Clinical manifestations

Presentation and course

Late-life migrainous accompaniments are the aura symptoms of migraine that precede the headache in migraine with aura. They can be visual, motor, sensory, or behavioral in nature and usually last several minutes or less, unless the symptoms are prolonged (over 1 hour), in which case they are classified as prolonged migraine aura. Today these late-life migraine accompaniments would be called “late-life migrainous equivalents” or migraine aura without headache and are recognized as generally benign in nature but of important diagnostic interest.

Migraine with aura (formerly called classic migraine) is distinguished from migraine without aura (formerly common migraine) by the neurologic symptoms of aura and not the headache symptoms. Headache can also occur in patients with transient ischemic attack or stroke (36; 25), although this is not always recognized or appreciated.

In his second communication, Fisher recapitulated the main diagnostic criteria for late-life migrainous accompaniments as follows:

In the 2 series, the most common symptoms of late-life migraine accompaniments were visual symptoms and, when scintillating scotomata were excluded, transient blindness, homonymous hemianopsia, blurring of vision, and difficulties with visual focusing (17; 19). The second most common complaints were sensory, in the form of paresthesias (tingling, pins-and-needles, and numbness). The third most common group of symptoms were related to the brainstem and cerebellum, and included ataxia, clumsiness, tinnitus, deafness, syncope, and incoordination. The last group of symptoms was speech disturbances, including dysarthria or aphasia that occurred separately or in combination with visual or sensory symptoms.

Prognosis and complications

Persistent neurologic deficits are rare, even when attacks continue for years. Fisher published a personal account of life with migrainous auras without headache (20). He noted 41 episodes of scintillating zigzags that occurred when he was between 59 and 85 years of age. These did not occur on a regular basis and were unrelated to season, time of day, activity at onset, diet, or emotional state. The visual symptoms, which were stereotyped and achromatic, began centrally and moved peripherally. The average duration of the visual symptoms was 15 minutes; both visual fields were equally involved, but never at the same time. Aring was well into his 80s when he summarized his own quarter-century experience with late-life migraine (03). He noted no personal sequelae and said in conclusion, “Migraine is a strange and wonderful disorder.”

Patients with late-life migrainous accompaniments probably have the same morbidity and mortality as do those with other forms of migraine; however, Shuaib and Lee reported cases of permanent sequelae following late-life migraine accompaniments (42). They reported 4 cases with infarctions: 2 in the occipital lobe, 1 in the frontoparietal lobe, and 1 in the cerebellum. They wondered if the ischemia was caused by vasospasm. On the other hand, stroke in patients with late-life migraine accompaniments could also be expected because migraine may on occasion lead to migrainous infarction and stroke is common in the elderly.

Clinical vignette

Three cases of late-life migraine accompaniments follow:

Case 1. A 58-year-old man had had 1 or 2 spells a year of combined visual and speech disturbance. He had experienced these symptoms for 5 years, but they began occurring 2 or 3 times a week 6 months previously. During a spell, he lost the ability to focus and the lateral parts of his visual field were filled with shimmering pinpoints of light. There was a “build-up” for 2 to 3 minutes; the symptoms remained at a peak for 30 minutes, and then faded and disappeared in 1 hour. At the height of the episode, the patient was unable to read and enunciation and fluency of speech were impaired. There were no paresthesias. The patient was aware of a slight pressure in his head at the onset but he did not call it a headache.

Interestingly, this is Case 12 from Fisher’s original series (17) and is representative of the cases seen with this disorder. This patient had the build-up, progression, and march from the neural origin of his visual symptoms presumably from his occipital cortex to the speech symptoms arising from his parietal and temporal speech centers. Headache is not seen in all cases, or it may be mild. In mid-life, as in this case, there can be a “flurry” of late-life migraine accompaniments.

Case 2. A man had 3 identical spells, at ages 30, 45, and 65 years, respectively. In each, he suddenly awakened from a deep sleep, jumped up, and developed weakness of the right side of his mouth and right hand and an inability to speak properly. This lasted about 10 minutes. All tests short of angiography were normal.

This is Case 21 of nonvisual symptoms from Fisher’s second series (19). This case is interesting as there is no time to observe any build-up, progression, or march of symptoms because of the sudden onset of symptoms on awakening. Also, in the absence of angiographic or other evidence to rule out transient ischemic attack or other etiology, one would be hard pressed at present to call these late-life migraine accompaniments. Nevertheless, a lifelong history, beginning as a young man, of the same stereotypical attacks could suggest that the attacks were migrainous in nature.

Many of Fisher’s reported cases may not have been late-life migraine accompaniments. Also, some cases, particularly in the second series, were young (19). One was aged 13 years (Case 2), and another, special Case 24, was 25 years of age and had multiple segmental narrowing on angiography, which raised the question of “arteritis” versus migraine. Given the age range and diagnostic uncertainty in some cases, it probably would be best to call these attacks transient migraine accompaniments or transient migraine equivalents.

An additional syndrome, that of transient global amnesia, might reasonably be added to the spectrum of late-life migraine accompaniments given observations on the pathogenesis of transient global amnesia and its relationship to migraine. The essential features of this disorder, originally described by Fisher and Adams, are of an episode of acute onset of transient anterograde amnesia of a global nature, with some involvement of retrograde memory, without any other major neurologic symptoms or signs (21). This disorder may be related pathophysiologically to migraine (see Etiology).

Case 3. Late-life migrainous accompaniments are common symptoms seen by neurologists; thus, it is no surprise that neurologists will frequently have such symptoms, given that neurologists (and headache specialists in particular) have high prevalence of migraine headaches (14). Given this predisposition, the author describes his own recent experience with late-life migrainous accompaniments. Having experienced such symptoms putatively makes them easier to recognize in other patients and gives a clearer understanding of other formes frustes of migraine. What follows is the recent history of the author.

History. A 72-year-old physician had a 23-year history of recurrent scintillating scotoma involving either the right or left visual hemifield.

These would last 20 minutes; they would occur in flurries over days and then abate for months. There were no other migraine symptoms, and his history was void of any headaches of any significance other than an occasional ice-cream-induced headache, a variant of ICHD 3 Headache attributed to ingestion or inhalation of a cold stimulus (25) and a few episodes of “airplane descent headache” (15).

Comment. This case illustrates some important clinical points: migraine is not always seen in its full clinical spectrum; aura and headache can be separated out clinically, as occurs in late-life migrainous accompaniments; other headaches with putative migraine associations can occur along with migraine, including “ice cream headache;” and a neurologist possibly having migraine or some of its subcomponents may have an enhanced ability to identify a migraine disorder--recognizing that the latter statement is not based on evidence but on a personal clinical experience, similar to the original description of the disorder by Dr Miller Fisher (17). As well, the long duration of his symptoms suggests a benign disorder to date.

Biological basis

Etiology and pathogenesis

Late-life migraine accompaniments are the neurologic aura migraine symptoms, often occurring without headache. The mechanism of aura may well be a homologue of the spreading depression of Leao (29; 28), and it is now recognized that there is relative hypoperfusion during the aura (34) and that the headache begins during the vasoconstrictive phase. This is in contrast to the older theories of migraine headache, which attribute the aura solely to vasoconstriction and the subsequent headache to vasodilation (50). It has been suggested that painful cephalic vasodilation may not occur in older patients with transient migraine accompaniments because of vascular rigidity and atherosclerosis (02; 32). It is now believed that the headache arises from activation of trigeminal afferents in the meninges.

The putative spreading depression can begin in cortical areas and spread gradually from 1 area to another (28). If it begins in visual cortex, contralateral scintillating scotomata and other visual phenomena can occur. A central scotoma that enlarges as the aura builds can be present as well. The cortical inhibition, which is preceded by a wave of excitation, may start in the sensory cortex, producing paresthesias and other sensory phenomena, sometimes without visual aura. This march across sensory homunculus can lead to a spread from face and tongue to hand and arm and, sometimes, leg. If the speech center is involved in the aura, word-finding difficulty and other speech symptoms occur. Involvement of motor cortex can also lead to a homuncular march with resultant hemiparesis or even hemiplegia.

Decreased cerebral blood flow, but not ischemia, during the prodrome has been documented using methods for measuring cerebral blood flow (Olesen and Friberg 1990; 31). A number of studies have shown that the aura phase is associated with a reduction of cerebral blood flow in the cortex of the posterior part of the hemisphere contralateral to the affected visual field, paresthesia, or other focal neurologic symptoms, and the cerebral blood flow reduction appears to move across the cortex at a rate of 3 mm/min to 6 mm/min and is preceded by a phase of hyperperfusion consistent with that seen in cortical spreading depression (06).

Wolff’s original studies reported temporary resolution of migrainous scotomata in several patients during amyl nitrate inhalation (50). Amyl nitrate caused cerebral vasodilation, and when the inhalation was stopped, the scotomata reappeared. Wolff concluded that cerebral vasospasm was responsible for the visual aura of migraine; however, that is not the modern view (28; 24).

Cerebral vasodilator capacitance measured by xenon-enhanced CT cerebral blood flow measurement before and after acetazolamide administration showed a significant decline with advancing age among normal patients, and even more among patients with late-life migrainous accompaniments (32). This could explain the reduction in frequency and severity of migrainous headache with age and the appearance of late-life migrainous accompaniments.

Although the pathophysiology of late-life migraine accompaniments is still uncertain, the mechanisms of their production are probably identical to migraine aura; they are really migraine variants or equivalents. It appears that late-life migraine accompaniments, like migraine auras, are due to the neurogenic process of cortical spreading depression. Ischemia could trigger migraine-like phenomena in a patient with a migraine tendency, but this would still suggest that it is still migraine that is being triggered. A case report suggests that an internal carotid artery stenosis mimicked late-life migraine accompaniments in a 65-year-old woman with a history of acephalgic migraine (01). Other mechanisms, such as down-regulation of serotonin vascular receptors in menopause and aging, may play a role, as many menopausal women and elderly patients have migraine aura without headache (08).

With respect to studies possibly linking migraine to transient global amnesia, a 1999 study using PET scanning done during an episode of transient global amnesia showed no change in the hippocampi; however, it did show reduced cerebral blood flow and metabolism in the frontal and temporal cortices with a mild reduction in cerebral blood flow and normal metabolism in the occipital cortex (12). It suggested that neocortical involvement may play an important role in the genesis of transient global amnesia and that transient global amnesia may be due to the spreading depression of Leao (28). Further studies using SPECT scans in a patient during an episode of transient global amnesia, 24 hours later, and 3 months after the episode, showed bilateral mesial temporal lobe hypoperfusion that partially resolved after 24 hours and returned to normal at 3 months; as the scan abnormalities abated, the patient’s memory problem resolved (27). The authors suggest that decreased local metabolism, such as cortical spreading depression, could be the mechanism of this case. Further, a transcranial Doppler study carried out during the acute phase of the amnesia showed no evidence of hemodynamic alterations or significant asymmetries; however, the test was repeated after clinical recovery and showed values that were similar to those reported in the previous study (26). The authors concluded that ischemia was an unlikely mechanism, but a mechanism producing spreading neurogenic depression similar to a migraine attack may be active during a transient global amnesia attack. (It should be noted that other mechanisms of transient global amnesia have been proposed and debated; readers are directed to the article on transient global amnesia. Nevertheless, transient global amnesia probably mimics late-life migraine accompaniments in mechanism and is clearly in the borderland of this disorder.)

Mechanisms remain important and are of great interest to neurologists who see cases of late-life migrainous accompaniments. Reviews in this disorder and migraine aura without headache, along with increasingly sophisticated imaging, particularly MR, which is increasingly available to diagnosticians, make it possible to learn the breadth and depth of late-life migrainous accompaniments and its mimics (47; 40).

Epidemiology

Migrainous visual accompaniments are not rare in late life. Wijman designed a questionnaire to elicit symptoms of transient ischemic attack that also may detect late-life transient visual symptoms similar to the visual aura of migraine, often without headache (49). In this study, 2110 subjects were questioned twice yearly for 17 years about visual symptoms. Twenty-six (1.23%) had migrainous visual episodes; most (77%) began after the age of 50 years; they were stereotypic in 65%. The episodes lasted 15 to 60 minutes in 50% of subjects; 58% never had headaches accompanying the episodes; and 42% had no headache history. Twelve percent of subjects sustained a stroke after the onset of migrainous visual symptoms, but in contrast, of 87 subjects with transient ischemic attack in the same study group, 33% developed a stroke, two thirds within 6 months of transient ischemic attack onset. They concluded that late-life-onset transient visual phenomena similar to the visual aura of migraine are not rare and often occur in the absence of headache. These symptoms appear not to be associated with an increased risk of stroke, and invasive diagnostic procedures or therapeutic measures are generally not indicated.

Late-life migrainous accompaniments occur more frequently in men than women (19; 22). More than 80% of those diagnosed with late-life migrainous accompaniments seek medical care within 4 years of symptom onset (45). A review of a large database of 12,750 African-American and white men and women found that 3% of participants had a history of migraine with aura (44). The mean age of the study population was 60 years, with 73% of the population 55 years of age and older. The population was 77% white and 56% female. It was shown that migraine with aura was strongly associated with stroke symptoms (OR 5.46, 95% CI: 3.64 to 8.18), transient ischemic attack symptoms (OR 4.28, 95% CI: 3.02 to 6.08), and verified ischemic stroke events (OR 2.81, 95% CI: 1.60 to 4.92). This, of course, is the age group in which most late-life migrainous accompaniments occur, and the authors concluded that more research on the relationship of stroke and migraine in this group is needed.

Current perspective (2020). Since the original description of late-life migrainous accompaniments, much has changed in the understanding of migraine and its pathophysiology (23). Migraine may reflect a state of the brain. Late-life migrainous accompaniments could be the residual of migraine, with a reduction in the headache part of the migraine attack. There is increased risk of stroke for migraine with aura (39), but not for late-life migrainous accompaniments.

This “clinical entity” of late-life migrainous accompaniments remains in the lexicon of clinical neurologists and is used frequently to differentiate patients with late-life migrainous accompaniments from those with other neurologic disorders, in particular TIA, stroke, and seizures. Because these patients can have typical aura without headache or typical aura with some headache with or without migraine characteristics, they don’t easily fit into the new ICHD3 classification unless they are coded for 2 variants of migraine with typical aura, 1.2.1.1 and 1.2.1.2 (25). Ultimately, patients may overlap with other migraine subtypes as they expand, including 1.4.2, which is persistent aura without infarction, although this relationship has not been proven to date and this subtype is rare.

Late-life migrainous accompaniments appear to be more a syndrome than a definite classifiable entity. Because microemboli can initiate aura, migraine with aura could exist on a continuum with ischemic stroke (05; 11; 04).

What distinguishes these cases from younger patients with migraine with aura without headache is the age of the patients. A study by Donnet and colleagues indicates that late-life-onset transient visual phenomena are not rare (10). Symptoms may occur for the first time after age 50 years in the absence of headache or in the presence of a headache that has the characteristics of typical aura with non-migraine headache.

Whether late-life migrainous accompaniments will still be considered benign in nature in the future awaits further research. Most appear transient, but some may herald more ominous outcomes, especially because these cases can occur in patients who also have major stroke-risk factors. The diagnosis of late-life migrainous accompaniments must be made carefully to ensure they are not mimics of cerebrovascular disease that need to be managed differently. In particular, the diagnosis of any transient focal neurologic episodes, which includes symptoms similar to migraine, needs to be explored particularly in the older age group because the diagnosis of cerebral amyloid angiopathy, which can present with lobar hemorrhage, can also present with transient focal neurologic episodes with local cortical subarachnoid hemorrhage (46). Here the investigation using T2-weighted grading imaging techniques or susceptible weighted imaging may be required to make the diagnosis (47).

The good news is that by and large late-life migrainous accompaniments generally are benign in outcome, but again that could change with new knowledge and even better imaging over time.

Prevention

Because late-life migraine accompaniments are really migraine aura without headache, it would appear that they may be prevented by using medications that abort migraine headache; however, this is usually not necessary as they are so transient in nature. In addition, most medications are directed to stopping headache and ancillary symptoms, not aura, per se. The most important thing is for the diagnostician and ultimately the patient to recognize what they are; if they are true late-life migraine accompaniments, the physician should reassure all who are concerned. Patients in the age group for late-life migraine accompaniments also are the ones who have risk factors for transient ischemic attack and stroke; management of these risks are important, but independent.

Differential diagnosis

Fisher’s criteria for late-life migraine accompaniments continue to be valid. They are over 20 years old, and although they would be modified today due to neuroimaging and other tests, they are still applicable. These late-life migraine accompaniments display a “build-up” and “progression” of symptoms that are not typical of stroke or transient ischemic attack symptoms. Further, the “march” of symptoms from 1 area of the body to another–visual to face to arm to hand, for example–is typical of late-life migraine accompaniments, but not of stroke (19). The duration of a late-life migraine accompaniment march (15 to 25 minutes) is much longer than a seizure march, which is usually 1 or 2 minutes. Sensory seizures, however, must be in the differential diagnosis (16). Transient ischemic attacks usually last less than 10 minutes (33).

Typical visual aura or photopsias consisting of scintillating scotomata are highly characteristic of migraine, especially when they are gradual in onset and progressive (02). In contrast, transient ischemic attack (09) and sensory stroke are sudden in onset and usually not reversible (18). Migraine sensory aura can involve the tongue and oral mucosa, in contrast to a transient ischemic attack, in which such involvement is rare (38; 19). This is an important clinical clue. Late-life migraine accompaniments can recur for years without sequelae; this would be unlikely in atherothrombotic, embolic, or cardioembolic stroke, as would full reversibility of any symptoms in these conditions. Patients with occipital lobe strokes, for example, usually have persistent or residual visual symptomology, unlike those who have late-life migraine accompaniments. In 1 study, vertebrobasilar transient ischemic attacks could be differentiated from late-life migrainous accompaniments by their lower regional cerebral blood flow and greater asymmetry of the anterior cerebral blood flow (37).

The most important differential diagnosis of late-life migraine accompaniments is transient ischemic attack or stroke. Usually the criteria noted can make diagnosis relatively straightforward, especially if the patient had similar symptoms earlier in life or many recent repeated stereotypical episodes. The distinctions can be made but must be done carefully because risk factors for stroke can be similar in these patients (35). In a study of transient ischemic attack, patients who had recurrent, predominantly sensory symptoms were felt to have a more benign course, and were probably migrainous in nature (07). However, if paresthesias are the presenting complaint, one must also consider pure sensory stroke of the thalamus if the symptoms are persistent (18). Vascular malformations or tumor can present with migraine-like symptoms and, like stroke, must be considered if there are any atypical features.

The most recent iteration of the International Headache Society’s Classification of Headache continues to take a careful new look at migraine and migraine with aura and makes some changes, which now include the following: typical aura without headache (which is really what constitutes most of the cases of late-life migraine accompaniments) and typical aura with headache (25). The latter is included to remind diagnosticians that nonmigraine headache can also follow typical aura. Thus, if the headache following presumed late-life migraine accompaniment does not meet the criteria for migraine, it becomes even more important to rule out another cause, particularly transient ischemic attack or a mimic of migraine.

The new classification from the Headache Classification Subcommittee of the International Headache Society describes typical aura as: aura consists of visual and/or sensory and/or speech/language symptoms, but no motor weakness, and is characterized by gradual development, duration of each symptom no longer than 1 hour, a mix of positive and negative features, and complete reversibility. Commonly, as patients become older, headaches lose the migraine characteristics or they disappear completely, with auras continuing. Men especially can have typical aura without headache from the onset.

Finally, one should never overlook the diagnosis of temporal arteritis in the elderly, as many elderly patients will present with visual symptoms, including amaurosis, and headache with no specific features. Constitutional symptoms, including weight loss, fatigue, polymyalgia rheumatica, jaw and tongue claudication, fever, anemia, and elevated erythrocyte sedimentation rate, usually lead to the diagnosis, the institution of steroid therapy, and a temporal artery biopsy. In essence, late-life migraine accompaniments are a diagnosis of exclusion if transient ischemic attack, stroke, arteritis, or other serious etiologies are being considered in any individual case.

Diagnostic workup

Late-life migraine accompaniments are often benign events that do not require investigation. However, a review of neuroimaging in migraine suggests neuroimaging may be considered for presumed migraine for the following reasons: atypical in nature, prolonged or persistent aura, increasing frequency, severity, or change in clinical features, first or worst migraine, migraine with brainstem aura, migraine with confusion, hemiplegic migraine, late-life migrainous accompaniments, aura without headache, side-locked headache, and posttraumatic headache (13). If necessary, magnetic resonance angiography (MRA), echocardiography, and Doppler ultrasound can be performed to exclude a source of cerebral embolism, such as atherosclerotic plaques, dissection of cranial arteries, and cardioembolic sources, whereas EEG can help exclude seizures. CT, CT angiography, MR, and MRA are also useful in detecting the presence of stroke and transient ischemic attack mimics, such as a tumor or aneurysm. Specialized MR sequences (47) or susceptibility weighted imaging may be needed to ensure that cases of cerebral amyloid angiopathy presenting with transient focal neurologic episodes in the elderly are not the underlying cause of similar symptoms due to focal subarachnoid hemorrhage. MR diffusion-weighted imaging is useful in diagnosing ischemic stroke. Because patients with migraine may have increased risk of complications following contrast angiography, this procedure should be avoided, if possible. However, in 1 study of 142 migraine patients, it appeared that migraine did not increase the risk of complications caused by angiography, and was felt to be safe; however, transient focal neurologic symptoms occurred in 2.6% of cases (41). Blood tests should be done to exclude platelet disorders, polycythemia, and hyperviscosity syndromes, as well as lupus anticoagulant, phospholipid antibodies, other rare coagulopathies, temporal arteritis, or other rare arteritides if there is an index of suspicion that these disorders may be present. However, investigation should not be done if the history is typical of late-life migraine accompaniments and abnormalities are not present on clinical examination (09; 08).

Management

There is no evidence-based information on how to treat late-life migraine accompaniments, and they may not need any specific intervention. Standard migraine therapy is suggested if there is headache, although vasoconstricting agents such as ergotamines and triptans should probably be avoided in these age groups, especially if there are any significant cardiovascular or cerebrovascular risk factors. Preventive therapeutic suggestions are anecdotal and have not been validated in large trials.

Special considerations

Pregnancy

Because patients with late-life migraine accompaniments are usually over age 45 years, pregnancy is rarely an issue. It is known that migraine symptoms may increase early in pregnancy and postpartum, but generally subside in the second and third trimester (43), so it is possible that some migraine accompaniments could occur during the course of pregnancy in middle-aged women; these would have to be diagnosed and managed appropriately.

Anesthesia

In theory, both local and general anesthetic agents should be well tolerated by patients with late-life migraine accompaniments, however, there are no evidence-based data to support that statement. Migraine may also be an independent risk factor for stroke (30). Older patients can have risk factors for transient ischemic attack, stroke, and cardiac disease, and these must be carefully sought and managed in any patient having anesthesia. Thus, the risk in these patients of any untoward event during anesthesia can never be zero.