Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection

Hautala, Timo; Mähönen, Saara-Mari; Sironen, Tarja; Hautala, Nina; Pääkkö, Eija; Karttunen, Ari; Salmela, Pasi; Ilonen, Jorma; Vainio, Olli; Glumoff, Virpi; Rytky, Seppo; Plyusnin, Alexander; Vaheri, Antti; Vapalahti, Olli; Kauma, Heikki

doi:10.3109/07853890.2010.480979

Cited by 43 publications

(62 citation statements)

References 27 publications

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“…24 Furthermore, the central nervous system was also shown to be affected by hantavirus infection, with reports of cerebral hemorrhage, the presence of Puumala virus RNA, and increased levels of the monocyte/macrophage activation marker neopterin in cerebrospinal fluid. [25][26][27][28] HFRS also causes intravascular damage 29 and dysfunctional platelets. 30 Endothelial cells are infected with hantaviruses with subsequent activation.…”

Section: Discussionmentioning

confidence: 99%

Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome

et al. 2014

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G lobally, cardiovascular diseases (CVDs) are the leading cause of death and a major source of disability. The majority of these are caused by ischemic heart disease such as acute myocardial infarction (AMI), stroke, and other cerebrovascular diseases.1 Several factors, including infectious diseases, have been associated with increased risk for CVD. [2][3][4][5][6] The host inflammatory response to infection often results in release of proinflammatory cytokines and activation of platelets, leukocytes, and endothelial cells that can activate procoagulant pathways and can inhibit anticoagulant pathways. 2,3 This can tip the balance of hemostasis toward a prothrombotic state, laying the foundation for acute cardiovascular events such as AMI and stroke. 2,3 Clinical Perspective on p 1302Viral hemorrhagic fevers are characterized by fever, hemorrhages, and shock. Abnormal coagulation and vascular dysfunction are common observations during viral hemorrhagic fevers, 7 which could be risk factors for CVD. Four viral families contain members that cause viral hemorrhagic fevers: Bunyaviridae, Flaviviridae, Filoviridae and Arenaviridae. Pathogenic hantaviruses in the Bunyaviridae family cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome in the Americas.8 HFRS caused by Puumala virus is considered a mild viral hemorrhagic fever 7 characterized by thrombocytopenia, enhanced coagulation and fibrinolysis, 9 and disseminated intravascular coagulopathy. 10In a highly endemic area for Puumala virus in Northern Sweden, we observed a tendency of HFRS patients to develop acute cardiovascular events. Furthermore, we have recently shown that CVD is a common cause of death during acute HFRS in Sweden.11 Together, these findings suggest a possible association between acute HFRS and CVD. Therefore, we decided to investigate in more detail whether HFRS is a risk factor for CVD. To test this, we compared the incidence of AMI and stroke Background-We recently observed that cardiovascular causes of death are common in patients with hemorrhagic fever with renal syndrome (HFRS), which is caused by hantaviruses. However, it is not known whether HFRS is a risk factor for the acute cardiovascular events of acute myocardial infarction (AMI) and stroke. Methods and Results-Personal identification numbers from the Swedish HFRS patient database (1997-2012; n=6643) were cross-linked with the National Patient Register from 1987 to 2011. Using the self-controlled case series method, we calculated the incidence rate ratio of AMI/stroke in the 21 days after HFRS against 2 different control periods either excluding (analysis 1) or including (analysis 2) fatal AMI/stroke events. The incidence rate ratios for analyses 1 and 2 for all AMI events were 5.53 (95% confidence interval [CI], 2.6-11.8) and 6.02 (95% CI, 2.95-12.3) and for first AMI events were 3.53 (95% CI, 1.25-9.96) and 4.64 (95% CI, 1.83-11.77). The incidence rate ratios for analyses 1 and 2 for all stroke events were 12.93 (95% CI, 5.62-29.74)...

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Section: Discussionmentioning

confidence: 99%

Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome

et al. 2014

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“…While renal insufficiency is the principal target-organ manifestations of HFRS, viral antigens can be found in the brains of animal models (59) and CNS-associated clinical signs and symptoms have been reported in some HFRS patients (10,(19)(20)(21)(22)24,55). Our data demonstrate that HTNV and MJNV efficiently replicate and induce N protein synthesis in human astrocytic cells and similarly cause the induction of innate immune responsive genes.…”

Section: Discussionmentioning

confidence: 71%

“…The mechanisms of hantavirus-induced pathogenesis are not fully understood, but both HFRS and HCPS share several clinical and pathologic features, including high fever, thrombocytopenia, increased capillary permeability and upregulation of tumor necrosis factor-a (TNF-a). Recent reports indicate less wellstudied complications of HFRS and HCPS, such as central nervous system (CNS) dysfunction (10,(19)(20)(21)(22)24,55). However, hantaviral antigens have not been detected in the brains of patients, so the mechanisms by which hantavirus infection might lead to neurological and neuropsychological complications are almost entirely unknown.…”

Section: Introductionmentioning

confidence: 99%

Hantaviruses Induce Antiviral and Pro-Inflammatory Innate Immune Responses in Astrocytic Cells and the Brain

Shin

Song²,

Kumar

et al. 2014

Viral Immunology

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Although hantaviruses are not generally considered neurotropic, neurological complications have been reported occasionally in patients with hemorrhagic fever renal syndrome (HFRS). In this study, we analyzed innate immune responses to hantavirus infection in vitro in human astrocytic cells (A172) and in vivo in suckling ICR mice. Infection of A172 cells with pathogenic Hantaan virus (HTNV) or a novel shrew-borne hantavirus, known as Imjin virus (MJNV), induced activation of antiviral genes and pro-inflammatory cytokines/chemokines. MicroRNA expression profiles of HTNV-and MJNV-infected A172 cells showed distinct changes in a set of miRNAs. Following intraperitoneal inoculation with HTNV or MJNV, suckling ICR mice developed rapidly progressive, fatal central nervous system-associated disease. Immunohistochemical staining of virus-infected mouse brains confirmed the detection of viral antigens within astrocytes. Taken together, these findings suggest that the neurological findings in HFRS patients may be associated with hantavirus-directed modulation of innate immune responses in the brain.

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“…During the Prodromal Stage (3-5 days) the patient is febrile with concomitant constitutional flu-like symptoms (headache, malaise, myalgia, anorexia, eye pain), whereas haemorrhagic manifestations (subconjunctival haemorrhage, petechiae and mucous membrane injection) may coexist [2]. In addition, cases of Pumala virus infection may present visual disturbances and photophobia (due to lens thickening) as well as neurological complications that may involve epileptic seizures, hemiparesis, structural central nervous system (CNS) lesions, encephalitis, Guillain-Barre syndrome and cranial nerve palsies [9,17]. According to literature pathogenesis of CNS involvement is not well understood, and it is considered a part of an autoimmune process, due to molecular mimicry of viral antigens and neural host antigens.…”

Section: Epidemiology Clinical Features and Disease Severity Of Hantmentioning

confidence: 99%

“…According to literature pathogenesis of CNS involvement is not well understood, and it is considered a part of an autoimmune process, due to molecular mimicry of viral antigens and neural host antigens. An example is Acute Disseminated Encephalomyelitis (ADEM) caused by Pumala virus [9,17].…”

Section: Epidemiology Clinical Features and Disease Severity Of Hantmentioning

confidence: 99%

Hantavirus Infections in the European Region: A Mini-Review of the Literature

Panos¹

2017

JMEN

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Central nervous system-related symptoms and findings are common in acute Puumala hantavirus infection

Abstract: CNS-related symptoms and inflammation in the CSF are common in acute NE. Genetic properties of the host may predispose to CNS involvement. It does seem that pituitary injury and subsequent hormonal insufficiency may complicate the recovery.

Cited by 43 publications

References 27 publications

Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome

Increased Risk of Acute Myocardial Infarction and Stroke During Hemorrhagic Fever With Renal Syndrome

Hantaviruses Induce Antiviral and Pro-Inflammatory Innate Immune Responses in Astrocytic Cells and the Brain

Hantavirus Infections in the European Region: A Mini-Review of the Literature

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