Fatal Subarachnoid Hemorrhage Research Articles

Decreased PDLIM1 expression in endothelial cells contributes to the development of intracranial aneurysm.

Intracranial aneurysm (IA) is a common vascular enlargement that occurs in the wall of cerebral vessels and frequently leads to fatal subarachnoid hemorrhage. PDZ and LIM domain protein 1 (PDLIM1) is a cytoskeletal protein that functions as a platform for multiple protein complex formation. However, whether PDLIM is involved in the pathogenesis of IA remains poorly understood. Loss-of-function and gain-of-function strategies were employed to determine the in vitro roles of PDLIM1 in vascular endothelial cells (VECs). A rat model of IA was generated to study the role of PDLIM1 in vivo. Gene expression profiling, Western blotting, and dual luciferase reporter assays were performed to uncover the underlying cellular mechanism. Clinical IA samples were used to determine the expression of PDLIM1 and its downstream signaling molecules. PDLIM1 expression was reduced in the endothelial cells of IA and was regulated by Yes-associated protein 1 (YAP1). Genetic silencing of PDLIM1 inhibited the viability, migratory ability, and tube formation ability of VECs. Opposite results were obtained by ectopic expression of PDLIM1. Additionally, PDLIM1 overexpression mitigated IA in vivo. Mechanistic investigations revealed that PDLIM1 promoted the transcriptional activity of β-catenin and induced the expression of v-myc myelocytomatosis viral oncogene homolog (MYC) and cyclin D1 (CCND1). In clinical settings, reduced expression of PDLIM1 and β-catenin downstream target genes was observed in human IA samples. Our study indicates that YAP1-dependent expression of PDLIM1 can inhibit IA development by modulating the activity of the Wnt/β-catenin signaling pathway and that PDLIM1 deficiency in VECs may represent a potential marker of aggressive disease.

Fatal Subarachnoid Hemorrhage in a Deep Brain Stimulation Patient: Displacement of Stimulation Leads for Deep Brain Stimulation Indicate Subarachnoid Hemorrhage on X-ray.

We depict the rare case of a patient with aneurysmatic subarachnoid hemorrhage previously treated with deep brain stimulation for Parkinson's disease. Initial CT scans showed a Fisher grade 4 subarachnoid hemorrhage with lead displacement due to midline-shift. CT angiogram revealed a supra-ophthalmic aneurysm of the internal carotid artery. The patient subsequently underwent clipping of the aneurysm and decompressive hemicraniecomy.

Retreatment with a pipeline embolization device for recanalized aneurysms following stent-assisted coiling embolization.

Flow diverters have emerged as viable alternatives for the retreatment of recanalized aneurysms following stent-assisted coiling embolization. In this study, we aim to present our experience of retreatment for such aneurysms using the pipeline embolization device (PED). This case series presents a retrospective single-center analysis of patients with recanalized aneurysms who underwent retreatment using the PED between July 2019 and April 2023, subsequent to stent-assisted coiling embolization. The study includes five female patients, whose relevant clinical data were recorded. All patients had aneurysms located in the internal carotid artery, comprising two blood blister-like aneurysms and two giant aneurysms. Prior to the retreatment, two LVIS stents, two enterprise stents, and one solitaire stent were implanted. Among the five patients, one experienced a fatal post-operative subarachnoid hemorrhage, while two patients achieved complete embolization, and another patient achieved near-complete embolization during the last follow-up. Furthermore, one patient faced challenges during the placement of the PED and was unable to achieve successful deployment. We propose four overlapping relationships between a newly implanted PED and a previously deployed stent: (1) PED covering only the proximal end of the previous stent, (2) PED covering only the distal end of the previous stent, (3) PED covering both the proximal and distal ends of the previous stent, and (4) PED deployed within the previous stent. Antiplatelet therapy at our center involved daily dual therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day) for at least 5 days before PED placement. Intra-arterial bolus administration of tirofiban (5 mcg/kg) was administered during or immediately after PED deployment, followed by a maintenance dose of 0.08 mcg/kg/min IV infusion for at least 24-48 h if necessary. Postprocedural dual antiplatelet therapy included clopidogrel (75 mg/day) for 6 months and aspirin (100 mg/day) for 12 months. The findings of this study support the efficacy of the PED for the retreatment of recanalized aneurysms following stent-assisted coiling embolization.

Survival of community-acquired Bacillus cereus sepsis with venous sinus thrombosis in an immunocompetent adult man – a case report and literature review

BackgroundBacillus cereus infections in immunocompetent patients are uncommon and mainly observed in fragile patients. It can cause lethal infections with multiple organ dysfunction syndrome (MODS). However, a patient presenting as venous sinus thrombosis and survival without sequela has not been reported.Case presentationA 20-year-old previously healthy male developed gastroenteritis after a meal, followed by fever, convulsions, and severe disturbance of consciousness. The patient had significant leukocytosis with a mildly elevated D-dimer, creatinine level, and respiratory failure. The CT(computed tomography) revealed fatal brain edema and subarachnoid hemorrhage. Previous blood culture in a local hospital revealed B. cereus, which was confirmed by mNGS(metagenomic next-generation sequencing) using blood and urine in our hospital. Accordingly, B. cereus sepsis with MODS were considered. Later, cerebral venous sinus thrombosis was proved. After anti-infection (linezolid 0.6 g, Q12h; and meropenem 1.0 g, Q8h), anti-coagulant (enoxaparin 6000U, Q12h), and other symptomatic treatments, the patient recovered completely without sequela at the 6-month follow-up.ConclusionsThis case suggests that in immunocompetent adults, there is still a risk of infection with B. cereus, causing severe MODS. Special attention should be paid to venous sinus thrombosis and subarachnoid hemorrhage in such cases, while, anti-coagulant is essential therapy.

Cerebral amyloid angiopathy: clinical presentations and management challenges in the Australian context.

Cerebral amyloid angiopathy (CAA) is a disease with several clinical manifestations. It is characterised by amyloid-beta deposition in cerebral blood vessels, making them prone to bleeding. The incidence of CAA increases with age and may be associated or co-exist with intraparenchymal neurodegenerative proteinopathies, which makes it an increasingly relevant condition for adult physicians in all areas of medical practice. The vast majority of cases of CAA are sporadic with a small minority of familial cases. CAA is asymptomatic in many older adults but increases the risk of fatal intracerebral or subarachnoid haemorrhage. We review the existing literature on CAA and summarise the key findings. We specifically explore clinical challenges relevant to CAA, particularly in diagnosis, management of intracranial haemorrhage and management of concurrent medical conditions.

Large internal carotid - ophthalmic artery aneurysm with anterior optic pathway compression

Internal carotid-ophthalmic artery aneurysms (IC-OA) are rare lesions that become symptomatic only when they are quite advanced or when complicated by subarachnoid hemorrhage (SAH). We report a case of IC-OA aneurysm in a middle-aged lady who presented with relative afferent pupillary defect, optic disc pallor, significant color vision impairment, and rather preserved visual acuity in the right eye. Magnetic resonance imaging revealed a fuso-saccular aneurysm of the ophthalmic segment causing a pressure effect on the optic nerve. This case emphasizes the importance of careful ocular examination supplemented by neuro-imaging in cases of unexplained visual loss. Early detection can prevent a potentially fatal subarachnoid hemorrhage.

The prognosis and treatment effectiveness of de novo aneurysm formation after radiation therapy for brain tumor.

Radiation therapy is a well-established, minimally invasive method of treating brain tumors. In recent years, the number of post-radiotherapy patients has increased, and delayed side effects are evident. De novo aneurysm formation after radiation often manifests as fatal subarachnoid hemorrhage (SAH), resulting in severe clinical outcomes. Nevertheless, the prognosis and therapeutic efficacy of radiation-induced aneurysms (RIAs) remain unclear. Using the PubMed database from 1980 to 2021, we screened 45 articles (53 individual cases) on RIAs; approximately 70% of RIAs were diagnosed after rupture. Of 38 ruptured RIAs, 12 (31.6%) had modified Rankin scale (mRS) 5-6. On the other hand, all unruptured RIAs (15 cases) recovered without neurological deficits (p = 0.012). Ten of the 39 ruptured RIAs were treated surgically, and 22 were treated endovascularly. There was no significant difference in mRS between treatment modalities (p = 0.393), but conservative therapy was significantly related to unfavorable outcomes (p = 0.025). To improve clinical outcomes, RIAs need to be diagnosed before rupture. Surgeons should be aware of de novo aneurysm formation in patients long after radiation therapy.

Epithelial\u2013mesenchymal transition related genes in unruptured aneurysms identified through weighted gene coexpression network analysis

Intracranial aneurysm (IA) can cause fatal subarachnoid hemorrhage (SAH) after rupture, and identifying patients with unruptured IAs is essential for reducing SAH fatalities. The epithelial–mesenchymal transition (EMT) may be vital to IA progression. Here, identified key EMT-related genes in aneurysms and their pathogenic mechanisms via bioinformatic analysis. The GSE13353, GSE75436, and GSE54083 datasets from Gene Expression Omnibus were analyzed with limma to identify differentially expressed genes (DEGs) among unruptured aneurysms, ruptured aneurysms, and healthy samples. The results revealed that three EMT-related DEGs (ADIPOQ, WNT11, and CCL21) were shared among all groups. Coexpression modules and hub genes were identified via weighted gene co-expression network analysis, revealing two significant modules (red and green) and 14 EMT-related genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that cytokine interactions were closely related. Gene set enrichment analysis revealed that unruptured aneurysms were enriched for the terms “inflammatory response” and “vascular endothelial growth”. Protein–protein interaction analysis identified seven key genes, which were evaluated with the GSE54083 dataset to determine their sensitivity and specificity. In the external validation set, we verified the differential expression of seven genes in unruptured aneurysms and normal samples. Together, these findings indicate that FN1, and SPARC may help distinguish normal patients from patients with asymptomatic IAs.

Церебральний венозний тромбоз (клінічний випадок)

Тромбоз мозкових вен і венозний тромбоз мозкових синусів зустрічається рідко (до 1 % від усіх випадків інфарктів мозку). За даними ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis, 2004), захворюваність щорічно становить 3–4 випадки на 1 млн у дорослих. Летальність при даному захворюванні становить від 5 до 30 %. Міжнародне дослідження тромбозу мозкових вен та венозних синусів (ISCVT) визначало частоту оклюзій за локалізацією так: поперечний синус — 86 %, верхній сагітальний синус — 62 %, прямий синус — 18 %, кортикальні вени — 17 %, внутрішні яремні вени — 12 %, вена Галена і внутрішні мозкові вени — 11 %. Основними факторами ризику розвитку тромбозу мозкових вен і венозного тромбозу мозкових синусів у популяції є інфекційні запальні процеси (отити, мастоїдити, синусити, септичні стани) і неінфекційні причини: черепно-мозкова травма, пухлини, хірургічні втручання в ділянці голови та шиї, а також імплантація кардіостимулятора чи постановка центрального венозного катетера. Захворювання, що сприяють даній патології: порушення гемодинаміки (застійна серцева недостатність, зневоднення організму), захворювання крові (поліцитемія, серпоподібноклітинна анемія, тромбоцитопенія) і коагулопатії (синдром дисемінованого внутрішньосудинного згортання крові, дефіцит антитромбіну, протеїну С і S), а також тромбофілітичні стани, пов’язані з вагітністю, родами та прийомом пероральних контрацептивів, антифосфоліпідний синдром, системні васкуліти. При цьому в 15 % випадків причина розвитку синус-тромбозу залишається невстановленою. Венозний тромбоз мозкових синусів характеризується дуже різноманітним клінічним перебігом, складною діагностикою, різноманітною етіологією і прогнозом. Одним з ускладнень тромбозу синусів є інсульт, що спостерігається приблизно в 30 % хворих та часто призводить до смерті хворого. У статті подано опис клінічного випадку церебрального венозного тромбозу, що ускладнився несумісним із життям двопівкульним субарахноїдально-паренхіматозним крововиливом.

Long Non-coding RNA MIAT Knockdown Prevents the Formation of Intracranial Aneurysm by Downregulating ENC1 via MYC.

Intracranial aneurysm (IA) is vascular enlargement occurred on the wall of cerebral vessels and can result in fatal subarachnoid hemorrhage when ruptured. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in IA treatment. This study identified functional significance of lncRNA myocardial infarction associated transcript (MIAT) in IA. Myocardial infarction associated transcript and ectodermal-neural cortex 1 (ENC1) expression was detected by reverse transcription quantitative polymerase chain reaction. Cell counting kit 8 assay flow cytometry were conducted to detect cell viability and apoptosis of endothelial cells in IA. The interaction among MIAT, ENC1, and myelocytomatosis oncogene (MYC) was analyzed by RNA pull down, RNA immunoprecipitation assay, chromatin immunoprecipitation assay, and dual luciferase reporter assay. Intracranial aneurysm was induced by ligating the left carotid artery and the bilateral posterior branch of the renal artery in rats for studying the role of MIAT and ENC1 in vivo. Myocardial infarction associated transcript and ENC1 were upregulated in IA. Endothelial cells in IA presented a decreased cell viability and an increased apoptotic rate. Myocardial infarction associated transcript could regulate the expression of ENC1, and MYC could bind to the promoter region of ENC1. High expression of MIAT increased endothelial cell apoptosis and vascular endothelial injury, while MIAT knockdown was identified to reduce the risk of IA both in vitro and in vivo through regulating ENC1. To sum up, MIAT silencing is preventive for IA occurrence by decreasing the MYC-mediated ENC1 expression, which represents a novel therapeutic target for IA.

Circular RNA expression profile in human primary multiple intracranial aneurysm.

Primary multiple intracranial aneurysm (MIA) is a vascular disease that frequently leads to fatal vascular rupture and subarachnoid hemorrhage. However, the epigenetic regulation associated with MIA has remained largely elusive. Circular RNAs (circRNAs) serve important roles in cardiovascular diseases; however, their association with MIA has remained to be investigated. The present study initially aimed to explore novel mechanisms of MIA through examining circRNA expression profiles. Comprehensive circRNA expression profiles were detected by RNA sequencing (RNA-Seq) in human peripheral blood mononuclear cells. The RNA-Seq results were validated by reverse transcription-quantitative PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested the functions of these circRNAs. A competing endogenous RNA network was constructed to reveal the circRNA-microRNA-mRNA relationship. Among the 3,328 differentially expressed circRNAs between the MIA and matched control groups, 60 exhibited significant expression changes (|log2 fold change|≥2; P<0.05). Among these 60 circRNAs, 20 were upregulated, while the other 40 were downregulated. A number of downregulated circRNAs were involved in inflammation. The most significant KEGG pathway was ‘leukocyte transendothelial migration’. The circRNAs Homo sapiens (hsa)_circ_0135895, hsa_circ_0000682 and hsa_circ_0000690, which were also associated with the above-mentioned pathway, were indicated to be able to regulate protein tyrosine kinase 2, protein kinase Cβ and integrin subunit αL, respectively. To the best of our knowledge, the present study was the first to perform a circRNA sequencing analysis of MIA. The results specifically predicted the regulatory role of circRNAs in the pathogenesis of MIA. ‘Leukocyte transendothelial migration’ may be critical for the pathogenesis of MIA.

Traumatic rupture of the circle of Willis with closed head injury: Its pathology and possible pathogenesis

Massive and fatal subarachnoid hemorrhage (SAH) with an injury on the circle of Willis may be caused by blunt force to the head; however, it is extremely rare, and the precise mechanism of arterial rupture remains unclear. We investigated the clinicopathologic appearance of four rare autopsy cases of massive SAH associated with the rupture of the circle of Willis. All four cases were men aged 17–75 years who presented with a loss of consciousness within a short interval after the injury. Autopsy revealed that the rupture site was located in the vertebral artery in two cases and in the anterior cerebral artery (ACA) in two cases. During our literature review, we found no previous report on traumatic ACA rupture. Based on the correlation of the autopsy findings and the circumstance of injury, we determined that the accidental excessive stretching of the selected artery by neck anteflexion or rotation after a blunt trauma to the posterior head might have caused this rare lethal injury. These cases demonstrated the diversity of the traumatic rupture site of the circle of Willis after a blunt head and/or neck injury. The topographical features of the circle of Willis, particularly in correlation with the surrounding tissue, might account for the occurrence and site of these rare injuries.

Smoking Causes Fatal Subarachnoid Hemorrhage

One of the largest twin studies to date suggested that subarachnoid hemorrhage (SAH) is mainly of nongenetic origin, but the causal effect of environmental factors on SAH is yet unknown. We hypothesized that if only one of the twins experience fatal SAH, they do not share the most important environmental risk factor for SAH, namely smoking. If true, such finding would suggest that smoking causes SAH. Through the nationwide cause-of-death register, we followed 16 282 same-sex twin pairs of Finnish origin from the older Finnish Twin Cohort between 1976 and 2018 and identified all participants who died from SAH. For the baseline, we collected risk factor information about smoking, hypertension, physical activity, body mass index, alcohol consumption, and education. We classified the pairs as monozygotic, dizygotic, or of unknown zygosity. We examined the within-pair risk factor differences in the pairs discordant for SAH, that is, where one twin died from SAH and the other did not. We computed both individual (whole cohort) and pairwise (discordant pair) hazard ratios and 95% CIs. During the 869 469 person-years of follow-up, we identified 116 discordant and 2 concordant (both died from SAH) twin pairs for fatal SAH. Overall, 25 of the discordant twin pairs were monozygotic. For the whole cohort, smoking (occasional/current) was associated with increased risk of SAH death (hazard ratio, 3.33 [CI, 2.24-4.95]) as compared with nonsmokers (never/former). In the pairwise analyses for discordant twin pairs, we found that the twin who smoked had an increased risk of fatal SAH (hazard ratio, 6.33 [CI, 1.87-21.4]) as compared with the nonsmoking twin. The association remained consistent regardless of the twin pairs' zygosity or sex. Our results provide strong evidence for a causal, rather than associative, role of smoking in SAH.

Fatal Subarachnoid Hemorrhage due to Intravascular Adrenaline Absorption

AbstractVasoconstrictors are commonly administered with local anesthetics (LAs) to decrease intraoperative bleeding. However, inadvertent systemic absorption of adrenaline is not uncommon and is associated with significant hemodynamic consequences and arrhythmias, which are usually inconsequential. We report a case of suspected intravascular adrenaline absorption in a 1-year-old girl with craniosynostosis, which led to subarachnoid hemorrhage, herniation, and death.

Rapid formation and rupture of an infectious basilar artery aneurysm from meningitis following suprasellar region meningioma removal: a case report

BackgroundInfectious basilar artery (BA) aneurysm has been occasionally reported to be generated from meningitis following transcranial operation. However, infectious BA aneurysm formed by intracranial infection after endoscopic endonasal operation has never been reported.Case presentationA 53-year-old man who was diagnosed with suprasellar region meningioma received tumor removal via endoscopic endonasal approach. After operation he developed cerebrospinal fluid (CSF) leak and intracranial infection. The patient ultimately recovered from infection after anti-infective therapy, but a large fusiform BA aneurysm was still formed and ruptured in a short time. Interventional and surgical measures were impossible due to the complicated shape and location of aneurysm and state of his endangerment, therefore, conservative anti-infective therapy was adopted as the only feasible method. Unfortunately, the aneurysm did not disappear and the patient finally died from repeating subarachnoid hemorrhage (SAH).ConclusionThough extremely rare, it was emphasized that infectious aneurysm can be formed at any stage after transnasal surgery, even when the meningitis is cured. Because of the treatment difficulty and poor prognosis, it was recommended that thorough examination should be timely performed for suspicious patient to make correct diagnosis and avoid fatal SAH.

Fatal Subarachnoid Hemorrhage From Ruptured Intracerebral Aneurysm After Carotid Endarterectomy

Concomitant carotid stenosis with cerebral aneurysm is a rare entity with an incidence reported to be about 1.9-3.2%. The effect of carotid revascularization on pre-existing cerebral aneurysm, along with risk factors for aneurysmal rupture, is not fully understood. We report a 61-year-old man who underwent carotid endarterectomy (CEA) for symptomatic carotid stenosis, and 6 days post-operatively the patient suffered a fatal subarachnoid hemorrhage from the rupture of a known basilar artery aneurysm. This rare but potentially fatal complication of a ruptured cerebral aneurysm after CEA warrants a discussion on the management of concomitant pathology. J Med Cases. 2020;11(1):12-15 doi: https://doi.org/10.14740/jmc3403

Risk factors for subarachnoid haemorrhage: a nationwide cohort of 950000 adults.

Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. We obtained individual participant data of 949683 persons (330334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. During 13704959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100000 person-years] in men and 13.8 [(11.4-16.2)/100000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

Takotsubo Cardiomyopathy Triggered by a Fatal Subarachnoid Hemorrhage

Takotsubo Cardiomyopathy Triggered by a Fatal Subarachnoid Hemorrhage

Systemic lupus erythematosus flare up as acute spinal subarachnoid hemorrhage with bilateral lower limb paralysis.

Subarachnoid hemorrhage (SAH) is an uncommon complication of systemic lupus erythematosus (SLE). Solitary association of fatal spinal SAH as a complication of SLE, has not been encountered much in literature although coexisting acute cerebral and spinal SAH have been associated with SLE. We present a 39-year old female with initial diagnosis of SLE eight years ago who suddenly developed a productive cough, acute abdomen and paralysis of the lower limbs. Magnetic resonance imaging of the spine revealed thoracic spinal SAH with varying degrees of thoracic spinal cord compression. The hemorrhage was total evacuated via surgery. She regained normal function of her lower limbers after the operation with no further neurological complications. One of the rare but fatal complications of SLE is solitary spinal SAH without cranial involvement. The best and most appropriate management of this kind of presentation is surgical decompression of the hematoma with total hemostasis. The cause of hemorrhage should be identified intra-operatively and treated appropriately.

Fatal Intracranial Aneurysms and Dissections Causing Subarachnoid Hemorrhage: An Epidemiological and Pathological Analysis of 607 Legal Autopsy Cases

There are no detailed reports, in terms of epidemiology and pathology, on intracranial aneurysms and on dissections that were found in unexpected fatal subarachnoid hemorrhage (SAH) cases. In this report we analyzed, based on large-sized medicolegal autopsy cases, the detailed epidemiology and pathological aspects of both lesions. We analyzed 607 autopsy cases of unexpected fatal SAHs including 496 aneurysms and 111 dissections. The following results were obtained: (1) Patients who died of dissections were younger than those who died of aneurysms; (2) symptom prevalence rates of aneurysms were 31.9%, appearing to be lower than those in previous studies; (3) a significantly higher prevalence of clinical symptoms was found in patients with dissections (60.5%) than patients with aneurysms; (4) hypertensive cardiomegaly was indicated in more than 80%, while no obvious difference in incidence in hypertensive cardiomegaly was noted between aneurysms and dissections; (5) aneurysms were found to occur much more frequently in the anterior communicating artery (31.9%) and vertebral arteries (7.5%), while dissections were found much more commonly in vertebral arteries (93.7%); and (6) the size of aneurysms was much smaller in general than that previously regarded as a risk factor of rupturing. These data might help in the prompt intervention in SAH and also in the prevention of lethal SAH in clinical settings.