1,720,969 research outputs found
Outcome after aneurysmal subarachnoid haemorrhage
No full textAneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of stroke associated with significant morbidity and mortality. It affects younger people than other stroke types and consequently has a disproportionately high socio-economic impact. Survivors often suffer a range of disabling symptoms including physical and cognitive deficits. These deficits lead to a reduced quality of life and impair ability to return to work following aSAH. In order to develop treatments to improve outcome after aSAH we need to better understand the mechanisms that underlie neurological injury. At present the calcium channel blocker, nimodipine which was developed in the 1980s, is the only licensed treatment to improve outcome following aSAH. Despite multiple trials there have been no major developments to improve outcome following haemorrhage for over 30 years and it is our lack of understanding of the pathophysiology of neurological injury that, at least in part, explains this lack of therapeutic innovation. This thesis focusses on understanding outcome after aSAH and has three main aims. First, to explore the burden of hidden disability by studying cognitive, auditory, headache and fatigue outcomes in the long-term following aSAH including the implications for quality of life and employment. Second, to improve outcome prediction following aSAH by including additional variables and advanced statistical learning methods. Third, to use a genetic approach to provide insight into the mechanisms underlying neurological injury following aSAH. The results reported in this thesis are that cognitive and auditory deficits, in addition to persistent headache and fatigue, are significantly more common in aSAH survivors compared to a control population. Auditory deficits are most in keeping with a central auditory processing disorder rather than a peripheral deficit and are closely linked to impaired cognition following aSAH. Cognitive deficits, persistent headache and fatigue all significantly contribute to unemployment following aSAH. In addition to the well-known clinical variables that predict outcome after aSAH, C-reactive protein (CRP) is an independent predictor of outcome following aSAH. The incorporation of CRP and the use of advanced predictive modelling methodology such as support vector machines improves outcome prediction following aSAH. Despite a statistical improvement these new models are unlikely to have major clinical impact and require validation in an external cohort. To identify genetic contribution to outcome after SAH, first a candidate gene approach was used. This identified that haptoglobin, a haemoglobin scavenging molecule, is implicated in outcome after aSAH, although the evidence is not conclusive. Genetic variation in NRF2, a transcription factor regulating haemoglobin scavenging, inflammation and oxidative injury, is also associated with outcome after aSAH. These findings provide insight into the pathophysiology of neurological injury following aSAH but are limited by the candidate nature of the analyses. A subsequent unbiased genome-wide analysis provides novel evidence for a role of the sphingosine1-phosphate signalling pathway in neurological injury and outcome following aSAH. This thesis concludes that aSAH leads to widespread long-term neurological symptoms which impact quality of life and employment. The inclusion of additional clinically available predictors and use of advanced statistical learning methods can improve outcome prediction following aSAH. However, the improvements are small and unlikely to influence clinical practice. Ultimately to improve outcome we need to better understand the mechanisms which drive neurological injury. Using both candidate and genome-wide analysis a number of mechanisms including haemoglobin scavenging, inflammation, oxidative injury and sphingolipid signalling have been implicated in outcome. These pathways may act as therapeutic targets to improve outcome after aSAH and warrant further study
Candidate molecular predictors of outcome after aneurysmal subarachnoid haemorrhage: a systematic review of haemoglobin metabolism, inflammation and oxidative injury pathways
No full textAneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of stroke associated with significant morbidity and mortality. Very little is known about the predictors of poor outcome and the pathophysiological mechanisms underlying neurological injury following aSAH. Three molecular pathways have been shown to be important: haemoglobin metabolism, inflammation and oxidative injury. The aim of this review is to use a systematic approach to identify a panel of key genes within these three pathways in order to focus future studies investigating predictors of poor outcome and the mechanisms of neurological injury following aSAH. Manual searching and bioinformatic mining tools were used. Studies of experimental or human SAH were included, and outcome was broadly defined to include all encountered readouts such as mortality, neurological scores, and neuropathological markers of tissue damage. If two or more molecules belonged to the same biochemical pathway, this pathway was examined in detail to identify all its components, which were then searched individually for any evidence of association with outcome using the same broad definition as before. This resulted in the identification of 58 candidate genes within the three pathways of interest (haemoglobin metabolism, inflammation and oxidative injury) potentially linked to outcome after aSAH
Acetylsalicylic acid and subarachnoid hemorrhage in the Nurses’ Health Study
No full textBackground: acetylsalicylic acid (aspirin) is known to increase the risk of bleeding throughout the body. However, there is also evidence to suggest that acetylsalicylic acid may have a protective role in the formation and rupture of intracranial aneurysms. Previous studies investigating acetylsalicylic acid and subarachnoid haemorrhage (SAH) have so far provided conflicting results.Aims: the aim of this study was to analyse the Nurse’s Health Study (NHS) using serial assessments to evaluate differences in rates of SAH in those participants taking acetylsalicylic acid and those not taking acetylsalicylic acid while considering dose, frequency, and duration as well as different types of SAH.Methods: the Nurse’s Health Study (NHS) is a prospective population-based cohort study of female nurses. Information on acetylsalicylic acid was first reported in 1980 until 2016 and included acetylsalicylic acid use, dose, frequency and duration. All stroke cases were classified by physicians. Cox proportional-hazards regression models were used to estimate the hazard ratio (HR) associated with acetylsalicylic acid use.Results: a total of 117,648 NHS participants were eligible for analysis with 357 cases of SAH observed over 4,091,239 years of follow up. There was no association between acetylsalicylic acid use and SAH (HR 1.02 [0.82, 1.28], p=0.85), aneurysmal SAH (1.04 [0.78, 1.39], p=0.78), or idiopathic SAH (HR 0.94 [0.65, 1.34], p=0.72). The number of acetylsalicylic acid tablets per week was associated with SAH (HR 1.03 [1.00, 1.06], p=0.02), specifically fatal SAH (HR 1.04 [1.00, 1.08], p=0.03). There was no association between frequency and SAH (HR 1.06 [0.99, 1.13], p=0.07).Conclusions: there was no evidence to support a protective association between acetylsalicylic acid and either SAH or aneurysmal SAH in female participants. In fact, there was some evidence to suggest increased SAH risk with increased acetylsalicylic acid dose in some but not all analyses
Auditory outcome following aneurysmal subarachnoid haemorrhage
No full textAuditory deficits are increasingly recognised following aneurysmal subarachnoid haemorrhage (aSAH) and are thought to be of central rather than peripheral origin. Central hearing impairment, also known as auditory processing disorder (APD), often coexists with cognitive deficits and it is thought that APD has both auditory and cognitive elements. The aim of this study was to assess auditory outcome following aSAH and its relationship with cognition. A retrospective case-controlled study design was employed with aSAH cases and matched controls identified from the UK Biobank. Auditory and cognitive outcomes were assessed using the digit triplet test (DTT) and a test of psychomotor reaction time, respectively. Best DTT score was compared between cases and controls using the t-test. A regression-based mediation analysis was performed to assess whether cognition mediated auditory outcome. 270 aSAH patients with auditory outcomes were identified with an average follow-up of 106 months. A matched control cohort of 1080 individuals was also identified. The aSAH cohort had significantly impaired best DTT scores compared to matched controls (p = 0.002). Cognition significantly mediated auditory outcome following aSAH, accounting for 9.8% of the hearing impairment after aSAH. In conclusion significant hearing impairment follows aSAH. The deficit is bilateral and non-progressive. There is a link with cognitive deficit, pointing to a central rather than peripheral source, in keeping with an auditory processing disorder. All aSAH patients should be asked about hearing difficulty at follow-up and when present it should be investigated with peripheral and central auditory assessments, as well as cognitive tests.Keywords: Health care; Hearing loss; Outcome assessment; Stroke; Subarachnoid haemorrhage.<br/
Risk of subarachnoid haemorrhage reduces with blood pressure values below hypertensive thresholds
No full textBACKGROUND: hypertension is a known risk factor for subarachnoid haemorrhage (SAH). The aim of this study was to describe the relationship between blood pressure and SAH using a large cohort study and perform a meta-analysis of the published literature.METHODS: participants in the UK Biobank were followed up via electronic records until 31 March 2017. Cox proportional hazards models were used to analyse the association between baseline blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP] and MABP [mean arterial blood pressure]) and subsequent aneurysmal SAH. Linearity was assessed by comparing models including and excluding cubic splines. Electronic databases were searched from inception until 11 February 2022 for studies reporting on blood pressure and SAH.RESULTS: a total of 500,598 individuals were included with 539 (0.001%) suffering from aneurysmal SAH. Nonlinear models including cubic splines visually appeared linear between SBP of 110 and 180 mmHg and there was minimal difference in fit between linear and nonlinear models. When values were stratified, those with SBP 120-130 mmHg were at higher risk compared to those with SBP <120 mmHg (hazard ratio [HR] 1.41 [1.02, 1.95]). The meta-analysis demonstrated a similar increased risk of SAH in individuals with SBP 120-130 mmHg relative to those with <120 mmHg (HR 1.41 [1.17, 1.72]). A stepwise increase in risk was also seen at each subsequent threshold (130-140 mmHg: HR 1.85 [1.53, 2.24], 140-160 mmHg: HR 2.16 [1.57, 2.98], 160-180 mmHg: HR 2.81 [1.85, 4.29], >180 mmHg: HR 5.84 [1.94, 17.54]).CONCLUSIONS: the rate of SAH increases linearly with higher SBP in the general population and specifically appears lower in those with SBP <120 mmHg.</p
Follow-up of arachnoid cysts: brain plasticity following surgery for arachnoid cysts
No full textImaging for arachnoid cysts (ACs) after surgery focuses on assessing for changes in cyst volume. Changes in volume are traditionally considered a marker of surgical success. This chapter provides an overview of relevant literature demonstrating that cysto-peritoneal shunting may provide a greater degree of cyst volume reduction than fenestration. However, multiple studies have demonstrated poor correlation between volume change and symptom improvement. The chapter will also discuss the timing of volume change post-operatively in cases of symptomatic ACs
Haptoglobin genotype and outcome after subarachnoid haemorrhage: new insights from a meta-analysis
Full text linkHaptoglobin (Hp) is a plasma protein involved in clearing extracellular haemoglobin and regulating inflammation; it exists as two genetic variants (Hp1 and Hp2). In a meta-analysis of six published studies, we confirm that Hp genotype affects short-term outcome (cerebral vasospasm and/or delayed cerebral ischemia) after subarachnoid haemorrhage (SAH), but not long–term outcome (Glasgow Outcome score and modified Rankin Scale between one and three months). Closer examination of the heterozygous group revealed that the short-term outcome of Hp2-1 individuals clustered with that of Hp1-1 and not Hp2-2, suggesting that the presence of one Hp1 allele was sufficient to confer protection. Since the presence of the Hp dimer is the only common feature between Hp1-1 and Hp2-1 individuals, the absence of this Hp moiety is most likely to underlie vasospasm in Hp2-2 individuals. These results have implications for prognosis after SAH and will inform further research into Hp-based mechanism of action and treatment
Safety, Accuracy, and Cost Effectiveness of Bedside Bolt External Ventricular Drains (EVDs) in Comparison with Tunneled EVDs Inserted in Theaters
Full text linkObjectives
External ventricular drain (EVD) placement is required frequently in neurosurgical patients to divert cerebrospinal fluid and monitor intracranial pressure. The usual practice is the tunneled EVD technique performed in operating theaters. EVD insertion through a bolt in intensive care also is described. We employ both practices in our institute. Herein, we compare the indications, accuracy, safety, and costs of the 2 techniques.
Methods
This was a retrospective cohort study of a prospectively maintained EVD database of all patients undergoing first frontal EVD placement between January 2010 and December 2015. Those patients with preceding cerebrospinal fluid infection were excluded. We compared bolt EVD with tunneled EVD techniques in terms of accuracy of EVD tip location by analyzing computed tomography scans to grade catheter tip location as optimal (ipsilateral frontal horn) or otherwise suboptimal, and complications that include infection and revision rates.
Results
In total, 579 eligible patients aged 3 months to 84 years were identified; 430 had tunneled EVDs and 149 bolt EVDs. The most frequent diagnosis was intracranial hemorrhage (73% bolt vs. 50.4% tunneled group; P < 0.001). Other diagnoses included tumor (4.7% bolt vs. 19.1% tunneled; P < 0.001) and traumatic brain injury (17.5% bolt vs. 17.4% tunneled). In the bolt EVD group 66.4% of EVD tips were optimal, compared with 61.0% in the tunneled group (P = 0.33). Infection was confirmed in 15 (10.0%) bolt EVDs compared with 61 (14.2%) tunneled EVDs (P = 0.2). Each bolt EVD kit costs £260, whereas placing a tunneled one in the theater costs £1316.
Conclusions
Bedside bolt EVD placement is safe, accurate, and cost effective in selective patients with hemorrhage-related hydrocephalus
Paediatric brain abscesses: a single centre experience
No full textIntroduction: brain parenchymal abscesses are relatively infrequent but potentially serious infections in the paediatric population. Surgical intervention in addition to a prolonged administration of antibiotics is generally appropriate management. This study presents our centre's experience of managing such patients in the context of relevant literature. Method: a single-centre retrospective case note review was conducted over a 15 year period (2003-2017). Patients were selected from electronic hospital records using ICD10 code G06.0. Patients <18 years of age with a confirmed intra-parenchymal abscess were included. Patient records were reviewed for abscess location, microbiology results, surgical intervention, and outcome using the Glasgow Outcome Score at 3 months. Results: twenty-four patients were identified (mean age: 7.4 ± 5.3 years, male n = 11). Twelve (50.0%) patients had an abscess in the frontal lobe and Streptococcus was the most common causative microorganism (n = 15). Nineteen patients (79.2%) had an identifiable source which included: ENT infections, congenital cardiac malformations, recent dental surgery and meningitis. All 24 patients underwent surgery with 20 patients having a total of 32 aspirations between them and the other 4 having craniotomy and excision. Twenty patients had 3 month follow-up data of which 18 patients scored GOS: 5, one was GOS: 4 and one was GOS: 3. Conclusions: brain parenchymal abscess remains an uncommon pathology in the paediatric population. The majority of patients have a preceding infection with Streptococcus as the most common causative organism. Antimicrobial therapy should be selected accordingly. All of our patients underwent surgical intervention and received intravenous antibiotics with favourable outcome and no mortality
Long-term cognitive outcome following aneurysmal subarachnoid haemorrhage
No full textObjectives: Survivors of aneurysmal subarachnoid haemorrhage (aSAH) frequently suffer from cognitive dysfunction. The aim of this study was to assess, in a large sample size with long term follow-up, the characteristics of cognitive dysfunction following aSAH and explore whether cognitive deficits mediate employment outcome. Materials and methods: In this retrospective case-controlled study, aSAH survivors (n = 884) were identified from the UK Biobank and compared to matched controls (n = 3536). Controls were propensity score matched according to age, sex, Townsend deprivation score, educational status and relevant medications known to influence cognition. Cognitive outcomes and employment status were compared between cases and controls using group comparison and cross-tabulation tests. A regression-based mediation analysis was performed to assess whether cognitive deficits mediate employment status following aSAH. Results: Psychomotor reaction time and employment status significantly differed between aSAH cases and controls with slower reaction times (p < 0.001) and more unemployment or inability to work due to illness (p < 0.001) in the aSAH cohort at a mean follow-up of 125 months. Psychomotor slowing was estimated to mediate a significant proportion (6.59%) of the effect of aSAH on employment status. Conclusions: Psychomotor reaction time and employment status differed significantly between aSAH cases and control matched individuals in the UK Biobank. Psychomotor slowing following aSAH had a discernible impact on employment status. Psychomotor reaction time and employment status are practical to acquire and can be used as surrogate measures of outcome in future studies of aSAH survivors.</p
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