Outcome prediction in aneurysmal subarachnoid hemorrhage: a comparison of machine learning methods and established clinico-radiological scores

Reliable prediction of outcomes of aneurysmal subarachnoid hemorrhage (aSAH) based on factors available at patient admission may support responsible allocation of resources as well as treatment decisions. Radiographic and clinical scoring systems may help clinicians estimate disease severity, but their predictive value is limited, especially in devising treatment strategies. In this study, we aimed to examine whether a machine learning (ML) approach using variables available on admission may improve outcome prediction in aSAH compared to established scoring systems. Combined clinical and radiographic features as well as standard scores (Hunt & Hess, WFNS, BNI, Fisher, and VASOGRADE) available on patient admission were analyzed using a consecutive single-center database of patients that presented with aSAH (n = 388). Different ML models (seven algorithms including three types of traditional generalized linear models, as well as a tree bosting algorithm, a support vector machine classifier (SVMC), a Naive Bayes (NB) classifier, and a multilayer perceptron (MLP) artificial neural net) were trained for single features, scores, and combined features with a random split into training and test sets (4:1 ratio), ten-fold cross-validation, and 50 shuffles. For combined features, feature importance was calculated. There was no difference in performance between traditional and other ML applications using traditional clinico-radiographic features. Also, no relevant difference was identified between a combined set of clinico-radiological features available on admission (highest AUC 0.78, tree boosting) and the best performing clinical score GCS (highest AUC 0.76, tree boosting). GCS and age were the most important variables for the feature combination. In this cohort of patients with aSAH, the performance of functional outcome prediction by machine learning techniques was comparable to traditional methods and established clinical scores. Future work is necessary to examine input variables other than traditional clinico-radiographic features and to evaluate whether a higher performance for outcome prediction in aSAH can be achieved

Factors of Cortical Plasticity in Brachial Plexus Injury

Cortical plasticity is the brain’s capability of decoding new information through growth and reorganization over our whole life spam. It is the basis for good outcomes after reinnervation and for rehabilitation of adult and obstetric brachial plexus injury. Knowledge about cortical reorganization is crucial to reconstructive surgeons and physiotherapists that aim to give their patients a reasonable prognosis. This chapter intends to present and summarize the current literature on how to detect and quantify cortical plasticity and how research on factors that influence cortical plasticity, mainly in relation to peripheral nerve and more precise brachial plexus injury progresses. Peculiarities of adult and obstetric brachial plexus injuries and their treatment are given. We present techniques that visualize and quantify cortical plasticity with focus on functional imaging like fMRI and nTMS as well as molecular aspects. Future research is needed to understand mechanisms of how molecular changes on a synaptic level of a neuron influence the macroscopic plasticity, to improve rehabilitative resources, to understand the exact prognostic value of nTMS in brachial plexus injury and to investigate the therapeutic capability of rTMS

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies

Analysis of routine blood parameters in patients with amyotrophic lateral sclerosis and evaluation of a possible correlation with disease progression—a multicenter study

ObjectiveAmyotrophic lateral sclerosis (ALS) pathogenesis is still unclear, its course is considerably variable, and prognosis is hard to determine. Despite much research, there is still a lack of easily accessible markers predicting prognosis. We investigated routine blood parameters in ALS patients regarding correlations with disease severity, progression rate, and survival. Additionally, we analyzed disease and patients' characteristics relating to baseline blood parameter levels.MethodsWe analyzed creatine kinase (CK), albumin (ALB), creatinine (CREA), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) levels around time of diagnosis in 1,084 ALS patients. We carried out linear regression analyses including disease and patients' characteristics with each blood parameter to detect correlations with them. Linear regression models were performed for ALSFRS-R at study entry, its retrospectively defined rate of decay and prospectively collected progression rate. Different survival analysis methods were used to examine associations between blood parameters and survival.ResultsWe found higher CK (p-value 0.001), ALB (p-value <0.001), CREA (p-value <0.001), and HDL levels (p-value 0.044) at time of diagnosis being associated with better functional status according to ALSFRS-R scores at study entry. Additionally, higher CREA levels were associated with lower risk of death (p-value 0.003).ConclusionsOur results indicate potential of CK, ALB, CREA, and HDL as disease severity or progression markers, and may also provide clues to ALS pathogenesis. However, these values are highly dependent on other variables, and further careful, longitudinal analyses will be necessary to prove the relevance of our findings

Improvement of diagnostics and therapy of cerebrovascular diseases: evaluation of new technologies and existing paradigms

Hintergrund: Die diagnostischen und therapeutischen Möglichkeiten cerebrovaskulärer Erkrankungen unterliegen einem stetigen Fortschritt. Unsere westlichen Gesellschaften befinden sich in einem ausgeprägten demografischen Wandel mit Einfluss auf das Vorkommen und die Ausprägung cerebrovaskulärer Erkrankungen. Am Beispiel der CT Diagnostik, des Ultrahochfeld MRTs sowie chirurgischen und intensivmedizinischen Behandlungsstandards sollen gängige diagnostische und therapeutische Paradigmen in diesem Kontext überprüft werden. Methodik: An der Charité Universitätsmedizin Berlin wurden die Behandlungsdaten und diagnostischen Charakteristika von Patienten mit cerebrovaskulären Erkrankungen retrospektiv (aneurysmatische Subarachnoidalblutung, ischämischer Schlaganfall) und prospektiv (Moyamoya- Erkrankung) untersucht. Die lokale Ethikkommission hat den Untersuchungsvorhaben jeweils zugestimmt (EA1/156/14, EA1/291/14, 7UP World Health Organization register No. DRKS00003193). Ergebnisse: Die 7 T MRA Diagnostik bei der Moyamoya-Erkrankung zeigt zwar eine mit der DSA vergleichbare Auflösung, die praktische Umsetzbarkeit durch lange Scanzeiten und eine erhöhte Anfälligkeit für Bewegungsartefakte ist jedoch limitiert. Die 7 T MPRAGE ist eine gute Alternative in Bezug auf Durchführbarkeit und Genauigkeit der Gefäßdarstellung. Die CT-Diagnostik bei aSAB lässt anhand der neuen BNI-Skala nicht nur eine Vorhersage des Auftretens eines angiografischen Vasospasmus, sondern auch die Vorhersage des Auftretens von neuen Infarkten und limitiertem Outcome zu. Elemente des BNI-Scores zusammen mit dem Auftreten eines akuten Hydrocephalus und einem schlechten Hunt und Hess Grades (≥ 4) erlauben im Rahmen der SDASH-Score-Kalkulation eine Vorhersage des chronischen Shunt-pflichtigen Hydrozephalus nach aSAB. Das Auftreten eines angiografischen Vasospasmus und ein reduziertes Patienten-Outcome bei aSAB korreliert mit niedrigen Dosierungen der Nimodipin-Prophylaxe. Nimodipin musste aufgrund des blutdrucksenkenden Effektes in vielen Fällen auf die Hälfte reduziert (28.6 %) oder gestoppt (27.7 %) werden. Die Überprüfung der neurochirurgischen Behandlungsstrategien beim ischämischen Schlaganfall ergab die vergleichbar sichere Durchführung einer extra-intracraniellen Bypass-Anlage für Patienten über vs. unter 70 Jahren. Eine erweiterte Dekompression beim malignen Schlaganfall zeigte in der untersuchten retrospektiven Kohorte keine Verbesserung des allgemeinen Patienten-Outcomes jedoch ein geringeres Ausmaß der Schwellung und der transtentoriellen Herniation. Schlussfolgerung: Die stetig fortschreitende technische Entwicklung macht eine genauere Abbildbarkeit der Ausprägung cerebrovaskulärer Erkrankungen möglich. Zusätzlich ergeben sich daraus genauere Möglichkeiten, den Verlauf cerebrovaskulärer Erkrankungen vorherzusagen. Die genauere Abbildbarkeit und Vorhersage lässt eine individuellere Einschätzung der Patienten und die Planung sowie Überprüfung ihrer neurochirurgischen Therapie zu. Die Veränderung der Demografie in den westlichen Gesellschaften fordert eine individuelle Anpassung der Therapiemöglichkeiten für ältere und sehr alte Patienten.Background: Advances in diagnostics and treatment of cerebrovascular diseases underlie constant changes. Demographic alterations in Western societies involve modifications of incidence and fatality of cerebrovascular diseases. We aimed to test and reevaluate current diagnostic paradigms and surgical concepts in that context. Methods: Data of clinical course and diagnostic modalities of patients with aneurysmal subarachnoid hemorrhage, ischemic infarction and Moyamoya vasculopathy treated at Charité Universitätsmedizin Berlin were analyzed. Data collection was approved by the local ethics committee (EA1/156/14, EA1/291/14, 7UP World Health Organization register No. DRKS00003193). Results: Spatial resolution of 7 T MRA and digital subtraction angiography were comparable but practical limitations included long scanning times and motion artefacts. 7 T MPRAGE proved to be a valid alternative displaying cerebral vessel pathology in Moyamoya vasculopathy. Quantification of subarachnoid blood on CT using the BNI scale in aneurysmal hemorrhage not only predicted angiographic vasospasm but also new cerebral infarction and unfavorable patient outcome. Calculation of the SDASH score including the factors thickness of subarachnoidal blood, presence of acute hydrocephalus, and poor clinical grade (Hunt and Hess ≥ 4) helped to predict shunt dependent chronic hydrocephalus after aneurysmal subarachnoid hemorrhage. Occurrence of angiographic vasospasm in patients with aneurysmal subarachnoid hemorrhage was associated with reduction of nimodipine dosages. Due to a significant reduction of blood pressure, nimodipine was reduced by 50 % in 28.6 % and stopped in 27.7 % of patients with aSAH. Evaluation of surgical strategies in patients with ischemic infarction revealed comparable results in patient below and above 70 years of age. The extension of decompressive hemicraniectomy in malignant hemispheric infarction did not result in a better overall patient outcome in our series, but transtentorial herniation and hemispheric swelling was significantly reduced in patients with extended craniectomies. Conclusion: Technical advances allow a more distinct visualization and therefore prediction of cerebrovascular diseases and their clinical course. This may lead to a more individual patient assessment and planning of therapy. Moreover, individual treatment concepts in our ageing western societies for elderly patients are necessary

Cellular changes in blood indicate severe respiratory disease during influenza infections in mice.

Influenza A infection is a serious threat to human and animal health. Many of the biological mechanisms of the host-pathogen-interactions are still not well understood and reliable biomarkers indicating the course of the disease are missing. The mouse is a valuable model system enabling us to study the local inflammatory host response and the influence on blood parameters under controlled circumstances. Here, we compared the lung and peripheral changes after PR8 (H1N1) influenza A virus infection in C57BL/6J and DBA/2J mice using virus variants of different pathogenicity resulting in non-lethal and lethal disease. We monitored hematological and immunological parameters revealing that the granulocyte to lymphocyte ratio in the blood represents an early indicator of severe disease progression already two days after influenza A infection in mice. These findings might be relevant to optimize early diagnostic options of severe influenza disease and to monitor successful therapeutic treatment in humans

The Barrow Neurological Institute Scale Revisited: Predictive Capabilities for Cerebral Infarction and Clinical Outcome in Patients With Aneurysmal Subarachnoid Hemorrhage

BACKGROUND: In 2012, a new computed tomography (CT) grading scale was introduced by the Barrow Neurological Institute group ("BNI scale") to predict angiographic and symptomatic vasospasm in aneurysmal subarachnoid hemorrhage. OBJECTIVE: To address the question of whether BNI grading is reliable in the prediction of cerebral infarction and clinical outcome and to compare BNI scores to existing radiographic and clinical models of outcome prediction. METHODS: Consecutive data of 260 patients with aneurysmal subarachnoid hemorrhage was retrospectively analyzed with respect to radiographic and clinical parameters. RESULTS: Patients presenting with more severe BNI grades were older ( P = .002), displayed lower Glasgow Coma Scale scores at admission ( P < .001) and were more often diagnosed with intraventricular hemorrhage ( P < .001). An increasing BNI grade was associated with higher rates of severe angiographic vasospasm ( P = .007), the occurrence of new cerebral infarction ( P < .001), and poor patient outcome ( P < .001). In contrast, analysis according to the Fisher grading system did not show a significant relationship to any outcome parameter. Multivariate analysis combining radiographic and clinical parameters showed significant results for clinical scores (Hunt and Hess and World Federation of Neurosurgical Societies) with radiographic information losing its predictive capability. CONCLUSION: The BNI scale is easily applicable and superior to the original Fisher scale regarding prediction of angiographic vasospasm, new cerebral infarction, and patient outcome. Presence of intraventricular hemorrhage and intracerebral hemorrhage are additional radiographic factors with outcome relevance that are not part of the BNI scale. Established clinical scores like World Federation of Neurosurgical Societies and Hunt and Hess grading were more relevant for outcome prediction than any radiographic information

A novel score to predict shunt dependency after aneurysmal subarachnoid hemorrhage

OBJECTIVE Feasible clinical scores for predicting shunt-dependent hydrocephalus (SDHC) after aneurysmal subarachnoid hemorrhage (aSAH) are scarce. The chronic hydrocephalus ensuing from SAH score (CHESS) was introduced in 2015 and has a high predictive value for SDHC. Although this score is easy to calculate, several early clinical and radiological factors are required. The authors designed the retrospective analysis described here for external CHESS validation and determination of predictive values for the radiographic Barrow Neurological Institute (BNI) scoring system and a new simplified combined scoring system. METHODS Consecutive data of 314 patients with aSAH were retrospectively analyzed with respect to CHESS parameters and BNI score. A new score, the shunt dependency in aSAH (SDASH) score, was calculated from independent risk factors identified with multivariate analysis. RESULTS Two hundred twenty-five patients survived the initial phase after the hemorrhage, and 27.1% of these patients developed SDHC. The SDASH score was developed from results of multivariate analysis, which revealed acute hydrocephalus (aHP), a BNI score of ≥ 3, and a Hunt and Hess (HH) grade of ≥ 4 to be independent risk factors for SDHC (ORs 5.709 [aHP], 6.804 [BNI], and 4.122 [HH]; p < 0.001). All 3 SDHC scores tested (CHESS, BNI, and SDASH) reliably predicted chronic hydrocephalus (ORs 1.533 [CHESS], 2.021 [BNI], and 2.496 [SDASH]; p ≤ 0.001). Areas under the receiver operating curve (AUROC) for CHESS and SDASH were comparable (0.769 vs 0.785, respectively; p = 0.447), but the CHESS and SDASH scores were superior to the BNI grading system for predicting SDHC (BNI AUROC 0.649; p = 0.014 and 0.001, respectively). In contrast to CHESS and BNI scores, an increase in the SDASH score coincided with a monotonous increase in the risk of developing SDHC. CONCLUSIONS The newly developed SDASH score is a reliable tool for predicting SDHC. It contains fewer factors and is more intuitive than existing scores that were shown to predict SDHC. A prospective score evaluation is needed

Pair wise statistical comparison of all granulocyte to lymphocyte ratios of C57BL/6J presented in Figure 2A.

<p>Data were analyzed for statistically significant differences using non-parametric Mann-Whitney-U-test. *: p-value<0.05; **: p-value<0.01; ***: p-value<0.001; ****: p-value<0.0001.</p

Flow cytometric analyses revealed quantitative and qualitative differences of the host response to PR8M versus PR8F infection.

<p>Lungs from infected C57BL/6J mice (2×10³ FFU) were extracted and cell suspensions were analyzed by flow cytometry on days 0, 2, 3, 5, 8 and 14 p.i. After excluding dead cells and gating on leukocytes (CD45⁺), four combinations of fluorochrome-labeled antibodies were used to differentiate various immune cell populations: CD11b⁺Ly6G⁺ (granulocytes, A); CD11b⁺CD115⁺ (macrophages, B); CD11c⁺MHCII⁺ (dendritic cells, C); NKp46⁺ and CD3⁺ (NK and T cells, D). The left panel illustrates the results of day 3 p.i. and indicates the population analyzed in the right panel. The right panel shows percentage of individual cell populations over time (mean±SEM). For each measurement two to three lungs were pooled and data from two independent experiments were combined (n = 3–6). Data were analyzed for statistically significant differences using non-parametric Mann-Whitney-U-test. *: p-value<0.05; **: p-value<0.01. Ratios of Ly6G⁺CD11b^high cells (granulocytes) vs. T cells (CD3⁺) or NK cells (NKp46⁺) in PR8M and PR8F infected mice revealed significant differences (p value as indicated) on day 5 p.i. (E).</p