Background/Objectives: Digital subtraction angiography (DSA) is the gold standard in the diagnosis of cerebral vasospasm, frequently observed after subarachnoid hemorrhage (SAH). However, less-invasive methods, such as computed tomography angiography (CTA), may be equally accurate. To further clarify comparability, this study evaluated the reliability of CTA in detecting cerebral vasospasm. Methods: This retrospective study included 51 patients with SAH who underwent both CTA and DSA within 24 h. The smallest diameter of the proximal cerebral arterial segments was measured in both modalities at admission and during the vasospasm period. The mean difference in diameter, the intraclass correlation coefficient (ICC) of CTA and DSA, the difference in grade of vasospasm and sensitivity, the specificity and the positive predictive value (PPV) for CTA were calculated. Results: A total of 872 arterial segments were investigated. At time of admission, arterial diameters were significantly smaller on CTA compared to DSA in all segments (−0.26 ± 0.12 mm; p < 0.05). At time of suspected vasospasm (day 9 ± 5), these differences remained significant only for the M1 segment (−0.18 ± 0.37 mm, p = 0.02), the P1 segment (−0.13 ± 0.24 mm, p = 0.04) and the basilar artery (−0.20 ± 0.37 mm, p = 0.0.04). The ICC between CTA and DSA was good (0.5–0.8). The sensitivity of CTA for predicting angiographic vasospasm was 99%, the specificity was 50% and the PPV was 92%. Conclusions: Arterial diameters measured on CTA may underestimate the arterial caliber observed in DSA; however, these absolute differences were minor. Importantly, vessel diameter alone does not fully reflect malperfusion, requiring additional imaging techniques such as CT perfusion.
There is accumulating evidence that cerebrospinal fluid (CSF) concentrations of nimodipine correlate with long‐term outcome of patients after subarachnoidal hemorrhage (aSAH) by impeding cerebral ischemia. However, pharmacological data on simultaneous serum vs. CSF and intraparenchymal nimodipine values are rarely reported in larger patient groups. Nimodipine concentrations were determined in plasma, CSF, and cerebral interstitial fluid (ISF), at steady state after oral (6 × 60 mg/day) and intravenous (0.5, 1, 1.5 and 2 mg/h) administrations in 10 patients after aSAH. Area under the concentration time curve (AUC 0–24 ) for intravenous nimodipine was highest at an infusion rate of 2 mg/h in plasma (1335.87 ± 591.09 mg*h/L), followed by CSF (39.53 ± 23.07 mg*h/L), resulting in an overall CSF penetration ratio of 3.8% (±1.5) (AUC CSF /AUC plasma ). In contrast, nimodipine levels were significantly lower in both plasma (AUC 0–24 298.32 ± 206.52 mg*h/L) and CSF (AUC 0–24 34.8 ± 16.56 mg*h/L) after oral administration. In cerebral ISF, low amounts of nimodipine were detectable in only 4 patients at an infusion rate of 1.5 and 2 mg/h as well as following oral administration. We found significantly higher CSF nimodipine levels in patients during intravenous compared to oral administration. In contrast, only low amounts of nimodipine were detected in the ISF after both oral and intravenous administration. Our findings strongly suggest that the main clinical nimodipine effect of impeding life threatening cerebral ischemia is mediated through significant higher CSF levels after intravenous administration, more likely effective than oral administration.
Abstract Embryonal tumor with multilayered rosettes (ETMR) is a distinct central nervous system tumor entity which is characterized by dysregulation of oncogenic micro RNAs (miRNA). In the majority of cases (approx. 90%), tumors are characterized by amplification of the C19MC locus accompanied by a fusion of this locus to the TTYH1 gene. Beside the very young age of the patients, ETMR is a highly aggressive brain tumor with a dismal clinical outcome. About half of the patients relapse within the first 6 months despite intensive therapy. Based on these facts, a more rapid diagnosis as well as more accurate and faster detection of tumor response or tumor relapse would significantly improve the management of these severely affected young patients. Liquid biopsy has emerged as a highly promising tool to enable minimal invasive detection of molecular parameters to facilitate diagnosis and patient monitoring. Here, we developed a miRNA based liquid biopsy tool and performed a comprehensive profiling of the miRNA landscape in 11 ETMR tumor tissues and matching liquid biopsy samples of patients. The screening of the initial liquid biopsy samples (plasma or serum) taken at diagnosis revealed distinctly enriched miRNA levels. Further, we evaluated the use of the miRNA levels as a longitudinal tumor-monitoring tool. We detected decreasing levels after tumor resection and in long-term survivors and vice versa increasing levels in patients with progressive tumor disease. In conclusion, we developed a reliable and fast method with a turnaround time of only 4 hours between blood draw and analysis of the aberrant expressed miRNA in liquid biopsy samples of ETMR patients correlating with the clinical course of the individual patient.
Meropenem is a broad spectrum carbapenem used for the treatment of cerebral infections. There is a need for data describing meropenem pharmacokinetics (PK) in the brain tissue to optimize therapy in these infections. Here, we present a meropenem PK model in the central nervous system and simulate dosing regimens. This was a population PK analysis of a previously published prospective study of patients admitted to the neurointesive care unit between 2016 and 2019 who received 2 g of meropenem intravenously every 8 h. Meropenem concentration was determined in blood, cerebrospinal fluid (CSF), and brain microdialysate. Meropenem was described by a six-compartment model: two compartments in the blood, two in the CSF, and two in the brain tissue. Creatinine clearance and brain glucose were included as covariates. The median elimination rate constant was 1.26 h-1, the central plasma volume was 5.38 L, and the transfer rate constants from the blood to the CSF and from the blood to the brain were 0.001 h-1 and 0.02 h-1, respectively. In the first 24 h, meropenem 2 g, administered every 8 h via intermittent and extended infusions achieved good target attainment in the CSF and brain, but continuous infusion (CI) was better at steady-state. Administering a 3 g loading dose (LD) followed by 8 g CI was beneficial for early target attainment. In conclusion, a meropenem PK model was developed using blood, CSF, and brain microdialysate samples. An 8 g CI may be needed for good target attainment in the CSF and brain. Giving a LD prior to the CI improved the probability of early target attainment.
