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Endothelial dysfunction represents a potential pathomechanism of neurological post-COVID-19 syndrome (PCS). A recent study demonstrated reduced cerebrovascular reactivity (CVR) in patients with PCS. The aim of this pilot study was to prospectively assess CVR in patients with PCS using breath-hold functional MRI (bh-fMRI). Fourteen patients with neurological PCS and leading symptoms of fatigue/memory issues/concentration disorder (PCSfmc), 11 patients with PCS and leading symptoms of myopathy/neuropathy (PCSmn), and 17 healthy controls underwent bh-fMRI. Signal change and time to peak (TTP) were assessed globally and in seven regions of interest and compared between the subgroups using one-way ANCOVA adjusting for age, time since infection, Fazekas score, and sex. No significant differences were observed. In PCS patients, the global CVR exhibited a slight, non-significant tendency to be lower compared to healthy controls (PCSfmc: 0.78 ± 0.11%, PCSmn: 0.84 ± 0.10% and 0.87 ± 0.07%). There was a non-significant trend towards lower global TTP values in the PCS subgroups than in the control group (PCSfmc: 26.41 ± 1.39 s, PCSmn: 26.32 ± 1.36 s versus 29.52 ± 0.93 s). Endothelial dysfunction does not seem to be the sole pathomechanism of neurological symptoms in PCS. Further studies in larger cohorts are required. [ABSTRACT FROM AUTHOR]

Simple Summary: The identification of gliomas and the differentiation between different types is essential to evaluate patients' prognosis and guide optimal clinical management. The ideal multiparametric magnetic resonance imaging (MRI) protocol for the assessment of gliomas is a current topic of research. This study aimed to explore the performance of dynamic contrast-enhanced (DCE) MRI and diffusion kurtosis imaging (DKI) in differentiating molecular subtypes of adult-type diffuse gliomas. The results showed that a combined evaluation of DCE-MRI and DKI parameters reveals the best prediction of high-grade vs. low-grade gliomas, IDH1/2 wildtype vs. mutated gliomas, and astrocytomas/glioblastomas vs. oligodendrogliomas. The aim was to explore the performance of dynamic contrast-enhanced (DCE) MRI and diffusion kurtosis imaging (DKI) in differentiating the molecular subtypes of adult-type gliomas. A multicenter MRI study with standardized imaging protocols, including DCE-MRI and DKI data of 81 patients with WHO grade 2–4 gliomas, was performed at six centers. The DCE-MRI and DKI parameter values were quantitatively evaluated in ROIs in tumor tissue and contralateral normal-appearing white matter. Binary logistic regression analyses were performed to differentiate between high-grade (HGG) vs. low-grade gliomas (LGG), IDH1/2 wildtype vs. mutated gliomas, and high-grade astrocytic tumors vs. high-grade oligodendrogliomas. Receiver operating characteristic (ROC) curves were generated for each parameter and for the regression models to determine the area under the curve (AUC), sensitivity, and specificity. Significant differences between tumor groups were found in the DCE-MRI and DKI parameters. A combination of DCE-MRI and DKI parameters revealed the best prediction of HGG vs. LGG (AUC = 0.954 (0.900–1.000)), IDH1/2 wildtype vs. mutated gliomas (AUC = 0.802 (0.702–0.903)), and astrocytomas/glioblastomas vs. oligodendrogliomas (AUC = 0.806 (0.700–0.912)) with the lowest Akaike information criterion. The combination of DCE-MRI and DKI seems helpful in predicting glioma types according to the 2021 World Health Organization's (WHO) classification. [ABSTRACT FROM AUTHOR]

Background: The relationship between heart rate variability (HRV) changes potentially indicating autonomic dysregulation following spontaneous intracerebral hemorrhage (ICH) and functional outcome has not yet been fully elucidated. This study investigated the effects of HRV during the initial 96 h after admission on 90-day functional outcome in ICH patients. Methods: We included patients with spontaneous ICH in a prospective cohort single-center study. Continuous HR data were retrieved from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) and analyzed within the following time intervals: 0–2, 0–8, 0–12, 0–24, 0–48, 0–72, and 8–16, 16–24, 24–48, 48–72, 72–96 h after admission. HRV was determined from all available HR values by calculating the successive variability (SV), standard deviation (SD), and coefficient of variation (CV). Low HRV was set as SD ≤ 11.4 ms, and high HRV as SD > 11.4 ms. The clinical severity of ICH was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome using the modified Rankin Scale (mRS). Good functional outcome was defined as mRS 0–2. Results: The cohort included 261 ICH patients (mean age ± SD 69.6 ± 16.5 years, 48.7% female, median NIHSS 6 (2, 12), median ICH score 1 (0, 2), of whom 106 (40.6%) had good functional outcome. All patients had the lowest HRV at admission, which increased during the first two days. Comparing ICH patients with low HRV (n = 141) and high HRV (n = 118), those with good outcome showed significantly lower HRV during the first three days (0–72 h: HRV SD good outcome 10.6 ± 3.5 ms vs. poor outcome 12.0 ± 4.0 ms; p = 0.004). Logistic regression revealed that advanced age, high premorbid mRS, and high NIHSS at admission were significant predictors of poor functional outcome, while reduced SD of HRV showed a non-significant trend towards good functional outcome (0–72 h: OR 0.898; CI 0.800–1.008; p = 0.067). Conclusions: Our results indicate autonomic dysfunction with sympathetic hyperactivity after spontaneous ICH, as reflected by the evidence of the lower HRV in the first days. Initially increased sympathetic tone appears to have a protective effect, as suggested by the comparatively lower HRV in patients with good functional outcome at the first days. [ABSTRACT FROM AUTHOR]

Before revascularization, moyamoya patients require hemodynamic evaluation. In this study, we evaluated the scoring system Prior Infarcts, Reactivity and Angiography in Moyamoya Disease (PIRAMID). We also devised a new scoring system, MRI-Based Assessment of Risk for Stroke in Moyamoya Angiopathy (MARS-MMA), and compared the scoring systems with respect to the capability to predict impaired [15O]water PET cerebral perfusion reserve capacity (CPR). We evaluated 69 MRI, 69 DSA and 38 [15O]water PET data sets. The PIRAMID system was validated by ROC curve analysis with neurological symptomatology as a dependent variable. The components of the MARS-MMA system and their weightings were determined by binary logistic regression analysis. The comparison of PIRAMID and MARS-MMA was performed by ROC curve analysis. The PIRAMID score correlated well with the symptomatology (AUC = 0.784). The MARS-MMA system, including impaired breath-hold-fMRI, the presence of the Ivy sign and arterial wall contrast enhancement, correlated slightly better with CPR impairment than the PIRAMID system (AUC = 0.859 vs. 0.827, Akaike information criterion 140 vs. 146). For simplified clinical use, we determined three MARS-MMA grades without loss of diagnostic performance (AUC = 0.855). The entirely MRI-based MARS-MMA scoring system might be a promising tool to predict the risk of stroke. [ABSTRACT FROM AUTHOR]

Aim: To assess how atypical language organization after early left‐hemispheric brain lesions affects grey matter in the contralesional hemisphere. Method: This was a cross‐sectional study with between‐group comparisons of 14 patients (six female, 8–26 years) with perinatal left‐hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age‐matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left‐hemispheric language organization (six female, 8–28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right‐hemispheric grey matter group differences by voxel‐based morphometry (VBM). Results: FMRI revealed left‐dominance in seven patients with typical language organization (TYP) and right‐dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel‐based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. Interpretation: Compatible with a non‐specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. What this paper adds: Perinatal stroke leads to decreased grey matter in the contralesional hemisphere.Atypical language organization is associated with grey matter increases in contralesional language areas. [ABSTRACT FROM AUTHOR]

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: Little is known about the growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival., Methods: We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1 mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined by multivariable., Results: Out of 749 patients screened, 13 had ≥3 preoperative MRI, 70 had 2 MRI and met the inclusion criteria. A curve estimation regression model showed the best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho = -0.59, P  < .001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log-rank: P  = .010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox regression model for patients after tumor resection., Conclusions: Especially small lesions suggestive of glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample., Competing Interests: Gh.T. has served on advisory boards (Bayer, Boehringer Ingelheim, CureVac, Novocure), as a consultant (Bayer, Boehringer Ingelheim, CureVac), as steering committee member in non-interventional trials (Bayer, Novocure) and financial compensation for all these activities was provided as institutional funding., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs., Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion., Methods and Design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial., Study Outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted., Sample Size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation., Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia., Trial Registrations: ClinicalTrials.gov: NCT03500939; EudraCT: 2017-001355-31., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.