Ilari Rautalin

Background and ObjectivesSubarachnoid hemorrhage (SAH) is associated with high mortality and long-term morbidity, as well as a considerable economic burden. Screening for unruptured intracranial an...

According to region-specific hospital-based studies, the location of ruptured intracranial aneurysm (RIA) influences the case fatality rate (CFR) of aneurysmal subarachnoid hemorrhage (SAH). However, little is known about whether CFRs vary by RIA location in population-based studies that include prehospital SAH deaths. We assessed whether CFRs and CFR-trends differ by RIA location using whole population data from Finland and New Zealand. We used externally validated administrative databases to identify all nonhospitalized and hospitalized SAH cases in Finland and New Zealand from 2001 to 2017. Using the ICD-10, we categorized RIAs into anterior communicating artery (Acom) (ICD-10 I60.2), internal carotid artery (ICA) (I60.0/I60.3), middle cerebral artery (MCA) (I60.1), and vertebrobasilar artery (VBA) (I60.4/I60.5) locations. To validate the location-specific SAH diagnoses, we used external hospital- and population-based datasets and autopsy data. We calculated sudden death rates (those occurring before admission to a ward) and overall 30-day CFRs, and computed age-, sex, and country-adjusted risk ratios using a Poisson regression model with 95% CIs. Among 13,470 SAH cases (5,056 from New Zealand; median age 58 years; 61.3% women), 26.6% had Acom, 18.4% ICA, 29.5% MCA, 11.5% VBA, and 14.0% other/unspecified RIAs. The overall 30-day CFRs were the greatest for VBA (54.1%), followed by MCA (40.5%), Acom (29.1%), and ICA (28.5%) RIAs. Location-specific sudden death rates were 33.0%, 21.6%, 11.9%, and 9.9%, respectively. Between 2001-2003 and 2015-2017, overall 30-day CFRs declined significantly for VBA (24%, 95% CI 13%-34%) and MCA (15%, 95% CI 5%-24%) RIAs. Location-specific differences in CFRs were similar between countries, but temporal decreases were observed only in Finland. Between 2001-2003 and 2014-2017, the proportion of VBA RIAs increased by 35.9% (from 10.3% to 14.0%). SAH CFRs vary significantly by RIA location, with VBA and MCA RIAs having the greatest CFRs, mainly due to high sudden death rates. It is unclear whether aneurysms with these high-risk locations could benefit from improved primary/secondary prevention or prehospital management strategies. These findings cannot be directly applied to the preventive treatment of unruptured intracranial aneurysms.

The growing use and improved accessibility of noninvasive imaging modalities have increased the detection of incidental intracranial findings, such as unruptured brain arteriovenous malformations (AVMs). At the same time, existing literature presents conflicting findings regarding whether the incidence of ruptured AVMs has increased or decreased. Considering these developments, we hypothesized that the detection rate of unruptured AVMs has increased, and the detection rate of ruptured AVMs has changed over the period of 18 years, potentially reflecting shifts in underlying vascular risk profiles and preventive health behaviors. In this retrospective population-based study, we identified all hospitalized and nonhospitalized (prehospital sudden death) individuals with AVMs in Southern Finland between 1998 and 2015 from the National Cause of Death Register autopsy reports (using ICD-10 codes I60.8, I61.0-I61.9, Q28.0-Q28.3) and the Helsinki AVM Register. European Standard Population age-standardized detection rates with 95% CIs were determined in 3-year intervals for both ruptured and unruptured AVMs. Significance in detection rate trends was analyzed with Poisson regression on 3-year sliding averages. Between 1998 and 2015, 288 individuals (minimum age 0.2 years, mean age 41.1 years, SD = 18.0 years, 48.3% women) with AVMs were identified; 284 were hospitalized, and 4 died from AVM at home (diagnosed at medicolegal autopsy). The overall (men and women) detection rate of both ruptured and unruptured AVMs decreased from 0.91 (95% CI 0.66-1.17) to 0.40 (95% CI 0.24-0.56)/100,000 person-years during 1998-2015. The annual decrease for ruptured and unruptured AVMs was 5.7% in men (95% CI 3.6%-7.8%), 5.9% in patients <30 years (95% CI 3.2%-8.7%), 4.8% in patients aged 30-59 years (95% CI 2.7%-7.0%), and 2.2% in women (95% CI 0.0%-4.3%). Detection rates decreased by 4.6% annually for ruptured AVMs (95% CI 2.6%-6.6%) and 3.1% for unruptured AVMs (95% CI 0.7%-5.4%). Contrary to our hypothesis, we observed a decline in the overall detection rate of unruptured AVMs over the 18-year study period. Moreover, we found a substantial reduction in the number of ruptured AVMs among men, women, and patients younger than 60 years. The reasons for these rapid changes remain unclear and warrant further investigation.

Importance: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective: To estimate the worldwide burden of SAH. Design, Setting, and Participants: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures: SAH and 14 modifiable risk factors. Main Outcomes and Measures: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

The number of unexpected prehospital deaths from brain arteriovenous malformations (AVMs) is unknown because existing mortality data are derived from hospital-based cohorts. In this study, we aimed to determine the rate and causes of AVM-related deaths in a large population-based cohort, both in and outside hospitals. We hypothesized that AVMs infrequently cause unexpected prehospital deaths, and when they do, it is typically due to hemorrhages rather than epileptic seizures. In this population-based cross-sectional study, we examined the AVM-related deaths within the Helsinki University Hospital (HUH) region during 1998-2015, including both diagnosed patients and undiagnosed individuals with prehospital deaths identified at autopsy. Autopsies are legally mandatory in Finland for all unexpected and sudden deaths. Prehospital deaths were identified through autopsy reports, which were obtained from the National Cause of Death Register (using the ICD-10 codes I60.8, I61.0-I61.9, or Q28.0-Q28.3), and the patients who were already diagnosed were identified from the Helsinki AVM Register. Age-standardized detection rates were calculated using the 2013 European Standard Population (ESP)-derived age-specific weights, with 95% CIs derived from the normal approximation of binomial distribution. Between 1998 and 2015, we identified 4 unexpected prehospital AVM deaths in undiagnosed individuals (median age 41 years, 50% female) in the HUH region from the National Cause of Death Register data. For the same period, the HUH AVM database revealed 284 newly diagnosed patients with AVM (mean age at diagnosis 41.1 years [SD 18.0 years], 48% female). Altogether, there were 6 AVM-related prehospital deaths, 2 in previously diagnosed patients. Four of the 6 prehospital deaths were caused by AVM-related epileptic seizures and 2 by AVM hemorrhage. Among individuals experiencing their first AVM-related hemorrhage (n = 168), 1.2% experienced prehospital deaths due to hemorrhage. Similarly, of those diagnosed with AVM-related epileptic seizures (n = 69), 5.8% experienced prehospital deaths from seizures. For people with unruptured and ruptured AVMs, 6-month case fatality rates (CIs) from detection were 5.8% (1.7%-10.8%) and 11.9% (7.1%-17.3%), respectively. The crude and ESP-standardized detection rates of AVMs (including prehospital deaths) were 0.80 (0.71-0.89) and 0.78 (0.69-0.87) per 100,000 person-years. AVM-related prehospital deaths are rare and often caused by epileptic seizures. Most AVM-related deaths occur in hospitals.

Although around one-third of survivors of aneurysmal subarachnoid hemorrhage (aSAH) suffer from anxiety and depression, studies focusing on suicide risk after aSAH are lacking. Thus, we aimed to investigate whether survivors of aSAH have an elevated risk of suicide death in comparison with the general population. Using 2 externally validated nationwide registers (Care Register for Health Care and Cause of Death Register), we identified all ≥15-year-old survivors of aSAH (alive 30 days after hospital admission) in Finland during 1998-2017 and followed these patients until death or the end of 2018. By calculating standardized mortality ratios (SMRs) with 95% CIs using the Mid-P exact test, we compared the observed suicide rates of survivors of aSAH with the expected rates based on the age-matched, sex-matched, and year-matched general Finnish population. We identified 5,708 survivors of aSAH (59% female, median age 55 years) of whom 19 (5 female patients and 14 male patients) died by suicide during a total of 53,060 person-years (median 8.9 years) of follow-up. Of all deaths by suicide, 7 were caused by self-poisoning, 6 by hanging/strangulation, 3 by a firearm, 2 by jumping, and 1 by a sharp object. The observed rate of suicide was 35.8 per 100,000 person-years compared with the expected rate of 20.4 per 100,000 person-years resulting in an overall SMR of 1.75 (95% CI 1.09-2.69). The risk of suicide was especially high among 15-39-year-old female and male patients (72.5 per 100,000 person-years; SMR = 3.57 [1.31-7.92]) and during the first year after aSAH (81.2 per 100,000 person-years; SMR = 3.64 [1.16-8.77]), after which the risk attenuated. Survivors of aSAH are at excessive risk of suicide death in comparison with the general population. Given that this risk seems to be the highest among young individuals and during the first year after aSAH, early assessment and management of psychological distress, especially in young survivors of aSAH may be warranted. Future studies should include detailed individual-level data on psychiatric comorbidities and aSAH-specific factors, as well as record both nonfatal and fatal suicide attempts.

Given the relatively low incidence, high prehospital death rate, substantial geographical differences, and complex disease origin (combination of genetic and environmental risk factors), epidemiologic research on subarachnoid hemorrhage (SAH) and its risk factors is challenging. In practice, we are more or less forced to exploit compromised study designs and nonrepresentative data in such circumstances where it is almost impossible to gather comprehensive data through an optimal design. For example, hospital-based patient cohorts, administrative data repositories, and short-term population-based studies from small geographical regions are often used to research the incidence, case fatality, and risk factors of SAH, regardless of their inherent and self-evident limitations. Since studies on the epidemiology of SAH focus largely on identifying possible risk factors that could aid in disease diagnostics, treatment, and prevention, we aimed to review recent evidence on modifiable risk factors for SAH. In this context, we also try to explain the methodological reasons behind some of the conflicting results and to discuss the primary strengths and limitations of different study designs used in the field of SAH epidemiology. Based on our findings, smoking, high blood pressure, and possibly low physical activity are the only risk factors with high-quality evidence supporting their causal role in SAH. In addition, since all 3 commonly used study designs in SAH epidemiology, namely, hospital-based, population-based, and administrative register-based studies, have their own strengths and limitations, the most robust risk factor estimates and other epidemiologic measures of SAH can likely be established by combining various overlapping and high-quality sources of information in the future.

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is more common in women than in men, contrary to most cardiovascular diseases. However, it is unclear whether the case fatality rate (CFR) of SAH also differs by sex. Thus, we performed a systematic review to address the relationship between sex and SAH CFRs. Methods: We conducted a systematic literature search in PubMed, Scopus, and Cochrane library databases. We focused on population-based studies that included both nonhospitalized and hospitalized SAHs and had either reported 1-month (28–31 day) SAH CFRs separately for men and women or calculated risk estimates for SAH CFR by sex. For quality classification, we used the Cochrane Collaboration Handbook and Critical Appraisal Skills Program guidelines. We pooled the study cohorts and calculated relative risk ratios (RRs) with 95% confidence intervals (CIs) for SAH death between women and men using a random-effects meta-analysis model. Results: The literature search yielded 5,592 initial publications, of which 33 study cohorts were included in the final review. Of the 33 study cohorts, only three reported significant sex differences, although the findings were contradictory. In the pooled analysis of all 53,141 SAH cases (60.3% women) from 26 countries, the 1-month CFR did not differ (RR = 0.99 [95% CI: 0.93–1.05]) between women (35.5%) and men (35.0%). According to our risk-of-bias evaluation, all 33 study cohorts were categorized as low quality. The most important sources of bias risks were related to the absence of proper confounding control (all 33 study cohorts), insufficient sample size (27 of 33 study cohorts), and poor/unclear diagnostic accuracy (27 of 33 study cohorts). Conclusion: Contrary to SAH incidence rates, the SAH CFRs do not seem to differ between men and women. However, since none of the studies were specifically designed to examine the sex differences in SAH CFRs, future studies on the topic are warranted.