Pathophysiology of Contrast-Induced Neurotoxicity: A Narrative Review of Possible Mechanisms.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly observed event following the administration of iodinated contrast. It presents as a spectrum of neurological symptoms that closely mimic ischaemic stroke, however, CIN remains a poorly understood clinical phenomenon. An appreciation of the underlying pathophysiological mechanisms is essential to improve clinical understanding and enhance decision-making. METHODS: A broad literature search of Medline (1946 to December 2022) and Embase (1947 to December 2022) was conducted. Articles discussing the pathophysiology of CIN were reviewed. SUMMARY: The pathogenesis of CIN appears to be multifactorial. A key step is likely blood-brain barrier (BBB) breakdown due to factors including ischaemic stroke, uncontrolled hypertension, and possibly contrast agents themselves, among others. This is followed by passage of contrast agents across the BBB, leading to chemotoxic sequelae on neural tissue. KEY MESSAGES: This review provides a clinically oriented review on the pathophysiology of CIN to enhance knowledge and improve decision-making among clinicians.

An efficient and scalable synthesis of a persistent abscisic acid analog (+)-tetralone ABA.

The plant hormone (S)-abscisic acid (ABA) is a signalling molecule found in all plants that triggers plants' responses to environmental stressors such as heat, drought, and salinity. Metabolism-resistant ABA analogs that confer longer lasting effects require multi-step syntheses and high costs that prevent their application in crop protection. To solve this issue, we have developed a two-step, efficient and scalable synthesis of (+)-tetralone ABA from (S)-ABA methyl ester. A challenging three-carbon insertion and a bicyclic ring formation on (S)-ABA methyl ester was achieved through a highly regioselective Knoevenagel condensation, cyclization, and oxidation in one-pot. Further we have studied the biological activity and metabolism of (+)-tetralone ABA in planta and found the analog is hydroxylated similarly to ABA. The biologically active hydroxylated tetralone ABA has greater persistence than 8'-hydroxy ABA as cyclization to the equivalent of phaseic acid is prevented by the aromatic ring. (+)-tetralone ABA complemented the growth retardation of an Arabidopsis ABA-deficient mutant more effectively than (+)-ABA. Taken together, this new synthesis allows the production of the potent ABA agonist efficiently on an industrial scale.

3'-(Phenyl alkynyl) analogs of abscisic acid: synthesis and biological activity of potent ABA antagonists.

We report here the synthesis and biological testing of 3'-(phenyl alkynyl) abscisic ABA analogs, a new class of potent ABA antagonists. These ABA analogs incorporate a rigid framework of eight carbon atoms attached at the 3'-carbon atom of ABA that prevents folding of the ABA analog-bound receptor required for ABA signalling. The two-step synthesis is based upon the optimized conversion of natural (S)-ABA to 3'-iodo ABA which can be coupled to phenyl acetylenes using Sonogashira conditions, or to styryl compounds through Suzuki chemistry. The parent 3'-(phenyl alkynyl) ABA analog 7 was obtained in 29% yield, 74% yield based on recovered starting material. In a lentil seed germination assay, compound 7 was found to have more potent activity than other known 3'-substituted ABA antagonists to date. In a structure activity study parasubstituted phenyl alkynyl analogs had comparable activity to the analog 7 while the 3'-styryl ABA 18 was only slightly less active. Analog 7 overcame ABA inhibition of germination and seedling growth in a wide range of mono and dicot plant species, including canola, lentil, soybean, rice, wheat, barley, cannabis and canary seed. 3'-(Phenyl alkynyl) ABA analogs have numerous potential practical agricultural applications including promoting ripening of crops, dormancy breaking of seeds and woody perennials, as well as promoting seed germination, and growth under stress conditions as demonstrated in this report.

Intravenous milrinone for treatment of delayed cerebral ischaemia following subarachnoid haemorrhage: a pooled systematic review.

Small trials have demonstrated promising results utilising intravenous milrinone for the treatment of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). Here we summarise and contextualise the literature and discuss the future directions of intravenous milrinone for DCI. A systematic, pooled analysis of literature was performed in accordance with the PRISMA statement. Methodological rigour was analysed using the MINORS criteria. Extracted data included patient population; treatment protocol; and clinical, radiological, and functional outcome. The primary outcome was clinical resolution of DCI. Eight hundred eighteen patients from 10 single-centre, observational studies were identified. Half (n = 5) of the studies were prospective and all were at high risk of bias. Mean age was 52 years, and females (69%) outnumbered males. There was a similar proportion of low-grade (WFNS 1-2) (49.7%) and high-grade (WFNS 3-5) (50.3%) SAH. Intravenous milrinone was administered to 523/818 (63.9%) participants. Clinical resolution of DCI was achieved in 375/424 (88%), with similar rates demonstrated with intravenous (291/330, 88%) and combined intra-arterial-intravenous (84/94, 89%) therapy. Angiographic response was seen in 165/234 (71%) receiving intravenous milrinone. Hypotension (70/303, 23%) and hypokalaemia (31/287, 11%) were common drug effects. Four cases (0.5%) of drug intolerance occurred. Good functional outcome was achieved in 271/364 (74%) patients. Cerebral infarction attributable to DCI occurred in 47/250 (19%), with lower rates in asymptomatic spasm. Intravenous milrinone is a safe and feasible therapy for DCI. A signal for efficacy is demonstrated in small, low-quality trials. Future research should endeavour to establish the optimal protocol and dose, prior to a phase-3 study.

Sex differences in aneurysmal subarachnoid haemorrhage (aSAH): aneurysm characteristics, neurological complications, and outcome.

BACKGROUND: Women are over-represented in aSAH cohorts, but whether their outcomes differ to men remains unclear. We examined if sex differences in neurological complications and aneurysm characteristics contributed to aSAH outcomes. METHODS: In a retrospective cohort (2010-2016) of all aSAH cases across two hospital networks in Australia, information on severity, aneurysm characteristics and neurological complications (rebleed before/after treatment, postoperative stroke < 48 h, neurological infections, hydrocephalus, seizures, delayed cerebral ischemia [DCI], cerebral infarction) were extracted. We estimated sex differences in (1) complications and aneurysm characteristics using chi square/t-tests and (2) outcome at discharge (home, rehabilitation or death) using multinomial regression with and without propensity score matching on prestroke confounders. RESULTS: Among 577 cases (69% women, 84% treated) aneurysm size was greater in men than women and DCI more common in women than men. In unadjusted log multinomial regression, women had marginally greater discharge to rehabilitation (RRR 1.15 95% CI 0.90-1.48) and similar likelihood of in-hospital death (RRR 1.02 95% CI 0.76-1.36) versus discharge home. Prestroke confounders (age, hypertension, smoking status) explained greater risk of death in women (rehabilitation RRR 1.13 95% CI 0.87-1.48; death RRR 0.75 95% CI 0.51-1.10). Neurological complications (DCI and hydrocephalus) were covariates explaining some of the greater risk for poor outcomes in women (rehabilitation RRR 0.87 95% CI 0.69-1.11; death RRR 0.80 95% CI 0.52-1.23). Results were consistent in propensity score matched models. CONCLUSION: The marginally poorer outcome in women at discharge was partially attributable to prestroke confounders and complications. Improvements in managing complications could improve outcomes.

Incidence of contrast-induced neurotoxicity following endovascular treatment of unruptured intracranial aneurysms: a single-centre cohort study.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is a recognised complication of endovascular procedures and has been increasingly observed in recent years. Amongst other clinical gaps, the precise incidence of CIN is unclear, particularly following intracranial interventional procedures. METHODS: A retrospective study of consecutive patients undergoing elective endovascular treatment of unruptured intracranial aneurysms (UIAs) was performed. Patients with previously ruptured aneurysms were excluded. The primary aim of this study was to determine the incidence of CIN following endovascular UIA treatment. Our secondary aim was to isolate potential predictive factors for developing CIN. RESULTS: From 2017 to 2023, a total of 158 patients underwent endovascular UIA treatment, with a median age of 64 years (IQR: 54-72), and 70.3% of female sex. Over the study period, the crude incidence of CIN was 2.5% (95% CI: 0.7 - 6.4%). The most common clinical manifestation of CIN was confusion (75%) and seizures (50%). Statistical analysis was conducted, and prolonged procedural duration was found be significantly associated with developing CIN (OR 12.55; p = 0.030). CONCLUSION: Clinicians should be aware of the risk of CIN following endovascular neurointervention, particularly following technically challenging cases resulting in prolonged procedural time.

Clinical management of contrast-induced neurotoxicity: a systematic review.

BACKGROUND: Contrast-induced neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures utilising contrast. It remains poorly understood with heterogenous clinical management strategies. The aim of this review was to identify commonly employed treatments for CIN to enhance clinical decision making. METHODS: A systematic search of Embase (1947-2022) and Medline (1946-2022) was conducted. Articles describing (i) patients with a clinical diagnosis of CIN, (ii) with radiological exclusion of other pathologies, (iii) detailed report of treatments, and (iv) discharge outcomes, were included. Data relating to demographics, procedure, symptoms, treatment and outcomes were extracted. RESULTS: A total of 73 patients were included, with a median age of 64 years. The most common procedures were cerebral angiography (42.5%) and coronary angiography (42.5%), and the median volume of contrast administered was 150 ml. The most common symptoms were cortical blindness (38.4%) and reduced consciousness (28.8%), and 84.9% of patients experienced complete resolution at the time of discharge. Management included intravenous fluids to dilute contrast in the cerebrovasculature (54.8%), corticosteroids to reduce blood-brain barrier damage (47.9%), antiseizure (16.4%) and sedative (16.4%) medications. Mannitol (13.7%) was also utilised to reduce cerebral oedema. Intensive care admission was required for 19.2% of patients. No statistically significant differences were observed between treatment and discharge outcomes. CONCLUSIONS: The clinical management of CIN should be considered on a patient-by-patient basis, but may consist of aggressive fluid therapy alongside corticosteroids, as well as other supportive therapy as required. Further examination of CIN management is required to define best practice.

Neuroradiological features of contrast-induced neurotoxicity: A systematic review and pooled analysis.

BACKGROUND: Contrast-induced neurotoxicity (CIN), is an increasingly recognised complication of endovascular procedures, presenting as a spectrum of neurological symptoms that mimic ischaemic stroke. The diagnosis of CIN remains a clinical challenge, and stereotypical imaging findings are not established. This study was conducted to characterise the neuroimaging findings in patients with CIN, to raise diagnostic awareness and improve decision making. METHODS: We performed a systematic review of PubMed and Embase databases from inception (1946/1947) to June 2023 for reports of CIN following administration of iodinated contrast media. Studies with a final diagnosis of CIN, which provided details of neuroimaging were included. All included cases were pooled and descriptive analysis was conducted. RESULTS: A total of 84 patients were included, with a median age of 64 years. A large proportion of patients had normal imaging (CT 40.8 %, MRI 53.1 %). CT abnormalities included cortical/subarachnoid hyperattenuation (42.1 %), cerebral oedema/sulcal effacement (26.3 %), and loss of grey-white differentiation (7.9 %). Frequently reported MRI abnormalities included brain parenchymal MRI signal change (40.8 %) and cerebral oedema (12.2 %), most commonly observed on FLAIR sequences (26.5 %). Characterisation of imaging findings according to anatomical location and clinical symptoms has been conducted. CONCLUSIONS: Neuroimaging is an essential part of the diagnostic workup of CIN. Analysis of the anatomical location and laterality of imaging abnormalities may suggest relationship between radiological features and actual clinical symptoms, although this remains to be confirmed with dedicated study. Radiological abnormalities, particularly CT, appear to be transient and reversible in most patients.

Subdural Versus Subgaleal Drain Placement After Minicraniotomy for Chronic Subdural Hematoma.

BACKGROUND AND OBJECTIVES: Surgical evacuation with placement of a postoperative drain is the standard treatment for symptomatic chronic subdural hematoma (cSDH). Subdural and subgaleal drains are equally effective after burrhole craniostomy, but the optimal location of the drain after craniotomy is not clear. We sought to compare the clinical and radiological outcomes of subdural and subgaleal drain placement in patients undergoing minicraniotomy for cSDH. METHODS: A retrospective review of 137 consecutive patients undergoing minicraniotomy for cSDH at a single institution was performed. Cases were stratified by location of postoperative drain. The primary outcome was change in functional status (modified Rankin Score, mRS) at 3 months from preoperative baseline. RESULTS: Among the patient cohort, 24.6% received subgaleal drain placement. After a median follow-up of 105 days, 79.4% (27/34) in the subgaleal group and 57.3% (59/103) in the subdural group (P = .02) had been discharged home. Worse premorbid mRS (P = .002), subdural drain location (P = .004), and decreased consciousness at presentation (Glasgow Coma Scale<15) (P < .002) were independent predictors of a discharge destination other than home. At the 3-month follow-up, the subgaleal group exhibited a mean improvement of 0.77 ± 1.2 points, while the subdural group had a deterioration of 0.14 ± 0.8 points (P < .01). Subgaleal drain location (P < .0001), better preoperative Glasgow Coma Scale (P = .01), and worse premorbid mRS (P = .0003) were independent predictors of improved mRS at 3 months. Recurrence requiring repeat surgery were more common in the subdural (13.6% (14/103) than the subgaleal 2.9% (1/34) group, P = .12), although the absolute incidence rates remained low. CONCLUSION: In patients undergoing minicraniotomy for cSDH, subgaleal drains are associated with shorter hospitalization, greater chance of discharge home, and better functional outcomes than subdural drains.

Microalbuminuria in HIV disease.

BACKGROUND/AIMS: Microalbuminuria is a marker for early kidney disease and cardiovascular risk. The purposes of this study were to determine the prevalence of microalbuminuria in an HIV-infected clinic population, to test the predictive value of a single urine albumin/creatinine ratio (ACR) to identify persistent microalbuminuria and to examine covariates of microalbuminuria. METHODS: We conducted a prospective cohort study of HIV-infected subjects (n = 182) without proteinuria (urine protein/creatinine ratio ≥0.5 g/g), elevated serum creatinine, diabetes, or chronic inflammatory conditions. Subjects completed three research visits within 9 months. Microalbuminuria was defined as the geometric mean ACR of 25-355 mg/g for females and 17-250 mg/g for males. RESULTS: The prevalence of microalbuminuria was 14%. The negative predictive value of a single urine ACR determination was 98%, whereas the positive predictive value was only 74%. Microalbuminuria was similar among Black (15%) and non-Black (14%) subjects (p = 0.8). Subjects with microalbuminuria were more likely to have hypertension (p = 0.02) and metabolic syndrome (p = 0.03). While duration of HIV infection and the level of HIV viremia were similar between groups, those with microalbuminuria were more likely to have a CD4 count <200 cells/µl (p = 0.0003). In a multivariate logistic regression analysis, the only significant independent predictors of microalbuminuria were low CD4 count (p = 0.018) and current ritonavir exposure (p = 0.04). CONCLUSION: The prevalence of microalbuminuria in an HIV-infected clinic population was similar to earlier reports, and was associated with hypertension and impaired immune function. A single normal ACR determination effectively excludes microalbuminuria, whereas an elevated ACR requires confirmation.

Is it time to rethink microsurgical training for the treatment of intracranial aneurysms in Australia?

BACKGROUND: Case volume and complexity for microsurgical treatment of cerebral aneurysms have changed due to the growing use of endovascular therapy in clinical practice. The authors sought to quantify the clinical exposure of Australian neurosurgery trainees to cerebral aneurysm microsurgery. METHODS: This observational, retrospective cross-sectional study examined the Australian National Hospital Morbidity database for all admissions related to microsurgical and endovascular treatment of aneurysmal subarachnoid haemorrhage (aSAH) and unruptured intracranial aneurysms (UIAs) for the years 2008 to 2018. Procedural volumes were compared with neurosurgical trainee figures to investigate the rate of procedural exposure relative to the neurosurgical workforce. RESULTS: A total of 8,874 (41.6%) microsurgical procedures (3,662 for aSAH, 5,212 for UIAs), and 12,481 (58.4%) endovascular procedures (6,018 for aSAH, 6,463 for UIAs) were performed. Trainee exposure to microsurgery in aSAH declined from 9.1 to 7.3 cases per trainee per annum (mean 7.7), with case complexity confined mostly to simple anterior circulation aneurysms. There are significant state-by-state differences in the preferred treatment modality for aSAH. During the same study period, the number of microsurgical cases for UIAs increased (from 8.9 to 13.5 cases per trainee per annum, mean 11.0). Significantly more endovascular procedures are performed than microsurgery (10.7 to 17.0, mean 12.7 cases, for aSAH; 8.0 to 21.5, mean 13.7 cases, for UIAs). CONCLUSIONS: Trainee exposure to open aneurysm surgery for aSAH have significantly declined in both case volume and complexity. There is an overall increase in the number of surgeries for elective aneurysms, but this varies widely from state-to-state.

The utility of arterial spin labelled perfusion-weighted magnetic resonance imaging in measuring the vascularity of high grade gliomas - A prospective study.

Background: Dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) currently remains the gold standard technique for measuring cerebral perfusion in glioma diagnosis and surveillance. Arterial spin labelling (ASL) PWI is a non-invasive alternative that does not require gadolinium contrast administration, although it is yet to be applied in widespread clinical practice. This study aims to assess the utility of measuring signal intensity in ASL PWI in predicting glioma vascularity by measuring maximal tumour signal intensity in patients based on pre-operative imaging and comparing this to maximal vessel density on histopathology. Methods: Pseudocontinuous ASL (pCASL) and DSC images were acquired pre-operatively in 21 patients with high grade gliomas. The maximal signal intensity within the gliomas over a region of interest of 100 mm2 was measured and also normalised to the contralateral cerebral cortex (nTBF-C), and cerebellum (nTBF-Cb). Maximal vessel density per 1 mm2 was determined on histopathology using CD31 and CD34 immunostaining on all participants. Results: Using ASL, statistically significant correlation was observed between maximal signal intensity (p < 0.05) and nTBF-C (p < 0.05) to maximal vessel density based on histopathology. Although a positive trend was also observed nTBF-Cb, this did not reach statistical significance. Using DSC, no statistically significant correlation was found between signal intensity, nTBF-C and nTBF-Cb. There was no correlation between maximal signal intensity between ASL and DSC. Average vessel density did not correlate with age, sex, previous treatment, or IDH status. Conclusions: ASL PWI imaging is a reliable marker of evaluating the vascularity of high grade gliomas and may be used as an adjunct to DSC PWI.

Microsurgical clipping of ruptured supraclinoid internal carotid artery aneurysm with extradural clinoidectomy.

BACKGROUND: Supraclinoid Internal Carotid Artery (ICA) aneurysms require additional access to standard pterional craniotomy via extradural clinoidectomy. Existing texts and surgical videos lack clarity, explanation and a clear step by step process. CASE DESCRIPTION: We present a case of a ruptured supraclinoid ICA aneurysm and extradural clinoidectomy along with 3D reconstructed imaging of the case anatomy to guide its resection. Real-time unedited on table rerupture provides an example of management. CONCLUSION: Extradural Anterior Clinoidectomy is a key maneuver in cerebrovascular surgical armamentarium for clipping of supraclinoid aneurysms. Stereotypical Pathological or Surgical Anatomy, its application, and availability with 3D imaging should be facilitates the framing and learning of normal physiological anatomy.

Microsurgical disconnection of a T12/L1 ventral intradural perimedullary arteriovenous fistula (type IV) via instrumented trans-pedicular approach.

CASE DESCRIPTION: We present a case of microsurgical disconnection of a PMAVF supplied by the artery of Adamkiewicz with fistulation at the ventral spinal cord.

Safety and effectiveness of spinal dural defect repair in the management of superficial siderosis: A systematic review and patient-level analysis.

OBJECTIVE: Superficial siderosis (SS) is a disabling neurodegenerative condition that may be caused by spinal dural defects. Surgical repair is increasingly performed, however clinical outcomes remain unclear. METHODS: A systematic search of PubMed, MEDLINE, and EMBASE was conducted (inception to February 2020). Studies reporting cases of (i) superficial siderosis, (ii) spinal dural defect, (iii) and surgical closure of the defect were included. Demographic characteristics, clinical presentation, operative technique and clinical outcome were extracted for patient-level analysis. RESULTS: A total of 26 publications were included, which reported 38 patients with a median age of 58 years, and a male predominance (78.9 %). Ataxia (85.7 %) and hearing loss (80.0 %) were the most common presenting symptoms. The causative dural defect was most commonly ventral in location (91.7 %) and most commonly identified by CT myelography (48.6 %). Operative technique was highly variable and included primary suture, fibrin glue, dural substitute, or tissue (fat or muscle) graft. Clinical improvement was reported in 21 %, with stabilisation of symptoms in the majority (66 %) and clinical deterioration in 13.2 %. Surgical complications were observed in 7.9 %. CONCLUSION: In patients with superficial siderosis and spinal dural defect, operative closure leads to improvement or stabilisation of symptoms in the vast majority (87%) of patients.

Current knowledge and perspectives of contrast-induced neurotoxicity: A survey of Australian clinicians.

BACKGROUND: Contrast-induced Neurotoxicity (CIN) is an increasingly recognised complication following endovascular procedures. It remains a relatively unexplored clinical entity, and we sought to characterise clinician perspectives towards CIN, as well as identify gaps in knowledge and provide directions for future research. METHODS: An online survey was distributed to members of the Australian and New Zealand Society of Neuroradiology, as well as several Australian tertiary hospitals. Questions related to clinical exposure to CIN, diagnosis, management and pathophysiology were explored. Descriptive analysis was conducted on survey responses, and statistical analysis was performed using Chi-square and Fisher's exact test as appropriate. RESULTS: A total of 95 survey responses were recorded (26.8% response rate). Only 28.4% of respondents were comfortable in diagnosing CIN, and even fewer (24.2%) were comfortable in independently managing CIN patients. Based on clinician opinion, symptoms including impaired consciousness and cortical blindness were thought to be most associated with CIN, whilst the radiological findings of parenchymal oedema and cortical enhancement were considered to be most indicative of CIN. Most clinicians agreed that further investigation is required related to pathophysiology (86.3%), diagnosis (83.2%), and treatment (82.1%). CONCLUSION: CIN is a poorly understood complication following endovascular procedures. Significant gaps in clinical understanding are evident, and further investigation is vital to improve diagnosis and management.

Recurrent haemorrhagic pontine cavernoma resection via a retrosigmoid microsurgical approach.

BACKGROUND: Brainstem cavernomas occasionally require surgical treatment. Appropriate patient selection and thorough understanding of the anatomy and technical nuances involved in microsurgical resection is a pre-requisite in undertaking these challenging cases. CASE DESCRIPTION: We present a video case of a patient with a recurrent haemorrhagic pontine cavernoma. A step-by-step commentary of surgical footage is provided along with clinical, anatomical and technical learning points pertinent to the safe surgical management of these lesions.

Influence of socioeconomic status on the incidence of aneurysmal subarachnoid haemorrhage and clinical recovery.

BACKGROUND: The relevance of socioeconomic status (SES) on the incidence of aneurysmal subarachnoid haemorrhage (aSAH) and discharge functional outcomes following treatment is not clear. METHODS: A retrospective cross-sectional study was performed on data retrieved from the Nationwide Hospital Morbidity Database for all aSAH cases in Australia between 2012 and 2018. Information on patient characteristics, procedures performed, discharge disposition and SES were extracted. SES data was derived from classifications by the Australian Bureau of Statistics. Putative risk factors were evaluated with univariate and multivariate logistic regression analysis to identify independent predictor of unfavourable discharge outcomes (defined as death or dependency). RESULTS: A total of 3,591 low SES patients (49.8%) were identified in our study cohort. Average crude incidence of aSAH was persistently higher among the SES disadvantaged (6.6 cases per 100,000 person-years, 95% CI 6.3 - 6.8), compared to the SES advantaged group (4.1 cases per 100,000 person-years, 95% CI 4.0-4.2) (p < 0.0001). Patients in the Low SES group were more likely to be active smokers, have type 2 diabetes mellitus, or live in non-metropolitan residence, and have overall worse discharge functional outcomes (27.7% versus 24.5%, p = 0.0015). Adjusting for well-established risk factors such as older age, and intracranial bleed (ICH and/or IVH), disadvantaged SES remained a significant predictor of poor discharge outcome following aSAH (p = 0.0003). CONCLUSION: aSAH occurs more frequently among low SES communities, and once ruptured, there is a greater risk of poor recovery..

Cumulative Time of Cigarette Smoking Is Associated with a Greater Risk of Aneurysmal Subarachnoid Hemorrhage and Younger Age at Presentation: A Nationwide Observation Study.

BACKGROUND: Smoking is known to be associated with an increased risk of intracranial aneurysm rupture; however, the risk in smokers stratified by age, sex, and aneurysm location is not clear. METHODS: A retrospective study of all aneurysmal subarachnoid hemorrhage (aSAH) cases in Australia between 2008 and 2018 was conducted. The relative risk of aSAH in smokers compared with nonsmokers was calculated on the basis of nationwide smoking statistics and was stratified according to sex, age group, and aneurysm location. RESULTS: Out of 12,915 aSAH patients, 3249 (25.2%) were active smokers. Across both men and women, smoking increased the risk of aSAH by 2.4× in 30- to 39-year-olds (95% CI 2.1-2.7), 2.4× in 40- to 49-year-olds (95% CI 2.2-2.7), 2.3× in 50- to 59-year-olds (95% CI 2.1-2.4), and 1.8× in 60- to 69-year-olds (95% CI 1.7-2.0) with less of an effect in smokers younger than 30 years (RR: 1.2, 95% CI 1.0-1.5) and older than 70 years (RR: 1.0, 95% CI 0.9-1.2). Compared with a nonsmoker younger than 30 years old, the relative risk of aSAH increased by an average of 7.2 for every decade spent smoking in women and an average of 4.0 for every decade spent smoking in men. Additionally, smokers were 5.2× more likely to present before 50 years of age. CONCLUSIONS: Smoking increased the risk of aSAH by 2-fold between the ages of 30 and 60. Smokers experienced aSAH at younger ages.

Aneurysmal subarachnoid haemorrhage in Indigenous and non-Indigenous Australians: A retrospective study assessing patient characteristics and outcome.

INTRODUCTION: Smoking and hypertension are prevalent among Indigenous Australians (Aboriginal and Torres Strait Islanders). We investigated if these risk factors suggest a greater rate of aneurysmal subarachnoid haemorrhage in Indigenous Australians (IA) compared to non-IA. MATERIALS AND METHODS: A retrospective cross-sectional study was performed on data retrieved from the Nationwide Hospital Morbidity Database for all aSAH cases in Australia between 2012 and 2018. Patient characteristics, radiological findings, aneurysm characteristics, treatment characteristics and discharge outcomes were assessed. Crude and age-adjusted incidences, trends of aSAH and case fatality rate over time were calculated. RESULTS: A total of 12,286 patients were included (285 IA, 12,001 non-IA). Indigenous aSAH patients were significantly younger than non-IA, with 89.8 percent of IA younger than 65 years old (p < 0.001). Crude annual incidences were similar between the 2 cohorts, however age-adjusted incidence shows a RR = 1.4 at 45-59 years in IA patients, compared with their non-IA counterparts. 30-day mortality was similar between the two groups, at 25.3 and 26.9% for IA and non-IA groups, respectively. CONCLUSION: This 10 year nationwide retrospective study highlights a disparity between the crude and age-adjusted incidence of aSAH in IA compared to non-IA.