Concepts and Mechanisms of Migraine Chronification
Concepts and Mechanisms of Migraine Chronification
Migraine is a chronic recurrent disorder with episodic manifestations that is progressive in some individuals. Migraine progresses clinically, physiologically, and anatomically. Progression may be a consequence of the mechanisms that generate the migraine attacks (eg, cortical spreading depression) or it may be a function of the activations generated by the attacks (eg, lesions in the periaqueductal gray area), a hypothesis supported by the increase in lesions with attack frequency. Progression may also be partially explained by common genetic or environmental risk factors. Finally, migraine with aura is associated with an elevated Framingham score and with risk factors for cardiovascular disease. Research on this issue is in its infancy and cautions are necessary before extrapolating this information into clinical practice.
Traditionally seen as an episodic disease, our understanding of migraine has evolved over the past decades. Interictally, migraineurs have an enduring predisposition to attacks, abnormalities in cortical processing, and impaired health-related quality of life. These findings all support the idea that migraine is not just an episodic disorder but a chronic disorder with episodic manifestations. Furthermore, some migraine sufferers have a clinically progressive disorder characterized by attacks of increasing frequency, at times leading to headaches more days than not. This state is often referred to as transformed or chronic migraine (TM or CM), a subtype of the chronic daily headaches (CDH). Finally, recent evidence suggests that migraine, particularly migraine with aura, is a risk factor for anatomical brain lesions. Therefore, migraine is now seen as a chronic disorder with episodic manifestations, progressive in some individuals.
Accordingly, some people with migraine experience long-term changes that may be conceptualized as complications of migraine and measured at clinical, function, and anatomic levels of analysis. Typically, progression refers to increases in attack frequency over time leading to CM, which characterizes clinical progression. A less discussed form of migraine progression may be defined in terms of physiological progression, where migraine leads to changes in the central nervous system which manifest themselves through alterations in nociceptive thresholds (allodynia) and alterations in pain pathways (eg, central sensitization). Finally, an even less discussed form of progression takes the form of definitive lesions (anatomical progression), and includes stroke, white matter lesions, and other enduring features (Fig.1).
(Enlarge Image)
Overall concept of migraine natural history. PAG = periaqueductal gray.
In this paper, we conceptualize migraine as a progressive disease and propose mechanisms to justify the current findings. We first clinically describe migraine progression. We then define the nonmutually exclusive forms of progression. We close by speculating on the mechanisms that may lead to migraine progression.
Migraine is a chronic recurrent disorder with episodic manifestations that is progressive in some individuals. Migraine progresses clinically, physiologically, and anatomically. Progression may be a consequence of the mechanisms that generate the migraine attacks (eg, cortical spreading depression) or it may be a function of the activations generated by the attacks (eg, lesions in the periaqueductal gray area), a hypothesis supported by the increase in lesions with attack frequency. Progression may also be partially explained by common genetic or environmental risk factors. Finally, migraine with aura is associated with an elevated Framingham score and with risk factors for cardiovascular disease. Research on this issue is in its infancy and cautions are necessary before extrapolating this information into clinical practice.
Traditionally seen as an episodic disease, our understanding of migraine has evolved over the past decades. Interictally, migraineurs have an enduring predisposition to attacks, abnormalities in cortical processing, and impaired health-related quality of life. These findings all support the idea that migraine is not just an episodic disorder but a chronic disorder with episodic manifestations. Furthermore, some migraine sufferers have a clinically progressive disorder characterized by attacks of increasing frequency, at times leading to headaches more days than not. This state is often referred to as transformed or chronic migraine (TM or CM), a subtype of the chronic daily headaches (CDH). Finally, recent evidence suggests that migraine, particularly migraine with aura, is a risk factor for anatomical brain lesions. Therefore, migraine is now seen as a chronic disorder with episodic manifestations, progressive in some individuals.
Accordingly, some people with migraine experience long-term changes that may be conceptualized as complications of migraine and measured at clinical, function, and anatomic levels of analysis. Typically, progression refers to increases in attack frequency over time leading to CM, which characterizes clinical progression. A less discussed form of migraine progression may be defined in terms of physiological progression, where migraine leads to changes in the central nervous system which manifest themselves through alterations in nociceptive thresholds (allodynia) and alterations in pain pathways (eg, central sensitization). Finally, an even less discussed form of progression takes the form of definitive lesions (anatomical progression), and includes stroke, white matter lesions, and other enduring features (Fig.1).
(Enlarge Image)
Overall concept of migraine natural history. PAG = periaqueductal gray.
In this paper, we conceptualize migraine as a progressive disease and propose mechanisms to justify the current findings. We first clinically describe migraine progression. We then define the nonmutually exclusive forms of progression. We close by speculating on the mechanisms that may lead to migraine progression.
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