Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. METHODS: The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. DISCUSSION: Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Carnitine Intake and Serum Levels Associate Positively with Postnatal Growth and Brain Size at Term in Very Preterm Infants.

Carnitine has an essential role in energy metabolism with possible neuroprotective effects. Very preterm (VPT, <32 gestation weeks) infants may be predisposed to carnitine deficiency during hospitalization. We studied the associations of carnitine intake and serum carnitine levels with growth and brain size at term equivalent age (TEA) in VPT infants. This prospective cohort study included 35 VTP infants admitted to Kuopio University Hospital, Finland. Daily nutrient intakes were registered at postnatal weeks (W) 1 and 5, and serum carnitine levels were determined at W1, W5, and TEA. The primary outcomes were weight, length, and head circumference Z-score change from birth to TEA, as well as brain size at TEA in magnetic resonance imaging. Carnitine intake at W1 and W5, obtained from enteral milk, correlated positively with serum carnitine levels. Both carnitine intake and serum levels at W1, W5, and TEA showed a positive correlation with weight, length, and head circumference Z-score change and with brain size at TEA. In linear models, independent positive associations of carnitine intake and serum carnitine levels with length and head circumference Z-score change and brain size at TEA were seen. In VPT infants, sufficient carnitine intake during hospitalization is necessary since it is associated with better postnatal growth and larger brain size at term age.

Brain atrophy and neuropsychological outcome after treatment of ruptured anterior cerebral artery aneurysms: a voxel-based morphometric study.

INTRODUCTION: Cognitive impairment after aneurysmal subarachnoid hemorrhage (aSAH) is frequently detected. Here, we describe the pattern of cerebral (gray matter) atrophy and its clinical relevance after treatment of aSAH caused by a ruptured anterior cerebral artery (ACA) aneurysm. METHODS: Thirty-seven aSAH patients with ACA aneurysm (17 surgical, 20 endovascular treatment) and a good or moderate clinical outcome (Glasgow Outcome Scale V or IV) and 30 controls underwent brain MRI. Voxel-based morphometric analysis was applied to compare the patients and controls. Patients also underwent a detailed neuropsychological assessment. RESULTS: The comparisons between controls and either all patients (n = 37) or the subgroup of surgically treated patients (n = 17) revealed bilateral cortical atrophy in the frontal lobes, mainly in the basal areas. The brainstem, bilateral thalamic and hypothalamic areas, and ipsilateral caudate nucleus were also involved. Small areas of atrophy were detected in temporal lobes. The hippocampus and parahippocampal gyrus showed atrophy ipsilateral to the surgical approach. In the subgroup of endovascularly treated patients (n = 15), small areas of atrophy were detected in the bilateral orbitofrontal cortex and in the thalamic region. Twenty patients (54%) showed cognitive deficits in neuropsychological assessment. CONCLUSION: Group analysis after aSAH and treatment of the ruptured ACA aneurysm revealed gray matter atrophy, principally involving the frontobasal cortical areas and hippocampus ipsilateral to the surgical approach. Areas of reduced gray matter were more pronounced after surgical than endovascular treatment. Together with possible focal cortical infarctions and brain retraction deficits in individual patients, this finding may explain the neuropsychological disturbances commonly detected after treatment of ruptured ACA aneurysms.

MR imaging of the brain 1 year after aneurysmal subarachnoid hemorrhage: randomized study comparing surgical with endovascular treatment.

PURPOSE: To prospectively evaluate, with magnetic resonance (MR) imaging, long-term outcome of the brain after endovascular versus neurosurgical treatment for aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. One hundred sixty-eight (77 men, 91 women; mean age +/- standard deviation, 51 years +/- 13) patients were randomly assigned to surgical versus endovascular treatment of the ruptured aneurysm with 138 (67 endovascular, 71 surgical) MR examinations 1 year after aSAH. The presence, localization, volumes, and cause of lesions were analyzed with chi(2), Mann-Whitney U, and Student t tests. Furthermore, correlation between MR-detectable brain parenchymal high-signal intensity (SI) lesions on T2- and intermediate-weighted MR images and neuropsychologic outcome was evaluated by using Spearman correlation coefficient. RESULTS: Only 44 (31.9%) of 138 patients had no lesions associated with aSAH. According to intention to treat, lesions were more frequent after surgical rather than endovascular treatment, predominating in the frontal (surgical: n = 50, [70.4%] vs endovascular: n = 34 [50.7%], P = .018) and temporal (n = 34 [47.9%] vs n = 15 [22.4%], P = .002) lobes. Only endovascular patients had subtentorial lesions (n = 4 [6.0%], P = .037). Ischemic lesions in the parental artery territory were more frequent in surgical (n = 33 [46.5%]) than in endovascular (n = 15 [22.4%], P = .003) patients, with corresponding mean lesion volumes of 20.9 cm(3) +/- 46.5 versus 17.6 cm(3) +/- 35.8 (P = .209). Ischemic lesions in remote vascular territories were equal in frequency and size. Retraction injuries were common in the surgical (n = 40, [56.3%]) treatment group. Ischemic lesion volumes correlated with neuropsychologic test scores. CONCLUSION: Parenchymal high-SI lesions on T2- and intermediate-weighted MR images are more frequent after early surgical rather than endovascular treatment of the ruptured aneurysm, and lesion volumes correlate with the neuropsychologic test performance.