Abstract
One hundred and sixty-three consecutive patients (129 females and 34 males) over 60 years of age attending the Headache Centre of the University of Perugia in the period January 2000-December 2001 were included in the study.
One hundred and fifty-two (93.3%) were affected by a primary headache disorder. According to the 1988 IHS Criteria, their prevailing attacks could be diagnosed as migraine without aura (MwoA) in 57.2% of cases (n = 87) and as migraine with aura (MwA) in 11.8% of cases (n = 18). Attacks both in MwoA and MwA were unilateral and of severe-to-moderate intensity in 45% and 50% of cases. Head pain was referred as pulsating by 56% and 38.9% of MwoA patients MwA patients, respectively. Aggravation with routine daily activities was present in 72.4% and 61.1% in MwoA and MwA patient groups. The most frequent accompanying symptoms were photophobia and phonophobia. Headache attacks were of shorter duration in MwA patients, but in 3.4% of MwoA patients attacks lasted between 2 and 4 h. Of patients affected by MwA, 55% referred, together with the typical attacks, symptoms of aura not followed by headache. A worsening of headache in the last 5 years was reported by 67.8% and 44.4% of MwoA and MwA patients, respectively. Of the patients with MwoA, 86.2% (n = 75), and 83.3% (n = 15) of those with MwA used symptomatic drugs for their attacks. In the majority of cases they took more than one analgesic or non steroidal anti-inflammatory drug. A total of 51.7% of patients with MwoA and 55.5% of patients with MwA were under prophylactic treatment. Preventive drugs included antidepressants, beta-blockers, calcium channel antagonists and antiepileptic drugs. The choice of symptomatic or prophylactic drugs was made, in the majority of cases, on the basis of concomitant diseases.
Keywords
Introduction
Primary headaches are the most frequent headaches reported by older people and even if secondary headache disorders more often occur in the elderly, they account for no more than 10–20% of headaches diagnosed over 65 years of age (1, 2).
The prevalence of migraine, which reaches a peak at 40 years of age, tends to decline thereafter, with a prevalence of about 7% for females and 3.5% for males over 65, as reported by the American Migraine Study (3, 4).
Migraine prevalence, although commonly observed to decline with age, ranges in other population studies from 3.4% to about 13%, and this variability depends, as in other age groups, on the different demographics and sample size of the population, the different study design and methods of data collection and analysis (5–9).
Gender ratio also dramatically varies with age: it peaks around 42 years of age and thereafter it begins to decline. Besides this, prevalence was substantially higher in women at any given age with values of 2 : 1 at 70 years of age, suggesting that cyclic hormonal factors cannot account for all of the difference between sexes (3).
Another common finding with age progression is the reduction in the frequency and intensity of attacks, as well as the presence of associated symptoms in patients suffering from migraine in adulthood (8). If this seems to be the rule, in 2–3% of the cases the first migraine attack can occur after 50 years of age (10).
Further studies specifically concern the elderly, and also in these cases percentages widely vary depending on the cohort examined and methodological differences (11–16).
A recent population study (17) has been carried out on a population of residents over 65 years of age in an area of central Italy. Diagnoses were made according to the IHS criteria, with the exception of chronic daily headache, for which the criteria of Silberstein et al. (18) were used. A prevalence of migraine of 11% emerged compared with a prevalence of tension-type headache of 44.5%, whereas the other primary headache types and secondary headache disorders accounted for 0.7% and 2.5%, respectively. The female preponderance of migraine was also maintained in the elderly people (F: 62% and M: 36.6%), and the decrease in the frequency of the most common primary headache disorders (both migraine and tension-type headaches) was confirmed. Chronic daily headache was diagnosed in 4.4% of cases, including both transformed migraine and chronic tension-type headache. Similar results were obtained in a community-based survey of registered residents, 65 years of age or older, in two townships in China. In this study, as in adults, analgesic overuse by elderly people suffering from chronic daily headache is a significant predictor of a poor outcome (19).
Characteristics of migraine in elderly people, the relationship with the previous migraine history, factors influencing its severity and concomitant pathologies have been little investigated with the exception of the menopausal period and hormonal replacement in female migraineurs (20–23).
The present study aimed to investigate the clinical characteristics of migraine in elderly people and was carried out on a group of patients over 60 years of age, selected from 1400 consecutive patients to the Headache Centre of the Neuroscience Department in the period January 2000–December 2001.
Patients
One hundred and sixty-three consecutive headache patients were included in the study, consisting of 129 females and 34 males. The mean age of the group was 68.3 ± 7.2 years (range 61–79 years).
Methods
A computerized semistructured interview was used to collect the clinical history and information on headache characteristics (frequency and duration of attacks, location, pain intensity, quality of head pain, aggravation with routine daily activities, accompanying symptoms, aura characteristics and duration) referred in the last year. Other questions included: age of onset, concomitant diseases and symptomatic and prophylactic therapy. Moreover, all patients underwent a physical and neurological examination conducted by a neurologist of the Headache Centre.
To verify changes in headache characteristics, patients were asked for the mean number of days per year with migraine referred in the last 5 years, with particular attention to the number of days with intense and disabling headache, and nausea or vomiting as accompanying symptoms. Frequency and intensity of migraine attacks were compared with those referred in the last 5 years. Headache diaries were helpful for this purpose in 80% of patients examined. An improvement was defined if there was a reduction of 30% or more of the number of days with intense or moderate migraine, a worsening if there was an increase of 30% or more. The relationship between the modification of migraine with menopause and hormonal replacement in women was also investigated.
Headache diagnoses were made according to the 1988 IHS criteria (24).
Statistical analysis
The frequencies and percentages of all categorial variables were calculated. Fisher χ2 was used for the comparison of percentages of migraine attack characteristics between MwoA and MwA patients. A statistical significance of P < 0.05 was chosen as the minimum level of statistical significance. Continuous variables were expressed as mean ± 2SD.
Results
Among the 163 out-patients examined, 152 (93.3%) were affected by a primary headache disorder. According to the 1988 IHS Criteria, their prevailing attacks could be diagnosed in order of frequency as migraine without aura (MwoA) in 57.2% of cases (n = 87), migraine with aura (MwA) in 11.8% of cases (n = 18), followed by chronic and episodic tension-type headaches, which were diagnosed in the remaining 11.1% (n = 17) and 9.9% (n = 15) of the patients, respectively. Twenty-four (22.8%) migraine patients (5 with MwA; 19 with MwoA) also had concomitant attacks of tension-type headache which, on the basis of frequency per month, could be classified as episodic in all cases. Only information concerning migraine patients is reported in detail.
The diagnosis of migrainous disorder not fulfilling IHS criteria was made in 34.4% of MwoA patients (n = 16), since not all the mandatory criteria were met (IHS code: 1.7). In particular, criterion B (headache attacks lasting 4–72 h), criterion C (at least two of the following characteristics: unilateral location, pulsating quality, aggravation by walking stairs or similar routine physical activity), and criterion D (at least one of the following: nausea and/or vomiting, photo- and phonophobia) were not satisfied, respectively, in 30.3%, 33.3% and 36.4% of the cases. Concerning sex distribution, a clear prevalence in females both in MwoA (F = 86.2%, M = 14.8%) and MwA (F = 77.7%, M = 22.3%) patient groups was evident.
The first attacks occurred under 18 years of age in 38% of MwoA patients and in a slightly higher percentage (42%) of cases in MwA patients. The percentage of age onset between 18 and 40 years of age was 49% and 48% in MwoA and MwA patients, respectively. In both migraine patient groups it then tended to decrease: 9% and 8% between 40 and 50 years of age and only 3% and 4% in MwoA and MwA patients, respectively, after age 50. The frequency of attacks was higher in MwoA than in MwA patients, who in 77.2% of the cases had less than 1 attack per month (χ2 P < 0.05). Of the patients with MwoA, 42.5% suffered from 2 or 3 attacks per week, and in 18.4% of cases from 4 or more attacks per week.
Using the criteria of Silberstein et al. (18) a CDH (transformed migraine) was present in 15 (17.2%) of MwoA patients, 7 (8%) of whom showed an abuse of simple and/or combination analgesics. The duration of attacks was significantly shorter in MwoA than in MwA patients (P < 0.04). In 55.6% of MwA patients, the mean duration of attacks was shorter than 4 h, and, in particular, in 11.1% of these cases it was between 1 and 2 h. In more than half (58.6%) of MwoA patients it ranged from 4 to 12 h, whereas in a small percentage (3.4%), attacks lasted 2–4 h. The duration of attacks exceeded 48 h in a low percentage of cases (4.7%) in MwoA patients, but in none of the MwA patients (Table 1).
Frequency and duration of attacks
Details of the characteristics of migraine attacks are shown in Table 2. The location of head pain was unilateral in almost 45% of the cases in both migraine patient groups. Generally, it began in the ocular, periocular and/or frontotemporal regions (MwA = 75% and MwA = 68%), and then spread to the entire head. Less frequently the location at onset was in the occipital region and the neck. The pain was pulsating in 56.3% of MwoA patients and 38.8% of MwA patients (χ2 P < 0.05). In the latter patient group, pain was described as pressing/tightening in 50% of the cases. This percentage was lower (36.8%) in MwoA patients. In 55.5% of the cases, both in MwoA and MwA patients, the intensity of head pain was moderate or severe, with the higher percentages of severe pain in the MwoA patient group (48.3% vs. 38.8%) (χ2 P < 0.05). Aggravation with routine physical activities was reported by 72.4% of patients with MwoA and by 61.1% of patients with MwA.
Characteristics of attacks in MwoA and MwA elderly out-patients
The most frequent accompanying symptoms were photo- and phonophobia, (90% and 88%, respectively, in MwoA, and 84% and 78% in MwA patients). Less frequently, nausea and vomiting were present. In the majority of MwA patients the aura included only visual deficit symptoms, whereas motor and sensory aura symptoms, mostly associated with a visual aura, occurred in only a few cases (3 patients). Visual aura showed the same pattern described in adults. The typical visual aura began as unilateral spots or zigzag lines (fortification spectra – 83.3%) and often flickering (77.7%). They were white (44.5%) or coloured (27.7%), rarely yellow, or black or colourless (11.1%). Negative or positive phenomena most often appeared in the centre of the visual field originating as a central scotoma (61.1%), and then tended to expand to the periphery (50%). More rarely, the aura symptoms started in the periphery of the visual field (27.7%), and in this case central vision was preserved in the majority of the cases (22.3%).
At least 50% of the patients affected by MwA referred, together with the typical attacks, symptoms of aura not followed by headache. We classified these on the basis of the benign course and the exclusion of risk factors for transitory ischaemic attacks as late-life migrainous accompaniments.
The evolution of migraine in terms of variations of frequency and/or intensity of attacks in the last 5 years was also investigated. The distribution of headache changes (frequency and intensity of headache attacks) by age and sex in MwA and MwoA patients in the last 5 years is reported in Table 3. An improvement of migraine emerged in only 8.0% and 16.6% of patients with MwoA and MwA. A worsening of migraine attacks was referred by 67.6% and 44.2% of MwoA and MwA patients, whereas no changes of frequency and/or intensity of attacks were reported in 24.0% and 38.8% of cases, respectively. Worsening was particularly evident in women with MwoA aged between 60 and 70 years.
Changes in number of days with intense and disabling migraine in the last 5 years distributed by age and sex in MwoA and MwA patients
The percentages were calculated with respect to MwoA and MwA patients groups.
Regarding the relationship between evolution of migraine and menopause, 73% of women suffering from MwoA and 43% of women suffering from MwA showed a worsening, whereas only 5% and 14%, respectively, had an improvement. Five women in the MwoA patient group and 2 women in the MwA patient group underwent surgical menopause. In all of them a worsening of attacks in terms of an increase in the frequency, duration, and intensity of attacks was evident. It was not possible to examine the effects of replacement hormonal therapy on headache evolution because only a small number of women (5 with MwoA and 3 with MwA) used it.
In our study 86.2% of patients with MwoA (n = 75) and 83.3% (n = 15) of patients with MwA used symptomatic drugs for their attacks (Table 4). In the majority of cases they took more than one analgesic or non steroidal anti-inflammatory drug (NSAIDs) (MwoA: 78.1%; MwA: 72.2%), whereas acetaminophen in association with codeine or combination analgesics were less frequently used (MwoA: 11.5%, MwA: 16.6%). Triptans were taken by 12.6% of MwoA patients and 11.1% of MwA patients. None of them were over age 65 or had suffered from cardio- or cerebrovascular diseases or had related risk factors. Ergot derivatives were used by a few patients (4.6% with MwoA and 11.1% of MwA). Prophylactic drugs were used by 51.5% of patients with MwoA and 55.4% of patients with MwA. They included antidepressant drugs, beta-blockers, calcium channel antagonists and antiepileptic drugs (Table 4). In specific cases, the choice of symptomatic or prophylactic drugs was also made on the basis of concomitant diseases, which are reported in Table 5.
Symptomatic and prophylactic drugs used by MwoA and MwA patients
∗The percentage sum of symptomatic drugs taken exceeded 100 % because some patients took more than 1 symptomatic drug to treat their attacks.
Co-existing diseases in MwoA and MwA patients
Discussion
Relatively few studies have been published until now on the prevalence and characteristics of primary headaches, and particularly migraine in the elderly. The majority of information has been obtained from population-based studies examining migraine prevalence in large communities, including individuals over 65 years of age (2, 3, 5–9).
Several epidemiological researches strictly focused on the prevalence of migraine in elderly people and they considered a resident elderly population (15, 17), elderly people in old people's homes (12) or elderly out-patients (12, 14). The cut-off to define elderly people in the above studies was 65 years of age, as accepted world-wide, although some studies reported those aged over 60 years. Migraine prevalence widely varies in the latter studies (from 2.9% to 15%) due to the difference in age in the population examined, but in any case, the clear preponderance in females is always confirmed. Although a decrease in the frequency and intensity of migraine with age is the rule, modifications of the attack characteristics in old age have been scarcely investigated in detail.
From the present study carried out on a population of headache out-patients attending a Headache Centre in Italy, a clear prevalence of migraine in females was found as in younger adults. Although the present research was carried out in an out-patient population, the percentages obtained for unilateral pain location (about 44% for both MwA and MwoA) and severe or moderate pain intensity (5% and 70% of the cases in MwA and MwoA patients, respectively) were lower than those found in epidemiological studies involving younger adults (2, 25, 26). Moreover, photophobia and phonophobia were the more frequent accompanying symptoms referred by our MwoA and MwA patients aged over 60.
In our study, attacks of shorter duration were reported by MwA patients compared with MwoA patients. The former had attacks shorter than 4 h in 55% of the cases, whereas in the latter, attacks lasting between 2 and 4 h were present in only 3.4% of the cases.
The above findings concur at least in part with the results of a recent population-based study which analysed, in 50–74-year-old women, the relationship between headache characteristics and coexisting symptoms. This study found a decline of intensity and nausea but no decline of disability with age, whereas neither frequency nor duration seemed to be influenced. This apparent discrepancy between headache intensity and nausea decline but no decline of disability with age has been attributed to the age-related reduction in the ability to cope with challenges in general and migraine pain, which may in part be due to hormonal factors in women.
In our research, a worsening of headache in the last 5 years was referred by 67.6% and 44.2% of MwoA and MwA patients. This may be one of the main reasons patients sought help at a specialized clinic. No conclusion could be reached regarding the evolution of headache in relationship with hormonal replacement, due to the small number of patients who underwent this treatment.
As in previous reports, patients with MwA often showed a reduction of headaches. Although the head-pain phase disappeared, the aura symptoms recurred and became prevalent. The auras, however, did not differ from those described in younger adults. In our research, 55.5% of patients with MwA referred visual aura symptoms not followed by headache other than their typical attacks of migraine with aura.
In this case, it is mandatory to verify the benign characteristic of such symptoms, and because secondary headaches occur more frequently in the elderly, it is necessary to consider the differential diagnosis with transitory ischaemic attacks. To this end, the clinical monitoring of patients, taking care to note modifications of the presentation pattern and duration of symptoms and carrying out adequate instrumental investigations are fundamental (27).
As regards the therapeutic approach, it should be mentioned that 86.2% (n = 75) of patients with MwoA and 83.3% (n = 15) of patients with MwA used one or more symptomatic drugs for their attacks. These included, in the majority of cases, simple or combination analgesics or non steroidal anti-inflammatory drugs. In our study, using the criteria of Silberstein et al. (18), a CDH (transformed migraine) was diagnosed in 17.2% of MwoA patients. This condition was associated in about half of the cases with a misuse of simple and/or combination analgesics, which can contribute to initiate, aggravate, and perpetuate the headache. Its recognition can allow effective prevention even in the elderly.
Other symptomatic drugs, such as triptans, ergot derivatives and antiemetics were taken by only a minority of patients in both MwoA and MwA groups. No adverse effects were referred by patients using triptans and ergot derivatives. Prophylactic drugs were used by 51.5% of patients with MwoA and 55.4% of patients with MwA and included all classes of preventive drugs.
The choice of both symptomatic and prophylactic drugs has been conditioned, at least in our patient groups, by the presence of coexisting diseases. In this regard, it should be noted that both symptomatic and prophylactic drugs should be carefully used in elderly patients. Pharmacological interactions should be taken into consideration in addition to coexistent diseases, due to the frequent use of other drugs for the treatment of concurrent pathological conditions.
Ischaemic heart disease, hypertension, depression, anxiety and sleep disorders are the diseases frequently encountered in elderly people and were also identified in our patients. Other pathologies that limit or condition the choice and dosages of certain antimigraine drugs, such as bronchial asthma, glaucoma, kidney insufficiency, and prostatic hypertrophy, etc. occur in only a few cases, at least in our out-patient group.
Even in the absence of coexisting pathologies, it should be remembered that the distribution and excretion of certain drugs can change in the elderly, and that higher blood levels can be reached. Altered pharmacokinetics and pharmacodynamics in elderly people may increase the likelihood of side-effects and drug interactions. Downward dose adjustments and simplifying medication regimens are often appropriate, as is using non pharmacologic therapies whenever possible (28). Due to frequent contraindications related to acute medications, non pharmacologic treatments assume greater prominence, especially when treating elderly people suffering from frequent and/or severe headaches (29). This is not the case with our elderly patients affected by migraine, none of whom used non pharmacologic strategies for the management of their attacks. However, it should be noted that the elderly do not respond as well as younger adults to non pharmacologic modalities.
Future efforts of our group will be directed towards investigating, over time, changes in the characteristics of all primary headaches (not exclusively in migraine), by an appropriate follow-up in a more numerous sample of out-patients over 65 years of age attending our Headache Centre. Our attention will also be focused on headaches which occur for the first time exclusively in people over 65 years of age.
Finally, the relationship between the peri-menopausal and menopausal period in women complaining of headache, and the effects on headache outcome by hormonal replacement will be more carefully investigated.
Footnotes
Acknowledgements
The authors express their gratitude to John A. Toomey for editing the English and Marisa M. Morson for technical assistance.