Transformed Migraine Elliott G. Gross, MD, FAAN New York, USA Controversies in Neurology Beijing, China October 13-16, 2011

Transformed Migraine I intend to substantiate that this is an accurate descriptive term which should be incorporated into the ICHD-2 criteria.

Transformed migraine Lumpers or Splitters Chronic Migraine Chronic Tension Type Headache Medication Overuse Headache

Lumpers F He who attaches more importance to similarities than to differences in classification. A TM is more than CM and/or CTTHA. S TM begins early as episodic migraine. T That is why it is called Transformed. Contrasted with Splitters.

Transformed From episodic headache to chronic daily headache and everything in between. A dynamic term, a process.

ICHD-2 Life is not simple, it evolves. Headaches are not simple, they can evolve. Transformed migraine is an evolutionary concept. Highly specific, fixed and distinct.

Transformed or Evolutive Migraine Not unlike the uniqueness of a new daily persistent headache which does not evolve. Transformed from another typical kind of headache. Not just chronic migraine per se. A unique condition Most commonly evolves due to medication overuse.

ICHD-2 Oversight 20 pages, 13 categories with numerous sub categories Why leave out this group Change is inevitable Addendums abound ICHD-2 is 7 years old

Examples from patients seen Many patients begin with straight forward migraine in their young adult life. They have a few migraine attacks a month. Then over the next 20 years or so they transformed into almost daily headaches. Some are like the migraines they used to have and some are milder with fewer migraine features which are more numerous. So in fact, they have migraine which has transformed. The history of patients with migraine is demonstrable.

 The traditional teaching considers migraine as a purely episodic phenomena, and daily headaches are categorized as muscle contraction or tension headache.  Clinical observation of Dalsgaard-Neilsen indicated that 73% of patients with migraine get frequent low grade headaches between their attacks. He concluded that headache is not just an episodic phenomena, but a permanent deviation from normal, because their biologic threshold for headache is lower than in the normal population.  Discussing the natural history of migraine, Graham observed that in some individuals headache may show an increasing frequency of attack until they become daily in occurrence.  In 1982, Mathew et al reported a series of patients who had a clear-cut history of episodic migraine in the past, whose headaches, over the years transformed into a daily or near daily headache. This communication is an extension of that paper with additional observations and a larger number of patients. Transformed or Evolutive Migraine Ninan T. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D.

Transformed or Evolutive Migraine Ninan T. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D. Reprint requests to: Ninan T. Mathew, M.D., Houston Headache Clinic, 1213 Hermann Dr. #350, Houston, Texas Accepted for Publication: January 20, 1987 SYNOPSIS  630 (39%) of 1600 patients seen in a Headache Clinic over a three year period had chronic daily headaches (CDH).  In 78% of these CDH patients, the daily headaches evolved out of a prior history of episodic migraine; these patients we designate as having "transformed" or "evolutive" migraine. The other 12% had migraine headaches which were daily from the start.

Transformed or Evolutive Migraine Ninan T. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D. Patients with transformed migraine, in contrast to those with daily headaches from the start, have a significantly higher incidence of: Positive family history of migraine. Menstrual aggravation of migraine. Identifiable trigger factors. Associated G.I. and neurological symptoms. Early morning awakening with headache.

Transformed or Evolutive Migraine Ninan T. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D. The CDH group in general over-used symptomatic medication and exhibited abnormalities on behavioral scale testing. Withdrawal of daily symptomatic medication, institution of a low tyramine low caffeine diet, initiation of prophylactic anti-migraine therapy, and biofeedback and behavioral therapy, gave worthwhile improvement in 76% of chronic daily headache patients.

Transformed or Evolutive Migraine Ninan T. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D. Factors which promote "evolution" of migraine from intermittent to chronic daily occurrence are not well- defined but may include medication abuse, medication withdrawal, and psychiatric disturbances.

Acute Migraine Medications and Evolution From Episodic to Chronic Migraine: A Longitudinal Population-Based Study Marcelo E. Bigal, MD, PhD; Daniel Serrano, MA; Dawn Buse, PhD; Ann Scher, PhD; Walter F. Stewart, PhD; Richard B. Lipton, MD Background.—Though symptomatic medication overuse is believed to play a major role in progression from episodic to chronic or transformed migraine (TM), population-based longitudinal data on these agents are limited. Objectives.—To assess the role of specific classes of acute medications in the development of TM in episodic migraine (EM) sufferers after adjusting for other risk factors for headache progression. Methods.—As a part of the American Migraine Prevalence and Prevention study (AMPP), we initially surveyed a population sample of 120,000 individuals to identify a sample of migraineurs to be followed annually over 5 years. Using logistic and linear regression, we modeled the probability of transition from EM in 2005 to TM in 2006 in relation to medication use status at baseline. Adjustments were made for gender, headache frequency and severity, and prevention medication use. Results.—Of 8219 individuals with EM in 2005, 209 (2.5%) had developed TM by Baseline headache frequency was a risk factor for TM. Using acetaminophen user as the reference group, individuals who used medications containing barbiturates (OR = 2.06, 95%CI = ) or opiates (OR = 1.98, 95%CI = ) were at increased risk of TM. A dose–response relationship was found for use of barbiturates. Use of triptans (OR = 1.25, 95%CI = ) at baseline was not associated with prospective risk of TM. Overall, NSAIDs (OR = 0.85, 95%CI = ) were not associated with TM. Indeed, NSAIDs were protective against transition to TM at low to moderate monthly headache days, but were associated with increased risk of transition to TM at high levels of monthly headache days. Conclusion.—EM sufferers develop TM at the rate of 2.5% per year. Any use of barbiturates and opiates was associated with increased risk of TM after adjusting for covariates, while triptans were not. NSAIDs were protective or inducers depending on the headache frequency.

Probability of developing transformed migraine in 2006 as a function of headache frequency and monthly use of antiinflammatory medications in 2005 overall (A), in men (B), and women (C).

Trigger Factors for Transformed Migraine Medication Overuse Obesity (vide infra) Hormonal factors Female Stress Low socio-economic status Some Examples

Trigger Factors for Transformed Migraine Abstract—Objective: To assess the influence of the body mass index (BMI) on the prevalence and severity of chronic daily headache (CDH) and its most frequent subtypes, transformed migraine (TM) and chronic tension-type headache (CTTH). Methods: The authors gathered information on headache, medical features, height, and weight using a computer-assisted telephone interview. Participants were divided into five categories, based on BMI: underweight (18.5), normal weight (18.5 to 24.9), overweight (25 to 29.9), obese (30 to 34.9), and morbidly obese (35). The prevalence and severity of CDH, TM, and CTTH were assessed. Multivariate analyses modeling these diagnoses as a function of BMI were conducted. Results: Among 30,215 participants, the prevalence of CDH was 4.1%; 1.3% had TM and 2.8% CTTH. In contrast with the normal weight group (3.9%), the prevalence of CDH was higher in obese (5.0% [odds ratio (OR) 1.3, 95% CI 1.1–1.6]) and morbidly obese (6.8% [OR 1.8, 95% CI 1.4 to 2.2]). BMI had a strong influence on the prevalence of TM, which ranged from 0.9% of the normal weighted to 1.2% of the overweight (OR 1.4 [1.1 to 1.8]), 1.6% of the obese (OR 1.7 [1.2 to 2.43]), and 2.5% of the morbidly obese (OR 2.2 [1.5 to 3.2]). The effects of the BMI on the prevalence of CTTH were just significant in the morbidly obese group. Adjusted analyses showed that obesity was associated with CDH and TM but not CTTH. Conclusions: Chronic daily headache and obesity are associated. Obesity is a stronger risk factor for transformed migraine than for chronic tension-type headache. Obesity is a risk factor for transformed migraine but not chronic tension-type headache Marcelo E. Bigal, MD, PhD; and Richard B. Lipton, MD

Transformed Migraine deserves a proper place in the ICHD-2 There are patients that we all have seen who fit this criteria. Neglecting this term leaves these patients misrepresented and misunderstood. They are of a unique type. Let us not neglect these migraineurs. CONCLUSION

For More Information Elliott G. Gross, MD, FAAN Thank you for your attention.