Headache after ischemic stroke: A systematic review and meta-analysis

Abstract

Objective: Headache associated with ischemic stroke is poorly understood. To gain further insight, we systematically reviewed studies examining the prevalence and characteristics of new-onset poststroke headache.

Methods: Medline and PubMed databases were queried. A total of 1,812 articles were identified. Of these, 50 were included in this systematic review. Twenty were included in a meta-analysis and meta-regression.

Results: Headache occurred in 6%-44% of the ischemic stroke population. Most headaches had tension-type features, were moderate to severe, and became chronic in nature. Meta-analysis using an inverse-variance heterogeneity model revealed a pooled prevalence of 0.14 (95% confidence interval [CI] 0.07-0.23) with heterogeneity among studies. Metaregression revealed a significant association between prevalence and study location, the source population's national human development index (HDI), and study quality. We found higher prevalence in European (0.22, 95% CI 0.14-0.30) and North American (0.15, 95% CI 0.05-0.26) studies compared with Middle Eastern and Asian studies (0.08, 95% CI 0.01-0.18). However, within each region, populations from countries with higher HDI (p = 0.03) and studies with higher quality (p = 0.001) had lower prevalence. Calculated crude odds ratios (ORs) showed that posterior circulation stroke (pooled OR 1.92, 95% CI 1.4-2.64; n = 7 studies) and female sex (pooled OR 1.25, 95% CI 1.07-1.46; n = 11 studies) had greater odds of headache associated with ischemic stroke.

Conclusions: Taken together, these data suggest that headache is common at the onset of or shortly following ischemic stroke and may contribute to poststroke morbidity. Better understanding of headache associated with ischemic stroke is needed to establish treatment guidelines and inform patient management.

Figure 1. Flow diagram of study inclusion/exclusion

Search strategies generated 1,812 articles using the search terms detailed in the Methods. Of these, 20 studies were included in the meta-analysis of prevalence.

Figure 2. Pooled prevalence of ischemic stroke headache

(A) Inverse variance heterogeneity model: forest plot shows prevalence by individual study and the % weight, which is inversely proportional to the squared value of the standard error. The pooled prevalence of ischemic stroke–related headache is 14%. (B) Random effects model: pooled prevalence of ischemic stroke headache using the random effects model yields a higher pooled estimate (22%). Because of the high degree of heterogeneity, the random effects model tends to unweight the studies, as demonstrated by the % weight values falling between a narrow range of 4.5–5.2. CI = confidence interval.

Figure 3. Assessment of publication bias

Given broad scatter of the funnel plot (A) and asymmetry of the doi plot (B), the prevalence estimate is likely affected by publication bias.

Figure 4. Study characteristics: geographic region and quality score (QS)

(A) Headache prevalence varies depending on regional location. European studies had higher prevalence values as compared to studies from other regions (Middle East and Asia). Likewise, studies whose source population was from the United States had higher prevalence values than those from Middle East and Asia. (B) Studies with a lower QS report a higher headache prevalence as compared to studies with higher QS (QS − fractional QS). CI = confidence interval.

Figure 5. Patient characteristics: posterior circulation (PC) stroke and female sex are associated with greater odds of ischemic stroke headache

(A) Headache prevalence for PC and anterior circulation (AC) stroke is reported for each study. The pooled headache prevalence for PC stroke is higher than that for AC stroke. The odds of having headache is 2-fold higher with PC stroke as compared with AC stroke. (B) Headache prevalence for female and male participants is reported for each study. There is a modestly higher prevalence of stroke-related headache in women as compared to men with a pooled odds ratio (OR) of 1.25. CI = confidence interval.