Identification of ruptured intracranial aneurysms using the aneurysm-specific prediction score in patients with multiple aneurysms with subarachnoid hemorrhages- a Chinese population based external validation study

Subarachnoid hemorrhage (SAH) caused by a ruptured intracranial aneurysm (RIA) has high mortality and disability rates [1]. RIAs should be treated as soon as possible to prevent rebleeding, and the choice of treatment method (microsurgical clipping or endovascular coiling) depends on the site of the RIA [2]. Approximately 30% of patients with intracranial aneurysms (IAs) have multiple IAs (MIAs) [3], and approximately one-third of MIAs have uncertain rupture sources [1]. Misdiagnosis of the location of the RIA may lead to postoperative rebleeding and a poorer outcome [4, 5]. Therefore, it is of great clinical value to accurately determine the RIA in MIAs if all IAs cannot be treated at the same time.

The hemorrhage pattern is generally the primary indicator of RIA; however, it is quite difficult to judge RIAs by diffuse or symmetrical bleeding [6]. Although high-resolution contrast-enhanced magnetic resonance vessel wall imaging helps to identify the site of RIA in patients with MIAs, scan time and spontaneous motion are notable limitations [7]. Some scholars used the population, hypertension, age, size, earlier subarachnoid hemorrhage, aneurysm site (PHASES) score and unruptured intracranial aneurysm treatment score (UIATS) to predict RIA [8‐11]. However, all these studies showed that the PHASES score and UIATS had a lower ability to identify RIA.

Recently, Hadjiathanasiou et al. [6] developed a novel prediction score, the aneurysm-specific prediction score, for simple and quick identification of RIAs. Encouragingly, the prediction score correctly identified the RIA in all the patients. However, it is not clear whether this score is highly applicable to the Chinese population. After all, in terms of genetics, the Chinese and Caucasian are not identical. Hence, we sought to identify whether the aneurysm-specific prediction score is able to predict RIA in the Chinese population.

One hundred and thirty-four patients with 290 MIAs (one ruptured and the other unruptured) were available for analysis (supplementary file). Among the 33 males and 101 females, the mean ages were 59.5 years for all patients, 54.7 years (range, 41–79 years) for males, and 60.9 years (range, 33–86 years) for females. There were 115 patients with 2 IAs, 16 patients with 3 IAs and 3 patients with 4 IAs.

Interobserver agreement on the CTA categorical factors was good (k = 0.951 for the shape of the IAs, k = 1.000 for the location of IAs). Table 1 summarizes the morphological characteristics of the IAs. The mean maximum diameter was 6.34 ± 3.07 mm (range, 1.8–20.7 mm). The mean aneurysm-specific prediction score was 0.28131 ± 0.48 (range, -0.49909–1.24993). The maximum diameter, irregular shape, location in the PcomA and ICA, and aneurysm-specific prediction score were significantly different between the ruptured and unruptured groups.

The diagnostic accuracy of the morphological characteristics of the IAs and the aneurysm-specific prediction score are listed in Table 2. When using maximum diameter alone, the sensitivity, specificity, false omission rate, diagnostic error rate, and diagnostic accuracy were 81.3%, 83.9%, 18.7%, 16.0% and 82.8%, respectively. When using irregular shape alone, the sensitivity, specificity, false omission rate, diagnostic error rate, and diagnostic accuracy were 29.1%, 23.0%, 70.8%, 76.9% and 25.7%, respectively. When using IA location alone, the overall diagnostic accuracy was 43.1–62.4%. When using the aneurysm-specific prediction score, the RIAs were misdiagnosed in 17 patients with 38 MIAs (Table 3). Six RIAs had a large maximum diameter, but due to the location and shape of IAs, the aneurysm-specific prediction score was reduced (Figs. 2 and 3). The sensitivity, specificity, false omission rate, diagnostic error rate, and diagnostic accuracy of the aneurysm-specific prediction score were 87.3%, 89.1%, 12.7%, 10.9%, and 88.3%, respectively.

The ROC analysis was performed for continuous data. The areas under the curve for maximum diameter, location, shape and the aneurysm-specific prediction score were 0.798, 0.536, 0.736 and 0.781, respectively (Fig. 4 and Table 4).

The aneurysm-specific prediction score was established according to IA size, location and shape and was developed to identify RIAs in SAH patients harboring MIAs [6]. In this study, we applied the aneurysm-specific prediction score in 134 SAH patients with MIAs and found that the sensitivity, specificity, false omission rate, diagnostic error rate, and diagnostic accuracy were 87.3%, 89.1%, 12.7%, 10.9%, and 88.3%, respectively.

Traditionally, size has been considered an important factor in IA rupture, and a large IA is considered more prone to rupture than a small IA. Some studies have reported that size is a significant predictive factor for IA rupture [12, 13]. Although Björkman et al. [14] indicated that IA size was associated with IA rupture, the RIA was not of the largest size in 13% of their study cohort, and they found that irregular shape may identify the RIA better than size in patients presenting with SAH and MIAs. In addition, Backes et al. [2] reported that RIA was not the largest IA in 29% of patients with MIAs. In this study, 18.7% (25/134) of the patients had an unruptured IA with the largest diameter, and 15 of them did not have the largest aneurysm-specific prediction score.

Irregular shape was thought to be associated with IA rupture [12, 13], possibly because the irregular shape increases the local hemodynamic stress [15]. Backes et al. [2] reported that irregular shape is associated with IA rupture independent of IA size and location and independent of patient characteristics. Björkman et al. [14] showed that shape and size had the best diagnostic value for identifying RIAs in patients presenting with SAH and MIAs, but shape may be better than size. However, Orning et al. [4] reported that it is unreliable to use morphological features of IA in determining rupture sites in nondefinitive SAH patterns. Another study also showed that morphological and hemodynamic parameters seem to have no or only low effect on the prediction of RIA in patients with MIAs [16]. The present results showed that 39 (29.1%) RIAs had regular shapes, and 36 (23.1%) unruptured IAs had irregular shapes.

IAs located in the AcomA, PcomA, or PC are considered to have a high risk of rupture [17‐19]. The American Heart Association/American Stroke Association indicated that the treatment decision regarding UIAs is based mainly on the size and location [20]. In this study, PcomA, AcomA and MCA were the most common sites in aneurysmal SAH patients. These results are consistent with previous study [21]. Although IAs located in the PcomA ruptured more often than IAs in other locations, the diagnostic accuracy was only 62.4%.

The aim in developing the aneurysm-specific prediction scoring system was to identify RIAs in SAH patients with MIAs, and the prediction score had high accuracy in a small prospective sample [6]. In this study, the aneurysm-specific prediction score had high sensitivity and specificity, but 17 UIAs were misdiagnosed as RIAs. On the other hand, the area under the curve of the aneurysm-specific prediction score was lower than that of maximum diameter, indicating that the performance of the aneurysm-specific prediction score was not satisfactory. One of the reasons is that IA size and shape may change after rupture. Another reason is the inherent flaws of the aneurysm-specific prediction scoring system: sometimes the location and shape of IAs may lead to a decrease in the aneurysm-specific prediction score. The coefficients need to be optimized to further improve the rate of recognition of RIAs. In addition, morphological characteristics such as location of bifurcation, small-diameter of the parent artery, and location of the AcomA with A1 dominance are risk factors for IA rupture [22, 23]. Some studies reported that an aspect ratio ≥ 1.3 or the size ratio were the best factor for identifying RIAs [2, 24]. Finally, different populations may lead to different results. It is well known that Japanese and Finnish patients have a higher risk of IA rupture than those from other geographic regions [25]. While, a nationwide epidemiological in China showed that among the patients with aneurysmal SAH, only 15.4% had MIAs [21], which less than Caucasian and Japanese population [17, 26].

We applied the aneurysm-specific prediction score to Chinese patients with MIAs and SAH to identify RIAs and found that the scoring system had high diagnostic accuracy but was not perfect. Larger cohorts for prospective evaluation are warranted in the future.