scholarly journals Clinical Manifestations and Pathogenesis of Acute Necrotizing Encephalopathy: The Interface Between Systemic Infection and Neurologic Injury

2022 ◽  
Vol 12 ◽  
Author(s):  
Priya Shukla ◽  
Abby Mandalla ◽  
Matthew J. Elrick ◽  
Arun Venkatesan
Keyword(s):  
Clinical Manifestations ◽  
Systemic Infection ◽  
Nucleocytoplasmic Transport ◽  
Neurological Deficits ◽  
Neurologic Injury ◽  
Multifunctional Protein ◽  
Acute Necrotizing Encephalopathy ◽  
Acute Necrotizing ◽  
The Central Nervous System ◽  
Systemic Infections

Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-CoV-2. Affected individuals typically present with rapid changes in consciousness, focal neurological deficits, and seizures. Neuroimaging reveals symmetric, bilateral deep gray matter lesions, often involving the thalami, with evidence of necrosis and/or hemorrhage. The clinical and radiologic picture must be distinguished from direct infection of the central nervous system by some viruses, and from metabolic and mitochondrial disorders. Outcomes following ANE are poor overall and worse in those with brainstem involvement. Specific management is often directed toward modulating immune responses given the potential role of systemic inflammation and cytokine storm in potentiating neurologic injury in ANE, though benefits of such approaches remain unclear. The finding that many patients have mutations in the nucleoporin gene RANBP2, which encodes a multifunctional protein that plays a key role in nucleocytoplasmic transport, may allow for the development of disease models that provide insights into pathogenic mechanisms and novel therapeutic approaches.

Tropheryma whipplei, Immunosuppression and Whipple's Disease: From a Low-Pathogenic, Environmental Infectious Organism to a Rare, Multifaceted Inflammatory Complex

2015 ◽  
Vol 33 (2) ◽  
pp. 190-199 ◽  
Author(s):  
Thomas Marth
Keyword(s):  
Heart Valves ◽  
Clinical Manifestations ◽  
Systemic Infection ◽  
Tropheryma Whipplei ◽  
Molecular Techniques ◽  
Whipple’S Disease ◽  
Whipple's Disease ◽  
New Findings ◽  
The Central Nervous System ◽  
Body Compartments

Background: The actinobacterium Tropheryma whipplei was detected 20 years ago by molecular techniques, and following its culture has been characterized as the cause of a systemic infection known as Whipple's disease (WD). T. whipplei occurs in the environment, is prevalent only in humans, is believed to be transmitted via oral routes and to be host dependent. Key Messages: The classical form of T. whipplei infection, i.e. classical WD (CWD), is rare. It is well defined as slowly progressing chronic infection with arthralgia, diarrhea and weight loss, mostly in middle-aged men. However, current research revealed a much broader spectrum of clinical features associated with T. whipplei infection. Thus, T. whipplei may cause acute and transient infections (observed primarily in children) and the bacterium, which is found in soil and water, occurs in asymptomatic carriers as well as in CWD patients in clinical remission. In addition, T. whipplei affects isolated and localized body compartments such as heart valves or the central nervous system. Subtle immune defects and HLA associations have been described. New findings indicate that the progression of asymptomatic T. whipplei infection to clinical WD may be associated with medical immunosuppression and with immunomodulatory conditions. This explains that there is a discrepancy between the widespread occurrence of T. whipplei and the rareness of WD, and that T. whipplei infection triggered by immunosuppression presents with protean clinical manifestations. Conclusions: This review highlights recent findings and the clinical spectrum of infection with T. whipplei and WD, focusing specifically on the role of host immunity and immunosuppression. Current concepts of the pathogenesis, diagnosis and therapy are discussed.

scholarly journals COVID-19 Associated Acute Necrotizing Encephalopathy in a Hospitalized Cohort in Oregon

2020 ◽  
Author(s):  
Holly Vanni ◽  
Austin D Jou ◽  
Christine E Choo ◽  
Eric C. Walter ◽  
Richard A. Mularksi
Keyword(s):  
Observational Studies ◽  
Viral Infections ◽  
Case Reports ◽  
Health Maintenance Organization ◽  
Time Frame ◽  
Health Maintenance ◽  
Acute Necrotizing Encephalopathy ◽  
Acute Necrotizing ◽  
The Central Nervous System ◽  
Novel Coronavirus

Abstract Background/Objective: Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) is a novel coronavirus strain that most commonly affects the respiratory system with observational studies and case reports suggesting this virus may target the central nervous system. To date there has been one case report of COVID-19 related acute necrotizing encephalopathy.Methods: Observational study of COVID-19 patients admitted to two hospitals of a large metropolitan health maintenance organization serving over 600,000 members using retrospective electronic and radiographic medical record evaluation across 4 months (March – June of 2020) after multiple cases of acute necrotizing encephalopathy were diagnosed.Results: During this time frame 216 patients were diagnosed with COVID-19, 106 (49%) required hospitalization, 21 (20%) required admission to the intensive care unit (ICU) and 18 (17%) required intubation. Of the 18, 4 (22%) had clinicoradiologic evidence of acute necrotizing encephalopathy (ANE) diagnosed, two with associated areas of hemorrhage.Conclusions: Acute necrotizing encephalopathy (ANE) with or without hemorrhage, is a rare CNS disease, usually seen in childhood as a complication of viral infections. We identified a high percentage of COVID-19 patients with clinicoradiologic evidence of acute necrotizing encephalopathy in our cohort. To our knowledge, ANE has not been reported in patients with SARS or MERS. Understanding the pathogenesis, neurotropism and effects of the SARS-CoV-2 virus is important in developing treatments and improving morbidity and mortality.

scholarly journals COVID-19–Associated Acute Asymmetric Hemorrhagic Necrotizing Encephalopathy: A Case Report

2022 ◽  
pp. 194187442110553
Author(s):  
Najo Jomaa ◽  
Tarek El Halabi ◽  
Jawad Melhem ◽  
Georgette Dib ◽  
Youssef Ghosn ◽  
...  
Keyword(s):  
Neurological Complications ◽  
Parahippocampal Gyrus ◽  
Biological Drugs ◽  
Acute Necrotizing Encephalopathy ◽  
Immune Mediated ◽  
Acute Necrotizing ◽  
History Of ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Right

Background: Coronavirus disease 2019 (COVID-19) has been associated with many neurological complications affecting the central nervous system. Purpose: Our aim was to describe a case of COVID-19 associated with a probable variant of acute necrotizing encephalopathy (ANE). Results: A 60-year-old man who presented with a 3-day history of dyspnea, fever, and cough tested positive for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Five days following his admission, the patient was intubated secondary to respiratory failure. Following his extubation 16 days later, he was found to have a left-sided weakness. Magnetic resonance imaging (MRI) of the brain showed hemorrhagic rim-enhancing lesions involving the right thalamus, left hippocampus, and left parahippocampal gyrus. These lesions showed decreased relative cerebral blood flow on MR perfusion and restricted on diffusion-weighted imaging. These neuroimaging findings were consistent with ANE. The left-sided weakness gradually improved over the subsequent weeks. Conclusions: We concluded that COVID-19 can be associated with ANE, a condition believed to be the result of an immune-mediated process with activation of the innate immune system. Future studies must address whether biological drugs targeting the pro-inflammatory cytokines could prevent the development of this condition.

scholarly journals RelapsingCampylobacter jejuniSystemic Infections in a Child with X-Linked Agammaglobulinemia

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Paola Ariganello ◽  
Giulia Angelino ◽  
Alessia Scarselli ◽  
Irene Salfa ◽  
Martina Della Corte ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Systemic Infection ◽  
Signs And Symptoms ◽  
Clinical History ◽  
Duration Of Treatment ◽  
Increased Risk ◽  
Bruton Tyrosine Kinase ◽  
Encapsulated Bacteria ◽  
Specific Association ◽  
Systemic Infections

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency of the humoral compartment, due to a mutation in theBruton tyrosine kinase (BTK)gene, characterized by a severe defect of circulating B cells and serum immunoglobulins. Recurrent infections are the main clinical manifestations; although they are especially due to encapsulated bacteria, a specific association withCampylobacterspecies has been reported. Here, we report the case of a boy with XLA who presented with relapsingCampylobacter jejunisystemic infections. His clinical history supports the hypothesis of the persistence ofC. jejuniin his intestinal tract. Indeed, as previously reported, XLA patients may become chronic intestinal carriers ofCampylobacter, even in absence of symptoms, with an increased risk of relapsing bacteraemia. The humoral defect is considered to be crucial for this phenomenon, as well as the difficulties to eradicate the pathogen with an appropriate antibiotic therapy; drug resistance is raising inCampylobacterspecies, and the appropriate duration of treatment has not been established.C. jejunishould always be suspected in XLA patients with signs and symptoms of systemic infection, and treatment should be based on antibiogram to assure the eradication of the pathogen.

scholarly journals COVID-19 Associated Acute Necrotizing Encephalopathy in a Hospitalized Cohort in Oregon

2020 ◽  
Author(s):  
Holly Vanni ◽  
Austin D Jou ◽  
Christine E Choo ◽  
Eric C. Walter ◽  
Richard A. Mularksi
Keyword(s):  
Observational Studies ◽  
Viral Infections ◽  
Case Reports ◽  
Health Maintenance Organization ◽  
Time Frame ◽  
Health Maintenance ◽  
Acute Necrotizing Encephalopathy ◽  
Acute Necrotizing ◽  
The Central Nervous System ◽  
Novel Coronavirus

Abstract Background/Objective: Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) is a novel coronavirus strain that most commonly affects the respiratory system with observational studies and case reports suggesting this virus may target the central nervous system. To date there has been one case report of COVID-19 related acute necrotizing encephalopathy.Methods: Observational study of COVID-19 patients admitted to two hospitals of a large metropolitan health maintenance organization serving over 600,000 members using retrospective electronic and radiographic medical record evaluation across 4 months (March – June of 2020) after multiple cases of acute necrotizing encephalopathy were diagnosed.Results: During this time frame 216 patients were diagnosed with COVID-19, 106 (49%) required hospitalization, 21 (20%) required admission to the intensive care unit (ICU) and 18 (17%) required intubation. Of the 18, 4 (22%) had clinicoradiologic evidence of acute necrotizing encephalopathy (ANE) diagnosed, two with associated areas of hemorrhage.Conclusions: Acute necrotizing encephalopathy (ANE) with or without hemorrhage, is a rare CNS disease, usually seen in childhood as a complication of viral infections. We identified a high percentage of COVID-19 patients with clinicoradiologic evidence of acute necrotizing encephalopathy in our cohort. To our knowledge, ANE has not been reported in patients with SARS or MERS. Understanding the pathogenesis, neurotropism and effects of the SARS-CoV-2 virus is important in developing treatments and improving morbidity and mortality.

scholarly journals Fatal H1N1-Related Acute Necrotizing Encephalopathy in an Adult

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Yu-Jin Lee ◽  
D. Scott Smith ◽  
Vivek A. Rao ◽  
Robert D. Siegel ◽  
Jon Kosek ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Influenza Infection ◽  
Neurological Complication ◽  
Fatal Case ◽  
H1n1 Influenza ◽  
Acute Necrotizing Encephalopathy ◽  
Molecular Studies ◽  
Acute Necrotizing ◽  
The Central Nervous System

Acute necrotizing encephalopathy (ANE) is a severe neurological complication of influenza infection, including H1N1 influenza. Many cases of ANE have been reported in the pediatric literature, but very few cases have been described in adults. The cause of ANE remains unknown—the influenza virus is not known to be neurotropic, and evidence of direct viral involvement of the central nervous system (CNS) has not been demonstrated in the limited cases of ANE in which pathological specimens have been obtained. Here we report a fatal case of ANE from H1N1 influenza infection in an adult. Neuroimaging and postmortem analysis both showed widespread brain edema, necrosis, and hemorrhage, but molecular studies and postmortem pathology revealed no evidence of direct viral involvement of the CNS. This case of fatal ANE in an adult is consistent with the hypothesis generated from pediatric cases that the host immune response, and not direct viral invasion of the CNS, is responsible for pathogenesis of ANE.

Postoperative cognitive dysfunction: progress mechanisms and clinical characteristics

2019 ◽  
Vol 2 (19) ◽  
pp. 29-33
Author(s):  
K. B. Manysheva ◽  
M. A. Akhmedov ◽  
A. A. Rakhmanova ◽  
S. M. Khutalieva
Keyword(s):  
Cognitive Dysfunction ◽  
Clinical Characteristics ◽  
Cognitive Deficit ◽  
Neuropsychological Testing ◽  
Postoperative Cognitive Dysfunction ◽  
Clinical Manifestations ◽  
Postoperative Recovery ◽  
Neuropsychological Rehabilitation ◽  
Brain Barrier Permeability ◽  
The Central Nervous System

The article is devoted to the study of postoperative cognitive dysfunction — a syndrome that is often found in the postoperative period and does not depend on the volume of surgeon. Based on the analysis of the results of modern studies, the authors cite the most likely etiological causes of the syndrome, grouped according to different categories of risk factors. The pathogenetic algorithm for cognitive dysfunction includes the appearance of systemic inflammation, improving blood-brain barrier permeability with the endothelial dysfunction, the migration of inflammatory agents into the central nervous system, and the formation of oxidative stress. The clinical manifestations of cognitive deficit in the outcome of surgeon performed under general anesthesia, the authors illustrate with their own observations of patients with a neurosurgical profile with spinal pathology operated on with the use of propofol anesthesia, comparing the results of neuropsychological testing with an assessment of the level of anxiety. In conclusion, the authors outline a strategy for the prevention of postoperative cognitive dysfunction and recommend conducting neuropsychological rehabilitation as an important component of postoperative recovery for all patients with a diagnosed cognitive deficit that occurred after surgery.

Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal

2019 ◽  
Vol 19 (8) ◽  
pp. 597-604
Author(s):  
Li Pang ◽  
Shouqin Ji ◽  
Jihong Xing
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Caspase 3 ◽  
Global Ischemia ◽  
Neurological Deficits ◽  
Global Cerebral Ischemia ◽  
Caspase 9 ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Transient Global Ischemia

Background: Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride. Methods: CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study. Results: CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats. Conclusion: Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.

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