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Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients. Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT 2A receptor (5-HT 2A R) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels. Results: At D0, patients exhibited a lower ( p = 10 -5 ) platelet SERT density, higher ( p < 10 -6 ) platelet 5-HT 2A R density, higher ( p = 10 -5 ) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT ( p = 0.011) and 5-HIAA ( p = 0.003) levels than controls. Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saccaro, Pico, Chadenat, Richard, Launay, Bastenaire, Jullien, Lambert, Feuga, Macquet, Callebert, Lambert and Spreux-Varoquaux.)

Background: Clinical and biological risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis (IT) have been well-established in several registries. The added value of magnetic resonance imaging (MRI) variables has been studied in small samples, and is controversial. We aimed to assess the added value of MRI variables in HT, beyond that of clinical and biological factors. Methods: We enrolled 474 consecutive patients with brain infarction treated by IT alone at our primary stroke center between January 2011 and August 2017. Baseline demographic, clinical, biological, and imaging characteristics were collected. MRI variables were: brain infarction volume in cm 3 ; parenchymal fluid attenuated inversion recovery (FLAIR) hyperintensity; FLAIR hyperintense vessel signs; number of microbleeds; subcortical white matter hyperintensity; and thrombus length. Results: Overall, 301 patients were included out of 474 (64%). The main causes of exclusion were combined thrombectomy ( n = 98) and no MRI before IT ( n = 44). In the bivariate analysis, HT was significantly associated with the presence of more FLAIR hyperintense vessel signs, thrombus length (>8 mm), and larger brain infarction volume (diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) < 500 × 10 -6 mm 2 /s). In the multivariable analysis, only brain infarction volume was significantly associated with HT. The discrimination value of the multivariable model, including both the DWI volume and the clinical model (area under the receiver operating characteristic curve, 0.80; 95% confidence interval 0.74-0.86), was improved significantly compared with the model based only on clinical variables ( P = 0.012). Conclusions: Brain infarction volume on DWI was the only MRI variable that added value to clinico biological variables for predicting HT after IT.