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PATHOPHYSIOLOGY AND ETIOLOGY OF MIGRAINE HEADACHES

OVERVIEW

The International Headache Society defines migraine headaches as recurrent head pain that is described by patients as causing discomfort that ranges from moderate to severe and can persist for hours to days. The pain often has a pulsating quality and is localized to one side of the cranium. Associated nausea is usually present, and episodes may or may not be accompanied by photophobia and phonophobia. Patients often report that the onset of migraine is related to a unique triggering event. Triggers can include emotional stress (including surgery), traveling motion, flashing lights, certain foods, and physical activity. Migraines are common ailments, and the impact on the individual is enormous in terms of pain, lifestyle disruption, and disability.

Migraine headaches are classified into common, classic, and complicated varieties. Common migraines are typified by a throbbing headache that is usually, but not always, unilateral. Patients with common migraines experience nausea, photophobia, and phonophobia. These patients do not experience the phenomenon known as an aura, which is a preceding sensation (perioral tingling), symptom (visual hallucinations), or feeling (nausea) of an impending headache. Aura is the distinctive characteristic of the next type of migraine headache, a classic migraine. Classic migraines are often called basilar migraines. However, this is a misnomer. Although the clinical presentation is similar to that of a classic migraine, a basilar migraine must present with at least 2 neurologic abnormalities. These abnormalities, which include visual field problems, dysarthria (improper function of the tongue), loss of consciousness, loss of sensory or motor function to the face or limbs, and ataxia (ina! bility to move in a coordinated fashion), are reflective of ischemia (lack of blood flow) to the brainstem, cerebellum, or occipital cortex. Complicated migraines are diagnosed if the neurologic symptoms outlast the headaches experienced by the patient.

ETIOLOGY

The age of onset of migraine with aura in males is approximately 6 years, with an incidence of 7 per 1,000. The most frequent age of onset of migraine without aura in males is 11 years, with an incidence of 10 per 1,000. New cases of migraine are uncommon in men aged 20-29 years. The age of onset in females with aura is approximately 13 years, with an incidence of 14 per 1,000. In females who do not report aura, the age of onset is approximately 17 years, with an incidence of 19 per 1,000 (Lipton, 1997).

The highest prevalence of migraines occurs in persons aged 25-55 years. The prevalence of migraine in the general population ranges from 5.7-20% in men and 17.6-29% in women. Vertigo is reported by 27-33% of patients with migraine; unsteadiness or disequilibrium is reported by 28-72% of patients (Reploeg, 2002). Classic migraines are responsible for 33-45% of the various causes of dizziness among all patients with this condition. Common and complicated migraines account for the remaining cases. Whatever the variety, vertigo can be an isolated finding and can predate the onset of headaches.

Benign paroxysmal vertigo of childhood is an early manifestation of migraine. This entity is characterized by brief attacks of vertigo, disequilibrium, anxiety, and cyclic vomiting in an otherwise healthy child. Approximately 2.8% of children are afflicted with benign paroxysmal vertigo (Neuhauser, 2004). Spells typically begin when the child is younger than 4 years and resolve by the time the child is aged 8 years. Roughly 50% of these children develop migraine headaches as adults (Lanzi, 1986). The diagnosis of migraine is primarily clinical (see diagnostic criteria below), and the physical examination results are typically normal.

DIAGNOSTIC CRITERIA FOR MIGRAINE

Migraine without aura

The diagnostic criteria for migraine without aura include the following:

1. Minimum of 5 attacks fulfilling criteria 2, 3, 4, and 5
2. Headache lasts 72 hours (untreated or unsuccessfully treated)
3. Headache has at least 2 of the following characteristics:
   1. Unilateral localization
   2. Pulsating quality
   3. Moderate or severe intensity
   4. Aggravation by walking stairs or physical activity
4. Headache has at least 1 of the following characteristics:
   1. Nausea, vomiting, or both
   2. Photophobia and phonophobia
5. History, physical examination, and neurological examinations do not suggest association with trauma, vascular disorders, withdrawal from drugs, infections, metabolic disorders, or disorder of cranial or facial structures (eg, temporomandibular joint syndrome).

Migraine with aura

The diagnostic criteria for migraine with aura include the following:

1. At least 2 attacks fulfilling criteria 2, 3, and 4
2. Aura consists of at least 1 of the following characteristics but no motor weakness:
   1. Fully reversible visual symptoms, including positive features (eg, flickering lights, spots, lines), negative features (loss of vision), or both
   2. Fully reversible sensory symptoms, including positive features (pins and needles), negative features (numbness), or both
   3. Fully reversible dysphasic speech disturbance
3. Aura symptoms meet at least 2 of the following conditions:
   1. Visual symptoms of the same field of each eye (homonymous), unilateral sensory symptoms, or both
   2. Minimum of 1 aura symptom develops gradually during more than 5 minutes, different aura symptoms occur in succession during more than 5 minutes, or both
   3. Symptoms last 5-60 minutes
4. Headache that fulfills criteria 2-4 for migraine without aura begins during the aura or follows aura within 1 hour
5. Not attributed to another disorder (see criterion 5 of migraine without aura).

IMPORTANT STUDIES AND THE FUTURE

The pathophysiology of migraine headaches is less clear. The exact site and mechanism of pathology is uncertain. Numerous blood flow studies performed with xenon-133 inhalation or internal carotid artery injection suggest an altered cerebral blood flow in patients with migraine headache. Whether this is a cause or an effect is not known. Parker postulates that the pain occurs secondary to wall stretching (1991). Dilatation causes an accumulation of histamine, plasma kinins, and serotonin and the symptoms described above (Parker, 1991). Bolay, on the other hand, theorizes that stimulation of the trigeminal nerve (he calls this cortical spreading depression [CSD]) activates vascular reflexes that sustain vasodilation and stimulate central pain pathways (2002).

Currently, several functional studies contradict the vascular theories. Instead, cortical depression that is secondary to oligemia, not ischemia, has been demonstrated, which suggests a neurogenic etiology (Cutrer, 1998; Lauritzen, 1994). These models suggest that an unknown trigger activates the ipsilateral cortex and leads to a hyperexcitable state (Welch, 1998; Ferrari, 1998). Baloh suggests that the trigger may be a result of channelopathy, which is a defective ion channel (1997).

BIBLIOGRAPHY

Baloh RW. Neurotology of migraine. Headache. 1997;37:615-21.

Bolay H, Reuter U, Dunn AK, et al. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med. 2002,8:136-42.

Cutrer FM, Sorensen AG, Weisskoff RM, et al. Perfusion weighted imaging defects during spontaneous migraine aura. Ann Neurol. 1998;43:25-31.

Ferrari MD. Migraine. Lancet. 1998;351:1043-51.

Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd ed. Cephalagia. 2004;24(supp 1):9-160.

Lanzi G, Ballotin U, Fazzi E, et al. Benign paroxysmal vertigo in childhood: a longitudinal study. Headache. 1986;26:494-7.

Lauritzen M. Pathophysiology of the migraine aura: The spreading depression theory. Brain. 1994;117:199-210.

Lipton RB, Stewart WF. Prevalence and impact of migraine. Neurol Clin. 1997;15:1-13.

Neuhauser H, Lempert T. Vertigo and dizziness related to migraine: a diagnostic challenge. Cephalalgia. 2004;24(2):83-91.

Parker W. Migraine and the vestibular system in adults. Am J Otol. 1991;12(1):25-34.

Reploeg MD, Goebel JA. Migraine associated dizziness: Patient characteristics and management options. Otol Neurotol. 2002;23(3);364-71.

Welch KM. Current opinions in headache pathogenesis: Introduction and synthesis. Curr Opin Neurol. 1998;11:193-7.