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Background: The study investigated the effectiveness of low-frequency sampling in detecting alterations in cerebrovascular reactivity (CVR) associated with changes in intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across different age groups. The primary objective was to investigate an ICP threshold that indicates a decrease in CVR as evidenced by a significant increase in the ultra-low-frequency pressure reactivity index (UL-PRx). Additionally, the study aimed to develop an age-based categorization method for patients with TBI to investigate the differences between these ICP thresholds in different age groups., Methods: In this retrospective analysis, data from 263 patients with TBI were prospectively collected. ICP and mean arterial pressure were extracted from the hospital database at 5-min intervals. Demographic details, clinical presentation, computed tomography scans, neurosurgical interventions, and 12-months outcome were recorded. ICP versus UL-PRx values were categorized into ICP bins and graphically represented with boxplots for each age group, illustrating how as ICP values rise, there is a bin (age-tailored ICP [AT-ICP]) beyond which UL-PRx shows a sudden increase, indicating CVR loss. Homogeneous age groups were established to obtain a consistent AT-ICP threshold. The discriminatory ability of the AT-ICP thresholds was compared with the guideline-recommended thresholds by calculating the area under the Receiver Operating Characteristic curve of the ICP-derived indices (dose above threshold, and the hourly dosage above threshold)., Results: Age groups 0-5, 6-20, 21-60, 61-70, and 71-85 years were the best age subdivisions, corresponding to AT-ICP thresholds of 20, 30, 35, 25, and 30 mmHg, respectively. The AT-ICP thresholds exhibited better discriminative ability compared with the guideline-recommended thresholds., Conclusions: The AT-ICP thresholds offer a novel approach for estimating CVR impairment and the developed method represents an alternative solution to address the age stratification issue in patients with TBI., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Effective pain management during labor induction for pregnancy termination is essential. However, to date, no effective treatment has been identified. The primary aim of this study was to measure the analgesic efficacy of a sufentanil sublingual tablet system during pregnancy termination and patient satisfaction by comparing nulliparous and multiparous women. The secondary aims were to characterize the safety profile by reporting any side effects or adverse events and to determine the need for rescue therapy., Methods: We conducted an observational, retrospective, single-center study involving 48 women. The data retrieved for analysis included the total and hourly doses of sublingual sufentanil, evaluations of pain management satisfaction using a 5-point rating scale (ranging from 1, indicating "not satisfied" to 5, denoting "completely satisfied"), occurrence of side effects and adverse events, and the rate of rescue analgesic use. Categorical and numerical variables were compared between the two groups, and a correlation analysis was performed., Results: The median total dose of sufentanil required was 60 mcg. Nulliparous women required a higher dose of sufentanil compared with multiparous women (105 mcg vs. 45 mcg; P = 0.01). Additionally, they underwent a longer labor, indirectly measured by the time of device usage (625 min vs. 165 min; P = 0.05). Regarding satisfaction, 40 patients (83.4%) were satisfied or completely satisfied, whereas only 8 patients (16.6%) reported dissatisfaction. Multiparous women exhibited higher satisfaction levels than did nulliparous women (P = 0.03). No adverse events were reported, and the most common side effects were nausea and vomiting (31.2%). Four patients (12%) required acetaminophen due to insufficient analgesia, with only one patient necessitating a switch to intravenous morphine., Conclusions: Sublingual sufentanil was effective in both nulliparous and multiparous women with minimal side effects. Therefore, sublingual sufentanil can be considered a valid strategy for analgesia during labor induction for pregnancy termination., (© 2024. The Author(s).)

Background: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed., Objective: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt)., Methods: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold., Results: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt., Conclusions: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies., Trial Registration: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21., (© 2024. The Author(s).)

Introduction: Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS., Methods: This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected., Results: A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively., Conclusions: In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function., (© 2024 S. Karger AG, Basel.)

Background: Traumatic brain injury (TBI) is a significant cause of death and disability, with no effective neuroprotective drugs currently available for its treatment. Mesenchymal stromal cell (MSC)-based therapy shows promise as MSCs release various soluble factors that can enhance the injury microenvironment through processes, such as immunomodulation, neuroprotection, and brain repair. Preclinical studies across different TBI models and severities have demonstrated that MSCs can improve functional and structural outcomes. Moreover, clinical evidence supports the safety of third-party donor bank-stored MSCs in adult subjects. Building on this preclinical and clinical data, we present the protocol for an academic, investigator-initiated, multicenter, double-blind, randomised, placebo-controlled, adaptive phase II dose-finding study aiming to evaluate the safety and efficacy of intravenous administration of allogeneic bone marrow-derived MSCs to severe TBI patients within 48 h of injury., Methods/design: The study will be conducted in two steps. Step 1 will enrol 42 patients, randomised in a 1:1:1 ratio to receive 80 million MSCs, 160 million MSCs or a placebo to establish safety and identify the most promising dose. Step 2 will enrol an additional 36 patients, randomised in a 1:1 ratio to receive the selected dose of MSCs or placebo. The activity of MSCs will be assessed by quantifying the plasmatic levels of neurofilament light (NfL) at 14 days as a biomarker of neuronal damage. It could be a significant breakthrough if the study demonstrates the safety and efficacy of MSC-based therapy for severe TBI patients. The results of this trial could inform the design of a phase III clinical trial aimed at establishing the efficacy of the first neurorestorative therapy for TBI., Discussion: Overall, the MATRIx trial is a critical step towards developing an effective treatment for TBI, which could significantly improve the lives of millions worldwide affected by this debilitating condition. Trial Registration EudraCT: 2022-000680-49., (© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.)

Background: The pressure reactivity index (PRx) has emerged as a surrogate method for the continuous bedside estimation of cerebral autoregulation and a predictor of unfavorable outcome after traumatic brain injury (TBI). However, calculation of PRx require continuous high-resolution monitoring currently limited to specialized intensive care units. The aim of this study was to evaluate a new index, the ultra-low-frequency PRx (UL-PRx) sampled at ∼0.0033 Hz at ∼5 minutes periods, and to investigate its association with outcome., Methods: Demographic data, admission Glasgow coma scale, in-hospital mortality and Glasgow outcome scale extended at 12 months were extracted from electronic records. The filtering and preparation of time series of intracranial pressure (ICP), mean arterial pressure and cerebral perfusion pressure (CPP), and calculation of the indices (UL-PRx, Δ-optimal CPP), were performed in MATLAB using an in-house algorithm., Results: A total of 164 TBI patients were included in the study; in-hospital and 12-month mortality was 29.3% and 38.4%, respectively, and 64% of patients had poor neurological outcome at 12 months. On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month mortality. After adjusting for age, Glasgow coma scale, ICP and CPP, mean UL-PRx and UL-PRx thresholds of 0 and +0.25 remained associated with 12-month mortality. Similar findings were obtained for in-hospital mortality. For mean UL-PRx, the area under the receiver operating characteristic curves for in-hospital and 12-month mortality were 0.78 (95% confidence interval [CI]: 0.69-0.87; P <0.001) and 0.70 (95% CI: 0.61-0.79; P <0.001), respectively, and 0.65 (95% CI: 0.57-0.74; P =0.001) for 12-month neurological outcome., Conclusions: Our findings indicate that ultra-low-frequency sampling might provide sufficient resolution to derive information about the state of cerebrovascular autoregulation and prediction of 12-month outcome in TBI patients., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: Older age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI., Methods: This was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated., Results: Sixty patients were studied, 65% were males, their age was 76 years (IQR 70-80) and their admission GCS was 8 (IQR 6-11) with a GCS motor score of 5 (IQR 4-5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9-55.2), p  < 0.0001 and 92% vs. 51% OR and 95% CI: 9.9 (2.1-46.3), p  = 0.002]. In univariate analysis patients with unfavorable outcome were more frequently male and vulnerable-frail, had a higher prevalence of pre-existing neurodegenerative disease, abnormal pupil, lower GCS and had worst CT scan characteristics. At multivariate analysis, only CFS ≥ 4 and traumatic subarachnoid hemorrhage remained associated to 6-month outcome., Conclusion: Frailty was associated with 6 month-outcome, suggesting that the pre-injury functional status could represent an additional indicator to stratify patient's severity and to predict outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zacchetti, Longhi, Zangari, Aresi, Marchesi, Gritti, Biroli and Lorini.)

Purpose: While clinical practice suggests that knowing the cerebral autoregulation (CA) status of traumatic brain injury (TBI) patients is crucial in assessing the best treatment, evidence in pediatric TBI (pTBI) is limited. The pressure reactivity index (PRx) is a surrogate method for the continuous estimation of CA in adults; however, calculations require continuous, high-resolution monitoring data. We evaluate an ultra-low-frequency pressure reactivity index (UL-PRx), based on data sampled at ∼5-min periods, and test its association with 6-month mortality and unfavorable outcome in a cohort of pTBI patients., Methods: Data derived from pTBI patients (0-18 years) requiring intracranial pressure (ICP) monitoring were retrospectively collected and processed in MATLAB using an in-house algorithm., Results: Data on 47 pTBI patients were included. UL-PRx mean values, ICP, cerebral perfusion pressure (CPP), and derived indices showed significant association with 6-month mortality and unfavorable outcome. A value of UL-PRx of 0.30 was identified as the threshold to better discriminate both surviving vs deceased patients (AUC: 0.90), and favorable vs unfavorable outcomes (AUC: 0.70) at 6 months. At multivariate analysis, mean UL-PRx and % time with ICP > 20 mmHg, remained significantly associated with 6-month mortality and unfavorable outcome, even when adjusted for International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-Core variables. In six patients undergoing secondary decompressive craniectomy, no significant changes in UL-PRx were found after surgery., Conclusions: UL-PRx is associated with a 6-month outcome even if adjusted for IMPACT-Core. Its application in pediatric intensive care unit could be useful to evaluate CA and offer possible prognostic and therapeutic implications in pTBI patients., Clinicaltrials: GOV: NCT05043545, September 14, 2021, retrospectively registered., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the "classic ARDS", showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning., Methods: This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups., Results: We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32-47) ml/cmH 2 O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO 2 /FiO 2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs., Conclusions: In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs., (© 2022. The Author(s).)

Prone positioning is frequently used for non-intubated hypoxemic patients with COVID-19, although conclusive evidence is still lacking. The aim of the present study was to investigate whether baseline CT-scans could predict the improvement in oxygenation in COVID-19 related Acute respira-tory syndrome (ARDS) patients when pronated., Methods: A retrospective study of COVID-19 patients who underwent non-invasive ventilation (NIV) and prone positioning was conducted., Results: Forty-five patients were included. On average, 50% of the overall lung volume was affected by the disease, as observed in the CT-scans, with ground glass opacities (GGOs) and consolidations accounting for 44% and 4%, respectively. The abnormalities were mainly posterior, as demonstrated by posterior/anterior distribution ratios of 1.5 and 4.4 for GGO and consolidation, respectively. The median PaO 2 /FiO 2 ratio during NIV in a supine position (SP1) was 140 [IQR 108-169], which improved by 67% (+98) during prone positioning, on average. Once supine positioning was resumed (SP2), the improvement in oxygenation was maintained in 28 patients (62% of the overall population, categorized as "responders"). We found no significant differences between responders and non-responders in terms of the extent ( p = 0.92) and the distribution of parenchymal abnormalities seen in the baseline CT ( p = 0.526)., Conclusion: Despite the lack of a priori estimation of the sample size, considering the absence of any trends in the differences and correlations, we can reasonably conclude that the baseline chest CT-scan does not predict a gas-exchange response in awake prone-positioned patients with COVID-19 related ARDS. Physicians dealing with this category of patients should not rely on the imaging at presentation when evaluating whether to pronate patients.

Background: Questions remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance regarding this topic. Specifically, in this manuscript (part 2), we aim to provide a list of experts' recommendations regarding the management of SAH patients in a center with neurosurgical/neuroendovascular facilities after aneurysm treatment., Methods: A multidisciplinary consensus panel composed by 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted., Results: A total of 33 statements were discussed, voted, and approved. Consensus was reached on 30 recommendations (28 strong and 2 weak). In 3 cases, where consensus could not be agreed upon, no recommendation was provided., Conclusions: This consensus provides practical recommendations (and not mandatory standard of practice) to support clinician's decision-making in the management of SAH patients in centers with neurosurgical/neuroendovascular facilities after aneurysm securing., (© 2022. The Author(s).)

Background: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension., Methods: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd., Results: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%)., Conclusions and Relevance: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available., Trial Registration: NCT02322970 ., (© 2022. The Author(s).)

Background: Issues remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI). In this manuscript, we aim to provide a list of experts' recommendations regarding the early management of SAH patients from hospital admission, in a center with neurosurgical/neuro-endovascular facilities, until securing of the bleeding aneurysm., Methods: A multidisciplinary consensus panel composed of 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different background (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted., Results: Among 19 statements discussed. The consensus was reached on 18 strong recommendations. In one case, consensus could not be agreed upon and no recommendation was provided., Conclusions: This consensus provides practical recommendations for the management of SAH patients in hospitals with neurosurgical/neuroendovascular facilities until aneurysm securing. It is intended to support clinician's decision-making and not to mandate a standard of practice., (© 2022. The Author(s).)

Background: The prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage (aSAH) remains incompletely elucidated. Furthermore, it is not clear whether these abnormalities impact patient outcomes. The aim of this study was to evaluate the prevalence of pituitary dysfunction after aSAH and its effect on outcomes., Methods: We carried out a prospective, cohort study including adult patients (18 y of age or older) with a diagnosis of aSAH who were admitted to the intensive care unit in 3 centers between January 2017 and January 2019. Exclusion criteria were previous hypopituitarism, hormonal replacement therapies for pituitary dysfunction or any corticosteroid treatment. Endocrine function was tested within the first 48 hours after aSAH onset (acute phase), after 1 to 3 weeks (subacute phase), and after 6 to 12 months (chronic phase). Clinical outcomes were assessed at 6 to 12 months using the modified Rankin Scale., Results: Fifty-six patients were included in the study; all were studied in the acute phase, 34 were studied in the subacute phase, and 49 in the chronic phase. Pituitary dysfunction was identified in 92.3% (95% confidence interval; [CI]: 86.6%-98.0%) of cases in the acute phase, in 83.3% (95% CI: 70.8%-95.8%) in the subacute phase, and in 83.3% (95% CI: 72.7%-93.9%) of cases in the chronic phase. The most commonly identified abnormality was dysfunction of the pituitary-gonadal axis. There was no correlation between pituitary dysfunction and clinical outcome., Conclusion: Pituitary dysfunction is common after aSAH, but does not affect 6 to 12-month clinical outcomes., Competing Interests: P.J.H. was supported by the NIHR-Research Professorship, Cambridge BRC, Brain Injury Medtech Co-operative and Global Health Research Group on Neurotrauma. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The immediate management of subarachnoid hemorrhage (SAH) patients in hospitals without neurosurgical/neurointerventional facilities and their transfer to a specialized center is challenging and not well covered in existing guidelines. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance., Methods: A multidisciplinary consensus panel composed by 19 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery and interventional neuroradiology) was created. A modified Delphi approach was adopted., Results: A total of 14 statements have been discussed. Consensus was reached on 11 strong recommendations and 2 weak recommendations. In one case, where consensus could not be agreed upon, no recommendation could be provided., Conclusions: Management of SAH in a non-specialized setting and early transfer are difficult and may have a critical impact on outcome. Clinical advice, based on multidisciplinary consensus, might be helpful. Our recommendations cover most, but not all, topics of clinical relevance., (© 2021. The Author(s).)

SARS-CoV-2 infection is associated with frequent thrombotic events, at the micro and macro-vascular level, due to the perpetuation of a state of hypercoagulability. The so-called 'COVID-19 associated coagulopathy' (CAC) represents a key aspect in the genesis of organ damage from SARS-CoV-2. The main coagulative alterations described in the literature are represented by high levels of D-dimer and fibrinogen. Although CAC has some common features with disseminated intravascular coagulation and sepsis-induced coagulopathy, there are important differences between these clinical pictures and the phenotype of CAC is unique. The pathogenesis of CAC is complex and is affected by the strong interconnection between the inflammatory system and coagulation, in the phenomenon of immunothrombosis and thrombo-inflammation. Several mechanisms come into play, such as inflammatory cytokines, neutrophils, the complement system as well as an alteration of the fibrinolytic system. Finally, an altered platelet function and especially endothelial dysfunction also play a central role in the pathophysiology of CAC. Heparin has several potential effects in CAC, in fact in addition to the anticoagulant effect, it could have a direct antiviral effect and anti-inflammatory properties. The high incidence of thrombo-embolic phenomena despite the use of antithrombotic prophylaxis have led some experts to recommend the use of anticoagulant doses of heparin, but at present the optimal anticoagulant regimen remains to be determined., (Published on behalf of the European Society of Cardiology. © The Author(s) 2021.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Cerebral ultrasound is a developing point of care tool for intensivists and emergency physicians, with an important role in the diagnosis of acute intracranial pathology, such as the assessment of cerebrovascular diseases and in the noninvasive intracranial pressure measurement both in the acute clinical settings and in intensive care unit (ICU). The traditional application of transcranial doppler (TCD) by assessing blood flow velocities in the main cerebral arteries, allows the evaluation and follow up of cerebral vasospasm, cerebral perfusion pressure, cerebral autoregulation and intracranial hypertension. The use of TCD, traditionally limited to the neurosonology laboratories settings, has expanded over the last years following the introduction of B-mode ultrasound and color Doppler, the transcranial color-coded duplex ultrasonography (TCCS), opening a new window to the assessment of cerebral anatomy not only in the neurocritical patients, but also in general ICU and emergency room patients. Here we report a brief review with the intent to up-to-date and describe the main applications and use of TCD/TCCS in the setting of Neurointensive Care.

Background: Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors., Methods: This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models., Results: We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66-0.82; increased to AUC = 0.79, 95% CI 0.71-0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65-0.81 increased to AUC = 0.80, 95% C.I. 0.69-0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups., Conclusions: PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS., Trial Registration: The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.

Cognitive involvement in beta-thalassaemia is strikingly controversial and poorly studied in adulthood. This multicentre prospective study investigated 74 adult neurologically-asymptomatic beta-thalassaemia patients (mean-age 34·5 ± 10·3 years; 53 transfusion-dependent [TDT], 21 non-transfusion dependent [NTDT]) and 45 healthy volunteers (mean-age 33·9 ± 10·7 years). Participants underwent testing with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), Brief Psychiatric Rating Scale (BPRS) and multiparametric brain 3T-magnetic resonance imaging (MRI) for parenchymal, vascular and iron content evaluation. Patients had lower Full-Scale Intelligence Quotient (FSIQ) than controls (75·5 ± 17·9 vs. 97·4 ± 18·1, P < 0·0001) even after correction for education level. Compared to TDT, NTDT showed a trend of higher FSIQ (P = 0·08) but a similar cognitive profile at WAIS-subtests. FSIQ correlated with total and indirect bilirubin (P < 0·0001 and P = 0·002, respectively); no correlation was found with splenectomy, intracranial MRI/magnetic resonance-angiography findings, brain tissue iron content or other disease-related clinical/laboratory/treatment data. FSIQ did not correlate with BPRS scores, although the latter were higher among patients (28·74 ± 3·1 vs. 27·29 ± 4·8, P = 0·01) mainly because of increased depression and anxiety levels. Occupation rate was higher among controls (84·4% vs. 64·9%, P = 0·004) and correlated with higher FSIQ (P = 0·001) and education level (P = 0·001). In conclusion, Italian adult beta-thalassaemia patients seem to present a characteristic cognitive profile impairment and an increased rate of psychological disorders with possible profound long-term socio-economic consequences., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Prognostic factors affecting outcome of traumatic brain injury (TBI), despite their importance, are still under discussion. The purpose of this study was to describe risk factors of in-hospital mortality and outcome at 1 year in a homogeneously treated population of patients with moderate/severe TBI., Methods: A total of 193 consecutive patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score 13-3, including patients with initial GCS score of 13 at high risk for subsequent neurologic deterioration), admitted to the intensive care unit, were retrospectively analyzed. In-hospital mortality and unfavorable outcome at 1 year, based on a Glasgow Outcome Scale-Extended score ≤4, were considered as primary and secondary outcomes., Results: At 1 year, unfavorable outcome occurred in 47.2%, including an in-hospital mortality of 19.7%. Increasing age, GCS motor score <3, coagulation disorders, and intracranial hypertension were acute risk factors of in-hospital mortality. In the 155 remaining survivors, Oxford Handicap Scale (OHS), posttraumatic cerebral infarction, cerebrospinal fluid disturbances, and length of intensive care unit stay were associated with unfavorable outcome at 1 year, in univariate analysis. A cutoff OHS score ≥3 discriminated the probability of an unfavorable outcome (area under the curve, 0.87; P < 0.001; specificity, 74%; sensitivity, 84%). Combining the effect of acute and subacute variables in a multivariate analysis, increasing age and OHS score were independent predictors of outcome., Conclusions: The results of this retrospective study confirmed age as the main acute risk factor and identified OHS as new potential subacute predictor of unfavorable outcome in moderate and severe TBI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Multi-factorial causes jeopardize brain integrity in β-thalassaemia. Intracranial parenchymal and vascular changes have been reported among young β-thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic β-thalassaemia patients (mean-age 35·2 ± 10·7 years; 52/75 transfusion-dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic-like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean-age 33·9 ± 10·8 years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0 ± 10·6 vs. 4·6 ± 9·1, P = 0·63), size and Fazekas' Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic β-thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Superficial siderosis of the central nervous system (SSCNS) is an uncommon and often unrecognized disorder that results from recurrent and persistent bleeding into the subarachnoid space. Currently, there is no effective treatment for SSCNS. The identification and surgical resolution of the cause of bleeding remains the most reliable method of treatment, but the cause of bleeding is often not apparent. The identified sources of recurrent bleeding have typically included neoplasms, vascular malformations, brachial plexus or nerve root injury or avulsion, and previous head and spinal surgery. An association between recurrent bleeding in the CNS and dural abnormalities in the spine has recently been suggested. Dural tears have been identified in relation to a protruding disc or osteophyte. Also in these patients, the exact mechanism of bleeding remains unknown because of a lack of objective surgical data, even in patients who undergo neurosurgical procedures.The present case concerns a 48-year-old man who presented with longstanding symptoms of mild hearing loss and mild gait ataxia. A diagnosis of SSCNS was made in light of the patient's history and the findings on physical examination, imaging, and laboratory testing. MRI and CT detected a small calcific osteophyte in the anterior epidural space of T8-9. The patient underwent surgical removal of the bone spur and dural tear repair. During the surgery, the authors detected a perforating artery, which was on the osteophyte, that was bleeding into the subarachnoid space. This case shows a possible mechanism of chronic bleeding from an osteophyte into the subarachnoid space. In the literature currently available, a perforating artery on an osteophyte bleeding into the subarachnoid space has never been described in SSCNS.

Purpose of Review: Anesthesiologists and intensivists may be involved in the management of aneurysmal subarachnoid hemorrhage (aSAH) patients at various stages of care. This article will review the recent advances in the periprocedural management of aSAH patients., Recent Findings: New scoring systems to assess gravity and prognosis of aSAH patients have been evaluated and proposed. Rebleeding still remains, with early aneurysmal treatment, a major challenge in the first hours of aSAH management. In the last decades, the treatment of the aSAH has shifted from clipping to coiling and more recently, the use of flow diversion technique has been introduced in selected patients. Although these improvements allow treatment of more complex aneurysms, they have implications for the anesthesiologist, including requiring the management of anticoagulation with its inherent risks. Even though knowledge, monitoring, and management of postprocedural phase of aSAH patients has improved, vasospasm and cerebral-delayed ischemia still remain the major and devastating complications in the postoperative course of aSAH patients., Summary: Despite recent progress in the scoring, diagnosis, and treatment of aSAH patients, the periprocedural management of these patients is still a major challenge for anesthesiologists and intensivists, who are involved from the first phase of the aneurysm rupture through the postoperative phases and vasospasm period.

Over the past 2 decades, a large number of guidelines for aneurysmal subarachnoid hemorrhage (aSAH) management have been proposed. The primary aim of these "evidence-based" guidelines is to improve the care of aSAH patients by summarizing and making current knowledge readily available to clinicians. However, an investigation into aSAH guidelines, their changes along time and their successful translation into clinical practice is still lacking.We performed a literature search of historical events and subarachnoid hemorrhage guidelines using the Entrez PubMed NIH, Embase, and Cochrane databases for articles published up to November of 2016. Data were summarized for guidelines on aSAH management and cross-sectional studies of their application. A total of 11 guidelines and 10 cross-sectional studies on aSAH management were analyzed. The use of nimodipine for the treatment of SAH is the only recommendation that remained consistent across guidelines over time (r=0.82; P<0.05). A shift in the definitive treatment for aneurysms from open surgical clipping to endovascular coiling was also noted (r=-0.91; r=0.96; P<0.005). In addition, definitive treatment for aneurysm is being performed earlier. The use of triple-H therapy and the long-term administration of anticonvulsive therapy has decreased. Finally, written protocols for aSAH management were not consistently used across tertiary care institutions (r=-0.46; P=0.43; confidence interval, -0.95 to -0.70).We conclude that guidelines related to the management of patients with SAH have evolved from a consensus-based approach into an evidence-based approach. Nevertheless, the translation into clinical practice is limited, suggesting that personalized approaches to care is inherent, and perhaps necessary for aSAH management.

Background: Moyamoya is a rare cerebrovascular disease characterized by the progressive occlusion of the intracranial carotid artery. Thyroid autoantibodies have been found to be associated with the disease, but their clinical significance has never been studied. The objective of this study was to investigate the relationship between thyroid autoantibodies and the clinical presentation of moyamoya., Methods: This is a prospective study including 37 patients with moyamoya disease (MMD) or unilateral moyamoya (uMM). Thyroid function and thyroid autoantibodies (e.g., antithyroperoxidase and antithyroglobulin) were investigated. We studied the effect of gender, age, type of moyamoya (uMM versus MMD), and thyroid autoantibodies on the clinical presentation, dichotomized into aggressive (hemorrhage, major stroke, or frequent transient ischemic attack [TIA]) and nonaggressive presentation (headache, rare TIAs, and incidental diagnosis) according to the criteria of the Research Committee on Spontaneous Occlusion of the Circle of Willis., Results: Of the 37 patients included in the study, the autoantibodies were elevated in 9 (24.3%). An aggressive presentation occurred in 21 patients (hemorrhage in 11, major stroke in 9, frequent TIAs in 1). The autoantibodies were elevated in 8 of the 21 patients (38.09%) with an aggressive presentation and in 1 of those presenting with minor symptoms (6.2%). The presence of elevated autoantibodies was the only variable associated with an aggressive presentation in the multivariate logistic analysis (P = .048)., Conclusions: When the serum concentration of the thyroid autoantibodies is increased, the patients have a higher risk of an aggressive presentation. Our results support the hypothesis that activation of immune-mediated processes affects the moyamoya physiopathology., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the prevalence of psychiatric symptoms in patients with oral lichen planus (OLP) compared to a control group. Eleven patients (mean age 65.2 years-old), with diagnosis of OLP and 13 controls (mean age 64.8 years-old) underwent a psychiatric evaluation with five psychometric scales: Visual Analogue Scale (VAS), Hamilton Rating Scale for Depression (HAM-D), State-Trait Anxiety Inventory (STAI 1-2), Distress Thermometer (DT) and Brief Fatigue Inventory (BFI). Seventy-three % of OLP group presented a VAS score of mild type; 9% had depressive symptoms; 100% of the sample had a score above the cut-off for state and trait anxiety; 45% presented Distress (36% moderate type). However, no statistical difference was found in comparison with the control group. In this study, there was no difference in these parameters between the OLP group and the control group. Perhaps, a larger cohort of patients could give different results.

To compare the results of psychometric tests in patients with BMS and controls, participants were tested for depression, anxiety, fatigue and distress. Patients with BMS had noticeably higher scores for depression, fatigue and distress, compared to controls. Depression and distress were significantly correlated with the burning symptom. Moreover, distress and burning symptoms proved to be interdependent. Depression seems to play a specific role in BMS. Burning symptoms affect quality of life of patients and they could be a predictor of distress.

Anesthetic management of patients undergoing endovascular procedures for treating intracranial aneurysms or cerebrovascular malformations must consider a number of specific challenges, in addition to those associated with anesthesia for other specialties. In addition to maintenance of physiological stability, manipulation of systemic and cerebral hemodynamic parameters may be required to treat any sudden unexpected catastrophic neurological events. A multidisciplinary group including neuro- and pediatric anesthesiologists, interventional neuroradiologists, neurosurgeons, and a clinical methodologist contributed to this document. This consensus working group from 21 Italian institutions identified open questions regarding the best practices for management of anesthesia during endovascular neuroradiological procedures for intracranial aneurysms and cerebrovascular malformations, and addressed these by formulating practical consensus statements. At the first meeting in November 2015, nine key areas were identified regarding choice of anesthetic, patient monitoring, hemodynamic targets, postoperative care, and the management of neuromuscular blockade, anticoagulant and/or antiplatelet therapy, and special considerations for pediatric patients. Nine subgroups were established and a medical librarian performed literature searches in the Cochrane and MEDLINE/PubMed databases for each group. Groups drafted literature summaries and provisional responses in the form of candidate consensus statements based on evidence, when possible, and clinical experience, when this was lacking. Final wording was agreed at a meeting in April 2016 and where possible evidence was graded using United States Preventive Services Task Force criteria. Consensus (defined as >90% agreement) was based on evidence, clinical experience, clinician preference, feasibility in the Italian healthcare system, and cost/benefit considerations.

Background: Moyamoya (MM) is a very rare cerebrovascular disease, particularly in Caucasians. We describe the results of an Italian case series where the mainstay of treatment was a bypass or a combined approach., Methods: An analysis of a prospectively collected database was carried out. The main objective was to investigate (1) the risk of perioperative stroke and surgical complications, (2) the risk of new ischemic events, and (3) the risk of new hemorrhages at follow-up (mean follow-up: 2.2 years)., Results: Between January 2011 and January 2015 we carried out 34 bypasses in 23 patients with MM (15 MM disease, 5 unilateral MM, 3 MM syndrome); mean age was 34 (range:1-57). The mortality and definitive morbidity rates were 0 %. Two patients suffered from transient aphasia and one developed partial palsy of the facial nerve. Five of the 12 patients with preoperative fixed deficits improved. No patient with preoperative ischemia experienced new ischemic symptoms. Rebleeding occurred in 1 of the 11 patients with a hemorrhagic presentation (9 %)., Conclusions: The bypass/combined approach to MM appears to have a favorable risk profile and preventive effectiveness, particularly on TIAs and ischemic stroke.

With the increasingly widespread illicit use of cocaine, a broad spectrum of clinical pathologies related to this form of drug abuse is emerging. The most frequently used method of administration of powdered cocaine is intranasal inhalation, or "snorting." Consequently, adverse effects of cocaine on the nasal tract are common. Habitual nasal insufflations of cocaine can cause mucosal lesions. If cocaine use becomes chronic and compulsive, progressive damage of the mucosa and perichondrium leads to ischemic necrosis of the septal cartilage and perforation of the nasal septum. Occasionally, cocaine-induced lesions cause extensive destruction of the osteocartilaginous structures of the nose, sinuses, and palate and can mimic other diseases such as tumors, infections, and immunological diseases. In the literature currently available, involvement of the craniovertebral junction in the cocaine-induced midline destructive lesions (CIMDLs) has never been reported. The present case concerns a 44-year-old man who presented with long-standing symptoms including nasal obstruction, epistaxis, dysphagia, nasal reflux, and severe neck pain. A diagnosis of CIMDL was made in light of the patient's history and the findings on physical and endoscopic examinations, imaging studies, and laboratory testing. Involvement of the craniovertebral junction in the destructive process was evident. For neurosurgical treatment, the authors considered the high grade of atlantoaxial instability, the poorly understood cocaine-induced lesions of the spine and their potential evolution overtime, as well as cocaine abusers' poor compliance. The patient underwent posterior craniovertebral fixation. Understanding, classifying, and treating cocaine-induced lesions involving the craniovertebral junction are a challenge.

Somatic illness is not only an individual experience of physical and psychological suffering, but also a psychosocial status that modulates the patient's interpersonal relationships. Receiving a diagnosis of cancer causes severe distress. The patient's family, too, feels the emotional ups and downs of the patient. Like the patient, they feel distressed during the onset, course and outcome of the disease. Minimizing the interpersonal impact of the illness contributes to an improved quality of life for both patients and caregivers. Thus, it is widely assumed that cancer treatments should include some kind of psychological support for the patient and family members. All of these treatments are aimed at improving collaboration and illness perception among family, patients and healthcare professionals, and support the family during the course of the disease and cancer therapies. The family system theory is a valuable framework to explain how the disease of the patient and the family's daily life are interconnected. The therapeutic alliance with the family is a powerful tool to improve the quality of life for the patient, as well as to relieve the psychological distress of the family members who are involved. The following pages describe the objectives and conversational techniques that can be a tool for psychosocial work with the family of a cancer patient. The goal of this intervention is to help the patient's family to understand their problems and acknowledge the anxiety and fear of mourning that can impede their capacity to face the everyday problems they must cope with. To achieve this goal, it is recommended that a meeting (or a series of meetings) be scheduled, and conducted both in hospital and in the home. The steps to set up and conduct a family meeting are described in the paper, with special emphasis on communication skills required to meet family expectations and discuss the crucial issues of their everyday life.

A 56-year-old female with a giant partially thrombosed unruptured carotid-ophthalmic aneurysm was treated with a Pipeline flow diverter. Three months after the procedure, in concomitance with the discontinuation of one of the antiplatelet medications, the patient suffered from a minor stroke and relapsing transient ischemic attacks. The angiography demonstrated the occlusion of the internal carotid artery, and a perfusion-weighted CT scan showed a condition of hypoperfusion. The patient underwent a double-barrel extraintracranial bypass. The postoperative course was uneventful and she has experienced no further ischemic events to date.

Penetrating injuries to the spine, although less common than motor vehicle accidents and falls, are important causes of injury to the spinal cord. They are essentially of two varieties: gunshot or stab wounds. Gunshot injuries to the spine are more commonly described. Stab wounds are usually inflicted by knife or other sharp objects. Rarer objects causing incidental spinal injuries include glass fragments, wood pieces, chopsticks, nailguns, and injection needles. Just few cases of penetrating vertebral injuries caused by pencil are described. The current case concerns a 42-year-old man with an accidental penetrating stonemason pencil injury into the vertebral canal without neurological deficit. After the self-removal of the foreign object the patient complained of a disabling orthostatic headache. The early identification and treatment of the intracranial hypotension due to the posttraumatic cerebrospinal fluid (CSF) sacral fistulae were mandatory to avoid further neurological complications. In the current literature acute pattern of intracranial hypotension immediately after a penetrating injury of the vertebral column has never been reported.

The cooccurrence of Marfan syndrome and psychiatric disorders has been reported for many years. Furthermore, neuropsychological deficits have been shown to be associated with Marfan syndrome. The aim of the present article is to summarize findings from the sparse studies and case reports available. The results hold clinical and therapeutic implications and suggest that psychological and neuropsychological domains in Marfan syndrome patients should be carefully assessed. In particular, some patients may require specific rehabilitation programs. On this basis, a multidisciplinary approach to Marfan syndrome treatment seems mandatory., (© The Author(s) 2015.)

Occlusion of the intracranial internal carotid artery (ICA) by a pituitary adenoma with resulting cerebral ischemia is a very rare but devastating occurrence. The authors present a case in which a condition of symptomatic ICA occlusion due to a giant pituitary adenoma was successfully treated using a preliminary extraintracranial bypass as a "bridge" to the tumor removal. A 52-year-old patient presented with a minor stroke followed by pressure-dependent transient ischemic attacks consistent with a condition of hypoperfusion. MR imaging and a digital subtraction angiography revealed a pituitary adenoma occluding the ICA on the right side. He underwent a superficial temporal artery to middle cerebral artery (STA-MCA) bypass with the aim of revascularizing the ischemic hemisphere and reducing the risk of perioperative stroke or stroke evolution. The patient was subsequently operated on to remove the adenoma through a transsphenoidal approach. The postoperative course was uneventful and the patient has suffered no further ischemic events. When there are no emergency indications to decompress the optical pathways but the patient is at risk of impending stroke because of ICA occlusion, a two-step strategy consisting of a bypass and subsequent removal of the pituitary adenoma may be a valuable option.

Background: Anterior spinal surgery has a predominant role in the treatment of traumatic lesions of the subaxial cervical spine. Plating is considered indispensable to achieve stability but may cause dysphagia, dysphonia, and adjacent-level ossification. Zero-P (Synthes GmbH, Oberdorf, Switzerland), an anchored interdisc spacer, can be used without an associated plate. The present study aimed to test if this new implant would be associated with a low rate of dysphagia and other short-term complications compared with the standard for anterior spinal fusion surgery and would be able to achieve a solid fusion and maintain correct metamere alignment., Material and Methods: This is a preliminary presentation of a clinical case series of patients with subaxial cervical injuries who underwent anterior interbody fusion. From July 2009 until September 2011, 12 patients were treated with a Zero-P cage. The data for analysis included operating time compared with the standard for spinal fusion surgery with a cage plus plate construct, intraoperative blood loss, clinical and radiographic results, and complications., Results: In the postoperative period no patient had neurologic worsening. One patient experienced transient dysphonia and moderate dysphagia. All the patients were followed up for a minimum of 6 months (mean: 13 months; range: 6-27 months). Stability and fusion were obtained in all patients together with correct metamere alignment., Conclusion: We presented the preliminary results of a clinical case series. Our results support the initiation of prospective randomized trials with more patients and longer follow-up., (Georg Thieme Verlag KG Stuttgart · New York.)

Streptococcus pyogenes is a rare but aggressive cause of meningitis, which often evolves in a poor outcome with fatal consequences. Although lumbar puncture and CT scan of the brain are the gold standard of diagnosis of cerebral infections, they can have some limitations. We report and describe the clinical history and neuroimaging of a 36-year-old woman admitted to the emergency department of our hospital three days after the onset of earache and otorrhoea. When the patient developed an emergent refractory status epilepticus, the CT scan of the brain showed an unusual pneumocephalus. However, the MRI study of the brain revealed a pachymeningitis with partial thrombosis of the right transverse sinus and subdural empyema due to a S. pyogenes otitis media. Prompt diagnosis and the specific findings of the MRI allowed rapid correct treatment and thus led to a good outcome for the patient.

Purpose: Knowledge of the cumulative balance of sodium (CBS) is important for the diagnosis of salt disorders and water homeostasis and has the potential to predict hypovolemic status in acute neurological patients. However, an extensive application of the use of CBS is still lacking in the intensive care setting, where salt and water homeostasis represents a priority., Methods: Records of consecutive series of acute neurological patients admitted to a neurointensive care unit over a 6-month period were retrospectively reviewed. CBS was calculated at the admission to the Emergency Department. Discrimination between cerebral salt-wasting syndrome (CSWS) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was performed on the basis of the classical criteria. Additionally, we used the findings of a negative CBS exceeding 2 mEq/kg for the diagnosis of CSWS. Two independent clinicians who were blinded to the CBS results performed diagnosis of the causes of hyponatremia and estimated the daily volemic status of the patients on the basis of clinical parameters. Logistic regression analysis was used to determine the independent prognostic factors of hypovolemia., Results: Thirty-five patients were studied for a total of 418 days. Four patients (11.4%) fitted the criteria of CSWS and three patients (8.5%) had SIADH. The unavailability of the CBS led to a wrong diagnosis in three of the eight hyponatremic patients (37.5%). The risk of developing hypovolemia in patients with negative CBS was 7.1 times higher (CI 3.86-13.06; p < 0.001). Multivariate analysis revealed that negative cumulative fluid balance, negative CBS >2 mEq/kg, and CVP ≤5 cmH2O were independent prognostic factors for hypovolemia., Conclusions: CBS is likely to be a useful parameter in the diagnosis of CSWS and a surrogate parameter for estimating hypovolemia in acute neurological patients.