Abstract
Migraine is one of the most prevalent neurological disorders among all age groups including the elderly, but the incidence and prevalence of migraine tend to decrease with age. The clinical phenotype of migraine also appears to be different in the elderly patient group in comparison to the younger patient group, with elderly migraine appearing to be more often bilateral and associated with what has become known as “late-life migraine accompaniments. Furthermore, difficulty in the differentiation of migraine from vascular insults such as transient ischemic attacks and amyloid angiopathy and other multiple comorbidities, polypharmacy and age-related changes in pharmacodynamics and pharmacokinetics makes treatments for this cohort challenging but necessary, especially given the worldwide increase in life expectancy, and likelihood of migraine continuing to be a major personal and public health problem.
Migraine (see Table 1 for the diagnostic criteria for migraine) is one of the most prevalent neurological disorders and the most neglected, under-diagnosed medical disorder worldwide [1-4]. Migraine is also the ostensible cause of significant disability worldwide [5]. Migraine generally begins during early childhood with a peak around puberty, (~12 years in boys and 15 years in girls [6] but may first appear at any age [7] with a small number first self-reporting in their sixth, seventh and eighth decades of life [8]. Indeed the literature [9, 10] suggests that migraine is most active between the third and fourth decades of life with the majority of elderly chronic migraine patients indicating an onset of migraine prior to 50 years [11-14]. Importantly, given the worldwide increase in life expectancy, older age migraine is likely to become a far greater personal and public health issue over the next 40 years as management is likely to be confounded by other health problems and consequent association with polypharmacy.
Diagnostic criteria for typical aura without headache and migraine with typical aura IHCD-3 [34]
![Diagnostic criteria for typical aura without headache and migraine with typical aura IHCD-3 [34]](https://karger.silverchair-cdn.com/karger/content_public/journal/ned/52/1-2/10.1159_000494758/2/m_000494758_t01.png?Expires=1704804625&Signature=3zDqBcHYKQfarW7UG4JXYeDuPRBGDulRFfE1svyNZcNNM5Q1Bf4GC7EzkBJCPUPNNX2QlUTRCAA3gi~~BoMjdlB6s1ED3TqnUXroDdPaxa1Q2tX8D6Vhtpmt~c16zmlqs~6ODInpvIVzAbETzcHsK8W0E6J~2bfDRF1jMP4r7DCihMZ6ZduL9w11madqgTm9xIQhtMHDRpnsrRYAp8AVvn4ncpgJ3RwHQwWAOp4CNDGCvruEcw0vn0kE3Ogm81oAJsueuBSbBA6sUf5N3mN9o0EtzSwsDagG6Ln~88Nkzxnyma9KVgv2UJIjO4rIw9rq7EKTCGO5S-gLUiXiUJR00g__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Migraine is the second commonest headache disorder after tension type headache in older adults with a one-year prevalence of about 10% [7, 15]. Interestingly, the clinical characteristics of migraine change with age [16] and as co-morbidities increase [11]. In a study of 260 consecutive patients with migraine, ranging in age from 3 to 69 years, marked differences in clinical features were observed with age [17]. The percentage of males with migraine decreased markedly from childhood to adulthood. In females, the duration of headache, unilateral pain, pulsating sensation, light sensitivity and noise sensitivity -increases with age. In contrast worsening of headache with physical activity decreased with age [17]. Neck pain also increases with acute attacks of migraine in the elderly [18]. Other studies have shown increase in autonomic symptoms (tachycardia, sweating, dry mouth, facial flush), while there was a reduction in sensory sensitivities as well as nausea and vomiting as patients got older [14]. Thus, treatment options for migraine in older individuals are complex and challenging and made more so by the exclusion of older patient groups (> 65 years) from the majority of clinical trials in migraine [19, 20].
The prevalence of chronic headaches (chronic migraine, chronic tension type headaches, medication overuse headaches [MOH]) in the elderly ranges from 5 to 22% and occurs more commonly in women [14, 21, 22]. Headache accounts for 14.9% of female patients and 6.1% of male patients general practitioner visits in Australia [2]. Worldwide, headache is the tenth most common symptom in elderly women and fourteenth most common symptom in elderly men [23]. Headache has the potential to adversely affect quality of life and limit domestic and community activities of daily living, and therefore carries a high burden of disability [24].
Although certain primary headaches, such as hypnic headache and primary cough headache, occur more commonly in the elderly, the prevalence and incidence of primary headaches decrease with age [11-14]. Conversely, secondary headache syndromes increase in incidence with aging and important differentials to consider include intracranial space-occupying neoplasms, intracranial haemorrhage, giant cell arteritis, trigeminal neuralgia or post-herpetic neuralgia, cervicogenic and cervical spine related headache and headache associated with comorbidities such as sleep-disordered breathing [13, 25].
Migraine in the elderly also tends to present less classically. In a Brazilian retrospective study on patients presenting to an outpatient headache clinic, migraine patients older than 60 years were more likely to be bilateral and less likely to have migraine associated symptoms (photophobia and phonophobia and/ or nausea or vomiting), compared to younger (aged 20–40 years) migraine patients [14]. Elderly patients may also present with aura only (acephalgic) migraines [23] and shorter attacks of migraine [24]. Fisher et al. [24] point out that concomitant mild cognitive impairment and changes in memory and thinking are not uncommon in the elderly. Therefore, the history of presenting complaint may be limited and therefore, a diagnosis of migraine may be challenging in this cohort. The association between cognition and migraine is controversial – with some evidence that the two are not associated [24, 26].
Another interesting aspect of migraine in the elderly is the onset of late life migraine accompaniments or migraine without aura (noted above), which is more common in the elderly [27-30]. In an important early consideration of migraine in 1980, Fisher [28] described this interesting condition for the first time in 1980 (120 cases in 1980, 85 cases in 1986 and 205 cases in total [27, 28]) proposing the term “late life migraine accompaniments (LLMA)” as a common differential diagnosis occurring in acute stroke population [31-33]. Fifty per cent of the cases experienced headaches with 23% of the cases in patients aged 40–49 years, while 40% were 50–59 years of age, 20% of the cases were patients aged 60–69 years and 16% were patients aged 70 years and over [27, 28]. Sixty five per cent of these patients had been diagnosed with recurrent headaches in the past [27, 28]. Of the 120 patients with “unexplained transient cerebral ischemic attacks” with normal cerebral angiograms in whom the transient episodes of neurological symptoms resembled the neurological accompaniments of migraine reported by Fisher [28] in 1980, 25 of these patients had visual and paraesthesia disturbances, 18 visual and speech disturbances, 7 visual and brain stem symptoms, 14 visual, paraesthesia and speech disturbances, 7 visual, paraesthesia and speech disturbances and paresis, 25 recurrence of old stroke deficit. The late life migraine accompaniments typically include spreading sensory, visual or speech disturbance that can occur suddenly, rarely and generally last for less than an hour [34]. Fisher noted that the neurological deficits of LLMA may occur before, during or after an attack of migraine.
Fisher went on to propose the following criteria to support the diagnosis of LLMA [27].
1. The presence of visual symptoms
2. Gradual build up, expansion or migration of symptoms of the scintillating display
3. A march of paraesthesia
4. The serial progression of one accompaniment to the other (e.g., visual to paraesthesia)
5. The occurrence 2 or more identical spell of symptoms
6. Headache noticed by at least 50% of cases
7. Slightly longer duration than transient ischemic attacks (TIAs) – 15–25 min in LLMA compared to the majority of TIAs that last less than 15 min
8. Benign clinical course trajectory
9. The occurrence of a cluster of LLMA spells in older subgroup (50–60)
10. No evidence of cerebral thrombo-embolism, dissection or prothrombotic status with blood tests
11. No evidence of atherosclerosis
12. Normal cerebral angiography.
Fisher later came up with 8 additional observations in 1986 [27].
1. At least 10 out of 205 patients described episodic horizontal or vertical diplopia which lasted from few seconds to few minutes
2. At least 20 out of 50 patients with numbness of various components of the body went on to describe numbness of the tongue. Fisher felt when the transient numbness is the only symptom in these patients, the diagnosis of migraine was of a prime consideration for him
3. The remarkability of focal distribution of the numbness that may be limited to one toe, one finger, the chin on one side, a small patch of the cheek, tip of the tongue appears to be more suggestive of migraine
4. The brevity of symptoms as many patients were quite certain that their numbness in the finger or hand lasted only a second or few seconds
5. Some patients described transient tinnitus, a sound in the ear or head
6. Few patients described sudden severe pain in the head which they described as “struck with a sledgehammer”
7. Few patients described “triggers” from telephone ringing, overwork at income tax time and stress over unresolvable problems
8. Few patients described a feeling of faintness or presyncope.
Unfortunately, Fisher [27] provides no details about the associated medical conditions of these patients. It would be very useful to know the number of patients with hypertension, diabetes and all medications being taken concurrently by these patients.
Challenges Related to Treatment
Treatment of migraine in the elderly is often difficult due to the multi comorbidities and polypharmacy [35, 36] associated with age, for example, diabetes, hypertension, heart disease and other cerebro-vascular occurrences. In addition, the older population is characterised by general physiological changes such as slowing of gastric emptying, reduced hepatic mass and blood flow (hence the changes in rate of metabolism of drugs in the liver), reduced renal mass and glomerular filtration rate with direct impact on pharmacokinetics and pharmacodynamics [37]. Furthermore, many age-specific pharmacokinetic and pharmacodynamic considerations associated with long-term therapeutic management of blood pressure, cholesterol (statins) diabetes and/or mood have been reported, thus highlighting the special consideration needed to be given to management of geriatric migraine in clinical practice. Furthermore, as many elderly patients may be taking analgesics for other painful conditions, such as arthritis, medication overuse in headache is not uncommon in this age group [23]. Indeed a French study at a tertiary headache centre has recently reported a prevalence of 30% of headache from medication overuse in the elderly [11].
Non-Pharmacological Interventions
Non-pharmacological measures such as good mental health hygiene including proper sleep, regular physical activity such as daily walking, proper hydration, positive stress management and avoidance of triggers such as hunger must be advised to all elderly migraine patients [38-41].
Acute Treatment
The goal of acute treatment is to achieve sustained pain free response, that is, to be pain free in 2 h time of the acute treatment and also in 24 h [42-46]. Simple analgesics such as paracetamol, acetylsalicylic acid, antiemetic drugs such as metoclopramide, NSAIDs, triptans can be used in acute treatment [45, 47-49]. However, it is also critically important to minimize potential for acute overuse treatment as this would invariably lead to MOH [50].
Longer-Term Preventative Treatments
Tricyclic antidepressants, beta blockers, sodium valproate, topiramate, lisinopril, candesartan, calcium channel blockers, onabotulinum toxin injections, CGRP antagonists or CGRP receptor antagonists are prescription alternatives currently approved for use as migraine prevention [51-66]. However, yet again it is important to use these medications with caution in the elderly – ideally at low doses initially and slow gradual increase [67]. It is also important to individualise the treatment (i.e., a patient with hypertension will be better off with initial preventative medications such as candesartan, which will be helpful for blood pressure control as well as monthly headache day reduction. A patient who is overweight may benefit from a medication such as topiramate that is known to cause weight loss.
Conclusion
The prevalence of migraine in older patients who are in their sixties and seventies is significant though less than in younger cohorts with both incidence and prevalence decreasing with age. The clinical phenotype also appears to be different (bilateral rather than hemispheric and MOH), with patient attacks being symptomatically less typical, for example, LLMA, in comparison to the younger patient group [14]. Treatment choices are also more difficult, given the multiple comorbidities and potential polypharmacy associated with increasing age. Furthermore, there are also many fewer published studies in the literature (see Table 2 for those found in PubMed using terms “migraine in elderly,” “Late life migraine accompaniments,” “elderly migraine,” “prevalence of elderly migraine” specifically designed to explore the features of migraine and chronic migraine or clinically trial medications in the elderly [older than 65] from 2002 to 2018). Thus, migraine as a severely neglected disorder, particularly in the elderly, needs better recognition and attention, with more extensive exploration of the specific pharmacokinetics and pharmacodynamics in comorbid-illness--induced drug-drug interactions. Lastly, research into -evidence-based management, both in terms of acute and preventative treatment, is a matter warranting high -priority.