Is Chronification the Natural History of Migraine?

OJAI, CA—Diagnosis, while critically important in the management of migraine, “is just half the picture,” said Robert Cowan, MD, Higgins Professor of Neurology and Neurosciences and Director of the Division of Headache and Facial Pain at Stanford University in California. Changes over time, attack frequency, chronification, comorbidity, and disability complicate the management of this disorder. At the 11th Annual Headache Cooperative of the Pacific’s Winter Conference, Dr. Cowan reviewed the clinical evidence suggesting that episodic and chronic migraine are two distinct entities, stressed the importance of classification and staging in the diagnosis and treatment of migraine, and elucidated the signs and symptoms of migraine chronification.

Robert Cowan, MD

Challenging Assumptions

For years, the prevailing perception among clinicians has been that patients with migraine progress from episodic migraine into a state of chronic headache at an annual conversion rate of about 3%. A wealth of data supports this concept. But recent studies have challenged the idea that episodic migraine and chronic migraine are the same entity differentiated only by attack frequency. Research by Schwedt and colleagues, for example, seemed to differentiate between episodic and chronic migraine purely on the basis of anatomy. Additionally, evidence suggests that there are differences between episodic and chronic migraine in regard to connectivity based on functional MRI mapping of pain processing networks. Chronic and episodic migraine seem to affect the brain in different ways, Dr. Cowan said. Structural, functional, and pharmacologic changes in the brain differentiate chronic migraine from episodic migraine.

Classification and Staging

There is evidence that years of headache may make a difference. “Over time, headache after headache can remodel certain areas of the brain, in some areas thickening cortex, and in others, thinning it. This is likely the result of recurrent migraine attacks over time,” Dr. Cowan said. “The patient who has had chronic headache for 30 years is likely to process sensory input differently from the patient who has gone from eight to 14 headaches per month in the last three months.” Currently, studies are under way at Stanford and elsewhere to determine if these changes are reversible with proper treatment. If chronic migraine and episodic migraine are distinct disorders, then clinicians should consider staging the disease. “In the same way the American Cancer Society not only gives patients a diagnosis, but also stages the disease and gives patients an idea as to what they can expect as far as prognosis, I am suggesting that we should be doing the same thing for our migraine patients,” Dr. Cowan said. To properly stage migraine, the following factors must be taken into account: years of headache; type(s) of headache; changes in frequency, severity, duration, disability; comorbidities; and medication use patterns.

The Physician’s Role in Chronification

Physicians themselves can play a role in migraine chronification. Misdiagnosis and underdiagnosis increase the risk of migraine chronification. “When a patient is not doing well, I think it is important to go back and revisit the diagnosis. Make sure that you have the right diagnosis and that the diagnosis has not changed. Are there additional diagnoses?” Other pitfalls that may lead to chronification include failure to recognize treatable comorbidities, inadequate or inappropriate medication use, and signs of chronification such as central sensitization. Weak or recall-biased intervisit data collection also may be a problem.

Risk Factors for Chronification

“It is useful to differentiate between modifiable and nonmodifiable factors,” Dr. Cowan said. Modifiable risk factors include medication overuse, ineffective acute treatment, obesity, depression, stressful life events, and low educational level. Nonmodifiable risk factors include age and female sex. “Another approach is to look at state-specific factors versus process-related factors,” Dr. Cowan said. State-specific factors include obesity, history of abuse, comorbid pain, and head injury. Process-related factors include years of headache, increasing frequency, catastrophizing, and medication overuse.

Chronification Patterns

Clinical clues that chronification may be occurring include increasing headache frequency, severity, or duration, emergence of a second headache type, and a change in pattern of symptoms unrelated to pain. Additionally, allodynia may be a marker of chronification, and central sensitization plays a large role in chronification. “These are things we can assess clinically,” Dr. Cowan said. “We should be thinking about all these things and asking our patients about them as we follow them from visit to visit.” As headache specialists, “our job is not done once we have a diagnosis and go through the Rolodex of treatments for that diagnosis.” NR

—Glenn S. Williams

Suggested Reading

Bigal ME, Lipton RB. Clinical course in migraine: conceptualizing migraine transformation. Neurology. 2008;71(11)848-855.

Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Ann Neurol. 2011;70(5):838-845.

May A, Schulte LH. Chronic migraine: risk factors, mechanisms and treatment. Nat Rev Neurol. 2016;12(8):455-464.

Schwedt TJ, Chong CD, Wu T, et al. Accurate classification of chronic migraine via brain magnetic resonance imaging. Headache. 2015;55(6):762-777.