Gabriël J.E. Rinkel

Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review.

BACKGROUNDnDuring the last three decades, new management strategies have been developed for patients with aneurysmal subarachnoid hemorrhage. To assess whether the case-fatality rate has improved after the introduction of new management strategies, we studied outcome in all population-based studies from 1960 onward.nnnSUMMARY OF REVIEWnTo identify population-based studies that reported on case-fatality rate in subarachnoid hemorrhage, we performed a MEDLINE search and checked all reference lists of the studies found. Two authors (J.W.H. and G.J.E.R.) independently assessed all studies for eligibility, using predefined criteria for case finding and diagnosis, and extracted data on case-fatality rates. We used weighted linear regression analysis to quantify change in case-fatality rate over time. We found 21 studies, describing 25 study periods between 1960 and 1992. Case-fatality rates varied between 32% and 67%, with the exception of one recent study. The case-fatality rate decreased by 0.5% per year (95% confidence interval, -0.1 to 1.2); the decline was steeper after adjustment for age and sex (0.9% per year; 95% confidence interval, -0.7 to 2.6; data from 12 studies).nnnCONCLUSIONSnThe case-fatality rate after subarachnoid hemorrhage has decreased during the last three decades. A plausible explanation for this decrease is the improved management of patients with subarachnoid hemorrhage.

Risk of Rupture of Unruptured Intracranial Aneurysms in Relation to Patient and Aneurysm Characteristics An Updated Meta-Analysis

Background and Purpose— We updated our previous review from 1996 on the risk of rupture of unruptured intracranial aneurysms, aiming to include the newly published articles. Methods— We reviewed all studies from our former meta-analysis and performed a Medline search for new studies published after 1996. We calculated overall risks of rupture for studies with a mean follow-up time of <5, 5 to 10, and >10 years. Relative risks (RR) were calculated by comparing the risk of rupture in patients with and without potential risk factors. We aimed to perform multivariable analyses of the different risk factors with meta-regression analysis. Results— We included 19 studies (10 new) with 4705 patients and 6556 unruptured aneurysms (follow-up 26 122 patient-years). The overall rupture risks were 1.2% (follow-up <5 years), 0.6% (follow-up 5 to 10 years), and 1.3% (follow-up >10 years). In the univariable analysis, statistically significant risk factors for rupture were age >60 years (RR 2.0; 95% confidence interval [CI], 1.1 to 3.7), female gender (RR 1.6; 95% CI, 1.1 to 2.4), Japanese or Finnish descent (RR 3.4; 95% CI, 2.6 to 4.4), size >5 mm (RR 2.3; 95% CI, 1.0 to 5.2), posterior circulation aneurysm (RR 2.5; 95% CI, 1.6 to 4.1), and symptomatic aneurysm (RR 4.4; 95% CI, 2.8 to 6.8). Meta-regression analysis yielded implausible results. Conclusions— Age, gender, population, size, site, and type of aneurysm should be considered in the decision whether to treat an unruptured aneurysm. Pooled multivariable analyses of individual data are needed to identify independent risk factors and to provide more reliable risk estimates for individual patients.

Incidence of Recurrent Subarachnoid Hemorrhage After Clipping for Ruptured Intracranial Aneurysms

Background and Purpose— Because intracranial aneurysms develop during life, patients with subarachnoid hemorrhage (SAH) and successfully occluded aneurysms are at risk for a recurrence. We studied the incidence of and risk factors for recurrent SAH in patients who regained independence after SAH and in whom all aneurysms were occluded by means of clipping. Methods— From a cohort of patients with SAH admitted between 1985 and 2001, we included those patients who were discharged home or to a rehabilitation facility. We interviewed these patients about new episodes of SAH. We retrieved all medical records and radiographs in case of reported recurrences. If patients had died, we retrieved the cause of death. We analyzed the incidence of and risk factors for recurrent SAH by Kaplan-Meier curves and Cox regression analysis. Results— Of 752 patients with 6016 follow-up years (mean follow up 8.0 years), 18 had a recurrence. In the first 10 years after the initial SAH, the cumulative incidence of recurrent SAH was 3.2% (95% confidence interval [CI], 1.5% to 4.9%) and the incidence rate 286 of 100 000 patient-years (95% CI, 160 to 472 per 100 000). Risk factors were smoking (hazard ratio [HR], 6.5; 95% CI, 1.7 to 24.0), age (HR, 0.5 per 10 years; 95% CI, 0.3 to 0.8) and multiple aneurysms at the time of the initial SAH (HR, 5.5; 95% CI, 2.2 to 14.1). Conclusions— After SAH, the incidence of a recurrence within the first 10 years is 22 (12 to 38) times higher than expected in populations with comparable age and sex. Whether this increased risk justifies screening for recurrent aneurysms in patients with a history of SAH requires further study.

Attributable Risk of Common and Rare Determinants of Subarachnoid Hemorrhage

Background and Purpose— Smoking, hypertension, alcohol consumption, autosomal dominant polycystic kidney disease (ADPKD), and positive family history for subarachnoid hemorrhage (SAH) are well-known risk factors for SAH. For effective prevention, knowledge about the contribution of these risk factors to the overall occurrence of SAH in the general population is pivotal. We therefore investigated the population attributable risks of the risk factors for SAH. Methods— We retrieved the relative risk and prevalence of established risk factors for SAH from the literature and calculated the population attributable risks of these risk factors. Results— Drinking alcohol 100 to 299 g/wk accounted for 11% of the cases of SAH, drinking alcohol ≥300 g/wk accounted for 21%, and smoking accounted for 20%. An additional 17% of the cases could be attributed to hypertension, 11% to a positive family history for SAH, and 0.3% to ADPKD. Conclusions— Screening and preventive treatment of patients with familial preponderance of SAH alone will cause a modest reduction of the incidence of SAH in the general population. Further reduction can be achieved by reducing the prevalence of the modifiable risk factors alcohol consumption, smoking, and hypertension.

Perimesencephalic Hemorrhage and CT Angiography A Decision Analysis

Background and Purpose The method of choice for detecting or excluding a vertebrobasilar aneurysm still is a matter of debate in patients with a characteristically perimesencephalic pattern of subarachnoid hemorrhage (SAH) on CT. We used decision analysis to compare possible diagnostic strategies in these patients. Methods A decision analytic model was developed to evaluate the effect of 4 different diagnostic strategies following a perimesencephalic pattern of SAH on CT: 1, no further investigation; 2, digital subtraction angiography (DSA) by catheter; 3, CT angiography as initial modality, not followed by DSA if negative; and 4, CT angiography as initial modality, followed by DSA. We used a 4% prevalence of a vertebrobasilar aneurysm given a perimesencephalic pattern of hemorrhage, a 97% sensitivity and specificity of CT angiography, and a 99.5% sensitivity and 100% specificity of DSA. In a prospectively collected series, the complication rate from DSA in patients with a perimesencephalic pattern of hemorrhage was 2.6%. We calculated the expected utility of each of the 4 diagnostic options and used sensitivity analyses to examine the influence of the plausible ranges of the various estimates used. Results The expected utilities were 99.09 for CT angiography only, 98.96 for no further investigation, 98.22 for DSA, and 96.34 for CT angiography plus DSA. The results of the sensitivity analysis indicate that over a wide range of assumptions, CT angiography only is the most beneficial option. Only when the complication rate of catheter angiography is <0.2% is DSA the preferred strategy. Conclusions Our decision analysis shows that in patients with a perimesencephalic pattern of hemorrhage on CT, CT angiography only is the best diagnostic strategy. DSA can be omitted in patients with a perimesencephalic pattern of hemorrhage and a negative CT angiogram.

Perimesencephalic Hemorrhage Exclusion of Vertebrobasilar Aneurysms With CT Angiography

BACKGROUND AND PURPOSEnIt is important to recognize a perimesencephalic pattern of hemorrhage in patients with subarachnoid hemorrhage (SAH), because in 95% of these patients the cause is nonaneurysmal and the prognosis is excellent. The purpose of this study was to investigate whether CT angiography can accurately exclude vertebrobasilar aneurysms in patients with perimesencephalic patterns of hemorrhage and therefore replace digital subtraction angiography (DSA) in this setting.nnnMETHODSnIn 40 patients with posterior fossa SAH as shown on unenhanced CT, 2 radiologists independently evaluated unenhanced CT for distinguishing between perimesencephalic and nonperimesencephalic pattern of hemorrhage and assessed CT angiography for detection of aneurysms. All patients subsequently underwent DSA or autopsy.nnnRESULTSnObservers agreed in 38 of 40 patients (95%) in differentiating perimesencephalic and nonperimesencephalic patterns of hemorrhage on unenhanced CT. On the CT angiograms, both observers detected a vertebrobasilar aneurysm in 16 patients and no aneurysm in 24 patients. These findings were confirmed by DSA or autopsy. No patients with a perimesencephalic pattern of hemorrhage were found to have an aneurysm on either CT angiography or DSA.nnnCONCLUSIONSnGood recognition of a perimesencephalic pattern of hemorrhage is possible on unenhanced CT, and CT angiography accurately excludes and detects vertebrobasilar aneurysms. DSA can be withheld in patients with a perimesencephalic pattern of hemorrhage and negative CT angiography.

Disorders of Sleep and Wake in Patients After Subarachnoid Hemorrhage

Background and Purpose— To determine the frequency and severity of disorders of sleep and wake and their relation to the quality of life (QoL) in patients who have survived an episode of subarachnoid hemorrhage (SAH). Methods— In a prospectively collected, consecutive series of 89 patients, 83 patients completed validated and frequently used questionnaires for the assessment of disorders of sleep and wake (SDL and Epworth Sleepiness Score) at least 1 year (range, 1 to 3.4 years) after the SAH. We used the modified Rankin scale for functional outcome and Short Form 36 (SF-36) to assess QoL. We related the occurrence of severe problems with sleep (insomnia or excessive daytime sleepiness score or both ≥3 on SDL) to functional outcome and to the QoL scores and compared the latter scores with data from a Dutch reference population. In a subset of 20 patients with severe problems with sleep, we performed polysomnographic and actigraphic studies at home during 48 hours. Results— Twenty eight (34%) patients had severe problems with sleep. Frequently reported problems are initiating (25%) or maintaining (31%) sleep, difficulty returning (28%) asleep, tiredness (31%), and excessive sleepiness during the day (6%). QoL was considerably reduced in patients with severe problems with sleep. During the sleep monitoring studies, severe sleep fragmentation, sleep apnea, restless legs syndrome/periodic limb movement disorder, or a combination of these disorders of sleep and wake occurred in 19 of 20 patients. Conclusion— Many patients who have survived an episode of SAH have disorders of sleep and wake, which are related to the QoL.

Life Expectancy After Perimesencephalic Subarachnoid Hemorrhage

Background and Purpose— Patients with a perimesencephalic nonaneurysmal subarachnoid hemorrhage are not at risk for rebleeding in the initial years after the hemorrhage. Nevertheless, uncertainty remains on the long-term prognosis after perimesencephalic hemorrhage, and former patients are often considered high-risk cases for health insurance or are denied life insurance. We performed a very long-term follow-up study of a large consecutive series of such patients and compared mortality in this cohort with that in the general population. Methods— All patients with a perimesencephalic hemorrhage (defined by pattern of hemorrhage on computed tomography within 72 hours after onset and absence of aneurysm) admitted between 1983 and 2005 to our service were followed-up by telephone. For patients who had died, we retrieved age and cause of death. We compared the age- and sex-specific mortality of this cohort with that of the general population by means of standardized mortality ratios with corresponding 95% confidence intervals. Results— The cohort consisted of 160 patients, with a total number of patient-years of 1213. No new episodes of subarachnoid hemorrhage had occurred. During follow-up 11 patients had died; the expected number of deaths based on mortality rates in the general population (adjusted for age and gender) was 18.1. The standardized mortality ratio was 0.61 (95% confidence interval, 0.34 to 1.1). Conclusions— Patients with perimesencephalic hemorrhage have a normal life expectancy and are not at risk for rebleeding. No restrictions should be imposed on these patients by physicians or health or life insurance companies.

Risk of Rebleeding After Treatment of Acute Hydrocephalus in Patients With Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— Cerebrospinal fluid drainage is often indicated in patients with acute hydrocephalus after aneurysmal subarachnoid hemorrhage but is believed to increase the risk of rebleeding. We studied the risk of rebleeding in patients with subarachnoid hemorrhage during treatment for acute hydrocephalus. Methods— We included patients with hydrocephalus treated with external ventricular drainage or lumbar punctures within 4 days after the hemorrhage and before aneurysm occlusion. Each treated patient was matched with a control patient with untreated hydrocephalus and a control patient without ventricular enlargement. Patients and controls were matched for interval since subarachnoid hemorrhage, duration of exposure, use of tranexamic acid, clinical condition on admission, and age. We used Cox regression to calculate hazard ratios and we adjusted for rebleeding that had occurred before starting the cerebrospinal fluid drainage. Results— In the group treated with external ventricular drainage, rebleeding occurred in seven of 34 patients (21%) with treatment, in seven of 34 controls (21%) with untreated hydrocephalus, and in six of 34 controls (18%) without hydrocephalus. In the group treated with one or more lumbar punctures, rebleeding occurred in one of 21 patients (5%) with treatment, in three of 21 controls (14%) with untreated hydrocephalus, and in none of the 21 controls without hydrocephalus. The hazard ratios for rebleeding were 1.0 (95% CI: 0.4 to 2.7) for external ventricular drainage treatment and 0.7 (95% CI: 0.1 to 6.4) for lumbar puncture treatment. Conclusion— This study does not confirm an importantly increased risk of rebleeding during external ventricular drainage or lumbar punctures for acute hydrocephalus after aneurysmal subarachnoid hemorrhage.

Electrocardiographic Abnormalities and Serum Magnesium in Patients With Subarachnoid Hemorrhage

Background and Purpose— ECG abnormalities and hypomagnesemia frequently occur after aneurysmal subarachnoid hemorrhage (SAH). Because hypomagnesemia is associated with several ECG abnormalities, we studied whether hypomagnesemia mediates ECG abnormalities after SAH. Methods— We prospectively studied a consecutive series of 62 patients admitted within 72 hours after aneurysmal SAH. A standard 12-lead ECG and serum magnesium measurement were routinely performed at admission. The relationship between serum magnesium and ECG abnormalities was assessed with linear regression analysis and the Mann-Whitney test in case of dichotomized ECG abnormalities. Results— Hypomagnesemia was present in 23 patients (37%), and 38 patients (61%) had a long QTc duration. Low serum magnesium was related to a long PR interval (P =0.001) and a shorter QTc interval (P =0.004). Adjustment for World Federation of Neurological Surgeons score, hydrocephalus, and the amount of cisternal and ventricular blood did not influence these relations. Conclusions— In patients with SAH, lower serum magnesium levels are related to less pronounced increase in the QTc interval. Although the direction of the relation was unexpected, decreased serum magnesium might be the missing link between SAH and ECG abnormalities.