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1.
BMJ Case Rep ; 13(9)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32907872

RESUMO

COVID-19 has challenged all medical professionals to optimise non-invasive positive pressure ventilation (NIV) as a means of limiting intubation. We present a case of a middle-aged man with a voluminous beard for religious reasons who developed progressive hypoxic respiratory failure secondary to COVID-19 infection which became refractory to NIV. After gaining permission to trim the patient's facial hair by engaging with the patient, his family and religious leaders, his mask fit objectively improved, his hypoxaemia markedly improved and an unnecessary intubation was avoided. Trimming of facial hair should be considered in all patients on NIV who might have any limitations with mask fit and seal that would hamper ventilation, including patients who have facial hair for religious reasons.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Ventilação não Invasiva/métodos , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Idoso , Encefalopatias/etiologia , Infecções por Coronavirus/complicações , Cabelo , Humanos , Intubação Intratraqueal , Masculino , Pandemias , Pneumonia Viral/complicações , Religião e Medicina , Insuficiência Respiratória/etiologia , Traqueostomia
3.
Int J Infect Dis ; 98: 398-400, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32712426

RESUMO

Concerning the letter by Moriguchi et al., we describe our experience with a case of encephalopathy with and atypical damage on magnetic resonance imaging (MRI) in a patient with severe infection due to the SARS-CoV2 virus. A 56-year-old woman, without previous pathologies, developed cough, fever, and respiratory failure for five days, after returning from a 6-day trip to Venice. Chest radiography shows a large bilateral interstitial infiltrate. In the first 24 hours, she was admitted to the Intensive Care Unit (ICU) for severe respiratory failure and positive protein chain reaction-PCR in nasal exudate. She needed intubation for ten days. In the first 48 hours outside the ICU, she developed an acute confusional syndrome (hyperactive delirium). Neurological examination showed temporal-spatial disorientation and incoherent fluent speech. An electroencephalogram (EEG) showed generalized hypovoltaic activity. Cranial magnetic resonance imaging showed a bilateral and symmetrical increase in the supratentorial white matter's signal intensity, with a discrete thickening of both temporal lobes, with a slight increase in signal intensity and a sequence of normal diffusion. The lumbar puncture showed no changes (glucose 71 mg/dL, protein 30 mg/dL, 1 leukocyte). Within 72 hours of starting symptoms, she was neurologically asymptomatic. Our final diagnosis was an inflammatory encephalopathy related to a SARS-CoV2 infection.


Assuntos
Betacoronavirus/fisiologia , Encefalopatias/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Encefalopatias/diagnóstico por imagem , Encefalopatias/imunologia , Encefalopatias/virologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia
4.
J Pharmacol Sci ; 144(2): 83-88, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32709559

RESUMO

Astrocytes generate robust intracellular Ca2+ signals that are assumed to be key regulators of astrocytic function. Among various Ca2+ mobilization mechanisms, Ca2+ release from the endoplasmic reticulum (ER) via the inositol 1,4,5-trisphosphate receptor (IP3R) has attracted attention as a major component of astrocytic Ca2+ signaling. Manipulation of astrocytic IP3-Ca2+ signaling, such as genetic deletion of the type 2 IP3R, has revealed multifaceted roles of astrocytic ER Ca2+ release in health and disease. Recent developments in Ca2+ imaging techniques including ER intraluminal Ca2+ imaging have been indispensable in determining the physiological and pathophysiological significance of astrocytic ER Ca2+ release via IP3Rs. Beneficial and detrimental roles of IP3R-dependent Ca2+ release in astrocytes have been revealed in wide variety of disorders in the brain, strongly suggesting astrocytic IP3-Ca2+ signaling as a novel and promising therapeutic target.


Assuntos
Astrócitos/metabolismo , Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/fisiologia , Animais , Encefalopatias/etiologia , Encefalopatias/genética , Encefalopatias/terapia , Deleção de Genes , Humanos , Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Imagem Molecular , Terapia de Alvo Molecular
7.
World Neurosurg ; 141: e437-e446, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474092

RESUMO

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic has had a dramatic impact on health care systems and a variable disease course. Emerging evidence demonstrates that severe acute respiratory syndrome coronavirus 2 is associated with central nervous system disease. We describe central nervous system manifestations in critical patients with COVID-19 at our tertiary center. METHODS: We conducted a single-center retrospective analysis of all actively critical patients with COVID-19 admitted to our tertiary care academic center in New Orleans, Louisiana, on April 22, 2020, with new onset of neurologic disease. Patients were grouped into 1 of 3 categories according to imaging and clinical features; encephalopathy, acute necrotizing encephalopathy, and vasculopathy. RESULTS: A total of 27 of 76 (35.5%) critical patients with COVID-19 met inclusion criteria. Twenty patients (74%) were designated with COVID-19-associated encephalopathy, 2 (7%) with COVID-19-associated acute necrotizing encephalopathy, and 5 (19%) with COVID-19-associated vasculopathy. Sixty-three percent of neurologic findings were demonstrated on computed tomography, 30% on magnetic resonance imaging, and 44% on electroencephalography. Findings most often included ischemic strokes, diffuse hypoattenuation, subcortical parenchymal hemorrhages, and focal hypodensities within deep structures. Magnetic resonance imaging findings included diffuse involvement of deep white matter, the corpus callosum, and the basal ganglia. For patients with large-territory ischemic stroke, all but one displayed irregular proximal focal stenosis of the supraclinoid internal carotid artery. CONCLUSIONS: Analysis of active critical COVID-19 admissions at our revealed a high percentage of patients with new neurologic disease. Although variable, presentations followed 1 of 3 broad categories. A better understanding of the neurologic sequalae and radiographic findings will help clinicians mitigate the impact of this disease.


Assuntos
Encefalopatias/etiologia , Transtornos Cerebrovasculares/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/diagnóstico por imagem , Encefalopatias/terapia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/terapia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/terapia , Comorbidade , Infecções por Coronavirus/diagnóstico por imagem , Cuidados Críticos , Estudos Transversais , Eletroencefalografia , Feminino , Humanos , Doença de Leigh/diagnóstico por imagem , Doença de Leigh/etiologia , Doença de Leigh/terapia , Louisiana , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Ann Neurol ; 88(1): 1-11, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32506549

RESUMO

In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1-11 ANN NEUROL 2020;88:1-11.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Encefalopatias/etiologia , Encefalopatias/fisiopatologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Infecções por Coronavirus/complicações , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/fisiopatologia , Encefalite/etiologia , Encefalite/fisiopatologia , Encefalomielite Aguda Disseminada/etiologia , Encefalomielite Aguda Disseminada/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Inflamação , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/fisiopatologia , Leucoencefalite Hemorrágica Aguda/etiologia , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Meningite Viral/etiologia , Meningite Viral/fisiopatologia , Doenças do Sistema Nervoso/etiologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/fisiopatologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Trombofilia/etiologia , Trombofilia/fisiopatologia
10.
Brain Behav Immun ; 88: 71-74, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561222

RESUMO

Corona Virus Disease 2019 (COVID-19) emerged in December 2019 from Wuhan, China. It typically presents with mild upper respiratory tract infection symptoms and may have life threatening complications, including acute respiratory distress syndrome, acute stroke, myocardial infarction, kidney failure, shock, and even death. Coronavirus infections are known to have neuroinvasive potential with consequent neuropsychiatric manifestations. We analyzed COVID-19 adult patients in the TriNetX database, which is a global health collaborative clinical research platform collecting real-time electronic medical records data from a network of health care organizations (HCOs) from January 20, 2020 to June 10th, 2020. 40,469 patients were diagnosed with COVID-19 among whom 9086 (22.5%) patients had neuropsychiatric manifestations. The most common neurologic manifestations included headache (3.7%) and sleep disorders (3.4%), Encephalopathy (2.3%), Stroke and transient ischemic attack (TIA) (1.0%) and 0.6% had seizures. Most common psychiatric manifestations included anxiety and other related disorders (4.6%), mood disorders (3.8%), while 0.2% patients had suicidal ideation. Early recognition and prompt management of neuropsychiatric manifestations in these patients have a potential to decrease overall morbidity and mortality.


Assuntos
Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/psicologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ageusia/etiologia , Ansiedade/etiologia , Ansiedade/psicologia , Betacoronavirus , Encefalopatias/etiologia , Infecções por Coronavirus/complicações , Bases de Dados Factuais , Feminino , Cefaleia/etiologia , Humanos , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/psicologia , Mialgia/etiologia , Transtornos do Olfato/etiologia , Dor/etiologia , Pandemias , Pneumonia Viral/complicações , Convulsões/etiologia , Transtornos do Sono-Vigília/etiologia , Acidente Vascular Cerebral/etiologia , Ideação Suicida , Adulto Jovem
11.
AJNR Am J Neuroradiol ; 41(8): 1380-1383, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32527843

RESUMO

Little is known about the neurologic sequelae of coronavirus disease 2019 (COVID-19). We assessed neuroimaging findings in 4 patients positive for COVID-19. All had abnormal mental status, deranged coagulation parameters, and markedly elevated D-dimer levels. CT/MR imaging showed a common pattern of multifocal subcortical/cortical petechial-type hemorrhages, while SWI showed more extensive multifocal abnormalities. The appearances are consistent with a thrombotic microangiopathy and may be due to the heightened level of thrombosis in patients with COVID-19.


Assuntos
Betacoronavirus , Encefalopatias/diagnóstico por imagem , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Encefalopatias/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Neuroimagem , Pandemias , Tomografia Computadorizada por Raios X
12.
Artigo em Inglês | MEDLINE | ID: mdl-32456003

RESUMO

Sepsis-associated brain dysfunction (SABD) with increased intracranial pressure (ICP) is a complex pathology that can lead to unfavorable outcome. Ultrasonographic measurement of optic nerve sheath diameter (ONSD) is used for non-invasive assessment of ICP. We aimed to assess the role of ONSD as a SABD screening tool. This prospective preliminary study covered 10 septic shock patients (5 men; aged 65, IQR 50-78 years). ONSD was measured bilaterally from day 1 to 10 (n = 1), until discharge (n = 3) or death (n = 6). The upper limit for ONSD was set at 5.7 mm. Sequential organ failure assessment score was calculated on a daily basis as a surrogate formulti-organ failure due to sepsis in the study population. On day 1, the medians of right and left ONSD were 5.56 (IQR 5.35-6.30) mm and 5.68 (IQR 5.50-6.10) mm, respectively, and four subjects had bilaterally elevated ONSD. Forty-nine out of 80 total measurements performed (61%) exceeded 5.7 mm during the study period. We found no correlations between ONSD and sequential organ failure assessment (SOFA) during the study period (right: R = -0.13-0.63; left R = -0.24-0.63). ONSD measurement should be applied for screening of SABD cautiously. Further research is needed to investigate the exact role of this non-invasive method in the assessment of brain dysfunction in these patients.


Assuntos
Encefalopatias , Pressão Intracraniana , Nervo Óptico , Sepse , Ultrassom , Idoso , Encéfalo/fisiopatologia , Encefalopatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/anatomia & histologia , Nervo Óptico/diagnóstico por imagem , Estudos Prospectivos , Sensibilidade e Especificidade , Sepse/complicações , Ultrassonografia
13.
Clin Neurophysiol ; 131(8): 2023-2031, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32405259

RESUMO

There are questions and challenges regarding neurologic complications in COVID-19 patients. EEG is a safe and efficient tool for the evaluation of brain function, even in the context of COVID-19. However, EEG technologists should not be put in danger if obtaining an EEG does not significantly advance diagnosis or change management in the patient. Not every neurologic problem stems from a primary brain injury: confusion, impaired consciousness that evolves to stupor and coma, and headaches are frequent in hypercapnic/hypoxic encephalopathies. In patients with chronic pulmonary disorders, acute symptomatic seizures have been reported in acute respiratory failure in 6%. The clinician should be aware of the various EEG patterns in hypercapnic/hypoxic and anoxic (post-cardiac arrest syndrome) encephalopathies as well as encephalitides. In this emerging pandemic of infectious disease, reduced EEG montages using single-use subdermal EEG needle electrodes may be used in comatose patients. A full 10-20 EEG complement of electrodes with an ECG derivation remains the standard. Under COVID-19 conditions, an expedited study that adequately screens for generalized status epilepticus, most types of regional status epilepticus, encephalopathy or sleep may serve for most clinical questions, using simplified montages may limit the risk of infection to EEG technologists. We recommend noting whether the patient is undergoing or has been placed prone, as well as noting the body and head position during the EEG recording (supine versus prone) to avoid overinterpretation of respiratory, head movement, electrode, muscle or other artifacts. There is slight elevation of intracranial pressure in the prone position. In non-comatose patients, the hyperventilation procedure should be avoided. At present, non-specific EEG findings and abnormalities should not be considered as being specific for COVID-19 related encephalopathy.


Assuntos
Encefalopatias/fisiopatologia , Infecções por Coronavirus/complicações , Eletroencefalografia/métodos , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto , Encefalopatias/diagnóstico , Encefalopatias/etiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Cuidados Críticos/normas , Eletroencefalografia/instrumentação , Eletroencefalografia/normas , Humanos , Pandemias , Posicionamento do Paciente/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia
14.
Gen Hosp Psychiatry ; 65: 47-53, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470824

RESUMO

INTRODUCTION: Neuropsychiatric manifestations of the coronavirus disease 2019 (COVID-19) have been described, including anosmia, ageusia, headache, paresthesia, encephalitis and encephalopathy. Little is known about the mechanisms by which the virus causes central nervous system (CNS) symptoms, and therefore little guidance is available regarding potential workup or management options. CASES: We present a series of four consecutive cases, seen by our psychiatry consultation service over a one-week period, each of which manifested delirium as a result of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). DISCUSSION: The four cases highlighted here all occurred in older patients with premorbid evidence of cognitive decline. Unique features seen in multiple cases included rigidity, alogia, abulia, and elevated inflammatory markers. In all four cases, a change in mental status was the presenting symptom, and three of the four cases lacked significant respiratory symptoms. In addition to discussing unique features of the cases, we discuss possible pathophysiologic explanations for COVID-19 delirium. CONCLUSIONS: Delirium should be recognized as a potential feature of infection with SARS-CoV-2 and may be the only presenting symptom. Based on the high rates of delirium demonstrated in prior studies, hospitals should consider adding mental status changes to the list of testing criteria. Further research is needed to determine if delirium in COVID-19 represents a primary encephalopathy heralding invasion of the CNS by the virus, or a secondary encephalopathy related to systemic inflammatory response or other factors.


Assuntos
Encefalopatias/etiologia , Infecções por Coronavirus/complicações , Delírio/etiologia , Pandemias , Pneumonia Viral , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/virologia , Disfunção Cognitiva/complicações , Infecções por Coronavirus/patologia , Delírio/virologia , Feminino , Humanos , Masculino
15.
Am J Emerg Med ; 38(7): 1549.e3-1549.e7, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32425321

RESUMO

BACKGROUND: Much of the focus regarding the global pandemic of coronavirus disease of 2019 (COVID-19) has been on the cardiovascular, pulmonary, and hematologic complications. However, neurologic complications have arisen as an increasingly recognized area of morbidity and mortality. OBJECTIVE: This brief report summarizes the neurologic complications associated with COVID-19 with an emphasis on the emergency medicine clinician. DISCUSSION: COVID-19 has infected over 3.5 million people and killed over 240,000 people worldwide. While pulmonary complications are profound, the neurologic system is also significantly impacted, with complications including acute cerebrovascular events, encephalitis, Guillain-Barré syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis. Additionally, patients on immunosuppressive medications for pre-existing neurologic issues are at an increased risk for complications with COVID-19 infection, and many of the currently proposed COVID-19 therapies can interact with these medications. CONCLUSIONS: When caring for COVID-19 patients, emergency medicine clinicians should be aware of the neurologic complications from COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Encefalopatias/etiologia , Encefalopatias/fisiopatologia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Infecções por Coronavirus/complicações , Encefalite/etiologia , Encefalite/fisiopatologia , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Pandemias , Pneumonia Viral/complicações
16.
AJNR Am J Neuroradiol ; 41(7): 1179-1183, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32467191

RESUMO

Coronavirus disease 2019 (COVID-19) is a serious public health crisis and can have neurologic manifestations. This is a retrospective observational case series performed March 1-31, 2020, at New York University Langone Medical Center campuses. Clinical and imaging data were extracted, reviewed, and analyzed. Two hundred forty-two patients with COVID-19 underwent CT or MRI of the brain within 2 weeks after the positive result of viral testing (mean age, 68.7 ± 16.5 years; 150 men/92 women [62.0%/38.0%]). The 3 most common indications for imaging were altered mental status (42.1%), syncope/fall (32.6%), and focal neurologic deficit (12.4%). The most common imaging findings were nonspecific white matter microangiopathy (134/55.4%), chronic infarct (47/19.4%), acute or subacute ischemic infarct (13/5.4%), and acute hemorrhage (11/4.5%). No patients imaged for altered mental status demonstrated acute ischemic infarct or acute hemorrhage. White matter microangiopathy was associated with higher 2-week mortality (P < .001). Our data suggest that in the absence of a focal neurologic deficit, brain imaging in patients with early COVID-19 with altered mental status may not be revealing.


Assuntos
Betacoronavirus , Encefalopatias/diagnóstico por imagem , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Pandemias , Estudos Retrospectivos , Estados Unidos
17.
J Clin Neurosci ; 76: 236-237, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-98074

RESUMO

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19. BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015). OBJECTIVE: To raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Encefalopatias/etiologia , Encefalopatias/patologia , Linfo-Histiocitose Hemofagocítica/complicações , Adulto , Betacoronavirus , Infecções por Coronavirus , Feminino , Humanos , Leucoencefalite Hemorrágica Aguda/etiologia , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral
19.
Life Sci ; 252: 117654, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32277979

RESUMO

BACKGROUND: Septic encephalopathy, the most frequent complication of sepsis, is orchestrated by a complex interplay of signals that leads to high mortality rates among intensive care unit patients. However, the role of the vascular endothelial growth factor receptor-2 (VEGFR2) in endoplasmic reticulum stress response (ERSR), during septic encephalopathy, is still elusive. AIM: This study was aimed to examine the effect of an in-house designed/synthesized VEGFR2 antagonist, named WAG4S, on septic encephalopathy using cecal ligation and perforation (CLP). MAIN METHODS: Rats were intraperitoneally injected with WAG-4S (1 mg/kg/d) for 7 days post-CLP. KEY FINDINGS: In septic animals, VEGFR2 antagonism declined the expression of cortical p-VEGFR2 and p-mammalian target of rapamycin complex-1 (p-mTORC1). It also worsened the behavioral and histopathological alterations beyond CLP. However, and contrary to CLP, WAG-4S decreased the p-protein kinase R-like ER kinase (p-PERK) and eukaryotic initiation factor-2α (p-eIF2α) expression. Moreover, VEGFR2 blockade upregulated the mRNA expression of activating transcription factor-4 (ATF4), binding immunoglobulin protein/glucose-regulated protein-78 (Bip/GRP78), growth arrest and DNA damage-34 (GADD34) and spliced X-box binding protein-1 (XBP1s) above CLP. Similarly, it boosted inositol requiring enzyme-1α (IRE1α) activation and redox imbalance. In the same context, WAG-4S augmented the protein levels of CLP-induced ERSR apoptotic markers, namely C/EBP homologous protein (CHOP/GADD153), c-jun N-terminal kinase (JNK) and caspase-3. SIGNIFICANCE: In conclusion, the PERK/eIF2α axis inhibition, during septic encephalopathy, is VEGFR2-independent, whereas the activated IRE1α/XBP1s/CHOP/JNK/caspase-3 cue promotes the ERSR execution module through VEGFR2 inhibition. This has turned VEGFR2 into a potential therapeutic target for ameliorating such an ailment.


Assuntos
Encefalopatias/fisiopatologia , Estresse do Retículo Endoplasmático/fisiologia , Sepse/complicações , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator 4 Ativador da Transcrição/genética , Animais , Encefalopatias/etiologia , Encefalopatias/prevenção & controle , Modelos Animais de Doenças , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , eIF-2 Quinase/metabolismo
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