonspecific Abortive Treatment

For mild migraines, certain nonspecific treatments may be effective. It is important that patients taking these medications be monitored closely, however, because overuse can lead to rebound headaches.

Acetaminophen. Both alone and in combination with aspirin and caffeine, acetaminophen has been shown to be effective in relieving migraine symptoms.

NSAIDs. Ibuprofen, diclofenac, and aspirin have demonstrated efficacy against migraine in several randomized placebo-controlled trials. For patients with nausea and vomiting, indomethacin is available in suppository form. Ketorolac is available in an injectable preparation and can be used for severe headaches.

Opioid analgesics. In an emergency department setting, opioid treatment for migraine should be avoided. Recent findings suggest that patients presenting with acute episodic migraine may develop chronic migraine after receiving parenteral opioids. This was found to be particularly problematic for patients who had been opioid-naive prior to treatment.

Antiemetics. Intravenous (IV) metoclopramide, IV or intramuscular (IM) prochlorperazine, and chlorpromazine (orally or rectally) have been found to be effective migraine therapy in randomized placebo-controlled trials. Metoclopramide is the best studied of these agents. A meta-analysis of 13 clinical trials published in 2004 concluded that metoclopramide should be considered a primary agent for acute migraine.

Anticonvulsant treatment. In the acute treatment of migraine headache, IV valproic acid has been used with some success.

Adjunctive treatments. Adjunctive treatments that address associated symptoms can provide synergistic pain relief. Antiemetics can be used with an NSAID, for example, to treat nausea and improve gastric motility. Sleep, caffeine, and biofeedback also can provide abortive relief.

Magnesium sulfate (1 gram by rapid IV push) also can be useful in aborting an acute attack of migraine. Patients receiving this medication will experience a hot flash within seconds of the injection. The sensation will flow from their head to their feet and will last less than a minute. Within two minutes, patients begin to feel relief from the migraine as well as associated symptoms. With this treatment, pain resolution approaches 80%. Cardiac monitoring is not required.

Specific Abortive Treatment

Used early in the course of a migraine, specific abortive treatment may stop the neurovascular cascade before it becomes difficult to reverse. A number of migraine-specific treatments are currently in use.

Dihydroergotamine (DHE 45). A semisynthetic ergot alkaloid, DHE 45 is an alpha-adrenergic blocker and a 5-hydroxytryptamine (5HT)_1D receptor agonist. It has more venoconstrictive than arterial vasoconstrictive activity and is available in IV, IM, subcutaneous, and intranasal forms. Combined with an antiemetic, DHE 45 is a treatment option for patients with nausea and vomiting. Several studies have shown that the combination of DHE 45 and an antiemetic provides superior migraine control than either agent individually.

In a study comparing DHE 45 with sumatriptan, no significant differences were noted in the rate of headache relief four hours after treatment. Ad-ditionally, DHE 45 was associated with a lower recurrence of headache at 24 hours and increased relief at 24 hours.

Because of its vasoconstrictive action, DHE 45 is contraindicated in elderly patients and those with ischemic heart disease, angina, or uncontrolled hypertension. It also has oxytotic activity and is contraindicated in pregnancy. Patients taking a monoamine oxidase inhibitor, ergotamine, or triptan should not take DHE 45 concurrently.

Ergotamine. Before the emergence of triptans, ergotamine was the mainstay of acute migraine therapy. Ergotamine is a nonselective (5HT)_1D agonist with additional affinity for dopaminergic, cholinergic, and alpha- and beta-adrenergic receptors. Ergotamine’s activity at multiple receptor sites is likely the reason for its association with such significant adverse effects as vascular occlusion, toxicity, exacerbated nausea and vomiting, and rebound headache.

Ergotamine is available in a belladonna-phenobarbital oral formulation and combined with caffeine in both a suppository and an oral formulation. The bioavailability of ergotamine is 2% orally and 5% rectally. It is unclear whether the therapeutic effect of ergotamine products is due to the ergotamine or to the other ingredients with which it is combined (caffeine, phenobarbital, or belladonna).

As with DHE 45, ergotamine has vasoconstrictive and oxytotic activity and should not be given to patients with ischemic heart disease, uncontrolled hypertension, or angina or to pregnant patients. It is also contraindicated in patients taking a monoamine oxidase inhibitor, a triptan, or DHE 45 concurrently, among many other potentially dangerous interactions.

Triptans. Triptans are 5HT₁ receptor-specific agonists. They have no affinity for dopaminergic, cholinergic, or alpha- or beta-adrenergic receptors.

Triptans act on multiple sites that are involved in the development of a migraine and associated pain. They bind to the 5HT_1B receptors on the vascular smooth muscle of meningeal, dural, and cerebral arteries, resulting in vasoconstriction. In activating 5HT₁ receptors of the nucleus caudalis, they block vasoactive peptide release and neuronal transmission. In activating 5HT_1B/1D receptors in the central trigeminal nerve terminals, they prevent the release of sensory neurotransmitters. Currently, seven triptans are available in the United States.

Numerous clinical trials have investigated the efficacy of triptans using a variety of outcome measures. Triptans have been found to work best if used at a maximum dose immediately after the onset of a migraine. More than 80% of patients will become pain free within two hours of using a triptan if the drug is administered within 90 minutes after the onset of the headache. Fewer than 15% of patients who delay taking the triptan for more than 90 minutes will become pain free within two hours. These patients are also more likely to experience adverse drug effects (chest pain, flushing, weakness) as well as headache recurrence.

Patients whose headache recurs or worsens may use one additional dose of the same triptan within a 24-hour period. Those with severe nausea may require a triptan (sumatriptan, zolmitriptan, or rizatriptan) that can be administered by parenteral injection, nasal spray, or dissolving tablet. Patients whose peak headache intensity is often delayed, those with menstrual migraine, and those who experience frequent headache recurrence may do best with a longer-acting agent (frovatriptan or almotriptan). Patients whose headache intensity usually peaks rapidly may do best with an injectable triptan (sumatriptan).

Generally, triptans should not be used more than six to eight times per month. As with all acute migraine medications, the risk of rebound headache increases with regular use.

When using a triptan, some patients report experiencing warmth, flushing, burning, or tightness in the face, chest, or limbs. These symptoms are most common in patients who delay using the triptan until they are in a state of allodynia.

There is also concern that triptans constrict coronary vessels by binding 5HT_1B receptors on coronary arteries. In a cohort study of 63,575 patients with migraine, 13,664 were treated with a triptan. No association was found between triptan use and stroke, cardiovascular events, or death.

It is important, however, to assess a patient’s cardiovascular risk factors (age, cholesterol profile, blood pressure, diabetes status, and smoking history) before prescribing a triptan. In patients with cardiovascular risk factors but no known coronary disease, the first dose of a triptan may be administered in an emergency department under direct medical supervision.

In addition to risk factor assessment, cardiac evaluation prior to triptan use may include functional cardiac evaluation. Triptans are contraindicated in patients with ischemic heart disease, angina pectoris, hemiplegic or basilar migraines, cerebral or peripheral vascular disease, or uncontrolled hypertension and in those who have used ergotamine or more than two doses of a triptan within the past 24 hours.

RESCUE THERAPY AND PROCEDURALLY ORIENTED TREATMENT

Some headache specialists are allowing migraineurs who occasionally fail abortive therapy to use olanzapine 10 mg as a rescue drug. Patients are instructed to use the olanzapine only if their headache worsens after taking two doses of the same triptan within 24 hours.

Olanzapine will induce a six- to eight-hour period of sleep, after which the patient will awaken pain free. This therapy is an excellent option for patients who travel frequently and wish to avoid treatment for acute migraine.

Other procedurally oriented treatments, including botulinum toxin A injection, trigger point injection, occipital nerve block, and sphenopalatine ganglion block, have been used to treat migraine as well. These are considered second- or third-line therapies that can be tried when other treatments have failed. They can also be used in combination with other treatments if a patient has a specific migraine trigger. A complete discussion of these treatments, however, is beyond the scope of this article, as is the topic of migraine prevention.

CHRONIC DISEASE

Migraine is a chronic condition that requires the kind of ongoing long-term care afforded other chronic diseases. The acute treatment strategies employed in emergency departments must be aligned with overall management goals.

Migraine diagnosis requires the practitioner to maintain a high index of suspicion. Once the diagnosis is made, treatment should be based on the severity of the patient’s symptoms and disability.

Effective acute treatment focuses on reducing patient disability and returning the patient to normal, pain-free function with minimal adverse effects. This may be accomplished through frequent assessment of treatment efficacy accompanied by any necessary adjustments in the patient's regimen.

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