Abstract
The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM+ would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM+ would be classified in those with ≥15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM+ would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7% of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81% and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+ should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.
Introduction
A systematic approach to headache classification and diagnosis is essential for good clinical management and useful research. Since 1988, the International Classification of Headache Disorders (ICHD) has been the accepted standard for headache diagnosis, establishing both uniform terminology and consistent operational diagnostic criteria for the entire range of headache disorders (1).
The primary chronic daily headaches (CDH) of long duration are frequent and debilitating disorders (2–4). The CDHs are usually divided in four entities: transformed migraine (TM), chronic tension-type headache, new daily persistent headache and hemicrania continua (5). In the population, the prevalence of CDH is around 4%, and TM and chronic tension-type headache seem to be equally common (6, 7). In specialty care, TM is by far the most common CDH subtype (8, 9).
One of the most frequent criticisms of the first edition of the ICHD (ICHD-1) was that three of the CDH subtypes were excluded from the classification; only chronic tension-type headache was included (10, 11). Based on knowledge that emerged since 1988, the second edition of the ICHD (ICHD-2, 2004) added the previously excluded disorders (12). In place of TM, a disorder called chronic migraine (CM) was added. CM is defined as migraine attacks occurring ≥15 days per month for at least three consecutive months. Criteria for TM required ≥15 headache days per month (not necessarily migraine) and a link to migraine (5). Another important difference is that TM is subdivided into those with and without medication overuse. The ICHD-2 system classifies as probable CM with probable medication overuse (CM+) those individuals who otherwise meet criteria for CM and are overusing acute medications. A large clinic-based study has shown that using daily headache diaries, just 5.6% of patients with TM without medication overuse met ICHD-2 criteria for CM. Similarly, just 10.2% of the subjects with TM with medication overuse were classified as CM+ (13).
The discrepancy between the criteria for TM and CM is problematic for several reasons. CM criteria appear to be very restrictive, excluding the majority of patients with TM. As a consequence, these patients might require multiple diagnoses when a more parsimonious approach might better correspond to biology. This discrepancy also creates problems in headache research.
Accordingly, alternative revisions to the CM criteria have been proposed. One idea was that CM and CM+ criteria should be modified to include probable migraine (PM) days (13). A second proposal suggested that CM should be classified if a patient had ≥15 days of headache per month, where at least 50% of the headache days were migraine or PM (Silberstein, to the Classification Committee of the American Headache Society, 2005). A third proposal suggested that CM should be diagnosed in those patients with ≥15 days of headache per month and at least 8 days of migraine or PM (Bigal et al. to the Classification Committee of the American Headache Society, 2005).
The utility of these proposed revisions requires empirical testing. Since the criteria specify a minimal number or proportion of migraine-days, a large diary study provides an ideal setting for field testing. Accordingly, we used a large database of CDH sufferers to compare the three sets of proposed criteria for CM and CM+.
Methods
The methods we used to collect the database were described in detail elsewhere (13). Briefly, we reviewed the clinical records and the headache diaries of 638 patients with CDH according to the criteria proposed by Silberstein and Lipton (5), seen from 1990 and 2001 at a headache centre.
During the entire time period reviewed, the clinic used a uniform clinical intake form and standardized headache calendars. At the time of the first visit a spreadsheet was completed by a nurse and subsequently checked by the headache specialist containing information regarding: (i) intensity of pain: pain was graded on a 4-point scale as severe, moderate, mild, or no pain. For all reported intensities of pain, we recorded in a standardized sheet: (ii) frequency of pain at the time of the first visit (current) and at onset; (iii) location of pain (unilateral, bilateral, and alternating sides); (iv) quality of pain (throbbing, squeezing, steady, knife-like, or other); (v) duration of pain; (vi) premonitory features; (vii) aura (description and frequency); (viii) associated symptoms (nausea, anorexia, vomiting, photophobia, phonophobia, osmophobia, dizziness, red eyes, ptosis, tearing, and other); and (ix) relationship between pain and physical activity.
Relevant information was transferred to a standardized form that included operational criteria for the ICHD-2 classification, and for the Silberstein and Lipton diagnostic criteria. Table 1 summarizes both sets of criteria. The ICHD-2 classifies CM as a complication of migraine in those cases where the headaches fulfil criteria for migraine in more than 15 days a month, and medication overuse is not present. If medication overuse is present, CM+ is the diagnosis. This system is considerably different from that of Silberstein and Lipton, which classifies TM in two situations: first, a primary CDH develops in a person with a previous history of headaches; second, one of the three following links with migraine are satisfied: (i) a prior history of ICHD migraine; (ii) a period of escalating headache frequency; and (iii) concurrent superimposed attacks of migraine that fulfil the ICHD criteria. Medication overuse is defined by the use of specific amounts of medication.
Diagnostic criteria for primary chronic daily headaches according to the ICHD-2 and the Silberstein and Lipton criteria
When medication overuse is present (i.e. fulfilling criterion B for any of the subforms of 8.2 Medication-overuse headache), the default rule is to code such patients according to the antecedent migraine subtype (usually 1.1 Migraine without aura) plus 1.6.5 Probable chronic migraine plus 8.2.7 Probable medication-overuse headache.
We also tested three proposals for changes to the CM/CM + criteria. According to proposal 1, CM or CM+ would be classified in those with CDH and at least 15 days of migraine or probable migraine. Proposal 2 suggests that the CM/CM + is classified in those with ≥15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Therefore, according to proposal 2, an individual with 20 headache days per month should have at least 10 of these days fulfilling criteria for migraine or PM. Finally, proposal 3 suggests that CM/CM + is classified in those with CDH and at least 8 days of migraine or probable migraine. The three proposals exclude individuals with new daily persistent headache.
Data were summarized using frequency tables and descriptive statistics. The proposals for revision of criteria and the ICHD-2 were compared with the McNemar test for proportions in repeated measurements.
Results
We assessed 638 patients with CDH, to identify 557 (87.3% of the CDHs) individuals with TM. The majority of the TM sufferers were female (70.9%) and ages ranged from 18 to 75 years.
Classification using ICHD-1 and ICHD-2
Among TM sufferers, 399 (62.5%) had TM with medication overuse, while 158 (37.5%) were not overusing medication. Table 2 compares the ICHD-1 and ICHD-2 classifications using the Silberstein and Lipton criteria for TM as a reference.
Classification of individuals with transformed migraine, according the Silberstein and Lipton criteria, using the ICHD-1 and ICHD-2
M, Migraine; MoA, migraine without aura; MA, migraine with aura; ETTH, episodic tension-type headache; CTTH, chronic tension-type headache; PM, probable migraine; MOH, medication overuse headache; CM+, probable chronic migraine with probable medication overuse.
Of the 158 patients with TM without overuse, just nine (5.6%) met ICHD-2 criteria for CM. Using the ICHD-1, most subjects were classified using combinations of migraine and chronic tension-type headache diagnoses, and none could be classified as a single diagnosis. We were able to classify all patients with TM without overuse with both the ICHD-1 (using six diagnostic groups) and the ICHD-2 criteria (using five diagnostic groups), but just a few with a single diagnosis.
Of the 399 individuals with TM with overuse, just 41 (10.2%) could be classified as CM+. Again, most individuals could be classified in the ICHD-1 and ICHD-2, but requiring a combination of diagnoses.
Proposed criteria for chronic migraine (Table 3)
Classification of individuals with transformed migraine, according the Silberstein and Lipton criteria, using three proposals of modification for the ICHD-2
TM, Transformed migraine; M, migraine; ETTH, episodic tension-type headache; CTTH, chronic tension-type headache; PM, probable migraine; MOH, medication overuse headache; CM+, probable chronic migraine with probable medication overuse; MoA, migraine without aura.
Changing the criteria of CM to ≥15 days of migraine or probable migraine (proposal 1) substantially improved the agreement between the criteria. Nearly half of the TM sufferers would receive a CM diagnosis (P = 0.03 vs. ICHD-2). However, 52.3% of the individuals would still require a combination of diagnoses, most often migraine and chronic tension-type headache (48.7%).
Proposal 2 (at least 50% of the days are migraine or PM) would dramatically increase the sensitivity of the criteria. Using it, 87.9% of the TM sufferers would be classified as CM (P < 0.001 vs. ICHD-2; P < 0.001 vs. proposal 1).
Finally, proposal 3 (≥8 days of migraine or PM over the month) would render a CM diagnosis to the vast majority (94.9%) (P < 0.001 vs. ICHD-2 and proposal 1; P = 0.02 vs. proposal 2). The other individuals were classified as migraine and chronic tension-type headache.
Proposed criteria for probable chronic migraine (Table 3)
A minority of subjects with TM with medication overuse had ≥15 days of migraine per month, and this explains why the ICHD-2 criteria for CM+ classifies only 10% of these individuals. Changing the criteria for ≥15 days of migraine or PM (proposal 1) would increase the proportion to 37.1% (P < 0.001 vs. ICHD-2). The vast majority would still need combinations of ICHD-2 diagnoses to be classified.
Using the criteria in proposal 2, 80.9% of the individuals with TM+ would receive a diagnosis of CM+ (P < 0.001 vs. ICHD-2 and proposal 1). The other 18.9% would require two different combinations of diagnoses.
Using the criteria from proposal 3, the vast majority (91%) would receive a CM+ diagnosis. Just one diagnostic group was found in this proposal (P < 0.001 vs. ICHD-2 and the other two proposals).
The proportion of individuals with TM– and TM+, respectively, classified as CM and CM+ using the ICHD-2 and the three proposals tested herein, are presented in Fig. 1.
Proportion of individuals with transformed migraine that are classified in the current and proposed criteria for the International Classification of Headache Disorders (ICHD-2). P-values are described in the text. CM, Chronic migraine; CM+, probable chronic migraine with probable medication overuse.
Discussion
Several studies show that TM is the most common type of CDH in subspecialty care. Mathew et al. found that 77% of patients with CDH had TM (9, 14). In our experience, TM represented 87.4% of the cases (10). However, most of the individuals with TM with or without medication overuse cannot be classified as CM or CM+ using the current ICHD-2 definition (13). The lack of agreement between Silberstein and Lipton TM and ICHD-2 CM criteria results from the fact that a minority of TM sufferers have ≥15 days of migraine per month. In addition, although PM is considered a migraine subtype by the ICHD-2, PM days are considered not counted as migraine days in the CM criteria.
In the absence of a true ‘gold standard’, it is difficult to develop an optimal definition for CM or TM or to map clinical definitions onto disease biology. It is clear that the current ICHD-2 criteria are so restrictive as to exclude the majority of patients with the disorder of interest and should be broadened. From a clinical perspective, it is well known that the phenotype of TM changes over time (2–4, 6, 9). Patients with TM typically have a past history of episodic migraine without aura. Subjects sometimes report a process of transformation over months or years, with an increased frequency and decreased overall intensity of headaches, with occasional typical attacks of migraine superimposed. This clinical hypothesis was recently tested in a study, where we showed that the proportion of TM subjects with ≥15 days of migraine per month decreased with age and with the time since the onset of CDH. In that study we proposed that CM was an earlier stage of TM (15). Additionally, in a study of adolescents we have shown that early in the process of transformation, migraine is more frequent and that as CDH evolves, fewer typical attacks of migraine occur (16).
Therefore, when the ICHD-2 system requires that CM sufferers present with >15 days of headache fulfilling the full criteria for migraine without aura, it fails to consider the main clinical feature of TM, the reduced intensity of the chronic headache over time. We tested three alternative definitions for CM to address these issues. Although all improved the current system, proposal 1 (15 days of migraine or probable migraine) still did not classify most individuals. Proposal 3 performed significantly better than the others. It also seems easier to use than proposal 2, where the number of required migraine or PM days varies as a function of the total number of headache days per month. According to proposal 2, if a subject has headaches every day, ≥15 days of migraine or PM would be required; in an individual with 16 headache days per month, the required days of migraine or PM would be eight. Classification would be less intuitive and more cumbersome.
Caution is required when interpreting our data. First, this study was retrospective. However, throughout the study, the clinic has used standardized questionnaires and headache calendars. To be included in this study, at least three consecutive monthly headache calendars had to be available for review. Ultimately, we retrospectively assigned diagnoses using prospectively collected data. Second, because this study was conducted in a headache centre, our data cannot be generalized for other levels of medical care or for the population. Third, and most importantly, we have been previously shown that the number of migraine days in individuals with TM declines with time since onset of TM and age (15, 16). Since most individuals in a headache clinic have CDH for many years or decades, our data may reflect an over-representation of TM sufferers with few migraine attacks. In the population it is possible that the ICHD-2 and proposal 1 perform better than what we found, although this would not negatively impact proposal 3. Further research should also model the classification performances of the CM criteria as a function of age and time since transformation.
CM and CM+ are important diagnoses in clinical practice. Modifications of the ICHD-2 are mandatory, so that the ICHD-2 definitions of CM/CM + achieve field characteristics similar to what is seen with the Silberstein and Lipton definition of TM. Based on our data, we propose that CM and CM+ be classified following the criteria shown in Table 4. As we were preparing this paper, and based in part on these data, the Classification Committee of the International Headache Society is drafting proposals for the addition of the criteria for CM-revised to the appendix of the ICHD-2. Although still subject to change, to the best of our knowledge, proposals are identical to what has been discussed herein.
Proposed criteria for chronic migraine and probable chronic migraine with probable medication overuse
