Neurometabolic Therapy in Patients with Encephalopathy Associated with COVID-19

The objective: to evaluate the effectiveness of neurometabolic therapy in patients with severe course of the new coronavirus infection of COVID-19 complicated by the development of encephalopathy.Subjects and Methods. A pilot prospective study was carried out with the participation of 61 patients with a severe course of COVID-19 complicated by encephalopathy. The patients were randomized into two groups: the study group (n = 34), the patients in which, in contrast to the control group (n = 27), received Cytoflavin in addition to the main therapy in a daily dose of up to 40 ml for 5 days. The dynamics of the general and neurological status was assessed on days 3‒4 and 6‒7 days of treatment using the NEWS (National Early Warning Score), Glasgow coma and ICDSC (Intensive Care Delirium Screening Checklist) scales. Additionally, the blood level of neuron-specific enolase (NSE) was investigated at baseline and on days 6‒7.Results. Patients in most cases were elderly or senile with a high comorbidity index (up to 4 points according to Charlson). The persistence of delirious symptoms correlated with their age and low SpO2 levels. In half of the cases (50.8%), the disease had an unfavorable outcome. In the study group, by the 6‒7th day of treatment, there was a significant positive dynamics of the general condition, assessed by the NEWS scale (p = 0.012), a tendency towards a faster recovery of the overall score on the Glasgow scale (p = 0.083), a tendency towards more rapid regression of delirious symptoms by ICDSC scale (p = 0.055) versus the comparison group.Conclusions. Given the high risk of an unfavorable outcome in patients with a severe course of COVID-19 complicated by the development of encephalopathy, the additional use of Cytoflavin is advisable since it contributes to the regression of the symptoms of encephalopathy and may have a positive effect on the course of the disease.

Prognosis in moderate-severe traumatic brain injury in a Swedish cohort and external validation of the IMPACT models

Background A major challenge in management of traumatic brain injury (TBI) is to assess the heterogeneity of TBI pathology and outcome prediction. A reliable outcome prediction would have both great value for the healthcare provider, but also for the patients and their relatives. A well-known prediction model is the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) prognostic calculator. The aim of this study was to externally validate all three modules of the IMPACT calculator on TBI patients admitted to Uppsala University hospital (UUH). Method TBI patients admitted to UUH are continuously enrolled into the Uppsala neurointensive care unit (NICU) TBI Uppsala Clinical Research (UCR) quality register. The register contains both clinical and demographic data, radiological evaluations, and outcome assessments based on the extended Glasgow outcome scale extended (GOSE) performed at 6 months to 1 year. In this study, we included 635 patients with severe TBI admitted during 2008–2020. We used IMPACT core parameters: age, motor score, and pupillary reaction. Results The patients had a median age of 56 (range 18–93), 142 female and 478 male. Using the IMPACT Core model to predict outcome resulted in an AUC of 0.85 for mortality and 0.79 for unfavorable outcome. The CT module did not increase AUC for mortality and slightly decreased AUC for unfavorable outcome to 0.78. However, the lab module increased AUC for mortality to 0.89 but slightly decreased for unfavorable outcome to 0.76. Comparing the predicted risk to actual outcomes, we found that all three models correctly predicted low risk of mortality in the surviving group of GOSE 2–8. However, it produced a greater variance of predicted risk in the GOSE 1 group, denoting general underprediction of risk. Regarding unfavorable outcome, all models once again underestimated the risk in the GOSE 3–4 groups, but correctly predicts low risk in GOSE 5–8. Conclusions The results of our study are in line with previous findings from centers with modern TBI care using the IMPACT model, in that the model provides adequate prediction for mortality and unfavorable outcome. However, it should be noted that the prediction is limited to 6 months outcome and not longer time interval.

CSF Neurofilament Light Chain Concentrations Predict Outcome in Bacterial Meningitis

Background and ObjectivesNeurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquired bacterial meningitis.MethodsWe measured NfL concentration CSF samples from a prospective cohort study of adults with community-acquired bacterial meningitis in The Netherlands and determined associations between NfL CSF concentrations, clinical characteristics, and outcome in multivariate analyses. We identified independent predictors of an unfavorable outcome (Glasgow Outcome Scale scores 1–4) by logistic regression.ResultsCSF NfL concentrations were evaluated in 429 episodes of 425 patients with community-acquired bacterial meningitis. The median age of 429 episodes was 62 years (interquartile range, 50–69 years). Of note, 290 of 422 (68%) episodes presented with an altered mental status (Glasgow Coma Scale score < 14). Most common causative pathogens were Streptococcus pneumoniae (73%), Neisseria meningitidis (7%), and Listeria monocytogenes (5%). The overall case fatality rate was 62 of 429 (15%), and unfavorable outcome occurred in 57 (37%) of 429 episodes. In multivariate analysis, predictors of unfavorable outcome were older age (OR 1.03, 95% CI 1.01–1.05), cranial nerve palsy (OR 4, 95% CI 1.6–10.3), high serum C-reactive protein concentration (OR 1.3, 95% CI 1.01–1.05), and high CSF NfL concentration (OR 1.5, 95% CI 1.07–2.00). CSF NfL concentrations were higher in patients presenting with focal cerebral deficits (717 pg/mL [416–1,401] vs 412 pg/mL [278–731]; p < 0.001). The area under the curve (AUC) for predicting unfavorable outcome in bacterial meningitis of CSF NfL concentration was 0.69 (95% CI, 0.64–0.74).DiscussionCSF NfL concentration is independently associated with unfavorable outcome in adults with community-acquired bacterial meningitis, suggesting that CSF NfL concentration may be a useful biomarker for prognostic assessment in bacterial meningitis.Classification of EvidenceCan the level of NfL in CSF (the index test) predict unfavorable outcome in patients with bacterial meningitis, in a cohort of bacterial meningitis patients with a favorable and unfavorable outcome? This study provides Class II evidence that NfL level in CSF is a moderate predictor, with the AUC for predicting unfavorable outcome in bacterial meningitis being 0.69 (95% CI, 0.64–0.74).

CLINICAL CASE OF ADVERSE OUTCOME OF NEONATAL LYSTERIOSIS

A clinical case of neonatal listeriosis with an unfavorable outcome is presented. The first symptoms of the disease in a newborn appeared on the 3rd day, intrauterine infection was suspected on the 5th day. A evolving clinical picture with death on day 9 is described. The issues of the ongoing antibiotic therapy are discussed. The diagnosis of neonatal listeriosis was confirmed by the results of postmortem and morphological examination of the deceased newborn. The cause of his death was an early form of listeria infection (septicemia) with damage mainly to the lungs and liver. Specialists who provide care for pregnant women, newborns and children should be alert for listeria infection.

Prediction of unfavorable outcome in ischemic stroke patients with chronic kidney disease

Patients with chronic kidney disease (CKD) have significantly poorer functional outcomes and greater mortality after suffering a stroke. The present study aimed to identify the prognostic factors of an unfavorable outcome of the ischemic stroke in patients with CKD. Methods and subjects. The current study was designed retrospectively and performed with data of patients who were hospitalized due to ischemic stroke to the neurological department. A complex clinical and neuroimaging investigation was carried out in 65 patients (30 men and 35 women) aged 53 to 81 years (mean age – (67.7 ± 5.9) years) with acute stroke and CKD. Patients underwent all the necessary ancillary investigations according to guidelines. According to the clinical outcome on the 21-st day by the modified Rankin scale (mRS) all patients were divided into two groups: 1-st –favorable stroke outcome (mRS=0-3) – 34 (52.3%), 2-nd – unfavorable stroke outcome – (mRS=4-6) – 31 (47.7%). Results. During comparing the basic characteristics of both groups, it was revealed that patients with unfavorable functional outcomes were almost twice as likely to have diabetes mellitus (51.6% vs. 26.5%, p<0.037) and atrial fibrillation (41.9% vs. 17.6%, p<0.032). In age-and sex-adjusted multifactor logistic regression it was found that ischemic stroke unfavorable outcome is associated with diabetes mellitus (OR – 2.5, CI: 1.6-8.3; p=0.014), atrial fibrillation – 2.7, CI: 0.7-9.6; p=0.043), dialysis therapy (OR – 3.4, CI: 2.3-8.1; p=0.007), GFR <42 ml/min/1.73 m2 (OR – 2.7, CI: 2.1-7.8; p=0.003). Conclusions. Determining prognostic factors of unfavorable course of the ischemic stroke in patients with CKD allows to optimize the management of such patients in the acute period of ischemic stroke and improve the prognosis.

Stroke Lateralization in Large Hemisphere Infarctions: Characteristics, Stroke-Related Complications, and Outcomes

Objectives: To assess the hemispheric differences in characteristics, stroke-related complications, and outcomes of patients with large hemisphere infarctions (LHI).Methods: We enrolled consecutive patients admitted within 24 h after the diagnosis of LHI (defined as an ischemic stroke involving more than 50% of the territory of the middle cerebral artery in computed tomography and/or magnetic resonance imaging). Univariate and multivariate analysis were performed to explore the association between lateralization and stroke-related complications and clinical outcomes.Results: A total of 314 patients with LHI were enrolled, with 171 (54.5%) having right hemispheric involvement. Right-sided patients with LHI had lower baseline National Institutes of Health Stroke Scale (NIHSS) score (18 vs. 22, p &lt; 0.001), higher frequency of atrial fibrillation (69.0 vs. 52.4%, p = 0.003), and higher proportion of cardio-embolism (73.1 vs. 56.6%, p = 0.013) than the left. Right-sided LHI had higher incidence rates of malignant brain edema (MBE) (48.5 vs. 30.8%, p = 0.001) and a composite of cardiovascular events (29.8 vs. 17.5%, p = 0.011) during hospitalization. The incidence rate of 1-month mortality (34.5 vs. 23.8%, p = 0.036) was higher in right-sided patients with LHI, but there were no hemispheric differences in the incidence rates of 3-month mortality and unfavorable outcome (both p &gt; 0.05). Multivariate analyses suggested right hemisphere involvement was independently associated with increased risk of MBE (adjusted OR 2.37, 95% CI 1.26–4.43, p = 0.007) and composite of cardiovascular events (adjusted OR 2.04, 95% CI 1.12–3.72, p = 0.020). However, it was not independently associated with 1-month death, 3-month mortality, and 3-month unfavorable outcome (all p &gt; 0.05).Conclusions: Right-sided patients with LHI had higher frequency of atrial fibrillation and cardio-embolism than the left-sided patients. Right hemisphere involvement was independently associated with increased risk of MBE and composite of cardiovascular events during hospitalization, whereas stroke lateralization was not an independent predictor of mortality and unfavorable outcome in patients with LHI.

Adverse Outcome in COVID-19 Is Associated With an Aggravating Hypo-Responsive Platelet Phenotype

Thromboembolic complications are frequently observed in Coronavirus disease 2019 (COVID-19). While COVID-19 is linked to platelet dysregulation, the association between disease outcome and platelet function is less clear. We prospectively monitored platelet activation and reactivity in 97 patients during the first week of hospitalization and determined plasma markers of platelet degranulation and inflammation. Adverse outcome in COVID-19 was associated with increased basal platelet activation and diminished platelet responses, which aggravated over time. Especially GPIIb/IIIa responses were abrogated, pointing toward impeded platelet aggregation. Moreover, platelet-leukocyte aggregate formation was diminished, pointing toward abrogated platelet-mediated immune responses in COVID-19. No general increase in plasma levels of platelet-derived granule components could be detected, arguing against platelet exhaustion. However, studies on platelets from healthy donors showed that plasma components in COVID-19 patients with unfavorable outcome were at least partly responsible for diminished platelet responses.Taken together this study shows that unfavorable outcome in COVID-19 is associated with a hypo-responsive platelet phenotype that aggravates with disease progression and may impact platelet-mediated immunoregulation.

PROGNOSTIC MEANING OF SERUM NSE AS THE FACTOR OF BAD OUTCOME IN SECONDARY BRAIN DAMAGE

This research is dedicated to the study of brain neuronspecific markers and indicators of brain damage outcome. Purpose of the study: To examine the prognostic role of serum NSE as the predictor of unfavorable outcome in traumatic and vascular brain damages. Methods: Prospective cohort study with 219 patients. Blood serum neuronspecific markers (NSE,S100B),acid-base state, blood gas were derived during the period of observation: upon enrolment, on the 3-rd, 5-th and 7-th days spent in the hospital in the intensive care unit. Results: The most significant risk factor of unfavorable outcome is the marker NSE with the cut point 12,5 ng|ml. The results of the analysis indicate the presence of a statistically significant direct relationship between NSE> 12.5 ng / ml and LDH, compared to other variables, 3.7 times more often; with an increase in blood lactate more than 4,1 mmol/l almost 3,8 times; with GCS 13 points below by 1,7 times; S100≥0,2 by 2,8 times; with an increase of PCO2 <38,5 it was documented more than 3 times often. The measure of certainty the resulting model by the pseudo R2 Nagelkerke criterion-250.6; logLikelihood - 154.04 which corresponds to the excellent predictive ability of the mathematical model. The best predictive value of the model is a cut-off point of 88.89%, AuROC-0.809; Se-51.59%; Sp-95.06%; NPV-55.80%; PPV-94.20%. This model can be used to predict the outcome in patients with acute cerebral pathology. Keywords: strokes, brain traumatic damages, neuronspecific markers, diagnostic and prognostic criterias, stroke outcomes.

Spontaneous angiogram-negative subarachnoid hemorrhage: a retrospective single center cohort study

Background Spontaneous angiogram-negative subarachnoid hemorrhage (SAH) is considered a benign illness with little of the aneurysmal SAH-related complications. We describe the clinical course, SAH-related complications, and outcome of patients with angiogram-negative SAH. Methods We retrospectively reviewed all adult patients admitted to a neurosurgical intensive care unit during 2004–2018 due to spontaneous angiogram-negative SAH. Our primary outcome was a dichotomized Glasgow Outcome Scale (GOS) at 3 months. We assessed factors that associated with outcome using multivariable logistic regression analysis. Results Of the 108 patients included, 84% had a favorable outcome (GOS 4–5), and mortality was 5% within 1 year. The median age was 58 years, 51% were female, and 93% had a low-grade SAH (World Federation of Neurosurgical Societies grading I–III). The median number of angiograms performed per patient was two. Thirty percent of patients showed radiological signs of acute hydrocephalus, 28% were acutely treated with an external ventricular drain, 13% received active vasospasm treatment and 17% received a permanent shunt. In the multivariable logistic regression model, only acute hydrocephalus associated with unfavorable outcome (odds ratio = 4.05, 95% confidence interval = 1.05–15.73). Two patients had a new bleeding episode. Conclusion SAH-related complications such as hydrocephalus and vasospasm are common after angiogram-negative SAH. Still, most patients had a favorable outcome. Only acute hydrocephalus was associated with unfavorable outcome. The high rate of SAH-related complications highlights the need for neurosurgical care in these patients.