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Background: Pathologically low brain glucose levels, referred to as neuroglucopenia, are associated with unfavorable outcomes in neurocritical care patients. We sought to investigate whether an increase in serum glucose levels would be associated with a reduction of neuroglucopenia., Methods: In this retrospective analysis of prospectively collected data, we included 55 consecutive patients with spontaneous subarachnoid hemorrhage who underwent cerebral microdialysis (CMD) monitoring. Neuroglucopenia was defined as CMD-glucose levels < 0.7 mmol/l. We identified systemic glucose liberalization events, defined as a day with median serum glucose levels < 150 mg/dl, followed by a day with median serum glucose levels > 150 mg/dl, and compared concentrations of cerebral metabolites between these days. Unfavorable outcome was defined as modified Rankin Scale score ≥ 3 at 3 months after the bleeding., Results: Episodes of neuroglucopenia were more frequent in patients with unfavorable outcome (19.8% [19.3-20.3%] vs. 10.9% [10.4-11.5%], p = 0.007). Sixty-nine systemic glucose liberalization events were identified in 40 patients. Blood glucose levels increased from 141.2 (138.7-143.6) mg/dl to 159.5 (157.0-162.2) mg/dl (p < 0.001), CMD-glucose levels increased from 1.44 (1.39-1.50) mmol/l to 1.68 (1.62-1.75) mmol/l (p = 0.001), and the frequency of neuroglucopenia decreased from 24.7% (22.9-26.5%) to 20.2% (18.7-21.8%) (p = 0.002) during these events. Liberalization was not associated with changes in CMD-lactate, CMD-pyruvate, CMD-lactate-to-pyruvate ratio, CMD-glutamate, or CMD-glycerol., Conclusions: In conclusion, the liberalization of serum glucose concentrations to levels between 150 and 180 mg/dl was associated with a significant reduction of neuroglucopenia., (© 2024. The Author(s).)

Background: Patients with spontaneous subarachnoid hemorrhage (SAH) frequently encounter cognitive dysfunction and mental health issues with negative effects on health-related quality of life (HR-QoL). Here, we aimed to describe the prevalence of cognitive deficits, mental health problems, and HR-QoL impairments 1 year after SAH., Methods: In this prospective observational study, 177 patients with SAH admitted to our neurointensive care unit over a time span of ten years followed the invitation for an in-person 1-year follow-up, including a standardized neuropsychological test battery. Mental health issues (anxiety and depression) and HR-QoL were evaluated using questionnaires (Hospital Anxiety and Depression Scale; 36-item Short Form questionnaire). Functional outcome was assessed with the modified Rankin Scale (mRS) score., Results: Patients were 54 years of age (interquartile range 47-62 years) and presented with a median Hunt and Hess score of 2 (interquartile range 1-3) at admission. Most patients (93%) achieved good functional 1-year outcomes (mRS score 0-2). Seventy-one percent of patients had deficits in at least one cognitive domain, with memory deficits being the most prevalent (51%), followed by deficits in executive functions (36%), visuoconstruction (34%), and attention (21%). Even patients with perimesencephalic SAH (18%) or with full functional recovery (mRS score = 0, 46%) had a comparable prevalence of cognitive deficits (61% and 60%, respectively). Symptoms of depression and anxiety were reported by 16% and 33% of patients, respectively. HR-QoL was impaired in 37% (55 of 147). Patients with cognitive deficits (p = 0.001) or mental health issues (p < 0.001) more frequently reported impaired HR-QoL., Conclusions: Most patients with SAH have cognitive deficits and mental health issues 1 year after SAH. These deficits impair patients' quality of life., (© 2023. The Author(s).)

Background: Intensive care unit (ICU) acquired weakness is a major contributor to poor functional outcome of ICU patients. Quantification of temporal muscle volume assessed on routine computed tomography (CT) scans may serve as a biomarker for muscle wasting in patients suffering from acute brain injury., Methods: This is a retrospective analysis of prospectively collected data. Temporal muscle volume was assessed on head CT scans of consecutive patients with spontaneous subarachnoid hemorrhage within prespecified time frames (on admission, then weekly ± 2 days). Whenever possible, temporal muscle volume was assessed bilaterally and averaged for the analysis. Poor functional outcome was defined as a 3-month modified Rankin Scale Score ≥ 3. Statistical analysis was performed using generalized estimating equations to handle repeated measurements within individuals., Results: The analysis comprised 110 patients with a median Hunt & Hess score of 4 (interquartile range 3-5). Median age was 61 (50-70) years, 73 patients (66%) were women. Baseline temporal muscle volume was 18.5 ± 0.78 cm 3 and significantly decreased over time (p < 0.001) by a mean of 7.9% per week. Higher disease severity (p = 0.002), hydrocephalus (p = 0.020), pneumonia (p = 0.032), and bloodstream infection (p = 0.015) were associated with more pronounced muscle volume loss. Patients with poor functional outcome had smaller muscle volumes 2 and 3 weeks after subarachnoid hemorrhage compared with those with good outcome (p = 0.025). The maximum muscle volume loss during ICU stay was greater in patients with poor functional outcome (- 32.2% ± 2.5% vs. - 22.7% ± 2.5%, p = 0.008). The hazard ratio for poor functional outcome was 1.027 (95% confidence interval 1.003-1.051) per percent of maximum muscle volume loss., Conclusions: Temporal muscle volume, which is easily assessable on routine head CT scans, progressively decreases during the ICU stay after spontaneous subarachnoid hemorrhage. Because of its association with disease severity and functional outcome, it may serve as a biomarker for muscle wasting and outcome prognostication., (© 2023. The Author(s).)

Background: Nimodipine is recommended to prevent delayed cerebral ischemia in patients with spontaneous subarachnoid hemorrhage (SAH). Here, we studied hemodynamic side effects of different nimodipine formulations (per os [PO] and intravenous [IV]) in patients with SAH undergoing continuous blood pressure monitoring., Methods: This observational cohort study includes consecutive patients with SAH (271 included in the IV group, 49 in the PO group) admitted to a tertiary care center between 2010 and 2021. All patients received prophylactic IV or PO nimodipine. Hemodynamic responses were evaluated based on median values within the first hour after continuous IV nimodipine initiation or PO nimodipine application (601 intakes within 15 days). Significant changes were defined as > 10% drop in systolic blood pressure (SBP) or diastolic blood pressure from baseline (median values 30 min before nimodipine application). With the use of multivariable logistic regression, risk factors associated with SBP drops were identified., Results: Patients were admitted with a median Hunt & Hess score of 3 (2-5; IV 3 [2-5], PO 1 [1-2], p < 0.001) and were 58 (49-69) years of age. Initiation of IV nimodipine was associated with a > 10% SBP drop in 30% (81/271) of patients, with a maximum effect after 15 min. A start or increase in noradrenaline was necessary in 136/271 (50%) patients, and colloids were administered in 25/271 (9%) patients within 1 h after IV nimodipine initiation. SBP drops > 10% occurred after 53/601 (9%) PO nimodipine intakes, with a maximum effect after 30-45 min in 28/49 (57%) patients. Noradrenaline application was uncommon (3% before and 4% after nimodipine PO intake). Hypotensive episodes to an SBP < 90 mm Hg were not observed after IV or PO nimodipine application. In multivariable analysis, only a higher SBP at baseline was associated with a > 10% drop in SBP after IV (p < 0.001) or PO (p = 0.001) nimodipine application, after adjusting for the Hunt & Hess score on admission, age, sex, mechanical ventilation, days after intensive care unit admission, and delayed cerebral ischemia., Conclusions: Significant drops in SBP occur in one third of patients after the start of IV nimodipine and after every tenth PO intake. Early recognition and counteracting with vasopressors or fluids seems necessary to prevent hypotensive episodes., (© 2023. The Author(s).)

Background: Despite improvements in the critical care management of subarachnoid hemorrhage (SAH), a substantial number of patients still suffer from disabilities. In most areas of the world, longitudinal follow-up is not routinely performed, and the patient's trajectory remains unknown., Methods: We prospectively collected data of 298 consecutive patients with spontaneous SAH and evaluated clinical trajectories at discharge, 3 months, and 1 year after SAH. In a subgroup of patients transferred to a local neurorehabilitation center (Rehab-Hochzirl), we studied the effects of rehabilitation intensity on clinical trajectories. Any decrease in the modified Rankin Scale (mRS) was defined as an improvement, with mRS ≤ 2 indicating good outcome. We used multivariate generalized linear models to investigate associations with clinical trajectories., Results: Out of the 250 surviving patients, 35% were transferred directly to Rehab-Hochzirl (n = 87 of 250; mRS at discharge = 4), 11% were transferred to another rehabilitation center (n = 27 of 250; mRS = 1), 1% were transferred to a nursing home (n = 3 of 250; mRS = 5), 21% were transferred to their country of origin (n = 52 of 250; mRS = 4), and 32% (n = 79 of 250; mRS = 1) were discharged home. Functional outcome improved in 57% (n = 122 of 215) of patients during the first 3 months, with an additional 16% (35 of 215) improving between 3 and 12 months, resulting in an overall improvement in 73% (n = 157 of 215) of survivors. After 1 year, 60% (n = 179 of 250) of patients were functionally independent. A lower Hunt and Hess scale score at intensive care unit admission, younger age, a lower mRS at intensive care unit discharge, fewer days on mechanical ventilation, and male sex were independently associated with better functional recovery. Although the subgroup of patients transferred to Rehab-Hochzirl were more severely affected, 60% (52 of 87) improved during inpatient neurorehabilitation., Conclusions: Our results indicate ongoing functional improvement in a substantial number of patients with SAH throughout a follow-up period of 12 months. This effect was also observed in patients with severe disability receiving inpatient neurorehabilitation., (© 2022. The Author(s).)

Background: The amount of intracranial blood is a strong predictor of poor outcome after subarachnoid hemorrhage (SAH). Here, we aimed to measure iron concentrations in the cerebral white matter, using the cerebral microdialysis (CMD) technique, and to associate iron levels with the local metabolic profile, complications, and functional outcome., Methods: For the observational cohort study, 36 patients with consecutive poor grade SAH (Hunt & Hess grade of 4 or 5, Glasgow Coma Scale Score ≤ 8) undergoing multimodal neuromonitoring were analyzed for brain metabolic changes, including CMD iron levels quantified by graphite furnace atomic absorption spectrometry. The study time encompassed 14 days after admission. Statistical analysis was performed using generalized estimating equations., Results: Patients were admitted in a poor clinical grade (n = 26, 72%) or deteriorated within 24 h (n = 10, 28%). The median blood volume in the subarachnoid space was high (SAH sum score = 26, interquartile range 20-28). Initial CMD iron was 44 µg/L (25-65 µg/L), which significantly decreased to a level of 25 µg/L (14-30 µg/L) at day 4 and then constantly increased over the remaining neuromonitoring days (p < 0.01). A higher intraventricular hemorrhage sum score (≥ 5) was associated with higher CMD iron levels (Wald-statistic = 4.1, df  = 1, p = 0.04) but not with the hemorrhage load in the subarachnoid space (p = 0.8). In patients developing vasospasm, the CMD iron load was higher, compared with patients without vasospasm (Wald-statistic = 4.1, degree of freedom = 1, p = 0.04), which was not true for delayed cerebral infarction (p = 0.4). Higher iron concentrations in the brain extracellular fluid (34 µg/L, 36-56 µg/L vs. 23 µg/L, 15-37 µg/L) were associated with mitochondrial dysfunction (CMD lactate to pyruvate ratio > 30 and CMD-pyruvate > 70 µM/L, p < 0.001). Brain extracellular iron load was not associated with functional outcome after 3 months (p > 0.5)., Conclusions: This study suggests that iron accumulates in the cerebral white matter in patients with poor grade SAH. These findings may support trials aiming to scavenger brain extracellular iron based on the hypothesis that iron-mediated neurotoxicity may contribute to acute and secondary brain injury following SAH., (© 2021. The Author(s).)

Background/objective: Monitoring of brain tissue oxygen tension (P bt O 2 ) provides insight into brain pathophysiology after intracerebral hemorrhage (ICH). Integration of probe location is recommended to optimize data interpretation. So far, little is known about the importance of P bt O 2 catheter location in ICH patients., Methods: We prospectively included 40 ICH patients after hematoma evacuation (HE) who required P bt O 2 -monitoring. P bt O 2 -probe location was evaluated in all head computed tomography (CT) scans within the first 6 days after HE and defined as location in the healthy brain tissue or perilesional when the catheter tip was located within 1 cm of a focal lesion (hypodense or hyperdense). Generalized estimating equations were used to investigate levels of P bt O 2 in relation to different probe locations., Results: Patients were 60 [51-66] years old and had a median ICH-volume of 47 [29-60] mL. Neuromonitoring probes remained for a median of 6 [2-11] days. P bt O 2 -probes were located in healthy brain tissue in 18/40 (45%) patients and in perilesional brain tissue in 22/40 (55%) patients. In the acute phase after HE (0-72 h), P bt O 2 levels were significantly lower (21 ± 12 mmHg vs. 29 ± 10 mmHg, p = 0.010) and brain tissue hypoxia (BTH) was more common in the perilesional area as compared to healthy brain tissue (46% vs. 19%, adjOR 4.0, 95% CI 1.54-10.58, p = 0.005). Episodes of BTH significantly decreased over time in patients with probes in perilesional location (p = 0.001) but remained stable in normal appearing area (p = 0.485). A significant association between BTH and poor functional outcome was only found when probes were located in the perilesional brain tissue (adjOR 6.6, 95% CI 1.3-33.8, p = 0.023)., Conclusions: In the acute phase, BTH was more common in the perilesional area compared to healthy brain tissue. The improvement of BTH in the perilesional area over time may be the result of targeted treatment interventions and tissue regeneration. Due to the localized measurement of invasive neuromonitoring devices, integration of probe location in the clinical management of ICH patients and in research protocols seems mandatory.

Background: The broad antibacterial spectrum of piperacillin/tazobactam makes the combination suitable for the treatment of nosocomial bacterial central nervous system (CNS) infections. As limited data are available regarding piperacillin CNS exposure in patients without or with low-grade inflammation, a clinical study was conducted (1) to quantify CNS exposure of piperacillin by cerebral microdialysis and (2) to evaluate different dosing regimens in order to improve probability of target attainment (PTA) in brain., Methods: Ten acute hemorrhagic stroke patients (subarachnoid hemorrhage, n = 6; intracerebral hemorrhage, n = 4) undergoing multimodality neuromonitoring received 4 g piperacillin/0.5 g tazobactam every 8 h by 30-min infusions for the management of healthcare-associated pneumonia. Cerebral microdialysis was performed as part of the clinical neuromonitoring routine, and brain interstitial fluid samples were retrospectively analyzed for piperacillin concentrations after the first and after multiple doses for at least 5 days and quantified by high-performance liquid chromatography. Population pharmacokinetic modeling and Monte Carlo simulations with various doses and types of infusions were performed to predict exposure. A T >MIC of 50% was selected as pharmacokinetic/pharmacodynamic target parameter., Results: Median peak concentrations of unbound piperacillin in brain interstitial space fluid were 1.16 (range 0.08-3.59) and 2.78 (range 0.47-7.53) mg/L after the first dose and multiple doses, respectively. A one-compartment model with a transit compartment and a lag time (for the first dose) between systemic and brain exposure was appropriate to describe the brain concentrations. Bootstrap median estimates of the parameters were: transfer rate from plasma to brain (0.32 h -1 ), transfer rate from brain to plasma (7.31 h -1 ), and lag time [2.70 h (coefficient of variation 19.7%)]. The simulations suggested that PTA would exceed 90% for minimum inhibitory concentrations (MICs) up to 0.5 mg/L and 1 mg/L at a dose of 12-16 and 24 g/day, respectively, regardless of type of infusion. For higher MICs, PTA dropped significantly., Conclusion: Limited CNS exposure of piperacillin might be an obstacle in treating patients without general meningeal inflammation except for infections with highly susceptible pathogens. Brain exposure of piperacillin did not improve significantly with a prolongation of infusions.

Background: Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH) and its contribution to hospital complications, length of intensive care unit stay, and functional outcome., Methods: This is a retrospective analysis of an ongoing prospective cohort study. Swallowing ability was assessed in consecutive non-traumatic SAH patients admitted to our neurological intensive care unit using the Bogenhausen Dysphagia Score (BODS). A BODS > 2 points indicated dysphagia. Functional outcome was assessed 3 months after the SAH using the modified Rankin Scale with a score > 2 defined as poor functional outcome., Results: Two-hundred and fifty consecutive SAH patients comprising all clinical severity grades with a median age of 57 years (interquartile range 47-67) were eligible for analysis. Dysphagia was diagnosed in 86 patients (34.4%). Factors independently associated with the development of dysphagia were poor clinical grade on admission (Hunt & Hess grades 4-5), SAH-associated parenchymal hematoma, hydrocephalus, detection of an aneurysm, and prolonged mechanical ventilation (> 48 h). Dysphagia was independently associated with a higher rate of pneumonia (OR = 4.32, 95% CI = 2.35-7.93), blood stream infection (OR = 4.3, 95% CI = 2.0-9.4), longer ICU stay [14 (8-21) days versus 29.5 (23-45) days, p < 0.001], and poor functional outcome after 3 months (OR = 3.10, 95% CI = 1.49-6.39)., Conclusions: Dysphagia is a frequent complication of non-traumatic SAH and associated with poor functional outcome, infectious complications, and prolonged stay in the intensive care unit. Early identification of high-risk patients is needed to timely stratify individual patients for dysphagia treatment.

Background: Subarachnoid hemorrhage (SAH) is a devastating disease associated with high mortality and morbidity. Besides neurological sequelae, neuropsychological deficits largely contribute to patients' long-term quality of life. Little is known about the pituitary gland volume (PGV) after SAH compared to healthy referents and the association of PGV with long-term outcome including cognitive function., Methods: Sixty consecutive non-traumatic SAH patients admitted to the neurological intensive care unit between 2010 and 2014 were enrolled. 3-Tesla magnetic resonance imagining was performed at baseline (16 days) and 12 months after SAH to measure PGV semi-automatically using the software iPlan Net 3.5.0. PGV was compared to age and sex matched healthy referents. The difference between baseline and 1-year-PGV was classified as increase (> 20 mm 3 PGV increase), stable (± 20 mm 3 ), or decrease (> 20 mm 3 PGV decrease). In addition, total intracerebral volume was calculated. Neuropsychological testing was applied in 43 SAH patients at 1-year follow up encompassing several domains (executive, attention, memory) and self-assessment (questionnaire for self-perceived deficits in attention [German: FEDA]) of distractibility in mental processes, fatigue and decrease in motivation. Multivariable regression with multivariable generalized linear models was used for comparison of PGVs and for subgroup analysis to evaluate a potential association between PGV and neuropsychological outcome., Results: Patients were 53 years old (IQR = 44-63) and presented with a median Hunt&Hess grade of 2 (IQR = 1-3). SAH patients had a significantly lower PGV both at baseline (360 ± 19 mm 3 , p < 0.001) and 1 year (367 ± 18 mm 3 p < 0.001) as compared to matched referents (mean 505 ± 18 mm 3 ). PGV decreased by 75 ± 8 mm 3 in 28 patients, increased by 120 ± 22 mm 3 in 22 patients and remained stable in 10 patients at 1-year follow-up. PGV in patients with PGV increase at 12 months was not different to healthy referents (p = 0.062). Low baseline PGV was associated with impaired executive functions at 1 year (adjOR = 8.81, 95%-CI = 1.46-53.10, p = 0.018) and PGV decrease within 1 year was associated with self-perceived worse motivation (FEDA; Wald-statistic = 6.6, df = 1, p = 0.010)., Conclusions: Our data indicate significantly lower PGVs following SAH. The association of sustained PGV decrease with impaired neuropsychological long-term outcome warrants further investigations including neuroendocrine hormone measurements.

Background: There is no uniform definition for cerebral microdialysis (CMD) probe location with respect to focal brain lesions, and the impact of CMD-probe location on measured molecule concentrations is unclear., Methods: We retrospectively analyzed data of 51 consecutive subarachnoid hemorrhage patients with CMD-monitoring between 2010 and 2016 included in a prospective observational cohort study. Microdialysis probe location was assessed on all brain computed tomography (CT) scans performed during CMD-monitoring and defined as perilesional in the presence of a focal hypodense or hyperdense lesion within a 1-cm radius of the gold tip of the CMD-probe, or otherwise as normal-appearing brain tissue., Results: Probe location was detected in normal-appearing brain tissue on 53/143 (37%) and in perilesional location on 90/143 (63%) CT scans. In the perilesional area, CMD-glucose levels were lower (p = 0.003), whereas CMD-lactate (p = 0.002), CMD-lactate-to-pyruvate-ratio (LPR; p < 0.001), CMD-glutamate (p = 0.002), and CMD-glycerol levels (p < 0.001) were higher. Neuroglucopenia (CMD-glucose < 0.7 mmol/l, p = 0.002), metabolic distress (p = 0.002), and mitochondrial dysfunction (p = 0.005) were more common in perilesional compared to normal-appearing brain tissue. Development of new lesions in the proximity of the CMD-probe (n = 13) was associated with a decrease in CMD-glucose levels, evidence of neuroglucopenia, metabolic distress, as well as increasing CMD-glutamate and CMD-glycerol levels. Neuroglucopenia was associated with poor outcome independent of probe location, whereas elevated CMD-lactate, CMD-LPR, CMD-glutamate, and CMD-glycerol levels were only predictive of poor outcome in normal-appearing brain tissue., Conclusions: Focal brain lesions significantly impact on concentrations of brain metabolites assessed by CMD. With the exception of CMD-glucose, the prognostic value of CMD-derived parameters seems to be higher when assessed in normal-appearing brain tissue. CMD was sensitive to detect the development of new focal lesions in vicinity to the neuromonitoring probe. Probe location should be described in the research reporting brain metabolic changes measured by CMD and integrated in statistical models.

Background: Brain tissue hypoxia (P bt O 2  < 20 mmHg) is common after subarachnoid hemorrhage (SAH) and associated with poor outcome. Recent data suggest that brain oxygen optimization is feasible and reduces the time spent with P bt O 2  < 20 mmHg from 45 to 16% in patients with severe traumatic brain injury. Here, we intended to quantify the brain tissue hypoxia burden despite implementation of a protocolized treatment approach in poor-grade SAH patients and to identify the simultaneous occurrence of pathologic values potentially amenable to treatment., Methods: We present a bi-centric observational cohort study including 100 poor-grade SAH patients admitted to two tertiary care centers who underwent multimodal brain monitoring and were managed with a P bt O 2 -targeted protocolized approach. P bt O 2 optimization (≥ 20 mmHg) included a stepwise neuro-intensive care approach, aiming to prevent low cerebral perfusion pressure (CPP), and blood hemoglobin, and to keep normocapnia, normoxemia, and normothermia. Based on routine blood gas analysis, hemoglobin, PaCO 2, and PaO 2 data were matched to 2-h averaged data of continuous CPP, P bt O 2 , core temperature, and to hourly cerebral microdialysis (CMD) samples over the first 11 days., Results: Patients had a Glasgow Coma Scale of 3 (IQR 3-4) and were 58 years old (IQR 48-66). Overall incidence of brain tissue hypoxia was 25%, which was not different between both sites despite differences in the treatment approach. During brain tissue hypoxia, episodes of CPP < 70 mmHg (27%), PaCO 2  < 35 mmHg (19%), PaO 2  < 80 mmHg (14%), Hb < 9 g/dL (11%), metabolic crisis (CMD-lactate/pyruvate ratio > 40, and CMD-glucose < 0.7 mmol/L; 7%), and temperature > 38.3 °C (4%) were common., Conclusions: Our results demonstrate that brain tissue hypoxia remains common despite implementation of a P bt O 2 -targeted therapy in poor-grade SAH patients, suggesting room for further optimization.

Background: Takotsubo cardiomyopathy (TC) is a well-known complication after aneurysmal subarachnoid hemorrhage and has been rarely described in patients with traumatic brain injury (TBI)., Methods: Case report and review of literature., Results: Here, we report a 73-year-old woman with mild traumatic brain injury (TBI) presenting in cardiogenic shock. Takotsubo cardiomyopathy (TC) was diagnosed by repeated echocardiography. Cardiovascular support by inotropic agents led to hemodynamic stabilization after initiation of levosimendan. Cardiac function fully recovered within 21 days. We performed an in-depth literature review and identified 16 reported patients with TBI and TC. Clinical course and characteristics are discussed in the context of our patient., Conclusion: Takotsubo cardiomyopathy is under-recognized after TBI and may negatively impact outcome if left untreated.

Introduction: Viral encephalitis is an emerging disease requiring intensive care management in severe cases. Underlying pathophysiologic mechanisms are incompletely understood and may be elucidated using invasive multimodal neuromonitoring techniques in humans., Methods: Two otherwise healthy patients were admitted to our neurological intensive care unit with altered level of consciousness necessitating mechanical ventilation. Brain imaging and laboratory workup suggested viral encephalitis in both patients. Invasive neuromonitoring was initiated when head computed tomography revealed generalized brain edema, including monitoring of intracranial pressure, brain metabolism (cerebral microdialysis; CMD), brain tissue oxygen tension (in one patient), and cerebral blood flow (in one patient)., Results: Brain metabolism revealed episodes of severe neuroglucopenia (brain glucose <0.7 mM/l) in both patients, which were not attributable to decreased cerebral perfusion or hypoglycemia. CMD-glucose levels changed depending on variations in insulin therapy, nutrition, and systemic glucose administration. The metabolic profile, moreover, showed a pattern of non-ischemic metabolic distress suggestive for mitochondrial dysfunction. Both patients had a prolonged but favorable clinical course and improved to a modified Rankin Scale Score of 1 and 0 three months later., Conclusion: Invasive multimodal neuromonitoring is feasible in poor-grade patients with viral meningoencephalitis and may help understand pathophysiologic mechanisms associated with secondary brain injury. The detection of neuroglucopenia and mitochondrial dysfunction may serve as treatment targets in the future., Competing Interests: The authors declare that they have no conflict of interest.

Background: Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting., Methods: We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects., Results: CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p < 0.001). Patients with brain edema on admission or during hospitalization (N = 20; 80 %) and patients developing DCI (N = 5; 20 %) had higher brain extracellular taurine levels compared to those without (Wald = 7.3, df = 1, p < 0.01; Wald = 10.1, df = 1, p = 0.001, respectively) even after adjusting for disease severity and CMD-probe location. There was no correlation between parenteral taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p < 0.001), lactate (r = 0.56, p < 0.02), pyruvate (r = 0.39, p < 0.01), potassium (r = 0.37, p = 0.01), and lactate-to-pyruvate ratio (r = 0.24, p = 0.02) was found., Conclusions: Significantly higher CMD-taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a potential biomarker deserves further investigation.