Trimethylamine-N-oxide is elevated in the acute phase after ischaemic stroke and decreases within the first days.

BACKGROUND AND PURPOSE: Trimethylamine-N-oxide (TMAO) is a biomarker of the gut microbiome and correlates with the risk of cardiovascular diseases. However, conflicting data exist on the specific role of TMAO in ischaemic stroke patients. We aimed to analyze the time course of TMAO levels in stroke patients compared with controls. METHODS: In this prospective, case-control study, patients suffering from ischaemic stroke (onset <24 h) and control patients with less than two cardiovascular risk factors were enrolled. Plasma TMAO levels were analyzed on admission, after 48 h and after 3 months. The primary endpoint was the difference in TMAO levels on admission between stroke patients and controls. RESULTS: A total of 196 patients with ischaemic stroke and 100 controls were included between February 2018 and April 2019. Plasma TMAO levels on admission were significantly higher in stroke patients than in controls [median value 4.09 (2.87-6.49) vs. 3.16 (2.08-5.16) µmol/L, P = 0.001]. There was a significant decrease in TMAO levels in stroke patients after 48 h [median at 48 h, 3.49 (2.30-5.39) µmol/L, P = 0.027]. TMAO levels increased again 3 months after stroke [median 4.23 (2.92-8.13) µmol/L, P = 0.047]. In controls, TMAO levels did not change between admission and after 48 h [median at 48 h, 3.14 (1.63-4.61) µmol/L, P = 0.11]. An inverse correlation between TMAO values and kidney function was found (Spearman rho -0.334, P < 0.001). CONCLUSIONS: Our study emphasizes the importance of the time course of TMAO levels after ischaemic stroke. Future studies should define the time point of TMAO analysis, preferably in the acute phase (<24 h).

Increased volumes of mildly elevated capillary transit time heterogeneity positively predict favorable outcome and negatively predict intracranial hemorrhage in acute ischemic stroke with large vessel occlusion.

OBJECTIVES: In patients with acute ischemic stroke, we aimed to investigate whether microvascular changes, as indexed by capillary transit time heterogeneity (CTH), contribute to the decline of the chance for favorable outcome over time and whether they are a predictor of an intracranial hemorrhage (ICH). METHODS: We retrospectively calculated CTH maps for 131 consecutive patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation who had a relevant MRI PWI-DWI mismatch and were treated with endovascular thrombectomy (ET). Multivariable logistic regressions were conducted with favorable outcome (mRS ≤ 2 after 3 months) and occurrence of an ICH as dependent variables and the volume of mildly elevated CTH as independent variable adjusted for age, successful recanalization, hypertension, diabetes, atrial fibrillation, NIHSS score on admission, DWI lesion volume, and symptom-onset-to-treatment time (OTT). RESULTS: A larger volume of mildly elevated CTH was a positive predictor of favorable outcome (OR 1.17; 1.03-1.33; p = 0.019) and a negative predictor of ICH (OR 0.83; 0.73-0.96; p = 0.009). As expected, successful recanalization (OR 5.54; 1.8-17; p = 0.003), low NIHSS on admission (OR 0.9; 0.82-1.00; p = 0.045), short OTT (OR 0.96; 0.94-0.99; p = 0.006), and low DWI volume (OR 0.68; 0.49-0.94; p = 0.021) were also predictors of favorable outcome, whereas other negative predictors of ICH were atrial fibrillation (OR 2.69; 1.10-6.57; p = 0.030), high NIHSS score on admission (OR 1.10 (1.01-1.19); p = 0.030), and large DWI volume (OR 1.51; 1.17-1.19; p = 0.002). CONCLUSION: An increased volume of mildly elevated CTH is a positive predictor of favorable outcome and a negative predictor for ICH in patients with acute ischemic stroke and mismatch undergoing ET. KEY POINTS: • The classification of potentially salvageable tissue and infarct core based on traditional net perfusion parameters (as Tmax or CBF) does not account for the microvascular distribution of blood. • However, the microvascular distribution of blood, as indexed by the capillary transit time heterogeneity (CTH), directly affects the availability of oxygen within the hypoperfused tissue and should therefore be respected in acute ischemic stroke imaging. • In our study, mildly elevated CTH is found to be a positive predictor for a favorable clinical outcome and a negative predictor for the occurrence of an intracranial hemorrhage in patients with acute ischemic stroke and homogenous mismatch who underwent ET.

Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. METHODS: This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. RESULTS: Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. CONCLUSIONS: Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.

Pulmonary and circulatory parameter guided anesthesia in patients with ischemic stroke undergoing endovascular recanalization.

BACKGROUND AND PURPOSE: Endovascular recanalization in ischemic stroke is often performed under general anesthesia. Some studies have shown a detrimental effect of general anesthesia. The reasons are unknown. METHODS: This was an observational study with retrospective and prospective phases. From 2008 to 2010, 60 patients treated by endovascular recanalization due to proximal vessel occlusion were analyzed with regard to ventilation parameters, blood gas values, blood pressure, and clinical parameters (pre-protocol phase). Subsequently, a protocol with target values for end-tidal CO2 (Petco2) and systolic blood pressure (SBP) was introduced and prospectively analyzed in 64 patients in 2012 (protocol phase). RESULTS: In the pre-protocol phase, significant hypocapnia (<30 mm Hg), a decrease in SBP after intervention (p<0.001), and an increase in SBP after extubation (p<0.001) were observed. After implementing the protocol in 2012, 63% of Petco2 values and 55% of SBP values (median) of the duration of intervention were within the predefined range. Severe hypocapnia and hypotension (SBP <100 mm Hg) after the intervention were significantly reduced. Longer duration of Petco2 values within 40-45 mm Hg, intracerebral hemorrhage, longer door to needle time, older age, unsuccessful recanalization, longer duration of endovascular treatment, and higher cumulative dose of norepinephrine were associated with an unfavorable outcome (modified Rankin Scale score >2). Intracerebral hemorrhage (OR 0.028, p=0.001), age (OR 0.9, p=0.013), and cumulative dose of norepinephrine (OR 0.142, p=0.003) were independent predictors of an unfavorable outcome. CONCLUSIONS: In patients receiving endovascular stroke treatment under general anesthesia, the cumulative dose of norepinephrine was an independent predictor of an unfavorable outcome. Further studies are needed to evaluate the optimal management of blood pressure in these patients, and whether avoidance of catecholamines could partly explain the improved outcomes for patients treated under conscious sedation in retrospective studies.

Posterior Circulation Acute Stroke Prognosis Early Computed Tomography Score Using Hypointense Vessels on Susceptibility Weighted Imaging Independently Predicts Outcome in Patients with Basilar Artery Occlusion.

PURPOSE: Appearance of hypointense vessels on susceptibility weighted imaging (SWI) has been reported to correlate with outcome in patients with ischemia of the anterior circulation. This study investigates the correlation between the appearance of hypointense vessels on SWI after recanalization therapy and outcome in patients with basilar artery occlusion. METHODS: Patients with basilar artery occlusion who were treated with endovascular recanalization or intravenous alteplase and received an MRI including SWI after therapy were retrieved from the hospital database for retrospective analysis. Posterior circulation Acute Stroke Prognosis Early Computed Tomography Score (pcASPECTS) was calculated based on regions displaying hypointense vessels on SWI and compared to lesions on diffusion weighted imaging (DWI). Subsequently, SWI based pcASPECTS was correlated with outcome determined with modified Rankin Scale (mRS), categorized as favorable outcome (mRS 0-2) or unfavorable outcome (3-6). RESULTS: Twenty-two MRI of patients with basilar artery occlusion were analyzed. In seven out of eight areas of the pcASPECTS hypointense vessels on SWI were significantly correlated to areas of restricted diffusion on DWI. In univariate analysis median pcASPECTS on SWI was significantly higher in patients with favorable outcome (7.5 vs. 5, p=0.02). In a multivariate analysis pcASPECTS on SWI was an independent predictor of favorable outcome (OR 2.02; CI [1.02;3,99]; p=0.04). CONCLUSION: pcASPECTS based on hypointense vessels on SWI after therapy predicts outcome in patients with basilar artery occlusion and might potentially be used as an additional imaging biomarker in the management of patients with stroke in the posterior circulation. This needs to be confirmed in larger prospective clinical trials.

GABA-B-receptor antibodies in paraneoplastic brainstem encephalitis.

BACKGROUND: Gamma-aminobutyric-acid B (GABA-B)-receptor encephalitis represents a novel entity among autoimmune CNS disorders. Most cases are characterised by limbic encephalitis. CASE REPORT: A 63-year-old patient presented with acute vertigo, nausea and vomiting, facial palsy and dysarthria. He developed dysphagia, gait ataxia and, finally, respiratory failure. Antibodies to GABA-B receptors were positive and declined under treatment with intravenous methylprednisolone and plasma exchange, followed by clinical improvement and stabilisation. Broad tumour screening revealed oesophageal carcinoma. CONCLUSION: The spectrum of neurological manifestations and tumours associated with the paraneoplastic variant of anti-GABA-B-receptor encephalitis may be broader than previously reported.