scholarly journals Cytokine Release Syndrome-Associated Encephalopathy in Patients with COVID-19

2020 ◽  
Author(s):  
Peggy Perrin ◽  
Nicolas Collongues ◽  
Seyyid Baloglu ◽  
Dimitri Bedo ◽  
Xavier Bassand ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Severe Disease ◽  
Brain Mri ◽  
Case Series ◽  
Neurological Manifestations ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Mri Findings ◽  
Depth Analysis

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

scholarly journals Cerebrospinal fluid features in COVID-19 patients with neurologic manifestations: correlation with brain MRI findings in 58 patients

2020 ◽  
Author(s):  
François Lersy ◽  
Ilies Benotmane ◽  
Julie Helms ◽  
Olivier Collange ◽  
Maleka Schenck ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Laboratory ◽  
Brain Mri ◽  
Oligoclonal Bands ◽  
Neurologic Manifestations ◽  
Neurological Manifestations ◽  
Rt Pcr ◽  
Mri Findings ◽  
Leptomeningeal Enhancement ◽  
Csf Analysis

Abstract Background Neurological manifestations are common in patients with COVID-19, but little is known about pathophysiological mechanisms. In this single-center study, we describe neurological manifestations of 58 patients, regarding cerebrospinal fluid (CSF) analysis and neuroimaging findings. Methods 58 COVID-19 patients with neurologic manifestations and SARS-CoV-2 RT-PCR screening on CSF analysis were included. Clinical, laboratory, and brain MRI data were retrospectively collected and analyzed. Results Patients were mostly men (66%) with a median age of 62 years. Encephalopathy was frequent (81%), followed by a pyramidal dysfunction (16%), seizures (10%), and headaches (5%). Protein and albumin levels in CSF were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient suggesting impaired blood-brain barrier integrity. CSF-specific IgG oligoclonal band was found in five (11%) cases, suggesting an intrathecal synthesis of IgG, and 26 (55%) patients presented identical oligoclonal bands in serum and CSF. Four (7%) patients harbored a positive SARS-CoV-2 RT-PCR in CSF. Regarding brain MRI, 20 (38%) patients presented leptomeningeal enhancement. Conclusions Brain MRI abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV 2 detection in CSF remained scanty.

Myelopathy Due to CAR-T Related Neurotoxicity Treated with Siltuximab

2021 ◽  
pp. 10.1212/CPJ.0000000000001078
Author(s):  
Yasmin Aghajan ◽  
Alison Yu ◽  
Caron A. Jacobson ◽  
Austin I. Kim ◽  
Leslie Kean ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Hematologic Malignancy ◽  
Case Series ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T ◽  
Large Case Series ◽  
Large Case

Chimeric antigen receptor T (CART) cell therapy is highly effective for relapsed/refractory hematologic malignancy [1,2]; however, cytokine release syndrome (CRS) and neurotoxicity are observed in up to 77% of patients [3]. In large case series, the most common presentations of neurotoxicity were encephalopathy (57%), headache (42%), tremor (38%) and aphasia (35%). CART mediated spinal cord toxicity is not well characterized. Structural neurologic damage (stroke and intracranial hemorrhage) was only observed in 1-2% and seizures were seen in 1%-8% of cases [3, 4]. Neuroimaging findings in patients with neurotoxicity are rare and not specific.

scholarly journals Factors Associated with Disease Severity and Mortality among Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Vignesh Chidambaram ◽  
Nyan Lynn Tun ◽  
Waqas Haque ◽  
Marie Gilbert Majella ◽  
Ranjith Kumar Sivakumar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Disease Severity ◽  
English Language ◽  
Clinical Decision Making ◽  
Clinical Laboratory ◽  
Data Extraction ◽  
Meta Analysis ◽  
Severe Disease ◽  
Factors Associated ◽  
Risk Of Mortality

Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45; 95%CI 1.23,1.71), dyspnea (RR 2.55; 95%CI 1.88,2.46), diabetes (RR 1.59; 95%CI 1.41,1.78), hypertension (RR 1.90; 95%CI 1.69,2.15). Congestive heart failure (OR 4.76; 95%CI 1.34,16.97), hilar lymphadenopathy (OR 8.34; 95%CI 2.57,27.08), bilateral lung involvement (OR 4.86; 95%CI 3.19,7.39) and reticular pattern (OR 5.54; 95%CI 1.24,24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

scholarly journals Magnetic resonance imaging of traumatic injury to the craniovertebral junction: a case-based review

2015 ◽  
Vol 38 (4) ◽  
pp. E3 ◽  
Author(s):  
Anil K. Roy ◽  
_ _ ◽  
Brandon A. Miller ◽  
Christopher M. Holland ◽  
Arthur J. Fountain ◽  
...  
Keyword(s):  
Clinical Judgment ◽  
Clinical Decision Making ◽  
Spinal Column ◽  
Case Series ◽  
Craniovertebral Junction ◽  
Significant Heterogeneity ◽  
Case Review ◽  
Ligamentous Injury ◽  
Mri Findings ◽  
Retrospective Case

OBJECT The craniovertebral junction (CVJ) is unique in the spinal column regarding the degree of multiplanar mobility allowed by its bony articulations. A network of ligamentous attachments provides stability to this junction. Although ligamentous injury can be inferred on CT scans through the utilization of craniometric measurements, the disruption of these ligaments can only be visualized directly with MRI. Here, the authors review the current literature on MRI evaluation of the CVJ following trauma and present several illustrative cases to highlight the utility and limitations of craniometric measures in the context of ligamentous injury at the CVJ. METHODS A retrospective case review was conducted to identify patients with cervical spine trauma who underwent cervical MRI and subsequently required occipitocervical or atlantoaxial fusion. Craniometric measurements were performed on the CT images in these cases. An extensive PubMed/MEDLINE literature search was conducted to identify publications regarding the use of MRI in the evaluation of patients with CVJ trauma. RESULTS The authors identified 8 cases in which cervical MRI was performed prior to operative stabilization of the CVJ. Craniometric measures did not reliably rule out ligamentous injury, and there was significant heterogeneity in the reliability of different craniometric measurements. A review of the literature revealed several case series and descriptive studies addressing MRI in CVJ trauma. Three papers reported the inadequacy of the historical Traynelis system for identifying atlantooccipital dislocation and presented 3 alternative classification schemes with emphasis on MRI findings. CONCLUSIONS Recognition of ligamentous instability at the CVJ is critical in directing clinical decision making regarding surgical stabilization. Craniometric measures appear unreliable, and CT alone is unable to provide direct visualization of ligamentous injury. Therefore, while the decision to obtain MR images in CVJ trauma is largely based on clinical judgment with craniometric measures used as an adjunct, a high degree of suspicion is warranted in the care of these patients as a missed ligamentous injury can have devastating consequences.

scholarly journals Tocilizumab May Be a Key in Therapy for Cytokine Release Syndrome in Older Patients With Severe Symptoms of COVID-19

2020 ◽  
Author(s):  
Xu Lengnan ◽  
Liu Xin ◽  
Zhou Yangwei ◽  
Liu Aihua ◽  
Xu Xiaomao ◽  
...  
Keyword(s):  
Computerized Tomography ◽  
Older Patients ◽  
Severe Disease ◽  
Total Mortality ◽  
High Sensitivity ◽  
Severe Illness ◽  
Therapeutic Effects ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Neutrophil Lymphocyte Ratio

Abstract Background Older adults are more susceptible to the novel coronavirus disease 2019 (hereafter, COVID-19) and more likely to develop severe illness. Cytokine release syndrome (CRS) may be an important factor in the development of severe disease in patients with COVID-19. Interleukin-6 (IL-6) is an important cytokine in CRS, and tocilizumab can block the IL-6 receptor. In this study, we analyzed the therapeutic effects and safety of tocilizumab on CRS in older patients with severe COVID-19. Methods Between February 10 and March 21, 2020, a total of 19 patients with severe or critical COVID-19 aged ≥ 60 years met the study inclusion criteria at Tongji hospital in Wuhan city, Hubei Province, China. Patients were divided into two groups: 1. The tocilizumab group, whose IL-6 levels exceeded the upper limit of normal by > 10-fold; and 2. The no tocilizumab group, with 1L-6 levels < 10-fold the upper normal limit. Results Patients in the tocilizumab group were older (73.20 ± 4.44 vs. 66.21 ± 5.06 years, P = 0.014); had lower lymphocyte counts (0.71 ± 0.18 vs. 1.18 ± 0.59 × 109/L, P = 0.016); and higher high-sensitivity C-reactive protein (hsCRP) levels (94.04 ± 57.24 vs. 51.65 ± 45.37 mg/L, P = 0.035). The increases in ferritin (FER) and hsCRP levels in patients in the tocilizumab group were marked. Except in one patient who died, IL-6, FER, and hsCRP levels, and the neutrophil/lymphocyte ratio, in the remaining four patients decreased following treatment with tocilizumab. Further, patient computerized tomography scan results improved after 3–8 days of tocilizumab treatment. Tocilizumab did not cause any serious adverse reactions. There were no differences in mortality or days until lung computerized tomography improvement between the two groups. The total mortality rate was 10.53%. Conclusions Our results support the therapeutic efficacy and safety of tocilizumab on older patients with severe COVID-19.

scholarly journals Staphylococcus aureus costochondritis and chest wall abscess in a COVID-19 patient treated with tocilizumab

2021 ◽  
Vol 67 (3) ◽  
pp. 382-385
Author(s):  
İlkay Ergenç ◽  
Canan Şanal Toprak ◽  
Zekaver Odabaşı
Keyword(s):  
Intensive Care Unit ◽  
Staphylococcus Aureus ◽  
Chest Wall ◽  
Distress Syndrome ◽  
Severe Disease ◽  
Severe Pneumonia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Chest Wall Abscess ◽  
Promising Treatment

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, causing a global health threat. Up to 15% of the confirmed cases develop severe disease, requiring hospitalization or intensive care unit (ICU) admission. Tocilizumab, an IL-6 receptor antagonist, is a promising treatment of severe pneumonia with acute respiratory distress syndrome (ARDS) or cytokine release syndrome (CRS) in the course of COVID-19. We report a suppurative costochondritis and chest wall abscess in a severe COVID-19 patient treated with tocilizumab.

scholarly journals Title: Cytokine release syndrome is not usually caused by secondary hemophagocytic lymphohistiocytosis in a cohort of 19 critically ill COVID-19 patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Georg Lorenz ◽  
Philipp Moog ◽  
Quirin Bachmann ◽  
Paul La Rosée ◽  
Heike Schneider ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Severe Disease ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Short Term ◽  
Therapeutic Implications ◽  
Neutrophil Lymphocyte Ratio ◽  
Independent Expert ◽  
Clinical Triad ◽  
Secondary Hemophagocytic Lymphohistiocytosis

Abstract Severe COVID-19 associated respiratory failure, poses the one challenge of our days. Assessment and treatment of COVID-19 associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis (sHLH) or cytokine release syndrome (CRS) with features of macrophage activation syndrome might drive severe disease trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach. Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death at time of analysis. The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia, persistent fever and organomegaly. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio > 3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n = 8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n = 9). Our study rules out virus induced sHLH as the leading cause of most severe-COVID-19 trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.

scholarly journals Methadone-Induced Encephalopathy: A Case Series and Literature Review

2020 ◽  
Author(s):  
Maryam Haghighi-Morad ◽  
Zahra Naseri ◽  
Nazila Jamshidi ◽  
Hossein Hassanian-Moghaddam ◽  
Nasim Zamani ◽  
...  
Keyword(s):  
White Matter ◽  
Brain Mri ◽  
Case Series ◽  
Neurological Deficits ◽  
Cerebral White Matter ◽  
High Signal ◽  
Mri Findings ◽  
Caudate Nuclei ◽  
Delayed Onset ◽  
Signal Abnormality

Abstract Background: Accidental ingestion or consumption of supra-therapeutic doses of methadone can result in neurological sequelae in humans. We aimed to determine the neurological deficits of methadone-poisoned patients admitted to a referral poisoning hospital using brain magnetic resonance (MR) and diffusion weighted (DW) imaging. Methods: In this retrospective study, brain MRIs of the patients admitted to our referral center due to methadone intoxication were reviewed. Methadone intoxication was confirmed based on history, congruent clinical presentation, and confirmatory urine analysis . Each patient had an MRI with Echo planar T1, T2, FLAIR, and DWI and apparent deficient coefficient (ADC) sequences without contrast media. Abnormalities were recorded and categorized based on their anatomic location and sequence. Results: Ten patients with abnormal MRI findings were identified. Eight had acute- and two had delayed-onset encephalopathy. Imaging findings included bilateral confluent or patchy T2 and FLAIR high signal intensity in cerebral white matter, cerebellar involvement, and bilateral occipito-parietal cortex diffusion restriction in DWI. Internal capsule involvement was identified in two patients while abnormality in globus pallidus and head of caudate nuclei were reported in another. Bilateral cerebral symmetrical confluent white matter signal abnormality with sparing of subcortical U-fibers on T2 and FLAIR sequences were observed in both patients with delayed-onset encephalopathy. Conclusions : Acute- and delayed-onset encephalopathies are two rare adverse events detected in methadone-intoxicated patients. Brain MRI findings can be helpful in detection of methadone-induced encephalopathy.

scholarly journals Cytokine release syndrome is not usually caused by secondary hemophagocytic lymphohistiocytosis in a cohort of 19 critically ill COVID-19 patients

2020 ◽  
Author(s):  
Georg Lorenz ◽  
Philipp Moog ◽  
Quirin Bachmann ◽  
Paul La Rosee ◽  
Heike Schneider ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Severe Disease ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Short Term ◽  
Therapeutic Implications ◽  
Neutrophil Lymphocyte Ratio ◽  
Independent Expert ◽  
Clinical Triad ◽  
Secondary Hemophagocytic Lymphohistiocytosis

Abstract Background: Severe COVID-19 associated respiratory failure, poses the one challenge of our days. Assessment and treatment of COVID-19 associated hyperinflammation may be key to improve outcomes. It was speculated that in subgroups of patients secondary hemophagocytic lymphohistiocytosis (sHLH) or cytokine release syndrome (CRS) with features of macrophage activation syndrome might drive severe disease trajectories. If confirmed, profound immunosuppressive therapy would be a rationale treatment approach.Methods: Over a median observation period of 11 (IQR: 8; 16) days, 19 consecutive confirmed severe COVID-19-patients admitted to our intensive-care-unit were tested for presence of sHLH by two independent experts. HScores and 2004-HLH diagnostic criteria were assessed. Patients were grouped according to short-term clinical courses: discharge from ICU versus ongoing ARDS or death at time of analysis.Results: The median HScore at admission was 157 (IQR: 98;180), without the key clinical triad of HLH, i.e. progressive cytopenia, persistent fever and organomegaly. Independent expert chart review revealed the absence of sHLH in all cases. No patient reached more than 3/6 of modified HLH 2004 criteria. Nevertheless, patients presented hyperinflammation with peripheral neutrophilic signatures (neutrophil/lymphocyte-ratio>3.5). The latter best paralleled their short-term clinical courses, with declining relative neutrophil numbers prior to extubation (4.4, [IQR: 2.5;6.3]; n=8) versus those with unfavourable courses (7.6, [IQR: 5.2;31], n=9).Conclusion: Our study rules out virus induced sHLH as the leading cause of most severe-COVID-19 trajectories. Instead, an associated innate neutrophilic hyperinflammatory response or virus-associated-CRS appears dominant in patients with an unfavourable clinical course. Therapeutic implications are discussed.

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