Risk of subarachnoid haemorrhage reduces with blood pressure values below hypertensive thresholds.

BACKGROUND: 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.

Aneurysm management in patients over 80 years old with good grade subarachnoid haemorrhage.

BACKGROUND: An increasing proportion of aneurysmal subarachnoid haemorrhage (aSAH) occurs in older patients, in whom there is widespread variability in treatment rates due to a different balance of risks. Our aim was to compare outcomes of patients over 80 years old with good grade aSAH who underwent treatment of their aneurysm with those who did not. METHODS: Adult patients with good grade aSAH admitted to tertiary regional neurosciences centres contributing to the UK and Ireland Subarachnoid Haemorrhage Database (UKISAH) and a cohort of consecutive patients admitted from three regional cohorts were included for analysis. Outcomes were functional outcome at discharge, three months and survival at discharge. RESULTS: In the UKISAH, patients whose aneurysm was treated were more likely to have a favourable outcome at discharge (OR 2.34, CI 1.12-4.91, p = .02), at three months (OR 2.29, CI 1.11-4.76, p = .04), and lower mortality (10% vs. 29%, OR 0.83, CI 0.72-0.94, p < .01). In the regional cohort, a similar pattern was seen, but after correction for frailty and comorbidity there was no difference in survival (HR 0.45, CI 0.12-1.68, p = .24) or favourable outcome at discharge (OR 0.83, CI 0.23-2.94, p = .77) and at three months (OR 1.03, CI 0.25-4.29, p = .99). CONCLUSIONS: Better early functional outcomes in those undergoing aneurysm treatment appear to be explained by differences in frailty and comorbidity. Therefore, treatment decisions in this patient group are finely balanced with no clear evidence overall of either benefit or harm in this cohort.

Aspirin and Subarachnoid Haemorrhage in the UK Biobank.

Previous studies investigating the relationship between aspirin use and subarachnoid haemorrhage (SAH) have yielded conflicting results. In this study, we aimed to clarify the association between aspirin and SAH in the general population. The UK Biobank is a prospective population-based cohort study. Sex, age, smoking, alcohol, medication use, hypertension, blood pressure, ischaemic heart disease and stroke were recorded at baseline assessments. Follow-up is conducted through linkages to National Health Service data including electronic, coded death certificate, hospital and primary care data. Cox proportional hazards modelling was used to analyse the association between aspirin use and SAH. Of the 501,060 participants included in the analysis, a total of 579 suffered from spontaneous SAH after their baseline assessment. There was no relationship between aspirin and SAH of all causes (HR, 1.16 [0.92-1.46]), aneurysmal SAH (HR, 1.15 [0.91-1.47]) or non-aneurysmal SAH (HR, 1.29 [0.54-3.09]). Aspirin use was associated with SAH resulting in death (HR, 1.69 [1.14-2.51]), especially out of hospital death (HR, 2.10 [1.13-3.91]). Despite reports of a protective association between aspirin and SAH in patients with known unruptured aneurysms, this study has not demonstrated the same effect in the general population. However, aspirin users were more likely to suffer SAH resulting in death, especially out of hospital.

Haptoglobin genotype and outcome after aneurysmal subarachnoid haemorrhage.

OBJECTIVE: After aneurysmal subarachnoid haemorrhage (aSAH), extracellular haemoglobin (Hb) in the subarachnoid space is bound by haptoglobin, neutralising Hb toxicity and helping its clearance. Two exons in the HP gene (encoding haptoglobin) exhibit copy number variation (CNV), giving rise to HP1 and HP2 alleles, which influence haptoglobin expression level and possibly haptoglobin function. We hypothesised that the HP CNV associates with long-term outcome beyond the first year after aSAH. METHODS: The HP CNV was typed using quantitative PCR in 1299 aSAH survivors in the Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, a retrospective multicentre cohort study with a median follow-up of 18 months. To investigate mediation of the HP CNV effect by haptoglobin expression level, as opposed to functional differences, we used rs2000999, a single nucleotide polymorphism associated with haptoglobin expression independent of the HP CNV. Outcome was assessed using modified Rankin and Glasgow Outcome Scores. SAH volume was dichotomised on the Fisher grade. Haemoglobin-haptoglobin complexes were measured in cerebrospinal fluid (CSF) of 44 patients with aSAH and related to the HP CNV. RESULTS: The HP2 allele associated with a favourable long-term outcome after high-volume but not low-volume aSAH (multivariable logistic regression). However rs2000999 did not predict outcome. The HP2 allele associated with lower CSF haemoglobin-haptoglobin complex levels. The CSF Hb concentration after high-volume and low-volume aSAH was, respectively, higher and lower than the Hb-binding capacity of CSF haptoglobin. CONCLUSION: The HP2 allele carries a favourable long-term prognosis after high-volume aSAH. Haptoglobin and the Hb clearance pathway are therapeutic targets after aSAH.

Paediatric brain abscesses: a single centre experience.

Introduction: 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.

Safety, Accuracy, and Cost Effectiveness of Bedside Bolt External Ventricular Drains (EVDs) in Comparison with Tunneled EVDs Inserted in Theaters.

OBJECTIVES: 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.

Image guidance and improved accuracy of external ventricular drain tip position particularly in patients with small ventricles.

OBJECTIVE: External ventricular drain (EVD) insertion is one of the most common emergency neurosurgical procedures. EVDs are traditionally inserted freehand (FH) in an emergency setting, but often result in suboptimal positioning. Image-guided surgery (IGS) is selectively used to assist placement. However, the accuracy and practicality of IGS use is yet to be reported. In this study, the authors set out to assess if IGS is practical and improves the accuracy of EVD placement. METHODS: Case notes and images obtained in patients who underwent frontal EVD placement were retrospectively reviewed. Ventriculomegaly was determined by the measurement of the Evans index. EVD location was classified as optimal (ipsilateral frontal horn) or suboptimal (any other location). Propensity score matching of the two groups (IGS vs FH) for the Evans index was performed. Data were analyzed for patient age, diagnosis, number of EVDs, and complications. Those without postoperative CT scans were excluded. RESULTS: A total of 607 patients with 760 EVDs placed were identified; 331 met inclusion criteria. Of these, 287 were inserted FH, and 44 were placed with IGS; 60.6% of all unmatched FH EVDs were optimal compared with 75% of the IGS group (p = 0.067). The IGS group had a significantly smaller Evans index (p < 0.0001). Propensity score matching demonstrated improved optimal position in the IGS group when compared with the matched FH group (75% vs 43.2%, OR 4.6 [1.5-14.6]; p = 0.002). Patients with an Evans index of ≥ 0.36 derived less benefit (75% in IGS vs 66% in FH, p = 0.5), and those with an Evans index < 0.36 derived more benefit (75% in IGS vs 53% in FH, p = 0.024). The overall EVD complication rate was 36% in the FH group versus 18% in the IGS group (p = 0.056). Revision rates were higher in the FH group (p = 0.035), and the operative times were similar (p = 0.69). Long intracranial EVD catheters were associated with tip malposition irrespective of the group. CONCLUSIONS: Image guidance is practical and improves the accuracy of EVD placement in patients with small ventricles; thus, it should be considered for these patients.

Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription.

OBJECTIVES: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. METHODS: We present a case report of a patient who developed this syndrome with various sequelae. RESULTS: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. CONCLUSIONS: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis.

Our objective was to identify whether rare genetic variation in amyotrophic lateral sclerosis (ALS) candidate survival genes modifies ALS survival. Candidate genes were selected based on evidence for modifying ALS survival. Each tail of the extreme 1.5% of survival was selected from the UK MND DNA Bank and all samples available underwent whole genome sequencing. A replication set from the Netherlands was used for validation. Sequences of candidate survival genes were extracted and variants passing quality control with a minor allele frequency ≤0.05 were selected for association testing. Analysis was by burden testing using SKAT. Candidate survival genes UNC13A, KIFAP3, and EPHA4 were tested for association in a UK sample comprising 25 short survivors and 25 long survivors. Results showed that only SNVs in UNC13A were associated with survival (p = 6.57 × 10-3). SNV rs10419420:G > A was found exclusively in long survivors (3/25) and rs4808092:G > A exclusively in short survivors (4/25). These findings were not replicated in a Dutch sample. In conclusion, population specific rare variants of UNC13A may modulate survival in ALS.