Abstract
Dear Sir It is well established that certain individuals with episodic migraine will develop chronic daily headaches, which suggests that migraine may be a clinically progressive disease in individuals at risk (1). Additionally, a recent study proposes that migraine may also be an anatomically progressive disease. Kruit et al., in a large cross-sectional population study, found that migraine sufferers were at significantly increased risk of clinically silent infarct-like lesions in the posterior circulation territory of the brain, notably in the cerebellum (2). The adjusted odds ratio (OR) was 13.7 [95% confidence interval (CI) 1.7, 112] for patients with migraine with aura compared with controls. The highest risk was in patients with migraine with aura with one attack or more per month (OR 15.8; 95% CI 1.8, 140). Furthermore, based on the radiological aspects of the lesions, they suggest that a combination of possible migraine attack-related hypoperfusion and embolism is the likeliest mechanism for PC infarction in migraine, and not atherosclerosis or small-vessel disease (2, 3).
Recent evidence also suggests that migraine (possibly more so migraine with aura), is comorbid with patent foramen ovale (PFO), which may explain some of the silent brain lesions (4). Finally, migraine with aura has been consistently suggested as a risk factor for stroke in young women (5, 6).
Based on these findings, there has been much interest in theoretical prospects for avoiding migraine progression, and proposals that the role of preventive treatment in the management of migraine must be reassessed, based on the fact that timely use of daily preventive treatment might modify the long-term outcome of migraine sufferers (7). According to some authors, preventive therapy should be used when patients experience as little as two migraines per month; have severe, recurring migraine; or are overusing or have failed acute medications. The argument is that reductions in attack frequency and severity by migraine prevention decrease the likelihood of drug overuse and may reduce the risk of facilitating pain transmission, neuroplasticity, and subsequent transformation to a more chronic, refractory and disabling form of migraine.
Although we absolutely agree that preventive medication is often underutilized and that the use of prevention may reduce attack frequency and severity and, therefore, pain and disability, we ask ourselves if we are not missing the point. Regarding preventive therapies, it is important to emphasize that:
It is not demonstrated that prevention changes neuroplasticity and decreases the risk of silent lesions in the brain.
In the Kruit study, lesions were more frequent in those with one or more headache day per month. Not all patients using prevention will have less than 1 day of headache per month. In specialty care, indeed, just the minority will, even with high doses of appropriate preventive medications. At these settings, most patients on prevention will have three to five migraine attacks per month or much more.
Finally, if some of the lesions in the brain are embolic in nature, prevention will not change the risk for these lesions.
On the other hand, there is little or no discussion about whether we should use antiplatelet therapy. This is relevant because:
Level 1a evidence supports the use of antiplatelet therapy with aspirin, clopidogrel, or the combination of aspirin and dipyridamole for the primary and secondary prevention of stroke, although not for migraine stroke (8).
It has been demonstrated that there is at least a small treatment effect of low-dose aspirin in the prevention of migraine (9), especially among middle-aged women (10).
Low-dose aspirin is safe and tolerable in most patients with migraine (8–10).
We do not believe that all subjects with migraine with aura should receive antiplatelet therapy, and are not even convinced that at least some of them should. It is our opinion that the current evidence on migraine as a risk factor for silent lesions should not be dogmatically accepted but rather questioned awaiting further evidence. As clearly pointed out by Goadsby, the causal relationship between migraine and cardiac right-to-left shunts deserves further investigation, the increase of stroke in migraine sufferers is numerically small, and the study by Kruit and colleagues is cross-sectional, providing a hypothesis, and not proof (11). However, if these associations hold true, it may be that antiplatelet therapy is more important than migraine prevention for groups at risk, not in reducing current pain and disability (which preventive medications indisputably do), but in reducing the risk of silent infarcts in the brain.