Stroke Alert: A Review of Current Clinical Stroke Literature
April 1, 2012 4 minutes read
Stroke Alert: A Review of Current Clinical Stroke Literature
By Dara Jamieson, MD, Associate Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Jamieson reports she is a retained consultant for Boehringer Ingelheim, Merck, and Ortho-McNeil, and is on the speakers bureau for Boehringer Ingelheim.
Headaches, Blood Pressure, Cerebral Autoregulation, and Ischemic Lesions
Synopsis: Antihypertensive treatment reduces the incidence of headache compared to placebo, but the magnitude of the effect differs between drug classes independent of the magnitude of blood pressure reduction. Dysautoregulation in the anterior and posterior circulation is associated with migraine with aura.
Sources: Webb AJS, Rothwell PM. The effect of antihypertensive treatment on headache and blood pressure variability in randomized controlled trials: A systematic review. J Neurol 2012;DOI 10.1007/s00415-012-6449-y.
Reinhard M, et al. Cerebellar and cerebral autoregulation in migraine. Stroke 2012 DOI: 10.1161/STROKEAHA.111.644674.
Antihypertensive drugs reduce headache, but it is unclear whether there are differences between drug classes. If so, there might be a correlation between drug-class effects on variability in systolic blood pressure (SBPV) and on headache. Webb and Rothwell evaluated antihypertensive class effects on SBPV and headache in a meta-analysis of 248 randomized clinical trials of antihypertensive medications in which there was documentation of the occurrence of headache. Antihypertensive drug classes were compared with each other, and across subtypes within classes. Pooled estimates of treatment effect on group variability in BP and on the odds ratio for headache were determined by random-effects meta-analysis. Antihypertensive drugs reduced the incidence of headache compared to placebo, but there was significant heterogeneity between drug classes. Beta-blockers reduced headaches compared to placebo or all other drug classes (without significant difference between non-selective and selective agents); calcium channel blockers were ineffective. Drug-class effects on headache were opposite to the effects on variability in SBP, but were unrelated to differences in mean SBP. Variability in SBP was reduced most by calcium channel blockers, reduced less by diuretics, and increased with randomization to a beta-blocker, compared to all other drugs or to placebo. These effects were not dependent on differences in mean SBP. The authors postulate that differences in variability in SBP could reflect effects on peripheral vascular tone and could correlate with changes in the cerebral circulation, partly explaining the differences in incidence of headache.
The cause and pathology of cerebral white matter lesions, commonly found in migraineurs with aura, are unknown. Asymptomatic brain lesions, presumed to be ischemic, are located in cerebellar border zones, which could imply an impairment of cerebellar blood flow autoregulation. Reinhard et al investigated the characteristics of interictal cerebellar autoregulation in patients with migraine with (n = 17) and without (n = 17) aura, compared to 35 age- and sex-matched controls, using triple simultaneous transcranial Doppler monitoring of one posterior inferior cerebellar artery (PICA), the right posterior cerebral artery (PCA), and the left middle cerebral artery (LMCA). Autoregulation dynamics were assessed from spontaneous blood pressure fluctuations (correlation coefficient index Dx) and from respiratory-induced 0.1-Hz blood pressure oscillations (phase and gain). Compared with controls, the autoregulatory index Dx was significantly higher (indicating less autoregulation) in the PICA (P = 0.0062) and MCA (P = 0.0078) in patients with migraine with aura, but not in migraine without aura. Phase and gain did not differ significantly between migraine patients and controls. No significant association of autoregulation with any clinical factor was found, including frequency of migraine attacks, time since last attack, time to next attack, and orthostatic intolerance. There was no specific cerebellar dysautoregulation in the interictal period. However, more static autoregulatory properties were impaired in persons with migraine with aura, both in the cerebellar and anterior circulation. The authors concluded that cerebellar predilection of ischemic lesions in migraine with aura might be a combination of altered autoregulation and additional factors, such as the end artery (poorly anastomotic) cerebellar angioarchitecture.
Commentary
The existence of a causal relationship between hypertension and headache is controversial, but some classes of antihypertensive drugs are effective prophylactic agents against headaches. Studies of headaches as a function of blood pressure must distinguish between the different etiologies of this pervasive symptom. While some headaches are related to elevated blood pressure, such as with posterior reversible encephalopathy syndrome, the association is rare, as reflected in hypertension's moniker "the silent killer." The analysis of headaches and antihypertensive therapy should distinguish between hypertension as a cause of headaches and the use of antihypertensive therapies to prevent headaches. The fact that antihypertensive medications decrease headaches does not imply that elevated blood pressure causes headaches. Nuances of the differential benefit of blood pressure lowering medications to prevent headaches (e.g., beta-blockers for migraines; verapamil for cluster headaches) reflect distinct pharmacological effects, rather than the global effect on blood pressure. This meta-analysis, which reviews headache complaints in randomized clinical trials of antihypertensive treatment, obviously cannot distinguish etiologies of pre-existent or subsequent headaches. These etiological distinctions may be reflected in the meta-analysis finding of significant differences in the magnitude of headache reduction between drug classes, independent of effects on mean SBP. The authors point out limitations in their analysis, as the trials lumped into the meta-analysis were not focused primarily on headache outcome data. Also, neuronal activation is likely to play a more prominent role in headache pathophysiology, than does cerebral autoregulation.
Just as patients with migraine headache are more sensitive to environmental perturbations, they may be more vulnerable to alterations in cerebral autoregulation. Reinhard et al found that migraine patients had a higher score of orthostatic intolerance and more often had a history of syncope. However, individual cerebellar or cerebral autoregulation in migraine patients interictally was not associated with syncope or orthostatic intolerance, so the authors concluded that a persisting alteration in autoregulation was not a likely explanation. The differential dysautoregulation, more pronounced in migraine with aura patients than in those without aura, is intriguing given the observed increased stroke risk in the group with aura. The MRI lesions in the brains of migraneurs are widespread, including in the cortical white matter and pons, so global, as opposed to exclusively cerebellar, dysautoregulation may not be surprising.
Antihypertensive treatment reduces the incidence of headache compared to placebo, but the magnitude of the effect differs between drug classes independent of the magnitude of blood pressure reduction. Dysautoregulation in the anterior and posterior circulation is associated with migraine with aura.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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