COVID-19 and Intracranial Hemorrhage: A Multicenter Case Series, Systematic Review and Pooled Analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). RESULTS: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. CONCLUSION: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.

An Automated Electronic Screening Tool (DETECT) for the Detection of Potentially Irreversible Loss of Brain Function.

BACKGROUND: A major reason for the low number of organ donors in Germany is a deficit in the recognition of patients who may have impending irreversible loss of brain function (ILBF) in hospitals capable of organ retrieval. METHODS: We used anonymized data from the German Organ Procurement Organization (Deutsche Stiftung Organtransplantation, DSO) to compare two 12-month periods (a reference period and an evaluation period) before and after the implementation of an electronic screening tool (DETECT) at the University Hospital Dresden (UKD) with four other university hospitals without tool implementation (comparative cohort). DETECT is intended to aid in the recognition of potentially impending ILBF. The study endpoints encompassed patients with potentially unrecognized ILBF, patients with recognized ILBF, organ donations performed, and reports to the DSO. Changes in absolute risk were compared with Breslow-Day tests. RESULTS: 309 patients who died with primary or secondary brain lesions were identified in the UKD in the reference and evaluation periods (164 and 145 patients, respectively), and 1060 (529, 531) in the comparative cohort. In the UKD, the number of unrecognized cases of possibly impending ILBF was 14/164 (8.54%) in the reference period and 1/145 (0.69%) in the evaluation period, yielding an absolute reduction of 7.85% (95% confidence interval [--3.36; --12.33]); by contrast, in the comparative cohort, there was a 0.55% absolute increase between the two periods ([--2.21; 3.30]; p = 0.002 for the comparison between the two cohorts). Only minor differences in absolute risk change were seen with regard to the probability of recognized ILBF (7.09% [0.29; 13.88] vs. 2.42% [1.18; 6.01]; p = 0.234), organ donation (4.70% [--0.89; 10.28] vs. 0.55% [--2.17; 3.26]; p = 0.214), or reporting to the DSO (4.17% [--1.77; 10.11] vs. 2.22% [--1.44; 5.89; p = 0.447); these changes may have arisen by chance. CONCLUSION: These findings suggest that the use of DETECT can help to reduce the deficit in the recognition of patients with impending or manifest ILBF.

Cerebral Abscess by Fonsecaea monophora-The First Case Reported in Germany.

We report the first case of cerebral Fonsecaea monophora infection in a German woman without immunodeficiency or travel history. F. monophora infection is a rare differential diagnosis of cerebral tumors; it was previously considered a tropical fungus. This case adds to the scarce reports in nontropical regions.

Decannulation and Functional Outcome After Tracheostomy in Patients with Severe Stroke (DECAST): A Prospective Observational Study.

BACKGROUND: Tracheostomy is performed in ventilated stroke patients affected by persisting severe dysphagia, reduced level of consciousness, or prolonged mechanical ventilation. The study aim was to determine the frequency and predictors of successful decannulation and long-term functional outcome in tracheotomized stroke patients. METHODS: A prospective single-center observational study recruited ventilated patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Follow-up visits were performed at hospital discharge, 3, and 12 months. Competing risk analyses were performed to identify predictors of decannulation. RESULTS: We included 53 ventilated stroke patients who had tracheostomy. One year after tracheostomy, 19 patients were decannulated (median [IQR] time to decannulation 74 [58-117] days), 13 patients were permanently cannulated, and 21 patients died without prior removal of the cannula. Independent predictors for decannulation in our cohort were patient age (HR 0.95 [95% CI: 0.92-0.99] per one year increase, p = 0.003) and absence of sepsis (HR 4.44 [95% CI: 1.33-14.80], p = 0.008). Compared to surviving patients without cannula removal, decannulated patients had an improved functional outcome after one year (median modified Rankin Scale score 4 vs. 5 [p < 0.001]; median Barthel index 35 vs. 5 [p < 0.001]). CONCLUSIONS: Decannulation was achieved in 59.4% of stroke patients surviving the first 12 months after tracheostomy and was associated with better functional outcome compared to patients without decannulation. Further prospective studies with larger sample sizes are needed to confirm our results.

Idiopathic normal pressure hydrocephalus: diagnostic and predictive value of clinical testing, lumbar drainage, and CSF dynamics.

OBJECTIVE The aim of the study was to analyze the diagnostic and predictive values of clinical tests, CSF dynamics, and intracranial pulsatility tests, compared with external lumbar drainage (ELD), for shunt response in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Sixty-eight consecutive patients with suspected iNPH were prospectively evaluated. Preoperative assessment included clinical tests, overnight intracranial pressure (ICP) monitoring, lumbar infusion test (LIFT), and ELD for 24-72 hours. Simple and multiple linear regression analyses were conducted to identify predictive parameters concerning the outcome after shunt therapy. RESULTS Positive response to ELD correctly predicted improvement after CSF diversion in 87.9% of the patients. A Mini-Mental State Examination (MMSE) value below 21 was associated with nonresponse after shunt insertion (specificity 93%, sensitivity 67%). Resistance to outflow of CSF (ROut) > 12 mm Hg/ml/min was false negative in 21% of patients. Intracranial pulsatility parameters yielded different results in various parameters (correlation coefficient between pulse amplitude and ICP, slow wave amplitude, and mean ICP) but did not correlate to outcome. In multiple linear regression analysis, a calculation of presurgical MMSE versus the value after ELD, ROut, and ICP amplitude quotient during LIFT was significantly associated with outcome (p = 0.04). CONCLUSIONS Despite a multitude of invasive tests, presurgical clinical testing and response to ELD yielded the best prediction for improvement of symptoms following surgery. The complication rate of invasive testing was 5.4%. Multiple and simple linear regression analyses indicated that outcome can only be predicted by a combination of parameters, in accordance with a multifactorial pathogenesis of iNPH.

Daily drained CSF volume is a predictor for shunt dependence - A retrospective study.

OBJECTIVES: Acute hydrocephalus ensues from various intracranial processes and is usually treated using external ventricular drainage (EVD). After the acute phase, a clamp trial is usually performed to identify patients requiring permanent CSF shunting. The aim of our study was to identify simple and clinically accessible factors that can help predict the result of the EVD clamp trial. METHODS: 86 patients were selected for this retrospective analysis. Average CSF drained volume over 3 days given a constant EVD pressure level of 15 cm H2O and other clinical and laboratory parameters were statistically compared with the result of an EVD clamp trial. RESULTS: The univariate analysis identified significant differences between the groups of patients who failed or passed the EVD clamp trial for the mean daily drained volume over 3 days (Mann-Whitney U-test, p<0.01). In the multivariate logistic regression, the average daily CSF output over 3 days was also significant (p=0.02), no other significant factors could be identified. Using hierarchical clustering, the best threshold daily value for EVD clamp trial failure was found at 130 ml (mean daily drained CSF volume) with the sensitivity of 64.5% and specificity of 83.6% (chi-square 20.6, p<0.01). CONCLUSION: We have identified a simple, clinically available factor for identifying patients who are likely to fail the EVD clamp trial.

The influence of lumbar spinal drainage on diffusion parameters in patients with suspected normal pressure hydrocephalus using 3T MRI.

BACKGROUND: Normal pressure hydrocephalus (NPH) has been an ongoing and challenging field of research for the past decades because two main issues are still not fully understood: the pathophysiologic mechanisms underlying ventricular enlargement and prediction of outcome after surgery. PURPOSE: To evaluate changes in diffusion tensor imaging (DTI) derived parameters in patients with suspected normal pressure hydrocephalus before and after withdrawal of cerebrospinal fluid (CSF). MATERIAL AND METHODS: Twenty-four consecutive patients with clinical and radiological suspicion of NPH and 14 age-matched control subjects were examined with DTI on a clinical 3T scanner. Patients were examined before and 6-36 h after CSF drainage (interval between scans, 5 days). Fifteen patients were finally included in data analysis. Fractional anisotropy (FA) and mean, parallel, and radial diffusivity (MD, PD, RD) were evaluated using a combination of a ROI-based approach and a whole-brain voxel-by-voxel analysis. RESULTS: Alteration of DTI parameters in patients with suspected NPH is regionally different. Compared to the control group, we found an elevation of FA in the subcortical white matter (SCWM) and corpus callosum, whereas the other diffusion parameters showed an increase throughout the brain in variable extent. We also found a slight normalization of RD in the SCWM in patients after lumbar drainage. CONCLUSION: Our results show that DWI parameters are regionally dependent and reflect multifactorial (patho-) physiological mechanisms, which need to be interpreted carefully. It seems that improvement of gait is caused by a decrease of interstitial water deposition in the SCWM.

Search for genetic variants in the ryanodine receptor 1 gene in patients with symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm is one of the most serious complications after subarachnoid hemorrhage (SAH). The cerebral artery diameter is regulated by complex physiological mechanisms. Among them the regulation of intracellular calcium homeostasis seems to play a crucial role. Recent data suggest that ryanodine receptors (RYRs) are involved in regulating the luminal calcium concentration in vascular smooth muscle cells. In this gene association investigation, we studied the question as to whether variants in the gene for the ryanodine receptors subtype 1 (RYR1) are associated with symptomatic cerebral vasospasm following SAH. METHODS: After informed consent genomic DNA analysis was performed from a whole blood sample in 46 patients suffering from aneurysmal SAH. 16 Patients were affected by symptomatic vasospasm. The RYR1 gene was screened for possible genetic variants by means of direct sequencing. The association of these variants was correlated to the development of symptomatic vasospasm, which was confirmed by clinical examination combined with cerebral angiography, transcranial doppler sonography, or CT scan. RESULTS: Three different genetic RYR1 variants (c.5360C>T, c.6178G>T, and c.7244G>A) were identified in the study. The G/T genotype of RYR1 c.6178G>T was associated with an increased risk for development of symptomatic vasospasm (odds ratio 6.4; 95% CI 1.1-37.8; P = 0.04). CONCLUSION: Our pilot study suggests that RYRs are involved in the complex pathophysiology of vasospasm development following SAH. The potential role of RYR1 as a biomarker for prediction of cerebral vasospasm after SAH has to be confirmed in a larger clinical trial.

Systematic user-based assessment of "Navigated Control Spine" / Systematische, nutzerzentrierte Evaluation von "Navigated Control Spine".

The aim of this study was the systematic preclinical assessment of a new mill for spinal surgery. This mill automatically switches off at predefined workspace margins. The system is called the "Navigated Control Spine". The workspace is planned intraoperatively with fluoroscopic images. Assessment was performed in a simulated surgical scenario with real surgical instruments and equipment, and the following criteria were measured: "milling accuracy" and "surgical workflow parameters". To simulate the patient, an anatomical spine model was created with a Rapid Prototyping machine. The models included electronic components that simulate injuries to the structures at risk. For the workflow parameters, the results show differences between experienced and inexperienced surgeons. The maximum accuracy for experienced surgeons was +0.31 mm and for inexperienced surgeons +0.57 mm. The dura, as one of the structures at risk, was never injured.

Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury.

OBJECTIVE: To evaluate the concept of a cerebrovascular pressure reactivity-guided optimal cerebral perfusion pressure after traumatic brain injury by analyzing the relationship between optimal cerebral perfusion pressure and brain tissue oxygen. DESIGN: Prospective observational cohort study. SETTING: Neurosurgical intensive care unit of a university hospital. PATIENTS: Thirty-eight patients after head injury. INTERVENTIONS: Continuous computerized monitoring of mean arterial pressure, intracranial pressure, and brain tissue oxygen for 5.3 +/- 2.6 days. The index of cerebrovascular pressure reactivity was calculated as a moving correlation coefficient between spontaneous low-frequency fluctuations of mean arterial pressure and intracranial pressure. Optimal cerebral perfusion pressure was defined as the cerebral perfusion pressure level with the lowest average index of cerebrovascular pressure reactivity. MEASUREMENTS AND MAIN RESULTS: Optimal cerebral perfusion pressure could be identified in 32 of 38 patients. Median optimal cerebral perfusion pressure was between 70 and 75 mm Hg (range, 60-100 mm Hg). Below the level of optimal cerebral perfusion pressure, brain tissue oxygen decreased in parallel to cerebral perfusion pressure, whereas brain tissue oxygen reached a plateau above optimal cerebral perfusion pressure. Optimal cerebral perfusion pressure correlated significantly with the cerebral perfusion pressure level, where brain tissue oxygen reached its plateau (r = .79; p < .01). Average brain tissue oxygen at optimal cerebral perfusion pressure was 24.5 +/- 6.0 mm Hg. CONCLUSIONS: This study supports the concept of cerebrovascular pressure reactivity-based individual optimal cerebral perfusion pressure. Driving cerebral perfusion pressure in excess of optimal cerebral perfusion pressure does not yield improvements in brain tissue oxygen after head injury and should be avoided, whereas cerebral perfusion pressure below optimal cerebral perfusion pressure may result in secondary cerebral ischemia.

Gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73.

Cks2 proteins are essential components of cyclin/cyclin-dependent kinase complexes and contribute to cell cycle control. We identify Cks2 as a transcriptional target downregulated by the tumor suppressor p53. Cks2 expression was found to be repressed by p53 both at the mRNA and the protein levels. p53 downregulates transcription from the Cks2 promoter in a dose-dependent manner and in all cell types tested. This repression appears to be independent of p53 binding to the Cks2 promoter. In contrast to p53, neither p63 nor p73 proteins can repress Cks2 transcription. Thus p53, rather than its homologues p63 and p73, may contribute to control of the first metaphase/anaphase transition of mammalian meiosis by downregulation of Cks2 expression.