Spectrum of illness: understanding biological patterns and relationships in chronic migraine.

Chronic migraine (CM) typically evolves from episodic migraine (EM) over months to years in susceptible individuals. Headaches increase in frequency over time, becoming less intense but more disabling and less responsive to treatment. The results of electrophysiologic and functional imaging studies indicate that CM is associated with abnormalities in the periaqueductal gray matter that may be progressive. In addition, CM is associated with a greater degree of impairment in cortical processing of sensory stimuli than EM, perhaps because of more pervasive or persistent cortical hyperexcitability. These findings fit with the model of migraine as a spectrum disorder, in which the clinical and pathophysiologic features of migraine may progress over time. This progression is postulated to result from changes in nociceptive thresholds and ensuing central sensitization caused by recurrent migraine in susceptible individuals, for whom risk factors have been described. Also, progression may lead to changes in baseline neurologic function between episodes of headache, evident in electrophysiologic and functional imaging studies and as an increase in depression, anxiety, nonhead pain, fatigue, gastrointestinal disorders, and other somatic complaints that may occur after years of EM. From the available research and migraine models, a concept of CM is emerging that identifies relatively permanent and pervasive central changes warranting novel, tolerable treatments. This model also implies that prevention of CM is an important goal in the management of EM, particularly for individuals who exhibit risk factors for chronic transformation.