PATHOPHYSIOLOGY OF MIGRAINE HEADACHES
A migraine headache is a neurovascular disorder often initiated by a trigger and characterized by a headache, which is preceded by an aura 20% of the time. The aura is either unilateral (40%) or bilateral (60%), reversible visual, sensory or other central nervous system symptom that gradually develops and last for minutes preceding the headache. The headache lasts 4 to 72 hours in adults and 1 to 48 hours in children and is typically a pulsatile headache of moderate to severe intensity with associated nausea, photophobia, and/or phonophobia and is typically worsened by routine physical activity. The International Headache Society establishes the diagnostic criteria for the various types of migraine, which are divided into multiple groups: migraine without aura (“common migraine”), migraine with aura (“classic migraine”), chronic migraine, complications of migraine, probable migraine, and episodic syndromes that may be associated with migraine. Further subdivisions of migraine with aura include migraine with typical aura with or without headache, migraine with brain stem aura, hemiplegic migraine, and retinal or ophthalmic migraine.41
The origin of migraine pain evolved from a vascular theory to a neurogenic theory but is still not fully elucidated. Migraine pain involves the trigeminovascular system as well as brain stem and diencephalic nuclei. Although the brain is insensate, the cerebral blood vessels, arteries, veins, and sinuses are innervated by C-fibers and A-δ-fibers of the trigeminal ganglion, and the dura mater is innervated by neurons from cervical dorsal root ganglia. Activation of these first-order neurons releases inflammatory neuropeptides such as calcitonin gene–related polypeptide (CRGP), vasoactive intestinal peptide (VIP), neurokinin A, substance P, and pituitary adenylate cyclase-activating peptide (PACAP). Pain impulses are relayed to the trigeminocervical complex composed of the trigeminal nucleus caudalis in lower medulla and the C1 and C2 region of the spinal cord. From there, nociceptive signals are relayed via second-order neurons via the trigeminothalamic tract to third-order neurons in the ventroposteromedial thalamus as well as the locus coeruleus, periaqueductal gray area, and hypothalamus. Thalamic third-order neurons in turn synapse with multiple higher and diffuse cortical areas. The trigeminocervical complex also produces retrograde parasympathetic impulses from the sphenopalatine ganglion and the superior salivatory nucleus in the pons through the sphenopalatine ganglion to the cerebral vessels.38
Migraine has a strong genetic component and particularly involving genetic abnormalities in the central nervous system (CNS) ion channels, namely, the P/Q calcium channels that predispose patients to specific triggers. Familial hemiplegic migraine is an autosomal dominant disorder with mutations affecting neuronal ion channels, leading to increased neuronal excitability. Four genes are known to be involved, three of these are involved in ion transport and the fourth is an axonal protein complex. Genomewide association studies have identified genes potentially involved in migraine susceptibility.34
Migraine auras are transient focal neurologic symptoms, which are present in about 25% to 30% of migraine patients and are typically visual although sensory, motor, speech or brain stem ...