Subsequent Subarachnoid Hemorrhage Research Articles

Geometric versus Hemodynamic Indexes for Rupture-Destined Aneurysms: A Retrospective Cohort and a Repeated-Measures Study

Plain Language SummaryThe incidence of intracranial aneurysm (IA) is 2–3% in the general population, and with the widespread use of neurovascular imaging techniques, more IAs are being diagnosed. IA management is crucial as it can lead to fatal subarachnoid hemorrhage, causing high mortality and neurological issues. About 1% of patients with IA experience severe hemorrhage annually, which raises questions about the best method to assess rupture risk. Past studies used geometric indexes and computational fluid dynamics to differentiate between ruptured and unruptured aneurysms. However, these studies mostly focused on cross-sectional data and did not analyze the evolutionary changes of ruptured aneurysms. In this study, we call such aneurysms rupture-destined aneurysms (RDAs) to differentiate from stable unruptured intracranial aneurysm (UIA). In the present study, the key findings could be summarized as below: (1) the RDA group showed a significantly higher hemodynamic instability than the UIA group; (2) the UIA group showed features of hemodynamic stability, even with geometric growth; (3) aneurysmal rupture risk should be assessed using both geometric and hemodynamic information.

Vertebral Artery Dissection Mimicking Migraine: A Case Report

Vertebral artery dissection (VAD) is caused by an intimal tear that leads to bleeding into the vascular wall, which may cause vascular occlusion by thrombus formation and subsequent distal emboli (leading to ischemic stroke), aneurysm formation and subarachnoid hemorrhage. Cervical artery dissections (either carotid or vertebral artery dissection) are an important cause of stroke in patients under 50-years of age. Headache with or without neck pain is a common symptom. Usually, it occurs with focal neurological signs but sometimes it may occur without any neurological deficits and may mimic migraine. Often it occurs spontaneously without trauma but sometimes there is history of minor traumas, sudden neck movements or chiropractic manipulation. Imaging modalities include magnetic resonance imaging (MRI) brain, magnetic resonance angiography (MRA), and computed tomography angiography (CTA). Treatment involves anticoagulation or antiplatelet agents.

Varicella-Zoster Virus Vasculitis: A Case Report of Enteric Reactivation with Vasculopathy Leading to Arterial Dissection, Stroke, and Subarachnoid Hemorrhage

Varicella-Zoster virus (VZV) reactivation is known to cause vascular remodeling and creating a hypercoagulable state, which can result in vasculopathy and subsequent thrombotic complications. Frequently, these complications involve intracranial and extracranial arteries leading to ischemic stroke, cerebral aneurysm formation, subarachnoid hemorrhage, cerebral vasculitis, and giant cell arteritis. Symptoms involving veins, such as cerebral sinus thrombosis, deep venous thrombosis, and pulmonary embolism, are rare. VZV reactivation is classically identified in neuronal ganglia that are derived from neural crest cells, primarily the dorsal root ganglia with the typical zoster dermatomal rash. In addition to the dorsal root ganglia, the enteric nervous system and adrenal glands are also of neural crest origin. However, VZV reactivation in these regions is rarely recognized due to a lack of cutaneous innervation. Enteric VZV reactivation can present with vague gastrointestinal symptoms instead of the typical zoster skin rash, which may be overlooked and delay the diagnosis. We report a rare case of VZV reactivation in the enteric nervous system and adrenal gland leading to vasculitis and subsequent Subarachnoid Hemorrhage (SAH), multifocal ischemic stroke, right Internal Carotid Artery (ICA) dissection, Deep Venous Thrombosis (DVT), and Pulmonary Embolism (PE).

Prevalence, predictors and prognosis of incidental intracranial aneurysms in patients with suspected TIA and minor stroke: a population-based study and systematic review

IntroductionUnruptured intracranial aneurysms (UIAs) are common incidental imaging findings, but there are few data in patients with transient ischaemic attack (TIA)/stroke. The frequency of UIA might be higher due to...

Supraclinoid Internal Carotid Artery Fenestration with Associated Aneurysm: Case Report and Literature Review

Fenestration of the supraclinoid internal carotid artery (ICA) is extremely rare and may occasionally be associated with saccular aneurysms; nevertheless, the natural history remains unclear. The authors reviewed the cases of fenestration of the supraclinoid ICA and evaluated the clinical characteristics and angioarchitecture with particular focus on the incidence for aneurysm development and rupture. Previously reported 24 cases and 1 new case from our institute were examined for the presence of aneurysms (including size and presence of bleb) leading to subsequent subarachnoid hemorrhage (SAH). Furthermore, 16 cases with sufficient information were classified into one of the three types according to the developmental condition of fenestration and fusion site: Type A (developed fenestration in which the ICA appears to duplicate [two cases]); Type B (hypoplastic fenestration fused to the ICA at the origin of the posterior communicating artery [Pcom] [six cases]); and Type C (hypoplastic fenestration fused to the Pcom itself or appeared to be a duplicated Pcom [eight cases]). In type A, the two cases had an aneurysm (100%), one of which caused SAH (50%). In type B, all six cases had an aneurysm (100%), and one of five led to SAH (20%) (one case lacked information regarding SAH). In type C, five of the eight cases had an aneurysm (62.5%), with no SAH (0%). The result suggested that the extent of development of fenestration and the location of fusion are related to the incidence of aneurysms and risk for rupture.

TLR4 (Toll-Like Receptor 4) Mediates the Development of Intracranial Aneurysm Rupture.

Inflammation is emerging as a critical factor in the pathophysiology of intracranial aneurysm. TLR4 (toll-like receptor 4) contributes not only to the innate immune responses but also to the inflammatory processes associated with vascular disease. Therefore, we examined the contribution of the TLR4 pathway to the development of the rupture of intracranial aneurysm. We used a mouse model of intracranial aneurysm. TLR4 inhibition significantly reduced the development of aneurysmal rupture. In addition, the rupture rate and levels of proinflammatory cytokines were lower in TLR4 knockout mice than the control littermates. Macrophage/monocyte-specific TLR4 knockout mice had a lower rupture rate than the control littermate mice. Moreover, the deficiency of MyD88 (myeloid differentiation primary-response protein 88), a key mediator of TLR4, reduced the rupture rate. These findings suggest that the TLR4 pathway promotes the development of intracranial aneurysmal rupture by accelerating inflammation in aneurysmal walls. Inhibition of the TLR4 pathway in inflammatory cells may be a promising approach for the prevention of aneurysmal rupture and subsequent subarachnoid hemorrhage.

Abstract P118: Inhibition of Endoplasmic Reticulum Stress Prevents Intracranial Aneurysmal Rupture in a Mouse Model

Background: Aneurysmal subarachnoid hemorrhage (SAH) can cause significant mortality and morbidity. To develop a therapy for prevention of intracranial aneurysmal rupture and subsequent SAH, it is important to clarify the mechanism of intracranial aneurysmal rupture. Stimulation of the renin-angiotensin system (RAS) causes hypertension and cardiovascular remodeling. Recent evidence shows that angiotensin II enhances endoplasmic reticulum (ER) stress and inhibition of ER stress prevents angiotensin II-induced vascular remodeling but not hypertension in mice. RAS has also been implicated in intracranial aneurysms. We have previously shown that angiotensin II receptor blocker (losartan) prevented intracranial aneurysmal rupture in a mouse model without affecting systemic hypertension. To clarify the mechanism of intracranial aneurysmal rupture via RAS, we have tested our hypothesis that inhibition of ER stress prevents intracranial aneurysmal rupture in a mouse model. Method: We used a mouse model of intracranial aneurysms in which spontaneous aneurysmal rupture causes neurologic symptoms. Intracranial aneurysms were induced in wild type mice by a single stereotactic injection of elastase (35mU) into the cerebrospinal fluid at right basal cistern and deoxycorticosterone (DOCA)-salt hypertension. Vehicle or 4-phenylbutyric acid (PBA, ER stress inhibitor , 100mg/kg/day) was subcutaneously injected into all mice once a day. To detect aneurysmal rupture, we performed daily neurological examinations. Symptomatic mice were euthanized immediately when they developed neurological symptoms, and all asymptomatic mice were euthanized 21 days after aneurysm induction. The incidence of aneurysms and rupture rate were compared between vehicle group and PBA group. Results: The incidence of aneurysms was not significantly different between two groups (100% in vehicle, 20 of 20 vs. 87% in PBA, 20 of 23, p=0.09). However, rupture rate was significantly lower in the PBA group (60%, 12 of 20) than the vehicle group (95%, 19 of 20). (p=0.008). Conclusion: Inhibition of ER stress reduced aneurysmal rupture in a mouse model of intracranial aneurysm induced by combination of elastase injection and DOCA-salt hypertension.

Invasive Orbital Apex Aspergillosis with Mycotic Aneurysm Formation and Subarachnoid Hemorrhage in Immunocompetent Patients.

Invasive orbital apex aspergillosis (IOAA) is an aggressive form of aspergillus infection that usually affects immunocompromised patients. It can cause orbital apex syndrome and, if not treated promptly, may progress rapidly causing fatal complications. Subarachnoid hemorrhage (SAH) secondary to ruptured mycotic aneurysms is a very rare complication of invasive aspergillosis. We aim to describe our management and the outcome of six immunocompetent patients with IOAA with subsequent SAH secondary to ruptured mycotic aneurysms. A retrospective review was undertaken of charts of patients treated for orbital involvement with aspergillosis between January 2003 and December 2015 at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. We identified all immunocompetent patients with IOAA who developed vascular complications. Six immunocompetent patients with IOAA complicated by SAH secondary to ruptured mycotic aneurysms were identified in the study period. Four patients were female, and patients' age ranged between 14 and 53 years (mean, 33.7 ± 13.4 years). All patients presented with progressive retro-orbital headache, visual impairment, and ophthalmoplegia; four had proptosis. Two patients had vasospasm and brain infarction. Antifungal therapy was used in all patients, and 4 underwent emergency craniotomy and clipping of an aneurysm. Five patients died as a consequence of SAH and infarction. IOAA is a serious disease that commonly causes catastrophic and fatal vascular complications.

Fatal subarachnoid hemorrhage following ischemia in vertebrobasilar dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a chronic disorder with various cerebrovascular and compressive manifestations, involving subarachnoid hemorrhage (SAH). Occurrence of SAH shortly after worsening of clinical VBD symptoms has occasionally been reported. The goal of the study was to examine this association, in particular its pathophysiology, clinical precursor signs, time course, and outcome.To this end, in a retrospective multicenter study, we analyzed 20 patients with VBD and SAH in regard to preceding clinical symptoms, presence of vertebrobasilar thrombosis and ischemia, outcome and neuropathological correlates.Median age of the 7 female and 13 male patients was 70 years (interquartile range [IQR] 18.3 years). Fourteen patients (70%) presented with new or acutely worsening posterior fossa signs at a median of 3 days prior to SAH (IQR 2, range 0.5–14). A thrombus within the VBD was detected in 12 patients (60%). Thrombus formation was associated with clinical deterioration (χ2 = 4.38, P = 0.04) and ponto-cerebellar ischemia (χ2 = 8.09, P = 0.005). During follow-up after SAH, 13 patients (65%) died, after a median survival time of 24 hours (IQR 66.2, range 2–264 hours), with a significant association between proven ponto-cerebellar ischemia and case fatality (χ2 = 6.24, P = 0.01).The data establish an association between clinical deterioration in patients with VBD, vertebrobasilar ischemia, and subsequent SAH. Antithrombotic treatment after deterioration appears controversial and SAH outcome is frequently fatal. Our data also indicate a short window of 3 days that may allow for evaluating interventional treatment, preferably within randomized trials.

Twin-like appearance of an unruptured intracerebral anterior communicating artery (ACom) aneurysm in a male sibling of a patient with a ruptured ACom aneurysm

Increased risk of intracranial aneurysm rupture with subsequent subarachnoid haemorrhage (SAH) is related to several possible factors, including first-grade familial aneurysms. Here we present a case of one ruptured and one unruptured identical twin-like anterior communicating artery (ACom) aneurysm present in two male siblings, without any proven genetic predisposition. According to evidence-based scores, aneurysm rupture risk for the younger (51years old) sibling (with an unruptured ACom aneurysm) would be low, leaving the decision for either treatment or clinical follow-up to the discretion of the treating physician. From a clinical neurosurgical perspective, however, especially since his older brother suffered an aneurysmal SAH at age 57 (i.e. 6 life-years later) from a twin-like-appearing ACom aneurysm, in our opinion rupture seems almost inevitable, thus prompting treatment at an early stage.

The CHESS score: a simple tool for early prediction of shunt dependency after aneurysmal subarachnoid hemorrhage.

Acute hydrocephalus is an early and common complication of aneurysmal subarachnoid hemorrhage (SAH). However, considerably fewer patients develop chronic hydrocephalus requiring shunt placement. Our aim was to develop a risk score for early identification of patients with shunt dependency after SAH. Two hundred and forty-two SAH individuals who were treated in our institution between January 2008 and December 2013 and survived the initial impact were retrospectively analyzed. Clinical parameters within 72 h after the ictus were correlated with shunt dependency. Independent predictors were summarized into a new risk score which was validated in a subsequent SAH cohort treated between January and December 2014. Seventy-five patients (31%) underwent shunt placement. Of 23 evaluated variables, only the following five showed independent associations with shunt dependency and were subsequently used to establish the Chronic Hydrocephalus Ensuing from SAH Score (CHESS, 0-8 points): Hunt and Hess grade ≥IV (1 point), location of the ruptured aneurysm in the posterior circulation (1 point), acute hydrocephalus (4 points), the presence of intraventricular hemorrhage (1 point) and early cerebral infarction on follow-up computed tomography scan (1 point). The CHESS showed strong correlation with shunt dependency (P = 0.0007) and could be successfully validated in both internal SAH cohorts tested. Patients scoring ≥6 CHESS points had significantly higher risk of shunt dependency (P < 0.0001) than other patients. The CHESS may become a valuable diagnostic tool for early estimation of shunt dependency after SAH. Further evaluation and external validation will be required in prospective studies.

Fenestrated azygos A2 segment: a rare anatomic variation

Advancement in neurovascular imaging has led to detection of abnormalities and normal anatomic variations. Most of anatomical variations in cerebral vasculature are asymptomatic and found incidentally; however, some may increase the risk of aneurysm formation and subsequent subarachnoid or intracranial hemorrhage. Here in, we report fenestration within an azygos A2 segment, as an incidental finding, which is an extremely rare anatomic variation in a patient suffering subarachnoid hemorrhage (SAH). However, there was no correlation found between SAH and the mentioned anatomic variation. To author’s knowledge this is the first report of such anatomic variation with providing source images of brain CT angiograms.

Relationship between Postmenopausal Estrogen Deficiency and Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is one of the most severe forms of stroke, which results from the rupture of a cerebral aneurysm. SAH is the only type of stroke with a female predominance, suggesting that reproductive factors may play a significant role in the etiology. Estrogen has important effects on vascular physiology and pathophysiology of cerebral aneurysm and SAH and, thus, potential therapeutic implications. There have been growing bodies of epidemiological and experimental studies which support the hypothesis of a significant relationship between estrogen deficiency and cerebral aneurysm formation with subsequent SAH. This hypothesis is the focus of this review as well as possible pathology-based therapeutics with regard to aspects of molecular pathophysiology, especially related to women's health.

Mouse models of intracranial aneurysm.

Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-α, the renin-angiotensin system and the β-estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and applying findings to patients.

Low risk for subsequent subarachnoid hemorrhage for emergency department patients with headache, bloody cerebrospinal fluid, and negative findings on cerebrovascular imaging.

OBJECT.: When patients present to the emergency department (ED) with acute headache concerning for subarachnoid hemorrhage (SAH) and a lumbar puncture (LP) shows blood in the CSF, it is difficult to distinguish the results of a traumatic LP from those of SAH. CT angiography (CTA) is often performed, but the long-term outcome for patients with a positive LP and normal neurovascular imaging remains uncertain. The primary objective of this study was to determine whether patients who presented to the ED with acute headache and had red blood cells (RBCs) in their CSF on LP but negative cerebrovascular imaging suffered subsequent SAH. A case series study of consecutive adult ED patients who incurred charges for LP between 2001 and 2009 was performed from 2010 through 2011. Inclusion criteria were: headache, > 5 RBCs/mm(3) in CSF, noncontrast head CT with no evidence of hemorrhage, and cerebrovascular CTA or MRA without aneurysm or vascular lesion within 2 weeks of the ED visit. Patients with less than 6 months of available follow-up were excluded. The primary outcomes were 1) subsequent nontraumatic SAH and 2) new vascular lesion. Secondary outcomes were complications related to SAH, or LP or angiography. Of 4641 ED patients billed for an LP, 181 patients (mean age 42 years) were included in this study. Over a median follow-up of 53 months, 0 (0%) of 181 patients (95% CI 0%-2.0%) had a subsequent SAH or new vascular lesion identified. Although not the primary outcome, there was 1 patient who was ultimately diagnosed with vasculitis. Eighteen (9.9%) of 181 patients (95% CI 6.0%-15.3%) had an LP-related complication and 0 (0%) of 181 patients (95% CI 0%-2.0%) had an angiography-related complication. Patients who present to the ED with acute headache concerning for SAH and have a finding of bloody CSF on LP but negative findings on cerebrovascular imaging are at low risk for subsequent SAH and thus are likely to be safe for discharge. Replacement of the CT/LP with a CT/CTA diagnostic algorithm merits further investigation.

Orbital apex syndrome due to aspergillosis with subsequent fatal subarachnoid hemorrhage

Background:Orbital apex syndrome has been described previously as a syndrome involving damage to the oculomotor nerve (III), trochlear nerve (IV), abducens nerve (VI), and ophthalmic branch of the trigeminal nerve (V1), in association with optic nerve dysfunction. It may be caused by inflammatory, infectious, neoplastic, iatrogenic, or vascular processes.Case Description:A 73-year-old female having hypertension and rheumatoid arthritis stage 4 under long-term corticosteroid therapy presented to us with the right side orbital apex syndrome. Her magnetic resonance imaging (MRI) of orbit showed progression of a lesion at the right orbital apex and adjacent right superior orbital fissure with mild extension to the right posterior ethmoid sinus. She underwent endoscopic endonasal transethmoid approach with the removal of the lesion. The pathology showed a picture of fungal infection and the culture of the specimen proved Aspergillus fumigatus. Her postoperative course was smooth until 5 days after surgery, when she suffered a massive spontaneous subarachnoid hemorrhage resulting from a ruptured aneurysm, which was proven by computed tomography angiography (CTA) of brain. Unfortunately, she expired due to central failure.Conclusion:In cases of immunocompromised patients having orbital apex syndrome, fungal infection should be kept in mind. One of the most lethal but rare sequels of CNS fungal infection is intracranial aneurysms. Early diagnosis and radical resection, combined with antifungal medications is the key to save this particular group of patients.

Subarachnoid Hemorrhage During Sexual Activity After Sildenafil Intake

We report and describe an autopsy case of a man dead for rupture of cerebral artery aneurysm with subsequent subarachnoid hemorrhage after sexual intercourse. Toxicologic analysis demonstrated that he had consumed sildenafil (Viagra). Although subarachnoid hemorrhage has been reported to be associated with sexual intercourse, it is not among the known adverse effects of sildenafil. However, sildenafil has been found to interact with vascular physiology via multiple mechanisms and in most of the vascular districts of the human body. This case provides an example of a very rare association between this drug and a fatal pathologic event and deserves to be added to the existing clinical knowledge about sildenafil and the pathophysiology of the events involved. This knowledge may be helpful in orienting further investigation into the mechanisms of action of sildenafil and their clinical implications.

Complementary inhibition of cerebral aneurysm formation by eNOS and nNOS

The rupture of cerebral aneurysm (CA) and subsequent subarachnoid hemorrhage can cause fatal results. Recent experimental findings have suggested that the mechanism of CA formation is based on chronic inflammation in arterial walls by hemodynamic force. Endothelial nitric oxide synthase (eNOS) protects arterial walls from vascular inflammation by relieving hemodynamic force through nitric oxide (NO) production. Thus, the expression and protective role of eNOS in CA formation have been investigated in this study. In this study, experimental induced rodent CA models by carotid ligation and systemic hypertension were used. The expression of eNOS was examined in rat CA models and revealed that it was decreased at the site of CA formation. Next, CA was induced in eNOS−/− mice to clarify the role of eNOS in CA formation. In eNOS−/− mice, the incidence of CA formation was similar to that found in wild-type mice. In CA walls of eNOS−/− mice, the expression of neuronal nitric oxide synthase (nNOS) was upregulated compared with that in wild-type mice, suggesting the compensatory effect of nNOS. Hence, eNOS−/− nNOS−/− mice were generated, underwent CA induction and confirmed that eNOS−/− nNOS−/− mice exhibited an increased incidence of CA formation accompanied by accelerated macrophage infiltration. These results suggested that the deficiency of eNOS could be compensated by nNOS upregulation in cerebral arteries and that the eNOS and nNOS complementarily had the protective role in CA formation. The results of this study will provide us with new insight about the mechanisms of CA formation and the functional redundancy between eNOS and nNOS in cerebral arteries.

Neuroform Stent-Assisted Embolization of Incidental Anterior Communicating Artery Aneurysms: Long-term Clinical and Angiographic Follow-up

Anterior communicating artery (A-comm) aneurysm is one of the most common intracranial aneurysms. Treatments include neurosurgical clipping or endovascular embolization. To retrospectively examine the long-term results of Neuroform stent-assisted coil embolization of incidental A-comms, with a focus on stent-associated stenosis, long-term angiographic aneurysm occlusion outcome, delayed stent-related thromboembolus, subsequent subarachnoid hemorrhage from the treated aneurysm, and procedural complications. Between January 7, 2003 and June 16, 2009, 44 Neuroform stents were placed as an adjunct to embolization of A-comms. Patient charts were reviewed retrospectively. Angiographic follow-up of at least 3 months (up to 6.5 years, mean 65 weeks) was available for 33 patients. Aneurysm occlusion success was determined using the Raymond classification for aneurysm remnants. Referencing the last angiogram in the follow-up course, complete occlusion, dog-ear residual, residual neck, and residual aneurysm were found in 24, 2, 3, and 4 patients, respectively. Stenosis (45% and asymptomatic) of the artery where the stent had been placed was found in 1 patient. One patient had delayed transient ischemic attack after dual antiplatelet therapy was stopped prematurely. Retreatment based on the presence of residual aneurysm was performed or recommended in 2 patients. In 2 patients with residual or recurrent aneurysm filling, their age or clinical condition did not warrant retreatment. Neuroform stent-assisted embolization provides long-term control of A-comms with a low incidence of aneurysm growth after treatment. The need for retreatment is uncommon, and retreatment is safe if performed. Subsequent bleeding from treated aneurysms was not observed in this study.

Venous thromboembolism and subsequent diagnosis of subarachnoid hemorrhage: a 20-year cohort study.

Venous thromboembolism is a predictor of subsequent risk of ischemic stroke and intracerebral hemorrhage, but no data are available regarding its association with risk of subarachnoid hemorrhage. To examine this issue, we conducted a nationwide cohort study in Denmark. Between 1977 and 2007, we identified 97,558 patients with a hospital diagnosis of venous thromboembolism and obtained information on risk of subsequent subarachnoid hemorrhage during follow-up in the Danish Registry of Patients. The incidence of subarachnoid hemorrhage in the venous thromboembolism cohort was compared with that of 453,406 population control cohort members. For patients with pulmonary embolism (PE), there was clearly an increased risk of subarachnoid hemorrhage, both during the first year of follow-up [relative risk 2.69; 95% confidence interval (CI), 1.32-5.48] and during later follow-up of 2-20 years (relative risk 1.40; 95% CI, 1.05-1.87). For patients with deep venous thrombosis (DVT) the risk was likewise clearly increased during the first year of follow-up (relative risk 1.91; 95% CI, 1.13-3.22), but not during later follow-up (relative risk 1.04; 95% CI, 0.81-1.32). We found evidence that PE is associated with an increased long-term risk of subarachnoid hemorrhage. The two diseases might share etiologic pathways affecting the vessel wall or share unknown risk factors.