Clinical Characteristics of Intracranial Aneurysms in Elderly Patents over 70 Years Old: a retrospective observational study

Abstract

Background

Although the characteristics of intracranial aneurysms (IAs) in different age groups have been well documented, they remain relatively unclear in elderly patients due to a lack of large sample studies.

Methods

Data from IA patients aged more than 70 years who were treated in our centre from January 2016 to January 2020 were retrospectively collected.

Results

A total of 290 elderly patients (75.9% female) with a mean age of 74.0 ± 4.7 years were analysed. Rupture occurred in 60.7% of patients, 38.6% of whom presented with meningeal irritation, and seizures were noted in 2.3%. A total of 48.9% of the patients with ruptured IAs had initial symptoms presenting with slow development, and the mean delay from ictus was prolonged to 264.2 ± 914.0 hours. In addition, 61.9% of the patients with ruptured IAs had lesions with a maximum diameter of less than 5 mm. A total of 30.3% of the patients had multiple aneurysms, 35.5% had aneurysms with irregular shapes and 54.8% had cerebrovascular atherosclerotic stenosis (CAS). Pulmonary infection (n = 138, 47.6%), hydrocephalus (n = 72, 24.8%), and thrombosis (n = 35, 12.1%) were common complications during hospitalization. By the end of the 1-year follow-up, 22.1% of the patients had unfavourable clinical outcomes, and the mortality rate was 23.4%.

Conclusions

Several characteristics regarding IAs in elderly patients were reported, including an obvious female predominance; mild, slow initial symptom development causing prolonged admission delay; a low incidence of meningeal irritation and seizures due to decreased electrophysiological activity of the neurons; increased percentages of CAS, multiple aneurysms, and aneurysms with daughter sacs causing a high risk of rupture even for small lesions; a high risk of complications during hospitalization; and relatively poor clinical outcomes.

Background

Intracranial aneurysm (IA) is a devastating cerebral vascular disease and a major threat to health worldwide. According to previous epidemiological reports, unruptured IAs are found in approximately 3.2% of the adult population worldwide, with the average annual incidence of IA-related subarachnoid haemorrhage (SAH) among people of all ages ranging from 6–27.63 per 100,000 persons^1,2. With the general ageing of the population and advances in neuroimaging diagnosis, an increasing number of elderly patients are being diagnosed with IA^3,4. A Japanese cohort study on the natural course of cerebral aneurysms reported that 28% of patients with unruptured IAs were older than 70 years⁵. However, due to a lack of large-sample studies, the overall clinical characteristics of IAs in elderly patients have yet to be fully elucidated. The present study was conducted to clarify the clinical characteristics of elderly patients (more than 70 years old) with IAs, to reveal some new findings and to assist in the choice of best clinical decision for these patients.

Methods

1. Study design

We performed a retrospective analysis in a single tertiary centre. This study was approved by the institutional review board (IRB) of West China Hospital. We used the hospital information system to collect the related medical data of elderly patients with IAs from January 2016 to January 2020. The inclusion criteria were as follows: 1) IA as identified by discharge diagnoses using the key words “intracranial aneurysm” or “aneurysmal subarachnoid haemorrhage”, IAs were diagnosed through computed tomography angiography (CTA) or digital subtraction angiography (DSA), and SAH was confirmed by the results of initial computerized tomography (CT) scan by experienced neuroimaging specialists; and 2) age more than 70 years. Two experienced neurosurgeons and two neuroradiologists who were blinded to the medical records were invited to confirm the diagnoses of the selected patients. Patients with an incorrect diagnosis or incomplete medical profiles were excluded.

2. Data collection and grouping

The following patient baseline information was retrieved from the hospital information system: age, sex, smoking, alcohol consumption, history of hypertension (treatment),  anaemia, hypoproteinaemia,  diabetes mellitus, electrolyte disturbance, coronary disease, hyperlipidaemia, haemorrhagic or ischaemic stroke, encephalatrophy and pulmonary infection, clinical presentations (including symptoms and signs), Glasgow Coma Scale (GCS) score on admission and upon discharge, Hunt-Hess grade, and duration from ictus to admission. Neuroradiological data were collected from the hospital imaging system to evaluate the angiographic metrics of the IAs, including their size (aneurysms with diameters larger than 25 mm were considered giant, and those between 15 and 25 mm were considered large), morphology and location and the presence of multiple aneurysms, based on the results of CTA or DSA. Vascular anomalies were also recorded, mainly including cerebrovascular atherosclerotic stenosis (CAS) and cerebral artery variants in the posterior cerebral artery (PCA), defined as foetal-type posterior cerebral artery (FTP). Irregular aneurysms were defined as the presence of a daughter sac in addition to the main saccular aneurysm. Treatment approaches were documented, and the occurrence of complications was tracked from the daily medical course record during hospitalization. Follow-up information was documented from clinic visits or telephone interviews at discharge and 1 month, 3 months, 6 months and 1 year after discharge. Patient clinical outcomes were measured by GCS upon discharge and modified Rankin scale (mRS) scores during follow-up. GCS scores ≥13 and mRS scores of 0–2 were considered favourable outcomes. The patients were divided into ruptured and unruptured groups, and comparisons were made between the two groups.

3. Statistical analysis

SPSS statistical software (version 22.0; SPSS Inc., Chicago, Illinois, USA) was used for all statistical analyses. The mean ± standard deviation (SD) was reported for quantitative data. Categorical data are expressed as frequencies and percentages. Bivariate analyses were conducted using the chi-square test or Fisher’s exact tests, Student’s t-tests, and Mann–Whitney U-tests as appropriate. Significance was defined as P<0.05, and 95% confidence intervals (CIs) were calculated for each variable.

Results

1. Baseline characteristics

A total of 2730 patients with IAs were treated in our hospital from January 2016 to January 2020; among them, 290 elderly patients (≥70 years old on admission) (10.6%) were analysed in the current study. The mean age of the patients was 74.0±4.7 years (range 70 to 95 years old); a total of 220 (75.9%) patients were female. Patient demographic information and history of previous illness are shown in Table 1. Compared with patients in the unruptured group (n=114, 39.3%), patients in the ruptured group (n=176, 60.7%) were significantly older (P<0.001) and had a significantly higher percentage of patients with hypoproteinaemia (P<0.001),  anaemia (P<0.001), diabetes mellitus (P<0.001), electrolyte disturbance (P=0.001), pulmonary infection (P=0.001), coronary disease (P=0.005), brain atrophy (P=0.032) and ischaemic stroke (P=0.009). The unruptured group had a significantly higher percentage of patients receiving routine treatment for hypertension than the ruptured group (P=0.024).

Table 1 Baseline information of elderly patients with intracranial aneurysms

Elderly patients: age ≥70 years old; SD: standard deviation;

2. Clinical presentation

Elderly patients with ruptured aneurysms

For the 176 (60.7%) patients who had ruptured aneurysms, the attacks commonly occurred in the morning after waking (n=49, 27.8%). Common inducements included straining during defecation (n=24, 13.6%), emotional fluctuation (n=15, 8.5%) and sneezing (n=8, 4.5%). Presentations included headache (n=148, 84.1%), vomiting (n=118, 67.0%), loss of consciousness (n=64, 36.4%), dizziness (n=22, 12.5%) and hemiparesis (n=20, 11.4%), while only 4 patients (2.3%) presented with seizures. Meningeal irritation (n=68, 38.6%) was the most common sign, followed by cranial nerve deficits (n=22, 12.5%). Slow, progressive development of initial symptoms was documented in 86 (48.9%) patients rather than the typical pattern of sudden onset. Consequently, the mean delay from ictus to admission was prolonged to 264.2±914.0 hours. On admission, a total of 130 patients (73.9%) had good clinical performance (Hunt-Hess grade I-III) (Table 2).

Table 2 Clinical presentations of elderly patients with ruptured intracranial aneurysms

Elderly patients: age≥70 years old; SD: standard deviation; GCS: Glasgow Coma Score; Good clinical presentation: Hunt-Hess grade (I-III);

Elderly patients with unruptured aneurysms

Among the remaining 114 (39.3%) patients with unruptured aneurysms, dizziness was the most common symptom (n=42, 36.8%), followed by headache (n=24, 21.1%), limb weakness (n=14, 12.3%) and vomiting (n=6, 5.3%). The most common sign was cranial nerve deficits (n=28, 24.6%) (Table 3).

Table 3 Clinical presentations of elderly patients with unruptured intracranial aneurysms

Elderly patients: age ≥70 years old; SD: standard deviation;

3. Radiological characteristics

Other radiological characteristics of the patients are shown in Table 4. The distribution of modified Fisher grade for the 176 ruptured cases (60.7%) showed that grades 3 and 4 accounted for 60.8% (n=107) of all ruptured cases. Multiple aneurysms were diagnosed in 88 patients (30.3%). The mean size of the aneurysms (largest diameter) was 5.8±4.6 mm. Notably, of the 176 patients with ruptured lesions, 109 (61.9%) had lesions with a largest diameter of less than 5 mm. In addition, 103 (35.5%) patients had irregular lesions with daughter sacs. Furthermore, CAS, brain atrophy and FTP were recorded in 159 (54.8%), 32 (11.0%) and 39 (13.4%) patients, respectively.

Compared with the unruptured group, the ruptured group had significantly higher percentages of patients with irregular aneurysms (P<0.001), CAS (P<0.001), and FTP (P=0.001). In addition, the mean lesion diameter in the ruptured group was significantly smaller (P<0.001), and the percentage of patients with small aneurysms was significantly higher than that in the unruptured group (P<0.001).

Table 4 Radiological characteristics of elderly patients with intracranial aneurysms

Elderly patients: age≥70 years old; SAH: subarachnoid haemorrhage; ICH: intracerebral haemorrhage; CAS: cerebrovascular atherosclerotic stenosis; FTP: foetal-type posterior cerebral artery; SD: standard deviation; ICA: internal carotid artery; MCA: middle cerebral artery; ACA: anterior cerebral artery; Acom: anterior communicating artery; PCA: posterior cerebral artery; PICA: posterior inferior cerebellar artery; VA: vertebral artery; BA: basilar artery;

4. Treatment and complications during hospitalization

The patients’ treatment modalities and incidence of complications are shown in Table 5. A total of 181 patients (62.4%) were treated by surgical intervention, including 91 (31.4%) with craniotomy clipping and 90 (31.0%) with an endovascular approach; the remaining 109 patients (37.6%) received conservative treatment. Pulmonary infection (n=138, 47.6%), hydrocephalus (n=72, 24.8%), and thrombosis (n=35, 12.1%) were common complications during hospitalization. Notably, some commonly seen complications in other age groups, such as seizures (1.7%) and vasospasm (2.8%), were not obvious in our series.

For the comparison between the two groups, the ruptured group had significantly higher percentages of patients who underwent craniotomy surgery (P<0.001), while the unruptured group had a significantly higher ratio of cases undergoing the endovascular approach (P<0.001). Regarding complications, the ruptured group had a significantly higher percentage of patients with thrombosis than the unruptured group (P=0.031).

Table 5 Treatment, complications and prognosis of elderly patients with intracranial aneurysms

Elderly patients: age ≥70 years old;

 5. Clinical outcomes

Patient clinical outcomes are shown in Table 6. The mean length of hospital stay was 9.5±10.7 days, ranging from 1 to 74 days. By the time of discharge, favourable clinical outcomes (GCS score≥13) were seen in 199 (68.6%) patients. A total of 35 patients (12.1%) died during their stay in the hospital. By the end of the 1-year follow-up, 158 patients (54.5%) demonstrated favourable outcomes (mRS score 0–2), while 33 additional patients had died, resulting in a total mortality rate of 23.4% (n=68). The remaining 64 (22.1%) patients demonstrated unfavourable outcomes (mRS score 3–5).

The clinical outcomes showed significant differences between the ruptured and unruptured groups. Patients in the ruptured group had a significantly longer length of hospital stay than those in the unruptured group (P=0.037). Additionally, the ruptured group had significantly better clinical outcomes at different follow-up time points, presenting as significantly higher percentages of unfavourable outcomes (P<0.05) and death (P<0.05) and significantly lower rates of patients who had favourable outcomes (P<0.001).

Table 6 Clinical outcomes of elderly patients with intracranial aneurysms

Elderly patients: age≥70 years old; SD: standard deviation; GCS: Glasgow Coma Score; Favourable outcomes: GCS score≥13 at discharge and Modified Rankin Scale of 0–2 during follow-up; Unfavourable outcomes: GCS score <13 at discharge and Modified Rankin Scale of 3-6 during follow-up;

Discussion

IAs in the elderly population are not very well documented due to a lack of large-sample studies. In addition, existing studies have mainly focused on patients with unruptured aneurysms^9–12. Subsequently, the overall characteristics of IAs in elderly patients remain unclear. In the present study, several clinical characteristics of elderly IAs were reported. The findings of our study will be helpful for obtaining a better understanding of IAs in elderly age subgroups and will be beneficial for medical professionals in making the best clinical decision.

Conclusions

Several findings regarding IAs in elderly patients were reported in this study, including an obvious female predominance; relatively mild initial symptoms causing prolonged admission delay; a low incidence of meningeal irritation, seizures and vasospasm due to decreased electrophysiological activity of neurons; increased percentages of CAS, multiple aneurysms, and aneurysms with daughter sacs causing a high risk of rupture even for small lesions; a high risk of complications during hospitalization; and relatively poor clinical outcomes.

Abbreviations

IA=intracranial aneurysm; SAH=subarachnoid hemorrhage; BA=basilar artery; GCS=Glasgow Coma Scale; CTA=computed tomography angiography; SD=standard deviation; DSA=digital subtraction angiography; CAS=cerebrovascular atherosclerotic stenosis; PCA=posterior cerebral artery; FTP=fetal-type posterior cerebral artery; mRS=modified Rankin scale; CI=confidence interval; CT=computed tomography; ICH=intracerebral hemorrhage; ICA=internal carotid artery; MCA=middle cerebral artery; ACA=anterior cerebral artery; Acom=anterior communicating artery; VA=vertebral artery; PICA=posterior inferior cerebellar artery;

Declarations

I, (Yi Liu), as the corresponding author of this aricle, certify that this manuscript is a unique submission and is not being considered for publication, in part or in full, with any other source in any medium.

Ethics approval and consent to participate

The study was approved by the institutional review board (IRB) of West China Hospital (No.2017217). Informed consent was obtained from all individual participants included in the study.

Consent for publication

Consent for publication was obtained from all individual participants included in the study

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

This study was funded by the fellowship of China Postdoctoral Science Foundation (2020M673237), Postdoctoral Science Foundation of West China Hospital (2020HXBH155) Science.

Authors' contributions

RC and DW analyzed and interpreted the patient data and were major contributors in writing the manuscript. AX and RG collected patients` medical profile and were contributors in writing the manuscript. CY helped design the work and interpreted the medical data. YL designed the study and substantively revised the manuscript.

Acknowledgements

Not applicable

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