Transformed Migraine. - Elliott G. Gross, MD

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
Contrasted with Splitters.
• He who attaches more importance to similarities
than to differences in classification.
• TM is more than CM and/or CTTHA.
• TM begins early as episodic migraine.
• That is why it is called Transformed.
A dynamic term, a process.
From episodic
headache to chronic
daily headache and
everything in
Highly specific, fixed and distinct.
Life is not
simple, it
are not
simple, they
can evolve.
migraine is an
Transformed or Evolutive Migraine
A unique condition
• 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.
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
The history of patients with migraine is demonstrable.
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.
Transformed or Evolutive Migraine
Ninan T. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D.
 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
 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 EvolutiveMigraine
NinanT. Mathew, M.D., F.R.C.P., Uri Reuveni, Ph.D. and Francisco Perez, Ph.D.
Reprint requests to: NinanT. Mathew, M.D., Houston Headache Clinic, 1213 Hermann Dr. #350, Houston, Texas
Accepted for Publication: January 20, 1987
 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
NinanT. 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
NinanT. 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
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
NinanT. 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 welldefined 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 2006. 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 = 1.3-3.1) or opiates (OR =
1.98, 95%CI = 1.4-2.2) were at increased risk of TM. A dose–response relationship was found for use of
barbiturates. Use of triptans (OR = 1.25, 95%CI = 0.9-1.7) at baseline was not associated with
prospective risk of TM. Overall, NSAIDs (OR = 0.85, 95%CI = 0.63-1.17) 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 antiinflammatorymedications in 2005 overall (A), in men (B), and women (C).
Trigger Factors for Transformed Migraine
Some Examples
Medication Overuse
Obesity (vide infra)
Hormonal factors
Low socio-economic status
Trigger Factors for Transformed Migraine
Obesity is a risk factor for transformed migraine but not chronic tension-type headache
Marcelo E. Bigal, MD, PhD; and Richard B. Lipton, MD
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.
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.
For More Information
Elliott G. Gross, MD, FAAN
[email protected]
Thank you for your attention.

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