Background

Although migraine has been a recognized clinical entity for centuries it remains a prevalent problem in our modern society. While the pathophysiology of migraine is a subject of much debate new approaches to treatment are providing relief for many migraine sufferers. Estimates are that as many as 3.4 million women and as many as 1.1 million men in our country experience one or more attacks per month. These migraineurs often experience loss of time from work or school and certainly this problem may have a significant impact on one's social life. Migraineurs account for very large expenditures for over-the-counter and prescription drugs.

Clinical Features

Migraine headache is currently classified by the International Headache Society as migraine with aura and migraine without aura. Migraine headache has been defined as a unilateral headache which may become generalized and does not occur on a daily basis or continuously.

Typical Migraine Headache

Migraine typically has its onset during adolescence or early adult life but frequently also begins during childhood. The initial onset of migraine rarely occurs after the age of 40 years and childhood migraine occurs equally in distribution between sexes but following puberty there is a clear predominance among women. Migraine has long been considered to be a familial disorder and more than half to as much as 70% of migraine sufferers will provide a family history.

A typical headache is unilateral in location, pulsating in quality, moderate to severe in intensity and frequently associated with nausea and/or vomiting along with photophobia or phonophobia. Migraine headaches do not occur on a daily basis though their frequency may vary greatly from patient to patient or even within the experience of a single patient. Characteristically the headache may involve either side of the head even in the same individual from headache to another. Portions of the neck and shoulder may also be involved. During the attack the patient may note tenderness of the scalp and this symptom may continue for several hours following the attack. The degree of severity is variable but these headaches may be incapacitating. They have a typical duration of 4 to 24 hours but may occasionally persist for longer periods. Patient may experience lethargy or fatigue for several days following an attack. Nausea and vomiting are frequently associated with the headache but are not necessary in order to establish the diagnosis.

Patients may describe premonitions of impending migraine attack as much as 72 hours prior to the onset. These are usually vague symptoms which include anorexia, drowsiness, depression, irritability, restlessness, or excessive levels of energy and possibly a feeling of euphoria. Specific prodromes occur frequently and are readily recognized by history. These include

1. scotomata (blind spots)
2. teichopsia (bright shimmering or wavy lines) or fortification spectra (zigzag pattern)
3. photopsia (flashing lights)
4. paresthesias
5. visual and/or auditory hallucination.

Precipitating Factors

A number of precipitating factors are recognized and reported by migraine sufferers and are sometimes termed as trigger factors. These may include external stimuli, physiological phenomena and/or psychological factors. Perhaps stress is the most commonly recognized trigger factor associated with migraine attack, though headache may actually occur following a stressful period rather than during it. Migraine sufferers are particularly sensitive to changes in both sleep and eating pattern and it is usually recommended that they avoid missing meals and adopt a regular sleep schedule. Both lack of sleep and fatigue, as well as excessive sleep, have been associated with a migraine attack. The subject of diet remains one of much controversy. However, there are known to be certain substances which act directly and are vasoactive. These include tyramine, nitrates, monosodium glutamate, and alcohol. These substances may be found as additives in a variety of foods or occur as products as fermentation. Caffeine is another commonly occurring vasoactive substance though its roll in the pathophysiology of migraine remains unclear. It is generally accepted that rapid changes in barometric pressure may provoke a migraine attack for some migraine sufferers. Finally, estrogen and progesterone in the case of women are understood to play a role in timing and occurrence of migraine attacks. For example, relationship between the menstrual cycle and migraine attacks has been well documented clinically. A reduction or cessation in the occurrence of migraine often accompanies menopause. Oral contraceptives should be avoided in migraine patients. Also, estrogen replacement therapy should generally be avoided in post menopausal migraineurs as these hormones frequently exacerbate and re-establish migraine attacks though this may be a matter of clinical judgment in individual cases.

Migraine Management

The management of migraine headache requires adequate communication between physician and patient and usually involves regular office visits. Treatment may include multiple drugs and it is important the patient have an adequate understanding of how each drug is to be used and be cognizant of potential drug interactions. Therapy is usually categorized as either abortive therapy; that which is employed in the treatment of the headache when it occurs and prophylactic therapy; therapy which is applied on a continuous basis with the goal of preventing attacks. A combination of both categories is frequently utilized and will depend upon the frequency of attacks, morbid conditions, allergies and other factors.

Treatment

Ergotamine preparations have long been the agents of choice in the abortive therapy of migraine. They are classified as vasoconstrictors and are understood to specifically counteract the vaso-dilatation which accompanied attacks. Ergotamines may be delivered by any of several routes including oral sublingual, rectal, and pyrantel but must be used early in the course of an attack in order to be efficacious. Nausea may be exacerbated or produced by the use of ergot preparations and hence the rectal suppository is often the most effective non-pyrantel preparation. Caffeine may be combined with the ergot preparation and is believed to act synergistically. Ergotamine preparation should never be repeated on the second or third day of a migraine attack and repeated use of an ergotamine may produce symptoms of toxicity. These agents should be avoided in the elderly and during pregnancy. An alternative to an ergotamine preparation is a combination agent containing isometheptene mucatate, dichloralphenazone, and acetaminophen (Midrin ®).

The advent of the triptans has greatly expanded options with regard to abortive therapy of migraine. The first agent in this category was sumatriptan, (Imitrex ®). This drug was first introduced in this country as a subcutaneous injection and was followed thereafter by an oral form, i.e. tablet 25 and 50 mg. each, and most recently by a nasal spray. This was followed later by zolmitriptan, (Zomig ®) which is available in a 2.5 and 5 mg. tablet and most recently naratriptan HCL (Amerge ®) as a 2.5 mg. tablet. The triptans have demonstrated efficacy in the majority of patients treated though the headache may recur as soon as a few hours following effective treatment and for this reason longer acting triptans have been underdevelopment with naratriptan being the first to reach the market.The triptans are serotonin receptor agonists and because of their vasoconstrictor properties they must be avoided in patients with established or suspected coronary artery disease.

Dihydroergotamine mesylate, (Migranal ®) is another new preparation which is being utilized in the abortive therapy of migraine attacks with a great deal of success. This drug is formulated as a nasal spray and whereas dihydroergotamine has been utilized in the past it was available only for pyrental or intramuscular administration. This form of the drug can be utilized by patients themselves and is gaining acceptance rapidly.

The prophylactic therapy of migraine has seen a wide variety of agents utilized, perhaps one of the most widely used being that of the beta adrenergic blocker Propranolol which is still considered a drug of choice for this indication. This drug, however, is contraindicated in patients with concurrent asthma. Alternatively a cardioselective beta blocker such as Metoprolol or Atenolol may be utilized.

Calcium channel blockers are known to inhibit arterial vasospasm and to block platelet serotonin release and aggregation. Verapamil is an example of this category of drug and is widely utilized in the prophylaxis of migraine. Of the calcium channel blockers, nimodipine (Nimotop ®) has the greatest selectivity for the cerebral vasculature but is approved only for management of vasospasm accompanying subarachnoid hemorrhage. Clonidine, an alpha agonist, has also demonstrated efficacy with regard to prophylaxis in the management of migraine. Cyproheptadine (Periactin ®) has been utilized successfully in the treatment of childhood migraine. Finally the tricyclic antidepressants also have been utilized for this Purpose though the tolerability of these drugs may vary widely from one individual to another. The most recent drug to be approved for the use of migraine prophylaxis is divalproex sodium (Depakote ®). This drug has been widely utilized over many years as an anticonvulsant but only recently came to be recognized as having efficacy with regard to migraine prophylaxis. This array of pharmacologic agents both for the abortive therapy and prophylaxis of migraine attacks offers numerous options for the clinician to choose from and hence to tailor treatment to the needs of each individual migraine sufferer.

Neurology and Neurosurgery Associates, P.A., - 50 2nd St. S.E., Winter Haven, FL 33880