ABSTRACT
OBJECTIVES: Delayed cerebral ischemia (DCI) is a major driver of morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Quantitative pupillometry has been shown to be of prognostic value after acute neurological injury. However, the evidence for the use of pupillometric features for the detection of DCI has been conflicting. The aim of this study was to investigate the prognostic value of frequent pupillometric monitoring for DCI detection. DESIGN: Observational cohort study from a prospective aSAH registry. SETTING: Tertiary referral center. PATIENTS: Adult patients with confirmed aSAH admitted to the ICU between March 2019 and December 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fourteen patients were included, of which 31 (27.2%) suffered from DCI. All patients underwent frequent pupillometry (every 3 hr). We determined the absolute value of the neurological pupil index (NPi) and constriction velocity (CV), and their value normalized to the maximal recorded value between the admission and the pupillometry measure to account for personalized baselines. The association between pupillometry values and the occurrence of DCI within 6-24 hours was investigated. Normalized CV had the best discriminative performance to identify DCI within 8 hours, with an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.69-0.91). NPi, as well as non-normalized metrics, were not significantly associated with DCI. CONCLUSIONS: Normalized CV has a clinically and statistically significant association with the occurrence of DCI after aSAH. Frequent quantitative pupillometry could improve the multimodal monitoring of patients after aSAH with the goal of improving the identification of patients likely to benefit from therapeutic interventions.
Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/physiopathology , Subarachnoid Hemorrhage/diagnosis , Male , Female , Middle Aged , Brain Ischemia/etiology , Brain Ischemia/diagnosis , Brain Ischemia/physiopathology , Prospective Studies , Aged , Adult , Cohort Studies , Pupil/physiology , Prognosis , Reflex, Pupillary/physiologyABSTRACT
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.
Subject(s)
Genome-Wide Association Study , Head , Neoplasms , Humans , Head/anatomy & histology , Neoplasms/genetics , Neoplasms/pathology , Female , Male , Polymorphism, Single Nucleotide/genetics , Genetic Variation , Organ Size/genetics , Signal Transduction/genetics , Adult , Genetic Predisposition to DiseaseABSTRACT
Background: The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Objective: Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Methods: Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. Results: We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Conclusion: Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.
ABSTRACT
Pituitary apoplexy (PA) may be complicated by development of subarachnoid hemorrhage (SAH). We conducted a literature review to evaluate the rate of PA-associated tumor rupture and SAH. We conducted a systematic literature search (PubMed, Web of Science, Medline) for patients with PA-associated SAH and report a case SAH following PA. Suitable articles, case series, and case reports were selected based on predefined criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We reviewed included publications for clinical, radiological, surgical, and histopathological parameters.We present the case of a patient with PA developing extensive SAH whilst on the MRI who underwent delayed transsphenoidal resection. According to our literature review, we found 55 patients with a median age of 46 years; 18 (32.7%) were female. Factors associated with PA-related SAH were hypertension, diabetes mellitus, prior trauma, anticoagulant, and/or antiplatelet therapy. The most common presenting symptoms included severe headache, nausea and/or vomiting, impaired consciousness, and meningeal irritation. Acute onset was described in almost all patients. Twenty-two of the included patients underwent resection. In patients with available outcome, 45.1% had a favorable outcome, 10 (19.6%) had persisting focal neurological deficits, 7 developed cerebral vasospasms (12.7%), and 18 (35.3%) died. Mortality greatly differed between surgically (9.1%) and non-surgically (44.8%) treated patients. PA-associated SAH is a rare condition developing predominantly in males with previously unknown macroadenomas. Timely surgery often prevents aggravation or development of severe neuro-ophthalmological defects and improves clinical outcome.
Subject(s)
Adenoma , Pituitary Apoplexy , Pituitary Neoplasms , Stroke , Subarachnoid Hemorrhage , Male , Humans , Female , Middle Aged , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/surgery , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/diagnostic imaging , Pituitary Apoplexy/complications , Pituitary Apoplexy/diagnostic imaging , Pituitary Apoplexy/surgery , Adenoma/complications , Adenoma/diagnostic imaging , Adenoma/surgery , Stroke/complicationsABSTRACT
BACKGROUND: Intracerebral haemorrhage (ICH) is a severe clinical consequence of cerebral small vessel disease (SVD), but associations between renal impairment and SVD in patients with ICH have not been fully characterised. METHODS: Using data from the CROMIS-2 ICH observational study, we compared SVD neuroimaging markers and total burden (score 0-3) identified using CT brain imaging in patients with and without renal impairment (estimated glomerular filtration rate, eGFR<60). We assessed functional outcome at 6-month follow-up using the modified Rankin scale. RESULTS: 1027 participants were included (mean age 72.8, 57.1% male); 274 with and 753 without renal impairment. 18.7% of the eGFR<60 group had moderate-to-severe SVD burden (score 2-3), compared with 14.0% of those with eGFR>60 (p = 0.039). SVD burden was associated with renal impairment after adjusting for hypertension (OR 1.36, 95% CI 1.04-1.77, p = 0.023), but not after adjusting for age. Cerebral atrophy was more prevalent in patients with eGFR<60 (81.2% vs. 72.0%, p = 0.002), as were WMH (45.6% vs. 36.6%, p = 0.026). Neither was associated with renal function after adjusting for age and vascular risk factors. Renal impairment was associated with functional outcome (OR 0.65, 95% CI 0.47-0.89, p = 0.007), but not after adjusting for age, pre-morbid function and comorbidities (OR 0.95, 95% CI 0.65-1.38, p = 0.774). CONCLUSION: In acute ICH, renal impairment is associated with a higher cerebral SVD burden independent of hypertension, but not age. Reduced eGFR is associated with worse functional outcome, but not independent of age and comorbidities. Since CT has limited sensitivity to detect SVD severity and distribution, further studies including MRI are needed.
Subject(s)
Cerebral Small Vessel Diseases , Hypertension , Humans , Male , Female , Prospective Studies , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/epidemiology , Cerebral Small Vessel Diseases/complications , Cerebral Small Vessel Diseases/diagnostic imaging , Magnetic Resonance Imaging , Hypertension/complications , Kidney/diagnostic imaging , Kidney/physiologyABSTRACT
Introduction: Anterior-only multilevel cervical decompression and fusion surgery (AMCS) on 3-5-levels is challenging due to potential complications. Also, outcome predictors after AMCS are poorly understood. Research Question: We hypothesize that in patients with at most mild/moderate cervical kyphosis (CK) of the cervical spine, restoration of cervical lordosis (CL) positively influences clinical outcomes. Methods: Analysis of consecutive patients presenting with symptomatic degenerative cervical disease or non-union undergoing AMCS. We measured CL from C2 to C7, Cobb angle of fused levels (fusion angle, FA), C7-Slope, and sagittal vertical axis C2-7 (cSVA, stratified into ≤4cm∖>4cm). Patients with excellent outcome were grouped in BEST-outcomes and with moderate/poor outcomes in WORST-outcomes. Results: We included 244 patients. Fifty-four percent had 3-, 39% 4-level and 7% had 5-level fusion. At mean follow-up of 26 months, 41% of patients achieved BEST-outcome and 23% WORST-outcome. Complications and reoperation rates did not significantly differ. Non-union significantly influenced outcomes. The number of patients with non-union was significantly higher in patients with a preoperative cSVA>4cm (OR 13.1 (95%CI:1.8-96.8). Our model, based on the multivariable analysis with WORST-outcome as outcome variable showed a high accuracy (NPV=73%, PPV=77%, specificity=79%, sensitivity=71%). Discussion and Conclusion: In 3-5-level AMCS, improvement of FA and cSVA were independent predictors of clinical outcome. Improvement of CL positively influenced clinical outcomes and rates of non-union.
ABSTRACT
Introduction: Hydrocephalus after aneurysmal subarachnoid haemorrhage (aSAH) is a common complication which may lead to insertion of a ventriculoperitoneal shunt (VPS). Our aim is to evaluate a possible influence of specific clinical and biochemical factors on VPS dependency with special emphasis on hyperglycaemia on admission. Patients and methods: Retrospective analysis of a monocentric database of aSAH patients. Using univariable and multivariable logistic regression analysis we evaluated factors influencing VPS dependency, with a special focus on hyperglycaemia on blood sample within 24 h of admission, dichotomised at 126 mg/dl. Factors evaluated in the univariable analysis were age, sex, known diabetes, Hunt and Hess grade, Barrow Neurological Institute scale, treatment modality, extra-ventricular drain (EVD) insertion, complications (rebleeding, vasospasm, infarction, decompressive craniectomy, ventriculitis), outcome variables and laboratory parameters (glucose, C-reactive protein, procalcitonin). Results: We included 510 consecutive patients treated with acute aSAH requiring a VPS (mean age 58.2 years, 66% were female). An EVD was inserted in 387 (75.9%) patients. In the univariable analysis, VPS dependency was associated with hyperglycaemia on admission (OR 2.56, 95%CI 1.58-4.14, p < 0.001). In the multivariable regression analysis after stepwise backward regression, factors associated with VPS dependency were hyperglycaemia >126 mg/dl on admission (OR 1.93, 95%CI 1.13-3.30, p = 0.02), ventriculitis (OR 2.33, 95%CI 1.33-4.04, p = 0.003), Hunt and Hess grade (overall p-value 0.02) and decompressive craniectomy (OR 2.68, 95%CI 1.55-4.64, p < 0.001). Conclusion: Hyperglycaemia on admission was associated with an increased probability of VPS placement. If confirmed, this finding might facilitate treatment of these patients by accelerating insertion of a permanent draining system.
Subject(s)
Cerebral Ventriculitis , Gastritis , Hyperglycemia , Subarachnoid Hemorrhage , Female , Humans , Male , Middle Aged , Cerebral Ventriculitis/complications , Gastritis/complications , Hyperglycemia/complications , Retrospective Studies , Subarachnoid Hemorrhage/complications , Ventriculoperitoneal Shunt/adverse effectsABSTRACT
OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.
Subject(s)
Hydrocephalus , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/surgery , Retrospective Studies , Switzerland , Weaning , Hydrocephalus/surgery , Hydrocephalus/complicationsABSTRACT
Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.
Subject(s)
Endometriosis , Female , Humans , Endometriosis/genetics , Endometriosis/metabolism , Genetic Predisposition to Disease , Genome-Wide Association Study , Pain , ComorbidityABSTRACT
Timely treatment of aneurysmal subarachnoid haemorrhage (aSAH) is key to prevent further rupture and poor outcome. We evaluated complications and outcome adjusting for time from haemorrhage to treatment. Retrospective analysis of aSAH patients admitted between 2006 and 2020. Data was collected using standardized case report forms. We compared risk factors using multivariable logistic regression. We included 853 patients, 698 (81.8%) were treated within 24 h. Patients with higher Hunt and Hess grades were admitted and treated significantly faster than those with lower grades (overall p-value < 0.001). Fifteen patients (1.8%) rebled before intervention. In the multivariable logistic analysis adjusting for timing, Barrow Neurological Institute score and intracerebral haemorrhage were significantly associated with rebleeding (overall p-value 0.006; OR 3.12, 95%CI 1.09-8.92, p = 0.03, respectively) but timing was not. Treatment > 24 h was associated with higher mortality and cerebral infarction in only the subgroup of lower grades aSAH (OR 3.13, 1.02-9.58 95%CI, p-value = 0.05; OR 7.69, 2.44-25.00, p-value < 0.001, respectively). Therefore treatment > 24 h after rupture is associated with higher mortality and cerebral infarction rates in lower grades aSAH. Delay in treatment primarily affects lower grade aSAH patients. Patients with lower grade aSAH ought to be treated with the same urgency as higher-grade aSAH.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/therapy , Subarachnoid Hemorrhage/complications , Retrospective Studies , Risk Factors , Cerebral Infarction/complications , Aneurysm, Ruptured/therapy , Aneurysm, Ruptured/complications , Treatment Outcome , Intracranial Aneurysm/complications , Intracranial Aneurysm/therapyABSTRACT
BACKGROUND AND PURPOSE: Nuclear factor erythroid 2-related factor 2 (NRF2; encoded by the NFE2L2 gene) has been implicated in outcome following aneurysmal subarachnoid haemorrhage (aSAH) through its activity as a regulator of inflammation, oxidative injury and blood breakdown product clearance. The aim of this study was to identify whether genetic variation in NFE2L2 is associated with clinical outcome following aSAH. METHODS: Ten tagging single nucleotide polymorphisms (SNPs) in NFE2L2 were genotyped and tested for association with dichotomized clinical outcome, assessed by the modified Rankin scale, in both a discovery and a validation cohort. In silico functional analysis was performed using a range of bioinformatic tools. RESULTS: One SNP, rs10183914, was significantly associated with outcome following aSAH in both the discovery (n = 1007) and validation cohorts (n = 466). The risk of poor outcome was estimated to be 1.33-fold (95% confidence interval 1.12-1.58) higher in individuals with the T allele of rs10183914 (pmeta-analysis = 0.001). In silico functional analysis identified rs10183914 as a potentially regulatory variant with effects on transcription factor binding in addition to alternative splicing with the T allele, associated with a significant reduction in the NFE2L2 intron excision ratio (psQTL = 1.3 × 10-7 ). CONCLUSIONS: The NFE2L2 SNP, rs10183914, is significantly associated with outcome following aSAH. This is consistent with a clinically relevant pathophysiological role for oxidative and inflammatory brain injury due to blood and its breakdown products in aSAH. Furthermore, our findings support NRF2 as a potential therapeutic target following aSAH and other forms of intracranial haemorrhage.
Subject(s)
Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/genetics , NF-E2-Related Factor 2/genetics , Polymorphism, Single Nucleotide/genetics , Genotype , AllelesABSTRACT
Candidate gene studies have identified genetic variants associated with clinical outcomes following aneurysmal subarachnoid haemorrhage (aSAH), but no genome-wide association studies have been performed to date. Here we report the results of the discovery phase of a two-stage genome-wide meta-analysis of outcome after aSAH. We identified 157 independent loci harbouring 756 genetic variants associated with outcome after aSAH (p < 1 × 10-4), which require validation. A single variant (rs12949158), in SPNS2, achieved genome-wide significance (p = 4.29 × 10-8) implicating sphingosine-1-phosphate signalling in outcome after aSAH. A large multicentre international effort to recruit samples for validation is required and ongoing. Validation of these findings will provide significant insight into the pathophysiology of outcomes after aSAH with potential implications for treatment.
Subject(s)
Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/complications , Genome-Wide Association Study , Longitudinal Studies , Treatment OutcomeABSTRACT
BACKGROUND: Cerebral amyloid angiopathy (CAA), a common cause of intracerebral hemorrhage (ICH), is diagnosed using the Boston criteria including magnetic resonance imaging (MRI) biomarkers (cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS). The simplified Edinburgh criteria include computed tomography (CT) biomarkers (subarachnoid extension (SAE) and finger-like projections (FLPs)). The underlying mechanisms and diagnostic accuracy of CT compared to MRI biomarkers of CAA are unknown. METHODS: We included 140 survivors of spontaneous lobar supratentorial ICH with both acute CT and MRI. We assessed associations between MRI and CT biomarkers and the diagnostic accuracy of CT- compared to MRI-based criteria. RESULTS: FLPs were more common in patients with strictly lobar CMB (44.7% vs 23.5%; p = 0.014) and SAE was more common in patients with cSS (61.3% vs 31.2%; p = 0.002). The high probability of the CAA category of the simplified Edinburgh criteria showed 87.2% (95% confidence interval (CI): 78.3-93.4) specificity, 29.6% (95% CI: 18.0-43.6) sensitivity, 59.3% (95% CI: 38.8-77.6) positive predictive value, and 66.4% (95%: CI 56.9-75.0) negative predictive value, 2.3 (95% CI: 1.2-4.6) positive likelihood ratio and 0.8 (95% CI 0.7-1.0) negative likelihood ratio for probable CAA (vs non-probable CAA), defined by the modified Boston criteria; the area under the receiver operating characteristic curve (AUROC) was 0.62 (95% CI: 0.54-0.71). CONCLUSION: In lobar ICH survivors, we found associations between putative biomarkers of parenchymal CAA (FLP and strictly lobar CMBs) and putative biomarkers of leptomeningeal CAA (SAE and cSS). In a hospital population, CT biomarkers might help rule-in probable CAA (diagnosed using the Boston criteria), but their absence is probably not as useful to rule it out, suggesting an important continued role for MRI in ICH survivors with suspected CAA.
Subject(s)
Cerebral Amyloid Angiopathy , Stroke , Humans , Cerebral Hemorrhage/epidemiology , Cerebral Amyloid Angiopathy/complications , Cerebral Amyloid Angiopathy/diagnostic imaging , Magnetic Resonance Imaging , Tomography, X-Ray Computed , BiomarkersABSTRACT
Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
Subject(s)
Bladder Exstrophy , Urinary Bladder Neoplasms , Humans , Animals , Mice , Bladder Exstrophy/genetics , Bladder Exstrophy/complications , Genome-Wide Association Study , Urinary Bladder Neoplasms/genetics , Transcriptome , Ephrin-A1/geneticsABSTRACT
Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.
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BACKGROUND AND OBJECTIVE: We investigated the associations between the APOE genotype, intracerebral hemorrhage (ICH), and neuroimaging markers of cerebral amyloid angiopathy (CAA). METHODS: We included patients from a prospective, multicenter UK observational cohort study of patients with ICH and representative UK population controls. First, we assessed the association of the APOE genotype with ICH (compared with controls without ICH). Second, among patients with ICH, we assessed the association of APOE status with the hematoma location (lobar or deep) and brain CT markers of CAA (finger-like projections [FLP] and subarachnoid extension [SAE]). RESULTS: We included 907 patients with ICH and 2,636 controls. The mean age was 73.2 (12.4 SD) years for ICH cases vs 69.6 (0.2 SD) for population controls; 50.3% of cases and 42.1% of controls were female. Compared with controls, any APOE ε2 allele was associated with all ICH (lobar and nonlobar) and lobar ICH on its own in the dominant model (OR 1.38, 95% CI 1.13-1.7, p = 0.002 and OR 1.50, 95% CI 1.1-2.04, p = 0.01, respectively) but not deep ICH in an age-adjusted analyses (OR 1.26, 95% CI 0.97-1.63, p = 0.08). In the cases-only analysis, the APOE ε4 allele was associated with lobar compared with deep ICH in an age-adjusted analyses (OR 1.56, 95% CI 1.1-2.2, p = 0.01). When assessing CAA markers, APOE alleles were independently associated with FLP (ε4: OR 1.74, 95% CI 1.04-2.93, p = 0.04 and ε2/ε4: 2.56, 95% CI 0.99-6.61, p = 0.05). We did not find an association between APOE alleles and SAE. DISCUSSION: We confirmed associations between APOE alleles and ICH including lobar ICH. Our analysis shows selective associations between APOE ε2 and ε4 alleles with FLP, a CT marker of CAA. Our findings suggest that different APOE alleles might have diverging influences on individual neuroimaging biomarkers of CAA-associated ICH.
Subject(s)
Cerebral Amyloid Angiopathy , Cerebral Small Vessel Diseases , Aged , Apolipoprotein E2/genetics , Apolipoprotein E4 , Apolipoproteins E , Biomarkers , Cerebral Amyloid Angiopathy/complications , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/genetics , Cerebral Small Vessel Diseases/complications , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: The Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus (HATCH) Score has previously shown to predict functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To validate the HATCH score. METHODS: This is a pooled cohort study including prospective collected data on 761 patients with aSAH from 4 different hospitals. The HATCH score for prediction of functional outcome was validated using calibration and discrimination analysis (area under the curve). HATCH score model performance was compared with the World Federation of Neurosurgical Societies and Barrow Neurological Institute score. RESULTS: At the follow-up of at least 6 months, favorable (Glasgow Outcome Score 4-5) and unfavorable functional outcomes (Glasgow Outcome Score 1-3) were observed in 512 (73%) and 189 (27%) patients, respectively. A higher HATCH score was associated with an increased risk of unfavorable outcome with a score of 1 showing a risk of 1.3% and a score of 12 yielding a risk of 67%. External validation showed a calibration intercept of -0.07 and slope of 0.60 with a Brier score of 0.157 indicating good model calibration and accuracy. With an area under the curve of 0.81 (95% CI 0.77-0.84), the HATCH score demonstrated superior discriminative ability to detect favorable outcome at follow-up compared with the World Federation of Neurosurgical Societies and Barrow Neurological Institute score with 0.72 (95% CI 0.67-0.75) and 0.63 (95% CI 0.59-0.68), respectively. CONCLUSION: This multicenter external validation analysis confirms the HATCH score to be a strong independent predictor for functional outcome. Its incorporation into daily practice may be of benefit for goal-directed patient care in aSAH.
Subject(s)
Hydrocephalus , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/therapy , Subarachnoid Hemorrhage/surgery , Cohort Studies , Prospective Studies , Hydrocephalus/etiology , Hydrocephalus/surgery , Prognosis , Treatment OutcomeABSTRACT
STUDY DESIGN: Retrospective, single-center case study. OBJECTIVE: Postoperative cervical imbalance with cervical sagittal vertical axis (cSVA) >4 cm can be predicted in 3-level to 5-level anterior-only cervical multilevel fusion surgery (ACMS). SUMMARY OF BACKGROUND DATA: Previous studies established correlations between cervical kyphosis (CK) correction and postoperative balance (cSVA ≤4 cm) with improved clinical outcomes. Understanding of what influences restoration of cervical lordosis (CL) in patients with degenerative disease with mild to moderate CK subjected to ACMS is important. To achieve a better understanding of geometric changes after ACMS, this study examines factors predicting perioperative alignment changes and regional interdependencies. MATERIALS AND METHODS: Analysis of patients with ACMS. Analysis included patient baseline characteristics, demographics and complications, and focused on radiographic measures including CL C2-7, fusion angle (FA), C7-Slope (C7S), T1-slope (T1S), T1-CL mismatch, and cSVA (cSVA ≤4 cm/>4 cm). We aimed to predict postoperative imbalance (cSVA >4 cm) and conducted a multivariable logistic regression analysis. RESULTS: Inclusion of 126 patients with 3-level to 5-level ACMS, mean age was 56 years and 4 fusion levels on average. Preoperative CK was present in 9%, mean FA-correction was 8 degrees, maximum 46 degrees. Postoperatively, 14 patients had cSVA >4 cm. A neural network model for prediction of cSVA >4 cm was established including preoperative cSVA, preoperative CL and correction of FA. The model achieved high performance (positive predictive value=100%, negative predictive value=94%, specificity=100%, sensitivity=20%). Also, variables such as nonunion, chronic lumbar pain or thoracolumbar multilevel fusion influenced the postoperative cSVA >4 cm rate. Alignment analysis highlighted strong correlations between C7S/T1S and cSVA/C2-tilt ( r =0.06/ r =0.7, P <0.0001). A formula was established to transfer cSVA data into C2-tilt data. CONCLUSION: This study identified independent variables predicting postoperative cSVA >4 cm including FA, which can be influenced by the surgeon. Our model supports the decision-making process targeting a postoperative cSVA ≤4 cm.
Subject(s)
Kyphosis , Lordosis , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Decompression , Humans , Kyphosis/diagnostic imaging , Kyphosis/surgery , Lordosis/diagnostic imaging , Lordosis/surgery , Middle Aged , Retrospective Studies , Thoracic Vertebrae/surgeryABSTRACT
BACKGROUND: Aneurysm treatment during cerebral vasospasm (CVS) phase is frequently considered as particularly dangerous, mainly because of the risk of cerebral infarct. OBJECTIVE: We aimed to evaluate the risk of aneurysmal subarachnoid haemorrhage (aSAH)-specific complications and functional outcome in patients treated during CVS phase. METHODS: We retrospectively analysed a large, retro- and prospectively collected database of aSAH patients admitted to our department between March 2006 and March 2020. We conducted a uni- and multivariable logistic regression analysis to evaluate influencing factors on rebleeding, cerebral infarct, Glasgow Outcome Score (GOS) at discharge and mortality and assessed the rate of angiographic vasospasm on admission. RESULTS: We included 853 patients. The majority of patients were female (66.6%), mean age was 57.3 years. Out of 853 included patients, 92 (10.8%) were treated during CVS phase, 312 (36.6%) underwent clipping and 541 (63.4%) endovascular treatment. Treatment during CVS phase was significantly associated with cerebral infarct in the multivariable logistic regression analysis, unrelated to the nature of intervention (OR 2.42, 1.29-4.54 95% CI p-value = 0.006). However, patients treated during CVS phase did not have increased risk of unfavourable outcome by GOS on discharge. In addition, they did not have a higher rate of rebleeding or mortality. CONCLUSIONS: Treatment during CVS phase was significantly associated with a higher rate of cerebral infarct as confirmed by imaging. This did not reflect on GOS on discharge, rebleeding, or mortality. Aneurysm treatment during CVS phase is relatively safe and should not be postponed due to the risk of rebleeding and subsequent devastating deterioration.
Subject(s)
Intracranial Aneurysm , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Angiography/adverse effects , Cerebral Infarction/complications , Female , Humans , Intracranial Aneurysm/complications , Male , Middle Aged , Retrospective Studies , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/diagnostic imaging , Subarachnoid Hemorrhage/therapy , Treatment Outcome , Vasospasm, Intracranial/diagnostic imaging , Vasospasm, Intracranial/epidemiology , Vasospasm, Intracranial/etiologyABSTRACT
Adult spinal ependymoma presents a rare low-grade tumor entity. Due to its incidence peak in the fourth decade of life, it mostly affects patients during a professionally and physically active time of life. We performed a retrospective monocentric study, including all patients operated upon for spinal ependymoma between 2009 and 2020. We prospectively collected data on professional reintegration, physical activities and quality-of-life parameters using EQ-5D and SF-36. Issues encountered were assessed using existing spinal-cord-specific questionnaires and free-text questions. In total, 65 of 114 patients agreed to participate. Most patients suffered from only mild pre- and postoperative impairment on the modified McCormick scale, but 67% confirmed difficulties performing physical activities in which they previously engaged due to pain, coordination problems and fear of injuries after a median follow-up of 5.4 years. We observed a shift from full- to part-time employment and patients unable to work, independently from tumor dignity, age and neurological function. Despite its benign nature and occurrence of formal only mild neurological deficits, patients described severe difficulties returning to their preoperative physical activity and profession. Clinical scores such as the McCormick grade and muscle strength may not reflect the entire self-perceived impairment appropriately.