Endovascular thrombectomy and post-procedural headache

Eligible patients were phone interviewed once, on average 1.6 years (range: 0.2–3.0) after EVT, using a purpose-developed semi-structured questionnaire. We collected information on headache status 1 year and 1 month before EVT and after EVT (3 months after and at time of interview).

All headaches were classified according to the International Classification of Headache Disorders 3, beta version [4].

Frequencies and percentages were calculated for categorical variables and medians and range for continuous variables. For comparisons of categorical data, we used the McNemar test. All p-values were two-sided and p-values below 0.05 were considered statistically significant. All analyses were performed using IBM® SPSS® Statistics version 23.

In total, ninety-six patients were eligible and included in the study (Table 1). Twenty-five subjects (26%) reported lifetime history of migraine, 14 of these (15%) had migraine with aura, and 25 subjects (26%) reported lifetime history of tension-type headache (TTH). One year prior to thrombectomy, sixteen subjects (17%) reported migraine, 11 of these (12%) had migraine with aura, and 15 subjects (16%) reported TTH.

Considering the focal intravascular manipulation inflicted on the vessels, headache after thrombectomy seems likely due to endothelial injury-induced inflammation of the intracranial vessel walls, activating sensory afferents. In support, a recent 3 T vessel wall MRI study reported contrast enhancement in arterial walls in patients treated with stent-retriever thrombectomy [5]. The bidirectional link between headache and EVT has thus far never been investigated, hence it is unknown whether history of headache may influence the endovascular procedure due to vascular complications such as distal embolization or dissection (Additional file 1: Table S2), and vice versa whether a complicated procedure may affect headache patterns after EVT. Studies on familial hemiplegic migraine type-1 mutant mice show larger infarcts and worse neurological outcomes after stroke compared to wild-type mice [6], specifically suggesting that a diagnosis of migraine with aura may predispose to vascular complications during the thrombectomy procedure.

As a major finding, we report a significant drop in migraine prevalence after thrombectomy for subjects with pre-EVT history of migraine, resulting in prevalence estimates close to those for the general population. We lacked a control group to assess for decline in migraine prevalence over time irrespective of EVT. However, we believe that the reduction of migraine observed in our study is beyond what one would expect from the natural history of this disorder [7]. This decrease could also be explained by the initiation of antithrombotic medication after thrombectomy [8]. No new prophylactic migraine treatment was initiated after EVT.

Contrary to migraine, we found that thrombectomy led to an increase in TTH after EVT, with a significantly larger prevalence compared to 1 month prior to treatment. However, when comparing the post-procedural prevalence with 1-year prior to thrombectomy, we observed no change, suggesting that thrombectomy does not result in added headache burden in the larger scope of life-time headache evolution. Differences in post-procedural medication (such as antithrombotic treatment) cannot explain this disparity between migraine and TTH, as all subjects were started on antithrombotic treatment after thrombectomy.

We also report new onset of headache in a subset of subjects (11%) who undergo thrombectomy. This headache resolves over time for some TTH cases, but persists for those reporting de novo migraine, suggesting that a fraction (8%) of subjects treated with thrombectomy may develop persistent new headache. Any de novo headache that occurs with close temporal relation to EVT is per definition a secondary headache, however, the current ICHD-3 beta criteria only allow any such headache to last up to 24 h [4]. This taxonomy is inadequate, as post-thrombectomy headache for the majority lasts at least 3 months, if not longer. Also, our results confirm the accepted notion that migraine with aura is overrepresented in a stroke cohort compared to the general population [9], and may even be larger in our cohort compared to other stroke case-based studies [10].

Finally, our results show that 12.5% of subjects undergoing thrombectomy experience peri-procedural complications. Albeit underpowered, these data suggest that migraine with aura does not increase the risk of complications during thrombectomy.

In conclusion, we have presented the first report of headache onset and prevalence after thrombectomy. Strengths of the study include a homogenous patient group, direct phone interviews, and ICHD-3 beta classification [5]. Limitations include recall bias and a relatively small sample size. Nevertheless, we believe the data help improve our understanding of post-procedural headache to optimize counseling of subjects who undergo thrombectomy with resultant headache. Larger, statistically robust prospective studies are warranted to establish the direction and magnitude of changes in migraine and other headaches after thrombectomy and to further explore migraine as a risk factor for peri-procedural complications.