Aneurysmal Subarachnoid Hemorrhage: Is the Time Until Intervention Related to Minor Disabilities in 6 Months?

Abstract

Background Aneurysmal subarachnoid hemorrhages (aSAHs) account for 5% of all strokes, an appalling number when it comes to the second most common cause of death worldwide. The basis of the treatment is clinical support and either endovascular or surgical intervention. The purpose of the present study is to analyze if the time from the onset of the thunderclap headache until treatment intervention is related to the degree of disability after 6 months.

Methods In the present prospective observational study, data were collected from all patients (n = 223) admitted to the hospital with a diagnosis of aSAH. Patients whose data were missing or who missed the follow-up after 6 months were excluded. Then, the number of days from the thunderclap headache until the surgical intervention (Delta T) was obtained. The degree of disability was evaluated using standardized scales, Rankin Scale (RS) and Glasgow Outcome Scale (GOS), at the time of discharge as well as 6 months later. Then, the RS and GOS were correlated with Delta T.

Results An average of 6.8 days was found from the onset of symptoms to the intervention, the average age was 54 years old, 73% were women and 55% were smokers. The mean Glasgow Coma Scale on admission was 13. The mean score on the Hunt and Hess scale was 2.1. From the radiological point of view, the mean size of the aneurysm was 6 mm, and the modified Fisher Scale was 3.1. Of the total number of patients at the end of the study (n = 78), 50 underwent microsurgical treatment (63%). Rankin scale at discharge was 1.9 and GOS was 4.5, with no statistically significant change at 6 months. Analyzing the data distribution using linear regression, no statistically significant correlation was found between the time until treatment and disability using RS and GOS (p > 0.05). The same results were found even analyzing age subgroups (≤ 45 years old, 45 to 55 years old, 55 to 70 years old, and > 70 years old with a p-value > 0.05).

Conclusions The present study suggests that there is no linear correlation between Delta T and disability at 6 months for the population studied. However, more studies are needed to assess whether these findings may be present in other populations, especially with a shorter time from symptoms to intervention, since the greatest risk of rebleeding occurs in the first 3 days after the event.

Keywords

aneurysmal subarachnoid hemorrhage - disability - treatment - outcomes

Introduction

Aneurysmal subarachnoid hemorrhage (aSAH) accounts for 5% of all strokes,[1] which are the second most common cause of death worldwide, accounting for 11% of all deaths, as shown by the Global Burden of Disease (GBD-2017). Although decreasing in fatality,[2] [3] the burden associated is high and affects economically active people, especially those < 55 years old, leading to many years lost due to disability (YLD), with variable geographic distribution ranging from 5 to 120 YLD per 100,000 ([Figure 1]).

Fig. 1 Geographic distribution of the Years lost due to disability (YLD) caused by subarachnoid hemorrhage. Global Burden of Disease 2017.

The cause of an aSAH is the rupture of a saccular aneurysm. Most of them are acquired and related to known risk factors such as smoking, hypertension, alcohol, and cocaine abuse.[4] Usually, the clinical presentation is characterized by a severe and sudden headache which can be described as the worst ever experienced achieving the peak within one hour (thunderclap headache), often with no other symptoms, but can include neck stiffness, focal symptoms, and loss of consciousness.[5] The standard approach to diagnosis, then, includes a head CT scan and, if negative, a lumbar puncture, achieving 98% of sensitivity, especially valuable to rule out this diagnosis.[6] Once confirmed, it is mandatory to grade the severity of SAH, which can be performed through grading systems such as that proposed by Hunt and Hess in 1968[7] complemented by the Fisher grading of vasospasm based on CT scan.[8]

The treatment aims to prevent complications such as rebleeding; thus, the repair with surgical clipping or endovascular coiling is imperative, recommended to be performed within 24 hours,[9] as a Level B of evidence, as well as clinical stabilization. Even with all efforts, disabilities are not uncommon, and their assessments help to guide the treatment and contribute to the better management of these patients. Hence, the purpose of the present study is to correlate the time from the onset of the symptoms (thunderclap headache) until the treatment (surgical or endovascular) and short and long-term disability using the Rankin Scale[10] (RS) and the Glasgow Outcome Scale (GOS)[11] aiming to evaluate if the impact of the surgical treatment is time-dependent linearly.

Methods

Study Design

The present prospective cohort collected data from all patients admitted to the tertiary care hospital (Hospital das Clínicas da FMUSP) from January 2018 to November 2019 with diagnosed aSAH either from lower complexity centers or from other hospitals of the institution. After initial stabilization, patients were selected for the microsurgical or endovascular treatment depending on imaging and clinical status, and, at discharge, were assessed using the standardized scales RS and GOS. Finally, in a 6-month outpatient consultation, patients were again assessed using the same scales evaluating long-term disability ([Figure 2]).

Fig. 2 Selection of patients eligible for the present study.

Population Data

In the aforementioned period, data were collected from 223 patients. Of those, were included 79 patients in the present study (n = 79). A consent form and a full questionnaire were offered for patients to evaluate risk factors, such as smoking, hypertension, diabetes, and drug abuse, as well as previous events of aSAH and onset of the headache.

Exclusion Criteria

Patients with missing data about the time of onset of symptoms or RS or GOS after 6 months were excluded.

Inclusion Criteria

Patients admitted to the Hospital das Clínicas da FMUSP between January 2018 and November 2019 with diagnosed aSAH, who agreed to participate in the study, from both sexes, > 18 years old, with a known time of onset of symptoms, diagnosed aSAH and who completed the 6-month follow-up.

Ethical Standards

The present research project was approved by the Ethics and Research Committee of the Hospital das Clínicas of FMUSP. Online registration CAPPesq: 15226 approved 06/20/2016. Approved on the Brazil platform CAAE number: 61719416.6.0000.0068.

Statistical Analysis

The time from onset of symptoms (considering the thunderclap headache) and the treatment (days) was calculated and called Delta. Linear regression was used to analyze Delta and the standardized RS and GOS in two moments: at discharge and at the 6-month follow-up. Additionally, the same linear regression was used to divide the population of the study into four age subgroups (≤ 45 years old, 45 to 55 years old, 55 to 70 years old, and > 70 years old).

Results

Of the total of 223 patients included, 145 were excluded due to either missing information or loss to follow-up in 6 months, resulting in 78 patients ([Figure 2]). The average age was 54, and 73% were women. At admission, the mean Glasgow Coma Scale was 13, and the Hunt and Hess Scale and World Federation Neurological Surgeons Grading (WFNS), were both 2.1 ([Table 1]). The average time from the onset of symptoms until intervention was 6.8 days. At discharge, the mean Rankin (RS) was 1.9 and the Glasgow Outcome Score was 4.5. At 6 months, the Rankin Score was 1.8. In the population studied, no correlation was found between the time from onset of symptoms until the treatment and better Rankin Scores, with an adjusted R-squared: 0.023 and p = 0.09. Using the same linear regression, but with the population stratified into four subgroups (≤ 45 years old, 45 to 55 years old, 55 to 70 years old, and > 70 years old) obtained similar results, with a p-value of 0.38, 0.92, 0.93, and 0.93, respectively.

Table 1 Population characteristics of the patients

Population with aSAH (n = 78)	n
Epidemiology
Age (years old)	54
Gender (female)	57 (73%)
Hypertension	53 (68%)
Diabetes	32 (41%)
Smoking	43 (55%)
Alcohol Consumption	18 (23%)
Previous aSAH	12 (15%)
Family History of aSAH (first degree)	4 (5%)
Clinical Features at Admission
Glasgow Coma Scale (mean)	13
Hunt and Hess Score (mean)	2.1
World Federation of Neurological Surgeons	2.1
Lowered Level of Consciousness	8 (10%)
Syncope	14 (18%)
Meningeal Signs	5 (6.4%)
Motor deficits	30 (38.5%)
Radiologic Features
Presence of Vasospasm	11 (14%)
Size of Aneurysm (mm)	6.0
More than one aneurysm	13 (16%)
Modified Fisher Grading (mean)	3.1

Abbreviation: aSAH, aneurysmal subarachnoid hemorrhage.

Additionally, a subgroup analysis was performed, and the patients were divided into four groups based on their ages: ≤45 years old, from 45 to 55 years old, from 55 to 70 years old, and > 70 years old. For each group, the same linear regression was used to investigate if there was a different outcome; however, no statistically significant difference was found. ([Table 2]).

Table 2 Age-based subgroup analysis of RS after 6 months and time until intervention

Subgroup (years old)	p-value
≤ 45	0.38
45–55	0.92
55–70	0.93
> 70	0.37

Using the same aforementioned strategy, other subgroup analyses were performed in a more detailed way ([Table 3]), considering other variables possibly involved on the outcomes,[12] such as gender, days until intervention, size of the aneurysm and previous aSAH and Glasgow Coma Scale at admission, and in none of these a linear correlation between the time until intervention and the disabilities measured by the RS in the 6-month follow-up was found.

Table 3 Detailed subgroup analysis of RS after 6 months and time until intervention

Subgroup	p-value
Gender
Male	0.76
Female	0.57
Time until intervention
≤ 3 days	0.66
≥ 4 days	0.78
Previous aSAH
Yes	0.15
No	0.17
Size of the aneurysm
≤ 5 mm	0.84
≥ 5 mm	0.81
Glasgow Coma Scale at Admission
15	0.40
13–14	0.67
9–12	0.63
≤ 8	0.27

Abbreviation: aSAH, aneurysmal subarachnoid hemorrhage.

Discussion

It is well-known that the outcomes of an aSAH are complex and depend on a myriad of variables, including characteristics of the patient (comorbidities), the size and location of the aneurysm, the extension of the bleeding,[12] and the time until the transfer to a specialized unit. Accordingly, the Cooperative Aneurysm Study has suggested that the risk of rebleeding achieves a peak during the first 24 hours after the event and subsequently decreases by 1 to 2% per day until the second week. Also, emerging data show that initial rebleeding rates can be of up to 15% in the first 24 hours, which is called ultra-early rebleeding.[13] Thus, after this critical time, the intervention may not be time-dependent for the limitations after 6 months measured by the GOS and the Rankin scales.

Conclusion

The present article suggests that there was no linear correlation between time until intervention and better outcomes using the Rankin scale or the GOS. Besides that, it is worth saying that emerging clinical therapies involving intensive care minimizing complications should be encouraged and incorporated.

Further studies are needed to understand what impacts best the life after aSAH.

Conflict of Interests

The authors have no conflict of interests to declare.

Disclosure

The authors have no personal, financial, or institutional interest in any of the drugs, materials or devices described in the present article.

Financial

The authors have no financial support to report.

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Publication History

Received: 31 October 2022

Accepted: 24 January 2023

Article published online:
29 September 2023