Risk factors for unfavorable outcome after spontaneous intracerebral hemorrhage in elderly patients.

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%), 30-days 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.

Linezolid brain penetration in neurointensive care patients.

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 fAUC0-24 was 57.6 (24.9-365) mg·h/L in plasma, 64.1 (43.5-306.1) mg·h/L in CSF, and 27.0 (10.7-217.6) mg·h/L in cerebral ISF. The median penetration ratio (fAUCbrain_or_CSF/fAUCplasma) 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 fAUC0-24/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.

Persistent Hydrocephalus, Shunt, and Subglottic Stenosis in a Newborn with Plasminogen Deficiency due to Delayed Treatment with Plasminogen Concentrates: A Case Report.

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.

Where to Draw Cerebrospinal Fluid from an External Ventricular Drain? Comparison of Cerebrospinal Fluid Parameters between Two Different Collection Sites.

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.

The Effect of Oral Nimodipine on Cerebral Metabolism and Hemodynamic Parameters in Patients Suffering Aneurysmal Subarachnoid Hemorrhage.

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.

Individualized surgical treatment of Chiari 1 malformation: A single-center experience.

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.

Predicting the need for cerebrospinal fluid shunt implantation after spontaneous intracerebral hemorrhage: a challenging task.

Objectives: The 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. Methods: We 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. Results: CSF-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. Conclusion: Volumetric analysis of ICH, IVH, and intraventricular CSF may improve the prediction of CSF shunt implantation in patients with spontaneous ICH.

Denosumab for Prevention of Acute Onset Immobilization-Induced Alterations of Bone Turnover: A Randomized Controlled Trial.

Metabolic bone disease is a devastating condition in critically ill patients admitted to an intensive care unit (ICU). We investigated the effects of early administration of the antiresorptive drug denosumab on bone metabolism in previously healthy patients. Fourteen patients with severe intracerebral or subarachnoid hemorrhage were included in a phase 2 trial. Within 72 hours after ICU admission, they were randomized in a 1:1 ratio to receive denosumab 60 mg or placebo subcutaneously. The primary endpoint was group differences in the percentage change of C-terminal telopeptide of type 1 collagen (CTX-1) levels in serum from denosumab/placebo application to 4 weeks thereafter. Changes in serum levels of bone formation markers and urinary calcium excretion were secondary outcome parameters. Regarding serum levels of CTX-1, changes over time averaged -0.45 ng/mL (95% confidence interval [CI] -0.72, -0.18) for the denosumab group and 0.29 ng/mL (95% CI -0.01, 0.58) for the placebo group. The primary endpoint, the group difference in changes between baseline and secondary measurement, adjusted for baseline serum levels and baseline neurological status, averaged -0.74 ng/mL (95% CI -1.14, -0.34; p = 0.002). The group difference in changes between baseline and secondary osteocalcin measurement averaged -5.60 ng/mL (95% CI -11.2, -0.04; p = 0.049). The group difference in averaged change between baseline and secondary measurement of 24-hour urine calcium excretion was significant (-1.77 mmol/L [95% CI -3.48, -0.06; p = 0.044]). No adverse events could be attributed to the study medication. The investigation proved that a single application of denosumab early after admission to an ICU prevents acute immobilization-associated increase in bone resorption among previously healthy individuals. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Meropenem Population Pharmacokinetics and Simulations in Plasma, Cerebrospinal Fluid, and Brain Tissue.

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.

Brain Tissue Oxygen Response as Indicator for Cerebral Lactate Levels in Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Early detection of cerebral ischemia and metabolic crisis is crucial in critically ill subarachnoid hemorrhage (SAH) patients. Variable increases in brain tissue oxygen tension (PbtO2) are observed when the fraction of inspired oxygen (FiO2) is increased to 1.0. The aim of this prospective study was to evaluate whether a 3-minute hyperoxic challenge can identify patients at risk for cerebral ischemia detected by cerebral microdialysis. METHODS: Twenty consecutive severe SAH patients undergoing continuous cerebral PbtO2 and microdialysis monitoring were included. FiO2 was increased to 1.0 for 3 minutes (the FiO2 challenge) twice a day and PbtO2 responses during the FiO2 challenges were related to cerebral microdialysis-measures, ie, lactate, the lactate-pyruvate ratio, and glycerol. Multivariable linear and logistic regression models were created for each outcome parameter. RESULTS: After predefined exclusions, 274 of 400 FiO2 challenges were included in the analysis. Lower absolute increases in PbtO2 (∆PbtO2) during FiO2 challenges were significantly associated with higher cerebral lactate concentration (P<0.001), and patients were at higher risk for ischemic lactate levels >4 mmol/L (odds ratio 0.947; P=0.04). Median (interquartile range) ∆PbtO2 was 7.1 (4.6 to 12.17) mm Hg when cerebral lactate was >4 mmol/L and 10.2 (15.76 to 14.24) mm Hg at normal lactate values (≤4 mmol/L). Median ∆PbtO2 was significantly lower during hypoxic than during hyperglycolytic lactate elevations (4.6 vs. 10.6 mm Hg, respectively; P<0.001). Lactate-pyruvate ratio and glycerol levels were mainly determined by baseline characteristics. CONCLUSIONS: A 3-minute FiO2 challenge is an easy to perform and feasible bedside diagnostic tool in SAH patients. The absolute increase in PbtO2 during the FiO2 challenge might be a useful surrogate marker to estimate cerebral lactate concentrations and might be used to identify patients at risk for impending ischemia.

Feasibility of intraoperative motor evoked potential monitoring during tethered cord surgery in infants younger than 12 months.

PURPOSE: Feasibility, reliability, and safety assessment of transcranial motor evoked potentials (MEPs) in infants less than 12 months of age. METHODS: A total of 22 patients with a mean age of 33 (range 13-49) weeks that underwent neurosurgery for tethered cord were investigated. Data from intraoperative MEPs, anesthesia protocols, and clinical records were reviewed. Anesthesia during surgery was maintained by total intravenous anesthesia (TIVA). RESULTS: MEPs were present in all patients for the upper extremities and in 21 out of 22 infants for the lower extremities. Mean baseline stimulation intensity was 101 ± 20 mA. If MEPs were present at the end of surgery, no new motor deficit occurred. In the only case of MEP loss, preoperative paresis was present, and high baseline intensity thresholds were needed. MEP monitoring did not lead to any complications. TIVA was maintained with an average propofol infusion rate of 123.5 ± 38.2 µg/kg/min and 0.46 ± 0.17 µg/kg/min for remifentanil. CONCLUSION: In spinal cord release surgery, the use of intraoperative MEP monitoring is indicated regardless of the patient's age. We could demonstrate the feasibility and safety of MEP monitoring in infants if an adequate anesthetic regimen is applied. More data is needed to verify whether an irreversible loss of robust MEPs leads to motor deficits in this young age group.

Risk Factors Promoting External Ventricular Drain Infections in Adult Neurosurgical Patients at the Intensive Care Unit-A Retrospective Study.

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.

Quantitative analysis of human brain microdialysate for target site pharmacokinetics of major anesthetics ketamine, midazolam and propofol.

Brain microdialysis samples of intensive care patients treated with the essential anesthetics ketamine, midazolam and propofol were investigated. Importantly, despite decades of clinical use, comprehensive human cerebral pharmacokinetic data of these drugs is still missing. To encounter this apparent lack of knowledge, we combined cerebral microdialysis with leading-edge analytical instrumentation to monitor the neurochemistry of living human patients. For the quantitative analysis, high performing analytical approaches were developed that can handle minute sample volumes and possible ultralow target analyte levels. The developed methods provided detection limits below 100 ng L-1 for all target analytes and high precision (below 4% RSD intraday). Methods were linear between LODs and 100 µg L-1 for ketamine, 75 µg L-1 for midazolam and 10 µg L-1 for propofol respectively, with coefficients of determination R2≥ 0.999. Further, being aware of the error-prone and demanding translation of microdialysis levels to interstitial concentrations, in vitro approaches for recovery testing of microdialysis probes as well as internal normalization approaches were conducted. Thus, we herein report the first cerebral pharmacokinetic data of ketamine, midazolam and propofol determined in microdialysis samples of 15 neurointensive care patients. We could prove blood-brain barrier penetration of all of the investigated anesthetics and could correlate applied dosages and actual brain exposition of ketamine. However, we emphasize the need of an expanded prospective study including individual microdialysis recovery testing as well as matched serum and/or cerebrospinal fluid collection for a more comprehensive cerebral pharmacokinetic understanding.

Meropenem concentrations in brain tissue of neurointensive care patients exceed CSF levels.

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.

Do standard surgical techniques lead to satisfying aesthetic results in nonsyndromic sagittal suture synostosis?

OBJECTIVE: Surgical correction of synostotic cranial sutures is typically performed early in an affected child's life. Depending on the severity of the cranial synostoses, different aspects of the surgical treatment may have varying degrees of importance. In this sense, the aesthetic appearance in children with normal neurological development in single-suture synostosis plays an important role in self-perception and social acceptance for both the patients themselves and their caregivers. Therefore, in this study, the authors aimed to evaluate the aesthetic outcome after surgical correction in a cohort of patients with nonsyndromic sagittal suture synostosis. METHODS: Between December 2002 and December 2019, a total of 99 patients underwent surgical correction of a synostotic sagittal suture at the Medical University of Vienna. Depending on their age, patients underwent either an extended midline strip craniectomy (EMSC) (< 4 months) or a modified pi procedure (MPP) (≥ 4 months). After the surgical procedure, the outcome was evaluated by the treating neurosurgeon at 1- and 12-month follow-up visits, and after approximately 5 years, before the patient entered elementary school. In addition to that, the patients' caregivers were asked to evaluate the aesthetic outcome of the surgical procedure after 12 months. These results were then compared to evaluate potential differences in the perception of the surgical outcome. RESULTS: After 12 months, the majority of the included patients were evaluated as having a good aesthetic outcome by the treating neurosurgeon (97%) and by their caregivers (89%). These differences did not show statistical significance (p = 0.11). Similarly, no differences in the aesthetic outcome depending on the surgical procedure performed could be found (p = 0.55). At the last follow-up visit, before entering elementary school, all available patients had an excellent or good surgical outcome. Moreover, the majority of caregivers (73%) reported that their child had a normal head shape appearance after surgical correction. CONCLUSIONS: The results of this study have suggested that surgical correction of sagittal suture synostosis by simple operative techniques leads to a good aesthetic outcome and a normal head shape appearance in the majority of patients. An analysis of the evaluation of the surgical outcome by either the treating neurosurgeon or the patient caregivers showed comparable results and, thus, early intervention with simple surgical techniques can be recommended.

The Evoked Potential Score for SSEP and BAEP-A Prognostic Marker for the Long-Term Neurological Outcome in Patients after Poor-Grade Subarachnoid Hemorrhage.

OBJECTIVE: Evoked potentials are widely used in comatose patients to evaluate neurological function; however, prognostic relevance in patients after SAH is barely investigated. Therefore, we aimed to investigate the prognostic value of the proposed Evoked Potential Score (EPS) for somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) on the neurological outcome in patients after poor-grade SAH. METHODS: We retrospectively analyzed patients after poor grade SAH (Hunt and Hess (HH) grade IV and V) that were admitted to the ICU at the Department of Neurosurgery, MUV, between 2014 and 2017. Measurements of SSEP and BAEP were evaluated separately as well as in a combined model, using the EPS at admission and before ventilator weaning and correlated with the grade of the modified ranking scale at the last available follow up. RESULTS: In total, 48 patients after SAH HH IV/V were included in this study. The EPS for SSEP at admission (p = 0.007) and both the EPS for SSEP (p = <0.0001) and BAEP (p = 0.036) before ventilator weaning were significant prognostic markers for neurological improvement at a mean follow-up period of 14.1 months. In addition, the combined model of the EPS for SSEP/BAEP performed as a prognostic marker for neurological improvement ("at admission" p = 0.007; "before ventilator weaning" p < 0.001). CONCLUSIONS: In the first series to date we found a high prognostic significance for the EPS as a combined model, as well as a separate analysis for SSEP and BAEP in patients after SAH IV and V. In the future, these findings potentially support physicians in ethically challenging decision-making processes and in advice for patients' families under consideration of an individual evaluation of each patient.

Myelomeningocele-Chiari II malformation-Neurological predictability based on fetal and postnatal magnetic resonance imaging.

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.

Detrimental effects of intrahospital transport on cerebral metabolism in patients suffering severe aneurysmal subarachnoid hemorrhage.

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.

Cerebral nitric oxide and mitochondrial function in patients suffering aneurysmal subarachnoid hemorrhage-a translational approach.

BACKGROUND: Cerebral ischemia and neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) are major contributors to poor neurological outcome. Our study set out to investigate in an exploratory approach the interaction between NO and energy metabolism following SAH as both hypoxia and inflammation are known to affect nitric oxide (NO) metabolism and NO in turn affects mitochondria. METHODS: In seven patients under continuous multimodality neuromonitoring suffering poor-grade aneurysmal SAH, cerebral metabolism and NO levels (determined as a sum of nitrite plus nitrate) were determined in cerebral microdialysate for 14 days following SAH. In additional ex vivo experiments, rat cortex homogenate was subjected to the NO concentrations determined in SAH patients to test whether these NO concentrations impair mitochondrial function (determined by means of high-resolution respirometry). RESULTS: NO levels showed biphasic kinetics with drastically increased levels during the first 7 days (74.5 ± 29.9 µM) and significantly lower levels thereafter (47.5 ± 18.7 µM; p = 0.02). Only during the first 7 days, NO levels showed a strong negative correlation with brain tissue oxygen tension (r = - 0.78; p < 0.001) and a positive correlation with cerebral lactate (r = 0.79; p < 0.001), pyruvate (r = 0.68; p < 0.001), glutamate (r = 0.65; p < 0.001), as well as the lactate-pyruvate ratio (r = 0.48; p = 0.01), suggesting mitochondrial dysfunction. Ex vivo experiments confirmed that the increase in NO levels determined in patients during the acute phase is sufficient to impair mitochondrial function (p < 0.001). Mitochondrial respiration was inhibited irrespectively of whether glutamate (substrate of complex I) or succinate (substrate of complex II) was used as mitochondrial substrate suggesting the inhibition of mitochondrial complex IV. The latter was confirmed by direct determination of complex IV activity. CONCLUSIONS: Exploratory analysis of our data suggests that during the acute phase of SAH, NO plays a key role in the neuronal damage impairing mitochondrial function and facilitating accumulation of mitochondrial substrate; further studies are required to understand mechanisms underlying this observation.

Peri-interventional Behavior of the Neutrophil to Lymphocyte Ratio in Patients with Intracranial Aneurysms.

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been investigated as an independent predictive marker for clinical outcomes in vascular diseases. This study aimed to investigate the peri-interventional behavior of the NLR in patients with ruptured and unruptured intracranial aneurysms (IAs). METHODS: A total of 117 patients with IAs, who were treated at our department and had available complete data, were retrospectively identified during a 10-year period. Routine laboratory parameters, including the neutrophil and lymphocytes counts, were evaluated before and after treatment. RESULTS: The baseline NLR showed significant differences between patients with ruptured and unruptured IAs (6.3 vs. 1.8; P < 0.001). In patients with ruptured IAs, the baseline NLR decreased significantly during the follow-up visits, whereas in unruptured IAs, the NLR remained low. Furthermore, higher baseline NLR values could also be observed in patients with ruptured IAs and fatal outcome than in surviving patients (8.0 vs. 5.4; P = 0.220). In patients with poor functional outcome, defined as modified Rankin score ≥3, the NLR was significantly higher before treatment (P = 0.047), at day 10 (P = 0.025), and 1 month after treatment (P = 0.001). CONCLUSIONS: The peri-interventional NLR was significantly different between patients with ruptured and unruptured IAs. In patients with ruptured IAs, elevated baseline NLR levels were associated with poor postoperative functional outcomes and decreased postoperatively, implying the potential prognostic value of NLR in patients with IAs.