Cerebral amyloid angiopathy decades after red blood cell transfusions: a report of two cases from a prospective cohort.

BACKGROUND AND PURPOSE: Patients who underwent red blood cell (RBC) transfusion from donors who later developed multiple spontaneous intracerebral hemorrhages (ICHs) have recently been identified to have increased risk of ICH themselves. This increased risk of ICH was hypothesized to be related to iatrogenic cerebral amyloid angiopathy (iCAA) transmission. Two cases are presented who had RBC transfusion as an infant and presented with CAA at a relatively young age decades later. METHOD: Cases were identified by prospectively asking all patients at our CAA outpatient clinic (November 2023 to January 2024) about a medical history with RBC transfusion or history with a high likelihood for RBC transfusion (e.g., hemolytic disease, trauma with massive hemorrhage). Eligible patients were all diagnosed with CAA, CAA with concomitant hypertensive arteriopathy or iCAA, and without hereditary CAA. RESULTS: Between November 2023 and January 2024, 2/35 (6%, 95% confidence interval 2%-19%) outpatient clinic patients had a history of RBC transfusion and none had a high likelihood medical history. The cases presented at age 47 and 57 and had already developed severe CAA. CONCLUSIONS: Red blood cell transfusion might be a possible mechanism for iCAA; however, further prospective data collection and experimental evidence concerning blood transmission of amyloid-ß are needed.

Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is a disease caused by the accumulation of the amyloid-beta protein and is a major cause of intracerebral hemorrhage (ICH) and vascular dementia in the elderly. The presence of the amyloid-beta protein in the vessel wall may induce a chronic state of cerebral inflammation by activating astrocytes, microglia, and pro-inflammatory substances. Minocycline, an antibiotic of the tetracycline family, is known to modulate inflammation, gelatinase activity, and angiogenesis. These processes are suggested to be key mechanisms in CAA pathology. Our aim is to show the target engagement of minocycline and investigate in a double-blind placebo-controlled randomized clinical trial whether treatment with minocycline for 3 months can decrease markers of neuroinflammation and of the gelatinase pathway in cerebrospinal fluid (CSF) in CAA patients. METHODS: The BATMAN study population consists of 60 persons: 30 persons with hereditary Dutch type CAA (D-CAA) and 30 persons with sporadic CAA. They will be randomized for either placebo or minocycline (15 sporadic CAA/15 D-CAA minocycline, 15 sporadic CAA/15 D-CAA placebo). At t = 0 and t = 3 months, we will collect CSF and blood samples, perform a 7-T MRI, and collect demographic characteristics. DISCUSSION: The results of this proof-of-principle study will be used to assess the potential of target engagement of minocycline for CAA. Therefore, our primary outcome measures are markers of neuroinflammation (IL-6, MCP-1, and IBA-1) and of the gelatinase pathway (MMP2/9 and VEGF) in CSF. Secondly, we will look at the progression of hemorrhagic markers on 7-T MRI before and after treatment and investigate serum biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov NCT05680389. Registered on January 11, 2023.

Quantitative measurement of cortical superficial siderosis in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease affecting the small arteries in the brain with hallmark depositions of amyloid-ß in the vessel wall, leading to cognitive decline and intracerebral hemorrhage (ICH). An emerging MRI marker for CAA is cortical superficial siderosis (cSS) as it is strongly related to the risk of (recurrent) ICH. Current assessment of cSS is mainly done on T2*- weighted MRI using a qualitative score consisting of 5 categories of severity which is hampered by ceiling effects. Therefore, the need for a more quantitative measurement is warranted to better map disease progression for prognosis and future therapeutic trials. We propose a semi-automated method to quantify cSS burden on MRI and investigated it in 20 patients with CAA and cSS. The method showed excellent inter-observer (Pearson's 0.991, P < 0.001) and intra-observer reproducibility (ICC 0.995, P < 0.001). Furthermore, in the highest category of the multifocality scale a large spread in the quantitative score is observed, demonstrating the ceiling effect in the traditional score. We observed a quantitative increase in cSS volume in two of the 5 patients who had a 1 year follow up, while the traditional qualitative method failed to identify an increase because these patients were already in the highest category. The proposed method could therefore potentially be a better way of tracking progression. In conclusion, semi-automated segmenting and quantifying cSS is feasible and repeatable and may be used for further studies in CAA cohorts.

Systematic Review - Combining Neuroprotection With Reperfusion in Acute Ischemic Stroke.

Background: Clinical trials of neuroprotection in acute ischemic stroke (AIS) have provided disappointing results. Reperfusion may be a necessary condition for positive effects of neuroprotective treatments. This systematic review provides an overview of efficacy of neuroprotective agents in combination with reperfusion therapy in AIS. Methods: A literature search was performed on the following databases, namely PubMed, Embase, Web of Science, Cochrane Library, Emcare. All databases were searched up to September 23rd 2021. All randomized controlled trials in which patients were treated with neuroprotective strategies within 12 h of stroke onset in combination with intravenous thrombolysis (IVT), endovascular therapy (EVT), or both were included. Results: We screened 1,764 titles/abstracts and included 30 full reports of unique studies with a total of 16,160 patients. In 15 studies neuroprotectants were tested for clinical efficacy, where all patients had to receive reperfusion therapies, either IVT and/or EVT. Heterogeneity in reported outcome measures was observed. Treatment was associated with improved clinical outcome for: 1) uric acid in patients treated with EVT and IVT, 2) nerinetide in patients who underwent EVT without IVT, 3) imatinib in stroke patients treated with IVT with or without EVT, 4) remote ischemic perconditioning and IVT, and 5) high-flow normobaric oxygen treatment after EVT, with or without IVT. Conclusion: Studies specifically testing effects of neuroprotective agents in addition to IVT and/or EVT are scarce. Future neuroprotection studies should report standardized functional outcome measures and combine neuroprotective agents with reperfusion therapies in AIS or aim to include prespecified subgroup analyses for treatment with IVT and/or EVT.

Evolutionary algorithms and decision trees for predicting poor outcome after endovascular treatment for acute ischemic stroke.

Despite the large overall beneficial effects of endovascular treatment in patients with acute ischemic stroke, severe disability or death still occurs in almost one-third of patients. These patients, who might not benefit from treatment, have been previously identified with traditional logistic regression models, which may oversimplify relations between characteristics and outcome, or machine learning techniques, which may be difficult to interpret. We developed and evaluated a novel evolutionary algorithm for fuzzy decision trees to accurately identify patients with poor outcome after endovascular treatment, which was defined as having a modified Rankin Scale score (mRS) higher or equal to 5. The created decision trees have the benefit of being comprehensible, easily interpretable models, making its predictions easy to explain to patients and practitioners. Insights in the reason for the predicted outcome can encourage acceptance and adaptation in practice and help manage expectations after treatment. We compared our proposed method to CART, the benchmark decision tree algorithm, on classification accuracy and interpretability. The fuzzy decision tree significantly outperformed CART: using 5-fold cross-validation with on average 1090 patients in the training set and 273 patients in the test set, the fuzzy decision tree misclassified on average 77 (standard deviation of 7) patients compared to 83 (±7) using CART. The mean number of nodes (decision and leaf nodes) in the fuzzy decision tree was 11 (±2) compared to 26 (±1) for CART decision trees. With an average accuracy of 72% and much fewer nodes than CART, the developed evolutionary algorithm for fuzzy decision trees might be used to gain insights into the predictive value of patient characteristics and can contribute to the development of more accurate medical outcome prediction methods with improved clarity for practitioners and patients.

On the ability to exploit signal fluctuations in pseudocontinuous arterial spin labeling for inferring the major flow territories from a traditional perfusion scan.

In arterial spin labeling (ASL) a magnetic label is applied to the flowing blood in feeding arteries allowing depiction of cerebral perfusion maps. The labeling efficiency depends, however, on blood velocity and local field inhomogeneities and is, therefore, not constant over time. In this work, we investigate the ability of statistical methods used in functional connectivity research to infer flow territory information from traditional pseudo-continuous ASL (pCASL) scans by exploiting artery-specific signal fluctuations. By applying an additional gradient during labeling the minimum amount of signal fluctuation that allows discrimination of the main flow territories is determined. The following three approaches were tested for their performance on inferring the large vessel flow territories of the brain: a general linear model (GLM), an independent component analysis (ICA) and t-stochastic neighbor embedding. Furthermore, to investigate the effect of large vessel pathology, standard ASL scans of three patients with a unilateral stenosis (>70%) of one of the internal carotid arteries were retrospectively analyzed using ICA and t-SNE. Our results suggest that the amount of natural-occurring variation in labeling efficiency is insufficient to determine large vessel flow territories. When applying additional vessel-encoded gradients these methods are able to distinguish flow territories from one another, but this would result in approximately 8.5% lower perfusion signal and thus also a reduction in SNR of the same magnitude.

Optical coherence tomography detects retinal changes in hereditary cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Investigating mutation carriers with Dutch-type hereditary (D-) cerebral amyloid angiopathy (CAA), offers the possibility to identify markers in pre- and symptomatic stages of CAA. Optical coherence tomography (OCT) has shown potential to detect retinal changes in several neurodegenerative diseases. The aim of the present exploratory study was to investigate thinning of retinal layers as a possible (early) biomarker in D-CAA mutation carriers. METHODS: Twenty-one D-CAA mutation carriers (n = 8 presymptomatic, n = 13 symptomatic, median age 50 years) and nine controls (median age 53 years) were scanned using spectral-domain OCT. Symptomatic mutation carriers were defined as having a history of ≥1 symptomatic intracerebral hemorrhage. D-CAA mutation carriers and controls were recruited from our D-CAA cohort and a healthy control cohort. Total peripapillary retinal nerve fiber layer (pRNFL) thickness, six regions of pRNFL, total macular volume (TMV), and individual macular region thickness were measured and analysed, adjusted for age. RESULTS: The overall median (interquartile range) thickness of pRNFL was lower in symptomatic, but not presymptomatic D-CAA mutation carriers compared with controls [91 (86-95) µm vs. 99 (87-108) µm; P = 0.006]. Both presymptomatic [111 (93-122) µm vs. 131 (123-143) µm; P < 0.001] and symptomatic carriers [119 (95-128) µm vs. 131 (123-143) µm; P = 0.034] had a thinner temporal-superior quadrant of the pRNFL versus controls. TMV or individual macular layer thickness did not differ between carriers and controls. CONCLUSIONS: Thinning of the retinal nerve fiber layer may be a candidate marker of disease in hereditary CAA. Further studies are needed to determine whether retinal thinning is present in sporadic CAA and estimate its value as a marker for disease progression.

Cold extremities in migraine: a marker for vascular dysfunction in women.

BACKGROUND AND PURPOSE: Migraine is recognized as a vascular risk factor, especially in women. Presumably, migraine, stroke and cardiovascular events share pathophysiological mechanisms. Self-reported cold extremities were investigated as a marker for vascular dysfunction in migraine. Secondly, it was hypothesized that suffering from cold extremities affects sleep quality, possibly exacerbating migraine attack frequency. METHODS: In this case-control study, a random sample of 1084 migraine patients and 348 controls (aged 22-65 years) from the LUMINA migraine cohort were asked to complete questionnaires concerning cold extremities, sleep quality and migraine. RESULTS: A total of 594 migraine patients and 199 controls completed the questionnaires. In women, thermal discomfort and cold extremities (TDCE) were more often reported by migraineurs versus controls (odds ratio 2.3, 95% confidence interval 1.4-3.7; P < 0.001), but not significantly so in men (odds ratio 2.5, 95% confidence interval 0.9-6.9; P = 0.09). There was no difference in TDCE comparing migraine with or without aura. Female migraineurs who reported TDCE had higher attack frequencies compared to female migraineurs without TDCE (4 vs. 3 attacks per month; P = 0.003). The association between TDCE and attack frequency was mediated by the presence of difficulty initiating sleep (P = 0.02). CONCLUSION: Women with migraine more often reported cold extremities compared with controls, possibly indicating a sex-specific vascular vulnerability. Female migraineurs with cold extremities had higher attack frequencies, partly resulting from sleep disturbances. Future studies need to demonstrate whether cold extremities in female migraineurs are a predictor for cardiovascular and cerebrovascular events.

Data-efficient deep learning of radiological image data for outcome prediction after endovascular treatment of patients with acute ischemic stroke.

Treatment selection is becoming increasingly more important in acute ischemic stroke patient care. Clinical variables and radiological image biomarkers (old age, pre-stroke mRS, NIHSS, occlusion location, ASPECTS, among others) have an important role in treatment selection and prognosis. Radiological biomarkers require expert annotation and are subject to inter-observer variability. Recently, Deep Learning has been introduced to reproduce these radiological image biomarkers. Instead of reproducing these biomarkers, in this work, we investigated Deep Learning techniques for building models to directly predict good reperfusion after endovascular treatment (EVT) and good functional outcome using CT angiography images. These models do not require image annotation and are fast to compute. We compare the Deep Learning models to Machine Learning models using traditional radiological image biomarkers. We explored Residual Neural Network (ResNet) architectures, adapted them with Structured Receptive Fields (RFNN) and auto-encoders (AE) for network weight initialization. We further included model visualization techniques to provide insight into the network's decision-making process. We applied the methods on the MR CLEAN Registry dataset with 1301 patients. The Deep Learning models outperformed the models using traditional radiological image biomarkers in three out of four cross-validation folds for functional outcome (average AUC of 0.71) and for all folds for reperfusion (average AUC of 0.65). Model visualization showed that the arteries were relevant features for functional outcome prediction. The best results were obtained for the ResNet models with RFNN. Auto-encoder initialization often improved the results. We concluded that, in our dataset, automated image analysis with Deep Learning methods outperforms radiological image biomarkers for stroke outcome prediction and has the potential to improve treatment selection.

Distinguishing core from penumbra by lipid profiles using Mass Spectrometry Imaging in a transgenic mouse model of ischemic stroke.

Detecting different lipid profiles in early infarct development may give an insight on the fate of compromised tissue. Here we used Mass Spectrometry Imaging to identify lipids at 4, 8 and 24 hours after ischemic stroke in mice, induced by transient middle cerebral artery occlusion (tMCAO). Combining linear transparency overlay, a clustering pipeline and spatial segmentation, we identified three regions: infarct core, penumbra (i.e. comprised tissue that is not yet converted to core), and surrounding healthy tissue. Phosphatidylinositol 4-phosphate (m/z = 965.5) became visible in the penumbra 24 hours after tMCAO. Infarct evolution was shown by 2D-renderings of multiple phosphatidylcholine (PC) and Lyso-PC isoforms. High-resolution Secondary Ion Mass Spectrometry, to evaluate sodium/potassium ratios, revealed a significant increase in sodium and a decrease in potassium species in the ischemic area (core and penumbra) compared to healthy tissue at 24 hours after tMCAO. In a transgenic mouse model with an enhanced susceptibility to ischemic stroke, we found a more pronounced discrimination in sodium/potassium ratios between penumbra and healthy regions. Insight in changes in lipid profiles in the first hours of stroke may guide the development of new prognostic biomarkers and novel therapeutic targets to minimize infarct progression.

[Women with migraine have an increased risk of cardiovascular disease; what are the consequences for the clinical management of young patients?] / Hoger cardiovasculair risico bij vrouwen met migraine.

Migraine is often regarded as a debilitating headache disorder without long-term consequences. However, migraine is an important risk factor for cardiovascular disease, especially in young women who suffer from migraine with aura. This increased risk is not limited to stroke but includes cardiac disease. The absolute risk for cardiovascular disease remains low in young women, however the prevalence of migraine is particularly high in this population. Migraine should therefore be incorporated as a factor in cardiovascular risk assessment. Mechanisms underlying the relationship between migraine and cardiovascular disease are complex and probably multifactorial. Endothelial dysfunction may play a pivotal role. Knowledge about the interaction of migraine with other risk factors and evidence-based recommendations on clinical management remain limited. Lifestyle advice, including the promotion of smoking cessation, is of utmost importance.

[Ischemic stroke in young women]. / Herseninfarct bij jonge vrouwen.

- In virtually all age groups, the incidence of ischemic stroke is higher in men. However, in women aged between 25-49 years the prevalence is higher than in men. Female-specific risk factors and disorders may explain this peak.- Pregnancy and the post-partum period are associated with physiological changes which can increase blood coagulation. Complications during pregnancy may also increase the risk of ischaemic stroke.- Migraine with aura and antiphospholipid syndrome are disorders which are also associated with an increased risk of ischaemic stroke. These disorders are more common in women compared to men. Furthermore, hormonal contraceptives containing oestrogen are also identified to increase the incidence of ischaemic stroke.- The acute treatment and secondary prevention of ischaemic stroke in young women is identical to that in elderly stroke patients, be it men or women, although thrombolysis and platelet aggregation inhibition in pregnant women should be approached with care.- Clinical outcomes after stroke for women under the age of 50 are worse compared to age-matched men.

Assessment of Collateral Status by Dynamic CT Angiography in Acute MCA Stroke: Timing of Acquisition and Relationship with Final Infarct Volume.

BACKGROUND AND PURPOSE: Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS: We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of ≥70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS: Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of ≥70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-slow collaterals) were analyzed separately; the results showed that compared with good and fast collaterals, a similar risk ratio was found for patients with good-but-slow collaterals (risk ratio, 1.3; 95% CI, 0.7-2.4). CONCLUSIONS: Dynamic CTA provides a more detailed assessment of collaterals than single-phase CTA and has a stronger relationship with infarct volume at follow-up. The extent of collateral flow is more important in determining tissue fate than the velocity of collateral filling. The timing of dynamic CTA acquisition in relation to intravenous contrast administration is critical for the optimal assessment of the extent of collaterals.

Safety of intra-arterial treatment in acute ischaemic stroke patients on oral anticoagulants. A cohort study and systematic review.

BACKGROUND AND PURPOSE: An elevated international normalized ratio (INR) of >1.7 is a contraindication for the use of intravenous thrombolytics in acute ischaemic stroke. Local intra-arterial therapy (IAT) is considered a safe alternative. The safety and outcome of IAT were investigated in patients with acute ischaemic stroke using oral anticoagulants (OACs). METHODS: Data were obtained from a large national Dutch database on IAT in acute stroke patients. Patients were categorized according to the INR: >1.7 and ≤1.7. Primary outcome was symptomatic intracerebral hemorrhage (sICH), defined as deterioration in the National Institutes of Health Stroke Scale score of ≥4 and ICH on brain imaging. Secondary outcomes were clinical outcome at discharge and 3 months. Occurrence of outcomes was compared with risk ratios and corresponding 95% confidence intervals. Further, a systematic review and meta-analysis on sICH risk in acute stroke patients on OACs treated with IAT was performed. RESULTS: Four hundred and fifty-six patients were included. Eighteen patients had an INR > 1.7 with a median INR of 2.4 (range 1.8-4.1). One patient (6%) in the INR > 1.7 group developed a sICH compared with 53 patients (12%) in the INR ≤ 1.7 group (risk ratio 0.49, 95% confidence interval 0.07-3.13). Clinical outcomes did not differ between the two groups. Our meta-analysis showed a first week sICH risk of 8.1% (95% confidence interval 3.9%-17.1%) in stroke patients with elevated INR treated with IAT. CONCLUSION: The use of OACs, leading to an INR > 1.7, did not seem to increase the risk of an sICH in patients with an acute stroke treated with IAT.

The value of CT angiography in patients with acute severe headache.

Patients with acute severe headache may have a secondary form of headache. Standard head computer tomography (CT) and cerebrospinal fluid (CSF) examination are often performed in the absence of neurological deficits to exclude subarachnoid hemorrhage (SAH). Increasingly, patients undergo subsequent CT angiography (CTA) to exclude cerebral venous thrombosis (CVT), dissection or reversible cerebral vasoconstriction syndrome (RCVS). It is unknown whether this additional imaging increases diagnostic yield. We aimed to evaluate the yield of CTA in patients with acute severe headache with normal neurological examination and no abnormalities at standard CT and CSF analysis. We included consecutive patients presenting to the emergency room between January 2008 and May 2011 with acute severe headache and without abnormalities at neurological examination, CT and CSF research, who received a CTA in the diagnostic process in our teaching hospital. All scans were rereviewed by an experienced neuroradiologist. We included 70 patients, 71% were women and average age was 45 years. We found a vascular abnormality in 13 (19%) of our patients. Four had either a prior aneurysm or CVT. Eight patients had an unruptured intracranial aneurysm (UIA) on CTA (11%), two had CVT (3%), two had RCVS (3%) and one had cerebral ischemia (1%). We found a high percentage of vascular abnormalities. A third of these patients had a prior episode of either an aneurysm or CVT. In patients with a history of UIA or CVT performing CTA despite normal CT and LP therefore seems warranted. A prospective study to delineate indications for CTA is needed.

Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters.

INTRODUCTION: Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. METHODS: In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. RESULTS: Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10% as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4% for the 8-cm, 7% for the 4-cm, and 13% for the 3-cm coverage size. CONCLUSION: This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage.

Pirandello's analogy: a source for a better understanding of the social impact of stroke.

BACKGROUND: Suffering a stroke has major implications for the patient. To understand human suffering, one should understand society. Pirandello described society as a higher entity than the individual, thereby justifying human adaptability to society. We explore a qualitative finding that suggests that social trends may influence how stroke patients prioritize aspects of their rehabilitation. METHODS: We compare a contemporary patient's experience of stroke recovery with that of a fictional character from the works of Luigi Pirandello. Both patients had two main residual symptoms: hemiparesis and aphasia. RESULTS: The rehabilitation priorities of the two patients differed, and appeared to reflect the contemporaneous demands of society. Mobility was prioritized in 1910; communication was prioritized in 2010. However, essential aspects of 'being a stroke patient' remained unchanged; both patients retained a sense of self and both coped emotionally by being hopeful. CONCLUSIONS: We conclude that stroke patients respond to society's contemporaneous demands and expectations. Currently, society demands participation in a large social environment and this is reflected in stroke patients' priorities. This analogy could enable medical professionals to better understand the social impact of stroke, and consequently offer appropriate interventions to improve rehabilitation outcomes for individual patients.

Long-term mortality and vascular event risk after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Patients with a history of subarachnoid haemorrhage (SAH) may be at risk for vascular events and excess mortality. METHODS: We interviewed 752 patients (mean age 50 years, 67% women, mean follow-up 8.1 years) clipped between 1985 and 2001 after SAH who had been discharged home or to a rehabilitation facility about new vascular events. We compared age- and sex-specific mortality after SAH with that of the general population by standardised mortality ratios (SMR). The incidence of vascular events in SAH patients was compared with that in patients after a transient ischaemic attack or minor stroke. RESULTS: The SMR for SAH patients was 1.7 (95% CI 1.4 to 2.1) overall and 3.2 (95% CI 0.8 to 13.1) for patients <40 years. In the first 10 years after SAH the cumulative incidence of a vascular event was 11.2% (95% CI 7.0 to 14.4), which was lower (hazard ratio 0.43, 95% CI 0.33 to 0.57) than that in patients with a minor stroke. CONCLUSION: SAH patients who recover to a functional independent state have an excess mortality compared with the general population. The risk of vascular events after SAH is lower than after minor stroke, but higher than the population risks reported in the literature.

Psychosocial impact of finding small aneurysms that are left untreated in patients previously operated on for ruptured aneurysms.

OBJECTIVES: In patients with previous subarachnoid haemorrhage (SAH) undergoing follow up screening, the authors assessed the impact of finding but not treating very small aneurysms by comparing quality of life (QOL), anxiety, and depression between patients with a newly detected aneurysm that was left untreated (cases) and patients with a negative screening (controls) as this should be incorporated in the evaluation of effectiveness of screening. METHODS: In patients with previous SAH undergoing screening for new aneurysms the authors compared QOL (SF-36, EURO-QOL, and a screening related questionnaire), anxiety, and depression (Hospital Anxiety and Depression Scale (HADS)) between cases and controls. Differences in scores on the SF-36, EURO-QOL, and HADS were assessed with Student's t test and differences in proportions of patients with HADS scores in the pathological range and screening related changes with chi2 analysis. The authors powered the study to detect a moderate, clinically relevant difference. RESULTS: Thirty five cases and 34 controls were included. Trends for health related QOL, anxiety, depression, and consequences in daily life pointed in the same direction of a less favourable situation for cases but all effects were small, and did not reach statistical significance. On the screenings specific questionnaire, cases more often (but not statistically significant) reported changes in daily life. CONCLUSIONS: The authors found no major or moderate impact on QOL, anxiety, and depression of the awareness of having an untreated aneurysm, which was detected at screening, although most items showed a trend towards more negative effects for cases. Minor effects on individual level cannot be excluded by this study.

Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms.

Intracranial aneurysms have long been considered a once in a lifetime event. Nevertheless, patients who survive after subarachnoid haemorrhage (SAH) may be at risk for new aneurysms. In a cohort of patients with clipped aneurysms, we studied the yield of screening in the years after the SAH and we tried to identify risk factors for formation of new aneurysms as well as for enlargement of aneurysms that were already present at the time of the SAH. We screened 610 patients who had been admitted between 1985 and 2001 for SAH by means of CT-angiography. Risk factors were evaluated by Cox regression analyses. With screening we detected 129 aneurysms in 96 (16%) patients, after a mean interval of 8.9 years. Of these, 24 (19%) were located at the site of the previously ruptured and clipped aneurysm and 105 (81%) at a site remote from the clip site. Of the aneurysms at a remote site 59 could be compared with the initial (CT)-angiogram. Of these, 19 were truly de novo (32%) and 40 (68%) were already visible in retrospect. Of the 53 aneurysms that were followed over time 13 (25%) had enlarged. Risk factors for aneurysm formation and growth were presence of multiple aneurysms at time of SAH (HR 3.2, 95% CI 1.2-8.6), current smoking (HR 3.8, 95% CI 1.5-9.4) and hypertension (HR 2.3, 95% CI 1.1-4.9). These results suggest that intracranial aneurysms should not be considered as a single event in a lifetime but rather as a continuous process. Patients with a previous SAH have a substantial risk for new aneurysm formation and enlargement of untreated aneurysms. Screening these patients might be beneficial, especially in patients with multiple aneurysms, hypertension and a history of smoking. The risks and benefits of screening, however, should be carefully weighed, for example, in a decision model.