The Characteristics and Risk Factors of Headache Development after the Coil Embolization of an Unruptured Aneurysm

Little is known about headaches post-aneurysm coiling. These authors treated 90 patients with unruptured aneurysms and no headaches. Nearly 56% developed headaches within 72 hours of treatment and all headaches resolved shortly thereafter. Only coil-packing attenuation was associated with presence of headaches. The authors concluded that though headaches were common, these were nearly always benign and resolved spontaneously. High packing attenuation may induce stretching of the aneurysm and inflammation that can result in headaches. BACKGROUND AND PURPOSE: Development of a headache after aneurysm coil embolization is not uncommon but has received little attention. The authors prospectively analyze the characteristics and risk factors of a headache after coiling in patients treated for an unruptured cerebral aneurysm. MATERIALS AND METHODS: Ninety patients treated for an unruptured cerebral aneurysm over a period of 1 year, and without a headache history within a month before coiling, were enrolled in this study. All coilings were successfully performed without neurologic complications. After coiling, headache development and intensities were recorded. RESULTS: Fifty (55.6%) patients experienced a headache (VAS score, 4.5 ± 2.02) at 7.9 (range, 0–72) hours, on average, after coiling, and all headaches resolved within an average of 73.0 (range, 3–312) hours. Univariate analysis showed that the following were significantly associated with the development of a headache: age ≤50 years (OR 4.636, 95% CI, 1.414–15.198), hypertension (OR 0.232, 95% CI, 0.095–0.571), a packing attenuation of >25% (OR 3.619, 95% CI, 1.428–9.174), and a previous headache history (OR 2.769, 95% CI, 1.120–6.849). However, binary logistic regression showed that only a packing attenuation of >25% (P = .013, adjusted OR 3.774, 95% CI, 1.320–10.790) and no history of hypertension (P = .019, adjusted OR 3.515, 95% CI, 1.233–10.021) were independently associated with the development of a headache. CONCLUSIONS: A headache frequently developed after the coiling of unruptured aneurysms. However, headaches were relatively benign and resolved within several days. The present study shows that no hypertension history and a packing attenuation of >25% are risk factors of headache development.

T he numbers of patients treated for an unruptured aneurysm by coil embolization continue to increase, and we have observed that many patients complain of a headache after coiling. Practically, headaches that develop after coiling are benign and resolve spontaneously in most patients. In our experience, the development of a headache is not uncommon but has received little attention. We considered that patients should be given instructions before the procedure regarding headache development after coiling. The aims of this prospective study were to document the characteristics of headaches that develop after coil embolization of an unruptured aneurysm and to identify risk factors.

Patient Collection
After obtaining institutional review board approval for this prospective study, patients with an unruptured aneurysm who were candidates for elective endosaccular coil embolization were considered for inclusion in this study. The exclusion criteria applied were as follows: 1) a nonsaccular aneurysm, such as fusiform or dissecting aneurysm; 2) therapeutic parent artery occlusion; 3) recoiling for a recanalized aneurysm; 4) a history of subarachnoid hemorrhage; 5) a history of another cerebrovascular disease, including arteriovenous malformation and Moyamoya disease; and 6) experience of a headache during the month before coiling. Having applied these criteria, 90 consecutive patients treated from September 2009 to November 2010 were enrolled in this study.

Coil Embolization Procedure
In all patients, aneurysm coiling was performed under general anesthesia using a biplane angiographic unit (Integris Allura; Philips Healthcare, Best, the Netherlands). One neurointerventionist (O.-K.K.) performed all coilings at 1 institute (Seoul National University Bundang Hospital). Preparation for, and the technical details of, the procedure were conventional and were previously described in detail. [1][2][3][4] All aneurysm embolizations were performed using detachable platinum coils, including the Guglielmi (Boston Scientific, Fremont, California), MicroPlex (MicroVention, Aliso Viejo, California), and Axium (ev3, Irvine, California) coils. Modified coils, such as the Matrix (Boston Scientific) and HydroCoil (MicroVention), were not used. Final postembolization angiography was performed to detect thrombus formation, parent artery compromise, or distal embolism. According to the study protocol, patients with any neurologic deficit after coiling or a procedural complication, such as hemorrhage, infarction, or any other complication capable of inducing a headache, would have been excluded, but all 90 coilings were performed successfully and none of these complications were encountered.

Patient Information, Aneurysmal Factors, and Procedural Factors
Much information was collected on factors that could potentially influence headache development, such as demographic data, social background (employment status, marriage, level of education), coexistent medical conditions (hypertension, diabetes mellitus, or others), previous headaches, and medication history. In addition, information on aneurysmal characteristics (diameter, neck size, and location) and procedural factors (methods used, packing attenuation, duration of anesthesia, total radiation dose, and radiation flow time) were collected. Aneurysm diameters were classified as small (Յ5 mm), medium (5-15 mm), or large (Ն15 mm), and neck sizes were classified as narrow (Յ4 mm) or wide (Ͼ4 mm). The following formulas were used to calculate packing attenuation: Packing attenuation (%) ϭ ͓coil volume͔/͓aneurysm volume͔ ϫ 100.

Headache Details
Headache intensities were measured using a 10-cm horizontal VAS before and after coiling. A headache after coiling was defined as 1 or more headaches of more than mild intensity, as determined by the International Classification of Headache Disorders (2nd edition). 5 Patients were monitored for headache development immediately after coiling, hourly for the first 6 hours, and then every 6 hours until discharge. When a patient began to feel a headache developing, onset time, intensity, characteristics, and duration of the headache were recorded, and when a patient requested analgesics, NSAIDs (usually 650 mg oral acetaminophen or 100 mg aceclofenac) were administrated until the headache improved, according to European Federation of Neurological Societies guidelines. 6 At 2 weeks after discharge, patients were re-evaluated for the presence of a headache at our outpatient clinic. For a patient whose headache did not resolve until discharge, we also recorded when the headache disappeared, if the headache resolved after discharge.

Statistical Analyses
Statistical analysis was conducted using SPSS version 17 (SPSS, Chicago, Illinois). The Mann-Whitney U test or Wilcoxon signed rank test was used to analyze numeric variables, and the 2 or Fisher exact test was used to analyze nominal variables. Binary logistic regression analysis was performed on variables with an unadjusted effect, with a P value of Ͻ.15 by univariate analysis, to identify risk factors of a headache after coiling. Statistical significance was accepted for P values Ͻ.05.
Basic clinical data, social backgrounds, aneurysmal characteristics, and procedure-related factors are summarized in the On-line Table. Patients who developed a headache (the headache group) were younger (54.7 Ϯ 12.36 versus 60.5 Ϯ 8.43 years; P ϭ .011) and more likely to be Յ50 years old (34.0% versus 10.0%, P ϭ .011; OR 4.636, 95% CI, 1.414 -15.198). In terms of coexistent medical conditions, the proportion of patients with hypertension was smaller in the headache group than in the nonheadache group (38.0% versus 72.5%, P ϭ .001; OR 0.232, 95% CI, 0.095-0.571). Furthermore, the proportion of patients with a previous headache history (usually a migraine type headache) was significantly higher in the headache group (48.0% versus 25.0%, P ϭ .030; OR 2.769, 95% CI, 1.120 -6.849). Interestingly, packing attenuation was higher in the headache group (30.0 Ϯ 7.01% versus 25.7 Ϯ 7.84%, P ϭ .007), and aneurysms with a packing attenuation of Ͼ25% were significantly more frequent in the headache group (80.0% versus 52.5%, P ϭ .007; OR 3.619, 95% CI, 1.428 -9.174). Social backgrounds, aneurysmal characteristics, method used, anesthesia time, radiation dose, and radiation flow time were not found to be significantly different in these 2 groups.

Discussion
This series shows that a headache developed in approximately half of our patients after coil embolization of an unruptured aneurysm. However, all headaches were benign and resolved on average at 3 days after coiling. The absence of a history of hypertension and a packing attenuation of Ͼ25% were found to be associated with the occurrence of a headache after coiling. In our practice, these findings are being used to provide information to patients before and after coiling. Dilation or stretching of intracranial arteries can produce a headache. [7][8][9][10][11][12][13][14][15][16] This dilation can be induced by mechanical forces as well as chemicals. It is well known that many patients experience a headache during angioplasty of the intracranial artery, 7,8,13 and a similar mechanism may apply to headache development after coil embolization. During and after coiling, if coil packing is enough to entrap blood and to not permit free blood flow, thrombosis can be induced in the coil frame and aneurysmal sac. The coil mass itself, and thrombosis in coiled aneurysms, cause distension of the aneurysmal wall, which can induce a headache. In addition, this thrombosis was also found to lead to local inflammation and subsequent headache. 17 These appear to explain the finding that headaches develop more frequently with a high (Ͼ25%) packing attenuation.
Healthy vessels unaffected by hypertension could be more distensible and elastic, [18][19][20][21] and thus the walls of aneurysms in patients without a hypertension history could be more affected by pressure increases within aneurysmal sacs, and may explain why patients without a hypertension history had a greater rate of headache development.
The present study has several limitations that warrant consideration. First, the study is limited by its relatively small cohort, which may have affected our analysis of some of the factors investigated. For example, some aneurysm locations were not well represented, especially aneurysms in posterior circulation, and thus we were not able to analyze the effect of location. Second, VAS may not be the best measure of headache intensity. However, VAS has most of characteristics that an ideal method for pain measurement should have. 22 In addition, in our experience before conducting this study, a headache after coiling was usually mild or moderate. VAS is known to be suitable for trials that include patients with mild and moderate headaches. 23,24 Furthermore, few patients who are candidates for elective coil embolization have factors impeding scale use, such as impaired abstract thinking ability or psychomotor problems. [25][26][27] Therefore, we chose VAS as a measurement tool of headache intensity. Finally, MR imaging was not performed after coiling to detect any other reasons that can cause a headache, including small embolic infarctions. However, a review of the literature failed to unearth any relationship between small infarctions and headaches. If MR imaging were performed in all of our study subjects, it would be more helpful to prove the relationship between thrombosis and inflammation, and the development of a headache after coiling. However, because the study reporting this finding was recently published, 17 we were unable to consider MR imaging evaluation for this purpose. Nevertheless, our findings demonstrate that headaches after coiling are benign, short-lived, and easily controlled. We hope that these results will be used by physicians to provide information about headache devel-opment to patients before and after coiling of an unruptured aneurysm.

Conclusions
A headache develops in approximately 50% of patients with an unruptured aneurysm after coiling. However, headaches are usually benign, short-lived, and easily controlled. This study shows that absence of a hypertension history indicates susceptibility to the development of a headache, and that a high coil packing attenuation is also a risk factor of headache development after coiling.