Patients with aneurysmal subarachnoid hemorrhage (aSAH) are at high risk of secondary ischemia, and timely insight into cerebral metabolism may improve clinical management. Cerebral microdialysis offers continuous metabolic monitoring but is invasive, focal, and confined to specialized centers. Peripheral blood and cerebrospinal fluid (CSF) could provide less invasive, more accessible surrogates for assessing cerebral metabolic status. This study aimed to evaluate glucose and lactate dynamics across blood, CSF, and brain parenchyma in patients with severe aSAH. A total of 39 patients with aSAH undergoing multimodal neuromonitoring were retrospectively analyzed. Glucose and lactate levels from plasma, CSF, and cerebral microdialysis were matched within 90-min intervals relative to each microdialysis measurement. Associations were analyzed using linear mixed-effects models. Plasma (p < 0.001) and CSF (p < 0.001) glucose levels were significantly associated with cerebral glucose concentrations. Moderate correlations were observed between plasma–brain (r = 0.54) and plasma–CSF (r = 0.55), while CSF–brain correlation was weaker (r = 0.36). For lactate, significant associations were found between CSF and brain (p = 0.04; r = 0.24) and between plasma and CSF (p < 0.001; r = 0.33), but plasma–brain lactate showed no significant relationship. The plasma–brain glucose association weakened slightly over time (p = 0.008) and strengthened during episodes of low brain tissue oxygenation (pbtO2 < 15 mm Hg; p = 0.01). Insulin had no effect on glucose relationships but significantly attenuated the plasma–brain lactate association (p < 0.001). The presence of metabolic crisis (lactate/pyruvate ratio > 40) strengthened the CSF–brain lactate association (p = 0.04). CSF cell count had no significant effect. In severe aSAH, glucose and lactate levels in blood and CSF reflect cerebral values in a compartment- and metabolite-specific manner, but with high variability influenced by clinical conditions. These findings suggest that blood and CSF provide only limited information about cerebral metabolism, highlighting the complementary value of cerebral microdialysis for individualized, brain-targeted monitoring.

An unimpaired neurological evaluation is essential for detecting delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. Nimodipine is currently the only drug approved for DCI prevention. Intravenous nimodipine infusion contains 23.7 vol% ethanol as an excipient, resulting in up to 45 g of ethanol being infused daily, which may interfere with neurological assessment. Therefore, we aimed to measure ethanol concentrations in plasma, cerebrospinal fluid (CSF), and brain parenchyma during the infusion of 0.5–2 mg of nimodipine per hour in aSAH patients to quantify the ethanol neuronal exposure. Ethanol concentrations were determined by headspace gas chromatography‐flame ionization detection in plasma and CSF and we set out brain parenchyma measurement using cerebral microdialysis, in 10 aSAH patients. In each compartment four samples were taken over a 6‐hour interval during steady‐state intravenous nimodipine infusion at four different doses (0.5, 1, 1.5 and 2 mg/hour). A total of 307 samples from plasma and CSF was measured. Ethanol levels were mostly below the quantification limit of 0.002 g/100 mL. In 36 samples ethanol concentration was ≥ 0.002 g/100 mL, ranging from 0.002 to 0.009 g/100 mL. These low values were not reproducible in a second measurement, suggesting these values likely reflected analytical variability rather than true ethanol concentrations. Nimodipine analysis in brain parenchyma was omitted due to insufficient microdialysate volume and low concentrations in blood and CSF. Continuous nimodipine infusion of up to 2 mg/hour is unlikely to impair neurological assessment in aSAH patients, as no significant CSF ethanol concentration (< 0.002 g/100 mL) was detected.

Achondroplasia is the most common skeletal dysplasia. With the development of new growth-promoting drug treatment for children and adolescents with achondroplasia, multidisciplinary care has become increasingly more important. In addition to orthopedic care, a specialized team comprised of pediatrics/endocrinology, radiology, neurosurgery, otorhinolaryngology, anesthesiology, physiotherapy, psychology and other disciplines is necessary to develop and implement a holistic concept to improve the quality of life for individuals affected by achondroplasia. The orthopedic management of achondroplasia has become even more complex and multidisciplinary due to these new medical and surgical developments. These new developments herald a new era of orthopedic and multidisciplinary care for achondroplasia.

INTRODUCTION:Here we present the case of a newborn baby boy with severe plasminogen deficiency causing occlusive hydrocephalus and ligneous conjunctivitis.CASE PRESENTATION:Shortly after birth, the hydrocephalus was treated with a ventriculoperitoneal shunt implantation. However, the child had to be readmitted soon afterward because of shunt obstruction. Subglottic microtrauma caused by the necessary intubations then led to another life-threatening complication - subglottic stenosis with pseudomembrane formation. Microsurgical removal had to be performed to secure the airway. Initially, regular plasma transfusions achieved slightly elevated plasminogen activity levels and short-term improvement of the respiratory situation. However, shunt dysfunction reoccurred, and alternative treatment options were needed. Since therapy with plasminogen concentrate is already available in the USA with encouraging results, this treatment option was organized in hopes of equally good results for this patient. Fortunately, under short-term substitution with plasminogen concentrates, the implantation of a new ventriculoperitoneal shunt was successful, and respiratory problems resolved.CONCLUSION:Plasminogen concentrates are critically needed in Europe and other parts of the world to improve the care of and prevent complications among patients with plasminogen deficiency.

Background: Linezolid exposure in critically ill patients is associated with high inter-individual variability, potentially resulting in subtherapeutic antibiotic exposure. Linezolid exhibits good penetration into the CSF, but its penetration into cerebral interstitial fluid (ISF) is unknown. Objectives: To determine linezolid penetration into CSF and cerebral ISF of neurointensive care patients. Patients and methods: Five neurocritical care patients received 600 mg of linezolid IV twice daily for treatment of extracerebral infections. At steady state, blood and CSF samples were collected from arterial and ventricular catheters, and microdialysate was obtained from a cerebral intraparenchymal probe. Results: The median fAUC(0-24) was 57.6 (24.9-365) mgh/L in plasma, 64.1 (43.5-306.1) mgh/L in CSF, and 27.0 (10.7-217.6) mgh/L in cerebral ISF. The median penetration ratio (fAUC(brain_or_CSF)/fAUC(plasma)) was 0.5 (0.25-0.81) for cerebral ISF and 0.92 (0.79-1) for CSF. Cerebral ISF concentrations correlated well with plasma (R = 0.93, P < 0.001) and CSF levels (R = 0.93, P < 0.001). The median fAUC(0-24)/MIC ratio was >= 100 in plasma and CSF for MICs of <= 0.5 mg/L, and in cerebral ISF for MICs of <= 0.25 mg/L. The median fT(>MIC) was >= 80% of the dosing interval in CSF for MICs of <= 0.5 mg/L, and in plasma and cerebral ISF for MICs of <= 0.25 mg/L. Conclusions: Linezolid demonstrates a high degree of cerebral penetration, and brain concentrations correlate well with plasma and CSF levels. However, substantial variability in plasma levels, and thus cerebral concentrations, may result in subtherapeutic tissue concentrations in critically ill patients with standard dosing, necessitating therapeutic drug monitoring.

INTRODUCTION Nimodipine is routinely administered to aneurysmal subarachnoid hemorrhage patients to improve functional outcomes. Nimodipine can induce marked systemic hypotension, which might impair cerebral perfusion and brain metabolism. METHODS Twenty-seven aneurysmal subarachnoid hemorrhage patients having multimodality neuromonitoring and oral nimodipine treatment as standard of care were included in this retrospective study. Alterations in mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), brain tissue oxygen tension (pbtO2), and brain metabolism (cerebral microdialysis), were investigated up to 120 minutes after oral administration of nimodipine (60 mg or 30 mg), using mixed linear models. RESULTS Three thousand four hundred twenty-five oral nimodipine administrations were investigated (126±59 administrations/patient). After 60 mg of oral nimodipine, there was an immediate statistically significant (but clinically irrelevant) drop in MAP (relative change, 0.97; P<0.001) and CPP (relative change: 0.97; P<0.001) compared with baseline, which lasted for the whole 120 minutes observation period (P<0.001). Subsequently, pbtO2 significantly decreased 50 minutes after administration (P=0.04) for the rest of the observation period; the maximum decrease was -0.6 mmHg after 100 minutes (P<0.001). None of the investigated cerebral metabolites (glucose, lactate, pyruvate, lactate/pyruvate ratio, glutamate, glycerol) changed after 60 mg nimodipine. Compared with 60 mg nimodipine, 30 mg induced a lower reduction in MAP (relative change, 1.01; P=0.02) and CPP (relative change, 1.01; P=0.03) but had similar effects on pbtO2 and cerebral metabolism (P>0.05). CONCLUSIONS Oral nimodipine reduced MAP, which translated into a reduction in cerebral perfusion and oxygenation. However, these changes are unlikely to be clinically relevant, as the absolute changes were minimal and did not impact cerebral metabolism.

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 (AUC0-24) 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) (AUCCSF/AUCplasma). In contrast, nimodipine levels were significantly lower in both plasma (AUC0-24 298.32 ± 206.52 mg*h/L) and CSF (AUC0-24 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.

Achondroplasie stellt die häufigste Skelettdysplasie dar. Mit der Entwicklung neuer wachstumsfördernder medikamentöser Therapien für Kinder und Jugendliche mit Achondroplasie rückt die multidisziplinäre Betreuung weiter in den Fokus der Aufmerksamkeit. Neben der orthopädischen Betreuung ist ein spezialisiertes Team, bestehend aus Pädiatrie/Endokrinologie, Radiologie, Neurochirurgie, HNO (Hals-Nasen-Ohren-Heilkunde), Anästhesie, Physiotherapie, Psychologie etc., nötig, um ein ganzheitliches Konzept zur Verbesserung der Lebensqualität von Achondroplasie betroffenen Personen zu erarbeiten und auch umzusetzen. Die orthopädische Betreuung der Achondroplasie ist durch die neuen medikamentösen und chirurgischen Entwicklungen noch komplexer und multidisziplinärer geworden. Diese neuen Entwicklungen leiten eine neue Ära der orthopädischen und multidisziplinären Betreuung der Achondroplasie ein.

Background: Spontaneous intracerebral hemorrhage (SICH) of the elderly is a devastating form of stroke with a high morbidity and economic burden. There is still a limited understanding of the risk factors for an unfavorable outcome where a surgical therapy may be less meaningful. Thus, the aim of this study is to identify factors associated with unfavorable outcome and time to death in surgically treated elderly patients with SICH. Methods: We performed a single-center retrospective study of 70 patients (age > 60 years) with SICH operated between 2008 and 2020. Functional outcome was assessed by modified Rankin Scale. Various clinical and neuroradiological variables including type of neurosurgical treatment, anatomical location of hemorrhage, volumetry and distribution of hemorrhage were assessed. Univariate and multivariate logistic regression models were performed. Length of stay (LOS) and hospital costs are presented. Results: The overall mortality (mean follow-up time of 22 months) in this study was 32/70 patients (45.71%), 30days mortality was 8/70 (11.42%), and 12-months mortality was 22/70 (31.43%). Average LOS was 73.5 days with a median of 58, 766 estimated in hospital costs per patient. Multivariate analysis for 12-months mortality was significant for intraventricular hemorrhage (IVH) (p = 0.007, HR = 1.021, 95% CI = 1.006 - 1.037). ROC analysis for 12-months mortality for IVH volume >= 7 cm3 presented an are under the curve of 0.658. Conclusions: We identified IVH volume > 7 cm3 as an independent prognostic risk factor for mortality in elderly patients after SICH. This may help clinicians in decision-making for this critical and growing subgroup of patients.

Background: High cerebrospinal fluid (CSF) sampling frequency is considered a risk factor for external ventricular drain (EVD)-associated infections. To reduce manipulation at the proximal port and potentially minimize the risk of an infection, we aimed to analyze whether CSF parameters sampled from the far distal collection bag could provide reliable results compared to the proximal port. Methods: We included patients who were treated with an EVD at our neurosurgical intensive care unit (ICU) between June 2021 and September 2022. CSF sampling, including microbiological analysis, was performed simultaneously from the proximal port and the collection bag. Spearman’s correlation coefficients were calculated to assess the correlation of CSF cell count, protein, lactate and glucose between the two sample sites. Results: We analyzed 290 pairs of CSF samples in 77 patients. Ventriculitis was identified in 4/77 (5%) patients. In 3/4 patients, microbiological analysis showed the same bacterial species at both sample sites at the same time. Spearman’s correlation coefficient showed that CSF cell count (r = 0.762), lactate (r = 0.836) and protein (r = 0.724) had a high positive correlation between the two collection sites, while CSF glucose (r = 0.663) showed a moderate positive correlation. Conclusion: This study shows that biochemical CSF parameters can be reliably assessed from the EVD collection bag.

OBJECTIVE:To present our experience with an individualized surgical approach to treat Chiari malformation type 1. METHODS:Based on (1) neurological symptoms, (2) the existence and extent of a syrinx and (3) the degree of the tonsillar descent we performed four types of approaches on a case-by-case basis in 81 patients: (1) foramen magnum decompression (FMD) with dura splitting (FMDds); (2) FMD with duraplasty (FMDdp); (3) FMD with duraplasty and tonsillar manipulation (FMDao); and (4) tonsillar resection/reduction (TR). Patient characteristics, Chiari Severity Index (CSI), fourth ventricular roof angle (FVRA) and Chicago Chiari Outcome Scale (CCOS) were analyzed. RESULTS:CCOS was between 13 and 16 points in 8/11 (73 %) patients after FMDds, 38/45 (84 %) patients after FMDdp, and 24/24 (100 %, one patient lost to follow-up) patients after TR. We experienced an overall complication rate of 13.6 % (11/81) in this series, whereas seven of these eleven complications (64 %) occurred in the FMDao group and the complication rate increased with the invasiveness of the approach (0 % FMDds; 4 % FMDdp; 12 % TR). CONCLUSION:Given the clear correlation between the extend of the approach and the complication rate the least invasive approach necessary to achieve clinical improvement should be selected. Due to the high complication rates, FMDao should not be used as a treatment option. The severity of the tonsillar descent, basilar invagination and current CM1 scores could be used to aid in the approach selection.

Abstract Langerhans cell histiocytosis (LCH) is a rare neoplasm predominantly affecting children. It occupies a hybrid position between cancers and inflammatory diseases, which makes it an attractive model for studying cancer development. To explore the molecular mechanisms underlying the pathophysiology of LCH and its characteristic clinical heterogeneity, we investigated the transcriptomic and epigenomic diversity in primary LCH lesions. Using single-cell RNA sequencing, we identified multiple recurrent types of LCH cells within these biopsies, including putative LCH progenitor cells and several subsets of differentiated LCH cells. We confirmed the presence of proliferative LCH cells in all analyzed biopsies using IHC, and we defined an epigenomic and gene-regulatory basis of the different LCH-cell subsets by chromatin-accessibility profiling. In summary, our single-cell analysis of LCH uncovered an unexpected degree of cellular, transcriptomic, and epigenomic heterogeneity among LCH cells, indicative of complex developmental hierarchies in LCH lesions. Significance: This study sketches a molecular portrait of LCH lesions by combining single-cell transcriptomics with epigenome profiling. We uncovered extensive cellular heterogeneity, explained in part by an intrinsic developmental hierarchy of LCH cells. Our findings provide new insights and hypotheses for advancing LCH research and a starting point for personalizing therapy. See related commentary by Gruber et al., p. 1343. This article is highlighted in the In This Issue feature, p. 1325

ObjectivesThe development of persistent hydrocephalus in patients after spontaneous intracerebral hemorrhage (ICH) is still poorly understood, and many variables predicting the need for a cerebrospinal fluid (CSF)-shunt have been described in the literature with varying results. The aim of this study is to find predictive factors for shunt dependency.MethodsWe performed a retrospective, single-center study of 99 neurosurgically treated patients with spontaneous ICH. Variables, including age, Glasgow Coma Scale (GCS), intraventricular hemorrhage (IVH), location of hemorrhage, acute hydrocephalus, and volumetric analysis of IVH, ICH, and intraventricular CSF were compared between patients with and without CSF-shunt implantation. Furthermore, receiver operating characteristics (ROC) for ICH, IVH, and intraventricular CSF volume parameters were calculated.ResultsCSF-shunt implantation was performed significantly more often in patients after thalamic (p = 0.03) and cerebellar ICH (p = 0.04). Moreover, a lower ratio between the total hemorrhage volume and intraventricular CSF volume (p = 0.007), a higher IVH distribution in the third ventricle, and an acute hydrocephalus (p < 0.001) with an increased intraventricular CSF volume (p < 0.001) were associated with shunt dependency. Our ROC model demonstrated a sensitivity of 82% and a specificity of 65% to predict the necessity for a shunt at a cutoff value of 1.9 with an AUC of 0.835.ConclusionVolumetric analysis of ICH, IVH, and intraventricular CSF may improve the prediction of CSF shunt implantation in patients with spontaneous ICH.

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.

Abstract OBJECTIVES To assesses the postoperative outcome and the applicability of current Chiari 1 malformation (CM1) scores in a tailored surgical treatment approach in patients with CM1. METHODS This retrospective single center study analyzed 81 surgically treated patients between 2000 and 2020. Based on our institutional policy, four types of approaches were performed in that period based on a case by case decision: 1) Foramen magnum decompression (FMD) with dura splitting (FMDds), 2) FMD with duraplasty (FMDdp), 3) FMD with duraplasty and tonsillar manipulation (FMDao) and 4) tonsillar resection/reduction (TR). Patient characteristics, the Chicago Chiari Outcome Scale (CCOS), Chiari Severity Index (CSI), and the fourth ventricular roof angle (FVRA) were compared among the four groups to establish a treatment algorithm. RESULTS FMDds, FMDdp, FMDao and TR was performed in 11 (14%), 24 (30%), 21 (26%) and 25 (31%) patients, respectively. After a mean follow-up time of 6.6 years, 8/11 (73%), 19/24 (79%), 19/21 (90%) and 24/24 (100%) patients had a CCOS of 13–16 points after FMDds, FMDdp, FMDao and TR, respectively. Overall, 6/11 (55%), 4/17 (24%), 3/18 (17%) and 7/24 (29%) patients had a CSI grade 1 before FMDds, FMDdp, FMDao and TR. A weak negative and statistically not significant correlation between CCOS and CSI was observed (p = 0.07, n = 69). The preoperative FVRA was < 65° in 9/11 (82%), 13/15 (87%), 7/14 (50%) and 13/22 (59%) patients after FMDds, FMDdp, FMDao and TR, respectively. Despite the proportion of patients with a FVRA of < 65° decreasing with a more invasive surgical technique, differences between the surgical groups were statistically not significant (p = 0.45). CONCLUSIONS An individualized surgical approach in patients with CM1 is safe and effective. Currently available scores, such as the CSI and FVRA, may be used to determine the appropriate surgical approach for patients with CM1.

Objective This systematic comparison between pre- and postnatal imaging findings and postnatal motor outcome assesses the reliability of MRI accuracy in the prognostication of the future long-term (mean, 11.4 years) ambulatory status in a historic group of postnatally repaired myelomeningocele (MMC) cases. Methods A retrospective, single-center study of 34 postnatally repaired MMC patients was performed. We used fetal and postnatal magnetic resonance imaging (MRI) to compare the fetal and postnatal radiological lesion level to each other and to the postnatal ambulatory level as a standard of reference and analyzed Chiari II malformation characteristics. Results In 13/15 (87%) and 29/31 (94%) cases, the functional level was equal to or better than the prenatal and postnatal radiological lesion level. A radiological lesion level agreement within two segments could be achieved in 13/15 (87%) patients. A worse than expected functional level occurred in cases with Myelocele (2/3 patients), coexistent crowding of the posterior fossa (2/3 patients) and/or abnormal white matter architecture, represented by callosal dysgenesis (1/3 patients). In all patients (2/2) with a radiological disagreement of more than two segments, segmentation disorders and scoliosis were observed. Conclusion Fetal and postnatal MRI are predictive of the long-term ambulatory status in postnatally repaired MMC patients.

Objectives: Multiple risk factors have been described to be related to external ventricular drain (EVD) associated infections, with results varying between studies. Former studies were limited by a non-uniform definition of EVD associated infection, thus complicating a comparison between studies. In this regard, we assessed risk factors promoting EVD associated infections and propose a modified practice-oriented definition of EVD associated infections.Methods: We performed a retrospective, single-center study on patients who were treated with an EVD, at the neurosurgical intensive care unit (ICU) at a tertiary center between 2008 and 2019. Based on microbiological findings and laboratory results, patients were assigned into an infection and a non-infection group. Patient characteristics and potential risk factors were compared between the two groups (p < 0.05). Receiver operating characteristics (ROC) for significant clinical, serum laboratory and cerebrospinal fluid (CSF) parameters were calculated.Results: In total, 396 patients treated with an EVD were included into the study with a mean age of 54.3 (range: 18–89) years. EVD associated infections were observed in 32 (8.1%) patients. EVD insertion at another hospital (OR 3.86), and an increased CSF sampling frequency of more than every third day (OR 12.91) were detected as major risk factors for an EVD associated infection. The indication for EVD insertion, surgeon's experience, the setting of EVD insertion (ICU vs. operating room) and the operating time did not show any significant differences between the two groups. Furthermore, ROC analysis showed that clinical, serum laboratory and CSF parameters did not provide specific prediction of EVD associated infections (specificity 44.4%). This explains the high overtreatment rate in our cohort with the majority of our patients who received intrathecal vancomycin (63.3%), having either negative microbiological results (n = 12) or were defined as contaminations (n = 7).Conclusions: Since clinical parameters and blood analyzes are not very predictive to detect EVD associated infections in neurosurgical patients, sequential but not too frequent microbiological and laboratory analysis of CSF are still necessary. Furthermore, we propose a uniform classification for EVD associated infections to allow comparability between studies and to sensitize the treating physician in determining the right treatment.

OBJECTIVE:Intrahospital transport for CT scans is routinely performed for neurosurgical patients. Particularly in the sedated and mechanically ventilated patient, intracranial hypertension and blood pressure fluctuations that might impair cerebral perfusion are frequently observed during these interventions. This study quantifies the impact of intrahospital patient transport on multimodality monitoring measurements, with a particular focus on cerebral metabolism. METHODS:Forty intrahospital transports in 20 consecutive patients suffering severe aneurysmal subarachnoid hemorrhage (SAH) under continuous intracranial pressure (ICP), brain tissue oxygen tension (pbtO2), and cerebral microdialysis monitoring were prospectively included. Changes in multimodality neuromonitoring data during intrahospital transport to the CT scanner and the subsequent 10 hours were evaluated using linear mixed models. Furthermore, the impact of risk factors at transportation, such as cerebral vasospasm, cerebral hypoxia (pbtO2 < 15 mm Hg), metabolic crisis (lactate-pyruvate ratio [LPR] > 40), and transport duration on cerebral metabolism, was analyzed. RESULTS:During the transport, the mean ICP significantly increased from 7.1 ± 3.9 mm Hg to 13.5 ± 6.0 mm Hg (p < 0.001). The ICP exceeded 20 mm Hg in 92.5% of patients; pbtO2 showed a parallel rise from 23.1 ± 13.3 mm Hg to 28.5 ± 23.6 mm Hg (p = 0.02) due to an increase in the fraction of inspired oxygen during the transport. Both ICP and pbtO2 returned to baseline values thereafter. Cerebral glycerol significantly increased from 71.0 ± 54.9 µmol/L to 75.3 ± 56.0 µmol/L during the transport (p = 0.01) and remained elevated for the following 9 hours. In contrast, cerebral pyruvate and lactate levels were stable during the transport but showed a significant secondary increase 1-8 hours and 2-9 hours, respectively, thereafter (p < 0.05). However, the LPR remained stable over the entire observation period. Patients with extended transport duration (more than 25 minutes) were found to have significantly higher levels of cerebral pyruvate and lactate as well as lower glutamate concentrations in the posttransport period. CONCLUSIONS:Intrahospital transport and horizontal positioning during CT scans induce immediate intracranial hypertension and an increase in cerebral glycerol, suggesting neuronal injury. Afterward, sustained impairment of neuronal metabolism for several hours could be observed, which might increase the risk of secondary ischemic events. Therefore, intrahospital transport for neuroradiological imaging should be strongly reconsidered and only indicated if the expected benefit of imaging results outweighs the risks of transportation.

BACKGROUND Inadequate antibiotic exposure in cerebral infections might have detrimental effects on clinical outcome. Commonly, antibiotic concentrations within the CSF were used to estimate cerebral target levels. However, the actual pharmacological active unbound drug concentration beyond the blood-brain barrier is unknown. OBJECTIVES To compare meropenem concentrations in blood, CSF and cerebral microdialysate of neurointensive care patients. PATIENTS AND METHODS In 12 patients suffering subarachnoid haemorrhage, 2000 mg of meropenem was administered every 8 h due to an extracerebral infection. Meropenem concentrations were determined in blood, CSF and cerebral microdialysate at steady state (n = 11) and following single-dose administration (n = 5). RESULTS At steady state, the free AUC0-8 was 233.2 ± 42.7 mg·h/L in plasma, 7.8 ± 1.9 mg·h/L in CSF and 26.6 ± 14.0 mg·h/L in brain tissue. The brain tissue penetration ratio (AUCbrain/AUCplasma) was 0.11 ± 0.06, which was more than 3 times higher than in CSF (0.03 ± 0.01), resulting in an AUCCSF/AUCbrain ratio of 0.41 ± 0.16 at steady state. After single-dose administration similar proportions were achieved (AUCbrain/AUCplasma = 0.09 ± 0.08; AUCCSF/AUCplasma = 0.02 ± 0.00). Brain tissue concentrations correlated well with CSF concentrations (R = 0.74, P < 0.001), but only moderately with plasma concentrations (R = 0.51, P < 0.001). Bactericidal thresholds were achieved in both plasma and brain tissue for MIC values ≤16 mg/L. In CSF, bactericidal effects were only reached for MIC values ≤1 mg/L. CONCLUSIONS Meropenem achieves sufficient bactericidal concentrations for the most common bacterial strains of cerebral infections in both plasma and brain tissue, even in non-inflamed brain tissue. CSF concentrations would highly underestimate the target site activity of meropenem beyond the blood-brain barrier.