Clinical course in migraine

Migraine is currently conceptualized as a chronic disease with episodic manifestations, with attacks that increase in frequency in a subgroup (migraine transformation or progression). T ransformation of migraine may be subdivided in three partially overlapping forms, although research in this area is still in infancy, and evidence is sometimes weak Typically, transformation refers to increases in attack frequency over time leading to chronic migraine; this process is termed clinical transformation. Additionally, in some patients with migraine, physiologic changes in the CNS manifest themselves through alterations in nociceptive thresholds (allodynia) and alterations in pain pathways (physiologic transformation). Finally, in some individuals, definitive brain lesions including stroke and deep white matter lesions emerge (anatomic transformation). Herein we discuss the evidence that migraine may transform and then consider potential mechanisms as well as risk factors. We close with a brief discussion of clinical strategies that arise based on this perspective on migraine. Neurology® 2008;71:848-855 GLOSSARY 888 = bloodbrain barner; BMI = body mass index; CA = cutaneous allodynia, CDEA = chronic disorder with episodic attacks; CDH = chronic daily headache; CM = chron1c migraine; CSD = cortical spreading depression; HFEM = highfrequency episodic m1graine; LFEM = low-frequency ep1sodic migraine; MMP = matnx metalloproteinase; NSAID = nonsteroidal anti-inflammatory drug; PAG = periaqueductal gray; PR = prevalence ratio; WMH = white matter hypenntens1ty The conceptual framework for understanding migraine has evolved over the past decade. Seen as a purely episodic disorder for a large part of the 20th century, 1 more recent evidence supports the concept that migraine is a chronic disorder with episodic attacks (CDEA). 2 Between headaches, patients with migraine have an enduring predisposition to attacks including abnormalities in brain excitability and impaired health-related quality of life. 3 Emerging evidence also suggests that migraine has a variable clinical course. Some patients with migraine remit becoming free of migraine.4 Others have a stable clinical course. Finally, a subset develops chronic migraine (CM), a condition characterized by headaches on 15 or more days per month. 5 This process is sometimes referred to as migraine transformation. 6·7 Accordingly, migraine is best conceptualized as a CDEA with attacks that increase in frequency in a subgroup. 6-8 From a conceptual perspective, transformation of migraine has been recently subdivided into three non mutually exclusive forms. 9 Typically, transformation refers to increases in attack frequency over time leading to CM; this process, termed clinical transformation, occurs in about 3% of episodic migraine sufferers in the general population over the course of a year. 911 A less discussed and characterized issue is physiologic transformation, 9 physiologic changes in the CNS manifested through alterations in nociceptive thresholds (allodynia) and in pain pathways.12 Finally, in some individuals, definitive brain lesions including stroke and deep white matter lesions emerge13 ; this process is of a potential anatomic transformation (as discussed below, the causal nature of the lesions is sometimes unclear) (figure 1). Although the data for anatomic changes are for patients with episodic migraine with aura only, herein we consider it a From rhe Department of Neurology (M.E.B., R.B.L.), Epidemiology and Population Healrh (R.B.L.), Albert Einstein College of Medicine, Bronx; Monrefiore Headache Center (R.B.L.), Bronx, NY; and Merck Research Laboratories (M.E.B.), Whitehouse Srarion, Nj. Disclosur~: This study was conducted wirhoU[ financial support. Dr. Marcelo E. Bigal is an employee of Merck Research Laboracories. The authors received research support and are/were on the speaker bureau of AmaZeneca, Merck, OrthoMcneil, GSK, Ailergan, NMT, MAP, ENDO, among ocher companies. None of these accivicies rela.te to chis article, which is a Views & Reviews. Copyright © 2008 by AAN Enterpnses. Inc