Annals of Neurosciences, Vol 14, No 2 (2007)
Annals of Neurosciences, Volume 14, Issue 2 (April), 2007
TRANSFORMED MIGRAINE: A STUDY OF 420 CONSECUTIVE PATIENTS FROM CENTRAL INDIA
Abstract
Objective: This study was carried out to analyze clinical features, transforming factors, associated co-morbidity like depression, anxiety and analgesic overuse in patients with transformed migraine.
Materials and methods: This is a retrospective analysis of 420 consecutive headache patients The clinical features of headache were analyzed, like duration of headache, frequency of attacks, migraine triggers, psychological co-morbidity and analgesic use.
Results: Approximately 30% patients had chronic daily headache of which transformed migraine constituted the largest group (61%). Fifty three percent patients had psychological co-morbidity. Analgesic overuse was noted in only 16% patients. Seventy five percent patients had more than one year of migraine headache.
Conclusion: Transformed migraine is the most common cause of chronic daily headache. The burden of recurrent migraine attacks is the main factor in the transformation of episodic to daily migraine.
Key words: Transformed migraine, Chronic daily headache, Chronic migraine, Medication overuse headache.
Introduction
Chronic daily headache is a common clinical problem, about 40% of patients seen in major headache clinics fall under this category(1). Various terms have been used to describe this condition "chronic daily headache, migraine with interparoxysmal headache, transformed migraine, evolutive migraine, mixed headache syndrome, and tension vascular headache. Mathew et al first introduced the concept of transformation of episodic migraine into chronic daily headache (2). Chakravarty reported misconceptions, unnecessary investigations and inappropriate therapy in chronic daily headache from India (3). Chronic daily headache has been defined in the present study as headaches occurring more than 15 days per month for more than 1 month 4. These can be further classified as per the duration of headache (more than 4hrs) which includes transformed migraine, chronic tension type headache, New daily persistent headache and hemicrania continua, with or without analgesics abuse and less than 4hrs including cluster headache, Short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and hypnic headache a rare form of short lasting headache which occurs in the elderly (4). The term "chronic migraine" has been introduced and defined by the International Headache Society (IHS). The diagnosis requires that patients have a history of episodic migraine attacks that increase in frequency over time and that the diagnostic criteria of migraine are fulfilled on more then 15 days per month (5). However it has certain limitations (see discussion). Transformed migraine (TM) was diagnosed by the criteria of Silberstein et al (6). This criteria has being used in clinical population and treatment studies during last 10 yrs (7) This analysis excludes patients of daily headache of short duration (<4hrs) with autonomic features and secondary headaches. This study is being carried out to analyze clinical features, transforming factors, co-morbidity like depression, anxiety and analgesic overuse in patients of transformed migraine.
Methods
This is a retrospective study in which charts of 420 consecutive headache patients attending the neuro clinic were reviewed. The various factors analysed were the duration of illness, frequency of attacks and duration of each attack associated features like nausea, vomiting, phonophobia, photophobia, location, character (pulsatile or nonpulsatile) and whether patient could carry out ADL during headache. Details were also noted regarding triggers, co-morbidity like depression, anxiety and analgesic use. Patients were diagnosed TM according to the diagnostic criteria of Silberstein and Lipton (1996) this criteria requires patients to have 1. Daily or almost daily (> 15 days/month) head pain for > 1 month, 2. average headache duration of > 4hrs/day (if untreated), 3. At least one of the following a: history of episodic migraine meeting any International Headache Society (IHS) criteria, b: history of increasing headache frequency with decreasing severity of migrainous features over at least 3 months, c: headaches at some time meets the IHS criteria for migraine, 4. Does not meet the criteria for new persistent headache or hemicrania continua and 5. Lastly headache not attributed to another disorder (6). Drug overuse was diagnosed as per Solomon's criteria that is at least one of the following for at least 1month: Simple analgesic use (> 100mg ASA/acetaminophen) > 5d/wk, Combination analgesics (> 3tabs/d) > 3d/wk, Narcotics(>1tab/d)>2/wk, use of Ergotamine (1mg PO or 0.5mg PR) >2d/wk(8).
Results
Of the 420 patients studied, chronic daily headache was diagnosed in 32% patients (137/420) Table No 1. Transformed migraine constituted the largest group 61.3%. There was no case of hemicrania continua. Women outnumbered men (M: F = 1: 3.6). Forty one patients had initially episodic migraine that transformed later into daily headache. Forty three patients had from the beginning a daily headache with intermittent full blown migraine attacks. Sixty percent patients were between 21 to 40yrs, 20.2% patients were less than twenty years, 17.8% between 41 to 60yrs, and 1.1% patients were between 61–80yrs. The duration of headache was 6 months to 1 year in twenty one patients (25%), l-5yrs in thirty one patients (36%), sixteen patients each had 5–10 yrs and more than l0yrs respectively. Other clinical features included bilateral headache in 69 patients (82.1%), unilateral 15 (17.8%). Family history of migraine was noted in 20 patients (23.8%), Migraine triggers like fasting, sunlight, sleep deprivation, extremes of cold, heat and traveling were noted in 34 patients (40%). Five patients (5.9%) had menstrual related aggravation. Of the 41 patients with episodic migraine 12 (29%) patients transformed in transformed migraine in less than 6 months and in more than 2 yrs in 29 (71%) patients. Irritability was noted in 28.5% (24/84) patients Table No 2 mentions details of psychological co-morbidity. Analgesic overuse was seen in 10 patients (16.6%) details shown in Table No 3.
| Total Patients 420, Feb 05 to Oct 05 | |
|---|---|
| Chronic daily headache Transformed Migraine CTTH NDPH |
137 (32.6%) 84 42 11 |
| Migraine without aura | 119 (28.3%) |
| Migraine with aura | 16 (3.8%) |
| ETTH | 14 (3.3%) |
| Tumors | 5 (1.19%) |
| Temporal arteritis | 2 (0.47%) |
| Episodic Cluster Headache | 3 (0.71%) |
| Chronic cluster headache | 1(0.23%) |
| Sinusitis | 5 (1.19%) |
| Post traumatic | 2 (0.47%) |
| Ocular Cause | 1 (0.23%) |
| Not Meeting IHS Criteria | 109 (25.9%) |
| Data incomplete | 5 (1.19%) |
| Atypical facial pain | 1 (0.23%) |
*Chronic daily headache not classified as per IHS (see text)
| Psychological morbidity | No of pts(%) |
|---|---|
| Irritability | 14(31.1%) |
| Features of Depression & Anxiety (not meeting the DSM criteria) | 8 (17.7%) |
| Irritability with features of Depression & anxiety | 7 (15.5%) |
| Anxiety* | 7(15.5%) |
| Depression* | 7(15.5%) |
| Depression & Panic* | 2 (4.4%) |
| Total No. of patients | 45 |
*As per DSM IV criteria
Discussion
Of the 137/420 (32.6%) patients of chronic daily headache, 84/137(61.3%) patients had transformed migraine. Forty eight percent (41/84), patients started as episodic migraine. The migraine attacks became more frequent and gradually patients developed low grade daily headaches with intermittent exacerbations with migrainous features ie severe, pulsatile headache associated with nausea, vomiting, photophobia or phonophobia. These migraine headaches were precipitated by typical migraine triggers like inadequate sleep, menses, fasting, sunlight and hot weather. Forty three patients (52%) had daily headache from the beginning as far as the patient could recall. When the duration of migraine extends over years the beginning of headache episodes may not be recalled. Majority of the patients gave a history of shorter duration (weeks to months) and it was only after repeated interrogation that they revealed history of recurrent migraine attacks of many years duration which they believed to be due to eye problems, cervical spondylosis and hyperacidity. All these patients did not mention their previous headache history as they thought it not to be significant. Poor memory and recall of initial intermittent headache may be the reason for high number of patients (52%) reporting from the beginning a daily headache as compared to Mathewetal who noted only 9% (57/630) patients in whom the pain started as daily or nearly daily headache with more severe headache with migrainous features which was classified as Type II in their classification of chronic daily headache(1).
Of the forty one patients who had episodic migraine 29 patients transformed into daily headache in 6 months, and remaining 12 patients transformed gradually from 6 months to over many years. None of the patients with episodic migraine reported sudden transformation in daily headache. Spierings et al reported gradual transition that took an average of 10.7years in 81% patients whereas 19% patients experienced abrupt transformation (9).
Chronic Tension type headache forms the second major category of CDH 30.6% (42/137). The headache in these patients was diffuse, bilateral, pressing, tightening quality and mild to moderate in severity. None of these patients had h/o migraine or intermittent exacerbations with migrainous features. Mathew et al. reported 13% (84/630) having chronic tension type headache in 630 patients of chronic daily headache(1). New daily persistent headache (NDPH) was seen in 8% (11/137) patients. None of these patients had previous history of migraine or tension type headache. All patients distinctly remembered the onset of headache. The female predominance was maintained in transformed migraine as also reported by others (2).
Analgesic abuse is attributed as a significant factor development of transformed migraine. Excessive use of medication was noted in 52.4% patients who had transformation of episodic migraine into daily headache (2). Bigal et al reported incidence of medication overuse in 74.3% patients in a tertiary headache center(10). Similarly Chakravarty reported analgesic overuse in 20% patients and ergot in 4% patients of transformed migraine(3). Ravishanker reported medication overuse in less than 5% of the patients with chronic migraine(11). In the present study Drug overuse (analgesic or ergot) was seen in 15.4% patients (10/84). The incidence of drug overuse may differ in a general neurologic out clinic and a tertiary headache center (11). In tertiary referral centers patients suffering from chronic daily headache may be of greater severity and duration and/or associated with more of psychiatric co-morbidity suggesting a referral bias(10). The low figure of drug over use in the present study may also be due to cultural factors of the population under study. Majority of patients avoided acute pain medication due to fear of adverse effects. This is partly due to the belief that allopathy is harmful (12). Partly it may be due to economical factors as no patient with triptans abuse was found in the present study. Similarly Chakravarti also reported no patient with triptans overuse which is an expensive drug (3). Diener also emphasized that use of drugs that lead to medication overuse headache (MOH) varies substantially from country to country and is influenced by cultural factors(13). The details of analgesics/ergot overuse are shown in table 3. In all the patients it was increasing headache which led to increasing use of analgesics rather then vice versa.
| S.No | A/S | Drugs | Quantity | Duration |
|---|---|---|---|---|
| 1. | 16/F | Dispirin (aspirin 350mg, cal.carb 105mg, anhydr.citric acid 35mg) | 5–20tab./month | 6 months |
| 2. | 16/M | Dispirin (aspirin 350mg, cal.carb 105mg, anhydr.citric acid 35mg) | 15–20tab./month | 1 month |
| 3. | 22/F | Migranil(Ergotamine 1mg, caffeine 100mg, belladona 10mg, paracetamol 250mg.) | 20tabs/month | 3 years |
| 4. | 32/M | Proxyvon (Paracetamol 400mg, dextropropoxyhene HC165mg) | 15–20tab/month | 2 months |
| 5. | 23/F | Analgin (amidopyprin) 500mg | 20tabs/month | 1, l/2month |
| 6. | 21/M | Xenobid (Naproxen 275mg) | 10tabs/month | 5 months |
| 7. | 22/F | Vasograin(Ergotamine 1mg, caffeine l00mg, paracetamol 250mg, prochlorperazine meleate 2.5mg) | 20tabs/month | 3 years |
| 8. | 30/F | Combiflam(Ibuprofen 400, paracetamol 325mg) | 20–25/month | 1 month |
| 9. | 32/F | Dispirin (aspirin350mg, cal.carb 105mg, anhydr.citric acid 35mg) | 15–20/month | Many years |
| 10. | 28/F | Combiflam (Ibuprofen 400, paracetamol 325mg) | 15–20/month | Many years |
This data indicates that analgesic overuse may not be a major factor to initiate or perpetuate transformed migraine in majority of the individuals and suggests other mechanisms particularly long duration of migraine headaches may be involved in the progression of episodic to transformed migraine. Majority of patients 59.4% (22/37) in the present study had more than 2 years history of chronic daily headache or longer as patients had difficulty in recalling the duration of illness. With the increasing burden of headache and duration of illness there is accumulation of iron in the peri-aqeuductal gray matter (PAG). Iron deposition occurs due to repeated episodes of hyperoxia during migraine attacks. PAG is the center of powerful descending anti-nociceptive network. The iron accumulation may be a marker of progressive PAG dysfunction. Impaired PAG may lead to dysfunctional central control of trigeminovascular nociceptive system and evolution of episodic to chronic head pain.(14). None of these patients had clinical features of medication induced headache like variation of headache in severity, type or location from time to time, physical or intellectual effort precipitating headache or associated symptoms of asthenia, nausea or other gastrointestinal symptoms as described by Diener (13). The clinical picture was more suggestive of transformed migraine in the present study. Another possible mechanism of transformation of episodic migraine into daily headaches may be due to peripheral/central sensitization in which frequent attacks of migraine may lead to neuroplastic changes in the second order nucleus caudalis neurons resulting in tonic state of increased excitability, spontaneous pain and reduced threshold of activation (ie central sensitization) (11).
Lastly transformation of migraine into daily migraine may be due to other factors like duration of migraine illness and certain medical conditions like hypertension, asthama, allergies, hypothyroidism, obesity, use of caffeine and snoring (sleep apnea, sleep disturbance) and stressful life events (15).
Fifty Three percent patients (45/84) had psychological comorbidity (table No 2). Irritability was the most common problem noted in 31% patients. This was present almost daily and throughout the day. Factors that led to irritability were stress at home, at work place, children's studies, family problems, problems with the maid servant. Irritability with features-of depression and anxiety were seen in another 15% patients. Seven patients (15%) each had diagnosed generalized anxiety disorder and depression as per DSM IV TR criteria(16). Chakravarty reported major depression in 20.5% patients, and mood disorder were seen in 44.4% patients using DSM IV criteria(3). Mathew et al reported significantly elevated depression (Zung & Beck) scale in patients with transformed migraine. Based on MPPI, abnormal personality profile was found in 61% of the patients with chronic daily headache. Fifty six percent patients showed features of hypochondriasis, depression and hysteria. Majority had neuroticism i.e. patients preoccupation with disease and his feelings of despair about its alleviation (2). Verri et al assessed the psychotic comorbidity by using the semi-structured clinical interview conducted according to DSM -IV R criteria in 88 consecutive pts of chronic daily headache. Sixty nine pts of chronic daily headache had generalized anxiety, 25% had major depression which was significantly more than dysthymia. Somatization disorders were found in only 5% patients. The authors found that 90% of the sample was diagnosed according to DSM IIIR criteria having a psychotic diagnosis. However such a high incidence may be due to referral bias ie population with more psychiatric morbidity might have been referred(17).
The IHS classification committee introduced a formal criteria for classifying chronic migraine. This requires patients having more than 15days of IHS -defined migraine per month for more than 3 months without medication overuse. The requirement that daily headache must meet the criteria for migraine without aura each day is a point of concern with the new IHS criteria(5). On the contrary during the process of transformation the frequency of migraine headache increases but the severity reduces. The associated migrainous features decline in prominence. There may be occasional full blown migraine on this background of nearly daily headache(18). Moreover even patients with episodic migraine do not always meet the IHS criteria for migraine during all the attacks. Lastly this criteria has not been field tested (19), therefore Silberstein's diagnostic criteria for transformed migraine has been used in this study (6).
The present study has limitations being retrospective, from a selective population visiting a Neuro-outpatient, small sample size, no data is available on other associated transforming factors and on follow up but in spite of these limitations some valid conclusions can be drawn as has been discussed.
Conclusion
Chronic daily headache is the commonest type of headache encountered in neuro out patients. Majority of these patients are transformed migraine. Females outnumber males. Approximately 50% of patients are daily headache from the onset and remaining 50% transformed from episodic migraine headache. Irritability, features of depression and anxiety were common psychological co-morbidity. Drug overuse was not found to be significant in the present study. All patients had long history of migraine and long duration of recurrent migraine attacks appears to be the major factor in development of transformed migraine.
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