Abstract
The International Headache Society (IHS) classification divides chronic cluster headache (CH) into two subtypes: chronic CH unremitting from onset (CCHU) and chronic CH evolved from episodic (CCHE). The purpose of our study was to point out any similarities and differences between the two chronic CH subtypes and to determine whether or not they can be considered as two separate clinical entities. We reviewed data about 31 CCHE patients and 38 CCHU patients referred to the Parma Headache Centre between 1975 and 1999. Clinically, CCHE patients exhibited statistically significant differences from CCHU patients, i.e. earlier CH onset and duration of attacks varying more frequently between 120 and 180 min. From the point of view of lifestyle, heavy alcohol and coffee drinkers prevailed among CCHU patients, while CCHE patients were more frequently heavy smokers. Based on clinical features, it seems reasonable to suppose that chronic CH may occur as two distinct entities.
Keywords
Introduction
Chronic forms account for about 10% of cluster headache (CH) in general (1). The 1988 International Headache Society (IHS) classification (2) makes a distinction between chronic CH evolved from episodic (CCHE), in which initially CH has an episodic temporal pattern, and chronic CH unremitting from onset (CCHU), in which CH has a temporal pattern typical of chronic forms since onset. These two chronic CH subtypes have never been studied separately, probably because their relatively rare occurrence makes it impossible for investigators to study large case series. The purpose of our study was to investigate a sufficiently large sample of CCHE and CCHU patients in order to determine: (i) whether there are any differences in the clinical features and patients' lifestyle between the two subtypes; and (ii) whether or not they may be considered as two separate entities.
Patients and methods
Our study population included all patients with CCHU (n = 38, 29 male and nine female) and with CCHE (n = 31, 22 male and nine female) consecutively seen for the first time at the Parma Headache Centre between December 1975 and June 1999.
All pre-1988 diagnoses made according to the 1962 criteria set by the Ad Hoc Committee on Classification of Headache (3) could be easily updated to match the IHS diagnostic criteria (2), as the clinical records used at our Centre have been unchanged since 1975 and contain all the necessary clinical parameters for diagnosis down to the four-digit level of the IHS classification. In fact, two CCHE patients out of 31 (6.5%) and six CCHU patients out of 38 (15.8%) should actually have been assigned to the 3.3 group of the IHS classification ‘Cluster headache-like disorder not fulfilling above criteria’, because they did not fulfil one of the parameters listed in 3.1. All the same, we thought it useful to include these patients in our study, because their failure to match the IHS classification criteria was actually negligible and they could therefore be considered as true CH sufferers. In both patient groups, we considered the male-to-female ratio and such clinical features as mean age at CH onset, decade of onset, pain side, frequency and duration of attacks, and the presence of associated symptoms as listed in the IHS classification. We also checked for past medical history of head injury and—for patients aged over 14 years—cigarette smoking, daily alcohol intake and coffee consumption.
Statistical analysis
After checking that the variables considered in the two samples had a normal distribution—which was a prerequisite for the application of the parameters tests—we proceeded with the χ2 test and Student's t-test for means comparison (of unpaired data). We applied the required adjustment parameters for multiple tests and we considered as statistically significant P values ≤0.05.
Results
The gender ratio was 3.2:1 for CCHU patients and 2.4:1 for CCHE patients.
In the CCHU group, mean age at onset was 36.7 years (SD 15.5), i.e. 43.3 years (SD 20.7) for females and 34.4 years (SD 13.0) for males. In the CCHE group, mean age at onset was 29.9 years (SD 13.4), i.e. 36.9 years (SD 14.9) for females and 27.0 years (SD 12.0) for males (difference for the overall sample between the two groups: P < 0.01). Onset distribution by patient's life decade showed a more consistent pattern for CCHU in both genders with no significant peak between 21 and 30 years as in CCHE (Table 1).
Decade of onset in patients with chronic cluster headache (CH) unremitting from onset (CCHU) and chronic CH evolved from episodic (CCHE)
χ2 = 6.24 P < 0.01.
χ2 = 7.23 P < 0.001.
CCHU patients reported a right-sided pain location more frequently than did CCHE patients. The frequency of attacks ranged from once every other day to twice a day in most patients of either group. However, gender-based analysis showed that CCHE females reported a larger number of daily attacks than did CCHU females (three to eight per day). Attacks lasted 15–120 min on average in both patient groups, but in the CCHE group there was a statistically significantly larger proportion of patients who reported attacks lasting 120–180 min. Some of the accompanying autonomic phenomena listed in the IHS classification, i.e. forehead/face sweating and eyelid oedema, were more frequently reported by CCHU than CCHE patients. By contrast, CCHE patients reported lacrimation, nasal congestion, rhinorrhoea and ptosis more frequently than did CCHU patients (Table 2).
Side, frequency and duration of attacks, and associated symptoms in patients with chronic cluster headache (CH) unremitting from onset (CCHU) and chronic CH evolved from episodic (CCHE)
Patients with consistently unilateral pain location, but with headache switching side in the course of the disease.
χ2 = 4.43, P < 0.03.
CCHU patients were less likely than CCHE patients to report head injury in their past medical history (34.2% vs. 54.8%, i.e. 13/38 vs. 17/31). Based on the temporal relation of age at CH onset to age at head injury, we were able to conclude that head injury preceded CH onset for most patients of either group: 76.9% (10/13) of CCHU patients vs. 64.7% (11/17) of CCHE patients. The average latency period—meaning the average number of years elapsing between trauma and CH onset—proved significantly different in the two groups, when the analysis was restricted to head-injured males having suffered loss of consciousness: 21.8 years (SD 12.1) for CCHU males vs. 5.5 years (SD 3.4) for CCHE males (P < 0.01).
A larger proportion of CCHE patients than CCHU patients were smokers at the time of their first visit at our Centre (87.1% vs. 65.8%, i.e. 27/31 vs. 25/38), the difference being statistically significant in the male population (P < 0.02), i.e. 95.5% (21/22) vs. 65.5% (19/29). In the CCHE group, 48.4% (15/31) smoked more than 20 cigarettes a day, compared with 21.1% (8/38) in the CCHU group.
At the time of their first visit at our Centre, 76.3% of CCHU patients (29/38) were regular drinkers vs. 64.5% of CCHE patients (20/31), with 27.6% (8/29) of CCHU patients drinking 50–100 g/day of alcohol compared with 15.0% of CCHE patients (3/20). Regular coffee drinkers were 89.5% of CCHU patients (34/38) vs. 90.3% of CCHE patients (28/31). However, 57.9% of the former (22/38) used to drink 5–7 cups of coffee a day vs. 32.3% of the latter (10/31) (P < 0.04).
Discussion
Scant evidence has been gathered to date on the clinical features of chronic CH, due to the difficulty of finding a large sample of patients affected with this particular CH type. In our study, too, we often compared data that concerned a small number of patients; however, we felt that a sample of 69 patients with chronic CH was larger than those reported so far in the literature and allowed us to make some interesting observations. In the two patient groups included in our study, the male-to-female ratio was 2.4:1 for CCHE and 3.2:1 for CCHU. This finding not only contradicts the commonly held belief—at least until a few years ago—that chronic CH is a type of CH affecting only the male population (4), but also lends credence to a recent report (5) about the progressive decrease of male preponderance over time. Data about mean age at CH onset confirm that it is older for CCHU (6–8). Analysis by decade of onset partly confirmed a previous report by Kudrow, who found a different pattern between his 30 CCHE patients and his 45 CCHU patients and, based on such a finding, assumed a possible aetiological distinction between the two chronic CH subtypes (9). In particular, our results show—as did Kudrow's—that CCHE onset tends to peak at an early age and that distribution by decade shows a more consistent pattern for CCHU than CCHE. Unlike Kudrow's, though, our results did not show any further peak of onset in the fifth decade of life in CCHE.
Our data about frequency and duration of attacks was quite comparable to other data published in the literature for CH in general (9–11), which, however, did not refer specifically to chronic forms. Indeed, our data suggest that patients with CCHE, especially females, are more likely to show a high frequency of long-lasting daily attacks, in agreement with the hypothesis advanced by Manzoni (10) of a larger number of attacks on a daily basis in chronic CH patients. We then checked the accuracy of CH diagnosis in females reporting three to eight attacks a day, as it appears that both CH and chronic paroxysmal hemicrania (CPH) match the ‘frequency of attacks’ criterion of the IHS classification in more or less the same way: in the five women in our sample who reported a higher frequency of attacks, their duration exceeded 45 min and therefore was not consistent with CPH diagnosis. The two patient groups differed also in the accompanying autonomic phenomena: CCHE patients were more likely to have their headache associated with lacrimation, nasal congestion, rhinorrhoea and ptosis, while CCHU reported more frequently facial sweating and eyelid oedema. CH patients are known to report head injury in their past medical history more frequently than do controls or patients with other forms of headache (9, 10). In our sample, there was a larger proportion of previously head-injured patients in the CCHE group than in the CCHU group; the remarkable differences found in latency hardly suggest a direct role of trauma in CH pathogenesis, but based on the shorter latency periods found in CCHE male patients, it is not unreasonable to assume that head injury accompanied by loss of consciousness does seem to worsen the course of the disease in these patients.
As regards non-essential consumption habits, our study results partially confirm earlier reports in the literature (9–11). While pointing to a considerable proportion of smokers among patients of both groups at the time of their first visit to our Centre, our study showed that their number was larger in the CCHE group, which also included a higher percentage of patients who used to smoke more than 20 cigarettes a day. Alcohol abuse has also been more frequently reported in chronic CH patients than in controls or other CH sufferers (9, 13), and our study showed that CCHU patients were more frequently heavy drinkers than CCHE patients at the time of their first visit to our Centre. We also found in our study that CCHU patients are more likely to overindulge in coffee consumption, as was recently reported in a survey of CCHU males (12).
In conclusion, CCHE patients exhibit significant clinical differences from CCHU patients. Based on our study results, it appears reasonable to assume that CCHE might actually be an episodic CH form that has had an unfavourable evolution over time. In this respect, it would be very interesting to identify possible factors involved in its evolution to a chronic form and consequently any unfavourable prognostic indicators. To support this working hypothesis and to assess the possible ‘reversal’ of CCHE from its assumed original form, we checked the few reports published so far in the literature on episodic CH evolved from chronic (11, 14–16). Unfortunately, most of these reports did not specify what chronic form evolved into episodic and, when they did so (1), the patient samples were too small to allow definite conclusions. Therefore, it might be useful to investigate the temporal evolution of the two chronic forms separately in an adequately sized sample. CCHU would then seem to be a different entity from CCHE and the differences found between the two forms in the affected patients' lifestyle and in the frequency of head injury might corroborate such an hypothesis. For any conclusive evidence on this subject, though, further studies are needed.
Footnotes
Acknowledgements
Work supported by Italy's Ministry for University Education and Scientific and Technological Research (MURST). Under the terms of the 1998 agreement for the allocation of funds to scientific research projects of national importance, MURST contributed to the funding of our study as part of the ‘Cluster headache pathophysiology’ research project.