Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome

Lindström, Johan; Grahn, Anna; Zetterberg, Henrik; Studahl, Marie

doi:10.1111/ejn.13403

Cited by 11 publications

(8 citation statements)

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“…CNS HSV and VZV infections may lead to the elevation of CSF sTREM2 via a similar mechanism. Regarding GFAP, there have been several reports of increased CSF GFAP in patents with herpes virus infections including HSV-1 encephalitis, Ramsay-Hunt syndrome, and VZV encephalitis, suggesting that astrocytic damage is also present in patients with herpes virus infections [29] [30] [31]. The results of the present study are consistent with those reports.…”

Section: Discussionsupporting

confidence: 92%

CSF biomarker profiles in CNS infection associated with HSV and VZV mimic pattern in Alzheimer’s disease.

Shinomoto

Kasai

Tatebe

et al. 2020

Preprint

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Background: Central nervous system (CNS) infections have been reported to have a certain etiological relevance to Alzheimer’s disease (AD). In particular, herpes simplex virus (HSV) and varicella zoster virus (VZV) infections has been reported as risk factors for AD. The aim of this study was to determine whether or not AD-related biomarkers were changed in patients with HSV or VZV CNS infections.Methods: Nine patients with HSV infection of the CNS, eight patients with VZV complicated by CNS involvement, and eighteen age-matched controls were enrolled. Amyloid β (Aβ)1-42, Aβ1-40, total-tau (t-tau), tau phosphorylated at threonine 181 (p-tau), neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (p-NfH), glial fibrillary acidic protein (GFAP), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in were measured in cerebrospinal fluid (CSF), and NfL in serum.Results: Compared with the control group, CSF Aβ1-42, Aβ1-40, and the Aβ1-42/ Aβ1-40 ratio were significantly decreased, and CSF t-tau, p-tau, sTREM2, and GFAP were significantly increased in the HSV and VZV combined group, in which biomarker changes were similar to those reported in AD. CSF NfL levels measured on admission were significantly correlated with the disease severity and a poor outcome after age adjustment. Serum NfL on admission was also associated with disease severity after age adjustment.Conclusions: The fact that the biomarker profile in patients with CNS HSV and VZV infections mimicked that in AD patients should be paid attention to as a potential confounding factor in CSF biomarker-based diagnosis of AD, and it suggests an etiological similarity between herpetic virus infection and AD. The CSF NfL concentration on admission may be useful as a predictive marker of severity and prognosis in patients with CNS HSV and VZV infections.

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Section: Discussionsupporting

confidence: 92%

CSF biomarker profiles in CNS infection associated with HSV and VZV mimic pattern in Alzheimer’s disease.

Shinomoto

Kasai

Tatebe

et al. 2020

Preprint

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“…CSF NFL concentrations have been reported to be higher in patients with VZV CNS infection compared with that of controls. This increase is most pronounced in patients with encephalitis, but is also seen in those with meningitis (Grahn et al 2013 ) and Ramsay Hunt syndrome (Grahn et al 2013 ; Lindstrom et al 2016 ), and may be a reflection of the degree of CNS injury.…”

Section: Introductionmentioning

confidence: 99%

“…In patients with VZV CNS infection, viral load and some other biomarkers have been investigated, such as neurofilament light chain (NFL), glial fibrillary acidic protein and S-100B protein (Aberle et al 2005 ; Grahn et al 2013 ; Lindstrom et al 2016 ; Persson et al 2009 ). Viral load of VZV in CSF was in one study shown to be higher in encephalitis patients (Aberle et al 2005 ), but could in another study not differ against meningitis patients and was not related to the outcome (Persson et al 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus

et al. 2020

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Varicella-zoster virus (VZV) is a common cause of viral central nervous system (CNS) infection, and patients may suffer from severe neurological sequelae. The biomarker neurofilament light chain (NFL) is used for assessment of neuronal damage and is normally measured in cerebrospinal fluid (CSF). Novel methods have given the possibility to measure NFL in serum instead, which could be a convenient tool to estimate severity of disease and prognosis in VZV CNS infections. Here, we investigate the correlation of serum and CSF NFL in patients with VZV CNS infection and the association of NFL levels in serum and CSF with different VZV CNS entities. NFL in serum and CSF was measured in 61 patients who were retrospectively identified with neurological symptoms and VZV DNA in CSF detected by PCR. Thirty-three herpes zoster patients and 40 healthy blood donors served as control groups. NFL levels in serum and CSF correlated strongly in the patients with VZV CNS infection. Encephalitis was associated with significantly higher levels of NFL in both serum and CSF compared with meningitis and Ramsay Hunt syndrome. Surprisingly, herpes zoster controls had very high serum NFL levels, comparable with those shown in encephalitis patients. We show that analysis of serum NFL can be used instead of CSF NFL for estimation of neuronal injury in patients with VZV CNS infection. However, high levels of serum NFL also in patients with herpes zoster, without signs of CNS involvement, may complicate the interpretation.

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“…In terms of pathogen-independent CSF parameters, pleocytosis is usually present in VZV reactivation affecting the CNS [ 10 ] but can be absent especially in immunocompromised patients [ 11 ] or complications such as VZV vasculopathy [ 12 ]. With respect to experimental markers, increased CSF concentrations of neurofilament protein and glial fibrillary acidic protein were recently described in VZV-infected patients with facial palsy, indicating neuronal damage and astrogliosis, but their levels did not correlate with outcome [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation

Kuhn

Sühs

Akmatov

et al. 2018

J Neuroinflammation

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BackgroundVaricella zoster virus (VZV) reactivation spans the spectrum from uncomplicated segmental herpes zoster to life-threatening disseminated CNS infection. Moreover, in the absence of a small animal model for this human pathogen, studies of pathogenesis at the organismal level depend on analysis of human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect critical aspects of host responses and end-organ damage in neuroinfection and neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to three clinically distinct forms of VZV reactivation and infectious and non-infectious disease controls in order to identify biomarkers for CNS involvement in VZV reactivation.MethodsMetabolite profiles were determined by targeted liquid chromatography-mass spectrometry in CSF from patients with segmental zoster (shingles, n = 14), facial nerve zoster (n = 16), VZV meningitis/encephalitis (n = 15), enteroviral meningitis (n = 10), idiopathic Bell’s palsy (n = 11), and normal pressure hydrocephalus (n = 15).ResultsConcentrations of 88 metabolites passing quality assessment clearly separated the three VZV reactivation forms from each other and from the non-infected samples. Internal cross-validation identified four metabolites (SM C16:1, glycine, lysoPC a C26:1, PC ae C34:0) that were particularly associated with VZV meningoencephalitis. SM(OH) C14:1 accurately distinguished facial nerve zoster from Bell’s palsy. Random forest construction revealed even more accurate classifiers (signatures comprising 2–4 metabolites) for most comparisons. Some of the most accurate biomarkers correlated only weakly with CSF leukocyte count, indicating that they do not merely reflect recruitment of inflammatory cells but, rather, specific pathophysiological mechanisms. Across all samples, only the sum of hexoses and the amino acids arginine, serine, and tryptophan correlated negatively with leukocyte count. Increased expression of the metabolites associated with VZV meningoencephalitis could be linked to processes relating to neuroinflammation/immune activation, neuronal signaling, and cell stress, turnover, and death (e.g., autophagy and apoptosis), suggesting that these metabolites might sense processes relating to end-organ damage.ConclusionsThe results provide proof-of-concept for the value of CSF metabolites as (1) disease-associated signatures suggesting pathophysiological mechanisms, (2) degree and nature of neuroinflammation, and (3) biomarkers for diagnosis and risk stratification of VZV reactivation and, likely, neuroinfections due to other pathogens.Trial registrationNot applicable (non-interventional study).Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1041-0) contains supplementary material, which is available to authorized users.

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Cerebrospinal fluid viral load and biomarkers of neuronal and glial cells in Ramsay Hunt syndrome

Cited by 11 publications

References 50 publications

CSF biomarker profiles in CNS infection associated with HSV and VZV mimic pattern in Alzheimer’s disease.

CSF biomarker profiles in CNS infection associated with HSV and VZV mimic pattern in Alzheimer’s disease.

Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus

Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation

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